Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis.

The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.

System of wheat intensification (SWI): Effects on lodging resistance, photosynthetic efficiency, soil biomes, and water productivity.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 µg TPF g-1 soil hr-1), arylsulfatase activity (82.8 µg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

Assessment of Dependency in Activities of Daily Living (ADL) and its Predictors: A Cross-Sectional Study among the Elderly Rural Population in a Sub-Himalayan UT of India.

Background: With an increase in life expectancy over the last few decades, there has been a parallel increase in the prevalence of disabilities among the elderly population. To estimate the prevalence of dependency in activities of daily living (ADL) and its predictors among the rural elderly population. Material and Methods: This was a cross-sectional study carried out in the community among the rural geriatric population in the field practice area of PG Department of Community Medicine, Government Medical College Jammu. The Barthel Scale Index was used to measure ADL dependency. PSPP software was used to analyze the data. Results: The mean age of study participants was 68.31 ± 7.9 years. ADL dependency was observed in 46.3% of the subjects, with the majority demonstrating mild to moderate dependence. Only 2.5% of the respondents reported a severe degree of ADL dependence. The mean ADL score was 94.47 ± 8.98. On multivariate logistic regression analysis, age, educational status, the presence of stress in the family, personal history, and the presence of co-morbidities emerged to be independent predictors of ADL dependence. Conclusion: High prevalence of physical disability in the geriatric population is now an area of major concern. This emphasizes the significance of setting up geriatric care centers especially in rural areas preferably integrating with health and wellness centers.

Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree.

INTRODUCTION: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. METHODS AND RESULTS: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). CONCLUSION: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Food Insecurity and its Association with Dietary Diversity: A Cross-Sectional Study in Rural Households in Jammu.

Background: Food insecurity is a matter of public health concern as it is associated with adverse health outcomes particularly among vulnerable population. Accessibility and availability of nutritious and culturally appropriate food is paramount to achieve zero hunger. To assess the prevalence of household food insecurity, to estimate the household dietary diversity and its association with household food insecurity. Material and Methods: Using multistage sampling 381 rural households were surveyed. Household Food Insecurity Access Scale and House hold Dietary Diversity Scale were used as study instruments. Chi square test was used to compare the two groups and P < 0.05 was considered to be statistically significant. Results: Prevalence of household insecurity was 33.3% (127) among the surveyed households and 8.1% (31) had severe food insecurity. The mean HFIS score was 6.85 ± 4.82. The household Dietary diversity score was 8.14 ± 1.54 for food secure and 6.51 ± 1.38 for severely food insecure households. There was a statistically significant difference in intake of milk and milk products, fruits, eggs and meat/poultry among food secure and insecure households (P < 0.001 respectively). Conclusion: Food insecurity was high in rural households and was associated with lower dietary intake of foods from protein group, necessitating a need to reinforce the food security programmes in rural India with focus to enhance protein rich diet.

A Detailed Assessment of Variations of Ethmoid Roof, Olfactory Fossa, and Anterior Ethmoidal Artery on CT Scan of Paranasal Sinuses of 200 Patients.

To study and analyse the variations in ethmoid roof anatomy and estimate the anatomical location and variations of AEA on CT scans. The study is conducted on 200 patients for detailed analysis of the olfactory fossa (OF) depth, supraorbital pneumatisation, and AEA location and distance from the skull base. In our study, Keros type II was predominant type seen followed by type I. Asymmetry was noted in 32/200 subjects (16%). The anterior ethmoidal artery (AEA) canal was seen in 341/400 sides (85.2%). We found Keros type II was the most common type in our study. We also found grade I anterior ethmoidal artery as the most common variant and the dangerous grade III anterior ethmoidal artery was least common type found in this study, and there was a significant association of Keros type II with increasing anterior ethmoidal artery grading.

The catalytic mechanism of the RNA methyltransferase METTL3.

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N6-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m6A. A crystal structure with a BA representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N6. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release, and suggests that the latter step is rate-limiting for METTL3. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.

The hidden threat: Environmental toxins and their effects on gut microbiota.

The human gut microbiota (GM), which consists of a complex and diverse ecosystem of bacteria, plays a vital role in overall wellness. However, the delicate balance of this intricate system is being compromised by the widespread presence of environmental toxins. The intricate connection between contaminants in the environment and human well-being has garnered significant attention in recent times. Although many environmental pollutants and their toxicity have been identified and studied in laboratory settings and animal models, there is insufficient data concerning their relevance to human physiology. Consequently, research on the toxicity of environmental toxins in GM has gained prominence in recent years. Various factors, such as air pollution, chemicals, heavy metals, and pesticides, have a detrimental impact on the composition and functioning of the GM. This comprehensive review aims to comprehend the toxic effects of numerous environmental pollutants, including antibiotics, endocrine-disrupting chemicals, heavy metals, and pesticides, on GM by examining recent research findings. The current analysis concludes that different types of environmental toxins can lead to GM dysbiosis and have various potential adverse effects on the well-being of animals. We investigate the alterations to the GM composition induced by contaminants and their impact on overall well-being, providing a fresh perspective on research related to pollutant exposure.

Laparoscopic choledochal cyst excision and biliary reconstruction in patients with previous surgery/ intervention: Feasibility and outcome.

INTRODUCTION: The aim of the study was to evaluate the feasibility and outcome of laparoscopic surgery in complicated choledochal cyst (CDC) with previous interventions (laparotomy or biliary drainage). PATIENTS AND METHODS: Patients with CDC who underwent surgery from July 2014 to July 2019 were evaluated. CDC without previous interventions (Group A) was compared with CDC that had previous interventions (Group B) to assess the feasibility and outcome of laparoscopic surgery. RESULTS: In 5 years' period, 38 patients were operated for CDC. The mean age was similar in both groups (3.78 ± 2.27 in Group A and 4.08 ± 2.73 in Group B). Out of six CDC with previous intervention (Group B), five patients were previously managed at other institutions as follows: (1) Laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) stenting. (2) Laparotomy for biliary peritonitis and ERCP. (3) Percutaneous drainage of the large cyst. (4) Laparoscopic cholecystectomy. (5) ERCP stenting. (6) Percutaneous drainage for biliary ascites. All patients underwent laparoscopic CDC excision and hepatico-duodenostomy. The mean duration of surgery was 160.3 ± 17.22 in Group A and 169.2 ± 17.5 in Group B ( P = 0.258). None required intraoperative blood transfusion. None had a bile leak. Drain was removed at 4.47 ± 0.98 in Group A, while at 4.17 ± 0.75 days in Group B ( P = 0.481). There was statistically no significant difference in feed starting time or length of stay. In follow-up of 6 months-3 years, all patients are asymptomatic. CONCLUSIONS: Laparoscopy in complicated CDC with previous intervention is technically tedious but is feasible. The procedure is safe and delivers a good outcome.

Changes in microbial community structure and yield responses with the use of nano-fertilizers of nitrogen and zinc in wheat-maize system.

The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat-maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat-maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

Trastuzumab Plus Gemcitabine-Cisplatin for Treatment-Naïve Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Adenocarcinoma: A Multicenter, Open-Label, Phase II Study (TAB).

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

Metagenomics and metatranscriptomics as potential driving forces for the exploration of diversity and functions of micro-eukaryotes in soil.

Micro-eukaryotes are ubiquitous and play vital roles in diverse ecological systems, yet their diversity and functions are scarcely known. This may be due to the limitations of formerly used conventional culture-based methods. Metagenomics and metatranscriptomics are enabling to unravel the genomic, metabolic, and phylogenetic diversity of micro-eukaryotes inhabiting in different ecosystems in a more comprehensive manner. The in-depth study of structural and functional characteristics of micro-eukaryote community residing in soil is crucial for the complete understanding of this major ecosystem. This review provides a deep insight into the methodologies employed under these approaches to study soil micro-eukaryotic organisms. Furthermore, the review describes available computational tools, pipelines, and database sources and their manipulation for the analysis of sequence data of micro-eukaryotic origin. The challenges and limitations of these approaches are also discussed in detail. In addition, this review summarizes the key findings of metagenomic and metatranscriptomic studies on soil micro-eukaryotes. It also highlights the exploitation of these methods to study the structural as well as functional profiles of soil micro-eukaryotic community and to screen functional eukaryotic protein coding genes for biotechnological applications along with the future perspectives in the field.

Interobserver reproducibility of RENAL nephrometry score in comparison to simplified PADUA Renal nephrometry score.

Introduction: Nephron-sparing surgery (NSS) is the standard of care for renal tumors, especially in the early stages. RENAL Nephrometry scores provide a comprehensive presurgical predictive module for the choice of NSS or Radical Nephrectomy. The validity and reliability of Nephrometry scores is being tested continuously with advancement in the surgical techniques. The Simplified PADUA Nephrometry score (SPARE NS) is a newer proposed score which aims to better the reproducibility of the previously established nephrometry scores. Materials and Methods: The retrospective observational study studied the comparative inter-observer reliability of RENAL (RENAL NS) and SPARE nephrometry scoring systems amongst two radiologists while assessing solid renal tumors in contrast-enhanced computed tomography scans of 42 patients. Interobserver reliability for all components of both scores, final scores and risk grading was done by Kendall's Concordance Coefficient (Tau). Results: Both RENAL NS and SPARE NS showed strong to excellent agreement (RENAL NS = 78.57% and SPARE NS = 88.09%) among observers with comparable correlation co-efficient (RENAL NS = 0.944 and SPARE NS = 0.935). Lesion radius and exophytic/endophytic properties were the most reproducible components of RENAL NS with 97.61% and 92.85% agreement, respectively. Location across polar lines was the least reproducible component with 85.71% agreement among observers. Exophytic rate (97.61%) and Rim location were the most reproducible components of SPARE NS. The final lesion risk stratification by both observers for both was concordant in 92.85% of cases. Conclusion: The SPARE system of scoring matches up to the RENAL NS in total score and risk stratification reproducibility. However, the individual components of the SPARE score are more reproducible than those of RENAL NS, bringing about better compliance among radiology consultants. Comparable reproducibility with the RENAL NS, lesser number of variables, and ease of doing make SPARE NS a plausible option for the customary preoperative assessment of renal tumors.

Optimizing polyhalite (POLY-4) use in the maize-wheat system: A comparative case study from upper and Trans Indo-Gangetic plains of India.

Increasing complexity in crop nutrient requirement in intensive crop production systems needs alternate multi-nutrient sources. Polyhalite (POLY-4) which contains 14% K2O along withcalcium (17% CaO), magnesium (6% MgO), and sulfur (19% S) can be a possible recourse in this regard. In maize-wheat systems, it was evaluated for productivity, profitability, nutrient usage, and nutrient use efficiency under Indo-Gangetic plain (IGP) zones for consecutive two years (2018-19 and 2019-20). The results revealed that 150% K through POLY-4 produced the maximum maize grain yield under the Trans Indo-Gangetic plains (TGP). The maize grain yield increased by 20.8% and 26.2% under 100% K (POLY-4) and 150% K (POLY-4) over No-K, respectively. But statistically, 100% K (POLY-4) stands similar with both 150% K (POLY-4) and 150% K through muriate of potash (MOP) and equivalent. The trends were noticed under upper Indo-Gangetic plain zones (UGP) also. Similarly, the maximum wheat grain yield (6.12 and 6.29 t/ha under TGP and UGP, respectively) was obtained under 150% K (POLY-4), and remained statistically at par with 100% K (POLY-4), but significantly higher than 150% K (MOP). Under both agro-ecologies i.e. TGP and UGP, the highest system productivity was obtained with recommended N, P, and 150% K application through POLY-4. The added return over NPK remained highest with 150% K (POLY-4) for both maize and wheat. However, higher partial factor productivity for N and S, agronomic, physiological, and translocation efficiencies were noticed under 150% K (POLY-4), and remained at par with 100% K (POLY-4). Increased system yield, added returns, partial factor productivity, agronomic, physiological, and translocation efficiencies under 100% K through POLY-4 (along with recommended N and P) proved its effectiveness as multi-nutrient source for the maize-wheat system under TGP and UGP.

Warming inhibits increases in vegetation net primary productivity despite greening in India.

India is the second-highest contributor to the post-2000 global greening. However, with satellite data, here we show that this 18.51% increase in Leaf Area Index (LAI) during 2001-2019 fails to translate into increased carbon uptake due to warming constraints. Our analysis further shows 6.19% decrease in Net Primary Productivity (NPP) during 2001-2019 over the temporally consistent forests in India despite 6.75% increase in LAI. We identify hotspots of statistically significant decreasing trends in NPP over the key forested regions of Northeast India, Peninsular India, and the Western Ghats. Together, these areas contribute to more than 31% of the NPP of India (1274.8 TgC.year-1). These three regions are also the warming hotspots in India. Granger Causality analysis confirms that temperature causes the changes in net-photosynthesis of vegetation. Decreasing photosynthesis and stable respiration, above a threshold temperature, over these regions, as seen in observations, are the key reasons behind the declining NPP. Our analysis shows that warming has already started affecting carbon uptake in Indian forests and calls for improved climate resilient forest management practices in a warming world.

Twenty-four years lucerne (Medicago sativa L.) breeder seed production in India: a retrospective study.

Lucerne (Medicago sativa L.) is the second most significant winter leguminous fodder crop after berseem in India. Breeder seed (BS) is the first stage of the seed production chain, as it is the base material for producing foundation and certified seeds. In India, lucerne BS demand has been reduced by 85.58% during the last 24 years (1998-1999 to 2021-2022), declining from 2150 kg to 310 kg. Out of 14 varieties released and notified so far, only nine varieties entered the seed chain since 1998-1999. It shows narrow varietal diversification and, hence, needs robust breeding programs towards enriching genetic variability and varietal development. The present study also highlights the disparity in BS demand and production over the years and puts forth the possible reasons behind the reduction in BS demand and production in the country. Out of the nine varieties, the BS demand of Anand-2 (53.11%) was highest, followed by Type-9 (19.44%) and RL-88 (13.60%). Varietal replacement rate (VRR) was found to be moderate, i.e., 23.67% for the varieties having <5 years old age in the last 3 years (2019-2020 to 2021-2022). It has also been estimated that BS produced (233 kg) during 2021-2022 can cover the approximate area of 6,300 ha at farmers' fields in 2024-2025 if the seed chain functions 100%, effectively. The present study provides a holistic overview of lucerne BS demand and production, challenges in BS production, and the way forward to develop more varieties and surplus BS production in the country.