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Pneumococcal conjugate vaccines (PCVs) have been developed to protect against pneumococcal diseases caused by the more than 100 serotypes of the bacterium Streptococcus pneumoniae. PCVs primarily prevent pneumococcal infections such as sepsis, bacteraemia, meningitis, otitis media, pneumonia, septicaemia, and sinusitis among infants, adults, elderly, and immunocompromised individuals. The current available PCVs only cover a limited number of serotypes, and there is an immense need for developing higher-valent PCVs that can protect against non-vaccine serotypes to overcome challenges like serotype replacement and antibiotic resistance. The main challenges for developing higher valent PCVs are the complexity of the manufacturing process comprising polysaccharide fermentation, purification, modification or sizing of multiple polysaccharides and conjugation between polysaccharides and carrier proteins, the stability of the conjugates, and the immunogenicity of the vaccine. Different manufacturing processes have been explored to produce higher valent PCVs using different serotypes of S. pneumoniae and conjugation with different carrier proteins. The global coverage of higher valent PCVs are still low, mainly due to the high cost and limited supply of the vaccine. This review focuses on the existing and emerging manufacturing processes and challenges associated with higher-valent pneumococcal PCV development.
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Androgenic alopecia is a common and major cause of progressive hair loss. Hair loss can be prevented by administrating concentrated growth factor concentrate (GFC) into the scalp where the person's own growth factors are effectively delivered deep within the layers of the scalp, promoting optimal results. This prospective study includes five patients with androgenic alopecia. Growth factor concentrates were injected subcutaneously into the scalp, and assessment was done before the procedure two and eight weeks after the first sitting. The treatment outcome was evaluated with macroscopic and trichoscopic microphotographs. The trichoscopic microphotographs provided further evidence of the notable improvement in hair density. Additionally, the hair pull test yielded negative results during the eight-week follow-up, confirming the positive outcomes of the GFC treatment. Patients were highly satisfied with the results: faster rate of hair growth, better quality of hair, and minimal side effects.
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Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.
Subject(s)
Anticonvulsants , Drug Discovery , Epilepsy , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Humans , Animals , Drug Discovery/methods , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Inflammasomes/metabolism , Inflammasomes/antagonists & inhibitors , Drug DevelopmentABSTRACT
BACKGROUND: Surgical resection of insular gliomas is a challenge. TO resection is considered more versatile and has lower risk of vascular damage. In this study, we aimed to understand the factors that affect resection rates, ischemic changes and neurological outcomes and studied the utility of IONM in patients who underwent TO resection for IGs. METHODS: Retrospective analysis of 66 patients with IG who underwent TO resection was performed. RESULTS: Radical resection was possible in 39% patients. Involvement of zone II and the absence of contrast enhancement predicted lower resection rate. Persistent deficit rate was 10.9%. Although dominant lobe tumors increased immediate deficit and fronto-orbital operculum involvement reduced prolonged deficit rate, no tumor related factor showed significant association with persistent deficits. 45% of patients developed a postoperative infarct, 53% of whom developed deficits. Most affected vascular territory was lenticulostriate (39%). MEP changes were observed in 9/57 patients. 67% of stable TcMEPs and 74.5% of stable strip MEPs did not develop any postoperative motor deficits. Long-term deficits were seen in 3 and 6% patients with stable TcMEP and strip MEPs respectively. In contrast, 25% and 50% of patients with reversible strip MEP and Tc MEP changes respectively had persistent motor deficits. DWI changes were clinically more relevant when accompanied by MEP changes intraoperatively, with persistent deficit rates three times greater when MEP changes occurred than when MEPs were stable. CONCLUSION: Radical resection can be achieved in large, multizone IGs, with reasonable outcomes using TO approach and multimodal intraoperative strategy with IONM.
Subject(s)
Brain Neoplasms , Glioma , Humans , Glioma/surgery , Glioma/pathology , Male , Female , Middle Aged , Adult , Brain Neoplasms/surgery , Retrospective Studies , Treatment Outcome , Aged , Insular Cortex/surgery , Neurosurgical Procedures/methods , Postoperative Complications/etiology , Young AdultABSTRACT
AIM: To evaluate and compare the sorption and solubility of two different core buildup materials in different pH media for periods of one day, one week, and one month. MATERIALS AND METHOD: Sixty samples were prepared and divided into Group A (30 resin-based samples) and Group B (30 glass ionomer cement (GIC)-based samples). The sorption and solubility of the different materials were calculated by weighing the samples before and after desiccation and media immersion for periods of one day, one week, and one month. Groups were compared using the Mann-Whitney U test, and for different media, the intragroup significance of the mean difference was performed using the Friedmann test and Wilcoxon signed rank test at a significance level of p<0.05. RESULTS: After immersion for different time periods, the resin-based core buildup material (Core X flow) showed less sorption and solubility as compared to the glass ionomer-based core buildup material (Secure Core Z) for all time periods, with a significant difference seen for a time period of one week and one month and being nonsignificant for a time period of one day. CONCLUSION: Core X flow had lower sorption and solubility values when compared to Secure Core Z, as per the International Organization for Standardization (ISO) 4049 standards, except for a one-month time period in alkaline media.
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Air pollution is known to be one of the major risk factors for premature morbidity and mortality globally, which are preventable. Therefore, the public is informed about air pollution through the Air Quality Index (AQI). The AQI represents integrated data of selected pollutants and produces a combined overall index for specific locations and time. The AQI algorithm generates a range of numbers and categories of colors that indicate likely health risks from air pollutants and the public's actions to minimize the risks. However, it lacks emerging evidence on chemical toxicity or composition. Hence, policymakers may also consider addinga toxicity matrix of fine particles to refine the algorithm, such as oxidative potential. Further, the risk is commonly communicated in numbers and not in color as dictated by the AQI. The AQI values and categories vary significantly between countries for the same pollution concentration, leading to confusion. Hence, we recommend developing a universal AQI (UAQI) with a consistent relationship between colors, concentrations, and toxicity to communicate air pollution risks to the public. Further, communication media should be encouraged to use universal color-coding rather than AQI values, i.e., numbers. Therefore, a global policy framework for regulatory authorities and policymakers is needed to communicate air pollution risk information consistently and to minimize public health exposure.
Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Humans , Environmental Monitoring/methods , Risk Assessment , Particulate Matter/analysis , Environmental Exposure , Algorithms , Public HealthABSTRACT
The normalization of RNA sequencing data is a primary step for downstream analysis. The most popular method used for the normalization is the trimmed mean of M values (TMM) and DESeq. The TMM tries to trim away extreme log fold changes of the data to normalize the raw read counts based on the remaining non-deferentially expressed genes. However, the major problem with the TMM is that the values of trimming factor M are heuristic. This paper tries to estimate the adaptive value of M in TMM based on Jaeckel's Estimator, and each sample acts as a reference to find the scale factor of each sample. The presented approach is validated on SEQC, MAQC2, MAQC3, PICKRELL and two simulated datasets with two-group and three-group conditions by varying the percentage of differential expression and the number of replicates. The performance of the present approach is compared with various state-of-the-art methods, and it is better in terms of area under the receiver operating characteristic curve and differential expression.
Subject(s)
RNA-Seq , RNA-Seq/methods , Humans , Algorithms , Sequence Analysis, RNA/methods , Computational Biology/methods , Gene Expression Profiling/methods , ROC Curve , SoftwareABSTRACT
PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.
Subject(s)
Meningeal Neoplasms , Meningioma , Octreotide , Octreotide/analogs & derivatives , Humans , Meningioma/radiotherapy , Meningioma/diagnostic imaging , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/diagnostic imaging , Female , Male , Octreotide/therapeutic use , Octreotide/administration & dosage , Middle Aged , Adult , Organometallic Compounds/therapeutic use , Aged , Treatment Outcome , Radiopharmaceuticals/therapeutic use , Receptors, Peptide , Tertiary Care Centers , Disease ProgressionABSTRACT
Background: Evaluation of type, nature, and prevalence of common oral pathology lesions involving periodontium and implant in patients of tertiary level dental hospital in Hazaribagh City, Jharkhand. Materials and Methods: A total of 2467 people were requested to take part in the oral examination. The current study cohort was made up of the 62.4% of the initial subgroup who participated in the clinical oral examination and granted their agreement for the use of the data. Between January 2023 and June 2023, the clinical oral examination was completed. Results: No changes were observed in 89.6% of study participants. 88.2% males had no changes while 90.4% females had no changes. Normal variations were observed in 3.4% of study participants. 4.3% males had normal variations while 2.7% females had normal variations. Infectious oral pathology was observed in 3.3% of study participants. 2.4% males had infectious oral pathology while 3.2% females had infectious oral pathology Ulcerative lesions were observed in 4.1% of study participants. 3.6% males had ulcerative lesions while 2.4% females had ulcerative lesions. White lesions were observed in 6.7% of study participants. 8.2% males had white lesions while 5.6% females had white lesions. Conclusion: This study provided a detailed evaluation of type, nature, and prevalence of different oral pathology lesions focusing on periodontium and implant.
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Background Removing gutta-percha manually can be a challenging task, especially when addressing densely packed root-filling material, particularly in cases where resin-based sealers are employed for obturation. The use of nickel-titanium (NiTi) rotary instruments not only effectively shapes the root canal but also efficiently removes the endodontic filling from the curved canal during retreatment. Hence, incorporating rotary NiTi instruments in retreatment cases can alleviate fatigue for both patients and operators. Objectives This study aims to compare the efficacy of Neo-Endo retreatment files, R-Endo retreatment files, and K and H files in the removal of endodontic filling material. Additionally, the remnants of gutta-percha in root canals are evaluated using cone beam computed tomography (CBCT). Materials and methods A total of 60 extracted first maxillary molar teeth were selected for this study. Canal preparation was conducted using the step-back method up to an apical size of 40 K-file. The obturation process involved the use of gutta-percha points and AH Plus sealer in a lateral compaction technique. Post-operative CBCT scans were taken. The samples were randomly divided according to the retreatment files used: group I included Neo-Endo retreatment files, group II included R-Endo retreatment files, and group III included conventional K-files and Hedstroem files (H-Files). The retreatment procedure was considered complete when the last instrument easily reached the working-length range and was physically clean. A stopwatch was used to record the time taken by each file to remove the obturating material. T1 represented the total time (including irrigation and change of file) required to reach the apex, while T2 indicated the complete removal of materials from the canal with the last instrument. The overall time recorded (TT) was calculated as T1 + T2. The removal process was analyzed with CBCT scans. Results The Neo-Endo retreatment files removed the filling materials better and more quickly than the other files. Conclusions Despite the presence of residual filling material in all samples, the Neo-Endo retreatment files left the least amount of residual filling material and achieved the shortest completion time.
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A quick evaluation of the effectiveness of additives is important in lubricant formulation. In this study, we employed a friction-force measurement approach using a newly designed lateral force-controlled tribometer. This tribometer evaluates the lubricant properties under boundary lubrication. In this lateral force-controlled tribometer, the absence of a stiffness-altering sensor enables the modeling of the actual contact conditions without altering the contact stiffness. Indirect friction force measurement ensures precise measurements of friction properties while avoiding common measurement errors encountered in conventional tribometers, such as sensor misalignment and changes in the stiffness of the machine due to the sensor. The tribometer designed and built consists of a pendulum that measures the rate of dissipation of the oscillation amplitude as a function of time. The unique characteristics of the machine are the possibility of changing the energy input into the tribosystem without altering the tribo-contact conditions and the capability to do experiments at higher temperatures. To evaluate the capabilities of this tribometer, the impact of temperature on the frictional properties of a base oil and a blend of base oil and stearic acid (SA) (a prominent Organic Friction Modifier) is investigated. The test result shows that frictional energy dissipation decreases when stearic acid is present in the lubricant. And, as the temperature of the oil increases, the energy dissipation increases for pure base oil but reduces for the blend. The observed frictional trends are attributed to the decrease in the viscosity of the base oil with an increase in the temperature. The decrease in friction for the SA blend is attributed to tribofilm formation. Fourier transform infrared (FTIR) and X-ray Photoelectron Spectroscopy (XPS) analyses confirm the presence of the SA tribofilm on the surface. XPS indicates an increase in tribofilm quantity with rising temperatures. The kinetics of film formation and thickness increase with temperature, consequently reducing the friction in the SA blend.
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The average global temperature is rising due to anthropogenic emissions. Hence, a systematic approach was used to examine the projected impacts of rising global temperatures on heatwaves in India and provide insights into mitigation and adaptation strategies. With over 24,000 deaths attributed to heatwaves from 1992 to 2015, there is an urgent need to understand India's vulnerabilities and prepare adaptive strategies under various emission scenarios.This situation is predicted to worsen as heatwaves become more frequent, intense, and long-lasting. Severe heatwaves can exacerbate chronic health conditions, vector-borne diseases, air pollution, droughts and other socio-economic pressures causing higher mortality and morbidity. Heatwaves with severe consequences have increased and are expected to become more frequent in Indian climatic and geographical conditions. As per the future projection studies, the temperature could rise ±1.2° C to ±3.5° C and will start reducing by the end of 2050. The study also provides data from the research that employs climatic models and statistical approaches for a more precise characterization of heat extremes and improved projections. Also, the study appraises the past, present and future heatwave trend projections. Most of these studies compute future projections using the Coupled Model Intercomparison Project (CMIP5) models and Representative Concentration Pathway (RCP). Limited systematic reports have been found using CMIP6, whereas the best-suited and widely used method was the RCP8.5. The study findings will aid in identifying the zones most susceptible to heatwave risk and provide actionable projections for policymakers to examine the existing evidence for developing proper planning and policy formulation, considering the future climate and temperature projections.
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Background: Neurocognitive function is a key outcome indicator of therapy in brain tumors. Understanding the underlying anatomical substrates involved in domain function and the pathophysiological basis of dysfunction can help ameliorate the effects of therapy and tailor directed rehabilitative strategies. Methods: Hundred adult diffuse gliomas were co-registered onto a common demographic-specific brain template to create tumor localization maps. Voxel-based lesion symptom (VLSM) technique was used to assign an association between individual voxels and neuropsychological dysfunction in various domains (attention and executive function (A & EF), language, memory, visuospatial/constructive abilities, and visuomotor speed). The probability maps thus generated were further co-registered to cortical and subcortical atlases. A permutation-based statistical testing method was used to evaluate the statistically and clinically significant anatomical parcels associated with domain dysfunction and to create heat maps. Results: Neurocognition was affected in a high proportion of subjects (93%), with A & EF and memory being the most affected domains. Left-sided networks were implicated in patients with A & EF, memory, and language deficits with the perisylvian white matter tracts being the most common across domains. Visuospatial dysfunction was associated with lesions involving the right perisylvian cortical regions, whereas deficits in visuomotor speed were associated with lesions involving primary visual and motor output pathways. Conclusions: Significant baseline neurocognitive deficits are prevalent in gliomas. These are multidomain and the perisylvian network especially on the left side seems to be very important, being implicated in dysfunction of many domains.
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Rice blast and bacterial leaf blight, are major disease, significantly threatens rice yield in all rice growing regions under favorable conditions and identification of resistance genes and their superior haplotypes is a potential strategy for effectively managing and controlling this devastating disease. In this study, we conducted a genome-wide association study (GWAS) using a diverse set of 147 rice accessions for blast and bacterial blight diseases in replications. Results revealed 23 (9 for blast and 14 for BLB) significant marker-trait associations (MTAs) that corresponded to 107 and 210 candidate genes for blast and BLB, respectively. The haplo-pheno analysis of the candidate genes led to the identification of eight superior haplotypes for blast, with an average SES score ranging from 0.00 to 1.33, and five superior haplotypes for BLB, with scores ranging from 1.52cm to 4.86cm superior haplotypes. Among these, superior haplotypes LOC_OS12G39700-H4 and LOC_Os06g30440-H33 were identified with the lowest average blast scores of 0.00-0.67, and superior haplotype LOC_Os02g12660-H39 exhibited the lowest average lesion length (1.88 - 2.06cm) for BLB. A total of ten accessions for blast and eight accessions for BLB were identified carrying superior haplotypes were identified. These haplotypes belong to aus and indx subpopulations of five countries (Bangladesh, Brazil, India, Myanmar, and Pakistan). For BLB resistance, eight accessions from six countries (Bangladesh, China, India, Myanmar, Pakistan, and Sri Lanka) and four subpopulations (aus, ind1A, ind2, and ind3) were identified carrying superior haplotypes. Interestingly, four candidate genes, LOC_Os06g21040, LOC_Os04g23960, LOC_Os12g39700, and LOC_Os01g24640 encoding transposon and retrotransposon proteins were among those with superior haplotypes known to play a crucial role in plant defense responses. These identified superior haplotypes have the potential to be combined into a single genetic background through haplotype-based breeding for a broader resistance spectrum against blast and bacterial blight diseases.
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Background Teledentistry, defined as the use of telecommunication technologies for dental care, has emerged as a transformative approach to oral health services. This prospective observational analysis aims to comprehensively assess the impact of teledentistry on patient outcomes and satisfaction, addressing key aspects such as diagnostic accuracy, longitudinal treatment outcomes, and economic and logistical considerations. Methods The study involved 242 participants selected from diverse dental clinics offering teledentistry services. Participants could choose between traditional in-person visits and teledentistry consultations. The teledentistry interventions included remote consultations, diagnostic evaluations, and treatment planning facilitated through virtual communication tools. Baseline assessments captured initial dental conditions, and follow-up assessments were conducted at three, six, and 12 months. Outcome measures included diagnostic accuracy, patient satisfaction, changes in dental conditions over time, and economic and logistical feedback. Results Descriptive statistics revealed baseline characteristics, with participants evenly distributed between in-person and teledentistry groups. However, the overall satisfaction with diagnoses was significantly lower in the teledentistry group as compared to the in-person group (p < 0.001). Longitudinal assessments demonstrated comparable changes in dental conditions between the two groups. Economic feedback highlighted a cost-saving advantage for teledentistry users, with 80% reporting reduced expenses. Conclusion This study highlights the transformative potential of teledentistry in expanding access to oral health services, reducing costs, and providing comparable treatment outcomes to traditional in-person care. Future efforts should focus on enhancing the teledentistry experience, addressing patient satisfaction concerns, and refining the delivery of remote dental care to maximize its benefits for both patients and healthcare systems.
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BACKGROUND: Rice (Oryza sativa L.) is one of the globally important staple food crops, and yield-related traits are prerequisites for improved breeding efficiency in rice. Here, we used six different genome-wide association study (GWAS) models for 198 accessions, with 553,229 single nucleotide markers (SNPs) to identify the quantitative trait nucleotides (QTNs) and candidate genes (CGs) governing rice yield. RESULTS: Amongst the 73 different QTNs in total, 24 were co-localized with already reported QTLs or loci in previous mapping studies. We obtained fifteen significant QTNs, pathway analysis revealed 10 potential candidates within 100kb of these QTNs that are predicted to govern plant height, days to flowering, and plot yield in rice. Based on their superior allelic information in 20 elite and 6 inferior genotypes, we found a higher percentage of superior alleles in the elite genotypes in comparison to inferior genotypes. Further, we implemented expression analysis and enrichment analysis enabling the identification of 73 candidate genes and 25 homologues of Arabidopsis, 19 of which might regulate rice yield traits. Of these candidate genes, 40 CGs were found to be enriched in 60 GO terms of the studied traits for instance, positive regulator metabolic process (GO:0010929), intracellular part (GO:0031090), and nucleic acid binding (GO:0090079). Haplotype and phenotypic variation analysis confirmed that LOC_OS09G15770, LOC_OS02G36710 and LOC_OS02G17520 are key candidates associated with rice yield. CONCLUSIONS: Overall, we foresee that the QTNs, putative candidates elucidated in the study could summarize the polygenic regulatory networks controlling rice yield and be useful for breeding high-yielding varieties.
Subject(s)
Genome-Wide Association Study , Oryza , Chromosome Mapping , Oryza/genetics , Plant Breeding , Quantitative Trait Loci/geneticsABSTRACT
Demyelination is the loss of myelin in CNS, resulting in damaged myelin sheath. Oxidative stress and neuroinflammation play a key role in inducing demyelinating diseases like MS; hence, controlling oxidative stress and neuroinflammation is important. Cuprizone (CPZ), a copper chelator, generates oxidative stress and neuroinflammation, thereby inducing demyelination. Therefore, the CPZ-induced demyelinating mouse model (CPZ model) is widely used in research. The present study was intended to unravel a mechanism of inhibition of demyelination by arsenic in a CPZ model, which is otherwise known for its toxicity. We investigated an alternative mechanism of inhibition of demyelination by arsenic through the reversal of SOD1 activity employing in silico analysis, analytical chemistry techniques, and in vitro and in vivo experiments. In vivo experiments showed protection of body weight, survivability, and myelination of the corpus callosum in CPZ and arsenic-co-exposed animals, where neuroinflammation was apparently not involved. In vitro experiments revealed that arsenic-mediated reversal of impaired SOD1 activity leads to reduced cellular ROS levels and better viability of primary oligodendrocytes. Reversal of SOD1 activity was also observed in the corpus callosum tissue isolated from experimental animals. In silico and analytical chemistry studies revealed that similar to copper, arsenic can potentially bind to CPZ and thereby make the copper freely available for SOD1 activity. Suitable neurobehavior tests further validated the protective effect of arsenic. Taken together, the present study revealed that arsenic protects oligodendrocytes and demyelination of corpus callosum by reversing CPZ-induced impaired SOD1 activity.
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Professor Rajeev K. Varshney's transformative impact on crop genomics, genetics, and agriculture is the result of his passion, dedication, and unyielding commitment to harnessing the potential of genomics to address the most pressing challenges faced by the global agricultural community. Starting from a small town in India and reaching the global stage, Professor Varshney's academic and professional trajectory has inspired many scientists active in research today. His ground-breaking work, especially his effort to list orphan tropical crops to genomic resource-rich entities, has been transformative. Beyond his scientific achievements, Professor Varshney is recognized by his colleagues as an exemplary mentor, fostering the growth of future researchers, building institutional capacity, and strengthening scientific capability. His focus on translational genomics and strengthening seed system in developing countries for the improvement of agriculture has made a tangible impact on farmers' lives. His skills have been best utilized in roles at leading research centres where he has applied his expertise to deliver a new vision for crop improvement. These efforts have now been recognized by the Royal Society with the award of the Fellowship (FRS). As we mark this significant milestone in his career, we not only celebrate Professor Varshney's accomplishments but also his wider contributions that continue to transform the agricultural landscape.