The main duct of von Ebner's glands is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

We have recently demonstrated that Sox10 -expressing ( Sox10 + ) cells give rise to mainly type-III neuronal taste bud cells that are responsible for sour and salt taste. The two tissue compartments containing Sox10 + cells in the surrounding of taste buds include the connective tissue core of taste papillae and von Ebner's glands (vEGs) that are connected to the trench of circumvallate and foliate papillae. In this study, we used inducible Cre mouse models to map the cell lineages of connective tissue (including stromal and Schwann cells) and vEGs and performed single cell RNA-sequencing of the epithelium of Sox10-Cre/tdT mouse circumvallate/vEG complex. In vivo lineage mapping showed that the distribution of traced cells in circumvallate taste buds was closely linked with that in the vEGs, but not in the connective tissue. Sox10 , but not the known stem cells marker Lgr5 , expression was enriched in the cell clusters of main ducts of vEGs that contained abundant proliferating cells, while Sox10-Cre/tdT expression was enriched in type-III taste bud cells and excretory ductal cells. Moreover, multiple genes encoding pathogen receptors are enriched in the vEG main ducts. Our data indicate that the main duct of vEGs is a source of Sox10 + taste bud progenitors and susceptible to pathogen infections.

Effect of School Closure During COVID-19 Lockdown on ADHD Symptoms Among Students.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder among children, with an estimated prevalence of 1.3 per 1000 in India. The nationwide lockdown imposed due to the COVID-19 pandemic has led to the closure of schools for an indefinite period. After the reopening of schools, the lockdown period was feared to have caused a deterioration in symptoms of existing mental health conditions among school-going children. This field study aimed to probe the association of school closures due to lockdown with any change in symptoms of ADHD in aged 6-15 years in the largest tertiary care hospital in Kolkata. Methods: A longitudinal observational study was conducted involving 34 prediagnosed ADHD patients attending the Clinical Psychology outpatient department (OPD) of a tertiary hospital for follow-up. Data was collected by face-to-face interviews with the patients' parents using a predesigned, pretested structured study schedule. Conners' Parent Rating Scale (CPRS) was used to assess the ADHD symptoms. Results: Twenty-three (67.65%) patients were observed to have worsened ADHD symptoms after lockdown. Significant worsening was observed in the ADHD indicator and the mood disorder indicator. Significant contributing factors were rural residence, nuclear family, non-attendance at school, and knowledge inadequacy among parents. Conclusion: There was a significant worsening of symptoms of ADHD owing to the school closure due to the lockdown.

In silico design and evaluation of a multiepitope vaccine targeting the nucleoprotein of Puumala orthohantavirus.

The Puumala orthohantavirus is present in the body of the bank vole (Myodes glareolus). Humans infected with this virus may develop hemorrhagic fever accompanying renal syndrome. In addition, the infection may further lead to the failure of an immune system completely. The present study aimed to propose a possible vaccine by employing bioinformatics techniques to identify B and T-cell antigens. The best multi-epitope of potential immunogenicity was generated by combining epitopes. Additionally, the linkers EAAAK, AAY, and GPGPG were utilized in order to link the epitopes successfully. Further, C-ImmSim was used to perform in silico immunological simulations upon the vaccine. For the purpose of conducting expression tests in Escherichia coli, the chimeric protein construct was cloned using Snapgene into the pET-9c vector. The designed vaccine showed adequate results, evidenced by the global population coverage and favorable immune response. The developed vaccine was found to be highly effective and to have excellent population coverage in a number of computer-based assessments. This work is fully dependent on the development of nucleoprotein-based vaccines, which would constitute a significant step forward if our findings were used in developing a global vaccination to combat the Puumala virus.

Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions.

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80-85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA damage, telomere shortening, and oncogene activation cause a prolonged cell cycle halt, known as senescence. Despite its initial role as a tumor-suppressing mechanism that slows cell growth, excessive or improper control of this process can cause age-related diseases, including cancer. Cellular senescence has two purposes in lung cancer. Researchers report that senescence slows tumor growth by constraining multiplication of impaired cells. However, senescent cells also demonstrate the pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported to promote cancer. This review will look at the role of cellular senescence in lung cancer, describe its diagnostic markers, ask about current treatments to control it, look at case studies and clinical trials that show how senescence-targeting therapies can be used in lung cancer, and talk about problems currently being faced, and possible solutions for the same in the future.

Morphological Variation of Mandibular Molars in Rohilkhand Population: An Original Research.

Introduction: In-depth knowledge of common and aberrant pulp morphology is essential for appropriate diagnosis and treatment planning before commencing root canal treatment. The radicular morphology of mandibular molars has been extensively studied. Considerable variation in the number of canals and roots found in these teeth has been reported. Aim: The purpose of this study is to investigate the root canal morphology of the mandibular molars among the Rohilkhand population using Dentascan. Materials and Methods: Dentascan images of mandibular molar were taken from 99 extracted teeth that were collected from the Department of Oral Surgery and Maxillofacial Surgery, Institute of Dental Sciences, Bareilly, and private clinics. The examination of root canal systems of the teeth was based on Vertucci's classification. Results: The mandibular molar (n = 99) were taken. Out of the 99 teeth examined, three canals were seen in 60 (60.6%) teeth, four canals in 39 (39.4%) teeth, 3% had extra distal roots, and 6% with C-shaped canals. Conclusion: Among mandibular first molars, only 3% had three roots. Mesial roots of the first molar typically present with two canals and two apical foramina with type IV or II canal configuration. Most distal roots of the first molar presented with a type I canal configuration. The remainder were distributed mainly between types II, IV, III, and V. Among 99 mandibular molars, 6% had single C-shaped roots.

Comparison of Antibacterial Activity of Various Additives to Glass Ionomer Restoration: An In Vitro Study.

Introduction: Glass-ionomer (GIC) cement was introduced in 1972 as a "new filling material of dentistry". It is bioactive and plays an important role in caries prevention due to its ability to release fluoride into the oral environment and remineralization of dental hard tissues. However, its properties such as moisture sensitivity, wear resistance, and bond strength are not sufficient to inflict the antimicrobial environment. This in vitro study aimed to evaluate the antibacterial property of four different GIC cements against S. mutans and L. acidophilus. Methodology: This study was conducted on 120 disk-shaped samples (30 for antibacterial activity), which were placed in Petri dishes holding Müeller Hinton agar. Bacterial strains were overhauled in the brain heart infusion culture medium, and by utilizing disposable straps on blood agar medium, 100 ml of the strain inoculum was plated out. Through the diffusion method on the solid medium, the antibacterial activity of GIC was determined. Results: The antibacterial activity was the highest for Riva silver and chemifill rock for 24 and 72 hours, respectively. For 48 hours, Equia forte and chemifill rock had the highest antibacterial activity, and there was a significant difference between the groups. Conclusion: Ketac™ molar easymix inhibited the growth of S. mutans and L. acidophilus but had the lowest antibacterial effect compared to other GICs.

Antibacterial Efficacy of Mineral Trioxide Aggregate, Bioactive Glass and Epoxy-Resin Based Sealer: An In-Vitro Interventional Study.

Aim: The aim and objective of this in vitro study was to evaluate the antibacterial efficacy of mineral trioxide aggregate, bioactive glass sealer, and epoxy-resin-based sealer. Materials and Methods: In the present study, 22 Mueller Hinton agar (MH agar) plates were employed and equally divided into two groups. Three holes were made by removal of agar at equidistant points and filled with root canal sealers. The strains of the bacteria used in this study were S. aureus (ATCC 6538) and C. albicans (ATCC 10231) and were divided into two groups and root canal sealers were divided into three subgroups: mineral trioxide aggregate (MTA) fillapex Sealer, Nishika Bioactive Glass sealer, and Syntex Epoxy Resin base sealer. For Staphylococcus aureus, peptone water was placed in a 2 mL test tube and bacteria were extracted from blood agar plates using a nichrome wire loop and poured into the peptone water-containing test tube and incubated for 2 hours and for C. albicans, fungi were grown at 37°C for 24 hours in MH Broth and seeded into MH agar to produce turbidity of 0.5 on the McFarland scale, which corresponds to a concentration of 108 CFU/mL. This MH broth was used as a second layer. The seeded agar was then added over the plates immediately after the insertion of sealer cement. After incubation, the diameters of zones of inhibition around the plates were measured. Results: The results of this study showed that the highest inhibition was recorded in Syntex sealer against Staphylococcus aureus followed by MTA fillapex sealer and Nishika sealer, whereas MTA fillapex showed the highest inhibition against C. albicans followed by Syntex sealer and Nishika sealer. Conclusion: Syntex sealer exhibits better antibacterial efficacy against Staphylococcus aureus and MTA fillapex exhibit better antibacterial efficacy against C. albicans.

"Tardus-parvus waveform" the only initial clue to mid-aortic syndrome- a rare cause of youth onset hypertension: A case report and a comprehensive review.

Middle aortic syndrome (MAS), an uncommon cause of secondary hypertension, is defined by obstructive narrowing of the abdominal aorta and ostia of its major branches like the renal and splanchnic arteries. Most of the cases of MAS are categorized as idiopathic; however, genetic disorders like Williams syndrome, mucopolysaccharidosis, neurofibromatosis type 1 (NF1), and Alagille syndrome, and acquired inflammatory diseases such as Takayasu arteritis and other nonspecific arteritis can also lead to MAS. MAS is commonly seen in children and young adults presenting with severe hypertension, congestive heart failure, renal failure, or severe leg claudication. The diagnosis of MAS on CT, MR, and conventional angiography is fairly straightforward. However, the spectrum of sonographic findings in MAS can be varied. Since ultrasound is frequently utilized as a first-line investigation for secondary causes of hypertension, it is especially crucial to understand the sonographic features of MAS. Here, we report a case of a young female who presented to our hospital with severe hypertension. On the Renal Doppler scan, the only clue of the renovascular etiology of her secondary hypertension was the "tardus-parvus waveform'' in the intrarenal arteries.

Recent Advances in the Detection of Food Toxins Using Mass Spectrometry.

Edibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.

Advanced targeted drug delivery by bioengineered white blood cell-membrane camouflaged nanoparticulate delivery nanostructures.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Leukocyte membrane coated nanoparticles (NPs) have attracted a lot of interest as an effective approach for delivering targeted drugs, capitalizing on the natural attributes of leukocytes to achieve site-specific accumulation, and heightened therapeutic outcomes. An overview of the present state of the targeted medication delivery research is given in this review. Notably, Leukocyte membrane-coated NPs offer inherent advantages such as immune evasion, extended circulation half-life, and precise homing to inflamed or diseased tissues through specific interactions with adhesion molecules. leukocyte membrane-coated NPs hold significant promise in advancing targeted drug delivery for precision medicine. As research progresses, they are anticipated to contribute to improved therapeutic outcomes, enabling personalized and effective treatments for a wide range of diseases and conditions. The review covers the method of preparation, characterization, and biological applications of leucocytic membrane coated NPs. Further, patents related factors, gap of translation from laboratory to clinic, and future prospective were discussed in detail. Overall, the review covers extensive literature to establish leucocytic membrane NPs for targeted drug delivery.

A Comprehensive review on Pharmacokinetic Studies of Vaccines: Impact of delivery route, carrier-and its modulation on immune response.

The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes former biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced.. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.

Coevolution based immunoinformatics approach considering variability of epitopes to combat different strains: A case study using spike protein of SARS-CoV-2.

In the recent past several vaccines were developed to combat the COVID-19 disease. Unfortunately, the protective efficacy of the current vaccines has been reduced due to the high mutation rate in SARS-CoV-2. Here, we successfully implemented a coevolution based immunoinformatics approach to design an epitope-based peptide vaccine considering variability in spike protein of SARS-CoV-2. The spike glycoprotein was investigated for B- and T-cell epitope prediction. Identified T-cell epitopes were mapped on previously reported coevolving amino acids in the spike protein to introduce mutation. The non-mutated and mutated vaccine components were constructed by selecting epitopes showing overlapping with the predicted B-cell epitopes and highest antigenicity. Selected epitopes were linked with the help of a linker to construct a single vaccine component. Non-mutated and mutated vaccine component sequences were modelled and validated. The in-silico expression level of the vaccine constructs (non-mutated and mutated) in E. coli K12 shows promising results. The molecular docking analysis of vaccine components with toll-like receptor 5 (TLR5) demonstrated strong binding affinity. The time series calculations including root mean square deviation (RMSD), radius of gyration (RGYR), and energy of the system over 100 ns trajectory obtained from all atom molecular dynamics simulation showed stability of the system. The combined coevolutionary and immunoinformatics approach used in this study will certainly help to design an effective peptide vaccine that may work against different strains of SARS-CoV-2. Moreover, the strategy used in this study can be implemented on other pathogens.

Altitudinal and seasonal distribution of benthic macroinvertebrates in River Tons - a tributary of Yamuna River, Uttarakhand, India.

The main tributary of the Yamuna, the Tons River, exhibits altitudinal changes in its macroinvertebrate community's diversity, abundance, and composition. Between May 2019 and April 2021, the study was conducted in the upper section of the river. A total of 48 numbers of taxa from 34 families and ten orders were recorded during the investigation. At this elevation of 1150 to 1287 m, the two most predominant orders are Ephemeroptera (32.9%) and Trichoptera (29.5%). During the premonsoon season, they had the lowest macroinvertebrate density (250-290 individuals/m2), and the post-monsoon season had the highest density (600-640 individuals/m2). During the post-monsoon season, the maximum larval forms (60%) of various insect orders were predominant. The findings indicated that lower altitudes (1150-1232 m) have higher macroinvertebrate abundance than higher ones. The diversity of dominance is shallow at site-I (0.0738) and strong at the site-IV during the premonsoon season (0.03837). Taxa richness, as measured by the Margalef index (D), peaked in the spring season (January to March) at 6.9 and reached its lowest point (5.74) in the premonsoon season (April to May). Only 16 taxa were discovered in site-I and site-II, but 39 taxa were discovered at low altitudes (site-IV, 1100 m) (1277-1287 m). The Tons River contains a total of 12 and 13 genera, respectively, that belong to the orders Ephemeroptera and Trichoptera, according to qualitative study of the macroinvertebrates. The current study supports the use of macroinvertebrates as bioindicator species for monitoring biodiversity and assessing the health of ecosystems.

Colostrum Feeding among Newborns Visiting the Outpatient Department of Pediatrics of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Colostrum is the thick yellowish breast milk that is produced during the first 3-5 days of childbirth. Feeding colostrum protects the newborn from various diseases, thus promoting the overall well-being of the newborn. The objective of this study was to find out the prevalence of colostrum feeding among newborns visiting the Department of Pediatrics in a tertiary care centre. Methods: A descriptive cross-sectional study was done among infants presenting to the Department of Pediatrics in a tertiary care centre. Ethical approval was taken from the Institutional Review Committee (Reference number: 2078/079/107). The duration of study was six month from 12 February 2022 to 12 August 2022. A pre-designed questionnaire was used for face-to-face interviews. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 350 newborns, colostrum was fed to 305 (87.14%) (83.63-90.65, 95% Confidence Interval) newborns. A total of 180 (59.02%) were breastfed within 1 hour of delivery. Conclusions: The prevalence of colostrum feeding was higher in our study than in other studies done in similar settings. Keywords: colostrum; exclusive breastfeeding; newborns; prevalence.

Clinical profile of children with acute post-streptococcal glomerulonephritis.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is common in developing countries with a high hospitalization rate. Most patients have acute nephritic syndrome features, although some occasionally present with unusual clinical features. This study aims to describe and analyze clinical features, complications, and laboratory parameters in children diagnosed with APSGN at presentation, 4 and 12 weeks later, in a resource-limited setting. METHODS: This cross-sectional study was conducted among children < 16 years with APSGN between January 2015 and July 2022. Hospital medical records and outpatient cards were reviewed for clinical findings, laboratory parameters, and kidney biopsy results. Descriptive analysis of multiple categorical variables was performed using SPSS version 16.0 and presented as frequencies and percentages. RESULTS: The study included 77 patients. Most (94.8%) were older than five years, and age group 5-12 years had highest prevalence (72.7%). Boys were affected more frequently than girls (66.2% vs. 33.8%). Edema (93.5%), hypertension (87%), and gross hematuria (67.5%) were the most frequent presenting symptoms, and pulmonary edema (23.4%) was the most common severe complication. Anti-DNase B and anti-streptolysin O titers were positive in 86.9% and 72.7%, respectively, and 96.1% had C3 hypocomplementemia. Most clinical features resolved in three months. However, at 3 months, 6.5% of patients had persistent hypertension, impaired kidney function, and proteinuria alone or in combination. Most patients (84.4%) had an uncomplicated course; 12 underwent kidney biopsy, 9 required corticosteroids, and 1 required kidney replacement therapy. There was no mortality during the study period. CONCLUSION: Generalized swelling, hypertension, and hematuria were most common presenting features. Persistent hypertension, impaired kidney function, and proteinuria persisted in a small proportion who had a significant clinical course and required kidney biopsy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer.

Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds' anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid-lipid and liquid-lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.

Development of QSAR model using machine learning and molecular docking study of polyphenol derivatives against obesity as pancreatic lipase inhibitor.

In developed countries and developing countries, obesity/overweight is considered a major problem, in fact, it is now recognized as a major metabolic disorder. Additionally, obesity is connected with other metabolic diseases, including cardiovascular disorders, type 2 diabetes, some types of cancer, etc. Therefore, the development of novel drugs/medications for obesity is essential. The best target for treating obesity is Pancreatic Lipase (PL), it breaks 50-70% triglycerides into monoglycerol and free fatty acids.The major aim of this in silico study is to generate a QSAR model by using Multiple Linear Regression (MLR) and to inhibit pancreatic lipase by polyphenol derivatives mainly flavonoids, plant secondary metabolites shows good inhibitory activity against PL, maybe with less unpleasant side effects.In this in silico study, a potent inhibitor was found through calculating drug likness, QSAR (Quantitative structure-activity relationship) and molecular docking. The docking was performed in Maestro 12.0 and the ADME (absorption, distribution, metabolism, and excretion) properties (drug-likeness) of compounds/ligands were predicted by the Qikprop module of Maestro 12.0. The QSAR model was developed to show the relationship between the chemical/structural properties and the compound's biological activity. We have found the best interaction between pancreatic lipase and flavonoids. The best docked compound is Epigallocatechin 3,5,-di-O-gallate with docking score -10.935 kcal/mol .All compounds also show drug-likeness activity.The developed model has satisfied all internal and external validation criteria and has square correlation coefficient (r2) 0.8649, which shows its predictive ability and has good acceptability, predictive ability, and statistical robustness.Communicated by Ramaswamy H. Sarma.

Screening of the Medicines for Malaria Venture Pandemic Response Box for Discovery of Antivirulent Drug against Pseudomonas aeruginosa.

Resistance development and exhaustion of the arsenal of existing antibacterial agents urgently require an alternative approach toward drug discovery. Herein, we report the screening of Medicines for Malaria Venture (MMV) Pandemic Response Box (PRB) through a cascade developed to streamline the potential compounds with antivirulent properties to combat an opportunistic pathogen, Pseudomonas aeruginosa. To find an agent suppressing the production of P. aeruginosa virulence factors, we assessed the potential of the compounds in PRB with quorum sensing inhibitory activity. Our approach led us to identify four compounds with significant inhibition of extracellular virulence factor production and biofilm formation. This provides an opportunity to expand and redirect the application of these data sets toward the development of a drug with unexplored target-based activity. IMPORTANCE The rise of drug-resistant pathogens as well as overuse and misuse of antibiotics threatens modern medicine as the number of effective antimicrobial drugs steadily decreases. Given the nature of antimicrobial resistance development under intense selective pressure such as the one posed by pathogen-eliminating antibiotics, new treatment options which could slow down the emergence of resistance are urgently needed. Antivirulence therapy aims at suppressing a pathogen's ability to cause disease rather than eliminating it, generating significantly lower selective pressure. Quorum sensing inhibitors are thought to be able to downregulate the production of virulence factors, allowing for smaller amounts of antimicrobials to be used and thus preventing the emergence of resistance. The PRB constitutes an unprecedented opportunity to repurpose new as well as known compounds with cytotoxicity and in vitro absorption, distribution, metabolism and excretion (ADME) profile available, thus shortening the time between compound discovery and medicinal use.