Alkalimonas mucilaginosa sp. nov. and Alkalimonas cellulosilytica sp. nov. isolated from alkaline Lonar lake, India.

Two alkaliphilic, Gram-stain-negative bacterial strains (MEB004T and MEB108T) were isolated from water samples collected from Lonar lake, India. The phylogenetic analysis of their 16S rRNA gene sequences showed the highest similarity to A. delamerensis DSM 18314T (98.4%), followed by A. amylolytica DSM 18337T and A. collagenimarina JCM 14267T (97.9%). The genome sizes of strains MEB004T and MEB108T were determined to be 3,858,702 and 4,029,814 bp, respectively, with genomic DNA G + C contents of 51.4 and 51.9%. Average Nucleotide Identity, DNA-DNA Hybridization and Amino Acid Identity values between strains (MEB004T and MEB108T) and A. amylolytica DSM 18337T were (82.3 and 85.5), (25.0 and 29.2) and (86.7 and 90.2%). Both novel strains produced industrially important enzymes, such as amylase, lipase, cellulase, caseinase, and chitinase at pH 10 evidenced by the genomic presence of carbohydrate-active enzymes encoding genes. Genomic analyses further identified pH tolerance genes, affirming their adaptation to alkaline Lonar Lake. Dominant fatty acids were Summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C16:0, Summed feature 3, Sum In Feature 2 and C12:0 3OH. The prevalent polar lipids included phosphatidyl ethanolamine, phosphatidyl glycerol, and diphosphatidyl glycerol. The major respiratory quinone was ubiquinone-8. Based on the polyphasic data, we propose the classification of strains MEB004T and MEB108T as novel species within the genus Alkalimonas assigning the names Alkalimonas mucilaginosa sp. nov. and Alkalimonas cellulosilytica sp. nov., respectively. The type strains are MEB004T (= MCC 5208T = JCM 35954T = NCIMB 15460T) and MEB108T (= MCC 5330T = JCM 35955T = NCIMB 15461T).

Meningothelial hamartoma of scalp mimicking encephalocele in an infant: A case report and review of literature.

ABSTRACT: An extremely rare benign lesion of the scalp is reported in a 2-month-old infant. The lesion had been present since birth. On examination, a 3 × 4 cm skin-colored soft mass over the occipital midline area was observed. On ultrasound, a diagnosis of occipital encephalocele was suggested. A complete excision of the mass was performed. Histological examination showed a subcutaneous lesion, which showed haphazardly arranged epithelioid cell nests admixed with connective tissue components, adipose tissues, and pseudovascular patterns within the deep dermis. Immunohistochemistry showed positive expression of Epithelial membrane antigen (EMA) and Vimentin. Tumor cells showed negative expression for Glial Fibrillary acidic protein (GFAP), chromogranin, S-100, Smooth muscle actin (SMA), and CD 34. Based on the clinical presentation, histologic features, and results of ancillary studies, a diagnosis of meningothelial hamartoma of the scalp was given. The clinical behavior of this lesion is benign but it often causes diagnostic confusion and may mimic malignant tumors. It is crucial to recognize the main features of this lesion.

Impact of Implementing Paris System on Diagnostic Precision and Management of Urinary Bladder Neoplasms.

The diagnosis of atypia has always been under question both by the pathologist and the clinician. It was one of the main aims of the Paris system (TPS) to reduce the number of cases under the AUC (Atypical urothelial cells) category. With the strict criteria laid down by the Paris system, the rate of diagnosis of this category has reduced markedly. This study was done to test the impact of implementing TPS categories and criteria in comparison to our previously used system. TPS is one of the important deciding factors for the management of the patient. The management of patients with AUC diagnosis often varies depending on the treating physician (urologist/nonurologist). For further categorization of the diagnosis of AUC, markers like p53 and Ki67 can be used. One hundred urinary cytology specimens received for the period of 6 months were included in the study. The presentation of the categorical variables was done in the form of numbers and percentages (%). Interrater kappa agreement was used to find out the strength of the agreement between the Paris system and the traditional system. Using histopathological diagnosis as the gold standard, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic accuracy were calculated. Immunohistochemistry was performed on the cell block for Ki67 and p53, and their values were correlated with histopathological examination, using Spearman's rank correlation. The interrater kappa agreement analyzed between the traditional reporting system and the Paris system was 0.522. Around 32% (6/19) of cases that were reported as AUC by the traditional system were recategorized under negative for high-grade urothelial carcinoma (NHGUC) by the Paris system. Thus, obliviating the need for further management and decreasing the unnecessary cost of the health care system with a decrease in patient anxiety. Histopathology was available in 28 cases and diagnostic accuracy of urine cytology classified by TPS was 89.2% with a sensitivity of 94.4%, specificity of 80%, positive likelihood ratio of 89.4, and negative likelihood ratio of 88.6. The correlation coefficient of p53 with grading of carcinoma was found to be strong at 0.864. The correlation coefficient of Ki67 with grading of carcinoma was also as strong as 0.885. TPS along with immunohistochemistry improves the performance of urine cytology by reclassifying the AUC category into other groups and increases the sensitivity for detecting HGUC.

Ureibacillus aquaedulcis sp. nov., isolated from freshwater well and reclassification of Lysinibacillus yapensis and Lysinibacillus antri as Ureibacillus yapensis comb. nov. and Ureibacillus antri comb. Nov.

A Gram-stain-positive aerobic, rod-shaped, spore-producing bacterium forming colonies with convex elevation and a smooth, intact margin was isolated from a freshwater sample collected from a well situated in an agricultural field. The 16S rRNA gene sequence of the isolated strain BA0131T showed the highest sequence similarity to Lysinibacillus yapensis ylb-03T (99.25%) followed by Ureibacillus chungkukjangi 2RL3-2T (98.91%) and U. sinduriensis BLB-1T (98.65%). The strain BA0131T was oxidase and catalase positive and urease negative. It also tested positive for esculin hydrolysis and reduction of potassium nitrate, unlike its phylogenetically closest relatives. The predominant fatty acids in strain BA0131T included were anteiso-C15:0, iso-C16:0, iso-C15:0, iso-C14:0 and the major polar lipids comprised were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The respiratory quinones identified in strain BA0131T were MK8 (H2) (major) and MK8 (minor). The strain BA0131T shared the lowest dDDH values with L. yapensis ylb-03T (21%) followed by U. chungkukjangi 2RL3-2T (24.2%) and U. sinduriensis BLB-1T (26.4%) suggesting a closer genetic relationship U. sinduriensis BLB-1T. The ANI percentage supported the close relatedness with U. sinduriensis BLB-1T (83.61%) followed by U. chungkukjangi 2RL3-2T (82.03%) and U. yapensis ylb-03T (79.57%). The core genome-based phylogeny constructed using over 13,704 amino acid positions and 92 core genes revealed the distinct phylogenetic position of strain BA0131T among the genus Ureibacillus. The distinct physiological, biochemical characteristics and genotypic relatedness data indicate the strain BA0131T represents a novel species of the genus Ureibacillus for which the name Ureibacillus aquaedulcis sp. nov. (Type strain, BA0131T = MCC 5284 = JCM 36475) is proposed. Additionally, based on extensive genomic and phylogenetic analyses, we propose reclassification of two species, L. yapensis and L. antri, as U. yapensis comb. nov. (Type strain, ylb-03T = JCM 32871T = MCCC 1A12698T) and U. antri (Type strain, SYSU K30002T = CGMCC 1.13504T = KCTC 33955T).

Risk assessment of trace elements in vegetables grown in river Yamuna floodplain in Delhi.

Urban agriculture is common in fertile river floodplains of many developing countries. However, there is a risk of contamination in highly polluted regions. This study quantifies health risks associated with the consumption of vegetables grown in the floodplain of the urban river 'Yamuna' in the highly polluted yet data-scarce megacity Delhi, India. Six trace elements are analyzed in five kinds of vegetable samples. Soil samples from the cultivation area are also analyzed for elemental contamination. Ni, Mn, and Co are observed to be higher in leafy vegetables than others. Fruit and inflorescence vegetables are found to have higher concentrations of Cr, Pb, and Zn as compared to root vegetables. Transfer Factor indicates that Cr and Co have the highest and least mobility, respectively. Vegetable Pollution Index indicates that contamination levels follow as Cr > Ni > Pb > Zn. Higher Metal Pollution Index of leafy and inflorescence vegetables than root and fruit vegetables indicate that atmospheric deposition is the predominant source. Principal Component Analysis indicates that Pb and Cr have similar sources and patterns in accumulation. Among the analyzed vegetables, radish may pose a non-carcinogenic risk to the age group of 1-5 year. Carcinogenic risk is found to be potentially high due to Ni and Cr accumulation. Consumption of leafy vegetables was found to have relatively less risk than other vegetables due to lower Cr accumulation. Remediation of Cr and Ni in floodplain soil and regular monitoring of elemental contamination is a priority.

Tobacco Imagery in Movies and Web Series Streaming in India and Their Compliance With the Recent Anti-tobacco Rules for Over-the-Top (OTT) Platforms.

INTRODUCTION: Internet access, smartphones, and televisions have significantly boosted over-the-top (OTT) movies and web series viewing in India, especially among youths. Despite restrictions, OTT platforms continue to promote tobacco products. India has recently enforced the revised OTT Rules 2023 effective September 1, 2023, to counter tobacco promotion in OTT shows. This study explores compliance with the OTT Rules 2023 in popular movies and web series on select OTT platforms in India. METHODS: About 29 movies and 31 web series from seven popular OTT platforms as of September 26, 2023, were analyzed in this study. The incidence of tobacco imagery and compliance with the OTT Rules 2023 were assessed using a standardized format with the help of seven trained coders. Descriptive statistics were used to describe instances of tobacco imagery and violations of the provisions of Indian law. RESULTS: The average incidence of tobacco imagery per included show was 3.95. None of the movies and web series fully complied with the provisions of health spots and audio-visual warnings. Only 35.7% of the shows (movies: 57.1%, web series: 14.3%) fully complied with the anti-tobacco static message provisions. The foreign-origin movies had zero compliance with static messages, though they had fewer tobacco images. Half of the shows for children up to 12 years old had tobacco imagery but fully complied with the static warning message provisions. CONCLUSION: The portrayal of tobacco imagery in OTT shows is prevalent, and their poor compliance with the OTT Rules 2023 is a concern. Therefore, monitoring and stricter enforcement of the OTT Rules should be given priority to protect viewers from tobacco promotion in OTT shows.

A slight degree of osteoarthritis appears to be present after anterior cruciate ligament reconstruction compared with contralateral healthy knees at a minimum of 20 years: A systematic review of the literature.

Purpose: The aim of the present systematic review was to quantitatively synthesize the best literature evidence regarding osteoarthritis developing after anterior cruciate ligament reconstruction (ACLR), including only studies with a follow-up duration of at least 20 years. Material and Methods: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on four electronic databases (PubMed, Scopus, EMBASE and Cochrane Library). The outcome measures extracted from the studies were failure rate, subsequent knee surgery on the same knee, radiographic development of osteoarthritis measured with Kellgren-Lawrence, International Knee Documentation Committee (IKDC) radiographic score and Ahlbäck classification. The health of both the ACLR knee and the contralateral knee was compared. Results: A total of 1552 patients were included in the study, of which 1290 (83.11%) were operated on using a patellar tendon graft, 190 (12.24%) with hamstrings, 27 (1.73%) with an iliotibial band and 45 (2.89%) with patellar tendon plus a ligament augmentation device (LAD). The mean age at the time of surgery was 25.18 ± 1.91 years, and the mean follow-up time was 23.34 ± 2.56 years. Analysing IDKC Score at final follow-up, ACLR Group showed a higher degree of OA compared with contralateral healthy knee (p < 0.01), but only 33.2% (324/976) of the patients showed a moderate to severe degree (Grade C or D) of osteoarthritis, while for Kellgren-Lawrence, ACLR Group showed a higher degree of OA compared with contralateral healthy knee (p < 0.01), but only 28.9% (196/678) of the patients showed a moderate to severe degree (Grade III or IV) of osteoarthritis. In total, 1552 patients were registered, 155 reruptures (9.98%) and a total of 300 (19.3%) new surgeries, of which 228 meniscectomy (14.69%), 21 (1.35%) knee arthroplasty and 17 (1.09%) hardware removal were recorded. Conclusions: ACL reconstruction appears to result in mild osteoarthritis in the long term in most of the patients and only less than 33.2% develop a moderate to severe degree of knee OA according to IKDC radiographic score. A slight degree of osteoarthritis appears to be present in ACLR knees compared with contralateral healthy knees. Level of Evidence: Level IV.

Quercetin prophylaxis protects the kidneys by modulating the renin-angiotensin-aldosterone axis under acute hypobaric hypoxic stress.

The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.

Draft genome sequence of 'Candidatus Phytoplasma asteris,' strain SW86 associated with sandal spike disease (SSD).

The sandal spike disease (SSD), related to 'Ca. Phytoplasma asteris' (Aster Yellows group), poses a significant threat to Indian sandalwood (Santalum album L.), making it the second most expensive wood globally due to declining population density. The epidemiology of SSD and the nature of the pathogen remain poorly understood. The SW86 isolate, collected from the Marayoor Sandalwood Reserve, was chosen for genome sequencing subsequent to confirming its titer and enriching phytoplasma DNA. Genome sequencing, utilizing Illumina and Oxford Nanopore Technology platforms, enabled a targeted hybrid metagenomic assembly resulting in 20 scaffolds totaling 554,025 bp, housing 436 protein-coding genes, 27 tRNA, and 1 rRNA operon. The genome analysis highlighted specific gene distributions, emphasizing translation, ribosomal structure, and biogenesis, with 352 genes assigned to 18 functional categories. Additionally, 322 proteins received functional assignments in the KEGG database, emphasizing 'Genetic Information Processing' and 'Environmental Information Processing'. Key potential pathogenicity factors, including signal peptide proteins and virulence proteins, were identified. Noteworthy findings include homologs of effectors genes like SAP11 and SAP05 and pathogenesis-related proteins, such as hemolysin III and SodA genes, in the SW86 genome. The duplicated cation-transporting P-type ATPase in the SW86 genome suggests a role in enhancing adaptability and contributing to the severity of SSD symptoms. This genome analysis provides crucial insights into the genomic features and potential virulence factors of 'Ca. Phytoplasma asteris' strain SW86, advancing our understanding of pathogenicity mechanisms and offering avenues for future disease management strategies in Indian sandalwood. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03952-5.

A rare urinary tract infection of multidrug-resistant Chryseobacterium urinae sp. nov. isolated from a diabetic, non-catheterized patient.

Chryseobacterium demonstrates a diverse environmental presence and a significant pathogenic potential across various ecosystems. This clinical case showcases a rare instance of bacterial infection in a 75-year-old male with untreated diabetes and recurrent urinary tract infections (UTIs). The patient presented symptoms of abdominal pain, burning urination, fever, and an elevated eosinophil count. A subsequent urine culture identified a Chryseobacterium-related bacterium as the causative agent, exhibiting sensitivity to piperacillin/tazobactam, trimethoprim/sulfamethoxazole, and nitrofurantoin, which led to successful treatment using oral nitrofurantoin. Analysis of the 16S rRNA gene sequence of APV-1T revealed a close relationship of 98.2% similarity to Chryseobacterium gambrini strain 5-1St1aT (AM232810). Furthermore, comparative genome analysis, incorporating Average Nucleotide Identity (ANI), Digital DNA-DNA Hybridization (dDDH) values, and comprehensive phylogenetic assessments utilizing 16S rRNA gene sequences, core genes, and amino acid sequences of core proteins, highlighted the unique phylogenetic positioning of APV-1T within the Chryseobacterium genus. Distinct carbon utilization and assimilation patterns, along with major fatty acid content, set APV-1T apart from C. gambrini strain 5-1St1aT. These findings, encompassing phenotypic, genotypic, and chemotaxonomic characteristics, strongly support the proposal of a novel species named Chryseobacterium urinae sp. nov., with APV-1T designated as the type strain (= MCC 50690 = JCM 36476). Despite its successful treatment, the strain displayed resistance to multiple antibiotics. Genomic analysis further unveiled core-conserved genes, strain-specific clusters, and genes associated with antibiotic resistance and virulence. This report underscores the vital importance of elucidating susceptibility patterns of rare pathogens like Chryseobacterium, particularly in immunocompromised individuals. It advocates for further analyses to understand the functional significance of identified genes and their implications in treatment and pathogenesis.

The Emerging Role of Non-Coding RNAs (ncRNAs) in Plant Growth, Development, and Stress Response Signaling.

Plant species utilize a variety of regulatory mechanisms to ensure sustainable productivity. Within this intricate framework, numerous non-coding RNAs (ncRNAs) play a crucial regulatory role in plant biology, surpassing the essential functions of RNA molecules as messengers, ribosomal, and transfer RNAs. ncRNAs represent an emerging class of regulators, operating directly in the form of small interfering RNAs (siRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). These ncRNAs exert control at various levels, including transcription, post-transcription, translation, and epigenetic. Furthermore, they interact with each other, contributing to a variety of biological processes and mechanisms associated with stress resilience. This review primarily concentrates on the recent advancements in plant ncRNAs, delineating their functions in growth and development across various organs such as root, leaf, seed/endosperm, and seed nutrient development. Additionally, this review broadens its scope by examining the role of ncRNAs in response to environmental stresses such as drought, salt, flood, heat, and cold in plants. This compilation offers updated information and insights to guide the characterization of the potential functions of ncRNAs in plant growth, development, and stress resilience in future research.

Granular Hemostatic Composite of Alginate, Calcium, and Zinc for Rapid and Effective Management of Post-Traumatic Hemorrhage.

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca2+ and Zn2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo. The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.

A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.

Fictibacillus fluitans sp. nov., isolated from freshwater pond.

A Gram-positive, aerobic, rod-shaped, spore-forming bacterium, designated NE201T, was isolated from a freshwater pond in Village Nerur, India. Growth was observed in the range of 15-45 °C temperature with optimum at 30 °C, pH range of 5-9 (optimum at 7.0), and at concentrations of NaCl ranging between 0 and 14% (optimum 0%, w/v). The 16S rRNA gene sequence showed the highest similarity with Fictibacillus enclensis NIO-1003T (JF893461) at 99.01% followed by F. rigui WPCB074T (EU939689) at 98.9% and F. solisalsi CGMCC 1.6854T (EU046268) at 98.66%. The digital DNA-DNA hybridization (dDDH) and orthoANI values for strain NE201T against F. enclensis NIO-1003T (GCA_900094955.1) were 33.7% and 87.68%, respectively. The phylogenetic analysis based on the 16S rRNA gene, 92 core genes derived from the genome, and 20 proteins involving over 20,236 amino acid positions revealed the distinct phylogenetic position of strain NE201T and the formation of a clearly defined monophyletic clade with F. enclensis. The strain NE201T showed a unique carbon utilization and assimilation pattern that differentiated it from F. enclensis NIO-1003T. The major fatty acids were anteiso -C15:0 (51.42%) and iso-C15:0 (18.88%). The major polar lipids were phosphatidylglycerol (PG), phosphatidylethanolamine (PE, and diphosphatidylglycerol (DPG). The antiSMASH analyzed genome of NE201T highlighted its diverse biosynthetic potential, unveiling regions associated with terpene, non-ribosomal peptide synthetases (NRPS), lassopeptides, NI-siderophores, lanthipeptides (LAP), and Type 3 Polyketide Synthases (T3PKS). The overall phenotypic, genotypic, and chemotaxonomic characters strongly suggested that the strain NE201T represents a novel species of genus Fictibacillus for which the name Fictibacillus fluitans sp. nov. is proposed. The type strain is NE201T (= MCC 5285 = JCM 36474).

PgxSAVy: A tool for comprehensive evaluation of variant peptide quality in proteogenomics - catching the (un)usual suspects.

Variant peptides resulting from single nucleotide polymorphisms (SNPs) can lead to aberrant protein functions and have translational potential for disease diagnosis and personalized therapy. Variant peptides detected by proteogenomics are fraught with high number of false positives, but there is no uniform and comprehensive approach to assess variant quality across analysis pipelines. Despite class-specific FDR along with ad-hoc filters, the problem is far from solved. These protocols are typically manual and tedious, and thus not uniform across labs. We demonstrate that variant peptide rescoring, integrated with intensity, variant event information and search result features, allows better discrimination of correct variant peptides. Implemented into PgxSAVy - a tool for quality control of variant peptides, this method can tackle the high rate of false positives. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy demonstrated high accuracy by identifying true variants with 98.43% accuracy on simulated data. Large-scale proteogenomic reanalysis of ∼2.8 million spectra (PXD004010 and PXD001468) resulted in 12,705 variant peptide spectrum matches (PSMs), of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants. PgxSAVy is freely available at https://pgxsavy.igib.res.in/ as a webserver and https://github.com/anuragraj/PgxSAVy as a stand-alone tool.

Poly(d,l-lactide-co-glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer.

A poly(d,l-lactide-co-glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance-Fourier transform infrared, 1H and 13C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log p < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers' nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin.

Nano-modified screen-printed electrode-based electrochemical immunosensors for oral cancer biomarker detection in undiluted human serum and saliva samples.

This proposed work reports the development of in-house made conductive ink-based screen-printed electrodes (SPEs) for label-free detection of oral cancer biomarkers. Carbon ink synthesis includes graphite powder, gum arabic, and water. The selectivity test of the fabricated SPE involves immobilizing antibodies specific to biomarkers and challenges with redox-active interference, other serum molecules, and non-target biomarkers. Three different biomarkers, cytokeratin-19 fragment (CYFRA 21-1), interleukin 8 (IL-8), and tumor protein p53 (TP-53), act as target entities for the detection of oral cancer in patients' samples (serum, N = 28, and saliva, N = 16) at an early stage. The standard technique enzyme-linked immunosorbent assay (ELISA) was employed to estimate the concentration of the biomarkers in serum and saliva samples. SPEs contain amine (-NH2) functional groups involved in covalent bonding with the carboxyl (-COOH) groups of antibody molecules. These immunosensors exhibited remarkably lower detection limits of 829.5 pg mL-1, 0.543 pg mL-1, and 1.165 pg mL-1, and excellent sensitivity of 0.935 µA mL pg-1 cm-1, 0.039 µA mL pg-1 cm-1, and 0.008 µA mL pg-1 cm-1 for CYFRA 21-1, IL-8, and TP-53 biomarkers, respectively. This sensing platform does not require any functionalization for biomolecule immobilization. Thus, it is a cost-effective, disposable, flexible, miniaturized, and sensitive strip to detect oral cancer biomarkers.