Deciphering the Mechanisms and Biotechnological Implications of Nanoparticle Synthesis Through Microbial Consortia.

Nanomaterial synthesis is a growing study area because of its extensive range of uses. Nanoparticles' high surface-to-volume ratio and rapid interaction with various particles make them appealing for diverse applications. Traditional physical and chemical methods for creating metal nanoparticles are becoming outdated because they involve complex manufacturing processes, high energy consumption, and the formation of harmful by-products that pose major dangers to human health and the environment. Therefore, there is an increasing need to find alternative, cost-effective, dependable, biocompatible, and environmentally acceptable ways of producing nanoparticles. The process of synthesizing nanoparticles using microbes has become highly intriguing because of their ability to create nanoparticles of varying sizes, shapes, and compositions, each with unique physicochemical properties. Microbes are commonly used in nanoparticle production because they are easy to work with, can use low-cost materials, such as agricultural waste, are cheap to scale up, and can adsorb and reduce metal ions into nanoparticles through metabolic activities. Biogenic synthesis of nanoparticles provides a clean, nontoxic, ecologically friendly, and sustainable method using renewable ingredients for reducing metals and stabilizing nanoparticles. Nanomaterials produced by bacteria can serve as an effective pollution control method due to their many functional groups that can effectively target contaminants for efficient bioremediation, aiding in environmental cleanup. At the end of the paper, we will discuss the obstacles that hinder the use of biosynthesized nanoparticles and microbial-based nanoparticles. The paper aims to explore the sustainability of microorganisms in the burgeoning field of green nanotechnology.

Current status of the biliary tract malformation.

The choledochal cyst (CC) can be better termed as biliary tract malformation because of the close association of embryology and etiology in the causation of CC. Contrary to Babbitt's postulation of reflux, damage and dilatation, reflux was not demonstrable as the causative factor in all varieties of CC. High pressure in the biliary system, otherwise termed ductal hypertension, is put forth as an alternative to explain the evolution of CC. The forme fruste type, which does not find a place in the standard classification, typifies the ductal hypertension hypothesis. Hence a closer, in-depth review would be able to highlight this apt terminology of biliary tract malformation.

16S rRNA based metagenomic analysis unveils unique oral microbial signatures in oral squamous cell carcinoma cases from Coastal Karnataka, India.

Oral Squamous cell carcinoma (OSCC) is the 14th most frequent cancer with 300,000 new cases and 100,000 deaths reported annually. Even with advanced therapy, the treatment outcomes are poor at advanced stages of the disease. The diagnosis of early OSCC is of paramount clinical value given the high mortality rate associated with the late stages of the disease. Recently, the role of microbiome in the disease manifestation, including oral cancer, has garnered considerable attention. But, to establish the role of bacteria in oral cancer, it is important to determine the differences in the colonization pattern in non-tumour and tumour tissues. In this study, 16S rRNA based metagenomic analyses of 13 tumorous and contralateral anatomically matched normal tissue biopsies, obtained from patients with advanced stage of OSCC were evaluated to understand the correlation between OSCC and oral microbiome. In this study we identified Fusobacterium, Prevotella, Capnocytophaga, Leptotrichia, Peptostreptococcus, Parvimonas and Bacteroidetes as the most significantly enriched taxa in OSCC lesions compared to the non-cancerous tissues. Further, PICRUSt2 analysis unveiled enhanced expression of metabolic pathways associated with L-lysine fermentation, pyruvate fermentation, and isoleucine biosynthesis in those microbes associated with OSCC tissues. These findings provide valuable insights into the distinctive microbial signatures associated with OSCC, offering potential biomarkers and metabolic pathways underlying OSCC pathogenesis. While our focus has primarily centred on microbial signatures, it is essential to recognize the pivotal role of host factors such as immune responses, genetic predisposition, and the oral microenvironment in shaping OSCC development and microbiome composition.

A µ-opioid receptor modulator that works cooperatively with naloxone.

The µ-opioid receptor (µOR) is a well-established target for analgesia1, yet conventional opioid receptor agonists cause serious adverse effects, notably addiction and respiratory depression. These factors have contributed to the current opioid overdose epidemic driven by fentanyl2, a highly potent synthetic opioid. µOR negative allosteric modulators (NAMs) may serve as useful tools in preventing opioid overdose deaths, but promising chemical scaffolds remain elusive. Here we screened a large DNA-encoded chemical library against inactive µOR, counter-screening with active, G-protein and agonist-bound receptor to 'steer' hits towards conformationally selective modulators. We discovered a NAM compound with high and selective enrichment to inactive µOR that enhances the affinity of the key opioid overdose reversal molecule, naloxone. The NAM works cooperatively with naloxone to potently block opioid agonist signalling. Using cryogenic electron microscopy, we demonstrate that the NAM accomplishes this effect by binding a site on the extracellular vestibule in direct contact with naloxone while stabilizing a distinct inactive conformation of the extracellular portions of the second and seventh transmembrane helices. The NAM alters orthosteric ligand kinetics in therapeutically desirable ways and works cooperatively with low doses of naloxone to effectively inhibit various morphine-induced and fentanyl-induced behavioural effects in vivo while minimizing withdrawal behaviours. Our results provide detailed structural insights into the mechanism of negative allosteric modulation of the µOR and demonstrate how this can be exploited in vivo.

Exploring Advancements in Early Detection of Alzheimer's Disease with Molecular Assays and Animal Models.

Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aß) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aß drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aß plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease.

Removal enhancement of persistent basic fuchsin dye from wastewater using an eco-friendly, cost-effective Fenton process with sodium percarbonate and waste iron catalyst.

In this comprehensive investigation, we evaluate the efficacy of the Fenton process in degrading basic fuchsin (BF), a resistant dye. Our primary focus is on the utilization of readily available, environmentally benign, and cost-effective reagents for the degradation process. Furthermore, we delve into various operational parameters, including the quantity of sodium percarbonate (SPC), pH levels, and the dimensions of waste iron bars, to optimize the treatment efficiency. In the course of our research, we employed an initial SPC concentration of 0.5 mM, a pH level of 3, a waste iron bar measuring 3.5 cm in length and 0.4 cm in diameter, and a processing time of 10 min. Our findings reveal the successful elimination of the BF dye, even when subjected to treatment with diverse salts and surfactants under elevated temperatures and acidic conditions (pH below 3). This underscores the robustness of the Fenton process in purifying wastewater contaminated with dye compounds. The outcomes of our study not only demonstrate the efficiency of the Fenton process but highlight its adaptability to address dye contamination challenges across various industries. Critically, this research pioneers the application of waste iron bars as a source of iron in the Fenton reaction, introducing a novel, sustainable approach that enhances the environmental and economic viability of the process. This innovative use of recycled materials as catalysts represents a significant advancement in sustainable chemical engineering practices.

Synergistic effects of covalently coupled eosin-Y with Ben-graphitic carbon nitride framework for improved photocatalytic activity in solar light-driven Biginelli product generation and NADH regeneration.

Elevated global pollution level is the prime reason that contributes to the onset of various harmful health diseases. The products of Biginelli reaction are enormously used in the pharmaceutical industry as they have antiviral, antibacterial, and calcium channel modulation abilities. This work reports a novel eosin Y sensitized boron graphitic carbon nitride (EY-Ben-g-C3N4) as a photocatalyst that efficiently produced 3,4-dihydropyrimidine-2-(1H)-one by the Biginelli reaction of benzaldehyde, urea, and methyl acetoacetate. The photocatalyst EY-Ben-g-C3N4 showed a successful generation of 3,4-dihydropyrimidine-2-(1H)-one (Biginelli product) in good yield via photocatalysis which is an eco-friendly method and has facile operational process. In addition to the production of Biginelli products, the photocatalyst also showed a remarkable NADH regeneration of 81.18%. The incorporation of g-C3N4 with boron helps increase the surface area and the incorporation of eosin Y which is an inexpensive and non-toxic dye, and in Ben-g-C3N4, enhanced the light-harvesting capacity of the photocatalyst. The production of 3,4-dihydropyrimidine-2-(1H)-one and NADH by the EY-Ben-g-C3N4 photocatalyst is attributed to the requisite band gap, high molar absorbance, low rate of charge recombination, and increased capacity of the photocatalyst to harvest solar light energy.

Declining Trend in Antimicrobial Sensitivity in Respiratory Tract Bacterial Pathogens against Commonly Used Drugs at a Tertiary Care Hospital.

OBJECTIVES: Antimicrobial resistance (AMR) is a major health issue. To determine trends in bacterial organisms in respiratory tract infections (RTIs) and their antibiotic sensitivity at a tertiary care center in India, we performed this study. METHODS: Successive samples received from January 2017 to December 2021 from the respiratory tract (sputum, endotracheal secretion, and bronchoalveolar lavage) from intensive care units and medical inpatients were processed for bacterial growth. The identification of isolates and antibiotic sensitivity patterns was performed using an automated VITEK-2 system. Descriptive statistics are reported. RESULTS: We received 7,204 respiratory samples. Significant bacterial growth was in 3,000 (41.6%), and 2,992 (41.5%) were gram-negative. Klebsiella pneumoniae was the most prevalent, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Enterobacter aerogenes. Increasing secular trends were observed for Klebsiella and Pseudomonas and declining trends for Acinetobacter and Escherichia (p < 0.05). Antimicrobial sensitivity patterns showed that Klebsiella, Pseudomonas, Acinetobacter, E. coli, and Enterobacter had a high sensitivity with colistin and polymyxin (99-100%). Moderate sensitivity was observed with carbapenems (Acinetobacter: 47.5%, Enterobacter: 62.0%, Escherichia: 76.5%, Klebsiella: 72.3%, Pseudomonas: 66.7%) and tigecycline (Acinetobacter: 50.4%, Enterobacter: 68.0%, Escherichia: 81.1%, Klebsiella: 66.6%, Pseudomonas: 0%). Aminoglycosides had <50% sensitivity for various organisms, and <25% sensitivity was observed with third-generation cephalosporins and quinolones. Trend analysis showed persistent sensitivity of various pathogenic bacteria to colistin and polymyxin and declining pharmacological sensitivity in Acinetobacter (carbapenems and tigecycline), Escherichia (carbapenems, quinolones, and tigecycline), Klebsiella (carbapenems, quinolones, aminoglycosides, and tigecycline), and Pseudomonas (carbapenems and aminoglycosides) species (p < 0.05). CONCLUSION: Common respiratory tract gram-negative bacterial pathogens at a tertiary care hospital are K. pneumoniae, P. aeruginosa, A. baumannii, and E. coli. All these bacteria demonstrate high sensitivity only with colistin and polymyxin. Significant AMR is observed to carbapenems, tigecycline, aminoglycosides, and third-generation cephalosporins. Secular trends show declining antimicrobial sensitivity among various bacterial pathogens.

Correlation of behavioral and psychological symptoms of dementia with patients' sociodemographic & clinical details and caregivers' distress.

Background: Behavioral and psychological symptoms of dementia (BPSD) influence dementia care significantly. BPSD can be affected by factors related to the patient's illness and socio-cultural background. Aim: This study aimed to find a relationship between BPSD with patients' socio-demographic and clinical profiles and their caregivers' distress in a tertiary care center. Materials and Methods: In this hospital-based cross-sectional study, the purposive sampling technique was used to select 100 dementia patients. A comprehensive record of socio-demographic and clinical details was made on a self-prepared semi-structured data sheet. The Neuropsychiatric Inventory Questionnaire was the principal tool to find the BPSD and related caregivers' distress. Results: The sample comprised predominantly Hindu (91%) male patients (66%) with Alzheimer's dementia (76%) coming from rural backgrounds (74%) and joint familial systems (96%), with a mean age of 71.77 ± 7.41 years. Patients' main caregivers were their children/children-in-law (65%). The severity of an overall BPSD and its variable individual domains were directly related to the duration of dementia, patients' age, their cognitive decline, and related decline in activities of living, as well as their caregivers' distress. In comparison to Alzheimer's disease patients, those with other dementia types had more impairment in cognitive functions and activities of daily living and they had a higher number and severity of BPSD. Conclusion: The advancing age, increased duration of dementia, and decline in cognition and related activities of daily living of the patients, as well as their caregivers' distress, are important correlates of BPSD. The findings are essential for the better management of dementia patients.

Isoptericola haloaureus sp. nov., a dimorphic actinobacterium isolated from mangrove sediments of southeast India, implicating biosaline agricultural significance through nitrogen fixation and salt tolerance genes.

Strain MP-1014T, an obligate halophilic actinobacterium, was isolated from the mangrove soil of Thandavarayancholanganpettai, Tamil Nadu, India. A polyphasic approach was utilized to explore its phylogenetic position completely. The isolate was Gram-positive, filamentous, non-motile, and coccoid in older cultures. Ideal growth conditions were seen at 30 °C and pH 7.0, with 5% NaCl (W/V), and the DNA G + C content was 73.3%. The phylogenic analysis of this strain based upon 16S rRNA gene sequence revealed 97-99.8% similarity to the recognized species of the genus Isoptericola. Strain MP-1014T exhibits the highest similarity to I. sediminis JC619T (99.7%), I. chiayiensis KCTC19740T (98.9%), and subsequently to I. halotolerans KCTC19646T (98.6%), when compared with other members within the Isoptericola genus (< 98%). ANI scores of strain MP-1014T are 86.4%, 84.2%, and 81.5% and dDDH values are 59.7%, 53.6%, and 34.8% with I. sediminis JC619T, I. chiayiensis KCTC19740T and I. halotolerans KCTC19646T respectively. The major polar lipids of the strain MP-1014T were phosphatidylinositol, phosphatidylglycerol, diphosphotidylglycerol, two unknown phospholipids, and glycolipids. The predominant respiratory menaquinones were MK9 (H4) and MK9 (H2). The major fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C14:0, C15:0, and C16:0. Also, initial genome analysis of the organism suggests it as a biostimulant for enhancing agriculture in saline environments. Based on phenotypic and genetic distinctiveness, the strain MP-1014 T represents the novel species of the genus Isoptericola assigned Isoptericola haloaureus sp. nov., is addressed by the strain MP-1014 T, given its phenotypic, phylogenetic, and hereditary uniqueness. The type strain is MP-1014T [(NCBI = OP672482.1 = GCA_036689775.1) ATCC = BAA 2646T; DSMZ = 29325T; MTCC = 13246T].

Variety-dependent responses of common tobacco with differential cadmium resistance: Cadmium uptake and distribution, antioxidative activity, and gene expression.

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.

Mimosa/quince seed mucilage-co-poly (methacrylate) hydrogels for controlled delivery of capecitabine: Simulation studies, characterization and toxicological evaluation.

This research focused on developing pH-regulated intelligent networks using quince and mimosa seed mucilage through aqueous polymerization to sustain Capecitabine release while overcoming issues like short half-life, high dosing frequency, and low bioavailability. The resulting MSM/QSM-co-poly(MAA) hydrogel was evaluated for several parameters, including complex structure formation, stability, pH sensitivity, morphology, and elemental composition. FTIR, DSC, and TGA analyses confirmed the formation of a stable, complex cross-linked network, demonstrating excellent stability at elevated temperatures. SEM analysis revealed the hydrogels' smooth, fine texture with porous surfaces. PXRD and EDX results indicated the amorphous dispersion of Capecitabine within the network. The QMM9 formulation achieved an optimal Capecitabine loading of 87.17 %. The gel content of the developed formulations ranged from 65.21 % to 90.23 %. All formulations exhibited excellent swelling behavior, with ratios between 65.91 % and 91.93 % at alkaline pH. In vitro dissolution studies indicated that up to 98 % of Capecitabine was released after 24 h at pH 7.4, demonstrating the potential for sustained release. Furthermore, toxicological evaluation in healthy rabbits confirmed the system's safety, non-toxicity, and biocompatibility.

Liquid phase selective oxidation of veratryl alcohol to veratraldehyde using pure and Mg-doped copper chromite catalysts.

Mg-doped copper chromite (CuCr2O4) nanocomposites were synthesised through conventional technique. The pure and doped CuCr2-xMgx O4 (x = 0.00-0.1, 0.2 and 0.3%) nanocomposites were characterized in terms of their morphology, crystal structure, surface area and catalytic performance. The chemical composition of CuCr2-xMgx O4 was confirmed via FT-IR. The formation of pure and doped catalysts was validated by XRD results. TEM/SEM confirmed the formation of CuCr2-xMgxO4 nanoparticles. Mg-doped samples possess a high specific surface area compared to pure CuCr2O4. Thus, the effects of temperature, solvent, time, oxidant and the amount of catalyst on the oxidation of veratryl alcohol were reported. Furthermore, detailed mechanisms of the catalytic oxidation of veratryl alcohol as well as the reusability and stability of the nanomaterial were investigated. The resulting composites were shown to be effective heterogeneous catalysts for the oxidation of veratryl alcohol.

Investigating lactic acid bacteria genus Lactococcus lactis properties: Antioxidant activity, antibiotic resistance, and antibacterial activity against multidrug-resistant bacteria Staphylococcus aureus.

Background: Lactic acid bacteria (LAB) are utilized as a starter culture in the manufacturing of fermented dairy items, as a preservative for various food products, and as a probiotic. In our country, some research has been carried out, even if LAB plays a principal role in food preservation and improves the texture and taste of fermented foods, that is why we tried to evaluate their probiotic effect. The objective of this research was to determine the antibacterial activity of Lactococcus lactis (L. lactis) against Staphylococcus aureus (S. aureus) ATCC 29213, investigate their antioxidant activity, and characterize their sensitivity against 18 antibiotics. Methods: A total of 23 LAB (L. lactis subsp. cremoris, L. lactis subsp. Lactis diacetylactis, L. lactis subsp. lactis) were isolated from cow's raw milk. The antibacterial activity was performed using two techniques, competition for nutrients and a technique utilizing components nature, using the disk diffusion method. The sensitivity of the studied LAB to different antibiotics was tested on Man rogosa sharp (MRS) agar using commercial antibiotic disks. All strains of LAB were examined for their antioxidant activity. The antioxidant activity of L. lactis was tested by 2,2-diphenyl-1 picrylhydrazyl (DPPH). Results: The results showed that the MRS medium was more adapted than Muller Hinton Agar (MHA) to investigate the antibacterial activity of L. lactis against S. aureus ATCC 29213. Also, L. lactis exhibited a notable degree of antibacterial activity against S. aureus ATCC 29213. L. Lactis subsp. Lactis displayed higher antibacterial activities, followed by L. lactis ssp. lactis biovar. diacetylactis, and lastly, L. lactis ssp. cremoris against S. aureus ATCC 29213. Lc 26 among all strains of L. lactis showed a high potential antibacterial activity reaching 40 ± 3 mm against S. aureus ATCC 29213. All strains of L. lactis showed a slightly moderate antioxidant activity (10.56 ± 1.28%-26.29 ± 0.05 %). The results of the antibiotic resistance test indicate that all strains of L. lactis were resistant to cefotaxime, sulfamethoxazole-trimethoprim, and streptomycin and were sensitive to Ampicillin, Amoxicillin, Penicillin G, Teicoplanin, Vancomycin, Gentamicin 500, Tetracycline, and Chloramphenicol. These test results indicate that this strain falls within the criteria of not posing any harmful effects on human health. The important antibacterial properties recorded for all L. Lactis strains were derived from the production of antibacterial active metabolites, such as protein, diacetyl, hydrogen peroxide, and lactic acid, together with the fight for nutrients. Conclusion: This study suggests that the strains of L. lactis could be added as an antibacterial agent against S. aureus ATCC 29213 and can provide an important nutritional property for their antioxidant potential.

Comparison of Wrinkle Patterns Generated by Intradermal and Intramuscular Botulinum Toxin Injections by Clinical Evaluation.

Purpose: Botulinum toxin has played a remarkable role in management of forehead wrinkles. Most used is intramuscular technique due to its deposition into the muscles, however, with adverse effects like brow ptosis. This study has been designed for the evaluation of efficacy for intradermal v/s intramuscular route of botulinum toxin injections for forehead wrinkles using clinical correlation. Methods: This study included a clinical trial of 32 facial halves divided equally into intradermal and intramuscular injection technique groups, receiving total dose of 8 U. Results were assessed by clinical examination upto 2 weeks and 4 weeks with parameters; objective wrinkle rate, eyebrow height, eyebrow movement, pain, and satisfaction after treatment. Result: Results showed least mean for objective wrinkle rate in intramuscular group, showing statistically significant improvement. Overall improvement in eyebrow height and eyebrow movement were slightly more for intramuscular group. Pain was lesser for intradermal group, whereas satisfaction of patient of patient post treatment is similar for both the groups. Conclusion: Among intradermal and intramuscular botulinum toxin injection technique, the effect and potency were better for intramuscular technique, whereas the patient comfort and compliance were better for intradermal technique.

Diagnostic Utility of Integration of Dynamic Contrast-Enhanced and Dynamic Susceptibility Contrast MR Perfusion Employing Split Bolus Technique in Differentiating High-Grade Glioma.

Background : Despite documented correlation between glioma grades and dynamic contrast-enhanced (DCE) magnetic resonance (MR) perfusion-derived parameters, and its inherent advantages over dynamic susceptibility contrast (DSC) perfusion, the former remains underutilized in clinical practice. Given the inherent spatial heterogeneity in high-grade diffuse glioma (HGG) and assessment of different perfusion parameters by DCE (extravascular extracellular space volume [Ve] and volume transfer constant in unit time [k-trans]) and DSC (rCBV), integration of the two into a protocol could provide a holistic assessment. Considering therapeutic and prognostic implications of differentiating WHO grade 3 from 4, we analyzed the two grades based on a combined DCE and DSC perfusion. Methods : Perfusion sequences were performed on 3-T MR. Cumulative dose of 0.1 mmol/kg of gadodiamide, split into two equal boluses, was administered with an interval of 6 minutes between the DCE and DSC sequences. DCE data were analyzed utilizing commercially available GenIQ software. Results : Of the 41 cases of diffuse gliomas analyzed, 24 were WHO grade III and 17 grade IV gliomas (2016 WHO classification). To differentiate grade III and IV gliomas, Ve cut-off value of 0.178 provided the best combination of sensitivity (88.24%) and specificity (87.50%; AUC: 0.920; p < 0.001). A relative cerebral blood volume (rCBV) of value 3.64 yielded a sensitivity of 70.59% and specificity of 62.50% ( p = 0.018). The k-trans value, although higher in grade III than in grade IV gliomas, did not reach statistical significance ( p = 0.108). Conclusion : Uniqueness of employed combined perfusion technique, treatment naïve patients at imaging, user-friendly postprocessing software utilization, and ability of Ve and rCBV to differentiate between grade III and IV gliomas ( p < 0.05) are the strengths of the present study, contributing to the existing literature and moving a step closer to achieving accurate MR perfusion-based glioma grading.

Spontaneous Subdiaphragmatic Hemorrhage From an Aneurysm of Inferior Phrenic Artery.

Inferior phrenic artery (IPA) aneurysms are the rarest type of visceral aneurysms. It usually occurs secondary to trauma, surgery, or as a complication of pancreatitis. In addition, it can be a manifestation of underlying systemic pathology such as vasculitis, collagen vascular disorders, sepsis, or segmental arterial mediolysis. It can be associated with hypertension in 43% of cases. The presentation of IPA aneurysm is nonspecific with abdominal pain, melena, hematochezia, and anemia. The ruptured and actively bleeding aneurysm can lead to hemorrhagic shock, and immediate management is required with angiography and endovascular embolization with coil or gel foam or stent etc. Inaccessible locations are reached with surgical intervention, but it is associated with high morbidity and mortality. We here report a rare case of spontaneously ruptured IPA pseudoaneurysm extending from the posterior mediastinum to the subdiaphragmatic area and managed with coil and gel foam embolization.

Real-World Data on Treatment Outcome of ALK-Positive Non-Small Cell Lung Cancer from an Indian Multicentric Cancer Registry.

Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, p = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( p = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.

Prognostic Factors and Outcomes of Early-Stage Hodgkin's Lymphoma: Multi-Institutional Data From South India.

Early-stage Hodgkin's lymphoma (ESHL) is highly curable, usually with a combination of chemotherapy and radiation. Real-world data may show differences in survival and prognostic factors when compared to clinical trials. There is limited published literature on ESHL from India. The data on the baseline characters, treatment, and outcomes of patients with ESHL (stage IA, IB, and IIA) were obtained from five institutions' medical records and entered in a common database. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan Meier method, and cox-regression analysis was used to identify prognostic factors. There were 258 patients [median age was 37 (18-75) years; [males:160 (62%); stage I: 41%; B symptoms: 17 (6%); bulky disease:19 (15%)] treated between 2000 and 2020 who were evaluable. The common chemotherapies used were ABVD [N = 180 (70%)], COPP-ABVD hybrid [N = 52 (21%)], and COPP [N = 14 (5%)]. Median number of cycles were 4 (2-8) and 93 (47%) received radiation at end of treatment. After a median follow-up of 60 months, the 5 years EFS was 87% and OS was 92%. On multivariate analysis, the following factors adversely affected the EFS: Male gender [hazard ratio (HR) = 2.23, P = 0.02] and Hemoglobin < 10.5g/dL [hazard ration (HR) = 2.20, P = 0.02], and the following adversely affected the OS: Hemoglobin < 10.5g/dL [hazard ratio (HR) = 4.05, P = 0.001], Male gender [hazard ratio (HR) = 3.59, P = 0.004], Stage 2 [hazard ratio (HR) = 2.65, P = 0.002] and ECOG PS (2-3) [hazard ratio (HR) = 3.35, P = 0.01]. Using the hemoglobin, stage and gender a 3-item prognostic score could identify patients with very good outcomes (score 0; 5 years OS:100%) and poor outcomes (score 3; 5 years OS; 49%). This is one of the first multi-center real-world data exclusively focusing on ESHL from India. Though the survival of the entire population was good, there are subsets of patients who have poor outcomes, which may be identified using simple parameters. These parameters need validation in a larger dataset. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01692-9.

A comparative survey between cascade correlation neural network (CCNN) and feedforward neural network (FFNN) machine learning models for forecasting suspended sediment concentration.

Suspended sediment concentration prediction is critical for the design of reservoirs, dams, rivers ecosystems, various operations of aquatic resource structure, environmental safety, and water management. In this study, two different machine models, namely the cascade correlation neural network (CCNN) and feedforward neural network (FFNN) were applied to predict daily-suspended sediment concentration (SSC) at Simga and Jondhara stations in Sheonath basin, India. Daily-suspended sediment concentration and discharge data from 2010 to 2015 were collected and used to develop the model to predict suspended sediment concentration. The developed models were evaluated using statistical indices like Nash and Sutcliffe efficiency coefficient (NES), root mean square error (RMSE), Willmott's index of agreement (WI), and Legates-McCabe's index (LM), supplemented by a scatter plot, density plots, histograms and Taylor diagram for graphical representation. The developed model was evaluated and compared with CCNN and FFNN. Nine input combinations were explored using different lag-times for discharge (Qt-n) and suspended sediment concentration (St-n) as input variables, with the current suspended sediment concentration as the desired output, to develop CCNN and FFNN models. The CCNN4 model with 4 lagged inputs (St-1, St-2, St-3, St-4) outperformed the other developed models with the lowest RMSE = 95.02 mg/l and the highest NES = 0.0.662, WI = 0.890 and LM = 0.668 for the Jondhara Station while the same CCNN4 model secure as the best with the lowest RMSE = 53.71 mg/l and the highest NES = 0.785, WI = 0.936 and LM = 0.788 for the Simga Station. The result shows the CCNN model was better than the FFNN model for predicting daily-suspended sediment at both stations in the Sheonath basin, India. Overall, CCNN showed better forecasting potential for suspended sediment concentration compared to FFNN at both stations, demonstrating their applicability for hydrological forecasting with complex relationships.