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The highly compressible nature of sludge and the presence of colloidal particles cause difficulties in sludge dewatering. Reducing the moisture content in secondary sludge is a key factor in reducing the capital costs, operational costs, and transportation costs in wastewater management. This investigation concerned the combined utilization of quicklime and granulated blast furnace slag (GBFS) to improve sludge dewatering. The experimental work included the initial characterization of the sludge and granulated blast furnace slag and evaluation of the dewatering ability of the treated sludge (CST, moisture content, turbidity, zeta potential, and heavy metal and biopolymer contents). Optimization using the Box-Behnken design (BBD) was carried out with various operational parameters, and the best performance was found to be at a pH of 10.2, a dose of 0.34 g/g DS, and a contact time of 14 min. A characterization study was carried out by scanning electron microscopy (SEM) in conjunction with EDS, X-ray diffractometry (XRD), and Fourier transform infrared spectroscopy (FTIR) to confirm the structural features (dense), elemental composition, and the presence of different functional groups. Hence, this study concluded that the use of quicklime with granulated blast furnace slag is suitable for conditioning during sludge dewatering. Graphical abstract

Regeneration is, in simple terms, ‘to re-grow’ damaged or lost parts of the body (e.g. cells, tissues and organs) and is a natural phenomenon occurring throughout the life of an organism. The regenerative capacity varies in the animal kingdom. Invertebrates have high regenerative capacity in contrast to higher vertebrates. This raises several fundamental questions related to the regeneration potential, evolutionary selection and its cellular and molecular mechanisms. An in-depth knowledge in regeneration is warranted to answer the fundamental questions that are still a challenge in regenerative medicine.Glycosaminoglycans (GAGs) are known to be involved in various physiological processes. Of several GAG types galactosaminoglycans are the focus of this thesis. Galactosaminoglycans such as chondroitin sulfate/dermatan sulfate (CS/DS) are anionic linear polysaccharides covalently linked to core proteins so called proteoglycans (PGs), and form an integral part of both cell surface and extracellular matrix components. Although CS/DS have been associated with different cellular processes from development to homeostasis, not many studies have been carried out to understand their role in regeneration. In this thesis, we aim to study galactosaminoglycans, their structure, and interaction with growth factors of biological importance in the process of regeneration using simple invertebrate model organisms - brittlestars.We have identified CS/DS as the major GAG present in brittlestars. Molecular characterization of these chains indicated a much higher level of sulfation in Amphiura filiformis than so far found in GAGs from invertebrates or vertebrates. This brittlestar CS/DS promotes FGF2 mediated cell signaling similar to heparin. Further, we studied the functional role of these CS/DS chains and their biosynthetic machinery during arm regeneration in A. filiformis. Regeneration is followed by an increase in GAG sulfation from blastema stage to the fully functional arm. Suppressing sulfation on the other hand by sodium chlorate treatment drastically affected the proliferation process and thereby regeneration. Thus our findings suggest a potential biological role of CS/DS in brittlestar limb regeneration that may have relevance to regenerative medicine in future.

Glioblastoma (GBM) is a highly invasive and heterogeneous brain tumor, where distinct patterns of growth and invasion critically influence disease progression and therapy response. However, the molecular drivers of these phenotypes remain poorly understood. Here, we present the HGCC Phenobank, a next-generation atlas of 76 patient-derived GBM cases engrafted in mice, integrating histopathology, transcriptomics, epigenomics, and proteomics. We identify two dominant invasion modes-diffuse parenchymal spread and perivascular/condensed growth-each governed by distinct gene regulatory programs. Using Multi-Omic Factor Analysis (MOFA), we link these invasion modes to patient survival, tumor-initiating capacity, and specific genetic alterations, revealing shared latent factors that structure GBM heterogeneity. The lead factor signature is defined by temporal lobe tumor localization, a high rate of successful xenografts with diffusely invasive growth, and recurrent mutations in TP53, DCHS2, and WNK2, and is associated with significantly worse patient survival. Through computational drug repurposing, we identify candidate inhibitors of invasive subtypes, including PIK-75, a multi-target PI3K/CDK/TAL1 inhibitor, and validate its efficacy across multiple models. Our findings offer a comprehensive framework for decoding GBM invasion and provide a resource for developing phenotype-guided therapies, accessible at hgcc.se/phenobank.

Small molecule immune checkpoint inhibitors targeting PD-1 and other pathways may offer advantages including ease of dosing, ability to manage immune-related adverse events (irAEs) due to their shorter pharmacokinetic exposure and opportunity to target more than one pathway for improving efficacy. Here we describe the identification and characterization of CA-170, an amino acid inspired small molecule inhibitor of PD-L1 and VISTA derived from the interface of PD-1 and PD-L1. CA-170 exhibited potent rescue of proliferation and effector functions of T cells inhibited by PD-L1/L2 and VISTA with selectivity over other immune checkpoint proteins as well as a broad panel of receptors and enzymes. Observed blocking of PD-L1 signaling and binding to PD-L1 in the cellular context without preventing the assembly of PD-1:PD-L1 complex support the formation of a defective ternary complex as the mechanism of action of CA-170. Oral administration of CA-170 resulted in increased proliferation and activation of T cells in the tumor, and significant anti-tumor efficacy in a number of immunocompetent mouse tumor models either as a single agent or in combination with approved therapeutics. These results prompted the advancement of CA-170 to human clinical trials.Sasikumar et al. describe the identification and characterization of CA-170, a small molecule inhibitor of PD-L1 and VISTA. They find that CA-170 activates T cells and exhibits anti-tumor efficacy in mouse models. This study highlights the potential of CA-170, which has advanced to human clinical trials, as an anti-cancer drug.

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.

Acute iron toxicity is usually seen in children with accidental ingestion of iron-containing syrups. However, the literature on acute iron toxicity with suicidal intent in adults is scant. We report an instance wherein an adult committed suicide by ingestion of multiple iron tablets. Delay in treatment was there due to misdiagnosis of the intoxicating agent. She developed fulminant hepatic failure with rapid clinical deterioration. Despite aggressive supportive management, the patient succumbed to the toxic doses of iron. Clinical course and postmortem features are discussed with a review of the literature.

Background: Yoga has been extensively used as an alternative or complementary therapy in psychiatric disorders depending on the type and severity of the disorders. However, data related to perspective on yoga services and the benefits and adverse effects attributed to yoga by patients with major psychiatric disorders is lacking. Aim: The aim of the study was to assess feedback of the patients who attended yoga sessions at a Yoga center in a tertiary neuropsychiatric hospital. Materials and Methods: This was a cross-sectional retrospective study using a specific questionnaire to get feedback from patients referred to the NIMHANS Integrated Center for Yoga, at the end of their yoga training. Results: Two hundred and one patients' data were included in this retrospective study. Most of the patients were referred by the doctors. The yoga module for schizophrenia was most commonly utilized, followed by depression. On an average, patients attended 13 sessions. Most of them practiced yoga for 1-2 weeks and had missed less than 2 sessions. The great majority of the patients reported that practicing yoga helped them. Spearman correlation analysis revealed positive associations between improvement attributed to yoga and variables affecting quality of yoga services at the center, including the quality of yoga sessions attended. Overall health and sleep improvement also positively correlated with improvement attributed to yoga. A minority of patients reported adverse effects, although these did not lead to discontinuation. Conclusion: In this retrospective study of patients referred to a Yoga center in a tertiary psychiatric facility, the majority of patients with major mental disorders were able to practice yoga under supervision and reported significant improvement in symptoms with minimal adverse effects.

BackgroundJudicious use of antibiotic therapy in preterm infants is necessary as prolonged and unwarranted use of antibiotics have been associated with adverse short-term and long-term outcomes.Local problemOur baseline data review revealed overuse and unnecessary prolonged antibiotic exposure among preterm infants despite a low suspicion for sepsis.Methods and interventionsThe baseline overall AUR was calculated retrospectively from our pharmacy database for a period of 4 months prior to the quality improvement (QI) initiative (pre-QI phase). The principal QI intervention included the development and implementation of guidance algorithms for evaluation and management of suspected sepsis incorporating key QI measures, such as an emphasis on early discontinuation of antibiotics by 36 h if blood culture remained negative and the introduction of multiplex polymerase chain reaction assay for early identification of causative organisms. This QI initiative was implemented through multiple Plan-Do-Study-Act cycles, starting in February 2016 (QI phase), with an objective to achieve a 10% reduction in the baseline overall AUR by December 2016, in preterm infants with gestational ages between 250/7 and 336/7 weeks. Data for the QI phase of the study were collected prospectively.ResultThe overall AUR (outcome measure) decreased from 154.8 to 138.4 days of treatment per 1000 hospital days (10.6% decrease, p < 0.05) over the 11-month period. However, the overall rate of adherence to guidance algorithm (process measure) remained below the target goal of 90%.ConclusionThis multiphase QI initiative was able to reduce the overall AUR at our NICU. The beneficial impact of this decrease in AUR in preterm infants remains to be determined.