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Friedreich ataxia (FRDA) is a multisystemic, autosomal recessive disorder caused by homozygous GAA expansion mutation in the first intron of frataxin (FXN) gene. FXN is a mitochondrial protein critical for iron-sulfur cluster biosynthesis and deficiency impairs mitochondrial electron transport chain functions and iron homeostasis within the organelle. Currently, there is no effective treatment for FRDA. We have previously demonstrated that single infusion of wild-type hematopoietic stem and progenitor cells (HSPCs) resulted in prevention of neurologic and cardiac complications of FRDA in YG8R mice, and rescue was mediated by FXN transfer from tissue engrafted, HSPC-derived microglia/macrophages to diseased neurons/myocytes. For a future clinical translation, we developed an autologous stem cell transplantation approach using CRISPR/Cas9 for the excision of the GAA repeats in FRDA patients CD34+ HSPCs; this strategy leading to increased FXN expression and improved mitochondrial functions. The aim of the current study is to validate the efficiency and safety of our gene editing approach in a disease-relevant model. We generated a cohort of FRDA patient-derived iPSCs and isogenic lines that were gene edited with our CRISPR/Cas9 approach. iPSC derived FRDA neurons displayed characteristic apoptotic and mitochondrial phenotype of the disease, such as non-homogenous microtubule staining in neurites, increased caspase-3 expression, mitochondrial superoxide levels, mitochondrial fragmentation, and partial degradation of the cristae compared to healthy controls. These defects were fully prevented in the gene edited neurons. RNASeq analysis of FRDA and gene edited neurons demonstrated striking improvement in gene clusters associated with endoplasmic reticulum (ER) stress in the isogenic lines. Gene edited neurons demonstrated improved ER-calcium release, normalization of ER stress response gene, XBP-1, and significantly increased ER-mitochondrial contacts that are critical for functional homeostasis of both organelles, as compared to FRDA neurons. Ultrastructural analysis for these contact sites displayed severe ER structural damage in FRDA neurons, that was undetected in gene edited neurons. Taken together, these results represent a novel finding for disease pathogenesis showing dramatic ER structural damage in FRDA, validate the efficacy profile of our FXN gene editing approach in a disease relevant model, and support our approach as an effective strategy for therapeutic intervention for Friedreichs ataxia.

Background and Aims: The quality of recovery (QoR)-40 score has been used worldwide and validated in many surgical cohorts to assess global patient recovery. We aim to translate and culturally adapt the QoR-40 score into Hindi and test the validity and reliability of the translated version in patients undergoing cancer surgery. Methods: The translation of the QoR-40 questionnaire was based on the forward and backward translation methods. Patients filled out the translated version of the QoR-40 preoperatively, on the third postoperative day in the morning (POD3) and the evening. The reliability of the translated questionnaire was checked for internal consistency, test-retest reliability and split-half reliability. Construct validity was assessed with a correlation coefficient value between the total QoR-40 score, visual analogue scale (VAS) for pain and total length of hospital stay. Content validity was evaluated for feasibility and understanding. Results: The questionnaire was completed by 350 patients. The correlation coefficient r for repeatability was 0.21, the split-half test was 0.92, and Cronbach's alpha was 0.82. The correlation between QoR-40 on POD3 with VAS score and length of stay was -0.35 and -0.67, respectively. The average time to complete the questionnaire was 3.8 minutes; 90% of the respondents found the translated questionnaire easy to understand, and 92% of the patients related the questions to their recovery. Conclusion: The Hindi translation of the QoR-40 questionnaire is a valid and reliable version of the original questionnaire in English to assess the QoR in Hindi-speaking patients after cancer surgery. Keywords: Cancer surgery, Hindi language, postoperative, quality of recovery score, QoR-40 score, reliability, translation, validation, Author(s): Nishith Govil (corresponding author) [1]; Rishika Rathore [1]; Ajeet Tiwari [2]; Pankaj K. Garg [2]; Kumar Parag [1]; Priyanka Mishra [1] INTRODUCTION A good quality of postoperative recovery means [...]

Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of β-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to "disease-associated microglia" in the cortex and "neurodegeneration-associated endothelial cells" in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease.

Author(s): Deepak K. Daunaria [1]; Girish K. Singh (corresponding author) [1]; Ankit Agarwal [1]; Priyanka Mishra [2] Dear Editor, We report a case of COVID-19-associated acute respiratory distress syndrome (C-ARDS) [...]

Uranium mineralization related to Na-metasomatism is known as Na-metasomatite or albitite-type. They represent the fourth-largest uranium resource globally and constitute fifty thousand tons of U resources. The present work gives details about well-known Na-metasomatic uranium occurrences worldwide in terms of structures, metasomatic stages, geochemical characteristics, fluid inclusions, and compositions of stable isotopes. The host rocks are granite, granitoid, and metamorphosed volcano-sedimentary rocks, and these rocks experienced two/three deformational stages. U mineralization is mainly confined to faults and characterized by granitic intrusive, cataclasis, mylonitization, and albitization. The albitized rocks exhibit two to three metasomatic and late hydrothermal stages. The first stage is marked by the replacement of pre-existing host minerals during a ductile shear regime. The second stage is related to U mineralization contemporaneous with the brittle deformation. The albitized rocks exhibit depletion in Si, K, Ba, and heavy rare-earth elements relative to the host rocks and enrichments in Na, Ca, U, Zr, P, V, Sr, and light rare-earth elements. U-enrichment is positively correlated with Na, Mo, Cu, and high-field strength elements. The pressure–temperature (P-T) conditions of U mineralization are considered to be epithermal and mesothermal. Fluid inclusion studies indicate that the mineralizing fluids were rich in Na+, Mg2+, Cl−, CO2, H2O, F−, and PO43− and meteoric–magmatic derived. The geological processes responsible for the genesis of Na-metasomatic U deposits of the North Delhi Fold Belt (India) are comparable with some international examples, i.e., Australia, Ukraine, Cameroon, Brazil, Guyana, China, and the USA. [ABSTRACT FROM AUTHOR]

Peri-urban catchment areas are increasingly susceptible to floods due to rapid land use transformations and unplanned urban expansion. This study comprehensively examines flood vulnerability in the rapidly developing peri-urban areas of North Bhubaneswar, focusing on significant changes in Land Use/Land Cover (LULC) and hydrological dynamics from 2004 to 2024, utilizing Geographic Information System (GIS) tools. The analysis reveals substantial shifts in land use patterns, with the urban footprint expanding by 71.8%, cropland decreasing by 21.7%, and forest areas by 13.6%. These changes have led to increased impervious surfaces, resulting in higher surface runoff and decreased groundwater recharge, thereby exacerbating flood risks in the region. The GRID-based vulnerability analysis classifies 90 villages within the catchment area based on their vulnerability levels, identifying 20 villages as high-risk areas requiring urgent attention, 44 villages as medium vulnerable, and 26 villages as low vulnerable. These classifications are based on factors such as proximity to drainage networks, slope, geomorphology, and LULC characteristics, with areas near drainage channels and low-lying regions being prone to flooding. The analysis integrates multiple factors to provide a comprehensive assessment of flood risk, highlighting the need for sustainable land use planning, conservation of vegetated areas, and the implementation of advanced flood prevention strategies in the peri-urban areas. Extending this research to other fringe regions could offer further valuable insights, guiding flood prevention and sustainable development strategies for areas undergoing significant land use transformations to effectively mitigate future flood risks. [ABSTRACT FROM AUTHOR]

The urban fringes are experiencing a significant surge in surface temperature during the transition from rural to urban, inducing imperceptible disturbances. The present study analyses the temperature modulations from 2000 to 2022 in Kalarahanga and Raghunathpurjali fringes in North Bhubaneswar to understand the relationship between spatiotemporal changes and land-surface temperature in the fringes. The investigations reveal a consistent decrease in the area under water bodies and crops, with an increase in the builtup area. Besides, there exists an inverse correlation between the area under high and medium temperature with the area under cropland (-0.820) and the area under water bodies (-0.799), and a positive correlation coefficient (0.813) with the built-up area/impervious surfaces. This insists on eco-sensitive planning of the urban fringes with consistent monitoring of land use and thermal dynamics for apt control of the changes in the urban microclimate. [ABSTRACT FROM AUTHOR]

Jarosite, an industrial waste, has the potential to be used as an alternative filler in biocomposites used as packaging material and can replace nondegradable thermoplastic. Such a novel approach of waste management strategy has not been studied till date. In this research work, different weight percentages of jarosite were mixed with poly(vinyl alcohol) (PVA) to fabricate polymer composites with better physico‐chemical, thermal, tensile, and biodegradation properties. The data indicate that a low concentration of jarosite (3 wt.%) improved the tensile strength by 198.7% and the composite showed higher thermal stability by 6.3% than that of the neat PVA. X‐ray diffractogram and transmission electron microscopic analysis revealed a strong interaction between PVA and jarosite. Interestingly, the addition of jarosite reduced the water absorption capacity and thickness swelling of the PVA composite by 58% and 54.7%, respectively. Jarosite‐incorporated composites showed lesser degradation potential (64%) than the control composites (84%) after 60 days under soil burial conditions, indicating that PVA‐jarosite composites have a higher shelf‐life, which is needed for packaging materials. These composites can also be good alternant for thermoplastic used in preparation of cuboid, sealing, and decorative materials. Also, this would be a novel sustainable approach for managing/reducing jarosite waste. Highlights: Jarosite was reinforced with PVA to fabricate biocomposites.The maximum tensile strength of the composite was achieved as 45.4 MPa.The thermal stability of mechanically optimized composite is found at 320°C.After 60 days under soil burial, the composite lost 64.8% of its original weight.Developed composites can be good alternant for nondegradable thermoplastic. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a class of bilevel programming problems (BLPP) in the framework of Euclidean space. We derive relationships among the solutions of approximate Minty-type variational inequalities (AMTVI), approximate Stampacchia-type variational inequalities (ASTVI), and local ϵ -quasi solutions of the BLPP, under generalized approximate convexity assumptions, via limiting subdifferentials. Moreover, by employing the generalized Knaster–Kuratowski–Mazurkiewicz (KKM)-Fan's lemma, we derive some existence results for the solutions of AMTVI and ASTVI. We have furnished suitable, non-trivial, illustrative examples to demonstrate the importance of the established results. To the best of our knowledge, there is no research paper available in the literature that explores relationships between the approximate variational inequalities and BLPP under the assumptions of generalized approximate convexity by employing the powerful tool of limiting subdifferentials. [ABSTRACT FROM AUTHOR]

Background: Physical fitness is key to a successful outcome. Physical fitness is directly related to the ability of an individual to perform physical activity or exercise. Physical fitness can be measured using cardiopulmonary efficiency tests such as the Physical Fitness Index (PFI %), which is an excellent indicator of cardiopulmonary efficiency. Body Mass Index (BMI) is often used as an indicator of obesity. Aims and Objectives: The present study is aimed to assess the relationship between physical fitness index and BMI among the students of age group 18-24 years. Materials and methods: A cross-sectional study was done to assess the relation between physical fitness index and body mass index. A total of 150 subjects (80 males and 70 females) in the age group 18-24 years participated in the study. Descriptive data for age (years), height (m), and weight (Kg) were obtained and BMI was calculated. Physical fitness index (PFI) was measured using Chester's step test. Results: Physical fitness index and Physical parameters like, mean height, weight, BMI were higher among male than female participants. Difference of weight, height, BMI and PFI among male and female were statistically significant. The study found negative association (r-value=-0.466) between BMI and physical fitness, which was statistically significant. Conclusion: The results showed that the physical fitness index of the subjects differed significantly, with the subjects of normal weight possessing a higher fitness than the overweight/obese subjects. Fitness index decreased progressively as the BMI increased. [ABSTRACT FROM AUTHOR]

Background: Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. Methods: This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. Results: Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type--48%, nongerminal center--52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). Conclusion: pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes. [ABSTRACT FROM AUTHOR]

Byline: Sachin. Sogal, Priyanka. Mishra, Nishith. Govil Sir, Cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HiPEC) is a popular topic of investigation for cancers with diffuse peritoneal metastasis.[1] Perioperative management for these [...]

Byline: Bhavna. Gupta, Gaurav. Jain, Priyanka. Mishra, Sharmishtha. Pathak Introduction Corona virus outbreak has increased the load of critically ill patients across the world and has overwhelmed the working capacity [...]