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The gene therapy approach for retinal disorders has been considered largely over the last decade owing to the favorable outcomes of the US Food and Drug Administration-approved commercial gene therapy, Luxturna. Technological advances in recent years, such as next-generation sequencing, research in molecular pathogenesis of retinal disorders, and precise correlations with their clinical phenotypes, have contributed to the progress of gene therapies for various diseases worldwide, and more recently in India as well. Thus, considerable research is being conducted for the right choice of vectors, transgene engineering, and accessible and cost-effective large-scale vector production. Many retinal disease-specific clinical trials are presently being conducted, thereby necessitating the collation of such information as a ready reference for the scientific and clinical community. In this article, we present an overview of existing gene therapy research, which is derived from an extensive search across PubMed, Google Scholar, and clinicaltrials.gov sources. This contributes to prime the understanding of basic aspects of this cutting-edge technology and information regarding current clinical trials across many different conditions. This information will provide a comprehensive evaluation of therapies in existing use/research for personalized treatment approaches in retinal disorders.

Introduction: Frozen Section (FS) is a diagnostic technique performed intraoperatively to obtain relevant information about the primary diagnosis, margin status, or sentinel lymph nodes, which helps guide the course of surgery. With the prevalent use of FS, it is imperative to recognise and scrutinise its diagnostic pitfalls and make efforts for rectification. Aim: To compare diagnostic results obtained on FS with final paraffin-embedded histopathology and calculate the Diagnostic Accuracy (DA) of FS. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology at a tertiary care hospital, DVVPFs Medical College in Ahmednagar district, Maharashtra, India over a period of two years from January 1, 2020, to December 31, 2021. The diagnosis provided on specimens received for intraoperative FS was compared with the final histopathological diagnosis, considered as the gold standard for the same specimen. The results were categorised as concordant, discordant, and deferred cases. The diagnosis on FS and the final histopathological diagnosis, along with relevant clinical data, were entered into an excel sheet. Further, the DA of FS was calculated. All the discordant cases were analysed. Statistical analysis utilised simple percentage calculations from the excel sheet. Results: A total of 130 cases were analysed using FS, with the most common indication being sentinel lymph node analysis to detect metastatic deposits in 72 (55.4%) cases. Out of the total 130 cases, 119 (91.5%) were concordant, 10 (7.7%) were discordant, and 1 (0.8%) was deferred due to an insufficient specimen. Therefore, the overall DA rate was found to be 91.5% with an error rate of 8.5%. Upon analysis of the 10 discordant cases, the cause of inaccuracy was technical error in 7 (70%) cases and interpretation error in 3 (30%) cases. Conclusion: The DA obtained in the present study was somewhat lower than expected due to technical errors during FS sectioning, leading to artifacts, especially during lymph node processing. Analysis of the discordant cases unveiled this deficit. Therefore, such assessment studies should be performed periodically as they assist in highlighting the shortfalls and provide a plan to boost DA.

Very few studies exist on tele-health models of parent-mediated interventions delivered in low resource developing countries. The global COVID-19 pandemic catalysed a pilot of an online delivery of an evidence-based parent-mediated intervention (Project ImPACT) for children with Autism Spectrum Disorder in Mumbai, India. Context and culture-specific adaptations were made in program structure and a mixed-methods approach was adopted to evaluate acceptability, feasibility and preliminary efficacy of this model. Quantitative results (n = 12) showed excellent completion rates, with significant improvement in parent fidelity to intervention and child social-communication skills. Analysis of qualitative data from focus groups with parents on completion revealed that parents found the online mode convenient and acceptable, found the synchronous model of sessions especially beneficial and perceived improvements in their own parenting skills and children's developmental profiles. Though piloted in pandemic times, the results from the study have implications for future service delivery models across similar settings in other developing countries.

Background: Progesterone-primed ovarian stimulation (PPOS) protocol is based on the principle of preventing pre-mature luteinising hormone surge during ovarian stimulation using progesterone. Aims: In this study, we aimed to compare the cost-effectiveness of PPOS over GnRH antagonist cycles in oocyte donor cycles where freeze all is a norm. Settings and Design: It is a prospective cohort study with 130 participants. Materials and Methods: We included all women undergoing oocyte donation using PPOS protocol and antagonist protocol at our centre. Fifty-seven belonged to the PPOS group and were given medroxyprogesterone acetate (MPA) and 73 belonged to the GnRH antagonist group who received cetrorelix. The primary outcome was the number of mature oocyte retrieved at OPU and the cost involved per stimulation cycle. Statistical Analysis Used: For normally distributed observations, we used t-test, and for the variables of non-normal distribution, Mann–Whitney U-test was used. The significance was accepted for P < 0.05. Results: The baseline clinical characteristics of the donors were comparable with a mean age of 25.42 ± 2.90 years, body mass index of 24.00 ± 4.00 kg/m2 and antral follicle count of 18.63 ± 5.23. The duration of stimulation was similar in both the groups as well as the total gonadotropin dose required was not significantly different. The number of mature oocytes retrieved was same in both the groups (10.41 ± 4.04 with antagonist and 10.25 ± 3.23 with PPOS, P = 0.964). There were no reported cases of severe ovarian hyperstimulation syndrome (OHSS) in any of the groups. The incidence of mild-to-moderate OHSS in the antagonist group was 5.4% and in the PPOS group was 3.6%, and the difference was not significant (P = 0.69). The cost per mature oocyte (M2) was significantly higher in the antagonist protocol in comparison to the PPOS protocol (INR 9485.69 ± 5751.11 vs. Rs. 5945.86 ± 2848.59, respectively, P < 0.001). Conclusion: Our study identifies PPOS protocol using MPA to be more cost-effective and patient-friendly than conventional GnRH antagonist protocol in oocyte donor cycles.

Land cover data is very significant for designing the earth system, managing the natural resources, and also for performing conservation planning. Time-series data are captured with their dynamic vegetation behavior using remote sensing technology, which is broadly utilized in land cover mapping. Most of the Vegetation Index (VI) such as the Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI) comprises commonly employed features that are obtained from the time-series spectral data. But, these VIs are not validated as the optimal techniques for generating the temporal profiles. Recent researches highly depend on optical satellite imagery for performing these above-mentioned tasks. Dynamic Time Warping (DTW) is said to be an effective optimal solution for solving the existing challenges, especially the improved version of DTW named Time-Weighted Dynamic Time Warping (TWDTW) is used for time-series analysis regarding the time-series vegetation classification. Yet, the TWDTW efficiency is not shown with other comparative machine learning approaches owing to the classification of vegetation type in the mountain areas. The major goal of this paper is to research and create a novel approach for distinguishing the kind of vegetation in a farm region near Ujani Dam in Solapur District, Maharashtra using time-series analysis. For time-series analysis employing satellite images, the suggested model offers a unique Adaptive Time-Weighted Dynamic Time Warping (ATWDTW). The farm's satellite images are first pre-processed before being sent to ATWDTW for examination. The TWDTW idea is optimized for classification performance using a new hybrid metaheuristic technique named Adaptive Coyote Crow Search Optimization (ACCSO). From the experimental results, the performance of the suggested ACCSO-ATWDTW correspondingly provides superior performance to the traditional approaches, where the designed model using ACCSO-ATWDTW provides 7.2%, 5.2%, 9.9%, 4.55%, and 2.33% higher MCC than the MFO-ATWDTW, BSA-ATWDTW, MF-BSA-ATWDTW, CSA-ATWDTW, and COA-ATWDTW at the maximum iteration of 200. This proved the robustness and less sensitivity to training samples of the TWDTW method when applied to mountain vegetation-type classifications. [ABSTRACT FROM AUTHOR]

There is rapidly emerging evidence from pre-clinical studies, patient samples and patient subpopulations that certain chemotherapeutics inadvertently produce prometastatic effects. Prior to this, we showed that doxorubicin and daunorubicin stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. Here, we investigate which other anti-cancer drugs might have similar prometastatic effects by altering the biophysical properties of cells. We treated myelogenous (K562) leukemic cancer cells with the drugs nocodazole and hydroxyurea and then measured their mechanical properties using a microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation and enables the measurement of cell mechanical properties via transit times through the device. We also quantified the morphological properties of cells to explore biophysical mechanisms underlying the MMM results. Results from MMM measurements show that nocodazole- and hydroxyurea-treated K562 cells exhibit significantly altered transit times. Nocodazole caused a significant (p < 0.01) increase in transit times, implying a stiffening of cells. This work shows the feasibility of using an MMM to explore possible biophysical mechanisms that might contribute to chemotherapy-induced metastasis. Our work also suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies in general.

Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.