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This study explores the impact of social media on market anomalies in Tier 2 cities, focusing specifically on Amravati. With the rise of social media platforms like Facebook, Instagram, and WhatsApp, consumer behavior in these cities is rapidly evolving, influenced by changing demographics and increased internet access. Market anomalies--such as sudden shifts in product demand and price fluctuations--are becoming more pronounced due to viral social media trends. This research employs a descriptive design, gathering data from 80 respondents through a systematic questionnaire distributed to over 100 customers in Amravati. The findings aim to assess the demographic profile of social media users, examine the influence of social media on purchasing decisions, and analyze how local businesses can adjust their marketing strategies to navigate the complexities of these digital-driven market dynamics. Despite limitations, including potential biases from convenience sampling and self-reported data, the study provides valuable insights into the interplay between social media and market behavior, highlighting emerging opportunities for businesses in Tier 2 cities. [ABSTRACT FROM AUTHOR]

O desiderato deste ensaio propõe submeter o pensamento, «em» doação, à linguagem [Sprache]. A linguagem enquanto o que gesta, recolhe, forma e conforma o Dasein em seus comportamentos. Urge pensá-la no modo da vontade de verdade, no modo da impessoalidade na saga do seu dizer, de saída, eivada de juízos valorativos e para além disso, pensar o seu outro, a saber, a poesia, para que «em» jornada a linguagem poética conclame para que desse modo habitemos propriamente o lugar sagrado. Pretende-se compreender a atmosfera regente dos modos de comportamentos deste ente [Dasein] na sua cotidianidade, ambientado cientificamente, politicamente e discursivamente. Neste diapasão, refletir-se-á a linguagem desde os comportamentos científicos, em sentido lato, até o ponto disruptivo onde a linguagem, como posse da verdade, se dê como possibilitadora de um salto para um pensar poético. E como consequência, a partir do gesto dito iluminado do poeta, a linguagem num dado abandono proporcione uma serenidade imperturbável.

Cryogenic treatment has been used commonly to high-speed tool steels to enhance the wear resistance of the materials. In the current research study, specimens of complex alloyed high-speed tool steel (M35) were hardened at 1473 K (1200 °C), triple tempered at 673 K (400 °C) and then cryogenically treated at 88 K (−185 °C) for varying lengths of period starting from 16 to 48 hours of cryosoaking followed by soft tempering at 373 K (100 °C). These treated specimens were studied as a function of cryosoaking period for their electrical resistivity, residual compressive stress, and its correlation with carbide density was established. TEM analysis indicated carbide size 0.156 to 1 μm, which confirms that the cryogenic treatment enhances the precipitation of finer carbides. Lower residual stresses in the higher carbide density regimes identified in 2D contour map were explained by the stress relaxation in the matrix through precipitation of incoherent carbides. [ABSTRACT FROM AUTHOR]

Sentiment analysis is the process of identifying the idea of a text. People share the comments on social media stating their knowledge of the event and would like to know if most other people had a good or bad experience at the same event. This distinction can be made through Emotional-Analysis. Sentiment analysis captures informal text comments, posts and images from all comments shared by different users and classifies comments into different categories as neutral, negative or positive. This is also called as polarity separation. Various different types of ML and in-depth learning methods may be utilised in Sentiment Analysis like Support Vector Machines, NB, Haar Cascade, LBPH, CNN, etc. Emerging rise in popularity in Social Media has established a trend of posting images in restaurants to express their opinion on the food, ambience, etc which can be a useful resource to obtain opinion and feedback from the Customers. In this paper, the implementation of Sentiment Analysis on images containing users along with their faces from the restaurants review revealing it more efficacious in classifying and identifying sentiments of review-images.

This research introduces a blind aid that uses a live object recognition system. People who are blind or partially sighted rely significantly on their other senses, such as touch and auditory cues, to comprehend their surroundings. There is a need to deploy a technology that assists visually impaired persons in their daily routines, as there is now very little aid. Existing solutions, such as Screen Reading software and Braille devices, assist visually impaired individuals in reading and gaining access to numerous gadgets. However, these technologies are rendered worthless When the blind need to perform basic activities like recognizing the situation before them, such as recognizing people or objects, technologies become ineffective. This method will benefit blind or visually challenged all across the world. The goal is to help a person with total or partial blindness obtain a second set of eyesight without the assistance of a guardian, allowing them to live a better and more independent life. This project outlines working to create a more welcoming and inclusive environment, focusing on assistive technology that provides services, resources, and information to those with visual disabilities.

Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned human IL-6-transgenic (hIL-6-transgenic) NSG (NSG+hIL6) mice reliably support the engraftment of malignant and premalignant human plasma cells, including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and postrelapse myeloma, plasma cell leukemia, and amyloid light chain amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells developed serum M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Single-cell RNA sequencing showed nonmalignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma-engrafted mice given CAR T cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish NSG+hIL6 mice as an effective patient-derived xenograft model for study and preclinical drug development of multiple myeloma and related plasma cell disorders.

Abstract: Patients with multiple myeloma (MM) treated with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells usually relapse with BCMA+ disease, indicative of CAR T-cell suppression. CD200 is an immune checkpoint that is overexpressed on aberrant plasma cells (aPCs) in MM and is an independent negative prognostic factor for survival. However, CD200 is not present on MM cell lines, a potential limitation of current preclinical models. We engineered MM cell lines to express CD200 at levels equivalent to those found on aPCs in MM and show that these are sufficient to suppress clinical-stage CAR T-cells targeting BCMA or the Tn glycoform of mucin 1 (TnMUC1), costimulated by 4-1BB and CD2, respectively. To prevent CD200-mediated suppression of CAR T cells, we compared CRISPR-Cas9-mediated knockout of the CD200 receptor (CD200RKO), to coexpression of versions of the CD200 receptor that were nonsignaling, that is, dominant negative (CD200RDN), or that leveraged the CD200 signal to provide CD28 costimulation (CD200R-CD28 switch). We found that the CD200R-CD28 switch potently enhanced the polyfunctionality of CAR T cells, and improved cytotoxicity, proliferative capacity, CAR T-cell metabolism, and performance in a chronic antigen exposure assay. CD200RDN provided modest benefits, but surprisingly, the CD200RKO was detrimental to CAR T-cell activity, adversely affecting CAR T-cell metabolism. These patterns held up in murine xenograft models of plasmacytoma, and disseminated bone marrow predominant disease. Our findings underscore the importance of CD200-mediated immune suppression in CAR T-cell therapy of MM, and highlight a promising approach to enhance such therapies by leveraging CD200 expression on aPCs to provide costimulation via a CD200R-CD28 switch., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent. We addressed these gaps and found that using mbIL15- versus mbIL21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL15 alone drove superior functionality by nearly all measures, whereas those expressing mbIL21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL21, whereas in sequence, NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine, highlighting the plasticity of NK cell differentiation. The sequence mbIL21 followed by mbIL15 was advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL15 alone in two of three xenograft models. Our findings define the impact of mbIL15 versus mbIL21 during NK expansion and reveal a previously underappreciated tradeoff between NK yield and function for which sequential use of mbIL21-based followed by mbIL15-based feeder cells may be the optimal approach in many settings., (©2023 The Authors; Published by the American Association for Cancer Research.)

Introduction: The essential goal of neoadjuvant chemotherapy (NACT) is to downstage the primary tumor making it amenable for breast conservation surgery (BCS). However, since the safety of this surgery is paramount, post-NACT breast conservation rates remain low. As per the recommendation of the 2018 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of long-term post-NACT follow-up, we have devised a protocol for imaging, localization, rad-path analysis, and documentation of radiotherapy techniques to ensure the safety of post-NACT breast conservation., Methods: This is a retrospective cohort of 180 breast cancer patients who received NACT and were operated on by a single surgical oncologist from 2015 to 2020. After selection based on published guidelines, patients were treated with neoadjuvant systemic (chemo or hormone) therapy. In cases where primary tumors responded and reduced to 1-2 cm in size mid-NACT, the residual tumors were localized by clips under ultrasound guidance and calcification was wire localized. All patients were treated using appropriate surgical and oncoplastic techniques where indicated. Negative margins were ensured by intra-operative rad-path analysis. Adjuvant chemotherapy and radiotherapy were given as per protocol., Results: In 81 cases that required mastectomy at presentation, we were able to achieve a 72.8% post-NACT BCS rate with the help of oncoplasty. Overall, 142 of 180 (80%) patients were treated with breast conserving surgery of which 80% (121 of 142) were oncoplasty. Margins were assessed on intra-operative frozen and re-excised in the same setting. No positive margins were reported in final histopath of 142 breast conservation procedures. Post-operative complication rates after breast conservation in the first year were at 17% (24 of 142 including two major complications). Patient reported outcomes were satisfactory with increased satisfaction for breast conservation compared with immediate breast reconstruction., Discussion: Employing oncoplastic breast surgery (OBS) techniques following stringent protocols for accurate localization of the residual tumor, intra-operative rad-path analysis, and adjuvant treatments, we show successful breast conservation in 72.8% of our mastectomy-qualified patients after downstaging by NACT. We also report satisfactory outcomes for post-NACT surgery, patient-reported satisfaction, and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koppiker, Kelkar, Kulkarni, Kadu, Pai, Dhar, Deshmukh, Varghese, Zamre, Jumle, Gangurde, Joshi, Unde, Banale, Namewar, Vaid, Busheri, Thomas, Nare, Pereira and Badve.)

In solid tumours, the abundance of macrophages is typically associated with a poor prognosis. However, macrophage clusters in tumour-cell nests have been associated with survival in some tumour types. Here, by using tumour organoids comprising macrophages and cancer cells opsonized via a monoclonal antibody, we show that highly ordered clusters of macrophages cooperatively phagocytose cancer cells to suppress tumour growth. In mice with poorly immunogenic tumours, the systemic delivery of macrophages with signal-regulatory protein alpha (SIRPα) genetically knocked out or else with blockade of the CD47-SIRPα macrophage checkpoint was combined with the monoclonal antibody and subsequently triggered the production of endogenous tumour-opsonizing immunoglobulin G, substantially increased the survival of the animals and helped confer durable protection from tumour re-challenge and metastasis. Maximizing phagocytic potency by increasing macrophage numbers, by tumour-cell opsonization and by disrupting the phagocytic checkpoint CD47-SIRPα may lead to durable anti-tumour responses in solid cancers., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM., Methods: All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures., Results: The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains., Conclusion: We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation., Competing Interests: CK is Managing Trustee - PCCM, Principal investigator at CTCR, Founding Director ISOS, Director Oncosciences at Jehangir Hospital. SJ, RM, DAK, AJ, JJ, SK, SmN, SaN, and MP are employed by CTCR. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koppiker, Joshi, Mishra, Kelkar, Chigurupati, Joshi, John, Kadu, Bagdia, Thakkar, Deshmukh, Allampati, Sharan, Dhar, Nare, Nagarkar, Busheri, Varghese and Pai.)

The macrophage checkpoint receptor SIRPα signals against phagocytosis by binding CD47 expressed on all cells - including macrophages. Here, we found that inhibiting cis interactions between SIRPα and CD47 on the same macrophage increased engulfment ('eating') by approximately the same level as inhibiting trans interactions. Antibody blockade of CD47, as pursued in clinical trials against cancer, was applied separately to human-derived macrophages and to red blood cell (RBC) targets for phagocytosis, and both scenarios produced surprisingly similar increases in RBC engulfment. Blockade of both macrophages and targets resulted in hyper-phagocytosis, and knockdown of macrophage-CD47 likewise increased engulfment of 'foreign' cells and particles, decreased the baseline inhibitory signaling of SIRPα, and linearly increased binding of soluble CD47 in trans , consistent with cis-trans competition. Many cell types express both SIRPα and CD47, including mouse melanoma B16 cells, and CRISPR-mediated deletions modulate B16 phagocytosis, consistent with cis-trans competition. Additionally, soluble SIRPα binding to human CD47 displayed on Chinese hamster ovary (CHO) cells was suppressed by SIRPα co-display, and atomistic computations confirm SIRPα bends and binds CD47 in cis Safety and efficacy profiles for CD47-SIRPα blockade might therefore reflect a disruption of both cis and trans interactions., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Background, Aim, and Scope: The focus of the present study is to know the potential of bacterial isolate for tannic acid degradation at low temperature. Also, we tried to evaluate the suitability of phytotoxicity testing protocol for the determination of tannic acid toxicity., Methods: Screening for tannic acid degrading bacterial strains was carried out by using microbial isolation techniques. The 16S rDNA amplicon of the isolate was used to identify the isolate. The effect of different concentrations of tannic acid and its degradation products on germination of Vigna unguiculata was evaluated. The study was carried out to determine total sugar and starch content of the used seeds and even to check the presence of α-amylase activity during seed germination., Results: The isolated bacterium was identified as Klebsiella sp NACASA1 and it showed degradation of tannic acid in 40 (±0.85***) h at 15°C and pH 7.0. A gradual decrease in root/shoot length was observed with increasing concentration of tannic acid. There was 95.11 (±0.24**)% inhibition in α-amylase activity at 20,000 ppm tannic acid, as compared to control. No such effects were observed on germination, root-shoot length, and α-amylase activity with tannic acid degradation products., Conclusions: The results obtained confirmed that tannic acid may act as a toxic agent in plant cells. The simple biodegradation process presented in this study was found to be effective in reducing toxicity of tannic acid. Also, it reveals the potential of soil bacterium to degrade tannic acid at low temperature.