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Abstract: Aesculus L. is a genus of 12 to 19 woody species, representing one of the most acclaimed examples of inter-continental incoherence of the plants native to temperate regions of the Northern Hemisphere. It is traditionally valued in Ayurveda and the Chinese system of medicine for its various species that possess antitumor, cardioprotective, anti-inflammatory and neuroprotective activities. Current studies on this genus have revealed the presence of specific saponins with a multi-spectrum of pharmacological actions and therapeutic applications. A repertoire of literature related to the biological, taxonomical, phytochemical and ethnopharmacological aspects of Aesculus genus and its uses in different indigenous populations was explored. An inventory of all the species of this genus that were found to be useful as per ethnopharmacological literature was prepared. The ethnobotany, phytochemistry and pharmacology of the individual species are outlined in this review. The extensive information cited here has adduced the likely areas where the important species of this genus can illustrate significant therapeutic intervention in the management of chronic disorders including diabetes, hypercholesterolemia and cancer. The wide range of its pharmacological actions is attributed to the distinct phytochemicals occurring in the species, especially the triterpenoidal saponins like aescin. This review amplifies the recent studies on phytochemical and pharmacological aspects, which alludes that these species have noteworthy therapeutic potential.

Fixed prosthodontics is a zestful and progressing branch because of the numerous advantages that it has over removable prosthesis. The oral cavity for each scenario has its own complications and hence every individual case has its own approach keeping in mind the comfort, function, and aesthetics of the patient. In some cases, we come across an edentulous space on both the sides, creating a lone free-standing tooth. This clinical scenario with a pier abutment needs to be taken into consideration during restoration of the arch as the masticatory forces applied on the abutment teeth at one end of fixed partial denture (FPD) can result in the pier abutment acting as a fulcrum resulting in ultimate failure of the FPD and trauma to the periodontium. To overcome this complication, use of non-rigid connectors is advised. Many innovative clinical designs with modifications to the conventional bridges have been proposed over the years to undertake such a scenario most diligently. Selection of the right type of connector is imperative for the success while undertaking such a case. This era is of digital dentistry; hence, an innovative, time saving, and cost-effective way of fabricating non-rigid connector using Exocad software and 3D printing of split pontic FPD is presented in this case report.

The lack of suitable experimental approaches to investigate and model functional heterogeneity in vivo has had a profound negative impact on our understanding of how heterogeneity affects the response to immunotherapy. To bridge this technological gap, we leverage a new platform that visualizes the spatial architecture of subclones and microenvironments. To study heterogeneous populations of cells and their clonal dynamics in vivo, we performed barcode lineage tracing with next-generation sequencing analysis. It allows a quantitative evaluation of the spatial distribution and temporal clonal dynamic in vivo with multiple pharmacological perturbations, such as immune checkpoint blockade (ICB). We found that treatment with a PD1 inhibitor, despite a limited effect on tumor volume, induced dramatic changes in tumor clonal architecture. Furthermore, we revealed that subclones from well-defined geographical domains in vivo share differential behavior upon immune checkpoint blockade (ICB). By visualizing 40 different markers with multiplexed staining technology, we further identified that the microenvironment also exhibits a high level of spatial heterogeneity. Therefore, we coupled spatial barcode sequencing with high-content imaging and revealed the differential microenvironment feature of sensitive and resistant clones. We will further explore the mechanisms of immune evasion at the subclonal level. Through isolation and deep characterization of clonal lineages endowed with a distinct ability to engage the immune response, we hope to identify new vulnerabilities to overcome resistance to ICB. Citation Format: Er-Yen Yen, I-Lin Ho, Chieh-Yuan Li, Charles Dyke, Shan Jiang, Francesca Citron, Sergio Attanasio, Rutvi Shah, Ko-Chien Chen, Giulio Draetta, Andrea Viale. Uncovering key microenvironmental features for immunotherapy response at the subclonal level in pancreatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5868.

Introduction: DNA replication is a tightly regulated, multi-step process involving licensing and replication factors that faithfully orchestrate a single duplication of the entire genome exclusively during S phase of the cell cycle. Although the mechanisms that prevent uncoordinated DNA replication are well characterized, it remains unclear how cells counteract its potentially harmful effects when it does occur, such as in cancer cells driven by aberrant oncogenic signaling and loss of cell cycle checkpoints. Here, we identify DPY30, an understudied component of all COMPASS complexes, as a modulator of DNA replication. We found upregulated DPY30 expression in pancreatic ductal adenocarcinoma (PDAC) as well as a correlation between increasing DPY30 expression level and higher tumor grade and poor clinical outcomes. Experimental procedure: Human- and mouse-derived PDAC cells silenced or knockout for DPY30 expression were generated and characterized for their in vivo growth in recipient mice with increasing level of immune pressure. Chromatin immunoprecipitation followed by massive parallel sequencing was used to measure the epigenetic landscape in DPY30 or WDR5 knockdown cells. Unbiased proteomics and transcriptomics analyses were performed to elucidate molecular mechanisms. Results: The canonical function of COMPASS complexes is to regulate histone methylation. Unexpectedly, DPY30 loss did not affect histone methylation patterns compared to WDR5 loss, the core member of the COMPASS-like complex. This prompted unbiased proteomics analysis, which showed that DPY30 interacts with members of the DNA helicase, possibly stabilizing the DNA replication fork progression. We found that DPY30 overexpression, by preventing Geminin ubiquitylation, strongly stabilizes its expression, which in turn suppresses Cdt1 activity in late S-phase, buffering the risk of uncoordinated DNA replication in G2/M phase. Consistently, DPY30 loss resulted in DNA re-replication and chromosomal instability, as manifested by DNA fiber and metaphasic spread. In vivo, whole-exome sequencing analysis of DPY30-knockout tumors revealed that DPY30 loss markedly increased mutational burden in immunodeficient mice. In syngeneic models, DPY30 loss strongly inhibited tumor growth, prolonged survival, and increased T cell infiltration of tumors. Moreover, the immune system selectively cleared tumor cells with complex karyotypes, and we observed improved anti-tumor efficacy with DPY30 knockdown and anti-PD-1 treatment compared to either condition alone. Conclusions: In summary, we have identified a previously undescribed function for DPY30 to stabilize the replisome machinery and prevent excessive DNA replication. Our findings indicate that, in PDAC, DPY30 promotes genome stability, thus providing a rationale for targeting DPY30 or its effector proteins in combination with immune-checkpoint inhibitors. Citation Format: Francesca Citron, Luigi Perelli, Yanshuo Chu, Sanjana Srinivasan, I-Lin Ho, Er-Yen Yen, Rutvi Shah, Sergio Attanasio, Luis Castillo Montanez, Mauro Di Pilato, Shan Jiang, Wantong Yao, Sisi Gao, Angela Deem, Giannicola Genovese, Linghua Wang, Virginia Giuliani, Andrea Viale, Giulio F. Draetta. DPY30 loss leads to DNA re-replication and immunoediting in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 303.

Defining tumor cell immune evasion Mouse models used to study cancer often lack a full immune system, allowing implantation of human tumors into the mice. By contrast, naturally evolving tumors must contend with a fully functional immune system and its destruction of some of the cells (see the Perspective by Ho and Wood). Two groups now report studies on mouse models with a fully intact immune system. Martin et al . started with preexisting murine tumor cell lines and examined their continued evolution in vivo, whereas Del Poggetto et al . examined the development of new pancreatic tumors in the context of inflammation, as is often seen in human patients. In each study, the authors found that the immune system exerted a selective pressure on cells that would give rise to tumors, promoting the survival of those that had lost expression of tumor suppressor genes or activated a specific oncogene. The findings suggest a major role for the immune system in driving tumor evolution across multiple types of cancer. —YN

The conventional stock market platform possesses vulnerabilities such as high transaction costs, centrally managed governance which is vulnerable to attacks, lack of market transparency activities and methodologies, third party intervention and an unreliable environment. Blockchain is a technological breakthrough that is rapidly evolving the digital world by providing a new perspective on system security, adaptability, and efficiency. It provides a safe and secure means of exchanging any form of goods, service, or transaction. The presented blockchain-based implementation addresses the inadequacies of the centralized stock market infrastructure by verifying the authenticity of user’s holdings, imposing self-enforced smart contracts and achieving democratic and precise execution and agreement decisions by consensus mechanisms. Thus replacing the need for a centralized authority which preserves the credibility of the stock exchange process. The solution is validated by executing a model in Ethereum. This contributes to a reduction in overall transaction costs owed to brokers and central authorities.

Aims: We have evaluated screen time usage among preschool-aged (≤6 years) children in rural Western India. In addition, we have evaluated various lifestyle factors and their impact on the screen time of these children. Materials and Methods: English-medium schools in the locality were chosen based on convenience. A self-report survey requesting family information and screen usage information was distributed to the parents. Daily screen time was categorized as a three-category variable. Ordered logistic regression with multivariable regression was performed to examine the association of risk factors with screen time. Results: Average screen time among the 379 (208 males, 171 female) children amounted to 2.7 hours (SD: 1.7), with average daily television screen time of 1.6 hours (SD: 1.1). Most children (87.2%) started screen use by the age of 3. Only 65 (17.2%) participants met AAP recommendation. Households with three devices and smartphone usage by mothers increased the odds of screen time by 60% and two-folds, respectively. Compared to weekdays, children had increased screen time exposure (3.5 vs 2.7 hours, P < 0.001), outdoor activity time (2.3 vs 1.6, P < 0.001), and reading hours (1.2 vs 1.1, P = 0.03) on weekends. No association was observed between screen time and mother's occupation. Conclusions: More than 80% of children exceeded the advised screen time with television and smartphone being the major contributors. This issue has to be dealt with at both individual and societal levels. Increased awareness about the high prevalence of inappropriate use of screen time use within the Indian context is needed to inspire attention and interventions for this emerging public health problem in India.

The association between tumors and inflammation is a long-established clinical observation. Although many studies demonstrated that the inflammatory microenvironment can promote tumor growth through the activation of survival and proliferation programs in cancer cells, the reason why inflammation, an evolutionarily conserved response to damage aimed at reestablishing tissue integrity upon injury, might be integral to tumorigenesis still remains unknown. Pancreatic ductal adenocarcinoma (PDAC), a tumor characterized by poor prognosis, represents a distinctive example of cooperation between inflammation and activated oncogenes. Frequently developed in a context of chronic pancreatitis, PDAC is always associated with an inflammatory microenvironment. As supported by a substantial body of evidence across a multitude of experimental models, when occurring in the context of pancreatitis, mutations of KRAS, the universal oncogenic driver of pancreatic cancer, lead to accelerated tumor development inducing the appearance of neoplastic precursor lesions, such as acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN), which can evolve into invasive tumors. Interestingly, preneoplastic pancreatic alterations, specifically ADM, have been previously identified in acute and chronic pancreatitis in the absence of oncogene activation. Investigating the effects of inflammation on normal pancreatic epithelial cells, we discovered that long after complete resolution a transient inflammatory event primes cells to cooperate with oncogenic KRAS. Indeed, upon recovery from a single acute inflammation, epithelial cells display an enduring adaptive response associated with sustained epigenetic and transcriptional reprogramming. Such adaptation facilitates the prompt reactivation of acinar-to-ductal metaplasia upon subsequent inflammatory events, representing a physiological mechanism for limiting tissue damage via rapid decrease of zymogen production. Because metaplastic lesions are mediated by the activation of MAPK signaling, we demonstrated that activating mutations of KRAS, maintaining an irreversible ADM, are protective against tissue damage in a contest of pancreatitis. Uncovering a new physiologic role of somatic oncogenic mutations in preserving tissue integrity during repeated damages, we propose that KRAS mutations represent a nearly universal event in pancreatic cancer because beneficial and under strong positive selection in the context of recurrent pancreatitis. Citation Format: I-Lin Ho, Edoardo Del Poggetto, Chiara Balestrieri, Er-Yen Yen, Francesca Citron, Rutvi Shah, Shaojun Zhang, Shan Jiang, Wantong Yao, Haoqiang Ying, Giannicola Genovese, Timothy Heffernan, Anirban Maitra, Linghua Wang, Timothy Wang, Giulio Draetta, Alessandro Carugo, Gioacchino Natoli, Andrea Viale. Epithelial memory of resolved inflammation cooperates with oncogenic KRAS to limit tissue damage while promoting pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1327.

Over the past few decades, nanomaterials exhibiting the properties of natural enzymes (nanozymes) have attracted a great research attention because they offer to overcome the limitations of natural enzymes. Nanozymes that display multiple activities have received increasing attention because they can be applied in numerous applications such as biosensing, tumor diagnosis, therapy, immunoassays, antibiofouling, and bioimaging. A vital advantage that nanozymes possess over natural enzymes is that they have a higher surface area to volume ratio, which offers nanomaterials to exhibit better catalytic activity. Moreover, nanozymes are stable colloidal suspension, low cost, and robust to harsh environment and require normal storage conditions, which makes them a better alternatives to natural enzymes. Furthermore, the catalytic activity of nanozymes can be modulated simply by altering their shape, size, and compositions as per the need of applications. In this chapter, we have discussed the different enzyme-like properties exhibited by a variety of nanomaterials. Major emphasis has been given to the nanomaterials reported to show peroxidase, catalase, superoxide dismutase, and oxidase enzyme-like activities. Additionally, nanomaterials exhibiting biological multienzyme complex-like activity have also been discussed, and a section on the strategies reported to boost the enzyme-like activity of nanomaterials is also included toward the end.

Identification of the exact location of the fracture regions in the images was done based on the active contour segmentation process. Image segmentation process identifies the regions in the images that contain the interested portions in the images. A process that identifies the fracture location in images lying on the contour extraction process is employed. The contour extraction process identifies the bone regions in the images. Extracted/fracture bone regions are identified using morphological operations and thresholding process. Morphological operations and thresholding process are used for the exact identification of the fracture location. It removes the excess regions segmented in the threading process, i.e., fracture pixels. The fracture location is identified by subtracting the two images resulting in the identification of the fracture region in the images. In this paper, a comparison of different fracture detection algorithms like region growing, level set segmentation, and active contour segmentation (proposed system) is done. Comparison analysis is done in terms of PSNR, accuracy, segmentation time, and detection ratio. Results obtained show the higher accuracy of proposed work over existing algorithm.

To audit hand-washing practices by video-surveillance. Six main steps (step 2 to step 7) of World Health Organization’s hand hygiene technique with soap and water were used for evaluation. Handwashing was categorized as excellent, acceptable and unacceptable. Of 1081 recordings, 403 (37.3%) were excellent, 521 (48.2%) were acceptable and 157 (14.5%) were unacceptable handwash. Unacceptable handwashing was more prevalent in the night in comparison to daytime (17.5% vs 12.5%). Thirteen people washed their face after washing their hands. Innovative interventions are required to improve handwashing during night shifts.

With the increase in the data storage and data acquisition technologies there is an increase in huge image database. Therefore we need to develop proper and accurate systems to manage this database. Here in this paper we focus on the transformation technique to search, browse and retrieve images from large database. Here we have discussed briefly about the CBIR technique for image retrieval using Discrete Cosine Transform for generating feature vector. We have researched on the different retrieval algorithms. The proposed work is experimented over 9000 images from MIRFLIKR Database (Huskies ACM International Conference on Multimedia Information Retrieval (MIR’08), 2008 [1]). We have focused on showing the difference between the precision and recall and also the time of different methods and its performance by querying an image from the database and a non-database image.

In medical domain the high quality image data is maintained with the help of highly efficient servers across the network. There are some areas of medicine where it is sufficient to maintain high image quality only for diagnostically important regions, for example, tumor region of the brain MRI. Thus, the regions of interest are compressed with almost zero data loss while transmitting and storing the images, while the rest of image may possess less quality. This paper represents a compression method based on ROI, its performance analysis focusing on Haar Wavelet transform technique.