KeratoEL: Detection of keratoconus using corneal parameters with ensemble learning.

Background and Aims: Keratoconus is a progressive eye condition in which the normally round cornea thins and bulges outwards into a cone shape. This irregular shape causes light to scatter in multiple directions as it enters the eye, leading to distorted vision, increased sensitivity to light and frequent changes in the prescription of glasses or contact lenses. Detecting keratoconus at an early stage is not only difficult but also challenging. Methods: The study has proposed an ensemble-based machine learning (ML) technique named KeratoEL to detect keratoconus at an early stage. The proposed KeratoEL model combines the basic machine learning algorithms, namely support vector machine (SVM), decision tree (DT), random forest (RF) and artificial neural network (ANN). Before employing the ML model for keratoconus detection, the data set is first preprocessed manually by eliminating some features that don't contribute any significant value to predict the exact class. Moreover, the output features are labelled into three different classes and Extra Trees Classifier is used to find out the important features. Then, the features are sorted in descending order and top 45, 30, and 15 features are taken as input datasets against the output. Finally, different machine learning models are tested using the input datasets and performance metrics are measured. Results: The proposed model obtains 98.0%, 98.9% and 99.8% accuracy for top 45, 30, and 15 number of features respectively. Overall experimental results show that the proposed ensemble model outperforms the existing machine learning models. Conclusion: The proposed KeratoEL model effectively detects keratoconus at an early stage by combining SVM, DT, RF, and ANN algorithms, demonstrating superior performance over existing models. These results underscore the potential of the KeratoEL ensemble approach in enhancing early detection and treatment of keratoconus.

Improved Ionic Transport Using a Novel Semiconductor Co0.6Mn0.4Fe0.4Al1.6O4 and Its Heterostructure with Zinc Oxide for Electrolyte Membrane in LT-CFCs.

Improving the ionic conductivity and slow oxygen reduction electro-catalytic activity of reactions occurring at low operating temperature would do wonders for the widespread use of low-operating temperature ceramic fuel cells (LT-CFCs; 450-550 °C). In this work, we present a novel semiconductor heterostructure composite made of a spinel-like structure of Co0.6Mn0.4Fe0.4Al1.6O4 (CMFA) and ZnO, which functions as an effective electrolyte membrane for solid oxide fuel cells. For enhanced fuel cell performance at sub-optimal temperatures, the CMFA-ZnO heterostructure composite was developed. We have shown that a button-sized SOFC fueled by H2 and ambient air can provide 835 mW/cm2 of power and 2216 mA/cm2 of current at 550 °C, possibly functioning down to 450 °C. In addition, the oxygen vacancy formation energy and activation energy of the CMFA-ZnO heterostructure composite is lower than those of the individual CMFA and ZnO, facilitating ion transit. The improved ionic conduction of the CMFA-ZnO heterostructure composite was investigated using several transmission and spectroscopic measures, including X-ray diffraction, photoelectron, and UV-visible spectroscopy, and density functional theory (DFT) calculations. These findings suggest that the heterostructure approach is practical for LT-SOFCs.

Curcumin Nanofibers: A Novel Approach to Enhance the Anticancer Potential and Bioavailability of Curcuminoids.

Development of novel treatment methods for cancer is needed given the limitations of current treatment methods, including side effects and chemotherapeutic resistance, which may provide new hope to cancer patients. Cancer is the second leading cause of global mortality. Curcumin, the active ingredient of turmeric, has been used since ancient times for various therapeutic purposes. Several studies have identified its activity against cancer. Despite the established anticancer activity of curcumin, its low aqueous solubility and bioavailability are barriers to its effectiveness. In an attempt to solve this problem, many studies have formulated curcumin nanofiber preparations using a variety of methods. Electrospinning is a simple and affordable method for the production of nanofibers. Studies have shown increased curcumin bioavailability in nanofibers resulting from their high surface/volume ratio and porosity. We have undertaken a detailed review of studies on the anticancer effects of curcumin nanofibers. Curcumin acts by inhibiting various biological cancer pathways, including NF-κB, mTOR, complex I, cytokines, expression of p-p65, Ki67, and angiogenesis-associated genes. It also induces apoptosis through activation of caspase pathways and ROS production in cancer cells. Curcumin-loaded PLA50/PVP50/Cur15 nanofibers were investigated in breast cancer, one of the most studied cancers, and was shown to have significant effects on the widely used HeLa-cell line. Most of the studies undertaken have been performed in cell lines in vitro, while relatively few animal studies have been reported. More preclinical and clinical studies are needed to evaluate the anticancer activity of curcumin nanofibers. Amongst studies undertaken, a variety of curcumin nanofibers of various formulations have been shown to suppress a variety of cancer types. Overall, curcumin nanofibers have been found to be more efficient than free curcumin. Thus, curcumin nanofibers have been observed to improvise cancer treatment, offering great potential for effective cancer management. Further studies, both in vitro and in vivo, involving curcumin nanofibers have the potential to benefit cancer management.

Radioprotective Role of Natural Polyphenols: From Sources to Mechanisms.

The identification and development of radioprotective agents have emerged as a subject matter of research during recent years due to the growing usage of ionizing radiation in different areas of human life. Previous work on synthetic radioprotectors has achieved limited progress because of the numerous issues associated with toxicity. Compounds extracted from plants have the potential to serve as lead candidates for developing ideal radioprotectors due to their low cost, safety, and selectivity. Polyphenols are the most abundant and commonly dispersed group of biologically active molecules possessing a broad range of pharmacological activities. Polyphenols have displayed efficacy for radioprotection during various investigations and can be administered at high doses with lesser toxicity. Detoxification of free radicals, modulating inflammatory responses, DNA repair, stimulation of hematopoietic recovery, and immune functions are the main mechanisms for radiation protection with polyphenols. Epicatechin, epigallocatechin-3-gallate, apigenin, caffeic acid phenylethylester, and silibinin provide cytoprotection together with the suppression of many pro-inflammatory cytokines owing to their free radical scavenging, anti-oxidant, and anti-inflammatory properties. Curcumin, resveratrol, quercetin, gallic acid, and rutin's radioprotective properties are regulated primarily by the direct or indirect decline in cellular stress. Thus, polyphenols may serve as potential candidates for radioprotection in the near future; however, extensive investigations are still required to better understand their protection mechanisms.

A Case Report of Giant Ascending Aortic Aneurysm: Role of Multimodality Imaging.

Giant ascending aortic aneurysm (AscAA >10 cm) is an uncommon entity with a variable presentation. The size of the aneurysm, rapid expansion, and calcification are associated with an increased risk of rupture. Atherosclerosis is the most common etiology of aortic aneurysm in the elderly population. Multimodality imaging can be wisely used for diagnosis, risk stratification, and follow-up. We herein report a case of successfully repaired giant calcified AscAA with a maximum diameter of 10 cm. We also provide a brief discussion on the role of multimodality imaging.

Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential.

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD.

Palynological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan, using light and scanning electron microscopy.

This was the first comprehensive pollen micromorphological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan. The pollen morphology of 10 species of the family Apocynaceae was observed and documented using light microscopy and scanning electron microscopy. Pollen was found subspheroidal in shape in most of the species, however peroblate shape was noted in Vinca major. Exine sculpturing patterns (psilate, rugulate, scabrate, and microreticulate) were observed. The result indicated that exine ornamentation of Apocynaceae taxa is systematically informative at generic and species levels. Most of the species have tricolporate type pollen but tetraporate pollen was also observed in Trachelospermum jasminoides and tetracolpate in V. major. Minimum equatorial diameter was noted in Carissa edulis (27.13 µm) and maximum in V. major (108.25 µm). Similarly, maximum exine thickness was found in Cascabela thevetia (9.5 µm). In the present findings, the pollen morphological data are compared with available other pollen studies to evaluate the taxonomic value of pollen traits in Apocynaceae taxa by using multiple microscopic techniques. Furthermore, molecular and phylogenetic studies were recommended to strengthen the systematics of Apocynaceae taxa.

netDx: interpretable patient classification using integrated patient similarity networks.

Patient classification has widespread biomedical and clinical applications, including diagnosis, prognosis, and treatment response prediction. A clinically useful prediction algorithm should be accurate, generalizable, be able to integrate diverse data types, and handle sparse data. A clinical predictor based on genomic data needs to be interpretable to drive hypothesis-driven research into new treatments. We describe netDx, a novel supervised patient classification framework based on patient similarity networks, which meets these criteria. In a cancer survival benchmark dataset integrating up to six data types in four cancer types, netDx significantly outperforms most other machine-learning approaches across most cancer types. Compared to traditional machine-learning-based patient classifiers, netDx results are more interpretable, visualizing the decision boundary in the context of patient similarity space. When patient similarity is defined by pathway-level gene expression, netDx identifies biological pathways important for outcome prediction, as demonstrated in breast cancer and asthma. netDx can serve as a patient classifier and as a tool for discovery of biological features characteristic of disease. We provide a free software implementation of netDx with automation workflows.

Reviving Phage Therapy for the Treatment of Cholera.

Cholera remains a major risk in developing countries, particularly after natural or man-made disasters. Vibrio cholerae El Tor is the most important cause of these outbreaks, and is becoming increasingly resistant to antibiotics, so alternative therapies are urgently needed. In this study, a single bacteriophage, Phi_1, was used to control cholera prophylactically and therapeutically in an infant rabbit model. In both cases, phage-treated animals showed no clinical signs of disease, compared with 69% of untreated control animals. Bacterial counts in the intestines of phage-treated animals were reduced by up to 4 log10 colony-forming units/g. There was evidence of phage multiplication only in animals that received a V. cholerae challenge. No phage-resistant bacterial mutants were isolated from the animals, despite extensive searching. This is the first evidence that a single phage could be effective in the treatment of cholera, without detectable levels of resistance. Clinical trials in human patients should be considered.

A global assessment of cancer genomic alterations in epigenetic mechanisms.

BACKGROUND: The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients. RESULTS: Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover a general trend in which transcriptional profiles and somatic mutations in tumor samples favor increased transcriptionally repressive histone methylation, and defective chromatin remodeling. CONCLUSIONS: This unbiased approach confirms previously published data, uncovers novel cancer-associated aberrations targeting epigenetic mechanisms, and justifies continued monitoring of chromatin-related alterations as a class, as more cancer types and distinct cancer stages are represented in cancer genomics data repositories.

ChromoHub V2: cancer genomics.

SUMMARY: Cancer genomics data produced by next-generation sequencing support the notion that epigenetic mechanisms play a central role in cancer. We have previously developed Chromohub, an open access online interface where users can map chemical, structural and biological data from public repositories on phylogenetic trees of protein families involved in chromatin mediated-signaling. Here, we describe a cancer genomics interface that was recently added to Chromohub; the frequency of mutation, amplification and change in expression of chromatin factors across large cohorts of cancer patients is regularly extracted from The Cancer Genome Atlas and the International Cancer Genome Consortium and can now be mapped on phylogenetic trees of epigenetic protein families. Explorators of chromatin signaling can now easily navigate the cancer genomics landscape of writers, readers and erasers of histone marks, chromatin remodeling complexes, histones and their chaperones. AVAILABILITY AND IMPLEMENTATION: http://www.thesgc.org/chromohub/.

Fear of death.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. For many, cancer is synonymous with death. Fearing death is a rational response. For too long, medicine has ignored this primeval fear. Increasingly, clinicians recognize and address end-of-life issues, facing patients' and our own emotional vulnerabilities in order to connect and explore problems and fears. Listening and learning from the patient guides us as we acknowledge much of the mystery that still surrounds the dying process. Rarely is there a simple or right answer. An empathetic response to suffering patients is the best support. Support is vital in fostering the adjustment of patients. A silent presence may prove more helpful than well-meant counsel for many patients. Through an examination of eight caregiver narratives of their patients' experiences, the role of the health care provider in the dying process, particularly in regard to challenging fear, is reviewed.