Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.

INTRODUCTION: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. CONTENT: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. SUMMARY AND OUTLOOK: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

An Evidence-based Preoperative Evaluation Documentation Template Improves Perioperative Communication.

OBJECTIVES: The number of surgeries performed in the United States has increased over the past two decades, with a shift to the ambulatory setting. Perioperative complications and mortality pose significant health care burdens. Inadequate preoperative assessment and documentation contribute to communication failure and poor patient outcomes. The aim of this quality improvement project was to design and implement a preoperative evaluation documentation template that not only improved communication during the perioperative pathway but also enhanced the overall user experience. METHODS: We implemented a revamped evidence-based documentation template in the electronic medical records of a health care organization across three internal medicine clinics on the downtown campus and seven satellite family medicine clinics. A pre- and postintervention design was used to assess the template utilization rate and clinician satisfaction. RESULTS: The preoperative template utilization rate increased from 51.2% at baseline to 66.5% after the revamped template "went live" (p < 0.001). Clinician satisfaction with the preoperative documentation template also significantly increased (30.6 vs. 80.0%, p < 0.001). CONCLUSION: Adopting a user-friendly, evidence-based documentation template can enhance the standardization of preoperative evaluation documentation and reduce the documentation burden.

Structure and Funding of Clinical Informatics Fellowships: A National Survey of Program Directors.

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures. OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses. METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, fellows, administrative support, funding sources, and expenses. We surveyed program directors of programs accredited by the Accreditation Council for Graduate Medical Education between 2014 and 2021. RESULTS: We invited 54 program directors, of which 41 (76%) completed the survey. The average administrative support received was $27,732/year. Most programs (85.4%) were accredited to have two or more fellows per year. Programs were administratively housed under six departments: Internal Medicine (17; 41.5%), Pediatrics (7; 17.1%), Pathology (6; 14.6%), Family Medicine (6; 14.6%), Emergency Medicine (4; 9.8%), and Anesthesiology (1; 2.4%). Funding sources for CI fellowship program directors included: hospital or health systems (28.3%), clinical departments (28.3%), graduate medical education office (13.2%), biomedical informatics department (9.4%), hospital information technology (9.4%), research and grants (7.5%), and other sources (3.8%) that included philanthropy and external entities. CONCLUSION: CI fellowships have been established in leading academic and community health care systems across the country. Due to their unique training requirements, these programs require significant resources for education, administration, and recruitment. There continues to be considerable heterogeneity in funding models between programs. Our survey findings reinforce the need for reformed federal funding models for informatics practice and training.

Identification of novel signal of Raynaud's phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches.

BACKGROUND: Calcitonin gene-related peptide (CGRP) antagonists are recently approved for the treatment of migraine. AIM: The main aim of the current study was to find out the association of CGRP antagonists with RP using data mining algorithms integrated with network pharmacological approaches. RESEARCH DESIGN AND METHODS: The individual case safety reports were extracted using OpenVigil2.1-MedDRA-V17 (2004Q1-2022Q3), the United States Adverse Event Reporting System (US FAERS). The data mining algorithms i.e. reporting odds ratio (ROR) with 95% confidence and proportionality reporting ratio (PRR) with associated chi-square value were calculated along with a minimum of three ICSRs to identify the signal. Further, the network was constructed using Cytoscape 3.7.2. Finally, molecular docking was performed using Glide, Schrodinger Inc. RESULTS: The PRR ≥2 with a linked chi-square value ≥4, add up of co-occurrence ≥3, and a lower limit of 95% confidence interval of ROR exceeding 2 indicates a positive signal of RP. Further, the network pharmacological and molecular docking results have shown the involvement of insulin-like growth factor 1-receptor (IGF1R) pathways. CONCLUSION: The RP is recognized as a novel signal with all CGRP antagonists.

Association of temozolomide with progressive multifocal leukoencephalopathy: a disproportionality analysis integrated with network pharmacology.

BACKGROUND: Temozolomide (TMZ) is an alkylating agent approved for the management of glioblastoma. The TMZ is not known for progressive multifocal leukoencephalopathy (PML). The main objective of the current study is to find out the association of TMZ with PML using disproportionality analysis of FDA Adverse Event Reporting System (FAERS) data integrated with network pharmacological approaches. RESEARCH DESIGN AND METHODS: OpenVigil tool was used to query the FAERS database. The disproportionality measures were calculated. The network has been constructed using Cytoscape. Finally, the possible binding interactions were studied using Glide, Schrödinger Inc. RESULTS: A total number of 3502 cases of PML were reported in the FAERS database. Out of these, 10 cases were found with TMZ. The subgroup analysis results have shown a greater number of cases in females. The network has indicated the involvement of human mitogen-activated protein kinase, 3-phosphoinositide-dependent protein kinase 1 protein, human mTOR complex protein, phosphatidylinositol 4,5-bisphosphate 3-kinase protein, and glycogen synthase kinase-3 beta protein. The docking results have indicated good interactions of TMZ with active site of glycogen synthase kinase-3 beta and mitogen-activated protein kinase 1 as compared to other identified targets. CONCLUSION: The PML is identified as novel signal with temozolomide.

Diverse Applications of Three-Dimensional Printing in Biomedical Engineering: A Review.

A three-dimensional (3D) printing is a robotically controlled state-of-the-art technology that is promising for all branches of engineering with a meritorious emphasis to biomedical engineering. The purpose of 3D printing (3DP) is to create exact superstructures without any framework in a brief period with high reproducibility to create intricate and complex patient-tailored structures for organ regeneration, drug delivery, imaging processes, designing personalized dose-specific tablets, developing 3D models of organs to plan surgery and to understand the pathology of disease, manufacturing cost-effective surgical tools, and fabricating implants and organ substitute devices for prolonging the lives of patients, etc. The formulation of bioinks and programmed G codes help to obtain precise 3D structures, which determines the stability and functioning of the 3D-printed structures. Three-dimensional printing for medical applications is ambitious and challenging but made possible with the culmination of research expertise from various fields. Exploring and expanding 3DP for biomedical and clinical applications can be life-saving solutions. The 3D printers are cost-effective and eco-friendly, as they do not release any toxic pollutants or waste materials that pollute the environment. The sampling requirements and processing parameters are amenable, which further eases the production. This review highlights the role of 3D printers in the health care sector, focusing on their roles in tablet development, imaging techniques, disease model development, and tissue regeneration.

Structure-based virtual screening for identification of potential CDC20 inhibitors and their therapeutic evaluation in breast cancer.

Cell division cycle 20 (CDC20), a critical partner of anaphase promoting complex (APC/C), is indispensably required for metaphase-to-anaphase transition. CDC20 overexpression in TNBC breast cancer patients has been found to be correlated with poor prognosis, hence, we aimed to target CDC20 for TNBC therapeutics. In silico molecular docking of large-scale chemical libraries (phytochemicals/synthetic drugs) against CDC20 protein structure identified five synthetic drugs and four phytochemicals as potential hits interacting with CDC20 active site. The molecular selection was done based on docking scores, binding interactions, binding energies and MM/GBSA scores. Further, we analysed ADME profiles for all the hits and identified lidocaine, an aminoamide anaesthetic group of synthetic drug, with high drug-likeness properties. We explored the anti-tumorigenic effects of lidocaine on MDA-MB-231 TNBC breast cancer cells, which resulted in increased growth inhibition in dose-dependent manner. The molecular mechanism behind the cell viability defect mediated by lidocaine was found to be induction of G2/M cell cycle arrest and cellular apoptosis. Notably, lidocaine treatment of TNBC cells also resulted in downregulation of CDC20 gene expression. Thus, this study identifies lidocaine as a potential anti-neoplastic agent for TNBC cells emphasizing CDC20 as a suitable therapeutic target for breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03554-7.

Structure-based virtual screening of chemical libraries as potential MELK inhibitors and their therapeutic evaluation against breast cancer.

New targeted therapy for triple negative breast cancer (TNBC) is an urgent need, as advanced disease responds poorly to conventional chemotherapy. Genomic and proteomic studies are currently investigating new genes and proteins as promising therapeutic targets. One of such therapeutic targets is a cell cycle regulatory kinase; Maternal Embryonic Leucine Zipper Kinase (MELK), overexpressed in TNBC and correlated with cancer development. We performed molecular docking for virtual screening of chemical libraries (phytochemicals/synthetic drugs) against MELK protein structure and identified 8 phytoconstituents (isoxanthorin, emodin, gamma-coniceine, quercetin, tenuazonic acid, isoliquiritigenin, kaempferol, and Nobiletin) and 8 synthetic drugs (tetrahydrofolic acid, alfuzosin, lansoprazole, ketorolac, ketoprofen, variolin B, orantinib, and firestein) as potential hits interacting with the active site residues of MELK based on bound poses, hydrogen bond, hydrophobic interactions and MM/GBSA binding free energies. ADME and drug-likeness prediction further identified few hits with high drug-likeness properties and were further tested for anti-tumorigenic potential. Two phytochemicals isoliquiritigenin and emodin demonstrated growth inhibitory effects on TNBC MDA-MB-231 cells while much lower effect was observed on non-tumorigenic MCF-10A mammary epithelial cells. Treatment with both molecules downregulated MELK expression, induced cell cycle arrest, accumulated DNA damage and enhanced apoptosis. The study identified isoliquiritigenin and emodin as potential MELK inhibitors and provides a basis for subsequent experimental validation and drug development against cancer.

An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections.

Herpes simplex virus (HSV) infection, the most prevalent viral infection that typically lasts for a lifetime, is associated with frequent outbreaks of oral and genital lesions. Oral herpes infection is mainly associated with HSV-1 through oral contact, while genital herpes originates due to HSV-2 and is categorized under sexually transmitted diseases. Immunocompromised patients and children are more prone to HSV infection. Over the years, various attempts have been made to find potential targets for the prevention of HSV infection. Despite the global distress caused by HSV infections, there are no licensed prophylactic and therapeutic vaccines available on the market against HSV. Nevertheless, there are numerous promising candidates in the pre-clinical and clinical stages of study. The present review gives an overview of two herpes viruses, their history, and life cycle, and different treatments adopted presently against HSV infections and their associated limitations. Majorly, the review covers the recent investigations being carried out globally regarding various vaccine strategies against oral and genital herpes virus infections, together with the recent and advanced nanotechnological approaches for vaccine development. Consequently, it gives an insight to researchers as well as people from the health sector about the challenges and upcoming solutions associated with treatment and vaccine development against HSV infections.

Recent Advances in Nanomaterials of Group XIV Elements of Periodic Table in Breast Cancer Treatment.

Breast cancer is one of the most common malignancies and a leading cause of cancer-related mortality among women worldwide. The elements of group XIV in the periodic table exhibit a wide range of chemical manners. Recently, there have been remarkable developments in the field of nanobiomedical research, especially in the application of engineered nanomaterials in biomedical applications. In this review, we concentrate on the recent investigations on the antiproliferative effects of nanomaterials of the elements of group XIV in the periodic table on breast cancer cells. In this review, the data available on nanomaterials of group XIV for breast cancer treatment has been documented, providing a useful insight into tumor biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Precision medicine: Ray of hope in overcoming cancer multidrug resistance.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.

Assessing perceived effectiveness of career development efforts led by the women in American Medical Informatics Association Initiative.

OBJECTIVE: We sought to ascertain perceived factors affecting women's career development efforts in the American Medical Informatics Association (AMIA) and to provide recommendations for improvements. MATERIALS AND METHODS: Data were collected using a 27-item survey administered via the AMIA newsletter and other social channels. Survey questions comprised 3 demographics, 15 Likert-scale, and 9 open-ended items. Likert-scale responses were summarized across respondent ages, career stages, and career domains, and open-ended responses were thematically analyzed. RESULTS: We received survey responses from 109 AMIA women members. Our findings demonstrate that AMIA had made strides in promoting career development, and the most effective AMIA efforts included social events (83%), panel discussions (80%), and scientific sessions (79%). However, despite these efforts, women members perceived that gender-specific challenges persisted within AMIA, and recognized the need for increased networking opportunities (96%), raising awareness of gender-specific challenges (95%), and encouraging gender proportional representation in leadership (92%). DISCUSSION: International and national biomedical informatics professional communities have put forth efforts to address gender-specific issues in career development. Yet, our study identified that some of these, including the deep-rooted gender power hierarchy and bias, are still perceived as profound in AMIA. CONCLUSION: Even though existing career development efforts for women are highly effective, important perceived gender-specific career development issues require further attention and investigation to improve existing AMIA activities.

An Evidence-Based Roadmap for the Provision of More Equitable Telemedicine.

OBJECTIVE: During the coronavirus disease 2019 pandemic, as a safety-net organization with a substantial percentage of patients of color and with limited English proficiency (LEP), we were wary of furthering health disparities in our community. We analyzed gaps in telemedicine (telephone and video) delivery in our communities, quantified the effects of our tests of change, and began the process of accumulating evidence to create a road map for other organizations. METHODS: We leveraged Lean problem-solving strategies to identify modifiable gaps across multiple domains that could inhibit equity in telemedicine. We implemented tests of change across domains of community engagement, technology, education, and access. We observed the proportion of telemedicine encounters across races and languages between April and November, 2020. Regression analyses tested the impact of race and language on telemedicine controlling for age, gender, insurance, and time. RESULTS: Several rounds of changes and enhancements were associated with changes in telemedicine use of +5.5% (p < 0.0001) for Hispanic, +4.0% (p < 0.0001) for Spanish-speaking, -2.1% for Black (p < 0.05), and -4.4% for White patients (p < 0.001). African-American, Hispanic, and non-English-speaking patients had between 2.3 and 4.6 times the odds of preferring telephone to video encounters (p < 0.0001), with increases in preferences for video use over time (p < 0.05). CONCLUSION: Our roadmap to improve equitable delivery of telemedicine was associated with a significant improvement in telemedicine use among certain minority populations. Most populations of color used telephone more often than video. This preference changed over time and with equity-focused changes in telemedicine delivery.

Repurposing Drugs as Novel Triple-negative Breast Cancer Therapeutics.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) is the most aggressive form of Breast Cancer (BC), with high rates of metastasis and recurrence and limited treatment options. Chemotherapy and radiotherapy, for example, have several harmful side effects, and no FDA-approved therapies are currently available. Repurposing old clinically approved drugs to target various TNBC targets is a novel method that has fewer side effects and leads to successful, low-cost drug development in a shorter amount of time. Medicinal plants containing various phytoconstituents (flavonoids, alkaloids, phenols, essential oils, tannins, glycosides, lactones) play a very crucial role in combating various types of diseases and are used in the drug development process because of having lesser side effects. OBJECTIVE: The present review summarizes various categories of repurposed drugs that target multiple targets of TNBC, as well as phytochemical categories that target TNBC singly or in combination with old synthetic drugs. METHODS: Literature information was collected from various databases such as Pubmed, Web of Science, Scopus, and Medline to understand and clarify the role and mechanism of repurposed synthetic drugs and phytoconstituents against TNBC by using keywords like "breast cancer", "repurposed drugs", "TNBC" and "phytoconstituents". RESULTS: Various repurposed drugs and phytochemicals that target different signaling pathways and exert their cytotoxic activities on TNBC cells ultimately lead to cell apoptosis, reducing the recurrence rate and stopping the metastasis process. CONCLUSION: Inhibitory effects can be seen at various levels, providing information and evidence to researchers in the drug development process. As a result, more research and investigations are needed to develop better therapeutic treatment options for TNBC.

Topical Tacrolimus Progylcosomes Nano-Vesicles As a Potential Therapy for Experimental Dry Eye Syndrome.

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.

Extracellular matrix extraction techniques and applications in biomedical engineering.

The concept of tissue engineering involves regeneration and repair of damaged tissue and organs using various combinations of cells, growth factors and scaffolds. The extracellular matrix (ECM) forms the integral part of the scaffold to induce cell proliferation thereby leading to new tissue formation. Decellularization technique provides decellularized ECM (dECM), free of cells while preserving the in vivo biomolecules. In this review, we focus on the detailed methodology of diverse decellularization techniques for various organs of different animals, and the biomedical applications employing the dECM. A culmination of different methods of decellularization is optimized, which offers a suitable microenvironment mimicking the native in vivo topography for in vitro organ regeneration. A detailed assessment of the dECM provides information on the microarchitecture, presence of ECM proteins, biocompatibility and cell proliferation. dECM has also been processed as scaffolds and drug-delivery vehicles, and utilized for regeneration.

Overcoming gaps: regional collaborative to optimize capacity management and predict length of stay of patients admitted with COVID-19.

OBJECTIVE: Ensuring an efficient response to COVID-19 requires a degree of inter-system coordination and capacity management coupled with an accurate assessment of hospital utilization including length of stay (LOS). We aimed to establish optimal practices in inter-system data sharing and LOS modeling to support patient care and regional hospital operations. MATERIALS AND METHODS: We completed a retrospective observational study of patients admitted with COVID-19 followed by 12-week prospective validation, involving 36 hospitals covering the upper Midwest. We developed a method for sharing de-identified patient data across systems for analysis. From this, we compared 3 approaches, generalized linear model (GLM) and random forest (RF), and aggregated system level averages to identify features associated with LOS. We compared model performance by area under the ROC curve (AUROC). RESULTS: A total of 2068 patients were included and used for model derivation and 597 patients for validation. LOS overall had a median of 5.0 days and mean of 8.2 days. Consistent predictors of LOS included age, critical illness, oxygen requirement, weight loss, and nursing home admission. In the validation cohort, the RF model (AUROC 0.890) and GLM model (AUROC 0.864) achieved good to excellent prediction of LOS, but only marginally better than system averages in practice. CONCLUSION: Regional sharing of patient data allowed for effective prediction of LOS across systems; however, this only provided marginal improvement over hospital averages at the aggregate level. A federated approach of sharing aggregated system capacity and average LOS will likely allow for effective capacity management at the regional level.

Role of phytoconstituents in the management of COVID-19.

BACKGROUND: COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. SCOPE AND APPROACH: This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.

Albumin-Coated Mesoporous Silica Nanoparticles of Docetaxel: Preparation, Characterization, and Pharmacokinetic Evaluation.

The potential of albumin-coated hollow mesoporous silica nanoparticles (A-HMSNs) to optimize the chemotherapeutic efficacy of docetaxel (DTX) was explored. The synthesized A-DTX-HMSNs had a nanometric size range, offered large surface area with numerous pores, and offered high drug entrapment and loading, that is, 79.18% ± 1.4% and 19.11% ± 1.30%, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry studies confirmed drug loading and the presence of albumin onto the developed systems, and the drug release followed Higuchi profile. A-HMSNs significantly enhanced the pharmacokinetic profile of DTX by eightfold vis-à-vis the pure DTX. The enhanced plasma levels (Cmax, Tmax, area under the curve), prolonged drug release, long circulation time, lower clearance, hemocompatability, and substantially higher drug loading offered by these nanocarriers inherit promise of a safer and efficacious formulation of DTX.