Evolutionary algorithms simulating molecular evolution: a new field proposal.

The genetic blueprint for the essential functions of life is encoded in DNA, which is translated into proteins-the engines driving most of our metabolic processes. Recent advancements in genome sequencing have unveiled a vast diversity of protein families, but compared with the massive search space of all possible amino acid sequences, the set of known functional families is minimal. One could say nature has a limited protein "vocabulary.

Three-Dimensional Printing of Drug-Eluting Implantable PLGA Scaffolds for Bone Regeneration.

Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.

CRISPR/Cas Technology: The Unique Synthetic Biology Genome-Editing Tool Shifting the Paradigm in Viral Diagnostics, Defense, and Therapeutics.

The emergence of the COVID-19 pandemic has starkly exposed our significantly limited ability to promptly identify and respond to emergent biological threats. Consequently, there is an urgent need to advance biotechnological methods for addressing both known and unforeseen biological hazards. Recently, the CRISPR/Cas system has revolutionized genetic engineering, enabling precise and efficient synthetic biology applications.

Rapidly Dissolving Trans-scleral Microneedles for Intraocular Delivery of Cyclosporine A.

Cyclosporine A (CsA) is a cyclic peptide immunosuppressant drug that is beneficial in the treatment of various ocular diseases. However, its ocular bioavailability in the posterior eye is limited due to its poor aqueous solubility. Conventional CsA formulations such as a solution or emulsion permeate poorly across the eye due to various static and dynamic barriers of the eye.

The impact of tumor microenvironment: unraveling the role of physical cues in breast cancer progression.

Metastasis accounts for the vast majority of breast cancer-related fatalities. Although the contribution of genetic and epigenetic modifications to breast cancer progression has been widely acknowledged, emerging evidence underscores the pivotal role of physical stimuli in driving breast cancer metastasis. In this review, we summarize the changes in the mechanics of the breast cancer microenvironment and describe the various forces that impact migrating and circulating tumor cells throughout the metastatic process.

3D-Printed Capsaicin-Loaded Injectable Implants for Targeted Delivery in Obese Patients.

Diet-induced obesity and hyperlipidemia are a growing public health concern leading to various metabolic disorders. Capsaicin, a major bioactive compound obtained from natural chili peppers, has demonstrated its numerous beneficial roles in treating obesity and weight loss. Current treatment involves either administration of antiobesity drugs or surgical procedures such as Roux-en-Y-gastric bypass or sleeve gastrectomy, both of which are associated with serious side effects and poor patient acceptance.

Metronomic Administration of Topotecan Alone and in Combination with Docetaxel Inhibits Epithelial-mesenchymal Transition in Aggressive Variant Prostate Cancers.

Unlabelled: Prostate cancer is the second leading cause of noncutaneous cancer-related deaths in American men. Androgen deprivation therapy (ADT), radical prostatectomy, and radiotherapy remain the primary treatment for patients with early-stage prostate cancer (castration-sensitive prostate cancer). Following ADT, many patients ultimately develop metastatic castration-resistant prostate cancer (mCRPC).

Gentamicin Eluting 3D-Printed Implants for Preventing Post-Surgical Infections in Bone Fractures.

A surgically implantable device is an inevitable treatment option for millions of people worldwide suffering from diseases arising from orthopedic injuries. A global paradigm shift is currently underway to tailor and personalize replacement or reconstructive joints. Additive manufacturing (AM) has provided dynamic outflow to the customized fabrication of orthopedic implants by enabling need-based design and surface modification possibilities.

Ratiometric Inclusion of Fibroblasts Promotes Both Castration-Resistant and Androgen-Dependent Tumorigenic Progression in Engineered Prostate Cancer Tissues.

To investigate the ratiometric role of fibroblasts in prostate cancer (PCa) progression, this work establishes a matrix-inclusive, 3D engineered prostate cancer tissue (EPCaT) model that enables direct coculture of neuroendocrine-variant castration-resistant (CPRC-ne) or androgen-dependent (ADPC) PCa cells with tumor-supporting stromal cell types. Results show that the inclusion of fibroblasts within CRPC-ne and ADPC EPCaTs drives PCa aggression through significant matrix remodeling and increased proliferative cell populations. Interestingly, this is observed to a much greater degree in EPCaTs formed with a small number of fibroblasts relative to the number of PCa cells.

Plantar threshold sensitivity assessment using an automated tool-Clinical assessment comparison between a control population without type 2 diabetes mellitus, and populations with type 2 diabetes mellitus, with and without neuropathy symptoms.

Diabetic peripheral neuropathy is often classified as a loss of sensation in the extremities, particularly in elderly populations. The most common diagnosis technique is with the use of the hand-applied Semmes-Weinstein monofilament. This study's first aim was to quantify and compare sensation on the plantar surface in healthy and type 2 diabetes mellitus populations with the standard Semmes-Weinstein hand-applied methodology and a tool that automates this approach.

Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments.

Neural-fuzzy machine learning approach for the fatigue-creep reliability modeling of SAC305 solder joints.

The accuracy of reliability models is one of the most problematic issues that must be considered for the life of electronic assemblies, particularly those used for critical applications. The reliability of electronics is limited by the fatigue life of interconnected solder materials, which is influenced by many factors. This paper provides a method to build a robust machine-learning reliability model to predict the life of solder joints in common applications.

Understanding post-surgical decline in left ventricular function in primary mitral regurgitation using regression and machine learning models.

Background: Class I echocardiographic guidelines in primary mitral regurgitation (PMR) risks left ventricular ejection fraction (LVEF) < 50% after mitral valve surgery even with pre-surgical LVEF > 60%. There are no models predicting LVEF < 50% after surgery in the complex interplay of increased preload and facilitated ejection in PMR using cardiac magnetic resonance (CMR).

Objective: Use regression and machine learning models to identify a combination of CMR LV remodeling and function parameters that predict LVEF < 50% after mitral valve surgery.

The Combined Impact of Hand-Arm Vibration and Noise Exposure on Hearing Sensitivity of Agricultural/Forestry Workers-A Systematic Literature Review.

Hand-arm vibration (HAV), which potentially causes vibration white finger (VWF), and occupational noise are serious issues in the agricultural and forestry industries. Generally, agricultural workers operate as single-family/small businesses and thus are exempted from Occupational Safety and Health Administration (OSHA) regulations/laws for noise and HAV otherwise applicable to other industries in general. The agricultural/forestry sectors are at increased risk as working hours are longer than a typical 8-h work shift putting them at greater risk of hearing loss.

Reliability modeling of the fatigue life of lead-free solder joints at different testing temperatures and load levels using the Arrhenius model.

Reliability of the microelectronic interconnection materials for electronic packages has a significant impact on the fatigue properties of the electronic assemblies. This is due to the correlation between solder joints reliability and the most frequent failure modes seen in electronic devices. Due to their superior mechanical and fatigue properties, SAC alloys have supplanted Pb-solder alloys as one of the most commonly used solder materials used as interconnection joints on electronic packages.

Integrating Pharmacogenomics Data-Driven Computational Drug Prediction with Single-Cell RNAseq to Demonstrate the Efficacy of a NAMPT Inhibitor against Aggressive, Taxane-Resistant, and Stem-like Cells in Lethal Prostate Cancer.

Metastatic prostate cancer/PCa is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and, therefore, androgen deprivation therapies/ADT-sensitive. However, eventual resistance to standard medical castration (AR-inhibitors) and secondary chemotherapies (taxanes) is nearly universal.

Enhanced Topical Co-delivery of Acyclovir and Lidocaine Gel Formulation Across Dermatomed Human Skin.

Acyclovir a widely used drug in the treatment of herpes simplex virus (HSV) infections and lidocaine a local anesthetic were combined in a topical gel formulation. The topical gel with Transcutol P (TP) or N-methyl 2-pyrrolidone (NMP) was prepared and tested for in vitro skin permeation across the intact and microneedle-treated human cadaver skin. The topical gels containing 5% each of acyclovir and lidocaine showed optimal pH, spreadability, and 100% drug release.

Interstitial Collagen Loss, Myocardial Remodeling, and Function in Primary Mitral Regurgitation.

Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation.

Mitigating urinary incontinence condition using machine learning.

Background: Urinary incontinence (UI) is the inability to completely control the process of releasing urine. UI presents a social, medical, and mental issue with financial consequences.

Objective: This paper proposes a framework based on machine learning for predicting urination time, which can benefit people with various degrees of UI.

Tunable three-dimensional engineered prostate cancer tissues for in vitro recapitulation of heterogeneous in vivo prostate tumor stiffness.

In this manuscript we report the establishment and characterization of a three-dimensional in vitro, coculture engineered prostate cancer tissue (EPCaT) disease model based upon and informed by our characterization of in vivo prostate cancer (PCa) xenograft tumor stiffness. In prostate cancer, tissue stiffness is known to impact changes in gene and protein expression, alter therapeutic response, and be positively correlated with an aggressive clinical presentation. To inform an appropriate stiffness range for our in vitro model, PC-3 prostate tumor xenografts were established.