The primate gut mycobiome-bacteriome interface is impacted by environmental and subsistence factors.

The gut microbiome of primates is known to be influenced by both host genetic background and subsistence strategy. However, these inferences have been made mainly based on adaptations in bacterial composition - the bacteriome and have commonly overlooked the fungal fraction - the mycobiome. To further understand the factors that shape the gut mycobiome of primates and mycobiome-bacteriome interactions, we sequenced 16 S rRNA and ITS2 markers in fecal samples of four different nonhuman primate species and three human groups under different subsistence patterns (n = 149).

The Value of Health Economics and Outcomes Research in Prosthetics and Orthotics.

The demand has increased for evidence regarding the effectiveness and value of prosthetic and orthotic rehabilitation interventions. Clinicians and managers are under pressure to provide treatment recommendations and demonstrate effectiveness through outcomes. It is often assumed that rehabilitation interventions, including the provision of custom-made and custom-fit orthotic and prosthetic devices, are beneficial to patients.

Value and Applicability of Large Administrative Healthcare Databases in Prosthetics and Orthotics Outcomes Research.

The goal of health economics and outcomes research is to improve healthcare decision making. In the absence of high-value clinical data, the availability and quality of administrative healthcare data could be vital in the generation of evidence for orthotics and prosthetics services. The purpose of this article is to provide a stronger understanding of administrative healthcare data analysis, an area that has been scarcely examined within prosthetics and orthotics despite the wealth of information available within such data.

A Retrospective Analysis of Feeding Practices and Complications in Patients with Critical Bronchiolitis on Non-Invasive Respiratory Support.

Limited data exist regarding feeding pediatric patients managed on non-invasive respiratory support (NRS) modes that augment oxygenation and ventilation in the setting of acute respiratory failure. We conducted a retrospective cohort study to explore the safety of feeding patients managed on NRS with acute respiratory failure secondary to bronchiolitis. Children up to two years old with critical bronchiolitis managed on continuous positive airway pressure, bilevel positive airway pressure, or RAM cannula were included.

Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016-2020).

: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus has been considered as effective anticancer drug targets. Many PI3K inhibitors have been developed and progressed to various stages of clinical trials, and some have been approved as anticancer treatment. In this review, we discuss the drug design and clinical development of PI3K inhibitors over the past 4 years.

An Updated Review on Betacoronavirus Viral Entry Inhibitors: Learning from Past Discoveries to Advance COVID-19 Drug Discovery.

Even after one year of its first outbreak reported in China, the coronavirus disease 2019 (COVID-19) pandemic is still sweeping the World, causing serious infections and claiming more fatalities. COVID-19 is caused by the novel coronavirus SARS-CoV-2, which belongs to the genus Betacoronavirus (β-CoVs), which is of greatest clinical importance since it contains many other viruses that cause respiratory disease in humans, including OC43, HKU1, SARS-CoV, and MERS. The spike (S) glycoprotein of β-CoVs is a key virulence factor in determining disease pathogenesis and host tropism, and it also mediates virus binding to the host's receptors to allow viral entry into host cells, i.

An Updated Review on SARS-CoV-2 Main Proteinase (M): Protein Structure and Small-Molecule Inhibitors.

[Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses with spike (S) protein projections that allow the virus to enter and infect host cells. The S protein is a key virulence factor determining viral pathogenesis, host tropism, and disease pathogenesis. There are currently diverse corona viruses that are known to cause disease in humans.

The use of copper to help prevent transmission of SARS-coronavirus and influenza viruses. A general review.

The SARS-CoV-2 is the causative agent of the COVID-19 disease, a severe acute respiratory syndrome-coronavirus (SARS-CoV). Its main transmission pathway is through large respiratory droplets, as well as direct and indirect contact. Copper in different formats has been used in research and clinical settings to reduce the risk of bacterial and viral contamination.

An Integrative Informatics Approach to Explain the Mechanism of Action of N1-(Anthraquinon-2-yl) Amidrazones as BCR/ABL Inhibitors.

Background: Drugs incorporating heterocyclic chemical skeletons possess a plethora of therapeutic activities such as anticancer, antimicrobial, antihypertensive, and antipsychiatric effects. It is becoming routine, nowadays, to use cheminformatics and bioinformatics methods to elucidate the mechanism(s) of action of such drugs.

Objective: This study aimed to probe the activity of a recently published series of N1- (anthraquinon-2-yl) amidrazone piperazine derivatives employing computational strategies[1], identify their structural basis of binding to BCR/ABL kinase domain, and explain their anticancer activities in human breast adenocarcinoma (MCF-7) and chronic myelogenous leukemia (K562) cell lines.

Portraits of Suzanne, an Osage Woman's Story of Loving the Sun and Living With Skin Cancer.

Suzanne, an elder of The Osage Nation, has been diagnosed with basal cell carcinoma, squamous cell carcinoma, and melanoma skin cancer. Her daughter, Bobbie, a cancer researcher working for the Youth Enjoy Science Research Education Program, conducted a case study to share Suzanne's story through written narrative and a series of images that present Suzanne's reflections on cancer prevention and treatment from a holistic perspective. Seven interview transcripts, as well as photographs, drawings, and paintings of Suzanne, were created and analyzed to explore Suzanne's lived experience of cancer.

Ligand-Based Drug Design: Synthesis and Biological Evaluation of Substituted Benzoin Derivatives as Potential Antitumor Agents.

Background: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design.

Objectives: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Kα complex interaction and antiproliferative activity.

Methods: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies.

Ask Me about My Pearls: Burn Care, Ethics, and Creative Writing.

Channeling feelings into the written word rather than the scalpel was at the heart of the creative writing challenge that the first author (DR) accepted when she joined the Seven Doctors Project at the University of Nebraska Medical Center in 2008. Burnout has become recognized as a factor undermining physicians' quality of life, and the practice of creative writing helps mitigate stress and sustain a successful practice. When physicians partner with and are mentored by a seasoned creative writer, creative writing can serve as an exercise in ethical reflection, which is particularly valuable at mid-career; this is the subject of the following dialogue between one physician writer and the facilitator of the Seven Doctors Project creative writing class.

A Science Products Inventory for Citizen-Science Planning and Evaluation.

Citizen science involves a range of practices involving public participation in scientific knowledge production, but outcomes evaluation is complicated by the diversity of the goals and forms of citizen science. Publications and citations are not adequate metrics to describe citizen-science productivity. We address this gap by contributing a science products inventory (SPI) tool, iteratively developed through an expert panel and case studies, intended to support general-purpose planning and evaluation of citizen-science projects with respect to science productivity.

A Science Products Inventory for Citizen-Science Planning and Evaluation.

Citizen science involves a range of practices involving public participation in scientific knowledge production, but outcomes evaluation is complicated by the diversity of the goals and forms of citizen science. Publications and citations are not adequate metrics to describe citizen-science productivity. We address this gap by contributing a science products inventory (SPI) tool, iteratively developed through an expert panel and case studies, intended to support general-purpose planning and evaluation of citizen-science projects with respect to science productivity.

Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

Background: Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design.

Objectives: Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds.

Methods: Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation.

Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

Background: Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design.

Objective: Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series.

Methods: Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies.

A Multivariate Assessment of Clinical Contributions to the Severity of Perceived Dysfunction Measured by the Cumberland Ankle Instability Tool.

Chronic ankle instability is a common pathological consequence of ankle sprains. However, screening tools which assess self-reported dysfunction offer little insight into clinical factors which may be useful to improve deficits. The purpose of this study was to identify factors that contribute most to self-reported dysfunction.

Modeling the protonation states of β-secretase binding pocket by molecular dynamics simulations and docking studies.

β-secretase (BACE1) is an aspartyl protease that processes the β-amyloid peptide in the human brain in patients with Alzheimer's disease. There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Although it is believed that the net charge of the Asp dyad is -1, the exact protonation state still remains a matter of debate.

CROSS-CULTURAL ADAPTATION AND VALIDATION OF THE KOREAN VERSION OF THE CUMBERLAND ANKLE INSTABILITY TOOL.

Background: The Cumberland Ankle Instability Tool (CAIT) is a valid and reliable patient reported outcome used to assess the presence and severity of chronic ankle instability (CAI). The CAIT has been cross-culturally adapted into other languages for use in non-English speaking populations. However, there are no valid questionnaires to assess CAI in individuals who speak Korean.

Advances in the Development of Class I Phosphoinositide 3-Kinase (PI3K) Inhibitors.

The PI3K signaling cascade is the key moderator of cell proliferation, survival, motility, and apoptosis. Class I PI3K proteins are well characterized and linked to thrombosis (PI3Kβ), rheumatoid arthritis (PI3Kδ), and cancer (PI3Kα). In this review, we explore the latest progress in the design and development of selective Class I PI3K inhibitors from the perspective of drug design and structure activity relationships.

Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway.

Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer.

Recent advances in small molecule inhibitors of VEGFR and EGFR signaling pathways.

Aberrant angiogenesis has been observed in many solid tumors. The formation and metastases of tumors such as non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) are very complex, often regulated by proangiogenic factors such as the vascular endothelial growth factor (VEGF) and other tyrosine kinases. The VEGFR, EGFR and mTOR pathways have played critical roles in controlling cell proliferation and angiogenesis.

Induced-fit docking studies of the active and inactive states of protein tyrosine kinases.

Inhibition of tyrosine kinases (such as the epidermal growth factor receptor, EGFR, and/or Abelson leukemia virus protein kinase, ABL) represents a major advancement in the treatment of solid tumors, supported by the clinical administration of gefitinib, erlotinib, imatinib, and dasatinib. The identification of the binding interactions in the EGFR/ligands and the ABL/ligands complexes can facilitate the structure-based design of new tyrosine kinase inhibitors. We carried out induced-fit docking studies of 18 structurally diverse kinase inhibitors against the EGFR, the active and inactive states of the ABL protein.

Brains Rule!: a model program for developing professional stewardship among neuroscientists.

Brains Rule! Neuroscience Expositions, funded through a National Institute on Drug Abuse Science Education Drug Abuse Partnership Award, has developed a successful model for informal neuroscience education. Each Exposition is a "reverse science fair" in which neuroscientists present short neuroscience teaching modules to students. This study focuses on results of assessments conducted with neuroscientist presenters during Expositions at two sites, Atlanta, Georgia and Corpus Christi, Texas.