Pharmacodynamics and safety in relation to dose and response of plant flavonoids in treatment of cancers.

Despite the recent advancements in developing bioactive nutraceuticals as anticancer modalities, their pharmacodynamics, safety profiles, and tolerability remain elusive, limiting their success in clinical trials. The failure of anticancer drugs in clinical trials can be attributed to the changes in drug clearance, absorption, and cellular responses, which alter the dose-response efficacy, causing adverse health effects. Flavonoids demonstrate a biphasic dose-response phenomenon exerting a stimulatory or inhibitory effect and often follow a U-shaped curve in different preclinical cancer models.

Comparative mitogenomic analysis of f. sp. suggests recombination events during its evolutionary history.

Introduction: Modern understanding of the concept of genetic diversity must include the study of both nuclear and organellar DNA, which differ greatly in terms of their structure, organization, gene content and distribution. This study comprises an analysis of the genetic diversity of the smut fungus f. sp.

An Overview of the Characteristics, Pathogenesis, Epidemiology, and Detection of Human Enterovirus in the Arabian Gulf Region.

Enteroviruses are RNA viruses that initiate infections through the gastrointestinal (GI) tract and are associated with enteric illness in individuals of all ages. Most serious infections of enteroviruses are in infants and young children where it is the common cause of aseptic meningitis and other systemic diseases, leading to a high mortality rate. Enteroviruses belong to the small non-enveloped family of the Picornaviridae family.

Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.

Whether neurodevelopmental defects underlie postnatal neuronal death in neurodegeneration is an intriguing hypothesis only recently explored. Here, we focus on spinal muscular atrophy (SMA), a neuromuscular disorder caused by reduced survival of motor neuron (SMN) protein levels leading to spinal motor neuron (MN) loss and muscle wasting. Using the first isogenic patient-derived induced pluripotent stem cell (iPSC) model and a spinal cord organoid (SCO) system, we show that SMA SCOs exhibit abnormal morphological development, reduced expression of early neural progenitor markers, and accelerated expression of MN progenitor and MN markers.

Temperature Dependence of Kinetic Friction: A Handle for Plastics Sortation?

Sortation is a crucial step in mechanical recycling of post-consumer plastics (PCR) whereby properties such as density or spectral signature are used to separate plastics. However it is difficult to sort polyolefin flakes at high throughput by these properties. We ask whether the frictional properties of plastics as a function of temperature may be used as an alternate sorting property.

Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator.

Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa.

Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair.

Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR.

The effects of using a flipped classroom pedagogy in nursing anesthesia education: a program evaluation.

Background: The flipped classroom (FC) pedagogy improves undergraduate student proficiency and satisfaction. However, its effectiveness has not been demonstrated in nursing anesthesia education.

Objectives: Pre- and post-FC tests and course evaluations were retrospectively compared to determine if FC was an effective pedagogy for a nursing anesthesia program (NAP).

Development of a Novel DNA Mono-alkylator Platform for Antibody-Drug Conjugates.

Although microtubule inhibitors (MTI) remain a therapeutically valuable payload option for antibody-drug conjugates (ADC), some cancers do not respond to MTI-based ADCs. Efforts to fill this therapeutic gap have led to a recent expansion of the ADC payload "toolbox" to include payloads with novel mechanisms of action such as topoisomerase inhibition and DNA cross-linking. We present here the development of a novel DNA mono-alkylator ADC platform that exhibits sustained tumor growth suppression at single doses in MTI-resistant tumors and is well tolerated in the rat upon repeat dosing.

Artificial selection of microbial communities: what have we learnt and how can we improve?

Microbial communities are capable of performing diverse functions with important bioindustrial and medical applications. One approach to improving community function is to breed new communities by artificially selecting for those displaying high community function ('community selection'). Importantly, community selection can improve the function of interest without needing to understand how the function arises, just like in classical artificial selection of individuals.

Virtual student-led neuroscience conferencing: a UK multicentre prospective study investigating delegate outcomes and delivery mode.

Background: Clinical neuroscience training programmes are becoming increasingly competitive to enter. UK university neuroscience societies act as a local environment for students to develop their career interests and provide portfolio building opportunities through hosting events such as annual conferences. Recently there has been a transition to more of these events being held online yet the impact of this, if any, remains unclear.

Discovery and Optimization of a STING Agonist Platform for Application in Antibody Drug Conjugates.

While STING agonists have proven to be effective preclinically as anti-tumor agents, these promising results have yet to be translated in the clinic. A STING agonist antibody-drug conjugate (ADC) could overcome current limitations by improving tumor accessibility, allowing for systemic administration as well as tumor-localized activation of STING for greater anti-tumor activity and better tolerability. In line with this effort, a STING agonist ADC platform was identified through systematic optimization of the payload, linker, and scaffold based on multiple factors including potency and specificity in both in vitro and in vivo evaluations.

An approach for in-situ detection of gold colloid aggregates amyloid formations within the hippocampus of the Cohen's Alzheimer's disease rat model by surface enhanced raman scattering methods.

Background: Amyloid beta (Aβ) peptides, such as Aβ or Aβ are regarded as hallmark neuropathological biomarkers associated with Alzheimer's disease (AD). The formation of an aggregates by Aβ or Aβ-coated gold nano-particles are hypothesized to contain conformation of Aβ oligomers, which could exist only at an initial stage of fibrillogenesis.

New Method: The attempt of in-situ detection of externally initiated gold colloid (ca.

The cost effectiveness of tranexamic acid for preventing periprosthetic joint infection following total shoulder arthroplasty: a break-even analysis.

Background: The use of tranexamic acid (TXA) has become widespread in orthopedics to promote hemostasis and has been successfully used to reduce blood loss and infection risk in joint arthroplasty. However, the cost effectiveness of routine TXA use for the prevention of periprosthetic infections in total shoulder arthroplasty remains unknown.

Methods: The acquisition cost of TXA ($5.

Exploring a global interpretation mechanism for deep learning networks when predicting sepsis.

The purpose of this study is to identify additional clinical features for sepsis detection through the use of a novel mechanism for interpreting black-box machine learning models trained and to provide a suitable evaluation for the mechanism. We use the publicly available dataset from the 2019 PhysioNet Challenge. It has around 40,000 Intensive Care Unit (ICU) patients with 40 physiological variables.

Critically Appraising Pragmatist Critiques of Evidence-Based Medicine: Is EBM Defensible on Pragmatist Grounds?

Significant contributions to debates in the philosophy of evidence-based medicine (EBM) have come from a variety of different philosophical quarters, yet mainstream discourse in the field has been largely devoid of contributions from scholars working in the pragmatist tradition. This is a particularly conspicuous omission, given pragmatism's commitment to the melioristic view that philosophy both can, and should, be about the business of concretely bettering the human estate. Two exceptions to this oversight come from Brian Walsh and Maya Goldenberg.

Evaluating the baseline auscultation abilities of second-year chiropractic students using simulated patients and high-fidelity manikin simulators: A pilot study.

Objective: To assess the ability of 2nd-year students to identify normal and abnormal findings during cardiac and lung auscultation using high-fidelity manikin simulators and standardized patients. A secondary objective was to assess students' perceived competence and confidence in their abilities.

Methods: This was a descriptive pilot study of randomly selected 2nd-year students at 1 chiropractic training program.

Discovery of novel polyamide-pyrrolobenzodiazepine hybrids for antibody-drug conjugates.

Pyrrolobenzodiazepine (PBD) dimers are well-known highly potent antibody drug conjugate (ADC) payloads. The corresponding PBD monomers, in contrast, have received much less attention from the ADC community. We prepared several novel polyamide-linked PBD monomers and evaluated their utility as ADC payloads.

DeepNC: a framework for drug-target interaction prediction with graph neural networks.

The exploration of drug-target interactions (DTI) is an essential stage in the drug development pipeline. Thanks to the assistance of computational models, notably in the deep learning approach, scientists have been able to shorten the time spent on this stage. Widely practiced deep learning algorithms such as convolutional neural networks and recurrent neural networks are commonly employed in DTI prediction projects.

Teaching Nurse Practitioner Students Advanced Health Assessment Skills During COVID-19.

The purpose of this project was to evaluate student outcomes before and during the coronavirus disease 2019 (COVID-19) pandemic in an advanced health assessment course that was offered in the summer semesters to nurse practitioner (NP) students as a hybrid course with online didactic and in-person lab components. Due to COVID-19, the summer 2020 course offering transitioned to being 100% online and innovative strategies replaced the in-person labs. Student outcomes from summer 2019, when the course was hybrid, were compared to summer 2020, when the course was changed to being 100% online.

Characteristics of Forces at the Clinician-Patient and Patient-Table Interfaces During Thoracic Spinal Manipulation in Asymptomatic Adults Are Consistent With Deformable Body Models.

Investigating all forces exerted on the patient's body during high-velocity, low-amplitude spinal manipulative therapy (SMT) remains fundamental to elucidate how these may contribute to SMT's effects. Previous conflicting findings preclude our understanding of the relationship between SMT forces acting at the clinician-patient and patient-table interfaces. This study aimed to quantify forces at the clinician-participant and participant-table interfaces during thoracic SMT in asymptnomatic adults.

Mechanistic and therapeutic implications of EphA-4 receptor tyrosine kinase in the pathogenesis of Alzheimer's disease.

Erythropoietin-producing hepatoma (Eph) receptors belong to a family of tyrosine kinase receptors that plays a pivotal role in the development of the brain. Eph can be divided broadly into two groups, namely, EphA and EphB, comprising nine and five members, respectively. In recent years, the role of EphA-4 has become increasingly apparent in the onset of Alzheimer's disease (AD).