The biochemical mechanisms of plastic biodegradation.

Since the invention of the first synthetic plastic, an estimated 12 billion metric tons of plastics have been manufactured, 70% of which was produced in the last 20 years. Plastic waste is placing new selective pressures on humans and the organisms we depend on, yet it also places new pressures on microorganisms as they compete to exploit this new and growing source of carbon. The limited efficacy of traditional recycling methods on plastic waste, which can leach into the environment at low purity and concentration, indicates the utility of this evolving metabolic activity.

From joint pains to hair gains: baricitinib's double duty for rheumatoid arthritis and alopecia areata.

Personalised medicine is a key goal across medical specialties today: using biomarkers and knowledge of pathophysiology to ensure the right patients get the right treatment. This becomes more challenging when patients have more than one disease requiring a targeted treatment. Autoimmune diseases commonly co-occur, and thus, multidisciplinary working is important in rheumatology.

Pituitary neuroendocrine tumors and granular cell pituicytomas at autopsy: Incidence, cell types, locations, and histogenesis in 150 pituitary glands.

Objectives: The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis.

Methods: In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000.

Sustainability Planning for a Community Network to Increase Participation in Evidence-Based Lifestyle Change Programs: A Mixed-Methods Approach.

Community-based chronic disease prevention programs can have long-term, broad public health benefits. Yet, only 40 to 60% of evidence-based health programs are sustained. Using established frameworks and evidence-based tools to characterize sustainability allows programs to develop structures and processes to leverage resources effectively to sustain effective program activities and systems.

Transcriptomics Studies Reveal Functions of Transglutaminase 2 in Breast Cancer Cells Using Membrane Permeable and Impermeable Inhibitors.

Transglutaminase 2 (TG2) performs many functions both under physiological and pathological conditions. In cancer, its expression is associated with aggressiveness, propensity to epithelial-mesenchymal transition, and metastasis. Since TG2 performs key functions both outside and inside the cell, using inhibitors with different membrane permeability we analyzed the changes in the transcriptome induced in two triple-negative cell lines (MDA-MB-436 and MDA-MB-231) with aggressive features.

Solvent Suppression in Pure Shift NMR.

Intense solvent signals in H solution-state NMR experiments typically cause severe distortion of spectra and mask nearby solute signals. It is often infeasible or undesirable to replace a solvent with its perdeuterated form, for example, when analyzing formulations in situ, when exchangeable protons are present, or for practical reasons. Solvent signal suppression techniques are therefore required.

Coupling during collective cell migration is controlled by a vinculin mechanochemical switch.

The ability of cells to move in a mechanically coupled, coordinated manner, referred to as collective cell migration, is central to many developmental, physiological, and pathophysiological processes. Limited understanding of how mechanical forces and biochemical regulation interact to affect coupling has been a major obstacle to unravelling the underlying mechanisms. Focusing on the linker protein vinculin, we use a suite of Förster resonance energy transfer-based biosensors to probe its mechanical functions and biochemical regulation, revealing a switch that toggles vinculin between loadable and unloadable states.

Equity-related 'knots' in theory of change development: Conceptualization and case illustrations.

Theory of change (ToC) is an approach widely used to guide planning, implementing, and evaluating change initiatives. While there is substantial guidance, there has been little attention on equity within ToC research and practice. We propose and illustrate the metaphor of 'knots' to frame practical and ethical challenges that arise when centering equity within ToC processes.

Framework for Radiation Oncology Department-wide Evaluation and Implementation of Commercial Artificial Intelligence Autocontouring.

Purpose: Artificial intelligence (AI)-based autocontouring in radiation oncology has potential benefits such as standardization and time savings. However, commercial AI solutions require careful evaluation before clinical integration. We developed a multidimensional evaluation method to test pretrained AI-based automated contouring solutions across a network of clinics.

High-Affinity Fluorogenic Substrate for Tissue Transglutaminase Reveals Enzymatic Hysteresis.

Transglutaminases (TGases) are a family of calcium-dependent enzymes primarily known for their ability to cross-link proteins. Transglutaminase 2 (TG2) is one isozyme in this family whose role is multifaceted. TG2 can act not only as a typical transamidase through its catalytic core but also as a G-protein via its GTP binding site.

Improved safety and quality in intravascular brachytherapy: A multi-institutional study using failure modes and effects analysis.

Purpose: Highlight safety considerations in intravascular brachytherapy (IVBT) programs, provide relevant quality assurance (QA) and safety measures, and establish their effectiveness.

Methods And Materials: Radiation oncologists, medical physicists, and cardiologists from three institutions performed a failure modes and effects analysis (FMEA) on the radiation delivery portion of IVBT. We identified 40 failure modes and rated the severity, occurrence, and detectability before and after consideration of safety practices.

Artificial intelligence (AI) and machine learning (ML) in precision oncology: a review on enhancing discoverability through multiomics integration.

Multiomics data including imaging radiomics and various types of molecular biomarkers have been increasingly investigated for better diagnosis and therapy in the era of precision oncology. Artificial intelligence (AI) including machine learning (ML) and deep learning (DL) techniques combined with the exponential growth of multiomics data may have great potential to revolutionize cancer subtyping, risk stratification, prognostication, prediction and clinical decision-making. In this article, we first present different categories of multiomics data and their roles in diagnosis and therapy.

Cell-Impermeable Inhibitors Confirm That Intracellular Human Transglutaminase 2 Is Responsible for the Transglutaminase-Associated Cancer Phenotype.

Transglutaminase 2 (TG2) is a multifunctional enzyme primarily responsible for crosslinking proteins. Ubiquitously expressed in humans, TG2 can act either as a transamidase by crosslinking two substrates through formation of an N(ɣ-glutaminyl)lysine bond or as an intracellular G-protein. These discrete roles are tightly regulated by both allosteric and environmental stimuli and are associated with dramatic changes in the conformation of the enzyme.

A Communitywide Collaboration to Increase Enrollment, Retention, and Success in Evidence-Based Lifestyle-Change Programs in Racial and Ethnic Minority Populations.

Purpose And Objectives: Chronic diseases (eg, diabetes, hypertension) are the leading causes of death in the US and disproportionally affect racial and ethnic minority populations. This disparity is partially due to the unequal burden of unmet social needs that stem from several factors, including racism.

Intervention Approach: The Alliance is a collaboration among health care, public health, and community organizations formed to improve referral, enrollment, and successful completion of evidence-based lifestyle-change programs, particularly among Black people.

Exploring Biopharmaceutical Analysis with Compact Capillary Liquid Chromatography Instrumentation.

A recent trend in the design of liquid chromatography (LC) instrumentation is the move towards miniaturized and portable systems. These smaller platforms provide wider flexibility in operation, with the opportunity for conducting analysis directly at the point of sample collection rather than transporting the sample to a centralized laboratory facility. For the manufacturing of pharmaceutical and biopharmaceutical products, these platforms can be implemented for process monitoring and product characterization directly in manufacturing environments.

Independent association of metabolic tumor response on FDG-PET with pulmonary toxicity following risk-adaptive chemoradiation for unresectable non-small cell lung cancer: Inherent radiosensitivity or immune response?

Background: In the context of a phase II trial of risk-adaptive chemoradiation, we evaluated whether tumor metabolic response could serve as a correlate of treatment sensitivity and toxicity.

Methods: Forty-five patients with AJCCv7 stage IIB-IIIB NSCLC enrolled on the FLARE-RT phase II trial (NCT02773238). [18F]fluorodeoxyglucose (FDG) PET-CT images were acquired prior to treatment and after 24 Gy during week 3.

Column selection considerations in compact capillary liquid chromatography.

Recent years have seen significant advances in compact, portable capillary LC instrumentation. This study explores the performances of several commercially available columns within the pressure and flow limits of both the columns and one of these compact LC instruments. The commercially available compact capillary LC system with UV-absorbance detector used in this study is typically operated using columns in the 0.

Resolving the complexity in human milk oligosaccharides using pure shift NMR methods and CASPER.

Human milk oligosaccharides belong to an important class of bioactive molecules with diverse effects on the development of infants. NMR is capable of providing vital structural information about oligosaccharides which can aid in determining structure-function relationships. However, this information is often concealed by signal overlap in H spectra, due to the narrow chemical shift range and signal multiplicity.

Ultra-selective, ultra-clean 1D rotating-frame Overhauser effect spectroscopy.

An ultra-selective 1D NMR experiment - GEMSTONE-ROESY - enables clear, unambiguous assignment of ROE signals in the not uncommon situation that traditional selective methods fail. Its usefulness is demonstrated in the analysis of the natural products cyclosporin and lacto--difucohexaose I, providing detailed insight into the structures and conformations of these molecules.

Novel irreversible peptidic inhibitors of transglutaminase 2.

Transglutaminase 2 (TG2), also referred to as tissue transglutaminase, plays crucial roles in both protein crosslinking and cell signalling. It is capable of both catalysing transamidation and acting as a G-protein, these activities being conformation-dependent, mutually exclusive, and tightly regulated. The dysregulation of both activities has been implicated in numerous pathologies.

Peptidic Inhibitors and a Fluorescent Probe for the Selective Inhibition and Labelling of Factor XIIIa Transglutaminase.

Factor XIIIa (FXIIIa) is a transglutaminase of major therapeutic interest for the development of anticoagulants due to its essential role in the blood coagulation cascade. While numerous FXIIIa inhibitors have been reported, they failed to reach clinical evaluation due to their lack of metabolic stability and low selectivity over transglutaminase 2 (TG2). Furthermore, the chemical tools available for the study of FXIIIa activity and localization are extremely limited.

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive to Change in Carotenoid Intake in a 6-Week Randomized Controlled Feeding Trial in a Racially/Ethnically Diverse Sample.

Background: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake.

Objectives: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial.

Coupling During Collective Cell Migration is Controlled by a Vinculin Mechanochemical Switch.

Collective cell migration (CCM) plays important roles in development, physiological, and pathological processes. A key feature of CCM is the dynamic mechanical coupling between cells, which enables both long-range coordination and local rearrangements. This coupling requires the ability of cell adhesions to adapt to forces.

A Multidisciplinary Approach Establishes a Link between Transglutaminase 2 and the Kv10.1 Voltage-Dependent K Channel in Breast Cancer.

Since the multifunctionality of transglutaminase 2 (TG2) includes extra- and intracellular functions, we investigated the effects of intracellular administration of TG2 inhibitors in three breast cancer cell lines, MDA-MB-231, MDA-MB-436 and MDA-MB-468, which are representative of different triple-negative phenotypes, using a patch-clamp technique. The first cell line has a highly voltage-dependent a membrane current, which is low in the second and almost absent in the third one. While applying a voltage protocol to responsive single cells, injection of TG2 inhibitors triggered a significant decrease of the current in MDA-MB-231 that we attributed to voltage-dependent K channels using the specific inhibitors 4-aminopyridine and astemizole.

PocketNet: A Smaller Neural Network for Medical Image Analysis.

Medical imaging deep learning models are often large and complex, requiring specialized hardware to train and evaluate these models. To address such issues, we propose the PocketNet paradigm to reduce the size of deep learning models by throttling the growth of the number of channels in convolutional neural networks. We demonstrate that, for a range of segmentation and classification tasks, PocketNet architectures produce results comparable to that of conventional neural networks while reducing the number of parameters by multiple orders of magnitude, using up to 90% less GPU memory, and speeding up training times by up to 40%, thereby allowing such models to be trained and deployed in resource-constrained settings.