Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development.

Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk.

Creative Arts Therapy Reduces Psychological Distress in Non-Patient-Facing Healthcare Workers.

Objective: To assess the feasibility, acceptability, and efficacy of a 12-week in-person Creative Arts Therapy intervention in reducing psychological distress and burnout symptoms in non-patient-facing healthcare workers.

Background: Burnout and psychological distress among non-patient-facing healthcare workers are significant and understudied problems in healthcare systems.

Methods: Non-patient-facing healthcare workers with burnout symptoms were randomly assigned to one of four Creative Arts Therapy modalities (art, music, creative writing, or dance/movement) or a control group.

Ultra-low-dose chest computed tomography with model-based iterative reconstruction in the analysis of solid pulmonary nodules: A prospective study.

Background: Incidental pulmonary nodules are an increasingly common finding on computed tomography (CT) scans of the thorax due to the exponential rise in CT examinations in everyday practice. The majority of incidental pulmonary nodules are benign and correctly identifying the small number of malignant nodules is challenging. Ultra-low-dose CT (ULDCT) has been shown to be effective in diagnosis of respiratory pathology in comparison with traditional standard dose techniques.

Characterization of the Ubiquitin-Modified Proteome of Recombinant Chinese Hamster Ovary Cells in Response to Endoplasmic Reticulum Stress.

Chinese hamster ovary (CHO) cells remain the most widely used host cell line for biotherapeutics production. Despite their widespread use, understanding endoplasmic reticulum (ER) stress conditions in recombinant protein production remains limited, often creating bottlenecks preventing improved production titers and product quality. Ubiquitination not only targets substrates (e.

Konnektor: A Framework for Using Graph Theory to Plan Networks for Free Energy Calculations.

Alchemical free energy campaigns can be planned using graph theory by building networks that contain nodes representing molecules that are connected by possible transformations as edges. We introduce Konnektor, an open-source Python package, for systematically planning, modifying, and analyzing free energy calculation networks. Konnektor is designed to aid in the drug discovery process by enabling users to easily setup free energy campaigns using complex graph manipulation methods.

Label-free liquid chromatography mass spectrometry analysis of changes in broiler liver proteins under transport stress.

Transportation duration and distance are significant concerns for animal welfare, particularly in the poultry industry. However, limited proteomic studies have investigated the impact of transport duration on poultry welfare. In this study, mass spectrometry based bottom up proteomics was employed to sensitively and impartially profile the liver tissue proteome of chickens, addressing the issue of animal stress and welfare in response to transportation before slaughter.

Analytical Tools for HCP Detection, Identification, and Quantitation.

Identifying and quantifying host cell proteins (HCPs) are crucial in developing and manufacturing biopharmaceutical products. ELISA has been used widely for identifying and quantifying HCPs in biopharmaceutical products. Liquid chromatography-mass spectrometry (LC-MS) has recently emerged as an orthogonal tool for HCP analysis, providing comprehensive and quantitative information on individual HCPs.

LC-MS/MS Analysis to Study the Ubiquitin-Modified Proteome of Recombinant Chinese Hamster Ovary Cells.

Ubiquitination is one of the most important post-translational modifications (PTMs) and involves the covalent attachment of ubiquitin to a lysine residue on a target protein. Despite ubiquitination playing a crucial role in regulating cellular processes, the ubiquitinated proteome has not been studied extensively in recombinant Chinese hamster ovary (CHO) cells. Moreover, ubiquitination modification in CHO cells is likely to have an impact on protein function related to the efficient productivity of biopharmaceuticals.

Phosphopeptide Enrichment and LC-MS/MS Analysis to Study the Phosphoproteome of Recombinant Chinese Hamster Ovary Cells.

The reversible phosphorylation of proteins on serine, threonine, and tyrosine residues is one of the most important post-translational modifications that regulates many biological processes. There have been relatively few studies on the phosphoproteome of recombinant Chinese hamster ovary (CHO) cells to date despite phosphorylation playing a crucial role in regulating many molecular and cellular processes relevant to bioprocess phenotypes including, for example, transcription, translation, growth, apoptosis, and signal transduction. In this chapter, we provide a protocol for phosphoproteomic analysis of CHO cells using phosphopeptide enrichment with metal oxide affinity chromatography (MOAC) and immobilized metal affinity chromatography (IMAC) techniques, followed by site-specific identification of phosphorylated residues using liquid chromatography mass spectrometry (LC-MS), multistage activation (MSA), and MS3 strategies.

Recent Advancements in Proteomic Sample Preparation from Recombinant Chinese Hamster Ovary Cells.

Chinese hamster ovary (CHO) cells are the most commonly used mammalian host cell line for biopharmaceutical production because of their ability to correctly fold and post-translationally modify recombinant proteins that are compatible with human use. Proteomics, along with other "omic platforms," are being used to understand the biology of CHO cells with the ultimate aim to enhance CHO cell factories for more efficient production of biopharmaceuticals. Liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis has become the standard technique for profiling proteomes.

Identification of blood lipid markers of docetaxel treatment in prostate cancer patients.

Docetaxel is commonly used for treatment of castration-resistant prostate cancer. Unfortunately, many prostate cancer patients develop resistance to docetaxel. Clinical markers less invasive than biopsies, such as blood samples, would be ideal for monitoring and predicting patient treatment outcomes to docetaxel.

Interfacility Patient Transfers During COVID-19 Pandemic: Mixed-Methods Study.

Introduction: The United States lacks a national interfacility patient transfer coordination system. During the coronavirus 2019 (COVID-19) pandemic, many hospitals were overwhelmed and faced difficulties transferring sick patients, leading some states and cities to form transfer centers intended to assist sending facilities. In this study we aimed to explore clinician experiences with newly implemented transfer coordination centers.

The psychometric properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system in neurorehabilitation populations: a systematic review.

Objective: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations.

Data Sources: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles.

Study Selection: Two independent reviewers screened selected articles and extracted data from 28 included studies.

Disentangling the Effects of Comorbidity and Polypharmacy on Cognitive Function and Physical Frailty in Individuals with HIV.

Objective: To estimate the extent to which comorbidity, polypharmacy, and anticholinergic/sedative burden interrelate to influence cognitive ability, perceived cognitive deficits and physical frailty in people living with HIV.

Design: Cross-sectional Structural Equation Modeling (SEM) of data from 824 older people living with HIV in Canada, participating in the Positive Brain Health Now study.

Method: SEM was used to link observed variables, including comorbidity, polypharmacy, anticholinergic and sedative burden, to cognitive ability and two latent constructs - physical frailty and perceived cognitive deficits (PCD).

The Association Between Serum Mature and Precursor Brain-Derived Neurotrophic Factor and Neurocognitive Function in People With Human Immunodeficiency Virus: A Longitudinal Study.

Background: Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-associated neurocognitive impairment persists. We investigated the association between serum levels of mature brain-derived neurotrophic factor (mBDNF), precursor brain-derived neurotrophic factor (proBDNF), and neurocognitive changes over time among adults with HIV in sub-Saharan Africa, seeking to elucidate the interplay between neurotrophic factors and neurocognitive outcomes post-ART.

Methods: Utilizing data from the ACTG 5199 study in Johannesburg and Harare, serum mBDNF and proBDNF levels were measured via enzyme-linked immunosorbent assay.

Machine-learned molecular mechanics force fields from large-scale quantum chemical data.

The development of reliable and extensible molecular mechanics (MM) force fields-fast, empirical models characterizing the potential energy surface of molecular systems-is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods.

Citrullination, a novel posttranslational modification of elastin, is involved in COPD pathogenesis.

Elastin is an extracellular matrix protein (ECM) that supports elasticity of the lung, and in patients with chronic obstructive pulmonary disease (COPD) and emphysema, the structural changes that reduce the amount of elastic recoil, lead to loss of pulmonary function. We recently demonstrated that elastin is a target of peptidyl arginine deiminase (PAD) enzyme-induced citrullination, thereby leading to enhanced susceptibility of this ECM protein to proteolysis. This study aimed to investigate the impact of PAD activity in vivo and furthermore assessed whether pharmacological inhibition of PAD activity protects against pulmonary emphysema.

The highly metastatic 4T1 breast carcinoma model possesses features of a hybrid epithelial/mesenchymal phenotype.

Epithelial-mesenchymal transitions (EMTs) are thought to promote metastasis via downregulation of E-cadherin (also known as Cdh1) and upregulation of mesenchymal markers such as N-cadherin (Cdh2) and vimentin (Vim). Contrary to this, E-cadherin is retained in many invasive carcinomas and promotes collective cell invasion. To investigate how E-cadherin regulates metastasis, we examined the highly metastatic, E-cadherin-positive murine 4T1 breast cancer model, together with the less metastatic, 4T1-related cell lines 4T07, 168FARN and 67NR.

Label-free liquid chromatography-mass spectrometry comparison of the breast muscle proteome profiles in two fast-growing broilers.

Poultry meat-production is increasing worldwide; leading to the selection of chickens for meat-production that show a fast growth. A label-free quantitative proteomic-approach and Western-blot were applied to investigate the dynamics of muscle protein under rapid growth conditions in two common fast-growing broiler genetic-lines (Ross 508 and AZ Extra Heavy Red-chicken). Muscle exudate from chicken Pectoralis major was used as substrate to unveil the proteome of these genetic-lines.

The impact of the COVID-19 pandemic on the performance of the Rapid Access Lung Cancer Clinic.

Background: The Rapid Access Lung Cancer Clinic (RALC) experienced fewer referrals during the COVID-19 pandemic in Ireland.

Aims: Our aim was to determine the impact of the pandemic on the key performance indicators (KPIs) of the Cork University Hospital (CUH) RALC, using a retrospective chart review of the referrals and attendances.

Methods: The medical charts of patients referred to CUH-RALC from 03/2019 to 02/2020 (period I), and from 03/2020 to 02/2021 (period II) were reviewed.

An MITF- and mTOR-dependent FLCN pathway suppresses TFE3-driven metastasis in melanoma.

Cancer cells have remarkable plasticity allowing them to acquire many biological states. Melanoma cells have the ability to switch from a proliferative melanocytic state to an invasive mesenchymal state and back again resulting in intratumoral heterogeneity. While microphthalmia-associated transcription factor (MITF) promotes the melanocytic phenotype, it is unclear what transcription factors drive the mesenchymal phenotype, and what mechanisms regulate the switch from the proliferative state to the mesenchymal state.

Cognitive impact of anticholinergic and sedative burden in people with HIV.

Objective: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV.

Design: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study.

Methods: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse).

The influence of threat on visuospatial perception, affordances, and protective behaviour: A systematic review and meta-analysis.

Perception has been conceptualised as an active and adaptive process, based upon incoming sensory inputs, which are modified by top-down factors such as cognitions. Visuospatial perception is thought to be scaled based on threat, with highly threatening objects or contexts visually inflated to promote escape or avoidance behaviours. This meta-analytical systematic review quantified the effect and evidence quality of threat-evoked visuospatial scaling, as well as how visuospatial scaling relates to affordances (perceived action capabilities) and behavioural avoidance/escape outcomes.