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Clinics in Sports Medicine Apr 2024Unconscious bias, also known as implicit bias, is the principal contributor to the perpetuation of discrimination and is a robust determinant of people's... (Review)
Review
Unconscious bias, also known as implicit bias, is the principal contributor to the perpetuation of discrimination and is a robust determinant of people's decision-making. Unconscious bias occurs despite conscious nonprejudiced intentions and interferes with the actions of the reflective and conscious side. Education and self-awareness about implicit bias and its potentially harmful effects on judgment and behavior may lead individuals to pursue corrective action and follow implicit bias mitigation communication strategies. Team physicians must follow existing communication strategies and guidelines to mitigate unconscious bias and begin an evolution toward nonbiased judgment and decision-making to improve athlete care.
Topics: Humans; Bias, Implicit; Physicians; Communication
PubMed: 38383110
DOI: 10.1016/j.csm.2023.07.002 -
Journal of Fungi (Basel, Switzerland) Jan 2024The escalating global food demand driven by a gradually expanding human population necessitates strategies to improve agricultural productivity favorably and mitigate... (Review)
Review
The escalating global food demand driven by a gradually expanding human population necessitates strategies to improve agricultural productivity favorably and mitigate crop yield loss caused by various stressors (biotic and abiotic). Biotic stresses are caused by phytopathogens, pests, and nematodes, along with abiotic stresses like salt, heat, drought, and heavy metals, which pose serious risks to food security and agricultural productivity. Presently, the traditional methods relying on synthetic chemicals have led to ecological damage through unintended impacts on non-target organisms and the emergence of microbes that are resistant to them. Therefore, addressing these challenges is essential for economic, environmental, and public health concerns. The present review supports sustainable alternatives, emphasizing the possible application of fungal endophytes as innovative and eco-friendly tools in plant stress management. Fungal endophytes demonstrate capabilities for managing plants against biotic and abiotic stresses via the direct or indirect enhancement of plants' innate immunity. Moreover, they contribute to elevated photosynthesis rates, stimulate plant growth, facilitate nutrient mineralization, and produce bioactive compounds, hormones, and enzymes, ultimately improving overall productivity and plant stress resistance. In conclusion, harnessing the potentiality of fungal endophytes represents a promising approach toward the sustainability of agricultural practices, offering effective alternative solutions to reduce reliance on chemical treatments and address the challenges posed by biotic and abiotic stresses. This approach ensures long-term food security and promotes environmental health and economic viability in agriculture.
PubMed: 38392787
DOI: 10.3390/jof10020116 -
Cancer Letters Feb 2024Osimertinib resistance is regarded as a major obstacle limiting survival benefits for patients undergoing treatment of epidermal growth factor receptor (EGFR)-mutant...
Osimertinib resistance is regarded as a major obstacle limiting survival benefits for patients undergoing treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, the underlying mechanisms of acquired resistance remain unclear. In this study, we report that estrogen receptor β (ERβ) is highly expressed in osimertinib-resistant NSCLC and plays a pivotal role in promoting osimertinib resistance. We further identified ubiquitin-specific protease 7 (USP7) as a critical binding partner that deubiquitinates and upregulates ERβ in NSCLC. ERβ promotes osimertinib resistance by mitigating reactive oxygen species (ROS) accumulation. We found that ERβ mechanistically suppresses peroxiredoxin 3 (PRDX3) SUMOylation and thus confers osimertinib resistance onto NSCLC. Furthermore, we provide evidence showing that depletion of ERβ induces ROS accumulation and reverses osimertinib resistance in NSCLC both in vitro and in vivo. Thus, our results demonstrate that USP7-mediated ERβ stabilization suppresses PRDX3 SUMOylation to mitigate ROS accumulation and promote osimertinib resistance, suggesting that targeting ERβ may be an effective therapeutic strategy to overcome osimertinib resistance in NSCLC.
Topics: Humans; Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Estrogen Receptor beta; Indoles; Lung Neoplasms; Mutation; Peroxiredoxin III; Protein Kinase Inhibitors; Pyrimidines; Reactive Oxygen Species; Sumoylation; Ubiquitin-Specific Peptidase 7
PubMed: 38097136
DOI: 10.1016/j.canlet.2023.216587 -
Free Radical Biology & Medicine Jul 2024Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its...
Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.
Topics: Animals; Mice; Apoptosis; Cardiotoxicity; Cyclopentanes; Doxorubicin; Mice, Inbred C57BL; Myocytes, Cardiac; NEDD8 Protein; Oxidative Stress; Pyrimidines; Ubiquitin-Activating Enzymes
PubMed: 38614228
DOI: 10.1016/j.freeradbiomed.2024.04.221 -
BioRxiv : the Preprint Server For... Dec 2023Z-lines are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-line-associated...
UNLABELLED
Z-lines are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-line-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-line proteome in vivo. We found palmdelphin (PALMD) as a novel Z-line-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed transverse tubules (T-tubules) and their association with sarcoplasmic reticulum, which formed the Z-line-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with disrupted localization of T-tubule markers caveolin-3 (CAV3) and junctophilin-2 (JPH2) and the reduction of nexilin (NEXN) protein, a crucial Z-line-associated protein that is essential for both Z-line and JMC structures and functions. PALMD was found to interact with NEXN and enhance its protein stability while the mRNA level was not affected. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.
HIGHLIGHTS
In vivo proximity proteomics uncover novel Z-line components that are undetected in in vitro proximity proteomics in cardiomyocytes.PALMD is a novel Z-line-associated protein that is dispensable for baseline cardiomyocyte function in vivo.PALMD mitigates cardiac dysfunction and myocardial injury after repeated isoproterenol insults.PALMD stabilizes NEXN, an essential Z-line-associated regulator of the junctional membrane complex and cardiac systolic function.
PubMed: 38106146
DOI: 10.1101/2023.12.06.570334 -
Water Research Oct 2023Microbial degradation to remove residual antibiotics in wastewater is of growing interest. However, biological treatment of antibiotics may cause resistance...
Microbial degradation to remove residual antibiotics in wastewater is of growing interest. However, biological treatment of antibiotics may cause resistance dissemination by mutations and horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). In this study, a Mn(Ⅱ)-oxidizing bacterium (MnOB), Pseudomonas aeruginosa MQ2, simultaneously degraded antibiotics, decreased HGT, and mitigated antibiotic resistance mutation. Intracellular Mn(II) levels increased during manganese oxidation, and biogenic manganese oxides (BioMnOx, including Mn(II), Mn(III) and Mn(IV)) tightly coated the cell surface. Mn(II) bio-oxidation mitigated antibiotic resistance acquisition from an E. coli ARG donor and mitigated antibiotic resistance inducement by decreasing conjugative transfer and mutation, respectively. BioMnOx also oxidized ciprofloxacin (1 mg/L) and tetracycline (5 mg/L), respectively removing 93% and 96% within 24 h. Transcriptomic analysis revealed that two new multicopper oxidase and one peroxidase genes are involved in Mn(II) oxidation. Downregulation of SOS response, multidrug resistance and type Ⅳ secretion system related genes explained that Mn(II) and BioMnOx decreased HGT and mitigated resistance mutation by alleviating oxidative stress, which makes recipient cells more vulnerable to ARG acquisition and mutation. A manganese bio-oxidation based reactor was constructed and completely removed tetracycline with environmental concentration within 4-hour hydraulic retention time. Overall, this study suggests that Mn (II) bio-oxidation process could be exploited to control antibiotic contamination and mitigate resistance propagation during water treatment.
Topics: Manganese; Anti-Bacterial Agents; Escherichia coli; Oxidation-Reduction; Oxides; Manganese Compounds; Tetracycline
PubMed: 37549546
DOI: 10.1016/j.watres.2023.120442 -
Occupational Medicine (Oxford, England) Feb 2024The COVID-19 pandemic created unprecedented challenges for the film industry. Following a shutdown of productions, The Safe Way Forward document was developed to outline...
BACKGROUND
The COVID-19 pandemic created unprecedented challenges for the film industry. Following a shutdown of productions, The Safe Way Forward document was developed to outline disease mitigation protocols. Despite this framework, many unanticipated scenarios arose during reopening of film production with the ongoing pandemic.
AIMS
To identify and document promising practices for mitigating COVID-19 transmission in the film industry that can inform future pandemics and other industries.
METHODS
We conducted a literature search to review research regarding COVID-19 disease mitigation efforts in the film industry. Through client-facing consultancy and consultant group meetings, we identified those factors most important for disease mitigation in the film industry and applicable to future pandemics and other industries. The Delphi Method enabled experts to review lessons learned as studio consultants during the COVID-19 pandemic; learnings were coded and analyzed for recurring themes.
RESULTS
We identified anxiety, mistrust, and poor communication as key contributors to decreased compliance with COVID-19 protocols. In response, our team demonstrated multi-specialty expertise, provided scientific explanations, and developed trust by listening empathetically and responding with clear, consistent messaging. These measures served to alleviate anxiety, improve compliance, and provide a safe return to production.
CONCLUSIONS
This study demonstrates the ability and agility of multi-disciplinary experts acting in the absence of clear guidance to support a safe return to film production. Workplace anxiety and non-compliance can be alleviated through effective communication by trusted experts. Lessons learned by our consultancy group can help protect workers across diverse industries in future pandemics.
Topics: Humans; COVID-19; Pandemics; SARS-CoV-2
PubMed: 36426811
DOI: 10.1093/occmed/kqac102 -
Experimental Neurology Apr 2024RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses...
RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses and cell death signaling pathways including apoptosis and necroptosis, which have been implicated in diverse physiological and pathological processes. Suppression of RIPK1 activation is a promising strategy for restraining the pathological progression of many human diseases. Neuroinflammation and neuronal apoptosis are two pivotal factors in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH). In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as marked by the phosphorylation of RIPK1 at serine 166. The upregulation of p-RIPK1(S166) resulted in a significant augmentation of inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1α, CCL2, and CCL5, as well as neuronal apoptosis. The activation of RIPK1 in microglia and neurons following SAH could be effectively suppressed by administration of Nec-1 s, a specific inhibitor of RIPK1. Consequently, inhibition of RIPK1 resulted in a downregulation of inflammatory cytokines and chemokines and attenuation of neuronal apoptosis after SAH in vitro. Furthermore, the administration of Nec-1 s effectively mitigated neuroinflammation, neuronal apoptosis, brain edema, and neurobehavioral deficits in mice following SAH. Our findings suggest that inhibiting RIPK1 kinase represents a promising therapeutic strategy for mitigating brain injury after SAH by attenuating RIPK1-driven neuroinflammation and neuronal apoptosis.
Topics: Animals; Mice; Apoptosis; Brain Edema; Brain Injuries; Chemokines; Cytokines; Neuroinflammatory Diseases; Rats, Sprague-Dawley; Receptor-Interacting Protein Serine-Threonine Kinases; Serine; Subarachnoid Hemorrhage
PubMed: 38290652
DOI: 10.1016/j.expneurol.2024.114705 -
International Journal of Health... Nov 2023African trypanosomiasis is a tsetse-borne parasitic infection that affects humans, wildlife, and domesticated animals. Tsetse flies are endemic to much of Sub-Saharan...
BACKGROUND
African trypanosomiasis is a tsetse-borne parasitic infection that affects humans, wildlife, and domesticated animals. Tsetse flies are endemic to much of Sub-Saharan Africa and a spatial and temporal understanding of tsetse habitat can aid surveillance and support disease risk management. Problematically, current fine spatial resolution remote sensing data are delivered with a temporal lag and are relatively coarse temporal resolution (e.g., 16 days), which results in disease control models often targeting incorrect places. The goal of this study was to devise a heuristic for identifying tsetse habitat (at a fine spatial resolution) into the future and in the temporal gaps where remote sensing and proximal data fail to supply information.
METHODS
This paper introduces a generalizable and scalable open-access version of the tsetse ecological distribution (TED) model used to predict tsetse distributions across space and time, and contributes a geospatial Bayesian Maximum Entropy (BME) prediction model trained by TED output data to forecast where, herein the Morsitans group of tsetse, persist in Kenya, a method that mitigates the temporal lag problem. This model facilitates identification of tsetse habitat and provides critical information to control tsetse, mitigate the impact of trypanosomiasis on vulnerable human and animal populations, and guide disease minimization in places with ephemeral tsetse. Moreover, this BME analysis is one of the first to utilize cluster and parallel computing along with a Monte Carlo analysis to optimize BME computations. This allows for the analysis of an exceptionally large dataset (over 2 billion data points) at a finer resolution and larger spatiotemporal scale than what had previously been possible.
RESULTS
Under the most conservative assessment for Kenya, the BME kriging analysis showed an overall prediction accuracy of 74.8% (limited to the maximum suitability extent). In predicting tsetse distribution outcomes for the entire country the BME kriging analysis was 97% accurate in its forecasts.
CONCLUSIONS
This work offers a solution to the persistent temporal data gap in accurate and spatially precise rainfall predictions and the delayed processing of remotely sensed data collectively in the - 45 days past to + 180 days future temporal window. As is shown here, the BME model is a reliable alternative for forecasting future tsetse distributions to allow preplanning for tsetse control. Furthermore, this model provides guidance on disease control that would otherwise not be available. These 'big data' BME methods are particularly useful for large domain studies. Considering that past BME studies required reduction of the spatiotemporal grid to facilitate analysis. Both the GEE-TED and the BME libraries have been made open source to enable reproducibility and offer continual updates into the future as new remotely sensed data become available.
Topics: Animals; Humans; Bayes Theorem; Entropy; Reproducibility of Results; Trypanosomiasis, African; Tsetse Flies
PubMed: 37974150
DOI: 10.1186/s12942-023-00349-0 -
Journal of the American College of... Sep 2023Despite the expert-level performance of artificial intelligence (AI) models for various medical imaging tasks, real-world performance failures with disparate outputs for... (Review)
Review
Despite the expert-level performance of artificial intelligence (AI) models for various medical imaging tasks, real-world performance failures with disparate outputs for various subgroups limit the usefulness of AI in improving patients' lives. Many definitions of fairness have been proposed, with discussions of various tensions that arise in the choice of an appropriate metric to use to evaluate bias; for example, should one aim for individual or group fairness? One central observation is that AI models apply "shortcut learning" whereby spurious features (such as chest tubes and portable radiographic markers on intensive care unit chest radiography) on medical images are used for prediction instead of identifying true pathology. Moreover, AI has been shown to have a remarkable ability to detect protected attributes of age, sex, and race, while the same models demonstrate bias against historically underserved subgroups of age, sex, and race in disease diagnosis. Therefore, an AI model may take shortcut predictions from these correlations and subsequently generate an outcome that is biased toward certain subgroups even when protected attributes are not explicitly used as inputs into the model. As a result, these subgroups became nonprivileged subgroups. In this review, the authors discuss the various types of bias from shortcut learning that may occur at different phases of AI model development, including data bias, modeling bias, and inference bias. The authors thereafter summarize various tool kits that can be used to evaluate and mitigate bias and note that these have largely been applied to nonmedical domains and require more evaluation for medical AI. The authors then summarize current techniques for mitigating bias from preprocessing (data-centric solutions) and during model development (computational solutions) and postprocessing (recalibration of learning). Ongoing legal changes where the use of a biased model will be penalized highlight the necessity of understanding, detecting, and mitigating biases from shortcut learning and will require diverse research teams looking at the whole AI pipeline.
Topics: Humans; Artificial Intelligence; Radiography; Radiology; Causality; Bias
PubMed: 37506964
DOI: 10.1016/j.jacr.2023.06.025