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Acta Biomaterialia Jun 2024The emergence of antimicrobial-resistant bacterial infections poses a significant threat to public health, necessitating the development of innovative and effective...
The emergence of antimicrobial-resistant bacterial infections poses a significant threat to public health, necessitating the development of innovative and effective alternatives to antibiotics. Photodynamic therapy (PDT) and immunotherapy show promise in combating bacteria. However, PDT's effectiveness is hindered by its low specificity to bacteria, while immunotherapy struggles to eliminate bacteria in immunosuppressive environments. In this work, we introduce an innovative near-infrared antimicrobial nanoplatform (ZFC) driven by bacterial metabolism. ZFC, comprising D-cysteine-functionalized pentafluorophenyl bacteriochlorin (FBC-Cy) coordinated with Zn, is designed for antimicrobial photodynamic-immune therapy (aPIT) against systemic bacterial infections. By specifically targeting bacteria via D-amino acid incorporation into bacterial surface peptidoglycans during metabolism, ZFC achieves precise bacterial clearance in wound and pulmonary infections, exhibiting an antimicrobial efficacy of up to 90% with minimal damage to normal cells under 750 nm light. Additionally, ZFC enhances the activation of antigen-presenting cells by 3.2-fold compared to control groups. Furthermore, aPIT induced by ZFC triggers systemic immune responses and establishes immune memory, resulting in a 1.84-fold increase in antibody expression against bacterial infections throughout the body of mice. In conclusion, aPIT prompted by ZFC presents a approach to treating bacterial infections, offering a broad-spectrum solution for systemic bacterial infections. STATEMENT OF SIGNIFICANCE: The new concept demonstrated focuses on an innovative near-infrared antimicrobial nanoplatform (ZFC) for antimicrobial photodynamic-immune therapy (aPIT), highlighting its reliance on bacterial metabolism and its non-damaging effect on normal tissues. ZFC efficiently targets deep-tissue bacterial infections by harnessing bacterial metabolism, thereby enhancing therapeutic efficacy while sparing normal tissues from harm. This approach not only clears bacterial infections effectively but also induces potent adaptive immune responses, leading to the eradication of distant bacterial infections. By emphasizing ZFC's unique mechanism driven by bacterial metabolism and its tissue-sparing properties, this work underscores the potential for groundbreaking advancements in antimicrobial therapy. Such advancements hold promise for minimizing collateral damage to healthy tissues, thereby improving treatment outcomes and mitigating the threat of antimicrobial resistance. This integrated approach represents a significant progress forward in the development of next-generation antimicrobial therapies with enhanced precision and efficacy.
PubMed: 38936751
DOI: 10.1016/j.actbio.2024.06.024 -
Physiological Measurement Jun 2024This study aims to address the challenges of imbalanced heartbeat classification using electrocardiogram (ECG). In this proposed novel deep-learning method, the focus is...
This study aims to address the challenges of imbalanced heartbeat classification using electrocardiogram (ECG). In this proposed novel deep-learning method, the focus is on accurately identifying minority classes in conditions characterized by significant imbalances in ECG data. Approach: We propose a Feature Fusion Neural Network enhanced by a Dynamic Minority-Biased Batch Weighting Loss Function. This network comprises three specialized branches: the Complete ECG Data Branch for a comprehensive view of ECG signals, the Local QRS Wave Branch for detailed features of the QRS complex, and the R Wave Information Branch to analyze R wave characteristics. This structure is designed to extract diverse aspects of ECG data. The dynamic loss function prioritizes minority classes while maintaining the recognition of majority classes, adjusting the network's learning focus without altering the original data distribution. Together, this fusion structure and adaptive loss function significantly improve the network's ability to distinguish between various heartbeat classes, enhancing the accuracy of minority class identification. Main Results: The proposed method demonstrated balanced performance within the MIT-BIH dataset, especially for minority classes. Under the intra-patient paradigm, the accuracy, sensitivity, specificity, and positive predictive value (PPV) for Supraventricular ectopic beat were 99.63%, 93.62%, 99.81%, and 92.98%, respectively, and for Fusion beat were 99.76%, 85.56%, 99.87%, and 84.16%, respectively. Under the inter-patient paradigm, these metrics were 96.56%, 89.16%, 96.84%, and 51.99% for Supraventricular ectopic beat, and 96.10%, 77.06%, 96.25%, and 13.92% for Fusion beat, respectively. Significance: This method effectively addresses the class imbalance in ECG datasets. By leveraging diverse ECG signal information and a novel loss function, this approach offers a promising tool for aiding in the diagnosis and treatment of cardiac conditions. .
PubMed: 38936397
DOI: 10.1088/1361-6579/ad5cc0 -
American Society of Clinical Oncology... Jun 2024This article endeavors to navigate the clinical journey of bispecific antibodies (BsAbs), from elucidating common toxicities and management strategies to examining novel... (Review)
Review
This article endeavors to navigate the clinical journey of bispecific antibodies (BsAbs), from elucidating common toxicities and management strategies to examining novel agents and broadening access in community health care. These drugs, commonly through T-cell activation, result in shared adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Variations in target antigens and designs, however, might introduce unique toxicities for different BsAbs, warranting specific management approaches. Recent US Food and Drug Administration approvals of BsAbs targeting CD3 T cells linked to CD20 for non-Hodgkin lymphoma and to B-cell maturation antigen or GPRC5D for multiple myeloma have transformed the treatment landscape for hematologic malignancies. Emerging new agents promise further enhancement and safety, exploring novel antigen targets, innovative structures such as trispecific antibodies, and the engagement of diverse immune cells. Simultaneously, the expansion of BsAbs into community practices is underway, demanding a multifaceted strategy that encompasses educational initiatives, operational adaptations, and collaborative frameworks. This ensures comprehensive treatment access, allowing every patient, irrespective of geographical or socioeconomic status, to benefit from these advancements in cancer therapy.
Topics: Humans; Antibodies, Bispecific; Multiple Myeloma; Lymphoma; Antineoplastic Agents, Immunological
PubMed: 38935881
DOI: 10.1200/EDBK_433516 -
PloS One 2024Tools screening depression and anxiety developed using the Western biomedical paradigm are still used with First Nations Peoples globally, despite calls for...
A Delphi study and development of a social and emotional wellbeing screening tool for Australian First Nations Peoples living in the Torres Strait and Northern Peninsula Area of Australia.
Tools screening depression and anxiety developed using the Western biomedical paradigm are still used with First Nations Peoples globally, despite calls for cross-cultural adaption. Recent work by this research team found that tools used to screen for depression and anxiety were inappropriate for use with Australian First Nations Peoples living in the Torres Strait and Northern Peninsula Area of Australia. The objective of this Delphi study, the second phase of a broader four-phase project, was to gain consensus from an expert mental health and/or social and emotional wellbeing (SEWB) panel to inform the development of an appropriate screening tool. This Delphi study took place between March and May 2023. Three sequential rounds of anonymous online surveys delivered using QualtricsTM were planned, although only two were needed to reach 75% consensus. The first round sought consensus on whether a new screening tool needed to be developed or whether existing tools could be used. The second round achieved consensus. Twenty-eight experts (47% response rate) participated across the two Delphi rounds. In the second round, 83% of these experts agreed or strongly agreed that a new screening tool, using the holistic First Nations concept of social and emotional wellbeing, be developed. Ninety-four percent of them agreed that it should take a Yarning approach. These findings enabled the development of a new SEWB screening tool that adopted a Yarning (narrative) approach designed for use in primary care and geriatric settings in the region. The new tool has four different Yarning areas: Community engagement and behaviour; Stress worries; Risk; and Feeling strong. Guidelines for tool use are integrated as well as Summary and Recommendation sections. At a macro-level this project responds to the need for new screening tools that are underpinned by First Nations worldviews.
Topics: Adult; Female; Humans; Male; Middle Aged; Anxiety; Australia; Delphi Technique; Depression; Emotions; Mass Screening; Mental Health; Surveys and Questionnaires; Australian Aboriginal and Torres Strait Islander Peoples
PubMed: 38935759
DOI: 10.1371/journal.pone.0306316 -
PloS One 2024The transformation of the food and industrial agricultural production system into adaptative and sustainable systems capable of being productive within social,...
The transformation of the food and industrial agricultural production system into adaptative and sustainable systems capable of being productive within social, environmental, and economic limits is a crucial factor in reducing the risk to food security and to economic growth. However, the analysis structure of the effect of these variables in sustainable environments remains unknown, whereby the technology and processes are considered as variables of the equivalent critical level as those already described. The purpose of this study is to design a model that enables the characterisation of the agri-food sector based on the determination of sustainable variables from a sustainable and integral systemic approach. Tools, such as the viable system model, are employed to analyse the dynamics and generate the balanced scorecard, to which the items of learning and continuous improvement are added. Lastly, the impact of the principles of sustainability versus the variation of sustainability in the agri-food system is revealed, which is useful in determining the appropriate levels to guarantee a balance in the foundations of circularity. From a systemic approach, this model can be adopted by agronomists and scientists to design alternative strategies for the management of food sustainability.
Topics: Agriculture; Models, Theoretical; Sustainable Development; Humans; Food Supply; Conservation of Natural Resources
PubMed: 38935702
DOI: 10.1371/journal.pone.0305743 -
Journal of Clinical Neurophysiology :... Jul 2024It took 50 years for stereoelectroencephalography (SEEG) to cross the Atlantic. Conceived and designed before the advent of computers and modern technology, this method... (Review)
Review
It took 50 years for stereoelectroencephalography (SEEG) to cross the Atlantic. Conceived and designed before the advent of computers and modern technology, this method turned out to be perfectly suited to brain imaging and modern video and electrophysiological tools. It eventually benefited from robotics and signal processing. However, a critical step remains accurate electrode implantation, which is based on individual patients' noninvasive phase I data. A limiting factor, especially in MRI-negative cases, is a thorough perictal and postictal clinical testing for ensuring meaningful electroclinical correlations. Adapted epilepsy monitoring units' architecture and specific technicians and nurses training are required to improve the granularity of information needed to generate valid hypotheses on localization. SEEG interpretation is based on a knowledge base in neural networks, cognitive/behavioral neuroscience, and electrophysiology quite distinct from electroencephalography. Tailored to the needs of focal epilepsy complexity exploration, SEEG does not fit well with simplification. Specific teaching and development of clinical research inside the epilepsy monitoring units will help to flatten the team learning curve and to build knowledge base from shared clinical experience.
Topics: Humans; Electroencephalography; Stereotaxic Techniques; Epilepsy; Brain; Electrodes, Implanted
PubMed: 38935651
DOI: 10.1097/WNP.0000000000001048 -
Experimental Physiology Jun 2024Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to...
Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.
PubMed: 38935545
DOI: 10.1113/EP091782 -
Journal of the American Chemical Society Jun 2024High-entropy alloy nanoparticles (HEA-NPs) show exceptional properties and great potential as a new generation of functional materials, yet a universal and facile...
High-entropy alloy nanoparticles (HEA-NPs) show exceptional properties and great potential as a new generation of functional materials, yet a universal and facile synthetic strategy in air toward nonoxidized and precisely controlled composition remains a huge challenge. Here we provide a laser scribing method to prepare single-phase solid solution HEA-NPs libraries in air with tunable composition at the atomic level, taking advantage of the laser-induced metastable thermodynamics and substrate-assisted confinement effect. The three-dimensional porous graphene substrate functions as a microreactor during the fast heating/cooling process, which is conductive to the generation of the pure alloy phase by effectively blocking the binding of oxygen and metals, but is also beneficial for realizing accurate composition control via microstructure confinement-endowed favorable vapor pressure. Furthermore, by combining an active learning approach based on an adaptive design strategy, we discover an optimal composition of quinary HEA-NP catalysts with an ultralow overpotential for Li-CO batteries. This method provides a simple, fast, and universal in-air route toward the controllable synthesis of HEA-NPs, potentially integrated with machine learning to accelerate the research on HEAs.
PubMed: 38935530
DOI: 10.1021/jacs.4c03658 -
IEEE Transactions on Biomedical... Jun 2024Bioinspired robotics and smart prostheses have many applications in the healthcare sector. Patients can use them for rehabilitation or day-to-day assistance, allowing...
Bioinspired robotics and smart prostheses have many applications in the healthcare sector. Patients can use them for rehabilitation or day-to-day assistance, allowing them to regain some agency over their movements. The most common way to make these smart artificial limbs is by adding a "human-like" electronic skin to detect force and emulate touch detection. This paper presents a fully integrated CMOS-based stress sensor design with a high dynamic range (100 kPa to 100 MPa) supported by an adaptive gain-controlled chopping amplifier. The sensor chip includes four identical sensing structures capable of measuring the chip's local stress gradient and complete readout circuitry supporting data transfer via I2C protocol. The sensor takes 10.2 ms to measure through all four structures and goes into a low-power mode when not in use. The designed chip consumes a total current of ~300 μA for one complete operation cycle and ~30 μA during low power mode in simulations. Moreover, the complete design is CMOS-based, making it easier for large-scale commercial fabrication and more affordable for patients in the long run. This paper further proposes the concept of a tactile smart skin by integrating a network of sensor chips with flexible polymers.
PubMed: 38935474
DOI: 10.1109/TBCAS.2024.3420171 -
Psychological Trauma : Theory,... Jun 2024Individuals who experience polyvictimization, or victimization across multiple life contexts, show particularly severe outcomes across a range of mental health...
OBJECTIVE
Individuals who experience polyvictimization, or victimization across multiple life contexts, show particularly severe outcomes across a range of mental health diagnoses, potentially related to difficulties in regulating emotion. However, prior research has been limited by reliance on cross-sectional designs and retrospective trait measures of emotion regulation. The present study used ecological momentary assessment to test associations between polyvictimization and emotion regulation in daily life.
METHOD
After completing a baseline survey assessing trauma exposure, mental health symptoms, and trait emotion regulation, undergraduates ( = 122) completed smartphone surveys assessing state emotion regulation four times per day for 14 days.
RESULTS
Low correspondence was observed between trait and state measures of emotion regulation. After accounting for baseline mental health symptoms, polyvictimization independently predicted lower scores on an aggregative measure of putatively adaptive strategies (i.e., reappraisal, acceptance, problem solving) in daily life. However, polyvictimization did not predict aggregate scores of putatively maladaptive strategies (i.e., cognitive and expressive suppression, rumination, impulsive behavior, avoidance). Baseline depression and posttraumatic stress predicted higher use of putatively maladaptive strategies.
CONCLUSIONS
Results suggest polyvictimization may be associated with less use of adaptive emotion regulation in daily life, whereas mental health symptoms may be associated with more use of maladaptive strategies. These findings highlight the utility of experience sampling approaches for increasing insight into emotion regulation difficulties among trauma survivors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38934932
DOI: 10.1037/tra0001745