Should a radiation mishap deposit radioactive material into a wound, it is categorized as an instance of internal contamination. oropharyngeal infection Materials are typically transported throughout the body in accordance with their biokinetic behavior within the body's systems. Internal dosimetry methods, while commonly used to calculate the committed effective dose due to the incident, may underestimate the protracted retention of some materials at the wound site, even after medical procedures like decontamination and surgical removal. Severe and critical infections The radioactive material's presence in this case elevates the local dose. This research sought to generate local dose coefficients for radionuclide-contaminated wounds, thus enhancing committed effective dose coefficients. Employing these dose coefficients, one can calculate activity limitations at the wound site that might result in a clinically significant dose. This data empowers emergency response teams to make informed decisions about medical treatment, including decorporation therapy. Using the MCNP radiation transport code, 38 radionuclides were considered while simulating the dose to tissue in wound models designed for injections, lacerations, abrasions, and burns. Biological removal of radionuclides from the wound site was a key aspect incorporated in the biokinetic models. Research findings suggest that radionuclides not effectively retained at the wound location are not a significant local concern, but for those with high retention, the projected local doses necessitate further review by medical and health physics specialists.
In various tumor types, antibody-drug conjugates (ADCs) have achieved clinical success through their ability to precisely deliver drugs to tumors. The antibody, payload, linker, conjugation technique, and the drug-to-antibody ratio (DAR) are all critical components affecting the safety and activity profile of an ADC. We developed Dolasynthen, a new ADC platform based on the auristatin hydroxypropylamide (AF-HPA) payload, in order to enable precise DAR control and site-specific conjugation, thereby optimizing ADC performance for a particular target antigen. The new platform enabled us to refine an ADC directed at B7-H4 (VTCN1), an immune-suppressing protein prominently overexpressed in breast, ovarian, and endometrial cancers. The site-specific Dolasynthen DAR 6 ADC, XMT-1660, achieved complete tumor regressions in xenograft models of both breast and ovarian cancers, and even in a syngeneic breast cancer model that proved unresponsive to PD-1 immune checkpoint blockade. For 28 breast cancer patient-derived xenografts (PDX), XMT-1660's action was clearly correlated with the level of B7-H4 expression. A Phase 1 clinical investigation (NCT05377996) focusing on XMT-1660 has recently been launched in a group of cancer patients.
This document endeavors to address the anxieties that the public commonly experiences regarding low-level radiation exposure situations. The ultimate intention is to confidently assure knowledgeable yet skeptical members of the public that situations involving low-level radiation exposure are not something to fear. Regrettably, simply ceding to a public apprehension of low-level radiation, unsupported by evidence, carries its own set of repercussions. This severe disruption significantly hinders the positive effects of harnessed radiation on human well-being. The paper's objective is to offer the scientific and epistemological foundations for regulatory transformation. This is accomplished through a review of the historical progression in quantifying, understanding, modeling, and controlling radiation exposure. The review incorporates the significant contributions of the United Nations Scientific Committee on the Effects of Atomic Radiation, the International Commission on Radiological Protection, and the multitude of international and intergovernmental organizations that establish radiation safety standards. The analysis also includes a deep look into the different interpretations of the linear no-threshold model, informed by the contributions of radiation pathologists, radiation epidemiologists, radiation biologists, and radiation protection specialists. In light of the deeply embedded linear no-threshold model in existing radiation exposure guidelines, despite the absence of concrete scientific proof on low-dose radiation effects, this paper outlines immediate approaches to optimize regulatory implementation and public service by potentially excluding or exempting negligible low-dose situations from regulatory purview. Several illustrations showcase how the public's unjustified concern with low-level radiation has thwarted the numerous benefits of controlled radiation in the modern world.
A groundbreaking advancement in immunotherapy, CAR T-cell therapy, is specifically applied in the treatment of hematological malignancies. Applying this therapy is encumbered by hurdles such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, immunosuppression, and hypogammaglobulinemia, which can persist and dramatically increase the risk of infections in patients. Cytomegalovirus (CMV) infection often culminates in disease and organ damage among immunocompromised patients, substantially increasing mortality and morbidity. A 64-year-old man, diagnosed with multiple myeloma, presented with a pre-existing and significant cytomegalovirus (CMV) infection. Post-CAR T-cell therapy, this CMV infection worsened, becoming increasingly difficult to manage due to concurrent cytopenias, myeloma progression, and emerging opportunistic infections. Prophylactic, therapeutic, and maintenance protocols for CMV infections in CAR T-cell recipients necessitate further development and exploration.
CD3 bispecific T-cell engaging agents, which incorporate a tumor-targeting moiety and a CD3-binding segment, operate by uniting target-positive tumors with CD3-expressing effector T cells, thereby enabling redirected tumor-killing mediated by the T cells. Although most clinically evaluated CD3 bispecific molecules rely on antibody-based binding domains for tumor targeting, numerous tumor-associated antigens are intracellular proteins and are thus unavailable for antibody-based approaches. MHC proteins display intracellular protein fragments, short peptides, on the cell surface, triggering recognition by T-cell receptors (TCR) located on T cells. The preclinical assessment and creation of ABBV-184, a novel bispecific TCR/anti-CD3 molecule, are detailed here. A highly selective soluble TCR is designed to target a peptide from the survivin (BIRC5) oncogene complexed with the HLA-A*0201 class I MHC molecule, which appears on tumor cells. This TCR is conjugated to a specific CD3 binding agent on T cells. ABBV-184 promotes a perfect intercellular space between T cells and target cells, enabling the highly sensitive identification of low-concentration peptide/MHC targets. Treatment with ABBV-184, in line with the survivin expression pattern seen across various hematological and solid malignancies, causes T-cell activation, proliferation, and potent redirected cytotoxicity against HLA-A2-positive target cell lines in both in vitro and in vivo models, including patient-derived acute myeloid leukemia (AML) samples and non-small cell lung cancer (NSCLC) cell lines. These results support ABBV-184's consideration as a worthwhile clinical candidate for both AML and NSCLC patients.
Self-powered photodetectors have garnered substantial attention due to their low power consumption and the crucial role they play in Internet of Things (IoT) applications. Miniaturization, high quantum efficiency, and multifunctionalization, when implemented together, present a complex challenge. see more Employing a sandwich-like electrode arrangement alongside two-dimensional (2D) WSe2/Ta2NiSe5/WSe2 van der Waals (vdW) dual heterojunctions (DHJ), we demonstrate a high-efficiency and polarization-sensitive photodetector. The DHJ device, owing to its improved light collection and dual built-in electric fields at the heterointerfaces, demonstrates a broad spectral response from 400 to 1550 nm, along with remarkable performance under 635 nm illumination. This includes an extremely high external quantum efficiency (EQE) of 855%, a noteworthy power conversion efficiency (PCE) of 19%, and a fast response time of 420/640 seconds, substantially exceeding that of the WSe2/Ta2NiSe5 single heterojunction (SHJ). The strong in-plane anisotropy of 2D Ta2NiSe5 nanosheets is a key factor in the DHJ device's highly competitive polarization sensitivities, which are 139 under 635 nm light and 148 under 808 nm light. Subsequently, a remarkable self-sufficient visible imaging ability, stemming from the DHJ device, is exemplified. These results offer a promising avenue for the implementation of high-performance, multifunctional self-powered photodetectors.
Biology, through the magic of active matter—matter transforming chemical energy into mechanical action—solves numerous seemingly insurmountable physical problems, leveraging emergent properties. Thanks to active matter surfaces, our lungs filter out a tremendous amount of particulate contaminants from the 10,000 liters of air we inhale each day, guaranteeing the proper function of the gas exchange surfaces. This Perspective will describe our attempts to create artificial active surfaces inspired by the active matter surfaces present in biology. We propose to construct surfaces capable of sustaining continual molecular sensing, recognition, and exchange by integrating basic active matter components, including mechanical motors, driven constituents, and energy sources. The successful implementation of this technology would produce multifaceted, living surfaces, merging the dynamic programmability of active matter with the molecular precision of biological surfaces, and applying them to fields like biosensors, chemical diagnostics, and other surface transport and catalytic processes. To understand and integrate native biological membranes into synthetic materials, our recent efforts in bio-enabled engineering of living surfaces involved the design of molecular probes.