Synthesis and Evaluation of a Bifunctional Chelator for Thorium-227 Targeted Radiotherapy.

Thorium-227 (Th) is an α-emitting radionuclide currently under investigation for targeted alpha therapy. Available chelators used for this isotope suffer from challenging multistep syntheses. Here, we present the synthesis and preclinical evaluation of a novel bifunctional chelator, SCN-Bn-DOTHOPO, which contains an isothiocyanate group that is suitable for conjugation to biological molecules.

Robust Magnetoelectric Backscatter Communication System for Bioelectronic Implants.

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.

Omnidirectional Wireless Power Transfer for Millimetric Magnetoelectric Biomedical Implants.

Miniature bioelectronic implants promise revolutionary therapies for cardiovascular and neurological disorders. Wireless power transfer (WPT) is a significant method for miniaturization, eliminating the need for bulky batteries in devices. Despite successful demonstrations of millimetric battery free implants in animal models, the robustness and efficiency of WPT are known to degrade significantly under misalignment incurred by body movements, respiration, heart beating, and limited control of implant orientation during surgery.

Endocisternal interfaces for minimally invasive neural stimulation and recording of the brain and spinal cord.

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid.

Slow Magnetic Relaxation in a Californium Complex.

We report the synthesis and characterization of the macrocyclic californium derivative Na[Cf(HO)(DOTA)] (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), , which was studied in comparison to its dysprosium counterpart, Na[Dy(HO)(DOTA)], . Divergent spectroscopic and magnetic behaviors were observed between and . Based upon spectroscopic measurements, we propose that accessible 5f → 6d transitions (potentially operating in tandem with charge-transfer transitions) are the major contributors to the observed broadband photoluminescence in .

Analytical Performance of a Multiplexed Microarray Assay for Rapid Identification and Quantification of a Multivalent mRNA Vaccine.

mRNA vaccines were highly effective in response to the COVID-19 pandemic, making them an attractive platform to address cancers and other infectious diseases. Many new mRNA vaccines in development are multivalent, which represents a difficulty for the standard assays commonly used to characterize the critical quality attributes of monovalent formulations. Here, we present a multiplexed analytical tool with nucleic acid microarray technology using the VaxArray platform that measures the identity and quantity of mono- and multivalent mixtures of naked mRNA and mRNA encapsulated in lipid nanoparticle formulations in under 2 h without any additional preparation steps, such as extraction or RT-PCR.

Consolidated Curium Reprocessing Procedure Inspires Molecular Design for Sensitized Curium Circularly Polarized Luminescence.

Curium's stable redox chemistry and ability to emit strong metal-based luminescence make it uniquely suitable for spectroscopic studies among the actinide series. Targeted ligand and coordination compound design can support both fundamental electronic structure studies and industrial safeguards with the identification of unique spectroscopic signatures. However, limited availability, inherent radioactive hazards, and arduous purifications have long inhibited such investigations of this element.

A Miniature Batteryless Bioelectronic Implant Using One Magnetoelectric Transducer for Wireless Powering and PWM Backscatter Communication.

Wireless minimally invasive bioelectronic implants enable a wide range of applications in healthcare, medicine, and scientific research. Magnetoelectric (ME) wireless power transfer (WPT) has emerged as a promising approach for powering miniature bio-implants because of its remarkable efficiency, safety limit, and misalignment tolerance. However, achieving low-power and high-quality uplink communication using ME remains a challenge.

Improved Energy Transfer in the Sensitization of Americium Enables Observation of Circularly Polarized Luminescence.

The first example of circularly polarized luminescence (CPL) from a molecular americium (Am) complex is reported. Coordination of Am(III) by a combination of thenoyltrifluoroacetonate and a chiral diphosphine oxide ligand yielded a complex with strong sensitized metal-centered luminescence. The energy transfer process for sensitization appears to occur via a unique resonant pathway, which results in the removal of the overlap between ligand phosphorescence and sensitized Am luminescence that has often been observed.

Actinium chelation and crystallization in a macromolecular scaffold.

Targeted alpha therapy (TAT) pairs the specificity of antigen targeting with the lethality of alpha particles to eradicate cancerous cells. Actinium-225 [Ac; t = 9.920(3) days] is an alpha-emitting radioisotope driving the next generation of TAT radiopharmaceuticals.

Transdermal Hydrogen Sulfide Delivery Enabled by Open-Metal-Site Metal-Organic Frameworks.

Hydrogen sulfide (HS) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, HS plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal HS delivery is a therapeutically viable option for the management of such disorders.

Miniature battery-free epidural cortical stimulators.

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 millimeters in width yet can safely receive enough wireless power using magnetoelectric antennas to deliver 14.

Ligand-Assisted Direct Lithography of Upconverting and Avalanching Nanoparticles for Nonlinear Photonics.

Upconverting nanoparticles (UCNPs) exhibit unique nonlinear optical properties that can be harnessed in microscopy, sensing, and photonics. However, forming high-resolution nano- and micropatterns of UCNPs with large packing fractions is still challenging. Additionally, there is limited understanding of how nanoparticle patterning chemistries are affected by the particle size.

Suspected geriatric onset of attention-deficit/hyperactivity disorder in a patient with comorbid bipolar disorder.

Background: An increasing number of adults over 60 years old are presenting with requests for treatment of attention-deficit/hyperactivity disorder (ADHD). However, the prevalence of ADHD in older adults in geriatrics is unknown. Further, comorbid bipolar disorder and adult ADHD are likely underrecognized with many patients only receiving treatment for one of these conditions.

An Industry Perspective on the use of Forced Degradation Studies to Assess Comparability of Biopharmaceuticals.

Forced degradation, also known as stress testing, is used throughout pharmaceutical development for many purposes including assessing the comparability of biopharmaceutical products according to ICH Guideline Q5E. These formal comparability studies, the results of which are submitted to health authorities, investigate potential impacts of manufacturing process changes on the quality, safety, and efficacy of the drug. Despite the wide use of forced degradation in comparability assessments, detailed guidance on the design and interpretation of such studies is scarce.

Re-imagining metastatic breast cancer care delivery: a patient-partnered qualitative study.

Purpose: While significant progress in metastatic breast cancer (MBC) treatment has prolonged survival and improved prognosis, there remain substantial gaps in providing patient-centered supportive care. The specific care delivery needs for metastatic cancer differ from that of early-stage cancer due to the incurable nature and lifelong duration of the condition. The objective of this study was to assess how patients living with MBC would re-imagine cancer care delivery.

Macrocyclic 1,2-Hydroxypyridinone-Based Chelators as Potential Ligands for Thorium-227 and Zirconium-89 Radiopharmaceuticals.

Thorium-227 (Th) is an α-emitting radionuclide that has shown preclinical and clinical promise for use in targeted α-therapy (TAT), a type of molecular radiopharmaceutical treatment that harnesses high energy α particles to eradicate cancerous lesions. Despite these initial successes, there still exists a need for bifunctional chelators that can stably bind thorium in vivo. Toward this goal, we have prepared two macrocyclic chelators bearing 1,2-hydroxypyridinone groups.

Siderocalin fusion proteins enable a new Y/Y theranostic approach.

The mammalian protein siderocalin binds bacterial siderophores and their iron complexes through cation-π and electrostatic interactions, but also displays high affinity for hydroxypyridinone complexes of trivalent lanthanides and actinides. In order to circumvent synthetic challenges, the use of siderocalin-antibody fusion proteins is explored herein as an alternative targeting approach for precision delivery of trivalent radiometals. We demonstrate the viability of this approach , using the theranostic pair Y (β, = 64 h)/Y (β, = 14.

A Qualitative Study of the Impact of the COVID-19 Pandemic on Metastatic Breast Cancer Care.

The COVID-19 pandemic substantially impacted the delivery of oncology care, particularly for individuals with metastatic cancers. The objective of this study was to qualitatively evaluate the impacts of COVID-19 on metastatic breast cancer (MBC) care among patients. This study consisted of 36 semi-structured qualitative interviews conducted virtually with people living with MBC, who were members of a patient support organization called Project Life.

Distributed Impact Wave Detection in Steel I-Beam with a Weak Fiber Bragg Gratings Array.

In this paper, acoustic, dynamic and static strain variations along a steel I-beam generated by an impact load are reconstructed simultaneously within a single measurement. Based on the chirped pulse φ-OTDR system with the single-shot measurement technique, both a higher strain-sensing resolution and a higher measurable vibration frequency are achieved. In addition, a weak fiber Bragg gratings array (WFBGA) with enhanced Rayleigh reflection is employed as a sensor, providing high signal-to-noise ratio Rayleigh traces, resulting in lower measurement uncertainty.

Dinuclear nitrido-bridged osmium complexes inhibit the mitochondrial calcium uniporter and protect cortical neurons against lethal oxygen-glucose deprivation.

Dysregulation of mitochondrial calcium uptake mediated by the mitochondrial calcium uniporter (MCU) is implicated in several pathophysiological conditions. Dinuclear ruthenium complexes are effective inhibitors of the MCU and have been leveraged as both tools to study mitochondrial calcium dynamics and potential therapeutic agents. In this study, we report the synthesis and characterization of Os245 ([Os(μ-N)(NH)Cl]) which is the osmium-containing analogue of our previously reported ruthenium-based inhibitor Ru265.

Measurement of Restrained and Unrestrained Shrinkage of Reinforced Concrete Using Distributed Fibre Optic Sensors.

Shrinkage is an important component of the behaviour of reinforced concrete (RC) structures, however, the number of variables that affect shrinkage make it a complex time-dependent phenomenon. Additionally, as new concrete materials with lower embodied carbon gain popularity, there is a need for an in-depth understanding into their shrinkage behaviour before they can be widely adopted by industry. Currently, the shrinkage behaviour of concrete is studied using discrete measurements on small-scale unrestrained prisms.