Embolization prior to Radiosurgery in Treatment of Arteriovenous Malformations: Defining Radiosurgery Target Dose with Nidal Volume Reduction.

INTRODUCTION: Arteriovenous malformations (AVMs) can be treated with observation, surgery, embolization, stereotactic radiosurgery (SRS) or a combination of therapies. SRS has been used for AVMs that pose a high risk of surgery, such as in deep or eloquent anatomic locations. Smaller AVMs, < 3cm, have been shown to have higher rates of complete obliteration after SRS. For AVMs that are a larger size, embolization prior to SRS has been used to reduce the size of the AVM nidus. In this study we analyzed embolization prior to SRS to reduce nidal volume and describe imaging techniques to target for SRS post embolization. METHODS: We retrospectively reviewed all patients at a single academic institution treated with embolization prior to SRS for treatment of AVMs. We then used contrast enhanced magnetic resonance imaging (MRI) to contour AVM volumes based on pre-embolization imaging and compared to post-embolization imaging. Planned AVM volume prior to embolization was then compared to actual treated AVM volume. RESULTS: We identified 11 patients treated with embolization prior to SRS from 2011-2023. Median AVM nidal volume prior to embolization was 7.69cc and post embolization was 3.61cc (p<0.01). There was a 45.5% obliteration rate at follow up in our series with 2 minor complications related to radiosurgery. CONCLUSION: In our cohort, embolization prior to SRS resulted in a statistically significant reduction in AVM nidal volume. Therefore, embolization prior to SRS can result in dose reduction at time of SRS treatment allowing for decreased risk of SRS complications without higher embolization complication rates.

Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

Fabrication of red-emitting perovskite LEDs by stabilizing their octahedral structure.

Light-emitting diodes (LEDs) based on metal halide perovskites (PeLEDs) with high colour quality and facile solution processing are promising candidates for full-colour and high-definition displays1-4. Despite the great success achieved in green PeLEDs with lead bromide perovskites5, it is still challenging to realize pure-red (620-650 nm) LEDs using iodine-based counterparts, as they are constrained by the low intrinsic bandgap6. Here we report efficient and colour-stable PeLEDs across the entire pure-red region, with a peak external quantum efficiency reaching 28.7% at 638 nm, enabled by incorporating a double-end anchored ligand molecule into pure-iodine perovskites. We demonstrate that a key function of the organic intercalating cation is to stabilize the lead iodine octahedron through coordination with exposed lead ions and enhanced hydrogen bonding with iodine. The molecule synergistically facilitates spectral modulation, promotes charge transfer between perovskite quantum wells and reduces iodine migration under electrical bias. We realize continuously tunable emission wavelengths for iodine-based perovskite films with suppressed energy loss due to the decrease in bond energy of lead iodine in ionic perovskites as the bandgap increases. Importantly, the resultant devices show outstanding spectral stability and a half-lifetime of more than 7,600 min at an initial luminance of 100 cd m-2.

Resolving length-scale-dependent transient disorder through an ultrafast phase transition.

Material functionality can be strongly determined by structure extending only over nanoscale distances. The pair distribution function presents an opportunity for structural studies beyond idealized crystal models and to investigate structure over varying length scales. Applying this method with ultrafast time resolution has the potential to similarly disrupt the study of structural dynamics and phase transitions. Here we demonstrate such a measurement of CuIr2S4 optically pumped from its low-temperature Ir-dimerized phase. Dimers are optically suppressed without spatial correlation, generating a structure whose level of disorder strongly depends on the length scale. The redevelopment of structural ordering over tens of picoseconds is directly tracked over both space and time as a transient state is approached. This measurement demonstrates the crucial role of local structure and disorder in non-equilibrium processes as well as the feasibility of accessing this information with state-of-the-art XFEL facilities.

Tunable liquid lens for three-photon excitation microscopy.

We demonstrate a novel electrowetting liquid combination using a room temperature ionic liquid (RTIL) and a nonpolar liquid, 1-phenyl-1-cyclohexene (PCH) suitable for focus-tunable 3-photon microscopy. We show that both liquids have over 90% transmission at 1300 nm over a 1.1 mm pathlength and an index of refraction contrast of 0.123. A lens using these liquids can be tuned from a contact angle of 133 to 48° with applied voltages of 0 and 60 V, respectively. Finally, a three-photon imaging system including an RTIL electrowetting lens was used to image a mouse brain slice. Axial scans taken with an electrowetting lens show excellent agreement with images acquired using a mechanically scanned objective.

Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?

Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Systematic Review of Gender and Sex Terminology Use in Arthroplasty Research: There Is Room for Improvement.

BACKGROUND: There is increasing appreciation of the distinction between gender and sex as well as the importance of accurately reporting these constructs. Given recent attention regarding transgender and gender nonconforming (TGNC) and intersex identities, it is more necessary than ever to understand how to describe these identities in research. This study sought to investigate the use of gender- and sex-based terminology in arthroplasty research. METHODS: The 5 leading orthopaedic journals publishing arthroplasty research were reviewed to identify the first twenty primary clinical research articles on an arthroplasty topic published after January 1, 2022. Use of gender- or sex-based terminology, whether use was discriminate, and whether stratification or adjustment based on gender or sex was performed, were recorded. RESULTS: There were 98 of 100 articles that measured a construct of gender or sex. Of these, 15 articles used gender-based terminology, 45 used sex-based terminology, and 38 used a combination of gender- and sex-based terminology. Of the 38 articles using a combination of terminology, none did so discriminately. All articles presented gender and sex as binary variables, and 2 attempted to explicitly define how gender or sex were defined. Of the 98 articles, 31 used these variables for statistical adjustments, though only 6 reported stratified results. CONCLUSIONS: Arthroplasty articles infrequently describe how gender or sex was measured, and frequently use this terminology interchangeably. Additionally, these articles rarely offer more than 2 options for capturing variation in sex and gender. Future research should be more precise in the treatment of these variables to improve the quality of results and ensure findings are patient-centered and inclusive.

Multifold Enhanced Photon Upconversion in a Composite Annihilator System Sensitized by Perovskite Nanocrystals.

Photon upconversion via triplet-triplet annihilation (TTA-UC) provides a pathway to overcoming the thermodynamic efficiency limits in single-junction solar cells by allowing the harvesting of sub-bandgap photons. Here, we use mixed halide perovskite nanocrystals (CsPbX3, X = Br/I) as triplet sensitizers, with excitation transfer to 9,10-diphenylanthracene (DPA) and/or 9,10-bis[(triisopropylsilyl)ethynyl]anthracene (TIPS-An) which act as the triplet annihilators. We observe that the upconversion efficiency is five times higher with the combination of both annihilators in a composite system compared to the sum of the individual single-acceptor systems. Our work illustrates the importance of using a composite system of annihilators to enhance TTA upconversion, demonstrated in a perovskite-sensitized system, with promise for a range of potential applications in light-harvesting, biomedical imaging, biosensing, therapeutics, and photocatalysis.

Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage.

BACKGROUND: It is established that the immune system, namely T cells, plays a role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this relationship in females. Rats with genetically deleted T cells via CD247 gene mutation on the Dahl SS background (SSCD247-/-) were utilized to interrogate the effect of sex and T cells on salt sensitivity. METHODS: We assessed the hypertensive and kidney injury phenotypes in male versus female SS and SSCD247-/- rats challenged with 3 weeks of high salt (4.0% NaCl). Differences in T cell activation genes were examined in renal T cells from male and female SS rats, and a sex-specific adoptive transfer was performed by injecting male or female splenocytes into either male or female SSCD247-/- recipients to determine the potential contribution of T cell sex. RESULTS: The lack of functional T cells in SSCD247-/- rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SSCD247-/- females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SSCD247-/- male recipients exacerbated hypertension and proteinuria compared with controls, while in SSCD247-/- female recipients, exacerbation of disease occurred only upon transfer of male, but not female, SS splenocytes. CONCLUSIONS: The absence of T cells in the SSCD247-/- normalized sex differences in blood pressure, though sex differences in renal damage persisted. Splenocyte transfer experiments demonstrated that salt sensitivity is amplified if the sex of the T cell or the recipient is male.

Structure-Activity Relationships, Deuteration, and Fluorination of Synthetic Cannabinoid Receptor Agonists Related to AKB48, 5F-AKB-48, and AFUBIATA.

Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an N-alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular N-alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug market rapidly. In response to the large number of SCRAs that have been detected, pharmacological evaluation of this NPS class has become increasingly common. Adamantane-derived SCRAs have consistently appeared throughout the market since 2011, and as such, a systematic set of these derivatives was synthesized and pharmacologically evaluated. Deuterated and fluorinated adamantane derivatives were prepared to evaluate typical hydrogen bioisosteres, as well as evaluation of the newly detected AFUBIATA.

Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors.

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Comparing the end correction of a spherically baffled piston to infinitely baffled and unbaffled circular radiators (L).

Models of acoustical systems commonly employ end corrections to represent the radiation impedance of a vibrating element. Although several analytic solutions appear in the literature, the end corrections of an infinitely baffled circular piston and an unbaffled semi-infinite circular pipe remain popular in modeling applications. This Letter compares the end correction of these two configurations to that of a radially vibrating cap on a sphere. The results show that the spherically baffled end correction, when expressed as a function of spherical-cap radius, falls between these two extremal boundary conditions.

Quantum barriers engineering toward radiative and stable perovskite photovoltaic devices.

Efficient photovoltaic devices must be efficient light emitters to reach the thermodynamic efficiency limit. Here, we present a promising prospect of perovskite photovoltaics as bright emitters by harnessing the significant benefits of photon recycling, which can be practically achieved by suppressing interfacial quenching. We have achieved radiative and stable perovskite photovoltaic devices by the design of a multiple quantum well structure with long (∼3 nm) organic spacers with oleylammonium molecules at perovskite top interfaces. Our L-site exchange process (L: barrier molecule cation) enables the formation of stable interfacial structures with moderate conductivity despite the thick barriers. Compared to popular short (∼1 nm) Ls, our approach results in enhanced radiation efficiency through the recursive process of photon recycling. This leads to the realization of radiative perovskite photovoltaics with both high photovoltaic efficiency (in-lab 26.0%, certified to 25.2%) and electroluminescence quantum efficiency (19.7 % at peak, 17.8% at 1-sun equivalent condition). Furthermore, the stable crystallinity of oleylammonium-based quantum wells enables our devices to maintain high efficiencies for over 1000 h of operation and >2 years of storage.

Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

[This corrects the article DOI: 10.1371/journal.pone.0246393.].

Right coronary artery obstruction following transcatheter aortic valve replacement by aortic valve mass.

A 93-year-old woman with symptomatic severe aortic stenosis and normal biventricular function was referred for transcatheter aortic valve replacement (TAVR) evaluation. Cardiac computed tomography revealed safe coronary heights and multiple large calcified mobile mass-like structures attached to the aortic valve (AV), confirmed also by transesophageal echocardiography, which were thought to be prominent Lambl's excrescences.

Examining Health Inequities in A1C Control over Time across Individual, Geospatial, and Geopolitical Factors among Adults with Type 2 Diabetes: Analyses of a Sample from One Commercial Insurer in a Southern State.

INTRODUCTION: Type 2 diabetes impacts millions and poor maintenance of diabetes can lead to preventable complications, which is why achieving and maintaining target A1C levels is critical. Thus, we aimed to examine inequities in A1C over time, place, and individual characteristics, given known inequities across these indicators and the need to provide continued surveillance. METHODS: Secondary de-identified data from medical claims from a single payer in Texas was merged with population health data. Generalized Estimating Equations were utilized to assess multiple years of data examining the likelihood of having non-target (>7% and ≥7%, two slightly different cut points based on different sources) and separately uncontrolled (>9%) A1C. Adults in Texas, with a Type 2 Diabetes (T2D) flag and with A1C reported in first quarter of the year using data from 2016 and 2019 were included in analyses. RESULTS: Approximately 50% had A1Cs within target ranges (<7% and ≤7%), with 50% considered having non-target (>7% and ≥7%) A1Cs; with 83% within the controlled ranges (≤9%) as compared to approximately 17% having uncontrolled (>9%) A1Cs. The likelihood of non-target A1C was higher among those individuals residing in rural (vs urban) areas (P < .0001); similar for the likelihood of reporting uncontrolled A1C, where those in rural areas were more likely to report uncontrolled A1C (P < .0001). In adjusted analysis, ACA enrollees in 2016 were approx. 5% more likely (OR = 1.049, 95% CI = 1.002-1.099) to have non-target A1C (≥7%) compared to 2019; in contrast non-ACA enrollees were approx. 4% more likely to have non-target A1C (≥7%) in 2019 compared to 2016 (OR = 1.039, 95% CI = 1.001-1.079). In adjusted analysis, ACA enrollees in 2016 were 9% more likely (OR = 1.093, 95% CI = 1.025-1.164) to have uncontrolled A1C compared to 2019; whereas there was no significant change among non-ACA enrollees. CONCLUSIONS: This study can inform health care interactions in diabetes care settings and help health policy makers explore strategies to reduce health inequities among patients with diabetes. Key partners should consider interventions to aid those enrolled in ACA plans, those in rural and border areas, and who may have coexisting health inequities.