Chiroptically active quantum nanonails.

In recent years, extensive research efforts have been dedicated to the investigation of CdSe/CdS-based quantum-confined nanostructures, driven by their distinctive properties. The morphologies of these nanostructures have been shown to directly affect their properties, an area which has proven to be an important field of study. Herein, we report a new morphology of CdSe/CdS core-shell heterostructures in the form of a 'nanonail' - a modified nanorod-like morphology, in which a distinctive triangular head can be observed at one end of the structure. In-depth studies of this morphology reveal a material with tuneable rod length and width, as well as exceptional photoluminescent properties. Following this, we have demonstrated the ability to induce chiroptical activity via ligand exchange, revealing the important role of the specific morphology, shell thickness and chiral ligand concentration in the effect of ligand induced chirality. In addition, the cellular uptake and cytotoxicity of obtained chiral nanostructures were evaluated on human lung-derived A549 cancer cells, revealing a significant enantioselectivity in biological activity. Finally, analysis on monolayers of the material demonstrate the complete absence of FRET processes. Overall, this CdSe/CdS heterostructure is another tuneable morphology of a very important nanomaterial, one which shows great advantages and a range of potential applications.

Analysis of intra-specific variations in the venom of individual snakes based on Raman spectroscopy.

The knowledge of variations in the composition of venoms from different snakes is important from both theoretical and practical points of view, in particular, at developing and selecting an antivenom. Many studies on this topic are conducted with pooled venoms, while the existence and significance of variations in the composition of venoms between individual snakes of the same species are emphasized by many authors. It is important to study both inter- and intra-specific, including intra-population, venom variations, because intra-specific variations in the venom composition may affect the effectiveness of antivenoms as strongly as inter-specific. In this work, based on venom Raman spectroscopy with principal component analysis, we assessed the variations in venoms of individual snakes of the Vipera nikolskii species from two populations and compared these intra-specific variations with inter-specific variations (with regard to the other related species). We demonstrated intra-specific (inter- and intra-population) differences in venom compositions which are smaller than inter-specific variations. We also assessed the compositions of V. nikolskii venoms from two populations to explain inter-population differences. The method used is rapid and requires virtually no preparation of samples, used in extremely small quantities, allowing the venoms of individual snakes to be analyzed. In addition, the method is informative and capable of detecting fairly subtle differences in the composition of venoms.

Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High Intensity Focused Ultrasound Therapy.

Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated to tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles. The main limitation of that method was its reliance on conventional wall filters used in Doppler imaging and optimized for imaging blood flow rather than transient scatterers. This study explores Bubble Doppler enhancement using dynamic mode decomposition (DMD) of a matrix created from a Doppler ensemble for mapping and extracting the characteristics of transient cavitation bubbles. DMD was first tested in silico with a numerical dataset mimicking the spatiotemporal characteristics of backscattered signal from tissue and bubbles. The performance of DMD filter was compared to other widely used Doppler wall filters - singular value decomposition (SVD) and infinite impulse response (IIR) highpass filter. DMD was then applied to an ex vivo tissue dataset where each HIFU pulse was immediately followed by a plane wave Doppler ensemble. In silico DMD outperformed SVD and IIR high pass filter and ex vivo provided physically interpretable images of the modes associated with bubbles and their corresponding temporal decay rates. These DMD modes can be trackable over the duration of pHIFU treatment using k-means clustering method, resulting in quantitative indicators of treatment progression.

Response of Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae) parasitized by the nematode Metaparasitylenchus hypothenemi Poinar (Tylenchida: Allantonematidae) to different colors of light.

Metaparasitylenchus hypothenemi is a nematode that naturally parasitizes Hypothenemus hampei in a coffee-producing region in Chiapas, Mexico. This study investigated changes in the attraction of parasitized borers to light. We compared the attraction of adult H. hampei females (parasitized and uninfected) to 14 different light wavelengths (350-670 nm) with a control (570 nm, yellow) under laboratory conditions. The response ranges of non-parasitized and parasitized borers were 370-650 nm and 340-650 nm, respectively. The attraction curve showed a similar shape in both borer groups (parasitized and non-parasitized), but a wide wavelength range (380-590 nm) attracted more parasitized than non-parasitized borers. The maximum response of the uninfected borers occurred at 520 nm (green), while parasitized borers exhibited three response peaks (380 nm, violet; 460 nm, blue; 520 nm, green). Parasitized borers were significantly more attracted to green light (520 nm) than to the control. The altered attraction to light in borers parasitized by M. hypothenemi is discussed from the perspective of possible host manipulation and the natural prevalence of this parasite.

Virion-incorporated CD14 enables HIV-1 to bind LPS and initiate TLR4 signaling in immune cells.

HIV-1 has a broad range of nuanced interactions with the immune system, and the incorporation of cellular proteins by nascent virions continues to redefine our understanding of the virus-host relationship. Proteins located at the sites of viral egress can be selectively incorporated into the HIV-1 envelope, imparting new functions and phenotypes onto virions, and impacting viral spread and disease. Using virion capture assays and western blot, we show that HIV-1 can incorporate the myeloid antigen CD14 into its viral envelope. Virion-incorporated CD14 remained biologically active and able to bind its natural ligand, bacterial lipopolysaccharide (LPS), as demonstrated by flow virometry and immunoprecipitation assays. Using a Toll-like receptor 4 (TLR4) reporter cell line, we also demonstrated that virions with bound LPS can trigger TLR4 signaling to activate transcription factors that regulate inflammatory gene expression. Complementary assays with THP-1 monocytes demonstrated enhanced secretion of inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and the C-C chemokine ligand 5 (CCL5), when exposed to LPS-loaded virus. These data highlight a new type of interplay between HIV-1 and the myeloid cell compartment, a previously well-established cellular contributor to HIV-1 pathogenesis and inflammation. Persistent gut inflammation is a hallmark of chronic HIV-1 infection, and contributing to this effect is the translocation of microbes across the gut epithelium. Our data herein provide proof of principle that virion-incorporated CD14 could be a novel mechanism through which HIV-1 can drive chronic inflammation, facilitated by HIV-1 particles binding bacterial LPS and initiating inflammatory signaling in TLR4-expressing cells.IMPORTANCEHIV-1 establishes a lifelong infection accompanied by numerous immunological changes. Inflammation of the gut epithelia, exacerbated by the loss of mucosal T cells and cytokine dysregulation, persists during HIV-1 infection. Feeding back into this loop of inflammation is the translocation of intestinal microbes across the gut epithelia, resulting in the systemic dissemination of bacterial antigens, like lipopolysaccharide (LPS). Our group previously demonstrated that the LPS receptor, CD14, can be readily incorporated by HIV-1 particles, supporting previous clinical observations of viruses derived from patient plasma. We now show that CD14 can be incorporated by several primary HIV-1 isolates and that this virion-incorporated CD14 can remain functional, enabling HIV-1 to bind to LPS. This subsequently allowed CD14+ virions to transfer LPS to monocytic cells, eliciting pro-inflammatory signaling and cytokine secretion. We posit here that virion-incorporated CD14 is a potential contributor to the dysregulated immune responses present in the setting of HIV-1 infection.

Safety Of The Pcsk9 Inhibitor Alirocumab: insights From 47,296 Patient-Years Of Observation.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared to that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection-site reactions. Further, the safety of alirocumab compared to placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Looking beyond year 1 in the molecular era of pediatric brain tumor diagnosis: confirmatory testing of germline variants found on tumor sequencing.

Purpose: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. Patients and Methods: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest. Results: Molecular sequencing of 88 patients' tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing. Conclusion: Clinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

Elastic Properties of Aging Human Hematoma Model In Vitro and Its Susceptibility to Histotripsy Liquefaction.

OBJECTIVE: Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0-10 d). METHODS: As an in vitro hematoma model, anticoagulated human blood samples (200 mL) were recalcified at different temperatures. In one set of samples, the shear modulus was measured by shear wave elastography during blood clotting at 10℃, 22℃ and 37℃, and then daily during further aging. The ultrastructure of the samples was analyzed daily with scanning electron microscopy (SEM). Another set of blood samples (50-200 mL) were recalcified at 37℃ for density and retraction measurements over aging and exposed to histotripsy at varying time points. Boiling histotripsy (2.5 ms pulses) and hybrid histotripsy (0.2 ms pulses) exposures (2 MHz, 1% dc, P+/P-/As = 182/-27/207 MPa in situ) were used to produce either individual cigar-shaped or volumetric (0.8-3 mL) lesions in samples incubated for 3 h, 5 d and 10 d. The obtained lesions were sized, then the lysate aspirated under B-mode guidance was analyzed ultrastructurally and diluted in distilled water for sizing of residual fragments. RESULTS: It was found that clotting time decreased from 113 to 25 min with the increase in blood temperature from 10℃ to 37℃. The shear modulus increased to 0.53 ± 0.17 kPa during clotting and remained constant within 8 d of incubation at 2℃. Sample volumes decreased by 57% because of retraction within 10 d. SEM revealed significant echinocytosis but unchanged ultrastructure of the fibrin meshwork. Liquefaction rate and lesion dimensions produced with the same histotripsy protocols correlated with the increase in the degree of retraction and were lower in retracted samples versus freshly clotted samples. More than 80% of residual fibrin fragments after histotripsy treatment were shorter than 150 µm; the maximum length was 208 µm, allowing for unobstructed aspiration of the lysate with most clinically used needles. CONCLUSION: The results indicate that hematoma susceptibility to histotripsy liquefaction is not entirely determined by its stiffness, and correlates with the retraction degree.

Developmental progression continues during embryonic diapause in the roe deer.

Embryonic diapause in mammals is a temporary developmental delay occurring at the blastocyst stage. In contrast to other diapausing species displaying a full arrest, the blastocyst of the European roe deer (Capreolus capreolus) proliferates continuously and displays considerable morphological changes in the inner cell mass. We hypothesised that developmental progression also continues during this period. Here we evaluate the mRNA abundance of developmental marker genes in embryos during diapause and elongation. Our results show that morphological rearrangements of the epiblast during diapause correlate with gene expression patterns and changes in cell polarity. Immunohistochemical staining further supports these findings. Primitive endoderm formation occurs during diapause in embryos composed of around 3,000 cells. Gastrulation coincides with elongation and thus takes place after embryo reactivation. The slow developmental progression makes the roe deer an interesting model for unravelling the link between proliferation and differentiation and requirements for embryo survival.

Systemic metabolic depletion of gut microbiome undermines responsiveness to melanoma immunotherapy.

Immunotherapy has proven to be a boon for patients battling metastatic melanoma, significantly improving their clinical condition and overall quality of life. A compelling link between the composition of the gut microbiome and the efficacy of immunotherapy has been established in both animal models and human patients. However, the precise biological mechanisms by which gut microbes influence treatment outcomes remain poorly understood. Using a robust dataset of 680 fecal metagenomes from melanoma patients, a detailed catalog of metagenome-assembled genomes (MAGs) was constructed to explore the compositional and functional properties of the gut microbiome. Our study uncovered significant findings that deepen the understanding of the intricate relationship between gut microbes and the efficacy of melanoma immunotherapy. In particular, we discovered the specific metagenomic profile of patients with favorable treatment outcomes, characterized by a prevalence of MAGs with increased overall metabolic potential and proficiency in polysaccharide utilization, along with those responsible for cobalamin and amino acid production. Furthermore, our investigation of the biosynthetic pathways of short-chain fatty acids, known for their immunomodulatory role, revealed a differential abundance of these pathways among the specific MAGs. Among others, the cobalamin-dependent Wood-Ljungdahl pathway of acetate synthesis was directly associated with responsiveness to melanoma immunotherapy.

Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27.

Dynamic Mode Decomposition for Transient Cavitation Bubbles Imaging in Pulsed High Intensity Focused Ultrasound Therapy.

Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated to tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles. The main limitation of that method was its reliance on conventional wall filters used in Doppler imaging and optimized for imaging blood flow rather than transient scatterers. This study explores Bubble Doppler enhancement using dynamic mode decomposition (DMD) of a matrix created from a Doppler ensemble for mapping and extracting the characteristics of transient cavitation bubbles. DMD was first tested in silico with a numerical dataset mimicking the spatiotemporal characteristics of backscattered signal from tissue and bubbles. The performance of DMD filter was compared to other widely used Doppler wall filters - singular value decomposition (SVD) and infinite impulse response (IIR) highpass filter. DMD was then applied to an ex vivo tissue dataset where each HIFU pulse was immediately followed by a plane wave Doppler ensemble. In silico DMD outperformed SVD and IIR high pass filter and ex vivo provided physically interpretable images of the modes associated with bubbles and their corresponding temporal decay rates. These DMD modes can be trackable over the duration of pHIFU treatment using k-means clustering method, resulting in quantitative indicators of treatment progression.

Traditional multilocus phylogeny fails to fully resolve Palearctic ground squirrels (Spermophilus) relationships but reveals a new species endemic to West Siberia.

Previous efforts to reconstruct evolutionary history of Palearctic ground squirrels within the genus Spermophilus have primarily relied on a single mitochondrial marker for phylogenetic data. In this study, we present the first phylogeny with comprehensive taxon sampling of Spermophilus via a conventional multilocus approach utilizing five mitochondrial and five nuclear markers. Through application of the multispecies coalescent model, we constructed a species tree revealing four distinct clades that diverged during the Late Miocene. These clades are 1) S. alaschanicus and S. dauricus from East Asia; 2) S. musicus and S. pygmaeus from East Europe and northwestern Central Asia; 3) the subgenus Colobotis found across Central Asia and its adjacent regions and encompassing S. brevicauda, S. erythrogenys, S. fulvus, S. major, S. pallidicauda, S. ralli, S. relictus, S. selevini, and S. vorontsovi sp. nov.; and 4) a Central/Eastern Europe and Asia Minor clade comprising S. citellus, S. taurensis, S. xanthoprymnus, S. suslicus, and S. odessanus. The latter clade lacked strong support owing to uncertainty of taxonomic placement of S. odessanus and S. suslicus. Resolving relationships within the subgenus Colobotis, which radiated rapidly, remains challenging likely because of incomplete lineage sorting and introgressive hybridization. Most of modern Spermophilus species diversified during the Early-Middle Pleistocene (2.2-1.0 million years ago). We propose a revised taxonomic classification for the genus Spermophilus by recognizing 18 species including a newly identified one (S. vorontsovi sp. nov.), which is found only in a limited area in the southeast of West Siberia. Employing genome-wide single-nucleotide polymorphism genotyping, we substantiated the role of the Ob River as a major barrier ensuring robust isolation of this taxon from S. erythrogenys. Despite its inherent limitations, the traditional multilocus approach remains a valuable tool for resolving relationships and can provide important insights into otherwise poorly understood groups. It is imperative to recognize that additional efforts are needed to definitively determine phylogenetic relationships between certain species of Palearctic ground squirrels.

Fully nonlinear three-dimensional modeling of parametric interactions in the field of a dual-frequency acoustic array.

An algorithm is developed for fully nonlinear three-dimensional (3D) simulation of a difference-frequency acoustic beam resulting from the interaction of two high-intensity pump waves. Simulations are performed in the frequency domain based on the Khokhlov-Zabolotskaya-Kuznetsov equation. A spectrum filtering method is used to enable accurate solutions for the difference-frequency fields in strongly nonlinear beams and with a high downshift frequency ratio using only dozens of spectral components retained in the algorithm. As an example, the dual-frequency operation of an underwater multi-element ellipsoidal array is considered, and numerical solutions describing parametric interactions in the array field are analyzed. It is shown that difference-frequency beams are more symmetric in transverse directions compared with the pump beams. The most efficient parametric generation of difference-frequency beams corresponded to close and beyond shock-forming conditions. Axial pressure amplitude of the difference frequency was shown to grow first quadratically with the source pressure following the quasi-linear solution and then linearly once shocks start to develop. The percentage of the total power converted to the difference frequency from pump waves increased at high power outputs without saturation. Up to twofold increase in directivity angles of difference-frequency beams under shock-forming conditions was observed compared with quasi-linear conditions.

Histotripsy: A Method for Mechanical Tissue Ablation with Ultrasound.

Histotripsy is a relatively new therapeutic ultrasound technology to mechanically liquefy tissue into subcellular debris using high-amplitude focused ultrasound pulses. In contrast to conventional high-intensity focused ultrasound thermal therapy, histotripsy has specific clinical advantages: the capacity for real-time monitoring using ultrasound imaging, diminished heat sink effects resulting in lesions with sharp margins, effective removal of the treated tissue, a tissue-selective feature to preserve crucial structures, and immunostimulation. The technology is being evaluated in small and large animal models for treating cancer, thrombosis, hematomas, abscesses, and biofilms; enhancing tumor-specific immune response; and neurological applications. Histotripsy has been recently approved by the US Food and Drug Administration to treat liver tumors, with clinical trials undertaken for benign prostatic hyperplasia and renal tumors. This review outlines the physical principles of various types of histotripsy; presents major parameters of the technology and corresponding hardware and software, imaging methods, and bioeffects; and discusses the most promising preclinical and clinical applications. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Gausemycin Antibiotic Family Acts via Ca2+-Dependent Membrane Targeting.

We report the molecular mechanism of action of gausemycins and the isolation of new members of the family, gausemycins C (1c), D (1d), E (1e), and F (1f), the minor components of the mixture. To elucidate the mechanism of action of gausemycins, we investigated the antimicrobial activity of the most active compounds, gausemycins A and B, in the presence of Ca2+, other metal ions, and phosphate. Gausemycins require a significantly higher Ca2+ concentration for maximum activity than daptomycin but lower than that required for malacidine and cadasides. Species-specific antimicrobial activity was found upon testing against a wide panel of Gram-positive bacteria. Membranoactivity of gausemycins was demonstrated upon their interactions with model lipid bilayers and micelles. The pore-forming ability was found to be dramatically dependent on the Ca2+ concentration and the membrane lipid composition. An NMR study of gausemycin B in zwitterionic and anionic micelles suggested the putative structure of the gausemycin/membrane complex and revealed the binding of Ca2+ by the macrocyclic domain of the antibiotic.

Histological and functional assessment of a Takotsubo cardiomyopathy model established by immobilization stress.

INTRODUCTION: Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease-specific diagnosis and treatment strategies. TTC accounts for approximately 5-6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress-induced cardiomyopathy in humans since stress is not an instantaneous event. METHODS: Rats were immobilized for 6 h per day for 1-14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open-Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT-PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. RESULTS: The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. CONCLUSIONS: Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs.

Treatment Planning and Aberration Correction Algorithm for HIFU Ablation of Renal Tumors.

High-intensity focused ultrasound (HIFU) applications for thermal or mechanical ablation of renal tumors often encounter challenges due to significant beam aberration and refraction caused by oblique beam incidence, inhomogeneous tissue layers, and presence of gas and bones within the beam. These losses can be significantly mitigated through sonication geometry planning, patient positioning, and aberration correction using multielement phased arrays. Here, a sonication planning algorithm is introduced, which uses the simulations to select the optimal transducer position and evaluate the effect of aberrations and acoustic field quality at the target region after aberration correction. Optimization of transducer positioning is implemented using a graphical user interface (GUI) to visualize a segmented 3-D computed tomography (CT)-based acoustic model of the body and to select sonication geometry through a combination of manual and automated approaches. An HIFU array (1.5 MHz, 256 elements) and three renal cell carcinoma (RCC) cases with different tumor locations and patient body habitus were considered. After array positioning, the correction of aberrations was performed using a combination of backpropagation from the focus with an ordinary least squares (OLS) optimization of phases at the array elements. The forward propagation was simulated using a combination of the Rayleigh integral and k-space pseudospectral method (k-Wave toolbox). After correction, simulated HIFU fields showed tight focusing and up to threefold higher maximum pressure within the target region. The addition of OLS optimization to the aberration correction method yielded up to 30% higher maximum pressure compared to the conventional backpropagation and up to 250% higher maximum pressure compared to the ray-tracing method, particularly in strongly distorted cases.

Somatic Versus Germline: A Case Series of Three Children With ATM-Mutated Medulloblastoma.

Somatic versus Germline-A Case Series of Three Children with ATM- mutated Medulloblastoma.