Anterior Vertebral Body Tethering: A Single-Center Cohort with 4.3 to 7.4 Years of Follow-up.

BACKGROUND: Vertebral body tethering (VBT) is a well-recognized, non-fusion alternative for idiopathic scoliosis in children with growth remaining. To date, there have been almost no published outcome studies with postoperative follow-up of >2 years. We aimed to fill this gap by evaluating mid-term outcomes in our first 31 consecutive patients. METHODS: We retrospectively assessed additional clinical and radiographic data (mean, 5.7 ± 0.7 years) from our first 31 consecutive patients. Assessments included standard deformity measures, skeletal maturity status, and any additional complications (e.g., suspected broken tethers or surgical revisions). Using the same definition of success (i.e., all residual deformities, instrumented or uninstrumented, ≤30° at maturity; no posterior spinal fusion), we revisited the success rate, revision rate, and suspected broken tether rate. RESULTS: Of our first 31 patients treated with VBT, 29 (of whom 28 were non-Hispanic White and 1 was non-Hispanic Asian; 27 were female and 2 were male) returned for additional follow-up. The success rate dropped to 64% with longer follow-up as deformity measures increased, and the revision rate increased to 24% following 2 additional surgical revisions. Four additional suspected broken tethers were identified, for a rate of 55%, with only 1 occurring beyond 4 years. No additional patients had conversion to a posterior spinal fusion. We observed a mean increase of 4° (range, 2° to 8°) in main thoracic deformity measures and 8° (range, 6° to 12°) in thoracolumbar deformity measures. CONCLUSIONS: With >5 years of follow-up, we observed a decrease in postoperative success, as progression of the deformity was observed in most subgroups, and an increase in the revision and suspected broken tether rates. No additional patients had conversion to a posterior spinal fusion, which may indicate long-term survivorship. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Scalable Generation of 3D Pancreatic Islet Organoids from Human Pluripotent Stem Cells in Suspension Bioreactors.

We describe a scalable method for the robust generation of 3D pancreatic islet-like organoids from human pluripotent stem cells using suspension bioreactors. Our protocol involves a 6-stage, 20-day directed differentiation process, resulting in the production of 104-105 organoids. These organoids comprise α- and ß-like cells that exhibit glucose-responsive insulin and glucagon secretion. We detail methods for culturing, passaging, and cryopreserving stem cells as suspended clusters and for differentiating them through specific growth media and exogenous factors added in a stepwise manner. Additionally, we address quality control measures, troubleshooting strategies, and functional assays for research applications.

Does Local Aqueous Tobramycin Injection Reduce Open Fracture-Related Infection Rates?

OBJECTIVES: To examine the effect of local aqueous tobramycin injection adjunct to perioperative intravenous (IV) antibiotic prophylaxis in reducing fracture-related infections (FRIs) following reduction and internal fixation of open fractures. METHODS: Design: Retrospective cohort study. SETTING: Single academic Level I trauma center. PATIENT SELECTION CRITERIA: Patients with open extremity fractures treated via reduction and internal fixation with (intervention group) or without (control group) 80 mg of local aqueous (2mg/mL) tobramycin injected during closure at the time of definitive fixation were identified from December 2018 to August 2021 based upon population-matched demographic and injury characteristics. OUTCOME MEASURES AND COMPARISONS: The primary outcome was FRI within 6 months of definitive fixation. Secondary outcomes consisted of fracture nonunion and bacterial speciation. Differences in outcomes between the two groups were assessed and logistic regression models were created to assess the difference in infection rates between groups, with and without controlling for potential confounding variables, such as sex, fracture location, and Gustilo-Anderson classification. RESULTS: An analysis of 157 patients was performed with 78 patients in the intervention group and 79 patients in the control group. In the intervention group, 30 (38.5%) patients were female with mean age of 47.1 years. In the control group, 42 (53.2%) patients were female with mean age of 46.4 years. The FRI rate was 11.5% in the intervention group compared to 25.3% in the control group (p=0.026). After controlling for sex, Gustilo-Anderson classification, and fracture location, the difference in FRI rates between groups remained significantly different (p=0.014). CONCLUSIONS: Local aqueous tobramycin injection at the time of definitive internal fixation of open extremity fractures was associated with a significant reduction in fracture-related infection rates when administered as an adjunct to intravenous antibiotics, even after controlling for potential confounding variables. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Strong angular and spectral narrowing of electroluminescence in an integrated Tamm-plasmon-driven halide perovskite LED.

Next-generation light-emitting applications such as displays and optical communications require judicious control over emitted light, including intensity and angular dispersion. To date, this remains a challenge as conventional methods require cumbersome optics. Here, we report highly directional and enhanced electroluminescence from a solution-processed quasi-2-dimensional halide perovskite light-emitting diode by building a device architecture to exploit hybrid plasmonic-photonic Tamm plasmon modes. By exploiting the processing and bandgap tunability of the halide perovskite device layers, we construct the device stack to optimise both optical and charge-injection properties, leading to narrow forward electroluminescence with an angular full-width half-maximum of 36.6° compared with the conventional isotropic control device of 143.9°, and narrow electroluminescence spectral full-width half-maximum of 12.1 nm. The device design is versatile and tunable to work with emission lines covering the visible spectrum with desired directionality, thus providing a promising route to modular, inexpensive, and directional operating light-emitting devices.

Deep learning of Parkinson's movement from video, without human-defined measures.

BACKGROUND: The core clinical sign of Parkinson's disease (PD) is bradykinesia, for which a standard test is finger tapping: the clinician observes a person repetitively tap finger and thumb together. That requires an expert eye, a scarce resource, and even experts show variability and inaccuracy. Existing applications of technology to finger tapping reduce the tapping signal to one-dimensional measures, with researcher-defined features derived from those measures. OBJECTIVES: (1) To apply a deep learning neural network directly to video of finger tapping, without human-defined measures/features, and determine classification accuracy for idiopathic PD versus controls. (2) To visualise the features learned by the model. METHODS: 152 smartphone videos of 10s finger tapping were collected from 40 people with PD and 37 controls. We down-sampled pixel dimensions and videos were split into 1 s clips. A 3D convolutional neural network was trained on these clips. RESULTS: For discriminating PD from controls, our model showed training accuracy 0.91, and test accuracy 0.69, with test precision 0.73, test recall 0.76 and test AUROC 0.76. We also report class activation maps for the five most predictive features. These show the spatial and temporal sections of video upon which the network focuses attention to make a prediction, including an apparent dropping thumb movement distinct for the PD group. CONCLUSIONS: A deep learning neural network can be applied directly to standard video of finger tapping, to distinguish PD from controls, without a requirement to extract a one-dimensional signal from the video, or pre-define tapping features.

Unveiling Competitive Adsorption in TiO2 Photocatalysis through Machine-Learning-Accelerated Molecular Dynamics, DFT, and Experimental Methods.

The efficient harnessing of solar power for water treatment via photocatalytic processes has long been constrained by the challenge of understanding and optimizing the interactions at the photocatalyst surface, particularly in the presence of nontarget cosolutes. The adsorption of these cosolutes, such as natural organic matter, onto photocatalysts can inhibit the degradation of pollutants, drastically decreasing the photocatalytic efficiency. In the present work, computational methods are employed to predict the inhibitory action of a suite of small organic molecules during TiO2 photocatalytic degradation of para-chlorobenzoic acid (pCBA). Specifically, tryptophan, coniferyl alcohol, succinic acid, gallic acid, and trimesic acid were selected as interfering agents against pCBA to observe the resulting competitive reaction kinetics via bulk and surface phase reactions according to Langmuir-Hinshelwood adsorption dynamics. Experiments revealed that trimesic and gallic acids were most competitive with pCBA, followed by succinic acid. Density functional theory (DFT) and machine learning interatomic potentials (MLIPs) were used to investigate the molecular basis of these interactions. The computational findings showed that while the type of functional group did not directly predict adsorption affinity, the spatial arrangement and electronic interactions of these groups significantly influenced adsorption dynamics and corresponding inhibitory behavior. Notably, MLIPs, derived by fine-tuning models pretrained on a vastly larger dataset, enabled the exploration of adsorption behaviors over substantially longer periods than typically possible with conventional ab initio molecular dynamics, enhancing the depth of understanding of the dynamic interaction processes. Our study thus provides a pivotal foundation for advancing photocatalytic technology in environmental applications by demonstrating the critical role of molecular-level interactions in shaping photocatalytic outcomes.

Differential effects of ganglioside lipids on the conformation and aggregation of islet amyloid polypeptide.

Despite causing over 1 million deaths annually, Type 2 Diabetes (T2D) currently has no curative treatments. Aggregation of the islet amyloid polypeptide (hIAPP) into amyloid plaques plays an important role in the pathophysiology of T2D and thus presents a target for therapeutic intervention. The mechanism by which hIAPP aggregates contribute to the development of T2D is unclear, but it is proposed to involve disruption of cellular membranes. However, nearly all research on hIAPP-lipid interactions has focused on anionic phospholipids, which are primarily present in the cytosolic face of plasma membranes. We seek here to characterize the effects of three gangliosides, the dominant anionic lipids in the outer leaflet of the plasma membrane, on the aggregation, structure, and toxicity of hIAPP. Our results show a dual behavior that depends on the molar ratio between the gangliosides and hIAPP. For each ganglioside, a low-lipid:peptide ratio enhances hIAPP aggregation and alters the morphology of hIAPP fibrils, while a high ratio eliminates aggregation and stabilizes an α-helix-rich hIAPP conformation. A more negative lipid charge more efficiently promotes aggregation, and a larger lipid headgroup improves inhibition of aggregation. hIAPP also alters the phase transitions of the lipids, favoring spherical micelles over larger tubular micelles. We discuss our results in the context of the available lipid surface area for hIAPP binding and speculate on a role for gangliosides in facilitating toxic hIAPP aggregation.

Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.

Biochemical crosstalk between two or more histone modifications is often observed in epigenetic enzyme regulation, but its functional significance in cells has been difficult to discern. Previous enzymatic studies revealed that Lys14 acetylation of histone H3 can inhibit Lys4 demethylation by lysine-specific demethylase 1 (LSD1). In the present study, we engineered a mutant form of LSD1, Y391K, which renders the nucleosome demethylase activity of LSD1 insensitive to Lys14 acetylation. K562 cells with the Y391K LSD1 CRISPR knockin show decreased expression of a set of genes associated with cellular adhesion and myeloid leukocyte activation. Chromatin profiling revealed that the cis-regulatory regions of these silenced genes display a higher level of H3 Lys14 acetylation, and edited K562 cells show diminished H3 mono-methyl Lys4 near these silenced genes, consistent with a role for enhanced LSD1 demethylase activity. These findings illuminate the functional consequences of disconnecting histone modification crosstalk for a key epigenetic enzyme.

Predicting peak inundation depths with a physics informed machine learning model.

Timely, accurate, and reliable information is essential for decision-makers, emergency managers, and infrastructure operators during flood events. This study demonstrates that a proposed machine learning model, MaxFloodCast, trained on physics-based hydrodynamic simulations in Harris County, offers efficient and interpretable flood inundation depth predictions. Achieving an average R 2 of 0.949 and a Root Mean Square Error of 0.61 ft (0.19 m) on unseen data, it proves reliable in forecasting peak flood inundation depths. Validated against Hurricane Harvey and Tropical Storm Imelda, MaxFloodCast shows the potential in supporting near-time floodplain management and emergency operations. The model's interpretability aids decision-makers in offering critical information to inform flood mitigation strategies, to prioritize areas with critical facilities and to examine how rainfall in other watersheds influences flood exposure in one area. The MaxFloodCast model enables accurate and interpretable inundation depth predictions while significantly reducing computational time, thereby supporting emergency response efforts and flood risk management more effectively.

Synthesis and functional evaluation of proteinogenic amino acid-derived synthetic cannabinoid receptor agonists related to MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA.

Synthetic cannabinoid receptor agonists (SCRAs) comprise the second largest class of new psychoactive substances (NPS), and typically α-amino acid moieties are incorporated as part of their design. Limited investigation has been performed into elucidating structure-activity relationships around commonly used α-amino acid-derived head groups, mainly with valine and tert-leucine-derived compounds previously described. As such, proactive synthesis, characterisation and pharmacological evaluation were performed to explore structure-activity relationships of 15 α-amino acid derivatives, with both the natural isomers and their enantiomers at CB1 and CB2 investigated using a fluorescence-based membrane potential assay. This library was based around the detected SCRAs MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA, with the latter showing significant receptor activation at CB1 (pEC50 = 8.34 ± 0.05 M; E max = 108 ± 3%) and CB2 (pEC50 = 8.13 ± 0.07 M; E max = 99 ± 2%). Most valine and leucine derivatives were potent and efficacious SCRAs, while smaller derivatives generally showed reduced activity at CB1 and CB2, and larger derivatives also showed reduced activity. SAR trends observed were rationalised via in silico induced fit docking. Overall, while natural enantiomers showed equipotent or greater activity than the unnatural isomers in most cases, this was not universal. As such, a number of these compounds should be monitored as emerging NPS, and various substituents described herein.

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.

A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes.

Aberrant regulation of chromatin modifiers is a common occurrence across many cancer types, and a key priority is to determine how specific alterations of these proteins, often enzymes, can be targeted therapeutically. MOZ, a histone acyltransferase, is recurrently fused to coactivators CBP, p300, and TIF2 in cases of acute myeloid leukemia (AML). Using either pharmacological inhibition or targeted protein degradation in a mouse model for MOZ-TIF2-driven leukemia, we show that KAT6 (MOZ/MORF) enzymatic activity and the MOZ-TIF2 protein are necessary for indefinite proliferation in cell culture. MOZ-TIF2 directly regulates a small subset of genes encoding developmental transcription factors, augmenting their high expression. Furthermore, transcription levels in MOZ-TIF2 cells positively correlate with enrichment of histone H3 propionylation at lysine 23 (H3K23pr), a recently appreciated histone acylation associated with gene activation. Unexpectedly, we also show that MOZ-TIF2 and MLL-AF9 regulate transcription of unique gene sets, and their cellular models exhibit distinct sensitivities to multiple small-molecule inhibitors directed against AML pathways. This is despite the shared genetic pathways of wild-type MOZ and MLL. Overall, our data provide insight into how aberrant regulation of MOZ contributes to leukemogenesis. We anticipate that these experiments will inform future work identifying targeted therapies in the treatment of AML and other diseases involving MOZ-induced transcriptional dysregulation.

The Effectiveness of Individualized Morphosyntactic Target Identification and Explicit Intervention Using the SHAPE CODING System for Children With Developmental Language Disorder and the Impact of Within-Session Dosage.

PURPOSE: We investigated the effectiveness of a highly individualized morphosyntactic intervention using the SHAPE CODING™ system delivered at different dosages. METHOD: Eight children with developmental language disorder aged 8;0-10;10 (years;months) received 10 hr of explicit individualized intervention for morphosyntax delivered in 30-min individual sessions once per week for 20 weeks. Following at least four baseline probe tests, two grammatical targets per session received explicit instruction until they reached criterion (90%), when the next target was introduced. To control for session length and teaching episode density, either both targets received 20 teaching episodes per session or one target received 10 teaching episodes and the other 30. Maintenance testing of completed targets was also carried out. RESULTS: Scores on probe tests post-intervention were significantly higher than during the baseline phase (d = 1.6) with no change during the baseline or maintenance phases. However, progress during the intervention phase was highly significant. One participant showed significantly faster progress with intervention, while one (with the lowest attention score) made little progress. When considering progress relative to cumulative intervention sessions, progress was faster with 30 teaching episodes per session and slower with 10. However, when cumulative teaching episodes were used as the predictor, all three within-session dosages showed very similar rates of progress, with the odds of a correct response increasing by 3.9% for each teaching episode. The targets that were achieved required an average of 40-60 teaching episodes. CONCLUSIONS: With the exception of one participant, the individualized intervention was highly effective and efficient. Thus, the individualized target identification process and intervention method merit further research in a larger group of children. The cumulative number of teaching episodes per target provided across sessions appeared to be key. Thus, clinicians should aim for high teaching episode rates, particularly if the number of sessions is constrained. Otherwise, intervention scheduling can be flexible. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25996168.

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, <3 cm, 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 7.69 mL and post embolization was 3.61 ML (P < 0.01). There was a 45.5% obliteration rate at follow up in our series, with 2 minor complications related to radiosurgery. CONCLUSIONS: 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.

Examination of COVID stress syndrome facets and relations to substance misuse using profile analysis via multidimensional scaling (PAMS).

The COVID-19 pandemic has contributed to significant societal challenges, including increased substance misuse. The COVID stress syndrome is a constellation of interrelated processes that occur in response to pandemics, including danger/contamination fears, fears concerning economic consequences, xenophobia, compulsive checking/reassurance-seeking, and pandemic-related traumatic stress symptoms. In the present study, using a sample of 812 adults collected during the early stages of the COVID-19 pandemic in May 2020, we examined the relations between identified profiles of the COVID Stress Scales (CSS) and behavioral and cognitive aspects of substance misuse. Using profile analysis via multidimensional scaling (PAMS), we identified two core profiles of the CSS, which explained 60 % of the variance in participant responding: 1) High compulsive checking & Low xenophobia and 2) High xenophobia & Low danger/contamination. The first profile is consistent with the COVID stress syndrome, while the second profile aligns with the COVID disregard syndrome, which is a constellation of interrelated processes distinguished by a denial or downplaying of the seriousness of the COVID-19 pandemic and lack of perceived vulnerability to disease. Both profiles demonstrated significant positive correlations with drug and alcohol misuse, respectively. However, only the High xenophobia & Low danger/contamination profile demonstrated relations with cognitive aspects of substance misuse via positive and negative correlations with positive and negative expectancies of alcohol use, respectively. These findings provide further support for the relationship between the COVID stress syndrome and substance misuse and offer insight into how unique profiles of this syndrome may impact pandemic-related mental and public health interventions.

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.

Modelling nanomagnet vertex dynamics through Coulomb charges.

We investigate the magnetization dynamics in nanomagnet vertices often found in artificial spin ices. Our analysis involves creating a simplified model that depicts edge magnetization using magnetic charges. We utilize the model to explore the energy landscape, its associated curvatures, and the fundamental modes. Our study uncovers specific magnonic regimes and transitions between magnetization states, marked by zero-modes, which can be understood within the framework of Landau theory. To verify our model, we compare it with micromagnetic simulations, demonstrating a noteworthy agreement.

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.