Stretchable OLEDs based on a hidden active area for high fill factor and resolution compensation.

Stretchable organic light-emitting diodes (OLEDs) have emerged as promising optoelectronic devices with exceptional degree of freedom in form factors. However, stretching OLEDs often results in a reduction in the geometrical fill factor (FF), that is the ratio of an active area to the total area, thereby limiting their potential for a broad range of applications. To overcome these challenges, we propose a three-dimensional (3D) architecture adopting a hidden active area that serves a dual role as both an emitting area and an interconnector. For this purpose, an ultrathin OLED is first attached to a 3D rigid island array structure through quadaxial stretching for precise, deformation-free alignment. A portion of the ultrathin OLED is concealed by letting it 'fold in' between the adjacent islands in the initial, non-stretched condition and gradually surfaces to the top upon stretching. This design enables the proposed stretchable OLEDs to exhibit a relatively high FF not only in the initial state but also after substantial deformation corresponding to a 30% biaxial system strain. Moreover, passive-matrix OLED displays that utilize this architecture are shown to be configurable for compensation of post-stretch resolution loss, demonstrating the efficacy of the proposed approach in realizing the full potential of stretchable OLEDs.

Understanding of Defect Passivation Effect on Wide Band Gap p-i-n Perovskite Solar Cell.

The wide band gap perovskite solar cells (PSCs) have attracted considerable attention for their great potential as top cells in high efficiency tandem cell application. However, the photovoltaic performance and stability of PSCs are constrained by nonradiative recombination, primarily stemming from defects within the bulk and at the interface of charge transport layer/perovskite and phase segregation. In this study, we systematically investigated the effects of 2-thiopheneethylammonium chloride (TEACl) on a wide band gap (∼1.67 eV) Cs0.15FA0.65MA0.20Pb(I0.8Br0.2)3 (CsFAMA) perovskite solar cell. TEACl was employed as a passivation layer between the perovskite and electron transport layer (ETL). With TEACl treatment, charged defects responsible for sub-band absorption and electrostatic potential fluctuation were effectively suppressed by the passivation of bulk defects. The incorporation of TEACl, which led to the formation of a TEA2PbX4/Perovskite (2D/3D) heterojunction, facilitated better band alignment and effective passivation of interface defects at the ETL/CsFAMA. Owing to these beneficial effects, the TEACl passivated PSC achieved a photo conversion efficiency (PCE) of 19.70% and retained ∼85% of initial PCE over ∼1900 h, surpassing the performance of the untreated PSC, which exhibited a PCE of 16.69% and retained only ∼37% of its initial PCE.

Comparison of Inter-Method Agreement and Reliability for Automatic Brain Volumetry Using Three Different Clinically Available Software Packages.

Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer's disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland-Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland-Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20-6.93) and between NQ and HAD (2.01-6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79-1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice.

Brightening deep-blue perovskite light-emitting diodes: A path to Rec. 2020.

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

(Phenoxyimine)nickel-Catalyzed C(sp2)-C(sp3) Suzuki-Miyaura Cross-Coupling: Evidence for a Recovering Radical Chain Mechanism.

Phenoxyimine (FI)-nickel(II)(2-tolyl)(DMAP) compounds were synthesized and evaluated as precatalysts for the C(sp2)-C(sp3) Suzuki-Miyaura cross coupling of (hetero)arylboronic acids with alkyl bromides. With 5 mol % of the optimal (MeOMeFI)Ni(Aryl)(DMAP) precatalyst, the scope of the cross-coupling reaction was established and included a variety of (hetero)arylboronic acids and alkyl bromides (>50 examples, 33-97% yield). A ß-hydride elimination-reductive elimination sequence from reaction with potassium isopropoxide base, yielding a potassium (FI)nickel(0)ate, was identified as a catalyst activation pathway that is responsible for halogen atom abstraction from the alkyl bromide. A combination of NMR and EPR spectroscopies identified (FI)nickel(II)-aryl complexes as the resting state during catalysis with no evidence for long-lived organic radical or odd-electron nickel intermediates. These data establish that the radical chain is short-lived and undergoes facile termination and also support a "recovering radical chain" process whereby the (FI)nickel(II)-aryl compound continually (re)initiates the radical chain. Kinetic studies established that the rate of C(sp2)-C(sp3) product formation was proportional to the concentration of the (FI)nickel(II)-aryl resting state that captures the alkyl radical for chain propagation. The proposed mechanism involves two key and concurrently operating catalytic cycles; the first involving a nickel(I/II/III) radical propagation cycle consisting of radical capture at (FI)nickel(II)-aryl, C(sp2)-C(sp3) reductive elimination, bromine atom abstraction from C(sp3)-Br, and transmetalation; and the second involving an off-cycle catalyst recovery process by slow (FI)nickel(II)-aryl → (FI)nickel(0)ate conversion for nickel(I) regeneration.

Ligand Field Sensitive Spin Acceleration in the Iron-Catalyzed [2 + 2] Cycloaddition of Unactivated Alkenes and Dienes.

Redox-active pyridine(diimine) (PDI) iron catalysts promote the reversible [2 + 2] cycloaddition of alkenes and dienes to cyclobutane derivatives that have applications ranging from fuels to chemically recyclable polymers. Metallacycles were identified as key intermediates, and spin crossover from the singlet to the triplet surface was calculated to facilitate the reductive coupling step responsible for the formation of the four-membered ring. In this work, a series of sterically and electronically differentiated PDI ligands was studied for the [2 + 2] cycloaddition of ethylene and butadiene to vinylcyclobutane. Kinetic studies revealed that the fastest and slowest turnover were observed with equally electron-deficient supporting ligands that either feature phenyl-substituted imine carbon atoms (MeBPDI) or a pyrazine core (MePZDI). While the oxidative cyclization was comparatively slow for both catalysts, the rate of reductive coupling─determined by stoichiometric 13C2H4 labeling studies─correlated with the turnover frequencies. Two-state density functional theory studies and the distinct electronic structures of related (iPrBPDI) and (iPrPZDI) iron methyl complexes revealed significantly different ligand field strengths due to either diminished ligand σ-donation (MeBPDI) or promoted metal π-backbonding (MePZDI). Spin acceleration, leading to fast reductive coupling and catalytic turnover, was promoted in the case of the weaker ligand field and depends on both the nature and position of the electron-withdrawing group. This study provides strong evidence for the role of two-state reactivity in C(sp3)-C(sp3) bond formation and insights on how ligand design either promotes or inhibits spin acceleration in earth-abundant metal catalysis.

Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target.

BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.

Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS-CoV-2 Variants.

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.

Postoperative Decrease in Bone Marrow Lesion Associated With Better Clinical Outcomes Following Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To assess serial changes of preoperative bone marrow lesion (BML) following medial open-wedge high tibial osteotomy (MOWHTO) up to 2 years and evaluate whether postoperative change of BML affected patient-reported outcome measures (PROMs) at 2 years' follow-up. Factors related to the postoperative changes in BML also were evaluated. METHODS: The current study retrospectively assessed prospectively collected data of consecutive patients between December 2016 and March 2018 who underwent MOWHTO for symptomatic knee osteoarthritis with varus malalignment (≥5°) and a minimum 2-year follow-up. Serial magnetic resonance imaging scans at preoperative and postoperative 3, 6, 18, and 24 months were performed, and the extent of BML was evaluated consecutively using 2 validated methods. Clinically, preoperative and postoperative PROMs and their achievement of minimal clinically important difference values were evaluated. The associations of the extent of BMLs with PROMs at each follow-up period over time were analyzed using a linear mixed model. Furthermore, factors related to the postoperative changes of BML were assessed. RESULTS: Of 26 patients, 21 (80.8%) had preoperative BML at medial femoral and tibial condyles. The postoperative decrease in BML was noted in 17 (81.0%) and 18 (85.7%) at medial femoral and tibial condyles. The BML decreased at postoperative 3 months and, thereafter, the extent of BML gradually reduced until postoperative 24 months. The proportion of patients achieved minimal clinically important difference was 84.6% for total Western Ontario and McMaster Universities Osteoarthritis Index scores and 80.8%, 76.9%, and 84.6% for KOOS symptom, pain, and activity of daily living subscales. Postoperative decrease in BML was significantly associated with better PROMs over postoperative 24 months. Furthermore, normo-correction (2°-5° valgus) was a significant factor for decreased BML following MOWHTO. CONCLUSIONS: Preoperative BML gradually decreased with time following MOWHTO, and the postoperative decrease in BML related with better PROMs over postoperative 24 months. Moreover, postoperative valgus alignment was a significant factor relating the postoperative decrease of BML. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Multicentric Epithelioid Angiosarcoma of Bones Showing Angiotropic Spread: A Case Report.

Epithelioid angiosarcoma is a rare variant of angiosarcoma characterized by an epithelioid morphology that mimics carcinoma. Therefore, multicentric epithelioid angiosarcoma is easily misdiagnosed as bone metastasis from carcinoma and has an aggressive clinical course. Here, we present a rare case of a 61-year-old male with multicentric epithelioid angiosarcoma of the bone. Plain radiography, CT, and MRI revealed multiple osteolytic lesions in both femurs; some lesions showed soft tissue extension with cortical bone destruction. Interestingly, PET-CT revealed that the lesions were only distributed along the bones of the lower extremities, including the pelvic bones, femurs, and tibiae. Despite histological analysis initially suggesting metastatic carcinoma, after additional immunohistological staining, including that for vascular markers (CD31 and ERG), the final diagnosis was epithelioid angiosarcoma. A better understanding of the clinicoradiological features of this disease may help eliminate diagnostic confusion and provide better management.

Somatic cancer driver mutations are enriched and associated with inflammatory states in Alzheimer's disease microglia.

Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-ß and tau1,2. Neuroinflammation mediated by microglia and brain-resident macrophages plays a crucial role in AD pathogenesis1-5, though the mechanisms by which age, genes, and other risk factors interact remain largely unknown. Somatic mutations accumulate with age and lead to clonal expansion of many cell types, contributing to cancer and many non-cancer diseases6,7. Here we studied somatic mutation in normal aged and AD brains by three orthogonal methods and in three independent AD cohorts. Analysis of bulk RNA sequencing data from 866 samples from different brain regions revealed significantly higher (~two-fold) overall burdens of somatic single-nucleotide variants (sSNVs) in AD brains compared to age-matched controls. Molecular-barcoded deep (>1000X) gene panel sequencing of 311 prefrontal cortex samples showed enrichment of sSNVs and somatic insertions and deletions (sIndels) in cancer driver genes in AD brain compared to control, with recurrent, and often multiple, mutations in genes implicated in clonal hematopoiesis (CH)8,9. Pathogenic sSNVs were enriched in CSF1R+ microglia of AD brains, and the high proportion of microglia (up to 40%) carrying some sSNVs in cancer driver genes suggests mutation-driven microglial clonal expansion (MiCE). Analysis of single-nucleus RNA sequencing (snRNAseq) from temporal neocortex of 62 additional AD cases and controls exhibited nominally increased mosaic chromosomal alterations (mCAs) associated with CH10,11. Microglia carrying mCA showed upregulated pro-inflammatory genes, resembling the transcriptomic features of disease-associated microglia (DAM) in AD. Our results suggest that somatic driver mutations in microglia are common with normal aging but further enriched in AD brain, driving MiCE with inflammatory and DAM signatures. Our findings provide the first insights into microglial clonal dynamics in AD and identify potential new approaches to AD diagnosis and therapy.

Valley-centre tandem perovskite light-emitting diodes.

Perovskite light-emitting diodes (PeLEDs) have emerged as a promising new light source for displays. The development roadmap for commercializing PeLEDs should include a tandem device structure, specifically by stacking a thin nanocrystal PeLED unit and an organic light-emitting diode unit, which can achieve a vivid and efficient tandem display; however, simply combining light-emitting diodes with different characteristics does not guarantee both narrowband emission and high efficiency, as it may cause a broadened electroluminescence spectra and a charge imbalance. Here, by conducting optical simulations of the hybrid tandem (h-tandem) PeLED, we have discovered a crucial optical microcavity structure known as the h-tandem valley, which enables the h-tandem PeLED to emit light with a narrow bandwidth. Specifically, the centre structure of the h-tandem valley (we call it valley-centre tandem) demonstrates near-perfect charge balance and optimal microcavity effects. As a result, the h-tandem PeLED achieves a high external quantum efficiency of 37.0% and high colour purity with a narrow full-width at half-maximum of 27.3 nm (versus 64.5 nm in organic light-emitting diodes) along with a fast on-off response. These findings offer a new strategy to overcome the limitations of nanocrystal-based PeLEDs, providing valuable optical and electrical guidelines for integrating different types of light-emitting device into practical display applications.

Machine-learning model predicting quality of life using multifaceted lifestyles in middle-aged South Korean adults: a cross-sectional study.

BACKGROUND: In the context of population aging, advances in healthcare technology, and growing interest in healthy aging and higher quality of life (QOL), have gained central focus in public health, particularly among middle-aged adults. METHODS: This study presented an optimal prediction model for QOL among middle-aged South Korean adults (N = 4,048; aged 30-55 years) using a machine-learning technique. Community-based South Korean population data were sampled through multistage stratified cluster sampling. Twenty-one variables related to individual factors and various lifestyle patterns were surveyed. QOL was assessed using the Short Form Health Survey (SF-12) and categorized into total QOL, physical component score (PCS), and mental component score (MCS). Seven machine-learning algorithms were used to predict QOL: decision tree, Gaussian Naïve Bayes, k-nearest neighbor, logistic regression, extreme gradient boosting, random forest, and support vector machine. Data imbalance was resolved with the synthetic minority oversampling technique (SMOTE). Random forest was used to compare feature importance and visualize the importance of each variable. RESULTS: For predicting QOL deterioration, the random forest method showed the highest performance. The random forest algorithm using SMOTE showed the highest area under the receiver operating characteristic (AUC) for total QOL (0.822), PCS (0.770), and MCS (0.786). Applying the data, SMOTE enhanced model performance by up to 0.111 AUC. Although feature importance differed across the three QOL indices, stress and sleep quality were identified as the most potent predictors of QOL. Random forest generated the most accurate prediction of QOL among middle-aged adults; the model showed that stress and sleep quality management were essential for improving QOL. CONCLUSION: The results highlighted the need to develop a health management program for middle-aged adults that enables multidisciplinary management of QOL.

Boosted micropollutant removal over urchin-like structured hydroxyapatite-incorporated nickel magnetite catalyst via peroxydisulfate activation.

In this work, urchin-like structured hydroxyapatite-incorporated nickel magnetite (NiFe3O4/UHdA) microspheres were developed for the efficient removal of micropollutants (MPs) via peroxydisulfate (PDS) activation. The prepared NiFe3O4/UHdA degraded 99.0 % of sulfamethoxazole (SMX) after 15 min in 2 mM PDS, having a first-order kinetic rate constant of 0.210 min-1. In addition, NiFe3O4/UHdA outperformed its counterparts, i.e., Fe3O4/UHdA and Ni/UHdA, by giving rise to corresponding 3.6-fold and 8.6-fold enhancements in the SMX removal rate. The outstanding catalytic performance can be ascribed to (1) the urchin-like mesoporous structure with a large specific surface area and (2) the remarkable synergistic effect caused by the redox cycle of Ni3+/Ni2+ and Fe2+/Fe3+ that enhances multipath electron transfers on the surface of NiFe3O4/UHdA to produce more reactive oxygen species. Moreover, the effects of several reaction parameters, in this case the initial solution pH, PDS dosage, SMX concentration, catalyst loading, co-existing MPs and humic acid level on the catalytic performance of the NiFe3O4/UHdA + PDS system were systematically investigated and discussed in detail. The plausible catalytic mechanisms in the NiFe3O4/UHdA + PDS system were revealed via scavenging experiments and electron paramagnetic resonance analysis, which indicated a radical (•OH and SO4•-) as the major pathway and a nonradical (1O2) as the minor pathway for SMX degradation. Furthermore, NiFe3O4/UHdA exhibited fantastic magnetically separation and retained good catalytic activity with a low leached ion concentration during the performance of four cycles. Overall, the prepared NiFe3O4/UHdA with outstanding PDS activation could be a promising choice for the degradation of persistent organic pollutants from wastewater.

High-Performing and Capacitive-Matched Triboelectric Implants Driven by Ultrasound.

In implantable bioelectronics, which aim for semipermanent use of devices, biosafe energy sources and packaging materials to protect devices are essential elements. However, research so far has been conducted in a direction where they cannot coexist. Here, the development of capacitance-matched triboelectric implants driven is reported by ultrasound under 500 mW cm-2 safe intensity and realize a battery-free, miniatured, and wireless neurostimulator with full titanium (Ti) packaging. The triboelectric implant with high dielectric composite, which has ultralow output impedance, can efficiently deliver sufficient power to generate the stimulation pulse without an energy-storing battery, despite ultrasound attenuation due to the Ti, and has the highest energy transmission efficiency among those reported so far. In vivo study using a rat model demonstrated that the proposed device system is an effective solution for relieving urinary symptoms. These achievements provide a significant step toward permanently implantable devices for controlling human organs and treating various diseases.

Comparison of Fixation Methods Between Transosseous Pull-Out Suture and Separate Vertical Wiring for Inferior Pole Fracture of Patella: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare, in a systematic review, Krakow transosseous (KT) suturing and separate vertical wiring (VW) fixation methods in inferior pole fractures of the patella and to evaluate whether the supplementary fixation affected bone union. DATA SOURCES: The MEDLINE, Embase, and Cochrane databases were searched from inception to January 15, 2023. The keywords were "patella inferior pole fracture", "patella distal pole fracture", "transosseous", "pull-out suture", "reattachment", and "vertical wiring". STUDY SELECTION: All clinical studies describing KT or VW techniques for inferior pole fracture of the patella and reporting bone union-related complications were included. DATA EXTRACTION: This meta-analysis included 16 studies with 274 patellae. Demographic data, surgical techniques, clinical outcomes, and complication rates were recorded. The Methodological Index for Non-Randomized Studies criteria were used to assess their quality. DATA SYNTHESIS: A meta-analysis was performed using random-effects models and meta-regression. The meta-analytic estimate of bone union-related complications was 3.8% (95% CI, 1.6%-6.0%) for either PO or VW techniques in inferior pole fractures of the patella. The bone union-related complication rates did not differ significantly between the two techniques (KT, 5.7%; VW, 3.0%; P = .277). Meanwhile, supplementation fixation was significantly associated with decrease in bone union-related complication rates ( p = .013). CONCLUSIONS: Fixation of inferior pole fractures of the patella using either KT or VW techniques provided satisfactory and similar clinical results with minimal bone union-related complications. Supplementary fixation has a positive impact on reducing bone union-related complications in inferior pole fractures of the patella following KT and VW techniques. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia.

While ATM loss of function has long been identified as the genetic cause of ataxia-telangiectasia (A-T), how it leads to selective and progressive degeneration of cerebellar Purkinje and granule neurons remains unclear. ATM expression is enriched in microglia throughout cerebellar development and adulthood. Here, we find evidence of microglial inflammation in the cerebellum of patients with A-T using single-nucleus RNA sequencing. Pseudotime analysis revealed that activation of A-T microglia preceded upregulation of apoptosis-related genes in granule and Purkinje neurons and that microglia exhibited increased neurotoxic cytokine signaling to granule and Purkinje neurons in A-T. To confirm these findings experimentally, we performed transcriptomic profiling of A-T induced pluripotent stem cell (iPSC)-derived microglia, which revealed cell-intrinsic microglial activation of cytokine production and innate immune response pathways compared to controls. Furthermore, A-T microglia co-culture with either control or A-T iPSC-derived neurons was sufficient to induce cytotoxicity. Taken together, these studies reveal that cell-intrinsic microglial activation may promote neurodegeneration in A-T.

Influence of Previous Arthroscopic Meniscectomy on Midterm to Long-term Outcomes After Medial Open-Wedge High Tibial Osteotomy.

Background: Few studies have evaluated the clinical and radiological outcomes of medial open-wedge high tibial osteotomy (MOWHTO) in patients who had previously undergone arthroscopic meniscectomy. Purpose: To verify whether previous arthroscopic meniscectomy affects the clinical and radiological outcomes of MOWHTO. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 183 consecutive knees that underwent MOWHTO and had a minimum 5 years of follow-up were retrospectively reviewed. We compared the preoperative and postoperative clinical and radiological data of 32 knees with a history of meniscectomy (previous meniscectomy group) to 151 control knees without a history of meniscectomy. Cartilage status was also compared at first- and second-look arthroscopic surgery according to the International Cartilage Repair Society grading system. Failure was defined as conversion to total knee arthroplasty or revision MOWHTO. On subgroup analysis, the previous meniscectomy group was divided into 2 subgroups based on the time from meniscectomy to MOWHTO (<3 vs ≥3 years). Results: The mean age at the time of surgery was 55.9 years (range, 38-70 years), and the mean follow-up period was 86.2 months (range, 60-164 months). The mean time between meniscectomy and MOWHTO was 48.9 months (range, 5-156 months), and all meniscectomy procedures were performed on the medial side. Preoperative patient characteristics were similar between the study groups. Clinical and radiological outcomes were not significantly different between the groups at the latest follow-up, and no significant between-group differences were observed regarding postoperative cartilage status on arthroscopic examination. One knee in the control group underwent conversion to total knee arthroplasty at 7 years postoperatively for arthritic progression. Subgroup analysis of the previous meniscectomy group indicated no significant differences in clinical outcomes based on the time from meniscectomy to MOWHTO. Conclusion: Based on the results, a history of meniscectomy did not adversely affect the midterm to long-term outcomes of MOWHTO. Furthermore, the time between previous meniscectomy and MOWHTO was not associated with the clinical outcomes of MOWHTO.

Somatic Mosaicism in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Reveals Widespread Degeneration from Focal Mutations.

Although mutations in dozens of genes have been implicated in familial forms of amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases of these conditions are sporadic (sALS and sFTD), with no family history, and their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present in some but not all cells, might contribute in these cases, by performing ultra-deep, targeted sequencing of 88 genes associated with neurodegenerative diseases in postmortem brain and spinal cord samples from 404 individuals with sALS or sFTD and 144 controls. Known pathogenic germline mutations were found in 20.6% of ALS, and 26.5% of FTD cases. Predicted pathogenic somatic mutations in ALS/FTD genes were observed in 2.7% of sALS and sFTD cases that did not carry known pathogenic or novel germline mutations. Somatic mutations showed low variant allele fraction (typically <2%) and were often restricted to the region of initial discovery, preventing detection through genetic screening in peripheral tissues. Damaging somatic mutations were preferentially enriched in primary motor cortex of sALS and prefrontal cortex of sFTD, mirroring regions most severely affected in each disease. Somatic mutation analysis of bulk RNA-seq data from brain and spinal cord from an additional 143 sALS cases and 23 controls confirmed an overall enrichment of somatic mutations in sALS. Two adult sALS cases were identified bearing pathogenic somatic mutations in DYNC1H1 and LMNA, two genes associated with pediatric motor neuron degeneration. Our study suggests that somatic mutations in fALS/fFTD genes, and in genes associated with more severe diseases in the germline state, contribute to sALS and sFTD, and that mosaic mutations in a small fraction of cells in focal regions of the nervous system can ultimately result in widespread degeneration.

Iridium-Catalyzed Hydrogenation of a Phenoxy Radical to the Phenol: Overcoming Catalyst Deactivation with Visible Light Irradiation.

Piano-stool iridium hydride complexes bearing phenylpyridine ligands are effective precatalysts for promoting the formation of element-hydrogen bonds using H2 as the stoichiometric H-atom source. Irradiation with blue light resulted in a profound enhancement of catalyst turnover for the iridium-catalyzed hydrogenation of the aryloxyl radical 2,4,6-tBu3-C6H2O• to the corresponding phenol. Monitoring the progress of the reaction revealed the formation of an iridium 3,3-dimethyl-2,3-dihydrobenzofuranyl compound arising from two C-H activation events following the proton-coupled electron transfer (PCET) step. Under thermal conditions, this compound was inactive for catalytic aryloxide hydrogenation, representing a deactivation pathway. Irradiation with blue light under H2 released the free heterocycle and regenerated the piano-stool iridium hydride precatalyst, establishing a pathway for catalyst recovery and overall enhanced turnover.