Somatic genomic changes in single Alzheimer's disease neurons.

Dementia in Alzheimer's disease progresses alongside neurodegeneration1-4, but the specific events that cause neuronal dysfunction and death remain poorly understood. During normal ageing, neurons progressively accumulate somatic mutations5 at rates similar to those of dividing cells6,7 which suggests that genetic factors, environmental exposures or disease states might influence this accumulation5. Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer's disease and neurotypical control individuals. We found that somatic DNA alterations increase in individuals with Alzheimer's disease, with distinct molecular patterns. Normal neurons accumulate mutations primarily in an age-related pattern (signature A), which closely resembles 'clock-like' mutational signatures that have been previously described in healthy and cancerous cells6-10. In neurons affected by Alzheimer's disease, additional DNA alterations are driven by distinct processes (signature C) that highlight C>A and other specific nucleotide changes. These changes potentially implicate nucleotide oxidation4,11, which we show is increased in Alzheimer's-disease-affected neurons in situ. Expressed genes exhibit signature-specific damage, and mutations show a transcriptional strand bias, which suggests that transcription-coupled nucleotide excision repair has a role in the generation of mutations. The alterations in Alzheimer's disease affect coding exons and are predicted to create dysfunctional genetic knockout cells and proteostatic stress. Our results suggest that known pathogenic mechanisms in Alzheimer's disease may lead to genomic damage to neurons that can progressively impair function. The aberrant accumulation of DNA alterations in neurodegeneration provides insight into the cascade of molecular and cellular events that occurs in the development of Alzheimer's disease.

Role of Gasdermin E in the Biogenesis of Apoptotic Cell-Derived Exosomes.

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

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.

(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.

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.

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.

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.

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.

CanISO: a database of genomic and transcriptomic variations in domestic dog (Canis lupus familiaris).

BACKGROUND: The domestic dog, Canis lupus familiaris, is a companion animal for humans as well as an animal model in cancer research due to similar spontaneous occurrence of cancers as humans. Despite the social and biological importance of dogs, the catalogue of genomic variations and transcripts for dogs is relatively incomplete. RESULTS: We developed CanISO, a new database to hold a large collection of transcriptome profiles and genomic variations for domestic dogs. CanISO provides 87,692 novel transcript isoforms and 60,992 known isoforms from whole transcriptome sequencing of canine tumors (N = 157) and their matched normal tissues (N = 64). CanISO also provides genomic variation information for 210,444 unique germline single nucleotide polymorphisms (SNPs) from the whole exome sequencing of 183 dogs, with a query system that searches gene- and transcript-level information as well as covered SNPs. Transcriptome profiles can be compared with corresponding human transcript isoforms at a tissue level, or between sample groups to identify tumor-specific gene expression and alternative splicing patterns. CONCLUSIONS: CanISO is expected to increase understanding of the dog genome and transcriptome, as well as its functional associations with humans, such as shared/distinct mechanisms of cancer. CanISO is publicly available at https://www.kobic.re.kr/caniso/ .

Mechanistic Investigations of Phenoxyimine-Cobalt(II)-Catalyzed C(sp2)-C(sp3) Suzuki-Miyaura Cross-Coupling.

The mechanism of phenoxyimine (FI)-cobalt-catalyzed C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling was studied using a combination of kinetic measurements and catalytic and stoichiometric experiments. A series of dimeric (FI)cobalt(II) bromide complexes, [(4-CF3PhFI)CoBr]2, [(4-OMePhFI)CoBr]2, and [(2,6-diiPrPhFI)CoBr]2, were isolated and characterized by 1H and 19F NMR spectroscopies, solution and solid-state magnetic susceptibility, electron paramagnetic resonance (EPR) spectroscopy, X-ray crystallography, and diffusion-ordered NMR spectroscopy (DOSY). One complex, [(4-CF3PhFI)CoBr]2, was explored as a single-component precatalyst for C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling. Addition of potassium methoxide to [(4-CF3PhFI)CoBr]2 generated the corresponding (FI)cobalt(II) methoxide complex as determined by 1H and 19F NMR and EPR spectroscopies. These spectroscopic signatures were used to identify this compound as the resting state during catalytic C(sp2)-C(sp3) coupling. Variable time normalization analysis (VTNA) of in situ catalytic 19F NMR spectroscopic data was used to establish an experimental rate law that was first-order in a (FI)cobalt(II) precatalyst, zeroth-order in the alkyl halide, and first-order in an activated potassium methoxide-aryl boronate complex. These findings are consistent with turnover-limiting transmetalation that occurs prior to activation of the alkyl bromide electrophile. The involvement of boronate intermediates in transmetalation was corroborated by Hammett studies of electronically differentiated aryl boronic esters. Together, a cobalt(II)/cobalt(III) catalytic cycle was proposed that proceeds through a "boronate"-type mechanism.

Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma.

Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding. We identified the single-chain variable fragment (scFv)-Fc format with the highest affinity toward the membrane-proximal domain of IL-5Rα in the IL-5Rα-binding arm showed the most potent cytotoxicity against IL-5Rα-expressing peripheral eosinophils by activating autologous primary T cells from healthy donors. This study proposes IL-5Rα × CD3 bsTCEs as potential alternatives for SEA treatment. Importantly, it demonstrates the first application of bsTCEs in eliminating disease-associated cells, including eosinophils, beyond cancer cells.

Quantum Dot-Siloxane Anchoring on Colloidal Quantum Dot Film for Flexible Photovoltaic Cell.

Lead sulfide (PbS) colloidal quantum dots (CQDs) are promising materials for next-generation flexible solar cells because of near-infrared absorption, facile bandgap tunability, and superior air stability. However, CQD devices still lack enough flexibility to be applied to wearable devices owing to the poor mechanical properties of CQD films. In this study, a facile approach is proposed to improve the mechanical stability of CQDs solar cells without compromising the high power conversion efficiency (PCE) of the devices. (3-aminopropyl)triethoxysilane (APTS) is introduced on CQD films to strengthen the dot-to-dot bonding via QD-siloxane anchoring, and as a result, crack pattern analysis reveals that the treated devices become robust to mechanical stress. The device maintains 88% of the initial PCE under 12 000 cycles at a bending radius of 8.3 mm. In addition, APTS forms a dipole layer on CQD films, which improves the open circuit voltage (VOC ) of the device, achieving a PCE of 11.04%, one of the highest PCEs in flexible PbS CQD solar cells.

Detection of Cerebral Microbleeds in MR Images Using a Single-Stage Triplanar Ensemble Detection Network (TPE-Det).

BACKGROUND: Cerebral microbleeds (CMBs) are microscopic brain hemorrhages with implications for various diseases. Automated detection of CMBs is a challenging task due to their wide distribution throughout the brain, small size, and visual similarity to their mimics. For this reason, most of the previously proposed methods have been accomplished through two distinct stages, which may lead to difficulties in integrating them into clinical workflows. PURPOSE: To develop a clinically feasible end-to-end CMBs detection network with a single-stage structure utilizing 3D information. This study proposes triplanar ensemble detection network (TPE-Det), ensembling 2D convolutional neural networks (CNNs) based detection networks on axial, sagittal, and coronal planes. STUDY TYPE: Retrospective. SUBJECTS: Two datasets (DS1 and DS2) were used: 1) 116 patients with 367 CMBs and 12 patients without CMBs for training, validation, and testing (70.39 ± 9.30 years, 68 women, 60 men, DS1); 2) 58 subjects with 148 microbleeds and 21 subjects without CMBs only for testing (76.13 ± 7.89 years, 47 women, 32 men, DS2). FIELD STRENGTH/SEQUENCE: A 3 T field strength and 3D GRE sequence scan for SWI reconstructions. ASSESSMENT: The sensitivity, FPavg (false-positive per subject), and precision measures were computed and analyzed with statistical analysis. STATISTICAL TESTS: A paired t-test was performed to investigate the improvement of detection performance by the suggested ensembling technique in this study. A P value < 0.05 was considered significant. RESULTS: The proposed TPE-Det detected CMBs on the DS1 testing set with a sensitivity of 96.05% and an FPavg of 0.88, presenting statistically significant improvement. Even when the testing on DS2 was performed without retraining, the proposed model provided a sensitivity of 85.03% and an FPavg of 0.55. The precision was significantly higher than the other models. DATA CONCLUSION: The ensembling of multidimensional networks significantly improves precision, suggesting that this new approach could increase the benefits of detecting lesions in the clinic. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

CT and MRI findings beyond the subchondral bone in osteonecrosis of the femoral head to distinguish between ARCO stages 2 and 3A.

OBJECTIVES: To determine the diagnostic values of deep changes beyond the subchondral bone in osteonecrosis of the femoral head (ONFH) to distinguish between Association Research Circulation Osseous (ARCO) stages 2 and 3A. METHODS: This retrospective study included 124 hips with ONFH of stages 2 (n = 49; 23 females; mean age, 50.7 years) and 3A (n = 75; 20 females; mean age, 53.2 years) from May 2017 to August 2022, who underwent CT (n = 124) and MRI (n = 85). Deep changes beyond subchondral bone were analyzed on CT (bone resorption area and cystic change) and on MRI (bone marrow edema [BME] and joint effusion). Diagnostic performance and multivariate analysis were evaluated for detecting stage 3A. RESULTS: Stage 3A showed more frequent bone resorption area (72.0% vs. 4.1%), cystic change (52.0% vs. 0.0%), BME (93.5% vs. 43.6%), and joint effusion (76.0% vs. 24.5%) than stage 2 (p < 0.001, all). Bone resorption area and cystic change showed low sensitivities (52.0~72.0%) but high specificities (96.0~100.0%), while BME and joint effusion showed high sensitivities (76.0~93.0%) but low specificities (56.0~76.0%) for stage 3A. Predictors were in the order of bone resorption area, cystic change, and joint effusion (odds ratio: 32.952, 26.281, 9.603, respectively), and combined bone resorption area and cystic change had the best predictive value (AUC, 0.900) for stage 3A. CONCLUSIONS: Among deep changes, bone resorption area and cystic changes were highly specific and BME and joint effusion were highly sensitive for stage 3A. Combined bone resorption area and cystic change had the best predictive value for predicting ARCO stage 3A. KEY POINTS: • The exact classification between ARCO stage 2 and 3A is essential but it is sometimes difficult to distinguish between ARCO stage 2 and 3A only by subchondral fracture, especially early post-collapse stage with preservation of femoral head contour. • The predictors of stage 3A were in the order of bone resorption area, cystic change, and joint effusion and combined bone resorption area and cystic change had the best predictive value for predicting stage 3A. • Analysis of deep changes beyond the subchondral bone may make it easier to distinguish between ARCO stage 2 and 3A.

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.

The effect of combining prewarming with intraoperative phenylephrine infusion on the prevention of hypothermia in patients undergoing urological surgery: a prospective, randomized, and controlled trial.

Background: Hypothermia is common in patients undergoing urological surgery; however, no single preventative modality is completely effective. This study evaluated the effects of combining prewarming with intraoperative phenylephrine infusion for the prevention of hypothermia in patients undergoing urological surgery. Methods: This prospective study enrolled 58 patients scheduled for urological surgery under general anesthesia. The patients were randomized into two groups (n = 29). Patients in the experimental (prewarming and phenylephrine infusion) group (PP group) received prewarming for 20 min and intraoperative phenylephrine infusion, whereas those in the control group (C group) received no active prewarming with only intermittent administration of vasoactive agents. The patient's sublingual temperatures before and after anesthesia and nasopharyngeal temperature during anesthesia were recorded as core temperatures. Results: The incidence of intraoperative hypothermia was higher in the C group than in the PP group (57.7% [15/26] vs. 23.1% [6/26], P = 0.01). The severity of intraoperative hypothermia was higher in the C group than in the PP group (P = 0.004). The nasopharyngeal temperature at the end of surgery was lower in the C group than in the PP group (35.8 ± 0.6°C vs. 36.3 ± 0.4°C, P = 0.002). The trend of core temperature decline during the first hour after anesthesia induction differed between the two groups (P = 0.003; its decline was more gradual in the PP group). Conclusions: The combination of prewarming for 20 min and intraoperative phenylephrine infusion reduced the incidence and severity of intraoperative hypothermia and modified the trend of decreasing core temperatures in patients undergoing urological surgery.

What Is New in Stage 3 of the 2019 Revised Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head: A Relationship to Bone Resorption.

PURPOSE: The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. MATERIALS AND METHODS: We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. RESULTS: All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance ( P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A ( P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. CONCLUSIONS: The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.

No difference in biomechanical properties of simple, horizontal mattress, and double row repair in Bankart repair: a systematic review and meta-analysis of biomechanical studies.

BACKGROUND: Arthroscopic Bankart repair is the most common procedure in patients with anterior shoulder instability. Various repair techniques using suture anchors have been used to improve the strength of fixation and surgical outcomes in arthroscopic Bankart surgery. However, evidence regarding which method is superior is lacking. This systematic review and meta-analysis study was designed to compare the biomechanical results of simple versus horizontal mattress versus double-row mattress for Bankart repair. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane Library databases was performed to identify comparative biomechanical studies comparing the simple, horizontal mattress, and double-row techniques commonly used in Bankart repair for anterior shoulder instability. Biomechanical results included the ultimate load to failure, stiffness, cyclic displacement, and mode of failure after the ultimate load. The methodological quality was assessed based on the Quality Appraisal for Cadaveric Studies (QUACS) scale for biomechanical studies. RESULTS: Six biomechanical studies comprising 125 human cadavers were included in this systematic review. In biomechanical studies comparing simple and horizontal mattress repair and biomechanical studies comparing simple and double-row repair, there were no significant differences in the ultimate load to failure, stiffness, or cyclic displacement between the repair methods. The median QUACS scale was 11.5 with a range from 10 to 12, indicating a low risk of bias. CONCLUSION: There was no biomechanically significant difference between the simple, horizontal mattress, and double-row methods in Bankart repair. Clinical evidence such as prospective randomized controlled trials should be conducted to evaluate clinical outcomes according to the various repair methods. LEVEL OF EVIDENCE: Systematic review, Therapeutic level IV.

Tenosynovial giant cell tumors of digits: MRI differentiation between localized types and diffuse types with pathology correlation.

OBJECTIVE: To compare the MRI findings between the localized- and diffuse-type tenosynovial giant cell tumors (TSGCTs) of digits with pathology correlation. METHODS: Twenty-eight patients with newly diagnosed TSGCTs of digits (22 localized and 6 diffuse types) who underwent preoperative MRI and surgical excision were included from Jan. 2015 to September 2021. MRI findings regarding nodularity, margins, morphology of hypointensity with pathology correlation, and disease extent (bone erosion, articular involvement, muscle involvement, tendon destruction, and neurovascular encasement) were assessed. RESULTS: Diffuse type was significantly larger (P = 0.006), more multinodular on both MRI and pathology (P = 0.038, both) with significant agreement, and infiltrative on both MRI and pathology (P < 0.001, both) with substantial agreement, and showed central granular on MRI and strong hemosiderin deposition on pathology (P = 0.022 and P = 0.021) with moderate agreement than localized type. Localized type showed significantly more frequent peripheral capsules on both MRI and pathology (P < 0.001, both) with moderate agreement than diffuse type. However, the septum on both MRI and pathology showed no statistically significant difference between the two groups (P = 0.529 and P = 0.372) without significant agreement. The disease extent was more severe in the diffuse type than the localized type regarding articular involvement (P < 0.001), muscle involvement (P < 0.001), and tendon destruction (P = 0.010). No statistically significant differences were found between the two groups regarding bone erosion (P = 0.196) or neurovascular bundle encasement (P = 0.165). CONCLUSIONS: Diffuse-type TSGCTs of digits presented as locally aggressive lesions with larger, multinodular, infiltrative masses exhibiting stronger hemosiderin deposition and more severe disease extents of articular, muscle, and tendon involvement than the localized type.

Acute left iliofemoral vein thrombosis: Comparison between simple and bony May-Thurner syndrome in CT venography.

OBJECTIVES: To explore the etiology of May-Thurner syndrome (MTS) with acute iliofemoral deep vein thrombosis (DVT) regarding imaging findings and clinical features. METHODS: We retrospectively analyzed 57 patients with acute left iliofemoral DVT from 2015 to 2020. The diameter of left common iliac vein (LCIV) at the maximal compression site and its percent compression regarding the average diameter of the uncompressed iliac vein were recorded in central and distal portions of the LCIV according to the location in the quadrant of lumbar vertebral body. Compression was categorized into simple and bony MTS; Simple MTS as LCIV compressed by the right common iliac artery (RCIA) versus Bony MTS as LCIV by lower lumbar degenerative changes regardless of RCIA compression. Initial computed tomographic venography (CTV) regarding chronic change of LCIV such as fibrotic atrophy or cordlike obliteration, extent of thrombus, and lumbar degenerative changes were evaluated. Therapeutic effect after initial therapy was assessed in follow-up CTVs after 3-6 months. RESULTS: All patients showed LCIV compression with 19 simple MTS (mean age, 42.8 ± 14.1 years [23-67 years]; 12 females; symptom for 4.4 ± 5.5 days) and 38 bony MTS (mean age, 73.0 ± 10.2 years [49-85 years]; 26 females; symptom for 5.5 ± 4.8 days). There was significant difference in age (p < .001) and no significant difference in sex or symptom duration between two groups (p = .691 and 0.415, respectively). All simple MTS showed compression only in the central LCIV and half of bony MTS showed compression in both central and distal LCIV (p < .001). Among the lumbar degenerative changes, symmetric anterolateral osteophyte (p < .001) and asymmetric osteophyte (p < .001) were significantly associated with bony MTS, but not scoliosis (p = .799), compared to simple MTS. Although there was no significant difference in chronic change of LCIV, thrombosis extent, and therapeutic effect between two groups (p > .05), chronic change of LCIV showed significant difference between single and dual compression (23.7% vs. 57.9%, p = .024) and residual thrombus after initial therapy was occurred in 21.1% of single compression and 47.4% in dual compression with non-significant trend (p = .082). CONCLUSION: Bony MTS related to lumbar degenerative changes with acute iliofemoral DVT occurs in older patients, presenting more than one stenosis at LCIV, inducing more chronic change with possibly weaker therapeutic effect than simple MTS.