C-H Activation of Pyridines by Boryl Pincer Complexes: Elucidation of Boryl-Directed C-H Oxidative Addition to Ir and Discovery of Transition Metal-Assisted Reductive Elimination from Boron at Rh.

Experimental and theoretical techniques were used to investigate the mechanism of pyridine C-H activation by diarylboryl/bis(phosphine) PBP pincer complexes of Ir. The critical intermediate (PBP)IrCO (4) contains a three-coordinate, Ir-bound boron that retains Lewis acidity in the perpendicular direction. Coordination of pyridine to this boron center in 4 leads to fast insertion of Ir into the 2-CH bond of pyridine, providing a different topology of direction than the conventional directed C-H activation where both the directing group coordination and C-H activation happen at the same metal center. Beyond this critical sequence, the system possesses significant complexity in terms of possible isomers and pathways, which have been thoroughly explored. Kinetic and thermodynamic preferences for the activation of differently substituted pyridines were also investigated. In experimental work, the key intermediate 4 is accessed via elimination of benzene from a phenyl/hydride containing precursor (PBPhP)IrHCO (3). Density functional theory (DFT) investigations of the mechanism of benzene loss from 3 revealed the possibility of a genuinely new type of mechanism, whereby the Ph-H bond is made in a concerted process that is best described as C-H reductive elimination from boron, assisted by the transition metal (TMARE). For Ir, this pathway was predicted to be competitive with the more conventional pathways involving C-H reductive elimination from Ir, but still higher in energy barrier. However, for the Rh analog 3-Rh, TMARE was calculated to be the preferred pathway for benzene loss and this prediction was experimentally corroborated through the study of reaction rates and the kinetic isotope effect.

Burnout among radiology residents: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prevalence of burnout among radiology residents. METHOD: Five databases (PubMed, Web of Science, Embase, PsycINFO, and Scopus) were searched for studies reporting burnout in radiology residents for the period up to November 7, 2022. RESULTS: A total of 423 studies were identified, and eventually, 16 studies were selected for the qualitative analysis, of which 11 studies were used in the meta-analysis. There was a total of 2164 radiology residents. Six studies reported the prevalence of burnout but the data could not be pooled due to their inconsistent definitions of burnout. The mean scores of three burnout subscales indicated a moderate to high degree of severity: emotional exhaustion = 25.2 (95% CI, 22.1-28.3; I2 = 94.4%), depersonalization = 10.2 (95% CI, 8.5-11.9; I2 = 93.0%), and low perception of personal accomplishment = 32.9 (95% CI, 30.5-35.4; I2 = 94.4%). The pooled prevalence of high-degree emotional exhaustion was 49.9% (95% CI, 43.6-56.1%; I2 = 55.7%), high-degree depersonalization was 45.1% (95% CI, 38.3-52.0%; I2 = 63.2%), and high-degree diminished personal accomplishment was 58.2% (95% CI, 36.0-77.6%; I2 = 84.9%). The impact of the COVID-19 pandemic on radiology residents was not investigated. In addition, there are inconsistent findings on the effects of female sex, seniority, and social support on burnout. CONCLUSIONS: About half of the radiology residents showed at least one of the three burnout manifestations (emotional exhaustion, depersonalization, and personal accomplishment), with a moderate to high degree of severity. CLINICAL RELEVANCE STATEMENT: Such a high prevalence and severity of burnout among radiology residents warrant the attention of residency program directors. KEY POINTS: • Burnout, not uncommon among radiology residents, has not been effectively analyzed. • Nearly half of the radiology residents experience at least one of the three manifestations of burnout to a moderate to high degree. • The high prevalence and severe degree of burnout among radiology residents warrant the attention of residency program directors.

Transcriptome Analysis Reveals the Mechanism of Exogenous Selenium in Alleviating Cadmium Stress in Purple Flowering Stalks (Brassica campestris var. purpuraria).

In China, cadmium (Cd) stress has a significant role in limiting the development and productivity of purple flowering stalks (Brassica campestris var. purpuraria). Exogenous selenium supplementation has been demonstrated in earlier research to mitigate the effects of Cd stress in a range of plant species; nevertheless, the physiological and molecular processes by which exogenous selenium increases vegetable shoots' resistance to Cd stress remain unclear. Purple flowering stalks (Brassica campestris var. purpuraria) were chosen as the study subject to examine the effects of treatment with sodium selenite (Na2SeO3) on the physiology and transcriptome alterations of cadmium stress. Purple flowering stalk leaves treated with exogenous selenium had higher glutathione content, photosynthetic capacity, and antioxidant enzyme activities compared to the leaves treated with Cd stress alone. Conversely, the contents of proline, soluble proteins, soluble sugars, malondialdehyde, and intercellular CO2 concentration tended to decrease. Transcriptome analysis revealed that 2643 differentially expressed genes (DEGs) were implicated in the response of exogenous selenium treatment to Cd stress. The metabolic pathways associated with flavonoid production, carotenoid synthesis, glutathione metabolism, and glucosinolate biosynthesis were among those enriched in these differentially expressed genes. Furthermore, we discovered DEGs connected to the production route of glucosinolates. This work sheds fresh light on how purple flowering stalks' tolerance to cadmium stress is improved by exogenous selenium.

Nonenhanced Chemical Exchange Saturation Transfer Cardiac Magnetic Resonance Imaging in Patients With Amyloid Light-Chain Amyloidosis.

BACKGROUND: Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. PURPOSE: To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. STUDY TYPE: Prospective. POPULATION: Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. ASSESSMENT: The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. STATISTICAL TESTS: Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P < 0.05. RESULTS: Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). DATA CONCLUSIONS: This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Disease activity in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: the utility of the SPARCC MRI scoring system for assessment of axial spine involvement.

OBJECTIVES: The aim of this study is to investigate the relationship between spinal MRI findings with disease activity and other clinical and serological parameters, and to determine the importance of MRI scoring system in evaluating disease activity of SAPHO syndrome. METHODS: Thirty patients with SAPHO syndrome underwent clinical, laboratory and MRI evaluation at baseline, 3 months, 6 months and 1 year. Magnetic resonance images were analysed using modified Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Correlations between MRI score and clinical and laboratory parameters were analysed using Spearman's rank correlation test. RESULTS: Persistent improvement was observed after 12 months in terms of total modified SPARCC scores (37(12,59) vs. 23(5,45) at baseline and 12 months, p<0.05). Total modified SPARCC scores showed Spearman correlations with hypersensitive C-reaction protein (hs-CRP), ankylosing spondylitis disease activity score (ASDAS) and bath ankylosing spondylitis metroloty index (BASMI) at baseline, 3 months, 6 months and 12 months (p varied from <0.001 to <0.05, and r varied from 0.418 to 0.601). Modified SPARCC scores of spine joint, as the largest contribution to the total scores with the mean score of 12(5,30) after 12 months vs. 26 (12,40) at baseline. CONCLUSIONS: The modified SPARCC score proposed in this study exhibits promising potential in the evaluation of extensive radiographic damage in SAPHO and the reflection the disease activity. Our study suggests that MRI could be used together with other parameters of disease activity in the assessment of symptomatic SAPHO patients with spine involvement.

Effect of biologics on radiographic progression of peripheral joint in patients with psoriatic arthritis: meta-analysis.

OBJECTIVES: To determine the efficacy of biologics in preventing radiographic progression in peripheral joints of PsA patients. METHODS: Studies were searched in MEDLINE, Web of Science, and abstracts from the last three EULAR and ACR meetings up to 31 December 2019. Primary and secondary endpoints were the proportion of patients without radiographic progression and the mean change in total radiographic score at week 24. RESULTS: Eleven studies, involving 5382 patients, 9 drugs and 18 treatments, were included. Patients receiving biologics were more likely to achieve radiographic non-progression compared with placebo [odds ratio: pooled: 2.40, 95% CI: 2.00, 2.87; TNF inhibitors (TNFi): 2.94, 95% CI: 2.38, 3.63; IL inhibitors (ILi): 2.15, 95% CI: 1.69, 2.74; abatacept: 1.54, 95% CI: 1.03, 2.28] and have significantly lower radiographic progression [standardized mean difference (SMD): pooled: -2.16, 95% CI: -2.91, -1.41; TNFi: -2.82, 95% CI: -4.31, -1.33; ILi: -1.60, 95% CI: -2.49, -0.72; abatacept: -0.40, 95% CI: -0.59, -0.21]. Concomitant MTX therapy was not superior to monotherapy (SMD: pooled: 0.01, 95% CI: -0.07, 0.08; biologics: 0.01, 95% CI: -0.09, 0.11; placebo: -0.01, 95% CI: -0.13, 0.12). The effect of ustekinumab and secukinumab on radiographic progression was not influenced by prior anti-TNF therapy (SMD: -0.08, 95% CI: -0.25, 0.10). CONCLUSION: Biologic agents may retard radiographic progression in PsA patients in terms of bone erosion and joint space narrowing compared with placebo. MTX seems to have no added effect. Prior anti-TNF therapy seems to not influence the radiographic efficacy of IL blockers.

Serum IgG4 elevation in SAPHO syndrome: does it unmask a disease activity marker?

OBJECTIVES: SAPHO syndrome is a rare inflammatory disorder with multiple phenotypes, including synovitis, acne, pustulosis, hyperostosis, and osteitis. IgG4 is a subclass of immunoglobulin G, and the elevation of IgG4 has been found in different autoimmune diseases. In the present study, we explored the clinical significance of serum IgG4 levels in patients with SAPHO syndrome. METHODS: Fifty-two patients who met the classification criteria of SAPHO syndrome were included in this study. Clinical data and disease activity markers were collected including erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), pain visual analogue scale (VAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Serum immunoglobin (IgA, IgM, and IgG) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) levels were determined using the immunonephelometric assay. RESULTS: Raised serum IgG4 levels (>1400 mg/dL) were detected in 23% (12/52) of patients. Patients with elevated sIgG4 levels had significantly higher pain VAS (5.42±2.76 vs. 3.08±1.78, p=0.02), BASMI (1.80±1.64 vs. 0.38±0.94, p=0.03) and ASDAS (3.20±0.65 vs. 1.74±0.58, p<0.001) levels compared with patients with normal sIgG4 levels. This difference was also observed for ESR (38.2 vs. 22.2 mm/h, p=0.01) and serum CRP (21.0 vs. 2.2 mg/L, p=0.04) levels, which also positively correlated with sIgG4 levels. We also included 4 patients whose IgG4 levels decreased and correlated with the decrease in hsCRP and ESR levels after treatment. CONCLUSIONS: Elevated sIgG4 levels are common in patients with SAPHO syndrome and are associated with high disease activity. Further investigations are needed for this phenomenon.

Three patterns of osteoarticular involvement in SAPHO syndrome: a cluster analysis based on whole body bone scintigraphy of 157 patients.

OBJECTIVES: To explore the patterns of osteoarticular involvement in SAPHO syndrome. METHODS: Baseline clinical characteristics and imaging data of 99mTc-MDP whole-body bone scintigraphy (WBBS) were collected from 157 out of 164 patients diagnosed with SAPHO syndrome. The twelve most frequently involved osteoarticular sites were analysed by hierarchical cluster analysis with the Ward minimum-variance method. RESULTS: Three distinctive patterns of osteoarticular involvement were identified: the spinal type (70 patients, 44.6%), with predominantly thoracic, lumbar or sacral vertebral lesions; the costal type (52 patients, 33.1%), with lesions of anterior ribs, particularly the first ribs; and the sternoclavicular type (35 patients, 22.3%), with predominantly sternal and bilateral sternoclavicular lesions, characterized by the typical bullhead sign. Notably, a total of 77 (49%) patients exhibited lesions of ribs on WBBS, of which 61.3% involved the first ribs. Interestingly, patients of spinal type were older at onset of cutaneous manifestations than those of sternoclavicular type (P = 0.036) and costal type (P = 0.035). The disease course was remarkably longer in sternoclavicular type than costal type (P = 0.001) and spinal type (P < 0.001). CONCLUSION: The osteoarticular involvement in SAPHO syndrome can be categorized as three distinct patterns with different corresponding clinical features. The costal involvement in SAPHO syndrome, which was under-recognized previously, may define a distinct sub-type of the disease.

Efficacy of bisphosphonates in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a prospective open study.

OBJECTIVES: To evaluate the clinical efficacy of bisphosphonates treatment for spinal bone marrow oedema (BME) in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: SAPHO syndrome patients presenting to Peking Union Medical College Hospital from 2015 to 2016 were recruited. Patients were administered pamidronate disodium 1 mg/kg/d intravenously, for 3 days, at baseline and 3 months later. The symptoms were evaluated using the Visual Analog Score (VAS) for pain, and other clinical measures including, spinal BME scores, ß-crosslaps, osteocalcin, and inflammatory factors, were collected. RESULTS: A total of 30 patients (20 women and 10 men) with a median age of 47.2 (interquartile range 8.8) years were recruited. In a short time, the patients showed a significant decrease in VAS (before vs. after; first treatment: 5.70±1.62 vs. 2.30±1.29 cm, second treatment: 4.03±1.88 vs. 2.17±1.23 cm) and ß-crosslaps (first treatment: 0.4441±0.1923 vs. 0.0859±0.0374 pg/ml, second treatment: 0.2891±0.1983 vs. 0.0962±0.0324 pg/ml) (all p<0.05). At 12-month follow-up, compared with the baseline, we noticed a significant drop in the VAS (5.70±1.62 vs. 2.43±1.25 cm), erythrocyte sedimentation rate (28.87±25.26 vs. 18.00±18.65 mm/h), high-sensitivity C-reactive protein level (11.76±10.19 vs. 5.84±5.88 mg/L), osteocalcin (2.30±1.27 vs. 1.65±0.80 ng/ml), and BME (30.50±24.09 vs. 22.13±27.79) (all p<0.05). No one had serious adverse events. CONCLUSIONS: Bisphosphonates can significantly and rapidly relieve symptoms in patients with SAPHO syndrome and have a long-term effect on inflammation and spinal BME. We suggest that bisphosphonates could be used as the first-line therapeutic drug for SAPHO syndrome, especially in patients with spinal BME.

SAW Torque Sensor Gyroscopic Effect Compensation by Least Squares Support Vector Machine Algorithm Based on Chaos Estimation of Distributed Algorithm.

As this study examined the issue of surface acoustic wave (SAW) torque sensor which interfered in high rotational speed, the gyroscopic effect generated by rotation was analyzed. Firstly, the SAW coupled equations which contained torque and rotation loads were deduced, and the torque calculation error caused by rotation was solved. Following this, the hardware of the SAW gyroscopic effect testing platform and the turntable experiment were designed to verify the correctness of the theoretical calculation. Finally, according to the experimental data, the gyroscopic effect was compensated by multivariate polynomial fitting (MPF), Gaussian processes regression (GPR), and least squares support vector machine algorithms (LSSVM). The comparison results showed that the LSSVM has the obvious advantage. For improving the function of LSSVM model, chaos estimation of distributed algorithm (CEDA) was proposed to optimize the super parameters of the LSSVM, and numerical simulation results showed that: (1) CEDA is superior to traditional estimation of distributed algorithms in convergence speed and anti-premature ability; (2) the performance of CEDA-LSSVM is better than genetic algorithms (GA)-LSSVM and particle swarm optimization (PSO)-LSSVM. After compensating by CEDA-LSSVM, the magnitude of the torque calculation relative error was 10-4 in any direction. This method has a significant effect on reducing gyroscopic interference, and it lays a foundation for the engineering application of SAW torque sensor.

When to Introduce Three-Dimensional Visualization Technology into Surgical Residency: A Randomized Controlled Trial.

Three-dimensional (3D) reconstructed images have been increasingly applied for medical education. Although many studies have described the benefits of such applications, the best time to introduce 3D technology into surgical training has not been determined. Therefore, we conducted a randomized study to determine a suitable period for the introduction of this technology. Seventy-one surgical residents were randomized into 2 groups (two-dimensional computed tomography (CT) group and 3D image group), and they completed a test on anatomy and imaging as well as a questionnaire. Post-graduate year 1 (PGY1) residents in the 3D group performed significantly better than those in the CT group, although the third-year residents did not present significant differences in either the score or the time spent answering the questions. Although residents in different years of training held different attitudes toward the difficulty of anatomy and imaging learning, they all showed a high level of acceptance of the 3D training. This study revealed that 3D images improved the junior residents' performance in imaging reasoning. Thus, systematically introducing 3D images early in a surgical resident training program may help produce a better anatomy-imaging-surgery system.

A Phosphine Oxide Functional Group Based [2]Rotaxane That Operates as a Multistable Molecular Shuttle.

A switchable [2]rotaxane based on a pyridinediamide crown ether macrocycle and a thread bearing phosphine oxide, urea, and dibenzylammonium functional groups was successfully developed and characterized by (1) H NMR and 2D NMR spectroscopy, mass spectrometry, and single-crystal analysis. The three recognition sites in the [2]rotaxane were sorted from strong to weak, according to their bonding abilities, so that the macrocycle could move along the thread from one side to the other in a directional way, operating as a multistable molecular shuttle.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome with mandibular involvement: Would surgical operation help?

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare autoinflammatory disease; its primary manifestation includes osteoarthropathy with skin involvement. Janus kinase (JAK) inhibitors, such as tofacitinib, were used for rheumatoid arthritis; however, due to its downregulation of immune cytokines including interleukin (IL)-6 and IL-8, it might be effective for SAPHO patients. CASE SUMMARY: We report the 1st case of mandibular-related SAPHO syndrome treated with tofacitinib. The patient underwent mandibular resection surgery twice and postoperative pathology showed "osteomyelitis". The patient developed sclerosing osteomyelitis in the left wrist 9 months after surgery and SAPHO syndrome was diagnosed. The patient was administered nonsteroidal anti-inflammatory drugs and corticosteroids therapy without much remission. A 3-month tofacitinib therapy provided remission from both systemic inflammation status and peripheral osteoarticular symptoms and no significant recurrence was observed during follow-up in this case. CONCLUSION: Mandibular involvement in SAPHO syndrome is easily misdiagnosed due to its rarity. Mandibular resection surgery should be applied carefully; after systemic treatment with tofacitinib, the patient had remission. We provide a successful experience for the treatment of mandibular-related SAPHO syndrome.