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.

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.

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.

CCL26 in primary biliary cholangitis - Is it a novel disease mediator?

AIM: To verify the role of CX3C chemokine ligand 1 - CX3C chemokine receptor 1 (CX3CL1-CX3CR1) pathway in the pathogenesis of primary biliary cholangitis (PBC). To explore whether CCL26, a novel functional ligand to CX3CR1, participates in the immunological mechanism of PBC. METHODS: Fifty-nine PBC patients and 54 healthy controls were recruited. Enzyme-linked immunosorbent assay and flow cytometry were used to measure CX3CL1 and CCL26 concentrations in plasma and CX3CR1 expression on peripheral lymphocytes, respectively. Chemotactic effects of CX3CL1 and CCL26 toward lymphocytes were detected by Transwell cell migration assays. CX3CL1 and CCL26 expressions in liver were assessed by immunohistochemical staining. Effects of CX3CL1 and CCL26 on stimulating cytokine production from lymphocytes were evaluated using intracellular flow cytometry. RESULTS: Significantly elevated CX3CL1 and CCL26 plasma concentration and CX3CR1 expression on CD4+ and CD8+ T cells were noted in PBC patients. CX3CL1 exhibited chemotactic activity toward CD8+ T, natural killer (NK) and NKT cells in a dose-dependent manner while such chemotactic effects were not detected for CCL26. In PBC patients, CX3CL1 and CCL26 were both increasingly expressed in biliary tracts and a concentration gradient of CCL26 in hepatocytes around portal areas was observed. Immobilized CX3CL1 could enhance interferon-γ production from T and NK cells while such effect was not exhibited by soluble CX3CL1 or CCL26. CONCLUSIONS: CCL26 expression is significantly elevated in plasma and biliary duct of PBC patients, yet does not appear to attract CX3CR1-expressing immune cells. CX3CL1-CX3CR1 pathway promotes the infiltration of T, NK and NKT cells into bile ducts and forms a positive feedback loop with T-helper 1 type cytokines in PBC.

Global competence of medical students: An assessment scale and preliminary investigation in China.

INTRODUCTION: The importance of global competence has been acknowledged in medical care as well as medical education. This study aims to develop a scale assessing the global competence of medical students, determine the factor structure and internal consistency of the scale and explore the underlying factors influencing the global competence of Chinese medical students in 8-year programs. METHODS: A questionnaire (Global Competence Assessment Scale for Medical Students, MS-GCAS) was developed, and a cross-sectional multicenter survey was conducted in 1062 medical students from 10 medical schools in China. Questionnaire data were analyzed using exploratory factor analysis and multiple linear regression. RESULTS: The exploratory factor analysis revealed a three-factor scale. The MS-GCAS has good internal consistency (Cronbach's alpha = 0.79 to 0.87). In the multivariate regression analyses, medical education stage (p<0.05), the frequency of communicating with foreigners (p<0.001), multilingual ability (p<0.05) and grade level (p<0.05) are associated with the MS-GCAS scores. DISCUSSION: The MS-GCAS has the potential to serve as a tool to measure the global competence of medical students. This three-factor scale can be used by medical education researches to improve future versions. Medical schools should conduct further educational reforms to promote students' global competence.

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.

Tumor necrosis factor inhibitors for pediatric patients with SAPHO syndrome associated with acne conglobata.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.

The Relative Contribution of Climatic, Demographic Factors, Disease Control Measures and Spatiotemporal Heterogeneity to Variation of Global COVID-19 Transmission.

Despite a substantial number of COVID-19 related research papers published, it remains unclear as to which factors are associated with the observed variation in global transmission and what are their relative levels of importance. This study applies a rigorous statistical framework to provide robust estimations of the factor effects for a global and integrated perspective on this issue. We developed a mixed effect model exploring the relative importance of potential factors driving COVID-19 transmission while incorporating spatial and temporal heterogeneity of spread. We use an integrated data set for 87 countries across six continents for model specification and fitting. The best model accounts for 70.4% of the variance in the data analyzed: 10 fixed effect factors explain 20.5% of the variance, random temporal and spatial effects account for 50% of the variance. The fixed effect factors are classified into climatic, demographic and disease control groups. The explained variance in global transmission by the three groups are 0.6%, 1.1%, and 4.4% respectively. The high proportion of variance accounted for by random effects indicated striking differences in temporal transmission trajectories and effects of population mobility among the countries. In particular, the country-specific mobility-transmission relationship turns out to be the most important factor in explaining the observed global variation of transmission in the early phase of COVID-19 pandemic.

Correction: Cooperative C-H activation of pyridine by PBP complexes of Rh and Ir can lead to bridging 2-pyridyls with different connectivity to the B-M unit.

[This corrects the article DOI: 10.1039/D1SC01850G.].

Spatial evolution patterns of public panic on Chinese social networks amidst the COVID-19 pandemic.

Novel coronavirus pneumonia has had a significant impact on people's lives and psychological health. We developed a stage model to analyse the spatial and temporal distribution of public panic during the two waves of the coronavirus disease 2019 (COVID-19) pandemic. We used tweets with geographic location data from the popular hashtag 'Lockdown Diary' recorded from 23 January to April 8, 2020, and 'Nanjing Outbreak' recorded from 21 July to 1 September 2021 on Weibo. Combining the lexicon-based sentiment analysis and the grounded theory approach, this panic model could explain people's panic and behavioural responses in different areas at different stages of the pandemic. Next, we used the latent Dirichlet allocation topic model to reconfirm the panic model. The results showed that public sentiments fluctuated strongly in the early stages; in this case, panic and prayers were the dominant sentiments. In terms of spatial distribution, public panic showed hierarchical and neighbourhood diffusion, with highly assertive expressions of sentiment at the outbreak sites, economically developed areas, and areas surrounding the outbreak. Most importantly, we considered that public panic was affected by the 17 specific topics extracted based on the perceived and actual distance of the pandemic, thus stimulating the process of panic from minimal, acute, and mild panic to perceived rationality. Consequently, the public's behavioural responses shifted from delayed, negative, and positive, to rational behavioural responses. This study presents a novel approach to explore public panic from both a time and space perspective and provides some suggestions in response to future pandemics.

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.

Cooperative C-H activation of pyridine by PBP complexes of Rh and Ir can lead to bridging 2-pyridyls with different connectivity to the B-M unit.

Pyridine and quinoline undergo selective C-H activation in the 2-position with Rh and Ir complexes of a boryl/bis(phosphine) PBP pincer ligand, resulting in a 2-pyridyl bridging the transition metal and the boron center. Examination of this reactivity with Rh and Ir complexes carrying different non-pincer ligands on the transition metal led to the realization of the possible isomerism derived from the 2-pyridyl fragment connecting either via B-N/C-M bonds or via B-C/N-M bonds. This M-C/M-N isomerism was systematically examined for four structural types. Each of these types has a defined set of ligands on Rh/Ir besides 2-pyridyl and PBP. A pair of M-C/M-N isomers for each type was computationally examined for Rh and for Ir, totaling 16 compounds. Several of these compounds were isolated or observed in solution by experimental methods, in addition to a few 2-quinolyl variants. The DFT predictions concerning the thermodynamic preference within each M-C/M-N isomeric match the experimental findings very well. In two cases where DFT predicts <2 kcal mol-1 difference in free energy, both isomers were experimentally observed in solution. Analysis of the structural data, of the relevant Wiberg bond indices, and of the ETS-NOCV partitioning of the interaction of the 2-pyridyl fragment with the rest of the molecule points to the strength of the M-C(pyridyl) bond as the dominant parameter determining the relative M-C/M-N isomer favorability. This M-C bond is always stronger for the analogous Ir vs. Rh compounds, but the nature of the ligand trans to it has a significant influence, as well. DFT calculations were used to evaluate the mechanism of isomerization for one of the molecule types.

Social Distancing in Tourism Destination Management during the COVID-19 Pandemic in China: A Moderated Mediation Model.

While protective measures in response to infectious diseases may reduce the freedom of tourists (regarding their behaviors), few studies have documented the effects of destination protective measures on the self-protective behaviors of tourists. By applying the protection motivation theory, this study examines the effects of perceived destination protective supports on the social distancing intentions of tourists during the COVID-19 pandemic. The results reveal significant relationships among perceived destination support, coping appraisal, threat appraisal, and the social distancing intentions of tourists. Moreover, two cognitive appraisals-toward the pandemic-partially mediate the relationship between perceived destination support and social distancing intention, and this mediational process is 'intervened' with by social norms. This has implications on whether tourist destinations apply more rigorous social distancing polices during the COVID-19 pandemic, to enhance the coping confidence behaviors of tourists, without causing anxiety and fear, and to achieve the goal of enhancing tourists' intentions to protect themselves.

Tonsillitis as a possible predisposition to synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome.

AIM: To present the prevalence of tonsillitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) patients, to compare the clinical characteristics and disease activities between SAPHO patients with and without tonsillitis and to preliminarily explore the efficacy of tonsillectomy in SAPHO syndrome. METHOD: A total of 58 SAPHO patients were included. Clinical data were collected, including demographic characteristics and acute phase reactants (erythrocyte sedimentation rate, high-sensitivity C-reactive protein). The visual analog scale (VAS), Palmoplantar Pustule Psoriasis Area Severity Index (PPPASI) and Nail Psoriasis Severity Index (NAPSI) were used to measure the severity of bone pain, skin lesions and nail lesions, respectively. Patients were referred to the otolaryngology department for tonsil examinations, including tonsil hypertrophy (grade ≥ 2), chronic congestion, inflammatory secretion and tonsil stones. The patients who underwent tonsillectomy were followed up after the surgery. RESULTS: A total of 67.2% of patients had tonsillitis. Patients with tonsillitis had markedly higher PPPASI (1.2 [0, 7.4] vs. 7.6 [1.75, 15.5], P = .018) and NAPSI (0 [0, 21] vs. 8 [3, 28], P = .032) scores. After tonsillectomy, the patients experienced significantly improved bone pain (VAS, 5 [4, 7] vs. 3 [1, 4], P = .034) and skin lesions (PPPASI, 16.2 [7.05, 18.35] vs 1.8 [0.7, 3.7], P = .028). CONCLUSION: Approximately 2/3 of SAPHO patients had tonsillitis. Patients with tonsillitis had more severe skin and nail lesions. Tonsillectomy might be associated with improved bone and skin symptoms in SAPHO patients. Future prospective controlled studies are warranted.

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.