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Aims Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance. Methods and results We used untargeted metabolomics and mass spectrometry to determine plasma succinate concentrations in 40 and 1665 individuals of the discovery and validation cohorts, respectively. Three different murine AAD models were used to determine the role of succinate in AAD development. We further examined the role of oxoglutarate dehydrogenase (OGDH) and its transcription factor cyclic adenosine monophosphate-responsive element-binding protein 1 (CREB) in the context of macrophage-mediated inflammation and established p38αMKO Apoe –/– mice. Succinate was the most upregulated metabolite in the discovery cohort; this was confirmed in the validation cohort. Plasma succinate concentrations were higher in patients with AAD compared with those in healthy controls, patients with acute myocardial infarction (AMI), and patients with pulmonary embolism (PE). Moreover, succinate administration aggravated angiotensin II-induced AAD and vascular inflammation in mice. In contrast, knockdown of OGDH reduced the expression of inflammatory factors in macrophages. The conditional deletion of p38α decreased CREB phosphorylation, OGDH expression, and succinate concentrations. Conditional deletion of p38α in macrophages reduced angiotensin II-induced AAD. Conclusion Plasma succinate concentrations allow to distinguish patients with AAD from both healthy controls and patients with AMI or PE. Succinate concentrations are regulated by the p38α–CREB–OGDH axis in macrophages.

Studies have reported on the regulation of clonal growth in Chinese sea buckthorn in response to environmental resource availability, but these studies have been limited to external mechanisms. In this report, we controlled irrigation to generate a soil moisture gradient in order to examine the photosynthetic physiological mechanisms regulating clonal growth in this species. The results indicated that as irrigation intensity increased, the soil water content increased vertically and tissue water content first increased and then decreased. Furthermore, Rubisco activase (RCA) and Mg-chelatase H subunit (CHLH) gene expression levels, photosynthetic capacity (net photosynthetic rate, transpiration rate, chlorophyll content, and stomatal conductance), and clonal growth (ramet growth, clonal proliferation, clonal propagation) all showed a quadratic parabolic change (i.e., first increasing and then decreasing). In addition, gene expression levels and tissue water content, photosynthetic capacity and gene expression levels, and clonal growth and photosynthetic capacity were all significantly positively correlated. When irrigation intensity (soil water content) is exceedingly low or high, the tissue water content is also low, RCA and CHLH gene expression levels are low, photosynthetic capacity is weak, clonal growth ability is inhibited, and clonal growth layout tends toward the “guerrilla type.” This type manifests as fewer and smaller clonal daughter ramets that are sparsely distributed with reduced clonal organ extension ability and branching intensity. When irrigation intensity (soil water content) is moderate, the tissue water content, gene expression levels, and photosynthetic capacity is high, clonal growth ability is completely uninhibited, and the clonal growth layout tends toward the “aggregated type.” This type is associated with numerous large clonal daughter ramets that are densely distributed with high clonal organ extension ability and branching intensity. Therefore, as irrigation intensity continuously changes from inordinately low to moderate to exceedingly high, Chinese sea buckthorn regulates clonal growth by photosynthetic capacity through photosynthetic gene expression. This results in a clonal growth layout continuum of “guerrilla-aggregated-guerrilla” that depends on irrigation intensity.

Functional mitral regurgitation (MR) in the setting of heart failure results from progressive dilatation of the left ventricle (LV) and mitral annulus. This leads to leaflet tethering with posterior displacement. Contrary to common assumptions, MR often does not resolve with LVAD decompression of the LV alone. The negative impact of significant (moderate-severe) mitral regurgitation in the LVAD setting is becoming better recognized in terms of its harmful effect on right heart function, pulmonary vascular resistance and hospital readmissions. However, controversies remain regarding the threshold for intervention and management. At present, there are no consensus indications for the repair of significant mitral regurgitation at the time of LVAD implantation due to the conflicting data regarding potential adverse effects of MR on clinical outcomes. In this review, we summarize the current understanding of MR pathophysiology in patients supported with LVAD and potential future management strategies.

Women with advanced heart failure receive advanced surgical therapies such as durable left ventricular assist device (LVAD) implantation or heart transplantation at a rate much lower compared to males. Reasons for this discrepancy remain largely unknown. Much of what is understood reflects outcomes of those patients who ultimately receive device implant or heart transplantation. Females have been shown to have a higher mortality following LVAD implantation and experience higher rates of bleeding and clotting phenomena and right ventricular failure. Beyond outcomes, the literature is limited in the identification of pre-operative factors that drive lower than expected LVAD implant rates in this population. More focused research is needed to define the disparities in advance heart failure therapy delivery in women and other underserved populations.

OBJECTIVE: To explore the normal distribution of cervical sagittal alignment and the relationship between cervical alignment and global spine balance in asymptomatic young adults. METHODS: A cohort of 272 asymptomatic Chinese adults (including 161 males and 111 females, with an average age of (23.2±4.4) years, ranging from 18 to 45 years) were prospectively recruited from November 2011 to December 2014. The C(0)-C(2) angle, disk angles from C(2)-C(3) to C(6)-C(7), vertebral angles from C(3) to C(7), T(1) slope, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), C(2)-C(7) sagittal vertical axis (C(2)-C(7)SVA), center of gravity of head to C(7)SVA (CGH-C(7)SVA), C(7)-S(1)SVA were measured and statistically analyzed. All the subjects were categorized with the Roussouly classification and the cervical morphologies were evaluated as lordotic, straight, sigmoid or kyphotic. Spinal sagittal alignment parameters were compared between different sexes and Roussouly classifications with independent student t test, analysis of variance (ANOVA) or Chi-square test. Correlations between cervical sagittal alignment and global spine sagittal alignment were calculated using the Pearson and Spearman correlation coefficient. Linear regression analysis was performed. RESULTS: Sixty-seven males and 59 females aged from 18 to 30 years old were included in the study. The mean value of C(0)-C(7) was 26.0°±12.8°, composed of 15.2°±6.7° for C(0)-C(2), 9.1°±12.1° for sum of disk angles from C(2)-C(3) to C(6)-C(7), and 1.4°±10.2° for sum of vertebral angles from C(3) to C(7). C(2)-C(7)SVA [(18.6±7.9) mm] and CGH-C(7)SVA [(22.9±12.3) mm]were offset ideally by C(7)-S(1)SVA [(-21.6±31.0) mm]. Males had a larger T(1) slope (P < 0.05) and accordingly, a larger cervical lordosis C(2)-C(7) (P < 0.01) and C(0)-C(7) angle (P < 0.01) than females. Males had a smaller C(7)-S(1)SVA (P < 0.01) and accordingly, a smaller CGH-C(7)SVA (P=0.165) than females. Significant difference was found between cervical alignment of different Roussouly types (P < 0.01). In general, a larger LL was consistent with a set of larger TK, C(2)-C(7)angle, C(0)-C(7) angle, and vice versa. There was no significant correlation between cervical morphology and the Roussouly classification (Chi-square=10.548, P=0.308). There was significant correlation between cervical alignment and T(1) slope (P < 0.01), TK (P < 0.01). There was significant correlation between adjacent segmental angles from T(1) slope up to C(0)-C(2) angle (P < 0.05). CONCLUSION: Normative values of each vertebral angle and disk angle were established. The cervical lordosis occurred mainly at C(0)-C(2) and disk levels, which was influenced by parameters of other parts of the spine, such as T(1) slope, TK and the Roussouly classification. There was significant correlation between adjacent disk angles.

To meet the requirement from the economy and society, China's emergency rescue has been developing towards specialization and professionalization. The working environment for emergency responders is special accompanying with tremendous challenges and uncertainties. To promote the research on occupational health and personal protection is an important guarantee for the workers in China to realize the goal of "decent work". This paper reviews the hazards that affect the occupational health of emergency rescue workers, the research progress of adverse outcomes caused from exposure to these hazards, and the related development issues of personal protection. In order to ensure the safety and health of emergency rescue workers, the direction of further research on occupational health of emergency rescue workers is put forward.随着社会与经济的发展，我国应急救援已经进入专业化与职业化的发展阶段。应急救援工作环境特殊，推进相关人员职业健康与个体防护研究是落实劳动者实现"体面劳动"的重要保障。本文综述了影响应急救援人员职业健康的危害因素以及可能导致的健康影响，对个体防护现状与存在的问题进行了总结，并提出了未来应急救援人员职业健康研究方向的建议。.

Selective oxidation of benzylic C−H compounds to ketones is important for the production of a wide range of fine chemicals, and is often achieved using toxic or precious metal catalysts. Herein, we report the efficient oxidation of benzylic C−H groups in a broad range of substrates under mild conditions over a robust metal–organic framework material, MFM‐170, incorporating redox‐active [Cu2 II(O2CR)4] paddlewheel nodes. A comprehensive investigation employing electron paramagnetic resonance (EPR) spectroscopy and synchrotron X‐ray diffraction has identified the critical role of the paddlewheel moiety in activating the oxidant tBuOOH (tert‐butyl hydroperoxide) via partial reduction to [CuIICuI(O2CR)4] species., The oxidation of benzylic C−H groups in a broad range of substrates under mild conditions has been achieved using a robust metal–organic framework, MFM‐170, incorporating redox‐active [Cu2 II(O2CR)4] paddlewheel nodes. EPR spectroscopy and synchrotron X‐ray diffraction have identified the critical role of the paddlewheel moiety in activating the oxidant tBuOOH (tert‐butyl hydroperoxide) via partial reduction to [CuIICuI(O2CR)4] species.

Failure to rescue (FTR), defined as death after a complication, is recognized as a principal driver of variation in mortality among hospitals. We evaluated FTR as a quality metric in patients who received durable left ventricular assist devices (LVADs) using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support.Data on 13,617 patients who received primary durable LVADs from April 2012 to October 2017 at 131 hospitals that performed at least 20 implants were analyzed from the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. Rates of major complications and FTR were compared across risk-adjusted in-hospital mortality terciles (low, medium, high) and hospital volume. Logistic regression was used to estimate expected FTR rates on the basis of patient factors for each major complication.The overall unadjusted in-hospital mortality rate was 6.96%. Risk-adjusted in-hospital mortality rates varied 3.1-fold across terciles (low, 3.3%; high, 10.3%; P trend.001). Rates of major complications varied 1.1-fold (low, 34.0%; high, 38.8%; P .0001). Among patients with a major complication, 854 died in-hospital for an FTR rate of 17.7%, with 2.8-fold variation across mortality terciles (low, 8.5%; high, 23.9%; P .0001). FTR rates were highest for renal dysfunction requiring dialysis (45.3%) and stroke (36.5%). Higher average annual LVAD volume was associated with higher rates of major complications (10 per year, 26.7%; 10-20 per year, 34.0%; 20-30 per year, 34.0%;30 per year, 40.1%; P trend.0001) whereas hospitals implanting10 per year had the highest FTR rate (10 per year, 23.5%; 10-20 per year, 16.5%; 20-30 per year, 17.0%;30 per year, 17.9%; P = .03).FTR might serve as an important quality metric for durable LVAD implant procedures, and identifying strategies for successful rescue after complications might reduce hospital variations in mortality.

Background As public health personnel and resources are redirected to COVID-19, sexually transmitted diseases (STD) programs have been unable to sustain pre-COVID-19 activities. Methods We used California (CA) surveillance data to describe trends in case reporting for gonorrhea, chlamydia, and syphilis of any stage in the pre- versus post-COVID-19 eras (January-June 2019 and January-June 2020). We also analyzed data from an electronic survey administered by the CA STD Control Branch to local health jurisdictions in April, June, and September of 2020, assessing the impact of COVID-19 on STD programs. Results There were sharp declines in cases of all reportable bacterial STDs occurring in conjunction with the March 19, 2020 CA stay-at-home order, most of which did not return to baseline by July. Comparing January-June 2020 to January-June of 2019, there were decreases in reported cases of chlamydia (31%), late syphilis (19%), primary/secondary syphilis (15%), early nonprimary nonsecondary syphilis (14%), and gonorrhea (13%). The largest percentage declines in STD case reporting were among Hispanic, Asian/Pacific Islander, and Black persons. Seventy-eight percent of local health jurisdiction respondents indicated that half or more of their workforce had been redeployed to COVID-19 by September 2020. Conclusions During the COVID-19 era, STD case reporting and programmatic functions have diminished throughout CA. Because this may contribute to decreases or delays in STD diagnosis and treatment-with resultant increases in STD transmission-providers and public health officials should prepare for potential increases in STD-related morbidity in the months and years to come.

Working from home has become a mainstream work practice in many organizations during the COVID-19 pandemic. While remote work has received much scholarly and public attention over the years, we still know little about how people with disabilities engage in remote work from their homes and what access means in this context. To understand and rethink accessibility in remote work, the present paper studies work-from-home practices of neurodivergent professionals who have Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, learning disabilities (e.g., dyslexia) and psychosocial disabilities (e.g., anxiety, depression). We report on interviews with 36 US-based neurodivergent professionals who have been working from home during the pandemic. Our findings reveal that while working from home, neurodivergent professionals create accessible physical and digital workspaces, negotiate accessible communication practices, and reconcile tensions between productivity and wellbeing. Our analysis reconsiders what access means in remote work for neurodivergent professionals and offers practical insights for inclusive work practices and accessibility improvements in remote collaboration tools.

Author(s): Chen, Yongtai; Tang, William C; Chu, Jinkui; Zhang, Ran; Li, Song | Abstract: An accurate sky polarization field map is a prerequisite for polarization navigation applications. In this article, a detector for sky full-polarization imaging detection is described, the major error-influencing factors (MEIFS ) are obtained, and the error propagation is modeled and analyzed. We reveal the relationship between the error of the inversed Stokes vector and the condition number of the detector matrix, which shows that the error of the inversed Stokes vector is affected by the Stokes vector of the incident light itself and the MEIFS together, with the MEIFS playing a decisive role. With the MEIFS optimized, the impact of detector error on the inversed Stokes vector is attenuated. A control equation for system calibration is also deduced which can establish the connection between the detector matrix design and calibration process. The work in this article provides a reference for optimization and calibration of sky full-polarization imaging detectors.

Women with a history of ductal carcinoma in situ (DCIS) have an elevated risk of a subsequent invasive breast cancer, but there are few established potentially modifiable factors known to lower this risk. Bisphosphonates are a commonly used treatment for patients with osteoporosis and have been shown to lower risks of recurrence and mortality in patients with invasive breast cancer; however, their use has not previously been investigated within the context of DCIS. Utilizing a population-based nested case–control design, we compared 301 cases of women diagnosed with DCIS and a subsequent breast cancer and 587 individually matched controls (on age, DCIS diagnosis year, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but never a subsequent breast cancer. Information on recency and duration of bisphosphonate use was ascertained from patient interviews and medical record reviews. Current users of bisphosphonates had a reduced risk of developing an invasive breast cancer compared with never users [OR = 0.50; 95% confidence interval (CI): 0.26–0.99]. Users of bisphosphonates for ≥48 months had a similar reduction in risk (OR = 0.45; 95% CI, 0.24–1.06). This is the first study to document that bisphosphonate use is associated with a lower risk of subsequent invasive breast cancer among women with a history of DCIS. This finding is consistent with the protective effect of bisphosphonates observed in other breast cancer settings. If validated by others, bisphosphonates may be an effective risk-reducing approach with the potential added benefits of its positive impacts on bone health and fracture risk. Significance: This study finds that bisphosphonate use among women with a history of DCIS is associated with lower risk of subsequent invasive breast cancer, providing a potential preventative approach for this high-risk population.

Purpose: Basal-like breast cancer (BLBC) is a particularly aggressive intrinsic molecular subtype of breast cancer that lacks targeted therapies. There is also no clinically useful test to risk stratify patients with BLBC. We hypothesized that a transcriptome-based phenotypic characterization of BLBC tumors and their microenvironments may overcome these challenges. Experimental Design: We conducted a retrospective correlative genomic sequencing study using a matched pairs design with validation in five independent cohorts. The study was conducted on a large population-based prospective cohort of the major molecular subtypes of breast cancer conducted in the greater Seattle-Puget Sound metropolitan area. Cases consisted of women 20–69 years of age first diagnosed with invasive breast cancer identified through the population-based Surveillance Epidemiology and End Results program. Patients for this analysis (n = 949) were identified from the 1,408 patients with stage I–III triple-negative breast cancer [estrogen receptor–negative (ER−), progesterone receptor–negative (PR−), HER2−]. Of the 949 women, 248 developed a recurrence after their initial diagnosis. A matched set of 67 recurrent and nonrecurrent BLBC tumors was subjected to transcriptome sequencing. Through RNA sequencing of the matched sets of recurrent and nonrecurrent BLBC tumors, we aimed to identify prognostic phenotypes. To identify nonredundant and uncorrelated prognostic genes, we used an ensemble of variable selection algorithms, which resulted in a ranking of genes on the basis of their expected utility in classification. Using leave-one-out cross-validation, we trained a random forest classifier on the basis of the top 21 genes (BRAVO-DX). Validations were performed in five independent triple-negative or BLBC cohorts, and biomarker robustness and transferability were demonstrated by employing real-time PCR. Results: We found that cancer cell intrinsic and immunologic phenotypes are independent predictors of recurrence. By simultaneously interrogating the tumor and its microenvironment, we developed a compound risk model that stratified patients into low-, medium-, and high-risk groups, with a 14%/56%/74% chance of recurrence, respectively. Biologically, the primary tumors of patients who developed a recurrence had increased growth factor signaling and stem-like features, while nonrecurrent tumors showed high lymphocyte infiltration with clonal expansion of T and B cells, as well as antitumor polarization of macrophages. We validated our model in five independent cohorts, including three large cohorts, where BRAVO-DX was highly informative in identifying patients with disease recurrence [HR, 6.79 (95% confidence interval (CI), 1.89–24.37); HR, 3.45 (95% CI, 2.41–4.93); and HR, 1.69 (95% CI, 1.17–2.46)]. A smaller gene set focused on the tumor immunophenotype, BRAVO-IMMUNE, was highly prognostic in all five cohorts. Conclusions: Together, these results indicate that phenotypic characteristics of BLBCs and their microenvironment are associated with recurrence-free survival and demonstrate the utility of intrinsic and extrinsic phenotypes as independent prognostic biomarkers in BLBC. Pending further evaluation and validation, our prognostic model has the potential to inform clinical decision-making for patients with BLBC as it identifies those at high risk of rapidly progressing on standard chemotherapy, as well as those who may benefit from alternative first-line therapies.

Previous multi-center imaging studies with 18F-FDG PET have established the presence of Parkinson's disease motor- and cognition-related metabolic patterns termed PDRP and PDCP in patients with this disorder. Given that in PD cerebral perfusion and glucose metabolism are typically coupled in the absence of medication, we determined whether subject expression of these disease networks can be quantified in early-phase images from dynamic 18F-FPCIT PET scans acquired to assess striatal dopamine transporter (DAT) binding. Methods: We studied a cohort of early-stage PD patients and age-matched healthy control subjects who underwent 18F-FPCIT at baseline; scans were repeated 4 years later in a smaller subset of patients. The early 18F-FPCIT frames, which reflect cerebral perfusion, were used to compute PDRP and PDCP expression (subject scores) in each subject, and compared to analogous measures computed based on 18F-FDG PET scan when additionally available. The late 18F-FPCIT frames were used to measure caudate and putamen DAT binding in the same individuals. Results: PDRP subject scores from early-phase 18F-FPCIT and 18F-FDG scans were elevated and striatal DAT binding reduced in PD versus healthy subjects. The PDRP scores from 18F-FPCIT correlated with clinical motor ratings, disease duration, and with corresponding measures from 18F-FDG PET. In addition to correlating with disease duration and analogous 18F-FDG PET values, PDCP scores correlated with DAT binding in the caudate/anterior putamen. PDRP and PDCP subject scores using either method rose over 4 years whereas striatal DAT binding declined over the same time period. Conclusion: Early-phase images obtained with 18F-FPCIT PET can provide an alternative to 18F-FDG PET for PD network quantification. This technique therefore allows PDRP/PDCP expression and caudate/putamen DAT binding to be evaluated with a single tracer in one scanning session.