Newly Diagnosed Mental Health Disorders in Patients With Breast Cancer Receiving Radiation Therapy.

PURPOSE: Patients with a mental health disorder (MHD) have higher age-adjusted mortality compared with the general population. Few reports investigate factors contributing to MHD among patients with breast cancer receiving radiation therapy. We report the incidence of acquired MHD after the diagnosis of breast cancer and treatment with radiation therapy. METHODS AND MATERIALS: Using a single institution, prospectively maintained database, we analyzed patients with breast cancer treated with radiation therapy between 2012 and 2017. We cross-referenced these patients with newly acquired International Classification of Diseases, Tenth Revision (ICD-10) MHD codes (F01-F99) within 3 years postbreast cancer diagnosis. The study included baseline National Comprehensive Cancer Network® (NCCN) distress tool scores and area deprivation index (ADI). Univariate and multivariable (MVA) Cox regression analyses were conducted to evaluate factors affecting new MHD onset. RESULTS: Of the 967 included patients, 318 (33%) developed an MHD after their breast cancer diagnosis, which was predominately anxiety (45.1%) and depression (20.1%) related, with a median (IQR) time to diagnosis of 30 (24-33) months. Univariate analysis showed lymph node-positive disease, receipt of chemotherapy, receipt of a mastectomy, high comorbidity index, divorced status, retired status, and fourth-quartile ADI as significant predictors. On MVA, only receipt of chemotherapy (hazard ratio [HR], 1.70; P = .014) and divorced status (HR, 2.04; P = .009) remained significant. Fourth-quartile ADI, retired status, and high comorbidity index showed trends toward significance (HR, 1.78, P = .065; HR, 1.46, P = .094; HR, 1.41, P = .059, respectively). On MVA examining the effects of the radiation therapy type on MHD, whole breast with regional nodal irradiation (HR, 2.31, P = .015) and postmastectomy radiation therapy (HR, 1.88, P = .024) were both strong predictors of MHD development. Additionally, an NCCN distress tool score of >3 was also predictive of MHD onset. CONCLUSIONS: In this cohort, 1 in 3 patients with localized breast cancer developed a new MHD, predominantly related to anxiety and depression. MHD risk was higher among divorced patients, those receiving chemotherapy, and patients receiving postmastectomy radiation therapy or whole breast with regional nodal irradiation. These findings highlight the importance of future studies and targeted interventions to support this vulnerable population.

Theoretical investigation of the magnetic and optical properties in a transition metal-doped GaTeCl monolayer.

We investigate the structural, magnetic, electronic and optical properties of a transition metal-doped GaTeCl monolayer, denoted as M@GaTeCl (M = V, Cr, Mn, Fe and Co), by using first-principles calculations. It is found that the magnetic ground state can be regulated by different M elements. In the meantime, the electronic structure is different with the doping of different M metal atoms, and thus the optical absorption changes correspondingly. The electronic calculations of M@GaTeCl suggest that V@GaTeCl, Cr@GaTeCl, Mn@GaTeCl and Fe@GaTeCl are semiconductors and the magnetic ground states are G-type antiferromagnetic (AFM), C-type AFM, A-type AFM and C-type AFM order, respectively, while Co@GaTeCl is a metal and the ground state is ferromagnetic (FM) order. The different magnetic ground states are discussed with the Heisenberg model. The rough estimation of the ferroelectric polarization value of M@GaTeCl suggests that M@GaTeCl still exhibits multiferroicity. The electronic structure is explained by the projected density of states, band structure and decomposed charge of the valence band maximum (VBM) and conduction band minimum (CBM). Simultaneously, the absorption coefficient calculations indicate that M@GaTeCl absorption shows anisotropic properties, as the same as in a pure GaTeCl monolayer, there exists enhanced visible light absorption in these M@GaTeCl monolayers relative to the pure GaTeCl one, which can be interpreted by the anisotropic structure and by the peculiar electronic structure. Thus, we found that the magnetic ground state, the electronic structure, and the absorption coefficient of M@GaTeCl can be tuned by doping different transition metal M atoms, and the ferroelectricity is still retained, which makes M@GaTeCl a potential multifunctional material in spintronics and optics.

Histone demethylases in the regulation of immunity and inflammation.

Pathogens or danger signals trigger the immune response. Moderate immune response activation removes pathogens and avoids excessive inflammation and tissue damage. Histone demethylases (KDMs) regulate gene expression and play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal expression of KDMs is closely associated with the pathogenesis of various inflammatory diseases such as liver fibrosis, lung injury, and autoimmune diseases. Despite becoming exciting targets for diagnosing and treating these diseases, the role of these enzymes in the regulation of immune and inflammatory response is still unclear. Here, we review the underlying mechanisms through which KDMs regulate immune-related pathways and inflammatory responses. In addition, we also discuss the future applications of KDMs inhibitors in immune and inflammatory diseases.

Development, validation, and use of a monitoring method for fipronil and its metabolites in chicken eggs by QuEChERS with online-SPE-LC-Q/Orbitrap analysis.

RATIONALE: The residues of fipronil and its metabolites in chicken eggs pose a threat to human health, so regular monitoring is necessary. However, the pretreatments of the existing detection methods are complex and time-consuming. A simple and streamlined pretreatment method is needed to improve the detection efficiency. METHOD: A rapid, efficient, and facile approach employing the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method with online solid-phase extraction liquid chromatography tandem Q Exactive Orbitrap high-resolution mass spectrometry (online-SPE-LC-HRMS) was established and evaluated for the determination of fipronil, fipronil-desulfinyl, fipronil-sulfone, and fipronil-sulfide in chicken eggs. An improved sample preparation technique combining QuEChERS and online-SPE was developed. Negative targeted ion fragmentation scanning and targeted-selected ion monitoring of HRMS were adopted to identify and quantify the target analytes. RESULTS: The proposed pretreatment method took a few steps in <13 min to achieve excellent recoveries and negligible interference. High selectivity was acquired with the adoption of Q/Orbitrap HRMS. The limit of quantification (LOQ) of the analytes was 2.5 µg kg-1 , meeting the detection requirements of the maximum residue level enacted by the Codex Alimentarius Commission, Japan, and the United States for the sum of fipronil and its metabolites. Extraction recoveries at three spiked concentration levels were within 84.56% to 93.84%, with relative standard deviation ≤5.87%. CONCLUSION: The established method is efficient and easy to operate and displays satisfactory LOQs, recoveries, accuracy, and precision. This approach serves as a reference method for monitoring eggs while providing potential solutions for fipronil determination in more complicated matrices.

Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants.

Objective: COVID-19 can rarely lead to severe illness in pediatric patients. The aim of this study was to determine if severe outcomes in pediatric COVID-19 have changed over the course of the pandemic. Methods: This was a multicenter, observational cohort analysis from a large regional healthcare system in metro Detroit using electronic health record data to evaluate emergency visits, hospitalization, and severe COVID-19 disease in pediatric patients. Consecutive pediatric patients presenting to the emergency department with a primary diagnosis of COVID-19 were included. Outcomes data was gathered from three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance (Time interval 1 (T1) 1/1/2021-6/30/2021: Alpha, T2 7/1/2021-12/31/2021: Delta, T3 1/1/2022-6/16/2022): Omicron. The primary outcome was severe disease inclusive of composite intensive care unit admission, mechanical ventilation, multisystem inflammatory syndrome in children (MIS-C), myocarditis, or death. Secondary outcomes included severe outcomes considering viral coinfection and vaccination status. Results: Between 1/1/2021 and 6/16/2022, there were 4517 emergency COVID-19 visits, of which 12.5% (566) of children were hospitalized. 24.4% (138), 31.6% (179), and 44.0% (249) of admissions occurred during T1, T2 and T3 respectively. Most patients were male (55.1%) and 59.9% identified as Caucasian. The median age was 5.0 (interquartile range 1.0, 13.0) with infants comprising 22.8% (129), toddlers 25.1% (142), children 23.0% (130), and teenagers 29.2% (165). Over the course of the pandemic, the proportion of infants in hospitalization increased from 16.7% in T1 to 19.6% in T2 to 28.5% in T3 (p < 0.01) while the proportion of teenagers in hospitalization decreased from 39.1% in T1 to 31.3% in T2 to 22.1% in T3 (p < 0.001). Oxygen therapy was required in a minority (29.9%) of cases with supplemental oxygen utilized the least in T3 (16.5%) and most in T2 (30.2%). Composite severe disease decreased throughout the pandemic occurring in 36.2% in T1, 27.4% in T2, and 18.9% in T3. A multivariable logistic regression analysis revealed the odds of composite severe disease was significantly lower in T3 compared to T1 (adjusted odds ratio [aOR] 0.35, 95% Confidence Interval 0.21-0.60, p < 0.001). Fully vaccinated or fully vaccinated and boosted admission rates remained low throughout all periods with 4.4% in T1, 4.5% in T2 and 8.4% in T3. Viral coinfection was most common during T2 (16.8%) followed by T3 (12.5%) and least common in T1 (5.1%) (p = 0.006). Coinfection occurred more commonly in younger children with a median age of 1.2 (0.0, 4.5) compared to those with mono-infection with a median age of 6 (1.0, 14.0) (p < 0.001). Severe outcomes occurred in 45.6% of coinfection cases compared to 22.1% without coinfection (p < 0.001). Conclusions: While Omicron cases had the highest admission frequency, severe illness was lower than Delta and Alpha variants. Coinfection with respiratory viruses increased the risk of severe outcomes and impacted infants more than older children. Funding: None.

An electronic medical record-based intervention to improve hepatitis A vaccination rates in the emergency department during a regional outbreak.

BACKGROUND: In response to the severe hepatitis A outbreak that occurred in Michigan between August 2016 and September 2019, our multihospital health system implemented an electronic medical record (EMR)-based vaccination intervention across its nine emergency departments (EDs). The objectives were to explore the impact of this intervention on increasing vaccination rates among high-risk individuals and to assess the barriers to use of a computerised vaccine reminder system. METHODS: All patients who were 18 years or older were screened using an electronic nursing questionnaire. If a patient was at high risk based on the questionnaire, an electronic best practice advisory (BPA) would trigger and give the physician or advanced practice provider the option to order the hepatitis A vaccine. We explored the vaccination rates in the 24-month preintervention and the 18-month intervention periods. We then administered a survey to physicians, advanced practice providers and nurses evaluating their perceptions and barriers to use of the EMR intervention. RESULTS: During the preintervention period, 49 vaccines were ordered (5.5 per 100 000 patient visits) and 32 were administered (3.6 per 100 000 patient visits). During the intervention period, 574 865 patient visits (74.3%) were screened. 2494 vaccines (322 per 100 000 patient visits) were ordered, and 1205 vaccines (155 per 100 000 patients visits) were administered. Physicians and advanced practice providers were initially compliant with the BPA's use, but compliance declined over time. Surveys revealed that the major barrier to use was lack of time. CONCLUSIONS: EMR screening tools and BPAs can be used in the ED as an effective strategy to vaccinate high-risk individuals. This may be translatable to outbreaks of other vaccine-preventable illnesses like influenza, measles or SARS-CoV-2. Providing ongoing education about the public health initiative and giving feedback to physicians, advanced practice providers and nurses about tool compliance are needed to sustain the improvement over time.

Accurate delivery of pristimerin and paclitaxel by folic acid-linked nano-micelles for enhancing chemosensitivity in cancer therapy.

Chemoresistance remains a huge challenge for effective treatment of non-small cell lung cancer (NSCLC). Previous studies have shown Chinese herbal extracts possess great potential in ameliorating tumor chemoresistance, however, the efficacy is clinically limited mainly because of the poor tumor-targeting and in vivo stability. The construction of nano-delivery systems for herbal extracts has been shown to improve drug targeting, enhance therapeutic efficacy and reduce toxic and side effects. In this study, a folic acid (FA)-modified nano-herb micelle was developed for codelivery of pristimerin (PRI) and paclitaxel (PTX) to enhance chemosensitivity of NSCLC, in which PRI could synergistically enhance PTX-induced growth inhibition of A549 cancer cell. PTX was firstly grafted with the FA-linked polyethylene glycol (PEG) and then encapsulated with PRI to construct the PRI@FA-PEG-PTX (P@FPP) nano-micelles (NMs), which exhibited improved tumor-targeting and in vivo stability. This active-targeting P@FPP NMs displayed excellent tumor-targeting characteristics without obvious toxicity. Moreover, inhibition of tumor growth and metastasis induced by P@FPP NMs were significantly enhanced compared with the combined effects of the two drugs (PRI in combination of PTX), which associated with epithelial mesenchymal transition inhibition to some extent. Overall, this active-targeting NMs provides a versatile nano-herb strategy for improving tumor-targeting of Chinese herbal extracts, which may help in the promotion of enhancing chemosensitivity of NSCLC in clinical applications.

Ameliorative effect of Berberidis radix polysaccharide selenium nanoparticles against carbon tetrachloride induced oxidative stress and inflammation.

Berberidis radix polysaccharide (BRP) extracted as capping agents was applied to prepare BRP-selenium nanoparticles (BRP-SeNPs) in the redox reaction system of sodium selenite and ascorbic acid. The stability and characterization of BRP-SeNPs were investigated by physical analysis method. The results revealed that BRP were tightly wrapped on the surface of SeNPs by forming C-O⋯Se bonds or hydrogen bonding interaction (O-H⋯Se). BRP-SeNPs presented irregular, fragmented and smooth surface morphology and polycrystalline nanoring structure, and its particle size was 89.4 nm in the optimal preparation condition. The pharmacologic functions of BRP-SeNPs were explored in vitro and in vivo. The results showed that BRP-SeNPs could heighten the cell viabilities and the enzyme activity of GSH-Px and decrease the content of MDA on H2O2-induced AML-12 cells injury model. In vivo tests, the results displayed that BRP-SeNPs could increase the body weight of mice, promote the enzyme activity like SOD and GSH-Px, decrease the liver organ index and the hepatic function index such as ALT, AST, CYP2E1, reduce the content of MDA, and relieve the proinflammation factors of NO, IL-1ß and TNF-α in CCl4-induced mice injury model. Liver tissue histopathological studies corroborated the improvement of BRP-SeNPs on liver of CCl4-induced mice. The results of Western blot showed that BRP-SeNPs could attenuate oxidant stress by the Nrf2/Keap1/MKP1/JNK pathways, and downregulate the proinflammatory factors by TLR4/MAPK pathway. These findings suggested that BRP-SeNPs possess the hepatoprotection and have the potential to be a green liver-protecting and auxiliary liver inflammation drugs.

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research.

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.

Comprehensive analyses of prognostic biomarkers and immune infiltrates among histone lysine demethylases (KDMs) in hepatocellular carcinoma.

BACKGROUND: Histone lysine demethylases (KDMs) are closely related to the occurrence and development of different tumors through epigenetic mechanisms. However, the prognosis and immune infiltration of KDMs in hepatocellular carcinoma (HCC) remain undefined. METHODS: In the current study, we analyzed the expression of KDMs on HCC patients using the Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, Metascape, GSEA, and TIMER databases. Finally, we investigated KDM expression in HCC by qRT-PCR, Western blotting, and IHC. RESULTS: We found that KDM3A/3B/5A/5B and KDM6A were upregulated in HCC patients, while KDM6B and KDM8 were downregulated. The high expressions of KDM1A/2B/3B/5B/5C were markedly related to tumor stages and grades of HCC patients. The abnormal expression of KDM1A/1B/3A/4A/5A/5C/6A/6B/7A and KDM8 were associated with HCC patients' prognosis. Also, we found that HCC tissues presented higher expression levels of KDM1A/2A/5A/5B and lower expression levels of KDM6B. The function of KDMs was primarily related to the histone demethylase activity and cell cycle, p53 signaling pathway, pathways in cancer, transcriptional mis-regulation in cancer, viral carcinogenesis, and FoxO signaling pathway. Furthermore, we indicated that the pathways most involved were the mitotic spindle and DNA repair. Additionally, we found that the expression of KDM1A/1B/3A/4A/5B/5C and KDM6A were significantly correlated with HCC immune infiltration. CONCLUSIONS: Overall, our current results indicated that KDM1A/1B/3A/4A/5B/5C and KDM6A could be novel prognostic biomarkers and provide insights into potential immunotherapy targets to HCC patients.

Glycyrrhizic Acid Alleviates Lipopolysaccharide (LPS)-Induced Acute Lung Injury by Regulating Angiotensin-Converting Enzyme-2 (ACE2) and Caveolin-1 Signaling Pathway.

Acute lung injury (ALI) is mainly caused by severe infection, shock, trauma, and burn, which causes the extensive release of inflammatory factors and other mediators. As a major bioactive constituent of traditional Chinese herb licorice, glycyrrhizic acid (GA) plays an important effect on inflammatory regulation. Nevertheless, the exact mechanism of this effect remains unclear. The present study aims to explore the potential protective effect of GA on LPS-induced ALI. Our results showed that GA significantly attenuated LPS-induced ALI and decreased the production of inflammatory factors, including IL-1ß, MCP-1, COX2, HMGB1, and adhesion molecules, such as E-selectin, VCAM-1, and modulated expression of angiotensin-converting enzyme 2 (ACE2). Moreover, treatment of ACE2 inhibitor (MLN-4760) reversed the effects of GA on the secretion of pro-inflammatory factors in ALI. Additionally, GA exerts its protective effect by regulating the ACE2 and caveolin-1/NF-κB signaling pathway. In conclusion, this study showed that GA alleviated LPS-induced ALI by upregulating ACE2 and inhibiting the caveolin-1/NF-κB signaling pathway.

Doomed peripheral intravenous catheters: Bad Outcomes are similar for emergency department and inpatient placed catheters: A retrospective medical record review.

INTRODUCTION: The survivorship of peripheral intravenous catheters (PIVCs) placed in hospitalized patients is shockingly poor and leads to frequent reinsertions. We aimed to evaluate differences in failure rates and IV insertion practices for PIVCs that are placed in the emergency department (ED) compared to those placed in the inpatient (IP) setting. METHODS: We conducted a retrospective electronic medical record review of PIVC survival at a single-site suburban, academic tertiary care referral center with 130,000 annual ED visits and 1100 inpatient beds. Adult patients admitted requiring at least one PIVC were included. The primary outcome was incidence of premature failure of PIVCs. Secondary outcomes included dwell time, completion of therapy, catheter diameter, and site of insertion as they relate to PIVC survival. RESULTS: Between January 2018 and July 2019, 90,743 IV catheters were included from 47,272 unique patient encounters in which 35,798 and 54,945 catheters were placed in the ED and IP units, respectively. There was no significant difference in failure rate between the ED and IP PIVCs, with 53.1% of ED PIVCs failing and 53.4% of IP PIVCs failing (p = 0.35). Mean dwell time for ED PIVCs was 3.4 days compared to a mean of 3.2 days for IP placed PIVCs (p < 0.001). 48% of ED PIVCs achieved completion of therapy at the first insertion compared to 59% of IP PIVCs (p < 0.001). The antecubital fossa and forearm had the lowest failure rate of 53% and 50%, respectively, and 22 gauge PIVCs had the highest failure rate of 60.5%. CONCLUSION: PIVCs have similar poor survival rates regardless of ED versus IP location of the insertion. The forearm and antecubital fossa sites should be preferentially used. Smaller diameter (22G) catheters have highest complications and poorest survival regardless of site of insertion. Larger diameter catheters (18 or 20 gauge) may offer improved outcomes.

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review.

Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online-solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry.

RATIONALE: Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin. METHODS: An online solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry (online-SPE-LC-HRMS) method was developed and applied for the determination of digoxin in plasma. The online SPE-LC steps included pretreatment and separation of plasma samples that were carried out using a Waters Oasis HLB cartridge and XBridge Shield RP18 column, respectively. A high-resolution Q Orbitrap mass spectrometer with targeted-selected ion monitoring in negative scan mode was applied to monitor formate-adduct ions [M + HCOO]- m/z 825.42781 for digoxin. RESULTS: Linearity was shown over the range 0.1-10 ng mL-1 for digoxin with correlation coefficients of R2 > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1 ng mL-1 . Extraction recoveries ranged from 82.61% to 94.28% for digoxin. The intra- and inter-day precision values were < 5.53% with accuracy ranging from 84.97% to 96.75%. The total running time was 10 min for each sample. CONCLUSION: The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.

Vaccination reduces need for emergency care in breakthrough COVID-19 infections: A multicenter cohort study.

BACKGROUND: While recent literature has shown the efficacy of the SARS-CoV-2 vaccine in preventing infection, it's impact on need for emergency care/hospitalization in breakthrough infections remain unclear, particularly in regions with a high rate of variant viral strains. We aimed to determine if vaccination reduces hospital visits in breakthrough COVID-19. METHODS: This observational cohort analysis compared unvaccinated (UV), partially vaccinated (PV), and fully vaccinated (FV) adult patients with SARS-CoV-2 infection requiring emergency care(EC)/hospitalization within an eight-hospital system in Michigan. Demographic and clinical variables were obtained from the electronic record. Vaccination data was obtained from the Michigan Care Improvement Registry and Centers for Disease Control vaccine tracker. Primary endpoint was rate of emergency care/hospitalization encounters among patients diagnosed with COVID-19. Secondary outcome was severe disease-composite outcome (ICU, mechanical ventilation, or in-hospital death). FINDINGS: Between December 15,2020 and April 30,2021, 11,834 EC encounters were included:10,880 (91.9%) UV, 825 (7%) PV, 129 (1.1%) FV. Average age was 53.0 ± 18.2 and 52.8% were female. Accounting for the SARS-CoV-2 vaccination population groups in Michigan, the ED encounters/hospitalizations rate relevant to COVID-19 was 96% lower in FV versus UV (multiplicative effect:0.04, 95% CI 0.03 to 0.06, p < 0.001) in negative binomial regression. COVID-19 EC visits rate peaked at 22.61, 12.88, and 1.29 visits per 100000 for the UV, PV, and FV groups, respectively. In the propensity-score matching weights analysis, FV had a lower risk of composite disease compared to UV but statistically insignificant (HR 0.84, 95% CI 0.52 to 1.38). INTERPRETATION: The need for emergency care/hospitalization due to breakthrough COVID-19 is an exceedingly rare event in fully vaccinated patients. As vaccination has increased regionally, EC visits amongst fully vaccinated individuals have remained low and occur much less frequently than unvaccinated individuals. If hospital-based treatment is required, elderly patients with significant comorbidities are at high-risk for severe outcomes regardless of vaccination status.

Mechanical, Structural and Electronic Properties of CO2 Adsorbed Graphitic Carbon Nitride (g-C3N4) under Biaxial Tensile Strain.

We investigate mechanical, structural and electronic properties of CO2 adsorbed graphitic carbon nitride (g-C3N4) system under biaxial tensile strain via first-principles calculations. The results show that the stress of CO2 adsorbed g-C3N4 system increases and then decreases linearly with the increasing biaxial strain, reaching maximum at 0.12 strain. This is primarily caused by the plane N-C stretching of the g-C3N4. Furthermore, both the Perdew-Burke-Ernzerhof (PBE) and Heyd- Scuseria-Ernzerhof screened hybrid functional (HSE06) band gaps show direct-indirect transitions under biaxial tensile strain and have the maximum also at 0.12 strain. It is found that there is large dipole transition matrix element around Γ point, leading high optical absorption coefficients of the deformed adsorption system, which would be of great use for the applications of new elastic nanoelectronic and optoelectronic devices.

Emergency Department Urosepsis and Abdominal Imaging.

Introduction Insufficient attention has been directed towards urosepsis. Notably, no protocols or clinical decision rules currently exist outlining the appropriate use of imaging in uroseptic patients. The primary objective of our study was to retrospectively evaluate uroseptic emergency department (ED) patients who underwent abdominal imaging, to report the proportion of patients with imaging findings necessitating emergent surgical consultation. Methods We retrospectively identified 1142 patients ≥ 18 years of age that presented to the ED from January 2009 to December 2012 with ICD9 code indicative of urosepsis. All included patients underwent ED-ordered abdominal computerized tomography (CT) or retroperitoneal ultrasound (US). Imaging and urinalysis (UA) results were categorized. We report proportions with odds ratios and 95% confidence intervals. Results Of 1142 patients, we excluded 80 for neg UA, 167 for < 2 SIRS (systemic inflammatory response syndrome), 320 for positive blood cultures, and 37 for incomplete data. This yielded 538 patients which the authors reviewed the results of the CT or US to determine the proportion who required emergent surgical consultation and who underwent surgical or interventional procedure. There were 243 (45%) that had CT or US results that necessitated emergency surgical consultation, of those 180 (33%) underwent surgical or interventional procedure. Similar rates of emergency surgical consultation occurred when sub-divided by positive versus equivocal UA, with 43% and 47%, respectively. Conclusions Forty-five percent of our abdominally imaged urosepsis cohort had imaging findings that necessitated emergent surgical consultation, with a similar proportion in the subset with positive versus equivocal UA. The utility of abdominal imaging in this population should be studied prospectively.

Epidemiology, Clinical Characteristics, and Outcomes of a Large Cohort of COVID-19 Outpatients in Michigan.

BACKGROUND: Most outpatients with coronavirus disease 2019 (COVID-19) do not initially demonstrate severe features requiring hospitalization. Understanding this population's epidemiological and clinical characteristics to allow outcome anticipation is crucial in healthcare resource allocation. METHODS: Retrospective, multicenter (8 hospitals) study reporting on 821 patients diagnosed with COVID-19 by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs and discharged home to self-isolate after evaluation in emergency departments (EDs) within Beaumont Health System in March, 2020. Outcomes were collected through April 14, 2020, with a minimum of 12 day follow-up and included subsequent ED visit, admission status, and mortality. RESULTS: Of the 821 patients, mean age was 49.3 years (SD 15.7), 46.8% were male and 55.1% were African-American. Cough was the most frequent symptom in 78.2% of patients with a median duration of 3 days (IQR 2-7), and other symptoms included fever 62.1%, rhinorrhea or nasal congestion 35.1% and dyspnea 31.2%. ACEI/ARBs usage was reported in 28.7% patients and 34.0% had diabetes mellitus. Return to the ED for re-evaluation was reported in 19.2% of patients from whom 54.4% were admitted. The patients eventually admitted to the hospital were older (mean age 54.4 vs 48.7 years, p=0.002), had higher BMI (35.4 kg/m2 vs 31.9 kg/m2, p=0.004), were more likely male (58.1% vs 45.4%, p=0.026), and more likely to have hypertension (52.3% vs 29.4%, p<0.001), diabetes mellitus (74.4% vs 29.3%, p<0.001) or prediabetes (25.6% vs 8.4%, p<0.001), COPD (39.5% vs 5.4%, p<0.001), and OSA (36% vs 19%, p<0.001). The overall mortality rate was 1.3%. CONCLUSION: We found that 80.8% of patients did not return to the ED for re-evaluation. Sending patients with COVID-19 home if they experience mild symptoms is a safe approach for most patients and might mitigate some of the financial and staffing pressures on healthcare systems.

Inferior Vena Cava Filter Retrieval Trends: A Single-Center Experience.

Recognition of the adverse events of inferior vena cava filters (VCFs) has prompted the Food and Drug Administration (FDA) to issue safety warnings (2010 and 2014), advocating for removal, once the risk of pulmonary embolism has abated. Despite an initial increase in retrieval rates, these remain low (25-30% at 1 year in 2014). We retrospectively investigated retrieval trends in adults with VCFs placed between 2015 and 2018 at a single institution. The rate of retrievable VCF removal accounting for the competing risk of death was the main outcome. There were 494 VCFs placed (305 retrievable). The cumulative incidence of retrieval remained low (21% at 1 year), even after the second FDA warning (2014). Patients who resumed anticoagulation (AC) at any time were more likely to have retrieval (hazard ratio [HR] = 3.6, p < 0.01) and had higher retrieval rates at every time point (31.4 vs. 7.6% at 1 year). Advanced age (HR = 0.98 per year, p = 0.004), stroke (HR = 0.28, p = 0.028), and active malignancy (HR = 0.42, p = 0.006) predicted nonretrieval. Device-related complications were infrequent (<1%) but thrombotic complications occurred early and were more common for nonretrieved VCFs (17 vs. 12%, p = 0.29). Revision of guidelines to recommend active surveillance for the ability to tolerate AC in the immediate postimplantation period may improve retrieval rates.

Single-molecule multiplexed profiling of protein-DNA complexes using magnetic tweezers.

Epigenetics, such as the dynamic interplay between DNA methylation and demethylation, play diverse roles in critical cellular events. Enzymatic activity at CpG sites, where cytosines are methylated or demethylated, is known to be influenced by the density of CpGs, methylation states, and the flanking sequences of a CpG site. However, how the relevant enzymes are recruited to and recognize their target DNA is less clear. Moreover, although DNA-binding epigenetic enzymes are ideal targets for therapeutic intervention, these targets have been rarely exploited. Single-molecule techniques offer excellent capabilities to probe site-specific protein-DNA interactions and unravel the dynamics. Here, we develop a single-molecule approach that allows multiplexed profiling of protein-DNA complexes using magnetic tweezers. When a DNA hairpin with multiple binding sites is unzipping, strand separation pauses at the positions bound by a protein. We can thus measure site-specific binding probabilities and dissociation time directly. Taking the TET1 CXXC domain as an example, we show that TET1 CXXC binds multiple CpG motifs with various flanking nucleotides or different methylation patterns in an AT-rich DNA. We are able to establish for the first time, at nanometer resolution, that TET1 CXXC prefers G/C flanked CpG motif over C/G, A/T, or T/A flanked ones. CpG methylation strengthens TET1 CXXC recruitment but has little effect on dissociation time. Finally, we demonstrate that TET1 CXXC can distinguish five CpG clusters in a CpG island with crowded binding motifs. We anticipate that the feasibility of single-molecule multiplexed profiling assays will contribute to the understanding of protein-DNA interactions.