Solid Lines Research Articles

Research on Comprehensive Evaluation and Early Warning of Transmission Lines' Operation Status Based on Dynamic Cloud Computing.

The current methods for evaluating the operating condition of electricity transmission lines (ETLs) and providing early warning have several problems, such as the low correlation of data, ignoring the influence of seasonal factors, and strong subjectivity. This paper analyses the sensitive factors that influence dynamic key evaluation indices such as grounding resistance, sag, and wire corrosion, establishes the evaluation criteria of the ETL operation state, and proposes five ETL status levels and seven principles for selecting evaluation indices. Nine grade I evaluation indices and twenty-nine grade II evaluation indices, including passageway and meteorological environments, are determined. The cloud model theory is embedded and used to propose a warning technology for the operation state of ETLs based on inspection defect parameters and the cloud model. Combined with the inspection defect parameters of a line in the Baicheng district of Jilin Province and the critical evaluation index data such as grounding resistance, sag, and wire corrosion, which are used to calculate the timeliness of the data, the solid line is evaluated. The research shows that the dynamic evaluation model is correct and that the ETL status evaluation and early warning method have reasonable practicability.

Does symmetry preclude the evolution of senescence? A comment on Pen and Flatt 2021

Does symmetry preclude the evolution of senescence? A comment on Pen and Flatt 2021

Quantitatively evaluate the cylindricity of Large size pipe fitting via laser displacement sensor and Digital twin technology

The rapid development of intelligent detection technology guarantees accuracy in the assembly process. Aiming to solve the quantitative inspection of the cylindricity of Large size pipe fitting, this paper presents an online method technology using a laser sensor and Digital twin technology. The detection system comprises visual positioning, servo drive, and laser displacement sensor information acquisition systems. After positioning by the machine vision camera system, the servo system and laser displacement sensor scan the large-size pipe fitting layer by layer and establish the information interaction between physical space and virtual space through digital twinning technology. The digital twin scatters information model was found to calculate the maximum tangent circle and minimum peripheral circle, fitting the curve area of the closed point cloud layer by layer. And the least square method was used to calculate the center of the layered circle. The radial deviation of pipe fitting was evaluated comprehensively. The system makes a linear fitting of the center of the most miniature square circle of each layer, compares its deflection Angle with the solid center line, and calculates the center line deviation of the hole. Finally, the precision of the proposed method was validated by varying experiments. The cylindricity measurement of pipe fittings with an inner diameter of 300mm and height of 270mm was carried out by a pair of C-shaped semicircles fixed by the radial assembly. The cylindricity of the pipe fitting is 0.2372mm.

Development of a mathematical model of the process of sorting municipal solid waste using elements of similarity of technical systems

The article studies the similarity of ensuring the technical condition of the solid municipal waste sorting line system. The functional dependence of the productivity of the waste sorting line is given, partial expressions and numerical values of the criteria for similarity of the functioning of the sorting process are obtained. A generalized criterion of similarity of the state of the solid municipal waste sorting process is also obtained, the nature of the influence of the parameters of functional dependence on the value of the output characteristic is investigated.

U-Turn Across Solid White Line

We are rolling into an explosive situation involving opponents on the contact line armed to the teeth. And there is even less unity of goals and objectives on both sides than there was during the Cold War.

Numerical investigation of the unsteady effect owing to oscillation on airfoil icing

Modeling the unsteadiness owing to body motion is essential for accurately simulating ice accretion on a moving object. For an oscillating airfoil, high-frequency oscillations have been assumed to occur in slow motion to apply a quasi-steady approach to numerical analysis. The method raised arbitrariness in the number of data exchanges and the initial angle of attack. Simultaneously, the oscillation owing to a change in the angle of attack was considered for each step. Subsequently, the quasi-unsteady approach was proposed, the results from which exhibited good agreement for a few ice shapes, unlike that of the extended quasi-steady approach. However, whether a quasi-unsteady approach is sufficiently accurate for simulating ice accretion on a two-dimensional oscillating airfoil under various conditions still remains unknown. This study analyzed the unsteady effect on collection efficiency and convective heat transfer using the quasi-unsteady approach. Furthermore, as the static case, this approach demonstrated that the roughness and laminar-turbulent transition model for the oscillating airfoil can improve the prediction of the ice shape. The results obtained from this approach using the improved model exhibited good agreement with previously reported experimental results.Fig. 11 compared predicted ice shape with different roughness height. Fig. 11(a) is Run 61 with a reduced frequency of 0.044 at an LWC = 1 g/m3, and Fig. 11(b) is Run 50 with a reduced frequency of 0.027 at an LWC =.55 g/m3 The dotted line indicates the experimental ice shape and the dashed line indicates the numerical results applied to the empirical roughness model. The solid line indicates ice shape with the roughness size when the direction and size of the ice horn closely match the experimental values. When an empirical roughness model is applied, the ice horns are usually concentrated near the leading edge. Roughness increases convective heat transfer and premature laminar turbulence in ice accretion. The convective heat transfer peaks near the leading edge with a high roughness value; therefore, the ice horn gathers near the leading edge. Low roughness delayed the formation of the ice horn due to the decreased heat transfer rate, which balances the latent heat of icing, thereby allowing the droplets to freeze before moving to the trailing edge. In Run 61, the ice shape was predicted accurately at 20 % of the empirical roughness and 40 % roughness height of Run 55. When the roughness height was reduced, such as in the case of Run 61 with 10 % empirical roughness, the primary horn reduced, whereas the secondary horns increased.

The determinants of saccade targeting strategy in neurodevelopmental disorders: The influence of suboptimal reading experience

Whether eye-movements deficits are causal in reading disorders (RD) or rather a consequence of linguistic processing difficulty experienced by disabled readers has been extensively debated.Since RD are frequently comorbid with the Neurofibromatosis type1 (NF1), children with NF1 were used as a comparison group for children with dyslexia in this study.Eye movements were recorded while 21 dyslexic, 20 NF1, and 20 typically developing children performed an oculomotor lateralized bisection task. In this experiment, we manipulated the type of stimulus - discrete (words and strings of hashes) versus continuous (solid lines) - and the visual field where the stimulus was displayed (left vs right). The results showed that (1) only proficient readers (TD and NF1 without RD) showed fully developed oculomotor mechanisms for efficient reading, with a clear preferred viewing location located to the left of the word's centre in both visual fields, and fine-tuned saccade targeting guided by the between-character space information and (2) NF1 poor readers mirrored the dyslexic eye movement behaviour, with less accuracy and more variability in saccadic programming, no sensitivity to the discreteness of the stimuli, particularly in the left visual field. We concluded that disruption to oculomotor behaviour reflectsthe fact that many of the processes involved in reading are not yet automatized for children with RD, independently of NF1. This suggests that the differences in saccade targeting strategy between children with and without RD would be secondary consequences of their reduced reading experience.

83. Infectious Outcomes of CAR T-cell Therapy: Longitudinal Follow Up and Risk Stratification

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is increasingly utilized in the treatment of a variety of hematologic malignancies. While efficacious, this therapy is associated with prolonged cytopenias and immunosuppression. Open questions remain regarding the distribution of infections beyond the first year of therapy and infectious risk stratification. We identified a cohort of CAR T-cell recipients to address these gaps in the literature. Methods We retrospectively analyzed adult patients who received CAR T-cell therapy at our center including their infectious outcomes up to two years following cell infusion. Descriptive statistics and Mann-Whitney testing were used when appropriate. A time-to-event analysis was made assessing time from cell infusion to first infection. Univariate Kaplan-Meier (KM) analyses with log-rank testing and cox regression analysis identified significant predictors for inclusion into a multi-variate cox model of risk of first infection. Results Baseline characteristics of the 75 patients are listed in Table 1. Etiology of infection changed in distribution over time from predominantly nosocomial pathogens more so to respiratory viruses and pneumonia (Figure 1). In univariate KM failure analyses, receipt of tocilizumab or development of neurotoxicity was associated with more rapid onset of first infection (log-rank p-values = 0.0361, 0.0417, respectively) (Figure 2). Multivariate cox regression demonstrated that higher neutrophil count at apheresis was inversely associated with onset of infection (hazard ratio (HR) 0.81; 95% CI .67-.98; p-value .028), while development of neurotoxicity (HR 5.51; 95% CI 1.15–26.5; p-value .033) and receipt of tocilizumab (HR 3.93; 95% CI 1.15–13.42; p-value .029) were associated with onset of infection. Baseline patient population characteristics as described by frequency (n) and percent of total population or median and inter-quartile range (IQR). Abbreviations - CAR: Chimeric Antigen Receptor. ECOG: Eastern Cooperative Oncology Group Performance Score. DLBCL: Diffuse large B cell lymphoma. HGBL: High grade B-cell lymphoma. TFL: Transformed follicular lymphoma. MCL: Mantle-cell lymphoma. PMBCL: Primary mediastinal large B-cell lymphoma. ALL: acute lymphoblastic leukemia. MM: Multiple myeloma. IVIG: Intravenous immune globulin. ANC: Absolute neutrophil count. ALC: Absolute lymphocyte count. IgG: Immunoglobulin G levels. *Indicates missing data on 1 patient, percent relative to n of 74 for these variables. The letter "a" indicates there was one patient each with PMBCL, ALL or MM. Abbreviations - RVI: Respiratory Viral Infection, UTI: Urinary Tract Infection, CDI: Clostridium dificile infection, CAR: Chimeric Antigen Receptor. *Indicates graphical result truncation of RVI number between 30 days and 1-year post-CAR T-cell infusion (n=24), which is the most predominant infection. “Other” infections within 30 days of cell infusion included 2 episodes of cellulitis, and one episode each of sialadenitis, Aspergillus pneumonia and empyema. “Other” infections between 30 days and 1-year post-cell infusion included 1 each of oral HSV, intra-abdominal infection, empyema, conjunctivitis, cellulitis, bacterial sinusitis and tooth abscess. “Other” infections between 1- and 2-years post-cell infusion included shingles and bacterial sinusitis (1 each). Kaplan-Meier failure curves of proportion of patients who developed their first infection (failure) following CAR T-cell infusion by day since cell infusion. Right censoring at two years of follow up, death, or disease progression, whichever came first. A. Curves separated by receipt of tocilizumab (red dashed line) versus no receipt of tocilizumab (solid blue line) during period of follow up. Log-rank test p = 0.0361. B. Curves separated by development of CAR T-cell neurologic toxicity (red dashed line), also known as immune effector cell-associated neurotoxicity syndrome (ICANS) as documented by diagnostic criteria from American Society of Transplant and Cellular Therapy (ASTCT) versus no ICANS (solid blue line). Log-rank test p = 0.0417. Conclusion The pattern of infections following CAR T-cell infusion changes over time, transitioning from nosocomial infections to respiratory viral infections. The multi-variate cox model of time to first infection demonstrated neutropenia at apheresis, tocilizumab receipt and development of neurotoxicity predicted more rapid onset of infection. Strategies to mitigate inflammatory complications may reduce infection. Disclosures All Authors: No reported disclosures.

2352. Analysis of National Infection Prevention and Control Programs on Sepsis Incidence: An Ecological Study

Abstract Background Annually, the World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations jointly administer the Tripartite Antimicrobial Resistance (AMR) country self-assessment survey (TrACSS), which asks participating countries to evaluate themselves on their progress in implementing policies to prevent and control AMR. Question 8.1 in the survey asks whether there is a functional national infection prevention and control (IPC) program or plan in human healthcare (question 8.1 in the survey). Our aim was to evaluate whether having an IPC plan correlates with a reduction in a country’s sepsis incidence. Methods We used 2017 estimates of total sepsis incidence per 100,000 people published previously by Rudd et al. We matched this data to a country’s respective response to question 8.1 of the 2016–2017 TrACSS. Table 1 lists the potential answers to question 8.1. Additional details about the survey methodology are available on the WHO TrACSS website. We compared the sepsis incidence in countries where IPC plans were implemented nationwide (answer D or E) to countries that did not implement a nationwide IPC plan (answer A, B, or C). Results 154 countries were surveyed, 140 of which responded to question 8.1 and had available sepsis data. 47 countries (33.6%) had nationwide implementation of IPC plans and 93 (66.4%) did not. Globally, countries who implemented nationwide IPC plans had lower sepsis incidence with less inter-country variability (median: 201, interquartile range [IQR]: 165–272) compared to countries who did not implement an IPC plan (439, IQR: 290–682). (Figure 1). Similar trends were observed when broken down by each individual WHO region (Figure 2). Multivariate Poisson regression adjusting for region found that countries who implemented nationwide IPC plans had a 37.2% (95% CI 35.7–38.9%, p < 0.001) lower incidence of sepsis. The height of the box represents the interquartile range (IQR). The solid line within each box represents the median. The whiskers represent the minimum and maximum for each respective group, excluding outliers. Outliers are defined as any data point that is greater or less than 1.5 x IQR from the third or first quartile, respectively. Outliers are depicted as individual data points outside of each box and whiskers. The red box represents countries that answered either a, b, or c. The turquoise box includes countries that answered either d or e. Box plot parameters are similar to that of figure 1. Each pair of red (countries answering a, b, or c) and turquoise boxes (countries answering d or e) represent a different WHO region, as listed on the x-axis. AFRO is the African Region. AMRO is the Region of the Americas. EMRO is the Eastern Mediterranean Region. EURO is the European Region. SEARO is the South-East Asian Region and WPRO is the Western Pacific Region. Conclusion This ecological study suggests that broad implementation of an IPC plan is associated with lower sepsis incidence. Additional time-series analysis and adjusting for gross domestic product would be important next steps to ascertain the true benefit of implementing a national IPC plan on rates of sepsis. Disclosures All Authors: No reported disclosures.

1539. A Nine-Gene Blood-Based Signature Meets the World Health Organization Target Product Profiles for Diagnosis of Active Tuberculosis and Predicting Progression from Latent to Active Disease

Abstract Background As part of its End TB strategy, the WHO has identified the need for non-sputum-based diagnostics that meet target product profiles (TPP) of 90% sensitivity and 70% specificity for diagnosis of Active TB (ATB) and 75% sensitivity and specificity for predicting progression from Latent TB (LTB) to ATB. The successful translation of a 3-gene blood-based signature, identified using diverse datasets, into a prototype point-of-care diagnostic, that meets the WHO TPPs, has demonstrated the power of integrating large amounts of heterogeneous data to identify generalizable disease signatures. We hypothesized that integration of more diverse datasets, comprising patients with ATB or other inflammatory lung diseases, would identify novel, robust signatures, for diagnosing ATB and predicting progression from LTB to ATB, that meet the WHO TPPs. Methods Using multi-cohort analyses, we integrated and analyzed data from 3,615 peripheral blood samples, in 49 publicly available transcriptomic datasets (discovery cohorts), from healthy controls and patients with LTB, ATB, and other diseases (COPD, viral infections, sarcoidosis, etc.). We used data from (1) 3,836 blood samples in 28 retrospective datasets and (2) 360 prospectively collected blood samples, from a household contact study in Moldova, as validation cohorts. Results Using the discovery cohorts we identified a 9-gene signature for diagnosing ATB patients from healthy controls, or individuals with LTB or other diseases. The signature achieved 90% sensitivity and 82% specificity in retrospective validation (Figure 1A) and 90% sensitivity and 69% specificity in the prospective cohort from Moldova (Figure 1B). In a longitudinal cohort of adolescents, the 9-gene signature predicted progression from LTB to ATB up to 1 year prior to sputum conversion with 76% sensitivity and 83% specificity (Figure 1C). Finally, the signature predicted prolonged lung inflammation post-treatment in the Catalysis Treatment Response Cohort (Figure 1D). 9-gene TB signature validates in independent retrospective and prospective cohorts. (A) ROC curves for comparing ATB vs. all other samples (All), or individually comparing ATB vs. Healthy, LTBI or Other Disease (OD) samples in independent retrospective validation and (B) a prospective Moldova cohort. (C) ROC curves comparing progressor and non-progressor samples collected at different time points in the Adolescent Cohort Study (ACS), for the 9-gene signature in solid lines and a previous 3-gene signature in dashed lines, (D) Distribution of the 9-gene score at different time points post-treatment in the Catalysis Treatment Response Cohort Study, for individuals with persistent lung inflammation at 24 weeks compared with those who had clear lungs at 24 weeks. Conclusion Overall, the 9-gene signature meets the WHO TPPs required for the End TB strategy. Disclosures Purvesh Khatri, PhD, Cepheid, Inc.: Advisor/Consultant|Inflammatix, Inc.: Advisor/Consultant|Inflammatix, Inc.: Inflammatix is in negotiations to license the 9-gene signature discussed here.|Inflammatix, Inc.: Stocks/Bonds.

1258. B/F/TAF in HIV-Infected Adults with Substance Use Disorders: BASE Week 48 Results

Abstract Background People with HIV (PWH) and substance use disorders (SUD) are at higher risk of non-adherence. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a Phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH and SUD. Methods Viremic (HIV RNA >1000 copies [c]/mL) treatment-naïve or -experienced PWH and ongoing SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was HIV RNA < 50 c/mL (FDA Snapshot Algorithm) at W48. Secondary endpoints were safety, adherence (dried blood spot [DBS] levels of emtricitabine-triphosphate [FTC-TP] and tenofovir-diphosphate [TVF-DP]), substance use (NIDA ASSIST) and quality of life (SF-12). Results Forty-three participants enrolled; 95% reported methamphetamine use. Median age was 38 years (range: 21-62); 19% female, 81% White, 14% Black, 16% Latinx. At W48, 21 participants (49%) had HIV RNA < 50 c/mL (ITT, Figure 1). Four participants (9%) experienced confirmed virologic failure; none developed treatment-emergent resistance. Seventeen participants (40%) experienced grade ≥3 adverse events; none attributed to B/F/TAF. Five participants reported suicidal ideation; none resulted in discontinuation. Observed mean FTC-TP and TVF-DP concentrations in DBS corresponded to 5-6 doses/week (FTC-TP: >3.6 pmol/7mm punches; TVF-DP: >1733 fmol/7 mm punches; Figure 2). NIDA ASSIST scores declined from baseline, with methamphetamine use decreasing most (-7.9 points; -29%). SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively, but remained below mean US scores. Longitudinal virologic outcomes, intent-to-treat analysis Mean observed intracellular emtricitabine triphosphate (FTC-TP) and tenofovir diphosphate (TFV-DP) in dried blood spots at weeks 6, 24, and 48 Thresholds for 2-3 doses/week (Solid Line) and 4-5 doses/week (Dashed Line) are noted for both FTC-TP and TFV-DP based on TAF-DBS data [Yager J, et al. JAIDS, 2020]. Notes: Y-axis represents femtomoles/punches Conclusion B/F/TAF among a high-risk population of PWH and ongoing SUD resulted in a 49% viral suppression rate at W48. No emergent resistance was noted supporting the high barrier to resistance provided by B/F/TAF. Disclosures Sara H. Bares, MD, Gilead Sciences: Expert Testimony|GSK ViiV Healthcare: Grant/Research Support|Janssen: Grant/Research Support Kimberly Scarsi, PharmD, Organon: Grant/Research Support.

1088. Evaluating the Effect of Donepezil on Mortality Among Alzheimer’s Disease Patients With and Without COVID-19 Infection

Abstract Background Dementia has been identified as an independent risk factor for increased severity of COVID-19 infection. Donepezil, a cholinesterase inhibitor approved for Alzheimer’s disease (AD), has anti-inflammatory properties. Previous studies have found that donepezil reduced all-cause mortality for people living with AD. The anti-inflammatory effects of donepezil have not been studied in patients with COVID-19 and AD. Here, we compare mortality rates of patients with AD to assess the impact of donepezil on the severity of COVID-19 infections. Survival following SARS-CoV2-2 test, stratified by result and Donepezil Kaplan-Meier curves of all-cause mortality for Veterans with Alzheimer’s Disease taking donepezil (black) compared to those who were not taking donepezil (grey), further stratified by those with a positive SARS-CoV-2 PCR test (solid lines) or no evidence of a COVID-19 infection during the study period (dashed lines). While donepezil has a positive effect on survival, the adjusted survival odds ratio is not greater among those with vs. without a COVID-19 infection. Methods Using administrative data from the Veterans Healthcare Administration (VHA), we conducted a national retrospective cohort study of Veterans with AD who were tested for SARS-CoV-2 between March 1, 2020 and December 31, 2021 in the VHA. Among these patients, we assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use and considered the interaction of these two factors. For Veterans with a positive test, the date of first positive test was used to assess mortality; for Veterans without a COVID-19 diagnosis or positive test, date of first negative test was used. Results During the study period, 582 Veterans with Alzheimer’s disease were positive for COVID-19 and 14430 had no test or diagnosis indicating COVID-19 infection. Among people with AD and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared to 38% (159/419) for those who were not. Among people with AD without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared to 7% (712/10241) for those who were not. In a multivariable logistic regression, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (OR (95% CI) = 0.71 (0.47, 1.07) vs. OR (95% CI) = 0.68 (0.57, 0.80), interaction P = 0.818). Conclusion While all-cause mortality was lower for patients taking donepezil compared to those not taking donepezil, the protective effect of donepezil was not increased in AD patients with COVID-19 over those without COVID-19. The population differences and inflammatory biomarkers of AD patients treated with and without donepezil merit further study. Disclosures Robin L. Jump, MD, PhD, Merck: Grant/Research Support|Pfizer: Advisor/Consultant.

LB1532. The Impact of COVID-19 on nursing home residents’ clinical, functional, and psychosocial outcomes

Abstract Background Data on COVID-19 related nursing home infections and mortality accumulated at a rapid pace; yet little is known about the impact of nursing homes’ response to COVID-19 on resident clinical, functional, and psychosocial outcomes. Methods We examined aggregated Minimum Data Set (MDS) assessments to describe resident outcomes using an interrupted times series methodology for three timeframes: pre-COVID (1/2019 to 2/2020), pandemic (3/2020–12/2021), and vaccination (1/2021-6/2021). Data included 307,558 federally mandated resident MDS assessments from 60,846 resident in 489 nursing homes in a Mid-Western state. We calculated MDS based quality measures (QM) using definitions available from Centers for Medicare and Medicaid Services. Each QM-based outcome was fit to a logistic regression model using the method of generalized estimating equations. Results None of the QMs displayed a statistically significant trend pre-COVID. The prevalence of excessive weight loss and ADL decline increased sharply during the pandemic and reversed that trend with vaccination. Pressure ulcers among high-risk residents followed a similar trend, although pandemic and vaccination-related regression parameters for that QM were only marginally significant (p = .08). Pain worsened during the pandemic and vaccination period approaching significance (p=.07). Antipsychotic medication use worsened in the pandemic (p< .001) and did not improve in the vaccination period. Other QMs including any fall, fall with major injury, and incontinence did not exhibit statistically significant change in trend. Prevalence Profiles Circles: Observed proportions, Dashed Line: Model expected value, Solid Lines: 95% confidence limits for expected values Conclusion We noted significant changes in QMs for antipsychotic use, ADL loss, and weight loss, with the latter two improving in the vaccination period. Isolation, disease outbreaks, and staffing issues in facilities could have affected these QMs. Data variability may have limited our ability to detect other changes. Antipsychotics may have increased with the need to reduce wandering and other behaviors common in the nursing home population; behaviors high risk for spreading COVID-19. Why antipsychotic use did not improve during the vaccination period is less clear. Data beyond June of 2021 may help clarify the pattern of antipsychotic use. Disclosures Lori Popejoy, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest Amy Vogelsmeier, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest Marilyn Rantz, PhD, RN, FAAN, New Path: Board Member|New Path: Ownership Interest.

1519. Increased incidence of colorectal cancer in Veteran Health Administration hospital patients with pyogenic liver abscess: A matched cohort study

Abstract Background Colorectal cancer (CRC) remains the third leading cause of death in the United States (US), and incidence has increased among patients < 50 years of age over the last few decades. Although many patients with early CRC remain asymptomatic, infections such as Streptococcus gallolyticus bacteremia, can be an early finding. There is increasing evidence that pyogenic liver abscesses (PLA) may also be associated with CRC. However, studies of US populations remain limited. Methods We retrospectively evaluated patients with a diagnosis of PLA at Veteran Health Administration hospitals across the US from 2003 to 2020. For each case, up to three uninfected controls matched for age (+/- 5), gender, and healthcare facilities at the time of index infection from the outpatient population were selected. PLA patients and matched controls were followed for ten years. Our primary outcome was a new diagnosis of CRC after index infection. Stratified cumulative incidence function plots with Gray’s test for equality were used to examine CRC incidence. Then we used Fine-Gray sub-distribution hazard regression models with interaction terms using the logarithm of time to estimate cause-specific time-dependent hazard ratios (HRs) for CRC incidence while accounting for mortality. Results We compared 8,294 PLA patients to 23,111 matched controls. Median age was 65.7 in PLA patients and 66.0 in matched controls. The median number of colonoscopies was ten in PLA patients and five in matched controls over the study period (p < 0.001). Our analysis revealed a 1.9% incidence of new CRC in the liver abscess group, compared to 0.8% in the matched cohort (p < 0.001, Figure 1). The multivariate sub-distribution hazard regression model showed higher time-dependent HRs of CRC up to two years from diagnosis of PLA but not higher afterward (Table 1). Incidence of colorectal cancer (CRC) in patients with liver abscess (dashed yellow line) compared to patients with no liver abscess (solid blue line). Our analysis revealed a 1.9% incidence of CRC in patients with liver abscess compared to 0.8% in the matched control cohort. Conclusion We found a significantly higher incidence of CRC for patients with PLA, especially during the first two years from diagnosis, although some of our findings may be explained by increased screening around the time of diagnosis. We believe our findings support the importance of CRC screening after the diagnosis of PLA. Disclosures Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.

Novel pyridine-containing histone deacetylase inhibitors strongly arrest proliferation, induce apoptosis and modulate miRNAs in cancer cells

After over 30 years of research, the development of HDAC inhibitors led to five FDA/Chinese FDA-approved drugs and many others under clinical or preclinical investigation to treat cancer and non-cancer diseases. Herein, based on our recent development of pyridine-based isomers as HDAC inhibitors, we report a series of novel 5-acylamino-2-pyridylacrylic- and -picolinic hydroxamates and 2′-aminoanilides 5–8 as anticancer agents. The hydroxamate 5d proved to be quite HDAC3/6-selective exhibiting IC50 values of 80 and 11 nM, respectively, whereas the congener 5e behaved as inhibitor of HDAC1-3, −6, −8, and −10 (class I/IIb-selective inhibitor) at nanomolar level. Compound 5e provided a huge antiproliferative activity (nanomolar IC50 values) against both haematological and solid cancer cell lines. In leukaemia U937 cells, the hydroxamate 5d and the 2′-aminoanilide 8f induced remarkable cell death after 48 h, with 76% and 100% pre-G1 phase arrest, respectively, showing a stronger effect with respect to SAHA and MS-275 used as reference compounds. In U937 cells, the highest dose- and time-dependent cytodifferentiation was obtained by the 2′-aminoanilide 8d (up to 35% of CD11c positive/propidium iodide negative cells at 5 μM for 48 h). The same 8d and the hydroxamates 5d and 5e were the most effective in inducing p21 protein expression in the same cell line. Mechanistically, 5d, 5e, 8d and 8f increased mRNA expression of p21, BAX and BAK, downregulated cyclin D1 and BCL-2 and modulated pro- and anti-apoptotic microRNAs towards apoptosis induction. Finally, 5e strongly arrested proliferation in nine different haematological cancer cell lines, with dual-digit nanomolar potency towards MV4-11, Kasumi-1, and NB4, being more potent than mocetinostat, used as reference drug.

1526. Time from last COVID-19 vaccination’s impact on rapidity of viral culture conversion following SARS-CoV-2 infection: a prospective cohort study

Abstract Background Vaccination is a fundamental element of pandemic control; however, insufficient data exists on vaccine’s impact on SARS-CoV-2 viral dynamics. We aimed to evaluate the relationship between time to negative viral culture conversion after diagnosis and time since most recent COVID-19 vaccination. Scatterplot illustrating relationship between time from last dose of a COVID-19 vaccine and time to culture conversion. Both participants who only received their initial series of COVID-19 vaccination and those who received a COVID-19 vaccine booster dose were included. The black solid line shows the best fit for the Spearman correlation model; Gray shading denotes 95% confidence interval around this estimate. Spearman correlation coefficient, R, and p-value were estimates for the model. Scatterplot illustrating relationship between time since completion of initial COVID-19 vaccine series and time to culture conversion among un-boosted participants. The vaccine type received has also been designated by plot labels. The black solid line shows the best fit for the Spearman correlation model; gray shading denotes 95% confidence interval around this estimate. Spearman correlation coefficient, R, and p-value were estimates for the model. Methods CoViD Post-vax is longitudinal cohort study collecting baseline clinical questionnaires, and daily anterior nasal swabs and symptom screens on enrolled Boston University SARS-CoV-2 PCR-positive cases detected through a serial screening testing program or symptomatic testing. Data was collected from November 2021 to March 2022. Participants were excluded from analysis if they lacked at least one positive culture or did not culture convert during their study involvement. Scatter plots comparing time to culture conversion to time from initial vaccine series were created. We calculated spearman correlation coefficients to determine the relationship between time to culture conversion and time from last vaccination for all participants, those who completed the initial vaccine series (unboosted), and those who were boosted. Scatterplot illustrating relationship between time since receiving a booster COVID-19 vaccine dose and time to culture conversion among boosted participants. The vaccine type received has also been designated by plot labels. The black solid line shows the best fit for the Spearman correlation model; Gray shading denotes 95% confidence interval around this estimate. Spearman correlation coefficient, R, and p-value were estimates for the model. Results Of 54 CoViD Post-Vax participants included in this analysis, the mean age was 21 years (SD=2) and culture conversion occurred after a median of 4 days (IQR=3–5.75). There was no association between time to culture conversion and time since last dose of a COVID-19 vaccination (R= -0.13, p= .34). When stratified by vaccination status, there was no association between time to culture conversion and time since initial COVID-19 vaccine series (R= -0.25, p= .21, n=26) or time since COVID-19 booster vaccination (R= -0.24, p= .22, n=28). Conclusion Our results show no significant relationship between time to culture conversion and time since most recent dose of COVID-19 vaccination in an initially culture positive, young, University-based cohort. More work needs to be done to understand the impact of symptom severity, disease burden, SARS-CoV-2 variants, and COVID-19 vaccine status on duration of transmissible SARS-CoV-2 infection. Disclosures Catherine M. Klapperich, Ph.D., BioSens8, LLC: Ownership Interest.

1899. The magnitude and durability of the antibody response to mRNA-based vaccination among SARS-CoV-2 seronegative and seropositive healthcare personnel

Abstract Background Development of robust vaccination guidelines against SARS-CoV-2 requires an understanding of the longitudinal antibody (Ab) response to vaccination and interactions with natural infection. Here, we leveraged an observational cohort study of healthcare personnel (HCP) to study the impact of prior SARS-CoV-2 infection on Ab binding and neutralization after mRNA-based vaccination over a 13 month period. Methods From July 2020 to February 2022, HCP at an academic medical center provided blood samples biweekly for 12 weeks and monthly thereafter. First and second vaccine doses became available in mid-December 2021 and boosters were available starting in October 2021. Individuals were excluded if they did not provide any samples, if baseline serostatus was unknown, and if they received a monoclonal Ab treatment for COVID. ELISA measured total immunoglobulin (Ig) and IgG binding to SARS-CoV-2 RBD. Neutralization was measured by live virus Nanoluc SARS-CoV-2ic assay. Demographics, serostatus, and vaccinations for the total study population and the sub-sample of participants with pre- and post-vaccination antibody measurements. Results Of 213 participants, 192 met inclusion criteria. A majority had detectable IgG levels 8 months after a second dose. Prior to vaccination, median total Ig was higher among seropositive vs. seronegative participants (3.7 vs 1.0, p< 0.001). After a first dose, the median total Ig response was two-fold higher in seropositive compared to seronegative participants (13.8 vs. 7.0, p=0.009). A similar pattern was noted with IgG binding and neutralization. After the second dose, median IgG increased to similar levels in both seropositive and seronegative participants (22.1 vs. 21.2, p=0.8). Neutralization after the second dose was slightly higher in seropositive vs. seronegative participants (log10 3.1 vs. 2.5, p=0.075). Durability of IgG responses after second dose of mRNA-based vaccination against SARS-CoV-2 IgG P/N measurements after 5 days post-V2 for the entire study cohort (incident seropositive: yellow circles, prevalent seropositive (red circles), seronegative (open circles) are shown. The solid lines represent Loess curves for incident and prevalent seropositive participants combined (orange line) and those who were seronegative (grey line). SARS-CoV-2-specific total Ig and IgG subtype responses among healthcare personnel before and after vaccination against SARS-CoV-2 with an mRNA-based vaccine. Total Ig P/N ratios at pre-vaccine, post-V1, post-vaccine 2 (post-V2), and post-booster dose (post-boost) timepoints by serostatus (seronegative: n(-), seropositive: n(+)) are shown in the left panel. For the pre-vaccine time point, the most recent antibody level prior to vaccination (for those who were vaccinated) or most recent antibody level overall (for those who were not vaccinated) is shown. For the post-vaccine time points, the first measurement after 5 days post-vaccination is included. Individuals who were infected with SARS-CoV-2 at any time after the first vaccine dose are shown as open circles with black outlines. The black numbers next to the circles indicate the number of days between vaccination and sample collection for seropositive individuals. SARS-CoV-2 specific IgG P/N ratios respectively at pre-vaccine, post-V1, post-V2, and post-boost timepoints by serostatus (seronegative: n(-), seropositive: n(+)) are shown in the right panel. One individual tested positive for SARS-CoV-2 by PCR shortly after the second vaccine dose (V2); post-V2 results were excluded for this participant. For the pre-vaccine time point, the most recent antibody level prior to vaccination (for those who were vaccinated) or most recent antibody level overall (for those who were not vaccinated) is shown. For the post-vaccine time points, the first measurement after 5 days post-vaccination is included. The dotted line is a P/N ratio of 2.4, the cut-off associated with 99.3% specificity (SARS-CoV-2 IgG-positive above the line, IgG-negative below). Individuals who were infected with SARS-CoV-2 at any time after the first vaccine dose are shown as open circles with black outlines. The black numbers next to the circles indicate the number of days between vaccination and sample collection for seropositive individuals. SARS-CoV-2 D614G live virus neutralization among healthcare personnel by serostatus prior to vaccination. Example neutralization curves are shown in Panel A. Panel B shows the SARS-CoV-2 D614G live virus neutralization titers displayed as EC50 for seropositive (prevalent and incident) individuals and a subset of seronegative individuals. Samples for seronegative individuals were selected by matching on age and time between vaccination and sample collection to the samples from seropositive individuals. Conclusion Antibody responses after SARS-CoV-2 vaccination persist up to 1 year with wide individual variability. Though prior infection was associated with greater Ab responses after a first dose, it did not significantly modify responses after second and third doses. Still, we observed overall slightly higher Ab levels among individuals that had a prior infection before any one of the 3 doses of vaccine. These results suggest that immunity against SARS-CoV-2 prior to vaccination has a role in initial response but does not significantly modify circulating Ab titers after multiple doses of vaccination. Disclosures All Authors: No reported disclosures.

Effects of ultra-high pressure solution treatment on microstructure and mechanical property of Zn-Li alloy

Due to the moderate degradation rate and acceptable biocompatibility, zinc and its alloys have become the promising candidates of the biomedical implant materials. Nonetheless, the poor mechanical properties limit their development and applications. Thus, to promote their mechanical properties, the Zn-xLi alloys were treated with ultra-high pressure solid solution (UHPS). The phase content of as-cast (AC) and UHPS Zn-xLi was calculated, and the solid solution line of Zn-xLi under 5 GPa was established according to the lever law. Obviously, the solid solution line was shifted to the left and the solid solution zone expanded. The UHPS samples showed higher solid solubility and compressive yield strength than the AC samples. The optimal strength for Zn-0.3Li and Zn-0.5Li were 537.4 MPa and 568.5 MPa, respectively. The ultra-high pressure solid solution treatment greatly improved the solid solvent of the Zn-Li alloys, and caused a strong solid solution reinforcement, which is the main reason for the high strength of UHPS samples.

Comparing neuroimaging and cerebrospinal fluid markers of amyloid, tau, and neurodegenerative biomarkers: implications for understanding the biology of the disease

AbstractBackgroundAlzheimer disease (AD) is a complex disorder characterized by changes in amyloid, tau, as well as neurodegeneration. Neuroimaging and cerebrospinal fluid (CSF) assays provide complimentary measures of these pathologies although the Correspondence between such biomarkers is not well elucidated.MethodsData from 313 cognitively unimpaired and 59 impaired individuals aged 45 to 91 was drawn from the Charles F. and Joanne Knight Alzheimer Disease Research Center. Participants had neuroimaging, CSF, and clinical data acquired within one year. Neuroimaging variables included summary measures of amyloid (Centiloids from either PiB or Florebetapir), tau (Flortaucipir), and atrophy (MRI cortical signature). CSF variables were the Aβ42/40 ratio, ptau181, and neurofilament light chain (NfL). Biomarker cutoffs were determined using Gaussian‐Mixture modeling as well as a Youden Index to maximally separate cognitively unimpaired individuals from those with a clinical AD diagnosis. Rank order congruence between biomarkers was determined using Kendall correlations (t).ResultsGaussian Mixture Modeling (dashed lines) and Youden Index (solid lines) approaches produced disparate cutoffs, particularly for neurodegenerative markers (NfL/atrophy) indicating the challenges inherent to binarizing continuous variables (Figure 1). Kendall’s t provide an estimate of pairwise congruence between biomarkers in cognitively unimpaired (CN, CDR=0, upper left diagonal) and impaired individuals (CI, CDR >0, lower right diagonal) (Figure 2). Measures of amyloid had generally high concordance (t ‐0.45 and ‐0.43 for CN and CI respectively ) than those of non‐specific neurodegeneration, which were quite low (t ‐0.16 and ‐0.23). Although ptau181 and tau were moderately related (t 0.21 and 0.23), ptau181 had higher Correspondence with both PET and CSF measures of amyloid. A sequential timing of biomarkers could be clearly seen when plotting z‐scored biomarkers as a function of amyloid PET (Figure 3).ConclusionsNeuroimaging and CSF markers provide complimentary information and help to deeply phenotype the AD biological cascade. While measures of amyloid are highly congruent, non‐specific markers of neurodegeneration have poor agreement., CSF measures of phosphorylated tau likely index a response to amyloidosis rather than being a marker of tau aggregation.

Comparing neuroimaging and cerebrospinal fluid markers of amyloid, tau, and neurodegenerative biomarkers: implications for understanding the biology of the disease

AbstractBackgroundAlzheimer disease (AD) is a complex disorder characterized by changes in amyloid, tau, as well as neurodegeneration. Neuroimaging and cerebrospinal fluid (CSF) assays provide complimentary measures of these pathologies although the Correspondence between such biomarkers is not well elucidated.MethodsData from 313 cognitively unimpaired and 59 impaired individuals aged 45 to 91 was drawn from the Charles F. and Joanne Knight Alzheimer Disease Research Center. Participants had neuroimaging, CSF, and clinical data acquired within one year. Neuroimaging variables included summary measures of amyloid (Centiloids from either PiB or Florebetapir), tau (Flortaucipir), and atrophy (MRI cortical signature). CSF variables were the Aβ42/40 ratio, ptau181, and neurofilament light chain (NfL). Biomarker cutoffs were determined using Gaussian‐Mixture modeling as well as a Youden Index to maximally separate cognitively unimpaired individuals from those with a clinical AD diagnosis. Rank order congruence between biomarkers was determined using Kendall correlations (t).ResultsGaussian Mixture Modeling (dashed lines) and Youden Index (solid lines) approaches produced disparate cutoffs, particularly for neurodegenerative markers (NfL/atrophy) indicating the challenges inherent to binarizing continuous variables (Figure 1). Kendall’s t provide an estimate of pairwise congruence between biomarkers in cognitively unimpaired (CN, CDR=0, upper left diagonal) and impaired individuals (CI, CDR >0, lower right diagonal) (Figure 2). Measures of amyloid had generally high concordance (t ‐0.45 and ‐0.43 for CN and CI respectively ) than those of non‐specific neurodegeneration, which were quite low (t ‐0.16 and ‐0.23). Although ptau181 and tau were moderately related (t 0.21 and 0.23), ptau181 had higher Correspondence with both PET and CSF measures of amyloid. A sequential timing of biomarkers could be clearly seen when plotting z‐scored biomarkers as a function of amyloid PET (Figure 3).ConclusionsNeuroimaging and CSF markers provide complimentary information and help to deeply phenotype the AD biological cascade. While measures of amyloid are highly congruent, non‐specific markers of neurodegeneration have poor agreement., CSF measures of phosphorylated tau likely index a response to amyloidosis rather than being a marker of tau aggregation.