Mechanistically based blood proteomic markers in the TGF-ß pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-ß pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-ß family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-ß based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.

Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection.

Herein, we review established clinical use cases for SARS-CoV-2 antibody measures, which include diagnosis of recent prior infection, isolating high titer convalescent plasma, diagnosing multisystem inflammatory syndrome in children (MIS-C), and booster dosing in the immunosuppressed and other populations. We then address whether an antibody correlate of protection (CoP) for SARS-CoV-2 has been successfully defined with the following considerations: Antibody responses in the immunocompetent, vaccine type, variants, use of binding antibody tests vs. neutralization tests, and endpoint measures. In the transition from the COVID-19 pandemic to endemic, there has been much interest in defining an antibody CoP. Due to the high mutability of respiratory viruses and our current knowledge of SARS-CoV-2 variants defining a CoP for prevention of infection is unrealistic. However, a CoP may be defined for prevention of severe disease requiring hospitalization and/or death. Most SARS-CoV-2 CoP research has focused on neutralization measurements. However, there can be significant differences in neutralization test methods, and disparate responses to new variants depending on format. Furthermore, neutralization assays are often impractical for high throughput applications (e.g., assessing humoral immune response in populations or large cohorts). Nevertheless, CoP studies using neutralization measures are reviewed to determine where there is consensus. Alternatively, binding antibody tests could be used to define a CoP. Binding antibody assays tend to be highly automatable, high throughput, and therefore practical for large population applications. Again, we review studies for consensus on binding antibody responses to vaccines, focusing on standardized results. Binding antibodies directed against the S1 receptor binding domain (S1-RBD) of the viral spike protein can provide a practical, indirect measure of neutralization. Initially, a response for S1-RBD antibodies may be selected that reflects the peak response in immunocompetent populations and may serve as a target for booster dosing in the immunocompromised. From existing studies reporting peak S1-RBD responses in standardized units, an approximate range of 1372-2744 BAU/mL for mRNA and recombinant protein vaccines was extracted that could serve as an initial CoP target. This target would need to be confirmed and potentially adjusted for updated vaccines, and almost certainly for other vaccine formats (i.e., viral vector). Alternatively, a threshold or response could be defined based on outcomes over time (i.e., prevention of severe disease). We also discuss the precedent for clinical measurement of antibodies for vaccine-preventable diseases (e.g., hepatitis B). Lastly, cellular immunity is briefly addressed for its importance in the nature and durability of protection.

Automated Segmentation and Morphological Characterization of Hepatic Steatosis and Correlation with Histopathology.

Background/objectives: Prevalence of nonalcoholic fatty liver disease (NAFLD) has increased to 25% of the world population. Hepatic steatosis is a hallmark feature of NAFLD and is assessed histologically using visual and ordinal fat grading criteria (0-3) from the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) scoring system. The purpose of this study is to automatically segment and extract morphological characteristics and distributions of fat droplets (FDs) on liver histology images and find associations with severity of steatosis. Methods: A previously published human cohort of 68 NASH candidates was graded for steatosis by an experienced pathologist using the Fat CRN grading system. The automated segmentation algorithm quantified fat fraction (FF) and fat-affected hepatocyte ratio (FHR), extracted fat morphology by calculating radius and circularity of FDs, and examined FDs distribution and heterogeneity using nearest neighbor distance and regional isotropy. Results: Regression analysis and Spearman correlation (ρ) yielded high correlations for radius (R2 = 0.86, ρ = 0.72), nearest neighbor distance (R2 = 0.82, ρ = -0.82), regional isotropy (R2 = 0.84, ρ = 0.74), and FHR (R2 = 0.90, ρ = 0.85), and low correlation for circularity (R2 = 0.48, ρ = -0.32) with FF and pathologist grades, respectively. FHR showed a better distinction between pathologist Fat CRN grades compared to conventional FF measurements, making it a potential surrogate measure for Fat CRN scores. Our results showed variation in distribution of morphological features and steatosis heterogeneity within the same patient's biopsy sample as well as between patients of similar FF. Conclusions: The fat percentage measurements, specific morphological characteristics, and patterns of distribution quantified with the automated segmentation algorithm showed associations with steatosis severity; however, future studies are warranted to evaluate the clinical significance of these steatosis features in progression of NAFLD and NASH.

Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection.

Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.

Strong Job Market for Pathologists: Results From the 2021 College of American Pathologists Practice Leader Survey.

CONTEXT.­: There has long been debate about whether and when there may be a shortage of pathologists in the United States. One way to assess this is to survey the hiring experiences of pathology practices. A 2018 survey revealed a strong demand for pathologists, with expectations of continued strength. This study updates that prior analysis using data from a 2021 survey of pathology practice leaders. OBJECTIVE.­: To assess the US pathologist job market and examine implications. DESIGN.­: We analyzed data from the 2021 College of American Pathologists Practice Leader Survey. This survey queried practice leaders, including regarding the hiring of pathologists, the level of experience being sought, success in filling positions, and expectations for hiring in the next 3 years. RESULTS.­: Among the 375 surveyed practice leaders (about one-third of all US pathology practices), 282 provided information about pathologist hiring in 2021. A total of 157 of these 282 practices (55.7%) sought to hire at least 1 pathologist in 2021, up from 116 of 256 practices (45.3%) in 2017; the mean number of pathologists hired per practice also increased. In 2021, a total of 175 of 385 positions (45.5%) were to fill new positions, compared with 95 of 249 positions (38.2%) in 2017. Most practice leaders were comfortable hiring pathologists with less than 2 years of posttraining experience. Practice leaders anticipated continued strong demand for hiring pathologists during the next 3 years. CONCLUSIONS.­: Our analysis confirms that the demand in pathologist hiring is strong and much increased from 2017. We believe, in combination with other job market indicators, that demand may outstrip the supply of pathologists, which is limited by the number of trainees and has remained constant during the past 20 years.

Occurrence of Thromboembolic Events and Mortality Among Hospitalized Coronavirus 2019 Patients: Large Observational Cohort Study of Electronic Health Records.

Background Most symptoms of coronavirus 2019 (COVID-19) are mild; however, some patients experience cardiovascular complications, including thromboembolic events and death. Data are needed to better inform prevention and treatment of these events. This analysis was designed to describe patient characteristics, medication use, thromboembolic events, and all-cause mortality in hospitalized COVID-19 patients in the United States. Methods This retrospective, observational cohort study identified adults hospitalized with COVID-19 (January 21, 2020-January 07, 2021) in the deidentified Optum COVID-19 Electronic Health Records dataset. Thromboembolic events and all-cause mortality were collected at any time during the variable follow-up period (up to 50 weeks). Results Of 181,995 COVID-19 patients who met eligibility criteria, 40,524 (22.3%) were hospitalized with COVID-19. Hospitalized patients had a mean age of 63 years and a Quan-Charlson comorbidity index of 1.3. Anticoagulants were used in 89.2% of patients during hospitalization and in 18.7% of postdischarge patients. Of hospitalized patients, 17.6% had a thromboembolic event during the entire follow-up period (mean time to the first event of 15 days), of whom 13.4% had an event during hospitalization; of discharged patients, 4.3% had a thromboembolic event (mean time from discharge to event of 43 days). Death during the follow-up period was reported in 15.0% of patients. Conclusions In this large, observational cohort study, patients hospitalized with COVID-19 had high rates of thromboembolic events during hospitalization and in the postdischarge period; mortality was also high in this population. Anticoagulant use was common during hospitalization. These findings support further studies to optimize in-hospital and extended prophylaxis for hospitalized COVID-19 patients.

Pathogenesis to management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer whose incidence continues to rise in many parts of the world due to a concomitant rise in many associated risk factors, such as alcohol use and obesity. Although early-stage HCC can be potentially curable through liver resection, liver-directed therapies, or transplantation, patients usually present with intermediate to advanced disease, which continues to be associated with a poor prognosis. This is because HCC is a cancer with significant complexities, including substantial clinical, histopathologic, and genomic heterogeneity. However, the scientific community has made a major effort to better characterize HCC in those aspects via utilizing tissue sampling and histological classification, whole genome sequencing, and developing viable animal models. These efforts ultimately aim to develop clinically relevant biomarkers and discover molecular targets for new therapies. For example, until recently, there was only one approved systemic therapy for advanced or metastatic HCC in the form of sorafenib. Through these efforts, several additional targeted therapies have gained approval in the United States, although much progress remains to be desired. This review will focus on the link between characterizing the pathogenesis of HCC with current and future HCC management.

Real-World Analysis of Thromboembolic Events and Mortality of COVID-19 Outpatients in the United States.

Limited data are available on thromboembolic events (TEEs) and mortality in outpatients with coronavirus disease 2019 (COVID-19). This retrospective, observational cohort study identified non-hospitalized COVID-19 outpatients (01/21/2020-01/07/2021) using de-identified Optum® COVID-19 Electronic Health Records data. Patient characteristics, occurrence of TEEs, all-cause mortality, and anticoagulant or thrombolytic medication use were evaluated. Of 1,246,067 patients with COVID-19 diagnosis, 141 471 met entry criteria. Mean (standard deviation [SD]) age was 46.1 (17.2) years, 56.8% were female, 72.9% Caucasian, 11.2% African American, and 11.1% Hispanic. Comorbidity burden was low (mean [SD] Quan-Charlson comorbidity index score of 0.43 [1.10]); however, of those with body mass index data, half were obese. During the follow-up period, a TEE occurred in 1.4%, with the proportion of patients with ischemic stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism being similar (approximately 0.4% each). All-cause mortality was 0.7%. Medications included corticosteroids (13.7%), anticoagulants (4.9%), and antiplatelets (2.9%). Overall, in this large cohort analysis, certain demographic and clinical characteristics of patients who experienced TEEs were identified and may help guide management decisions and future clinical trials for COVID-19 outpatients.

Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies.

Background: Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies. Methods: In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders). Results: Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes. Conclusions: In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.

Impaired reciprocal regulation between SIRT6 and TGF-ß signaling in fatty liver.

Dysregulated transforming growth factor-beta (TGF-ß) signaling contributes to fibrotic liver disease and hepatocellular cancer (HCC), both of which are associated with fatty liver disease. SIRT6 limits fibrosis by inhibiting TGF-ß signaling through deacetylating SMAD2 and SMAD3 and limits lipogenesis by inhibiting SREBP1 and SREBP2 activity. Here, we showed that, compared to wild-type mice, high-fat diet-induced fatty liver is worse in TGF-ß signaling-deficient mice (SPTBN1+/- ) and the mutant mice had reduced SIRT6 abundance in the liver. Therefore, we hypothesized that altered reciprocal regulation between TGF-ß signaling and SIRT6 contributes to these liver pathologies. We found that deficiency in SMAD3 or SPTBN1 reduced SIRT6 mRNA and protein abundance and impaired TGF-ß induction of SIRT6 transcripts, and that SMAD3 bound to the SIRT6 promoter, suggesting that an SMAD3-SPTBN1 pathway mediated the induction of SIRT6 in response to TGF-ß. Overexpression of SIRT6 in HCC cells reduced the expression of TGF-ß-induced genes, consistent with the suppressive role of SIRT6 on TGF-ß signaling. Manipulation of SIRT6 abundance in HCC cells altered sterol regulatory element-binding protein (SREBP) activity and overexpression of SIRT6 reduced the amount of acetylated SPTBN1 and the abundance of both SMAD3 and SPTBN1. Furthermore, induction of SREBP target genes in response to SIRT6 overexpression was impaired in SPTBN1 heterozygous cells. Thus, we identified a regulatory loop between SIRT6 and SPTBN1 that represents a potential mechanism for susceptibility to fatty liver in the presence of dysfunctional TGF-ß signaling.

In utero exposure to maternal anti-aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring.

The fetal brain is constantly exposed to maternal IgG before the formation of an effective blood-brain barrier (BBB). Here, we studied the consequences of fetal brain exposure to an antibody to the astrocytic protein aquaporin-4 (AQP4-IgG) in mice. AQP4-IgG was cloned from a patient with neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that can affect women of childbearing age. We found that embryonic radial glia cells in neocortex express AQP4. These cells are critical for blood vessel and BBB formation through modulation of the WNT signaling pathway. Male fetuses exposed to AQP4-IgG had abnormal cortical vasculature and lower expression of WNT signaling molecules Wnt5a and Wnt7a. Positron emission tomography of adult male mice exposed in utero to AQP4-IgG revealed increased blood flow and BBB leakiness in the entorhinal cortex. Adult male mice exposed in utero to AQP4-IgG had abnormal cortical vessels, fewer dendritic spines in pyramidal and stellate neurons, and more S100ß+ astrocytes in the entorhinal cortex. Behaviorally, they showed impairments in the object-place memory task. Neural recordings indicated that their grid cell system, within the medial entorhinal cortex, did not map the local environment appropriately. Collectively, these data implicate in utero binding of AQP4-IgG to radial glia cells as a mechanism for alterations of the developing male brain and adds NMOSD to the conditions in which maternal IgG may cause persistent brain dysfunction in offspring.

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

Background: In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies." SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. Methods: To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. SARS-CoV-2 serology standard reference material and First WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. Results: SeroNet institutions reported development of a total of 27 ELISA methods, 13 multiplex assays, 9 neutralization assays, and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. Conclusions: SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 virus and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons.

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.

Generating Discretionary Income in an Academic Department of Pathology.

The 2021 Association of Pathology Chairs Annual Meeting included a chairs' session and a premeeting discussion-group webinar sponsored by the Senior Fellows Group (former chairs of academic departments of pathology who have remained active in the Association of Pathology Chairs) focused on generating discretionary income for departments. Discretionary income was defined as revenue that can be used by the department with few, if any, restrictions. Such income is particularly desirable given limitations on departmental budgets. Four discussion-group panelists presented the funds-flow model in their respective institutions and how they derived and used discretionary income. Discretionary income was obtained from both external sources (eg, philanthropy, indirect cost recovery, partnerships with outside entities, medical education courses, research laboratory agreements, clinical trials) and internal sources (eg, core facilities, institutional programmatic support, institutional incentive programs). Significant departmental variations were associated with differences in institutional financial structure and policies, revenue-generating capabilities of the department and individual faculty, practice plan policies, donor intentions, and geographic market forces. Most finances were dependent upon a robust funds-flow model. Uses of discretionary funds included salary support, recruitment expenses (including start-up packages), research equipment, space renovation, social events, support of academic programs, and travel. Panelists also discussed particular challenges of discretionary-fund generation and use during the coronavirus disease 2019 pandemic. Notably, each institution had its own unique methodology for generating discretionary income, and no obvious standard approach was identified. The 2 moderators emphasized the importance of identifying and understanding opportunities, issues, and institutional culture surrounding generation and use of discretionary funds.

The New York State SARS-CoV-2 Testing Consortium: Regional Communication in Response to the COVID-19 Pandemic.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.

Evidence-Based Alignment of Pathology Residency With Practice II: Findings and Implications.

This article presents findings from a 4-year series of surveys of new-in-practice pathologists, and a survey of physician employers of new pathologists, assessing how pathology graduate medical education prepares its graduates for practice. Using the methodology described in our previous study, we develop evidence for the importance of residency training for various practice areas, comparing findings over different practice settings, sizes, and lengths of time in practice. The principal findings are (1) while new-in-practice pathologists and their employers report residency generally prepared them well for practice, some areas-billing and coding, laboratory management, molecular pathology, and pathology informatics-consistently were identified as being important in practice but inadequately prepared for in residency; (2) other areas-autopsy pathology, and subspecialized apheresis and blood donor center blood banking services-consistently were identified as relatively unimportant in practice and excessively prepared for in residency; (3) the notion of a single comprehensive model for categorical training in residency is challenged by the disparity between broad general practice in some settings and narrower subspecialty practice in others; and (4) the need for preparation in some areas evolves during practice, raising questions about the appropriate mode and circumstance for training in these areas. The implications of these findings range from rebalancing the emphasis among practice areas in residency, to reconsidering the structure of graduate medical education in pathology to meet present and evolving future practice needs.

Plasma-Induced Catalytic Conversion of Nitrogen and Hydrogen to Ammonia over Zeolitic Imidazolate Frameworks ZIF-8 and ZIF-67.

Microporous crystals have emerged as highly appealing catalytic materials for the plasma catalytic synthesis of ammonia. Herein, we demonstrate that zeolitic imidazolate frameworks (ZIFs) can be employed as efficient catalysts for the cold plasma ammonia synthesis using an atmospheric dielectric barrier discharge reactor. We studied two prototypical ZIFs denoted as ZIF-8 and ZIF-67, with a uniform window pore aperture of 3.4 Å. The resultant ZIFs displayed ammonia synthesis rates as high as 42.16 µmol NH3/min gcat. ZIF-8 displayed remarkable stability upon recycling. The dipole-dipole interactions between the polar ammonia molecules and the polar walls of the studied ZIFs led to relatively low ammonia uptakes, low storage capacity, and high observed ammonia synthesis rates. Both ZIFs outperform other microporous crystals including zeolites and conventional oxides in terms of ammonia production. Furthermore, we demonstrate that the addition of argon to the reactor chamber can be an effective strategy to improve the plasma environment. Specifically, the presence of argon helped to improve the plasma uniformity, making the reaction system more energy efficient by operating at a low specific energy input range allowing abundant formation of nitrogen vibrational species.