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We examined associations between two forms of testosterone therapy (TT) and risks of seven cancers among men.SEER-Medicare combines cancer registry data from the Surveillance, Epidemiology, and End Results programme with Medicare claims. Our population-based case-control study included incident cancer cases diagnosed between 1992-2015: prostate (n = 130,713), lung (n = 105,466), colorectal (n = 56,433), bladder (n = 38,873), non-Hodgkin lymphoma (n = 17,854), melanoma (n = 14,241), and oesophageal (n = 9116). We selected 100,000 controls from a 5% random sample of Medicare beneficiaries and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI).TT was associated with lower risk of distant-stage prostate cancer (injection/implantation OR = 0.72, 95% CI: 0.60-0.86; topical OR = 0.50, 95% CI: 0.24-1.03). We also observed inverse associations for distant-stage colorectal cancer (injection/implantation OR = 0.75, 95% CI: 0.62-0.90; topical OR = 0.11, 95% CI: 0.05-0.24). Risks of distant-stage colorectal and prostate cancers decreased with time after initiating TT by injection/implantation. By contrast, TT was positively associated with distant-stage melanoma (injection/implantation OR = 1.70, 95% CI: 1.37-2.11). TT was not associated with bladder cancer, oesophageal cancer, lung cancer or non-Hodgkin lymphoma.TT was inversely associated with distant-stage prostate and colorectal cancers but was positively associated with distant-stage melanoma. These observations may suggest an aetiologic role for TT or the presence of residual confounding.

It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear-cell renal cell carcinoma (ccRCC). Here we performed whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identified myeloid-derived IL6 as a key mediator. Furthermore, a novel myeloid gene signature strongly correlated with disease recurrence and overall survival on uni- and multivariate analyses and is linked to TP53 inactivation across multiple data sets. Strikingly, effector T-cell gene signatures, infiltration patterns, and exhaustion markers were not associated with disease recurrence. Targeting immunosuppressive myeloid inflammation with an adenosine A2A receptor antagonist in a novel, immunocompetent, Tp53-inactivated mouse model significantly reduced metastatic development. Our findings suggest that myeloid inflammation promotes disease recurrence in ccRCC and is targetable as well as provide a potential biomarker-based framework for the design of future immuno-oncology trials in ccRCC. Significance: Improved understanding of factors that influence metastatic development in localized ccRCC is greatly needed to aid accurate prediction of disease recurrence, clinical decision-making, and future adjuvant clinical trial design. Our analysis implicates intratumoral myeloid inflammation as a key driver of metastasis in patients and a novel immunocompetent mouse model. This article is highlighted in the In This Issue feature, p. 2221

It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear-cell renal cell carcinoma (ccRCC). Here we performed whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identified myeloid-derived IL6 as a key mediator. Furthermore, a novel myeloid gene signature strongly correlated with disease recurrence and overall survival on uni- and multivariate analyses and is linked to TP53 inactivation across multiple data sets. Strikingly, effector T-cell gene signatures, infiltration patterns, and exhaustion markers were not associated with disease recurrence. Targeting immunosuppressive myeloid inflammation with an adenosine A2A receptor antagonist in a novel, immunocompetent, Tp53-inactivated mouse model significantly reduced metastatic development. Our findings suggest that myeloid inflammation promotes disease recurrence in ccRCC and is targetable as well as provide a potential biomarker-based framework for the design of future immuno-oncology trials in ccRCC.Significance:Improved understanding of factors that influence metastatic development in localized ccRCC is greatly needed to aid accurate prediction of disease recurrence, clinical decision-making, and future adjuvant clinical trial design. Our analysis implicates intratumoral myeloid inflammation as a key driver of metastasis in patients and a novel immunocompetent mouse model.This article is highlighted in the In This Issue feature, p. 2221

Supplementary Figure from A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma

The barbershop is a landmark in the Black community, providing a site for cultural exchange, discussion forums and a point of psychological connection for African American men. Barbershops offer safe spaces for culturally responsive engagement, discourse, and guidance without stigma. Researchers and service providers have utilized Black barbershops for physical health outreach, understanding Black masculinity, exploring intersections of sexuality, and informal mental health support. The Black barbershop offers a nuanced, culturally relevant perspective of African American men, which is valuable to current and future human service providers, educators, and stakeholders in formulating effective interventions and practices with Black men. Utilizing video voice participatory action research (PAR) qualitative methodology, this study explored the experiences of African American (or Black) men using community barbershops as informal mental health care settings. The study explored the experiences of ten (N = 10) African American men, ages 18-75, from either the San Bernardino County or Los Angeles County areas who utilized Black barbershops as informal mental health care settings. The results suggested that African American men were willing to embark on conversations about their mental health within their barbershops, reporting that these experiences yielded them significant psychological, emotional, and social well-being. The authors recommend future collaboration efforts to join with existing informal mental healthcare settings such as Black barbershops to support community-based, culturally relevant healing spaces for African American men.

Background Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk. Methods Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer. Results Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n Conclusion These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.

Overlap syndromes (OS) describe the simultaneous presentation of more than one immune-mediated liver disease in a singular patient, and present unique challenges both in diagnosis and treatment. Here we report a case of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) OS, ultimately treated with Vancomycin. A 30-year-old female with known ulcerative pancolitis (UC) and alcoholic cirrhosis in the setting of AIH presented to the ED with severe abdominal pain, bloody diarrhea, and bilious emesis. Initial labs showed ESR 48 mm/hr, CRP 32.97 mg/L, fecal calprotectin 1131.2 µg/mg, AST 45 IU/L, and total protein 9.1 g/dL. Clostridium Difficile and stool studies were negative. Patient was admitted with concern for acute UC flare. CT scan showed mild worsening of intrahepatic and extrahepatic biliary ductal dilatation suspicious for PSC, and a cirrhotic liver with signs of portal hypertension and splenomegaly (Fig. 1a). Endoscopy revealed multiple non-bleeding duodenal ulcers and grade II esophageal varices. Colonoscopy found moderately active UC Mayo score 2, worsened from prior exam. MRCP was significant for cirrhotic liver morphology with nodular surface contour, and intrahepatic and extrahepatic biliary dilatation with beading and irregularity of the intrahepatic biliary tree and cystic duct, consistent with PSC (Fig. 1b). She was diagnosed with PSC-AIH OS and underwent treatment with Prednisone, Azathioprine, and Ustekinumab with minimal improvement. Only after the addition of Vancomycin was there normalization of biochemical markers and clinical status. Autoimmune liver disease is generally categorized into hepatic (AIH) or cholestatic (PSC and PBC) predominance. PSC is known to be associated with IBD, specifically UC. It is hypothesized that PSC evolves in UC patients due to uptake into the enterohepatic circulation of proinflammatory cells from the colon; these agents typically concentrate in the biliary system where they ultimately cause the biliary ductal damage frequently seen with PSC. By targeting enteric bacteria, Vancomycin decreases the absorption of these inflammatory biliary toxins. For PSC patients with UC and co-occurring AIH, the addition of Vancomycin could significantly reduce mortality and disease burden. Several case reports and one pilot study have investigated Vancomycin’s role in the treatment of PSC. However, it remains a vastly underutilized therapy, and its role specifically in PSC-AIH OS has not been previously reported. There remains an evident need for a large double blind randomized placebo-controlled clinical trial to further support the addition of Vancomycin to the standard treatment regimen for PSC, and to establish clear parameters on effective dosage and length of treatment. In the meantime, clinicians should be aware of the possible use of Vancomycin to treat patients with PSC +/- AIH and IBD. Figure 1a: CT abdomen pelvis with IV contrast highlighting stigmata of cirrhosis with portal hypertension and splenomegaly. Image also shows worsening of intrahepatic and extrahepatic biliary ductal dilatation in the setting of PSC given the patient’s underlying history of ulcerative colitis. Figure 1b: MRCP showing beading and irregularity of the intrahepatic biliary tree and cystic duct, in keeping with known history of primary sclerosing cholangitis. This image also highlights the dilation of the intrahepatic and extrahepatic biliary system.

Technical feasibility and safety of portal vein thrombectomy with suction thrombectomy utilizing a large bore thrombectomy device for portomesenteric venous thrombosis (PMVT) METHODS: After IRB approval, patients undergoing PMVT treatment utilizing a large-bore aspiration thrombectomy device between 07/2019 - 06/2021 were identified at two medical centers. Charts were reviewed for demographic information, imaging findings, and procedural details. PMVT was categorized utilizing the Yerdel grading system. The thrombectomy procedure was performed via transjugular access via the existing TIPS, new TIPS, or trans-splenic or trans-hepatic approach. Technical success was defined by successful clot reduction and restoration of portal venous flow at the conclusion of the procedure. Patient outcomes based on clinical presentation, adverse events, and thrombectomy associated adverse events were recorded.20 patients (Median Age 58 (Range: 23-72) years old) underwent large bore aspiration thrombectomy, which was technically successful in 19/20 (95%) patients. In 9/20 (45%) the 20Fr device was used, 9/20 (45%) for the 16 Fr device and 2/20 (10%) patients, the 24Fr device. 14 patients had a pre-existing TIPS, and 6 patients had a TIPS created. In 5/20 (25 %) patient's overnight lysis was performed in conjunction with Inari thrombectomy. Thrombus resolution with restoration of flow, was achieved in 19/20 (95%) cases. There were no thrombectomy associated adverse events. The mean follow-up time was 70 days (+/- 113) at which time primary patency of the portal venous system was present in 16/20 (80%) patients.Large bore aspiration portal vein thrombectomy is a feasible for portomesenteric venous thrombosis.

We provide a polynomial-time, scalable algorithm for equilibrium computation in multi-agent influence games on networks, extending work of Bindel, Kleinberg, and Oren (2015) from the single-agent to the multi-agent setting. In games of influence, agents have limited advertising budget to influence the initial predisposition of nodes in some network towards their products, but the eventual decisions of the nodes are determined by the stationary state of DeGroot opinion dynamics on the network, which takes over after the seeding (Ahmadinejad et al. 2014, 2015). In multi-agent systems, how should agents spend their budgets to seed the network to maximize their utility in anticipation of other advertising agents and the network dynamics? We show that Nash equilibria of this game are pure and (under weak assumptions) unique, and can be computed in polynomial time; we test our model by computing equilibria using mirror descent for the two-agent case on random graphs.

In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal “SHIELD: Target, Test, and Tell” program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed >1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university.

In the Fall of 2020, many universities saw extensive transmission of SARS-CoV-2 among their populations, threatening the health of students, faculty and staff, the viability of in-person instruction, and the health of surrounding communities.1, 2 Here we report that a multimodal “SHIELD: Target, Test, and Tell” program mitigated the spread of SARS-CoV-2 at a large public university, prevented community transmission, and allowed continuation of in-person classes amidst the pandemic. The program combines epidemiological modelling and surveillance (Target); fast and frequent testing using a novel and FDA Emergency Use Authorized low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD (Test); and digital tools that communicate test results, notify of potential exposures, and promote compliance with public health mandates (Tell). These elements were combined with masks, social distancing, and robust education efforts. In Fall 2020, we performed more than 1,000,000 covidSHIELD tests while keeping classrooms, laboratories, and many other university activities open. Generally, our case positivity rates remained less than 0.5%, we prevented transmission from our students to our faculty and staff, and data indicate that we had no spread in our classrooms or research laboratories. During this fall semester, we had zero COVID-19-related hospitalizations or deaths amongst our university community. We also prevented transmission from our university community to the surrounding Champaign County community. Our experience demonstrates that multimodal transmission mitigation programs can enable university communities to achieve such outcomes until widespread vaccination against COVID-19 is achieved, and provides a roadmap for how future pandemics can be addressed.

The possibility of noncompliant behavior is a challenge for cybersecurity professionals and their auditors as they try to estimate residual control risk. Building on the recently proposed InfoSec Process Action Model (IPAM), this work explores how nontechnical assessments and interventions can indicate and reduce the likelihood of risky individual behavior. The multi-stage approach seeks to bridge the well-known gap between intent and action. In a strong password creation experiment involving 229 participants, IPAM constructs resulted in a marked increase in R2 for initiating compliance behavior with control expectations from 47 percent to 60 percent. Importantly, the model constructs offer measurable indications despite practical limitations on organizations' ability to assess problematic individual password behavior. A threefold increase in one measure of strong password behavior suggested the process positively impacted individual cybersecurity behavior. The results suggest that the process-nuanced IPAM approach is promising both for assessing and impacting security compliance behavior.

To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model.All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30 days, and 6 months post-treatment.Sixty radioembolizations were performed in 54 patients (age 68 ± 9 years, 48-87 years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200 Gy for primary and 80-200 Gy for metastatic liver cancers) was 1.7 GBq (0.3-6.4) compared with 0.6 GBq (0.12-2.1) if BSA had been used (p 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30 days (10%) and 6 months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred.MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200 Gy can be successfully administered without prophylactic embolization in selected patients.•MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

While much of the extant InfoSec research relies on single assessment models that predict intent to act, this article proposes a multi-stage InfoSec Process Action Model (IPAM) that can positively change individual InfoSec behavior. We believe that this model will allow InfoSec researchers to focus more directly on the process that leads to action and develop better interventions that address problematic security behaviors. Building on successful healthcare efforts that resulted in smoking cessation, regular exercise, and a healthier diet, among others, IPAM is a hybrid predictive process approach to behavioral InfoSec improvement. IPAM formulates the motivational antecedents of intent as separate from the volitional drivers of behavior. Singular fear appeals often seen in InfoSec research are replaced by more nuanced treatments appropriately differentiated to support behavioral change as part of a process; phase-appropriate measures of self-efficacy are employed to more precisely assess the likelihood that a participant will act on good intentions; and decisional balance assessment of pro and con perceptions is monitored over time. These notions better align InfoSec research with both leading security practice and successful comparators in healthcare. We believe IPAM can both help InfoSec research models better explain actual behavior and better inform practical security behavior improvement initiatives.

The commercial release of crops with engineered resistance to 2,4-D and dicamba will alter the spatial and temporal use of these herbicides. This, in turn, has elicited concerns about off-target injury to sensitive crops. In 2014 and 2015, studies were conducted in Tifton, GA, to describe how herbicide (2,4-D and dicamba), herbicide rate (1/75 and 1/250 field use), and application timing (20, 40, and 60 DAP) influence watermelon injury, vine development, yield, and the accumulation of herbicide residues in marketable fruit. In general, greater visual injury and reductions in vine growth, relative to the non-treated check, were observed when herbicide applications were made before watermelon plants had begun to flower. Although the main effects of herbicide and rate were less influential than the timing of applications with respect to plant development, the 1/75 rates were more injurious than the 1/250 rates; dicamba was more injurious than 2,4-D. In 2014, the 1/75 and 1/250 rates of each herbicide reduced marketable fruit numbers 13 to 20%, but only for the 20 DAP application. The 1/75 rate of each herbicide when applied at either 20 or 40 DAP reduced the number of fruit harvested per plot in 2015. Dicamba residues were detected in marketable fruit when the 1/75 rate in 2014 and 2015 and the 1/250 rate in 2015 was applied to plants at 40 or 60 DAP. Residues of 2,4-D were detected in 2015 when the 1/75 and 1/250 rates were applied at 60 DAP. Across both years, the maximum level of residue detected was 0.030 ppm. While early season injury may reduce watermelon yields, herbicide residue detection is more likely in marketable fruit when an off-target contact incident occurs closer to harvest.Nomenclature: 2,4-D; dicamba; watermelon; Citrullus lanatus, (Thunb.) Matsum. & Nakai

International audience; The gtsummary package provides an elegant and flexible way to create publication-ready summary tables in R. A critical part of the work of statisticians, data scientists, and analysts is summarizing data sets and regression models in R and publishing or sharing polished summary tables. The gtsummary package was created to streamline these everyday analysis tasks by allowing users to easily create reproducible summaries of data sets, regression models, survey data, and survival data with a simple interface and very little code. The package follows a tidy framework, making it easy to integrate with standard data workflows, and offers many table customization features through function arguments, helper functions, and custom themes.

Lonicera japonica has been shown to have antibacterial, antiviral, and anti-inflammatory properties. Given these properties, varying preparations of L. japonica are being used increasingly as immune enhancers. However, isolated compounds from L. japonica can inhibit lymphocyte functions, which would oppose the ability of L. japonica to serve as an immune enhancer. Prior studies in our laboratory demonstrated that an herbal powder extracted from the leaves of L. japonica inhibits T lymphocyte proliferation and survival. Because both T- and B-cell functions and interactions are required for effective immune responses, the effect of L. japonica on LPS-stimulated B-lymphocyte functions was assessed. Our data demonstrate that while total and IgM+ B cells are not largely diminished as a result of L. japonica treatment, IgM production was decreased, potentially as a consequence of suppressed proliferation.