Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Correlates of Recent HIV Testing Among People Who Inject Drugs in Rural Areas: A Multi-site Cross-Sectional Study, 2018-2020.

The Rural Opioid Initiative surveyed 2693 people who inject drugs (PWID) in eight rural U.S. areas in 2018-2020 about self-reported HIV testing in the past 6 months. Correlates of interest included receipt of any drug-related services, incarceration history, and structural barriers to care (e.g., lack of insurance, proximity to syringe service programs [SSP]). Overall, 20% of participants reported receiving an HIV test within the past 6 months. Multivariable generalized estimating equations showed that attending substance use disorder (SUD) treatment (OR 2.11, 95%CI [1.58, 2.82]), having health insurance (OR 1.42, 95%CI [1.01, 2.00]) and recent incarceration (OR 1.49, 95%CI [1.08, 2.04]) were positively associated with HIV testing, while experiencing a resource barrier to healthcare (inability to pay, lack of transportation, inconvenient hours, or lack of child care) had inverse (OR 0.73, 95%CI [0.56, 0.94]) association with HIV testing. We found that the prevalence of HIV testing among rural PWID is low, indicating an unmet need for testing. While SUD treatment or incarceration may increase chances for HIV testing for rural PWID, other avenues for expanding HIV testing, such as SSP, need to be explored.

Hidden flaws in e-cigarette industry-funded studies.

Electronic cigarette (e-cigarette) use has increased since e-cigarettes were introduced to the market nearly 20 years ago. Researchers continue to conduct studies to understand the health risks and benefits of e-cigarettes to inform health education and promotion efforts as well as public policy. Studies funded by the tobacco industry examining the potential risks and benefits of e-cigarettes have also been conducted and are sometimes published in the scientific literature. Frequently, tobacco and e-cigarette industry-funded researchers report findings that contradict research funded by other sources. While many industry-funded studies may appear methodologically sound at first glance, in some cases, industry-funded studies include methodological flaws that result in misleading conclusions. The tobacco industry's use of biased research to influence tobacco-related policy decisions in the past is well-documented. This commentary provides specific examples of recent e-cigarette research funded by the tobacco/e-cigarette industry in which methodological flaws result in misleading conclusions that support industry goals. Given the long history of biased research conducted by the tobacco industry, there is a need to assess whether research funded by the e-cigarette industry similarly contains methodological flaws. We emphasise the need for tobacco and e-cigarette-funded research to be scrutinised by non-industry-funded subject matter experts and call for journals to not consider manuscripts that have received support from the tobacco or e-cigarette industry.

Beet Soil-Borne Virus Is a Helper Virus for the Novel Beta vulgaris Satellite Virus 1A.

Sugar beet (Beta vulgaris) is grown in temperate regions around the world as a source of sucrose used for natural sweetening. Sugar beet is susceptible to a number of viral diseases, but identification of the causal agent(s) under field conditions is often difficult due to mixtures of viruses that may be responsible for disease symptoms. In this study, the application of RNAseq to RNA extracted from diseased sugar beet roots obtained from the field and from greenhouse-reared plants grown in soil infested with the virus disease rhizomania (causal agent beet necrotic yellow vein virus; BNYVV) yielded genome-length sequences from BNYVV, as well as beet soil-borne virus (BSBV). The nucleotide identities of the derived consensus sequence of BSBV RNAs ranged from 99.4 to 96.7% (RNA1), 99.3 to 95.3% (RNA2), and 98.3 to 95.9% (RNA3) compared with published BSBV sequences. Based on the BSBV genome consensus sequence, clones of the genomic RNAs 1, 2, and 3 were obtained to produce RNA copies of the genome through in vitro transcription. Capped RNA produced from the clones was infectious when inoculated into leaves of Chenopodium quinoa and B. vulgaris, and extracts from transcript-infected C. quinoa leaves could infect sugar beet seedling roots through a vortex inoculation method. Subsequent exposure of these infected sugar beet seedling roots to aviruliferous Polymyxa betae, the protist vector of both BNYVV and BSBV, confirmed that BSBV derived from the infectious clones could be transmitted by the vector. Co-inoculation of BSBV synthetic transcripts with transcripts of a cloned putative satellite virus designated Beta vulgaris satellite virus 1A (BvSat1A) resulted in the production of lesions on leaves of C. quinoa similar to those produced by inoculation with BSBV alone. Nevertheless, accumulation of genomic RNA and the encoded protein of the satellite virus in co-inoculated leaves was readily detected on Northern and Western blots, respectively, whereas no accumulation of satellite virus products occurred when satellite virus RNA was inoculated alone. The predicted sequence of the detected protein encoded by BvSat1A bears hallmarks of coat proteins of other satellite viruses, and virions of a size consistent with a satellite virus were observed in samples testing positive for the virus. The results demonstrate that BSBV is a helper virus for the novel satellite virus BvSat1A.

Alcohol to-go sales policies at on-premise drinking establishments near large public US universities during the COVID-19 pandemic.

AIMS: Sweeping policy changes during the COVID-19 pandemic increased alcohol availability through permitted to-go sales, potentially posing unique risks to college students. While to-go sales may make binge drinking more convenient, little remains known about these practices. Therefore, this study aimed to assess whether drinking establishments' to-go sales practices are associated with their other operational practices and state policy. METHOD: This cross-sectional analysis included 221 randomly selected bars, nightclubs, and restaurants within two miles of a large public university. Telephone interviews assessed establishment practices, and the Alcohol Policy Information System provided state alcohol to-go laws. Regression models tested whether establishment to-go sales practices were associated with their business practices (logistic regression) and state policy (generalized estimating equations). RESULTS: Nearly one-half (44.8%) of drinking establishments sold alcohol to-go. Establishments with higher vodka prices had nearly 30% higher odds of selling spirits to-go (aOR = 1.29) and establishments offering happy hours specials had more than twice the odds of selling beer (aOR = 2.22), wine (aOR = 2.53), and spirits to-go (aOR = 2.60). Additionally, establishments that implemented physical distance requirements had higher odds of selling wine to-go (aOR = 3.00). State to-go laws were associated with higher odds of selling wine (aOR = 3.99) and spirits to-go (aOR = 5.43) in the full sample and beer to-go (aOR = 4.92) in urban counties. CONCLUSIONS: Establishments that sell alcohol to-go tend to engage in other practices designed to drive sales. Evaluations of alcohol to-go sales laws on risky consumption among priority populations, including college students, are urgently needed to inform decisions about how to appropriately regulate sales.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

Clinical Trial Design Principles and Outcomes Definitions for Device-Based Therapies for Hypertension: A Consensus Document From the Hypertension Academic Research Consortium.

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Device Therapy of Hypertension.

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.

Selecting patients for interventional procedures to treat hypertension.

Purpose: Interventional approaches to treat hypertension are an emerging option that may be suitable for patients whose BP control cannot be achieved with lifestyle and/or pharmacotherapy and possibly for those who do not wish to take drug therapy.Materials and Methods: Interventional strategies include renal denervation with radiofrequency, ultrasound and alcohol-mediated platforms as well as baroreflex activation therapy and cardiac neuromodulation therapy. Presently renal denervation is the most advanced of the therapeutic options and is currently being commercialised in the EU.Results: It is apparent that RDN is effective in both unmedicated patients and patients with more severe hypertension including those with resistant hypertension.Conclusion: However, at present there is no evidence for the use of RDN in patients with secondary forms of hypertension and thus evaluation to rule these out is necessary before proceeding with a procedure. Furthermore, there are numerous pitfalls in the diagnosis and management of secondary hypertension which need to be taken into consideration. Finally, prior to performing an intervention it is appropriate to document presence/absence of hypertension-mediated organ damage.

RDN has emerged as a safe and effective approach to treat hypertension with BP lowering efficacy equivalent to antihypertensive monotherapy albeit with guaranteed 'adherence'Presently populations most likely to respond to RDN are not clearly defined but given the costs of the procedure it is likely to be initially made available to those with resistant hypertension and those at highest cardiovascular riskThere is no evidence to support the use of RDN in patients with secondary forms of hypertension and thus this should be thoroughly screened for prior to offering the procedure, especially in the setting of resistant hypertensionOptimisation of lifestyle and drug therapy is key to good hypertension management and should be undertaken prior to an invasive procedure such as RDN being offeredThere are numerous pitfalls in the screening process for secondary hypertension which means that hypertension specialists should be involved in this component of the pathwayRDN can be offered by interventional radiologist, interventional cardiologists or angiologists who have had appropriate trainingClinical pathways for RDN must ultimately involve a multidisciplinary team overview with hypertension specialists, interventionists and imaging specialists combining efforts to ensure appropriate patient selection. This without question must involve patients in the decision-making process.

The Impact of Temporary Assistance for Needy Families Benefit Requirements and Sanctions on Maternal Material Hardship, Mental Health, and Parental Aggravation.

INTRODUCTION: Temporary Assistance for Needy Families requirements can be stress-inducing, difficult for families to complete, and may be detrimental during early life. We assessed the impact of TANF requirements on primary caregiving mothers' experiences of material hardship, anxiety, depression, and parental aggravation in the first year of a child's life. METHODS: Survey responses were selected from mothers in the Future of Families and Childhood Wellbeing Study, who received TANF in the first year of their child's life (N = 1085). RESULTS: Survey-weighted regression models showed associations between: presence of any requirements and increased material hardship, work requirements and increased material hardship, requirement to name the father of their child and increased depression, benefit cuts and increased parental aggravation, and benefit cuts and increased material hardship. DISCUSSION: Federal and state policies should revise requirement programs to increase program accessibility and support the mental health and financial stability of mothers applying for TANF to facilitate sustainable movement into employment.

#Delta8: a retailer-driven increase in Delta-8 THC discussions on Twitter from 2020 to 2021.

Background: Delta-8 tetrahydrocannabinol (THC) has experienced significant cultivation, use, and online marketing growth in recent years.Objectives: This study utilized natural language processing on Twitter data to examine trends in public discussions regarding this novel psychoactive substance.Methods: This study analyzed the frequency of #Delta8 tweets over time, most commonly used words, sentiment classification of words in tweets, and a qualitative analysis of a random sample of tweets containing the hashtag "Delta8" from January 1, 2020 to September 26, 2021.Results: A total of 41,828 tweets were collected, with 30,826 unique tweets (73.7%) and 11,002 quotes, retweets, or replies (26.3%). Tweet activity increased from 2020 to 2021, with daily original tweets rising from 8.55 to 149. This increase followed a high-engagement retailer promotion in June 2021. Commonly used terms included "cbd," "cannabis," "edibles," and "cbdoil." Sentiment classification revealed a predominance of "positive" (30.93%) and "trust" (14.26%) categorizations, with 8.42% classified as "negative." Qualitative analysis identified 20 codes, encompassing substance type, retailers, links, and other characteristics.Conclusion: Twitter discussions on Delta-8 THC exhibited a sustained increase in prevalence from 2020 to 2022, with online retailers playing a dominant role. The content also demonstrated significant overlap with cannabidiol and various cannabis products. Given the growing presence of retailer marketing and sales on social media, it is crucial for public health researchers to monitor and promote relevant Delta-8 health recommendations on these platforms to ensure a balanced conversation.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Fungal social influencers: secondary metabolites as a platform for shaping the plant-associated community.

Fungal secondary metabolites (FSMs) are capable of manipulating plant community dynamics by inhibiting or facilitating the establishment of co-habitating organisms. Although production of FSMs is not crucial for survival of the producer, their absence can indirectly impair growth and/or niche competition of these fungi on the plant. The presence of FSMs with no obvious consequence on the fitness of the producer leaves questions regarding ecological impact. This review investigates how fungi employ FSMs as a platform to mediate fungal-fungal, fungal-bacterial and fungal-animal interactions associated with the plant community. We discuss how the biological function of FSMs may indirectly benefit the producer by altering the dynamics of surrounding organisms. We introduce several instances where FSMs influence antagonistic- or alliance-driven interactions. Part of our aim is to decipher the meaning of the FSM 'language' as it is widely noted to impact the surrounding community. Here, we highlight the contribution of FSMs to plant-associated interaction networks that affect the host either broadly or in ways that may have previously been unclear.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.

Development of a semi-automated method for tumour budding assessment in colorectal cancer and comparison with manual methods.

AIMS: Tumour budding (TB) is an established prognostic feature in multiple cancers but is not routinely assessed in pathology practice. Efforts to standardise and automate assessment have shifted from haematoxylin and eosin (H&E)-stained images towards cytokeratin immunohistochemistry. The aim of this study was to compare manual H&E and cytokeratin assessment methods with a semi-automated approach built within QuPath open-source software. METHODS AND RESULTS: TB was assessed in cores from the advancing tumour edge in a cohort of stage II/III colon cancers (n = 186). The total numbers of buds detected with each method were as follows: manual H&E, n = 503; manual cytokeratin, n = 2290; and semi-automated, n = 5138. More than four times the number of buds were identified manually with cytokeratin assessment than with H&E assessment. One thousand seven hundred and thirty-four individual buds were identified with both manual and semi-automated assessments applied to cytokeratin images, representing 75.7% of the buds identified manually (n = 2290) and 33.7% of the buds detected with the semi-automated method (n = 5138). Higher semi-automated TB scores were due to any discrete area of cytokeratin immunopositivity within an accepted area range being identified as a bud, regardless of shape or crispness of definition, and to the inclusion of tumour cell clusters within glandular lumina ('luminal pseudobuds'). Although absolute numbers differed, semi-automated and manual bud counts were strongly correlated across cores (ρ = 0.81, P < 0.0001). All methods of TB assessment demonstrated poorer survival associated with higher TB scores. CONCLUSIONS: We present a new QuPath-based approach to TB assessment, which compares favourably with established methods and offers a freely available, rapid and transparent tool that is also applicable to whole slide images.

Popularity of Delta-8 THC on the Internet Across US States, 2021.

Objectives. To assess the popularity of an emergent drug, delta-8 tetrahydrocannabinol (THC), and compare interest levels between US states with or without legalized recreational cannabis. Methods. We used Google Trends to assess the growth of interest among delta-8 THC-related search terms from May 17, 2020, to May 9, 2021. We examined differences between states with or without legalized cannabis using state-level Google Trends data from February 13 to May 13, 2021, and policy data from the National Conference of State Legislatures. Results. Interest in delta-8 THC increased starting in mid-June 2020, with search volumes for delta-8 THC queries currently at 35% of the "marijuana" query. States where recreational cannabis is illegal had higher relative queries than did states with legalized recreational cannabis (52.3 vs 14.8; t = 40.9; P < .001). Conclusions. There has been rapid growth in interest in delta-8 THC. Findings between state policy contexts likely indicate delta-8 THC's role as a substitute good for delta-9 THC. Public Health Implications. Digital signals such as search volumes may point to an emergent use trend in the substance delta-8 THC. Further studies are needed to assess potential harms and correlates of delta-8 THC use. (Am J Public Health. 2022;112(2):296-299. https://doi.org/10.2105/AJPH.2021.306586).

Predictors of Discussing Lung Cancer Screening with a Health Care Provider Among Current and Former Smokers in HINTS: A Secondary Data Analysis.

INTRODUCTION: Lung cancer screening is greatly underutilized among those who may benefit from early detection. METHODS: We analysed data from a subsample (n = 929) of the 2020 Health Information National Trends Survey. We tested multivariable logistic regression models of associations of cancer worry, information insufficiency, and perceived information gathering capacity with reports of having discussed lung cancer screening with a health care provider. RESULTS: Among former smokers, no factors were associated significantly with lung cancer screening information seeking. However, for current smokers, extreme cancer worry was positively and significantly associated with having discussed lung cancer screening with a health care provider (OR: 12.95; 95% CI: 2.11, 79.39). CONCLUSION: To increase uptake of lung cancer screening, public health campaigns and healthcare providers will face the dual challenge of increasing perceived need for screening among former smokers while directing current smokers with high levels of worry to see the benefits of early detection.

A national assessment of on-premise drinking establishments near public universities: Drink prices, drink specials, indoor tobacco use, and state-level alcohol laws.

BACKGROUND: Inexpensive drinks and price promotions increase alcohol consumption and have been observed at on-premise drinking establishments near large colleges. Some bars may sell tobacco products and allow indoor tobacco use to encourage patrons to stay and drink more. This study examined drink prices/specials and associated practices of on-premise drinking establishments including tobacco sales and policies regarding tobacco use. METHODS: In 2018, telephone calls about prices/practices were made to 403 randomly selected bars/nightclubs within 2 miles of large residential universities in each U.S. state. The Alcohol Policy Information System provided data on state-level alcohol laws. Multivariable linear and logistic regression models examined associations between alcohol prices/specials, state laws, and establishment practices. RESULTS: The average price for the least expensive draft beer and a vodka shot at each location were $3.62 (SD = $1.15) and $4.77 (SD = $1.16), respectively. Most establishments (65%) had happy hour specials, 6% had 2-for-1 specials, 91% sold food, 9% sold cigarettes, 8% allowed smoking indoors, and 18% permitted electronic cigarette (e-cigarette) use indoors. Allowing e-cigarette use indoors (b = -0.54) and selling cigarettes (b = -0.79) were associated with lower vodka prices; allowing cigarette smoking indoors (b = -0.46) was associated with lower beer prices. Lower beer prices (OR = 1.38), selling food (OR = 2.97), and no state law banning happy hour specials altogether (OR = 4.24) or with full-day price reduction exemptions (OR = 12.74) were associated with higher odds of having happy hour specials. Allowing e-cigarette use indoors was associated with having 2-for-1 specials (OR = 6.38). CONCLUSION: In bars near large public universities, beers and shots were often available for less than $5 and drink specials were prevalent. Further, some establishments allowed tobacco use indoors and/or sold cigarettes. Laws that increase alcohol taxes, set minimum drink prices, and ban the sale and indoor use of tobacco products at on-premise drinking locations are important harm reduction tools.

Seedborne Cercospora beticola Can Initiate Cercospora Leaf Spot from Sugar Beet (Beta vulgaris) Fruit Tissue.

Cercospora leaf spot (CLS) is a globally important disease of sugar beet (Beta vulgaris) caused by the fungus Cercospora beticola. Long-distance movement of C. beticola has been indirectly evidenced in recent population genetic studies, suggesting potential dispersal via seed. Commercial sugar beet "seed" consists of the reproductive fruit (true seed surrounded by maternal pericarp tissue) coated in artificial pellet material. In this study, we confirmed the presence of viable C. beticola in sugar beet fruit for 10 of 37 tested seed lots. All isolates harbored the G143A mutation associated with quinone outside inhibitor resistance, and 32 of 38 isolates had reduced demethylation inhibitor sensitivity (EC50 > 1 µg/ml). Planting of commercial sugar beet seed demonstrated the ability of seedborne inoculum to initiate CLS in sugar beet. C. beticola DNA was detected in DNA isolated from xylem sap, suggesting the vascular system is used to systemically colonize the host. We established nuclear ribosomal internal transcribed spacer region amplicon sequencing using the MinION platform to detect fungi in sugar beet fruit. Fungal sequences from 19 different genera were identified from 11 different sugar beet seed lots, but Fusarium, Alternaria, and Cercospora were consistently the three most dominant taxa, comprising an average of 93% relative read abundance over 11 seed lots. We also present evidence that C. beticola resides in the pericarp of sugar beet fruit rather than the true seed. The presence of seedborne inoculum should be considered when implementing integrated disease management strategies for CLS of sugar beet in the future.

Resilience of T cell-intrinsic dysfunction in transplantation tolerance.

Following antigen stimulation, naïve T cells differentiate into memory cells that mediate antigen clearance more efficiently upon repeat encounter. Donor-specific tolerance can be achieved in a subset of transplant recipients, but some of these grafts are rejected after years of stability, often following infections. Whether T cell memory can develop from a tolerant state and whether these formerly tolerant patients develop antidonor memory is not known. Using a mouse model of cardiac transplantation in which donor-specific tolerance is induced with costimulation blockade (CoB) plus donor-specific transfusion (DST), we have previously shown that systemic infection with Listeria monocytogenes (Lm) months after transplantation can erode or transiently abrogate established tolerance. In this study, we tracked donor-reactive T cells to investigate whether memory can be induced when alloreactive T cells are activated in the setting of tolerance. We show alloreactive T cells persist after induction of cardiac transplantation tolerance, but fail to acquire a memory phenotype despite becoming antigen experienced. Instead, donor-reactive T cells develop T cell-intrinsic dysfunction evidenced when removed from the tolerant environment. Notably, Lm infection after tolerance did not rescue alloreactive T cell memory differentiation or functionality. CoB and antigen persistence were sufficient together but not separately to achieve alloreactive T cell dysfunction, and conventional immunosuppression could substitute for CoB. Antigen persistence was required, as early but not late surgical allograft removal precluded the acquisition of T cell dysfunction. Our results demonstrate transplant tolerance-associated T cell-intrinsic dysfunction that is resistant to memory development even after Lm-mediated disruption of tolerance.