Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). Materials and methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Understanding and Addressing Prostate Cancer Disparities in Diagnosis, Treatment, and Outcomes Among Black Men.

Despite advances in screening, diagnosis, and treatment for prostate cancer (PCa), Black men tend to be diagnosed at younger ages, have higher mortality rates, and are at increased risk of recurrence or metastasis compared to their White counterparts. PCa disparities among Black men are caused by a complex interaction of social, behavioral, and biological factors across the public policy, community, organizational, interpersonal, and individual levels. Key contributing factors include mistrust in the health care system, poor communication between patients and providers, low awareness of screening guidelines, and high medical costs. These disparities are further exacerbated by the low representation of Black men in clinical trials, which limits access to high-quality cancer care and generalizability for PCa treatments. In this narrative review of the existing literature, we examined the epidemiology and identified contributing factors, and propose multi-level strategies to address and mitigate disparities among Black men with PCa.

Bridging Health Disparities in the Data-Driven World of Artificial Intelligence: A Narrative Review.

BACKGROUND: Artificial intelligence (AI) holds exciting potential to revolutionize healthcare delivery in the United States. However, there are concerns about its potential to perpetuate disparities among historically marginalized populations. OBJECTIVE: Following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted a narrative review of current literature on AI and health disparities in the United States. We aimed to answer the question, Does AI have the potential to reduce or eliminate health disparities, or will its use further exacerbate these disparities? METHODS: We searched the Ovid MEDLINE electronic database to identify and retrieve publications discussing AI and its impact on racial/ethnic health disparities. Articles were included if they discussed AI as a tool to mitigate racial health disparities with or without bias in developing and using AI. RESULTS: This review included 65 articles. We identified six themes of limitations in AI that impact health equity: (1) biases in AI can perpetuate and exacerbate racial and ethnic inequities; (2) equity in algorithms should be a priority; (3) lack of diversity in the field of AI is concerning; (4) the need for regulation and testing algorithms for accuracy; (5) ethical standards for AI in health care are needed; and (6) the importance of promoting transparency and accountability. CONCLUSIONS: While AI promises to enhance healthcare outcomes and address equity concerns, risks and challenges are associated with its implementation. To maximize the use of AI, it must be approached with an equity lens during all phases of development.

Patient experiences with blood pressure measurement methods for hypertension diagnosis: Qualitative findings from the BP-CHECK study.

BACKGROUND: Out-of-office blood pressure (BP) measurement is recommended when making a new hypertension diagnosis. In practice, however, hypertension is primarily diagnosed using clinic BP. The study objective was to understand patient attitudes about accuracy and patient-centeredness regarding hypertension diagnostic methods. METHODS: Qualitative study within a randomized controlled diagnostic study conducted between May 2017 and March 2019 comparing the accuracy and acceptability of BP measurement methods among patients in an integrated healthcare delivery system. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM), plus either clinic BP, home BP monitoring (HBPM), or kiosk BP diagnostic testing. Qualitative interviewees (aged 31-76 years, n=35) were recruited from the main study. RESULTS: Participants who completed HBPM found it to be comfortable and low burden, and believed it produced accurate results. Participants in the clinic arm described clinic measurements as inconvenient. Participants in the kiosk arm overall did not favor kiosks due to concerns about accuracy and privacy. Participants described ABPM as the most accurate method due to repeated measurements over the 24-hour period in real-world contexts, but many found it uncomfortable and disruptive. Participants also noted methods that involved repeated measures such as HBPM and ABPM particularly influenced their understanding of whether or not they had hypertension. CONCLUSIONS: Hypertension diagnostic methods that include more BP measurements help patients gain a deeper understanding of BP variability and the lower reliability of infrequent measurements in clinic. These findings warrant implementing strategies to enhance out-office BP diagnostic testing in primary care.

Addressing differences in cancer: a framework for synergistic programming in cancer prevention and control.

Background: Cancer remains a leading cause of death worldwide and continues to disproportionately impact certain populations. Several frameworks have been developed that illustrate the multiple determinants of cancer. Expanding upon the work of others, we present an applied framework for cancer prevention and control designed to help clinicians, as well as public health practitioners and researchers, better address differences in cancer outcomes. Methods: The framework was developed by the Cancer Prevention and Control Research Network's Health Behaviors Workgroup. An initial framework draft was developed based on workgroup discussion, public health theory, and rapid literature review on the determinants of cancer. The framework was refined through interviews and focus groups with Federally Qualified Health Center providers (n=2) and cancer patients (n=2); participants were asked to provide feedback on the framework's causal pathways, completeness, and applicability to their work and personal life. Results: The framework provides an overview of the relationships between sociodemographic inequalities, social and structural determinants, and key risk factors associated with cancer diagnosis, survivorship, and cancer morbidity and mortality across the lifespan. The framework emphasizes how health-risk behaviors like cigarette smoking interact with psychological, psychosocial, biological, and psychosocial risk factors, as well as healthcare-related behavior and other chronic diseases. Importantly, the framework emphasizes addressing social and structural determinants that influence health behaviors to reduce the burden of cancer and improve health equity. Aligned with previous theory, our framework underscores the importance of addressing co-occurring risk factors and disease states, understanding the complex relationships between factors that influence cancer, and assessing how multiple forms of inequality or disadvantage intersect to increase cancer risk across the lifespan. Conclusions: This paper presents an applied framework for cancer prevention and control to address cancer differences. Because the framework highlights determinants and factors that influence cancer risk at multiple levels, it can be used to inform the development, implementation, and evaluation of interventions to address cancer morbidity and mortality.

Is Hypertension Diagnostic Testing and Diagnosis Associated With Psychological Distress?

BACKGROUND: Psychological impacts of hypertension diagnostic testing and new hypertension diagnoses are unclear. METHODS: BP-CHECK was a randomized diagnostic study conducted in 2017-2019 in an integrated healthcare system. Participants with no hypertension diagnosis or medications and elevated blood pressure (BP) were randomized to one of three diagnostic regimens: (i) Clinic, (ii) Home, or (iii) Kiosk. Participants completed questionnaires at baseline, after completion of the diagnostic regimens, and at 6 months. Outcomes included changes from baseline in health-related quality of life (HRQOL), BP-related worry, and thoughts about having a stroke or heart attack. RESULTS: Participants (n = 482) were mostly over age 50 (77.0%), and White race (80.3%). HRQOL did not significantly change from baseline to 3 weeks or 6 months. Among all participants, BP-related worry and concerns about having a heart attack or stroke increased significantly from baseline to 3 weeks, with heart attack and stroke concerns significantly higher in the Kiosk compared Clinic and Home groups. At 6 months, thoughts about having a heart attack or stroke returned to baseline overall and in the Kiosk group, however BP-related worry was significantly higher among those with, compared to those without, a new hypertension diagnosis. CONCLUSIONS: The hypertension diagnostic process did not lead to short-term or intermediate-term changes in self-reported HRQOL. However, BP-related worry increased short-term and persisted at 6 months among individuals with a new hypertension diagnosis. Results warrant validation in more representative populations and additional exploration of the impacts of this worry on psychological well-being and hypertension control. CLINICALTRIALS.GOV IDENTIFIER: NCT03130257.

Decay of enveloped SARS-CoV-2 and non-enveloped PMMoV RNA in raw sewage from university dormitories.

Introduction: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA has been frequently detected in sewage from many university dormitories to inform public health decisions during the COVID-19 pandemic, a clear understanding of SARS-CoV-2 RNA persistence in site-specific raw sewage is still lacking. To investigate the SARS-CoV-2 RNA persistence, a field trial was conducted in the University of Tennessee dormitories raw sewage, similar to municipal wastewater. Methods: The decay of enveloped SARS-CoV-2 RNA and non-enveloped Pepper mild mottle virus (PMMoV) RNA was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in raw sewage at 4°C and 20°C. Results: Temperature, followed by the concentration level of SARS-CoV-2 RNA, was the most significant factors that influenced the first-order decay rate constants (k) of SARS-CoV-2 RNA. The mean k values of SARS-CoV-2 RNA were 0.094 day-1 at 4°C and 0.261 day-1 at 20°C. At high-, medium-, and low-concentration levels of SARS-CoV-2 RNA, the mean k values were 0.367, 0.169, and 0.091 day-1, respectively. Furthermore, there was a statistical difference between the decay of enveloped SARS-CoV-2 and non-enveloped PMMoV RNA at different temperature conditions. Discussion: The first decay rates for both temperatures were statistically comparable for SARS-CoV-2 RNA, which showed sensitivity to elevated temperatures but not for PMMoV RNA. This study provides evidence for the persistence of viral RNA in site-specific raw sewage at different temperature conditions and concentration levels.

SARS-CoV-2 raw wastewater surveillance from student residences on an urban university campus.

The COVID-19 pandemic brought about an urgent need to monitor the community prevalence of infection and detect the presence of SARS-CoV-2. Testing individual people is the most reliable method to measure the spread of the virus in any given community, but it is also the most expensive and time-consuming. Wastewater-based epidemiology (WBE) has been used since the 1960s when scientists implemented monitoring to measure the effectiveness of the Polio vaccine. Since then, WBE has been used to monitor populations for various pathogens, drugs, and pollutants. In August 2020, the University of Tennessee-Knoxville implemented a SARS-CoV-2 surveillance program that began with raw wastewater surveillance of the student residence buildings on campus, the results of which were shared with another lab group on campus that oversaw the pooled saliva testing of students. Sample collection began at 8 am, and the final RT-qPCR results were obtained by midnight. The previous day's results were presented to the campus administrators and the Student Health Center at 8 am the following morning. The buildings surveyed included all campus dormitories, fraternities, and sororities, 46 buildings in all representing an on-campus community of over 8,000 students. The WBE surveillance relied upon early morning "grab" samples and 24-h composite sampling. Because we only had three Hach AS950 Portable Peristaltic Sampler units, we reserved 24-h composite sampling for the dormitories with the highest population of students. Samples were pasteurized, and heavy sediment was centrifuged and filtered out, followed by a virus concentration step before RNA extraction. Each sample was tested by RT-qPCR for the presence of SARS-CoV-2, using the CDC primers for N Capsid targets N1 and N3. The subsequent pooled saliva tests from sections of each building allowed lower costs and minimized the total number of individual verification tests that needed to be analyzed by the Student Health Center. Our WBE results matched the trend of the on-campus cases reported by the student health center. The highest concentration of genomic copies detected in one sample was 5.06 × 107 copies/L. Raw wastewater-based epidemiology is an efficient, economical, fast, and non-invasive method to monitor a large community for a single pathogen or multiple pathogen targets.

Willingness to participate in various nontherapeutic cancer research activities among urban and rural African American and Latinx healthy volunteers.

PURPOSE: Inclusion of racial/ethnic minorities in cancer research can reduce disparities in health outcomes; however, data regarding barriers and motivators to participation are sparse. This study assessed African American (AA) and Latinx healthy volunteers' perspectives regarding willingness to participate in noninvasive and invasive research activities. METHODS: Using a 38-item questionnaire adapted from the Tuskegee Legacy Project Questionnaire, we assessed willingness to participate in 12 research activities, offering 27 possible barriers and 14 motivators. The sample was segmented into four subgroups by AA/Latinx and rural/urban. RESULTS: Across five states and Puerto Rico, 533 participants completed questionnaires. Overall, participants were more willing to participate in noninvasive versus invasive procedures, although, all subgroups were willing to participate in research if asked. Rural AA were most willing to complete a survey or saliva sample, while rural Latinx were least willing. Urban AA were least willing to provide cheek swab, while rural counterparts were most willing. Self-benefit and benefit to others were among the top three motivators for all subgroups. Curiosity was a primary motivator for urban AA while obtaining health information motivated rural Latinx. Primary barriers included fears of side effects and being experimented on, lack of information, and lack of confidentiality. CONCLUSIONS: Latinx and AAs are willing to participate in the continuum of nontherapeutic research activities suggesting their lack of participation may be related to not being asked. Inclusive enrollment may be achieved by assessing needs of participants during the design phase of a study in order to reduce barriers to participation.

Comparison of the survival of different isolates of SARS-CoV-2 in evaporating aerosols.

Numerous variants of SARS-CoV-2 with increased transmissibility have emerged over the course of the pandemic. Potential explanations for the increased transmissibility of these variants include increased shedding from infected individuals, increased environmental stability, and/or a lower infectious dose. Upon exhalation of a respiratory particle into the environment, water present in the particle is rapidly lost through evaporation, resulting in a decrease in particle size. The aim of the present study was to compare the losses of infectivity of different isolates of SARS-CoV-2 during the rapid evaporation of aerosol particles that occurs immediately post-generation to assess if there are differences suggestive of increased survival, and ultimately greater transmissibility, for more recent variants. Losses of infectivity of several isolates of SARS-CoV-2 suspended in viral culture media were assessed following aerosolization and evaporation in a flowing chamber. The results demonstrate that losses of infectivity measured post-evaporation were similar for three different isolates of SARS-CoV-2, including isolates from the more recent Delta and Omicron lineages. The average loss in infectivity across all three isolates was 61 ± 15% (-0.46 ± 0.17 log10 TCID50/L-air) at a relative humidity <30%. These results, together with those from several previous studies, suggest that it is unlikely that an increase in environmental stability contributes to the observed increases in transmissibility observed with more recent variants of SARS-CoV-2.

Coding-Complete Genome Sequence of a SARS-CoV-2 Variant Obtained from Raw Sewage at the University of Tennessee-Knoxville Campus.

Reported here is a coding-complete genome sequence of a SARS-CoV-2 variant obtained from raw wastewater samples at the University of Tennessee-Knoxville campus. This sequence provides insight into SARS-CoV-2 variants that circulate on large college campuses but remain mostly undetected.

Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Pulse- and field-resolved THz-diagnostics at 4 t h generation lightsources.

Multi-color pump-probe techniques utilizing modern accelerator-based 4th generation light sources such as X-ray free electron lasers or superradiant THz facilities have become important science drivers over the past 10 years. In this type of experiments the precise knowledge of the properties of the involved accelerator-based light pulses crucially determines the achievable sensitivity and temporal resolution. In this work we demonstrate and discuss the powerful role pulse- and field-resolved- detection of superradiant THz pulses can play for improving the precision of THz pump - femtosecond laser probe experiments at superradiant THz facilities in particular and at 4th generation light sources in general. The developed diagnostic scheme provides real-time information on the properties of individual pulses from multiple accelerator based THz sources and opens a robust way for sub femtosecond timing. Correlations between amplitude and phase of the pulses emitted from different superradiant THz sources furthermore provide insides into the properties of the driving electron bunches and is of general interest for the ultra-fast diagnostics at 4th generation light sources.

An open-source high-frequency lock-in amplifier.

We present characterization of a lock-in amplifier based on a field programmable gate array capable of demodulation at up to 50 MHz. The system exhibits 90 nV/√Hz of input noise at an optimum demodulation frequency of 500 kHz. The passband has a full-width half-maximum of 2.6 kHz for modulation frequencies above 100 kHz. Our code is open source and operates on a commercially available platform.

Clinical relevance of non-tuberculous mycobacteria isolated from respiratory specimens: seven year experience in a UK hospital.

The frequency of isolation of non-tuberculous mycobacteria (NTM) species from respiratory specimens is increasing, however the clinical relevance of such identifications vary by mycobacterial species and geographical location. A retrospective study of 853 NTM isolates from respiratory samples from 386 patients over seven years was performed. Clinical records and radiographic information were examined. Clinical significance was assessed by American Thoracic Society diagnostic criteria. 25% of all patients with respiratory isolates met criteria for non-tuberculous mycobacterial pulmonary disease (NTM-PD). Significant symptoms were weight loss, fever, night sweats, productive cough and haemoptysis. HIV co-infection was a significant risk factor for disease. Cavities, nodules and tree-in-bud were significant radiographic findings. Mycobacterium avium complex (MAC) were the dominant species isolated from this patient cohort. Mycobacterium abscessus (M. abscessus) was the species most likely to cause clinically significant disease and be sputum smear positive, thus warranting particular attention.

On-chip THz spectrometer for bunch compression fingerprinting at fourth-generation light sources.

The layout of an integrated millimetre-scale on-chip THz spectrometer is presented and its peformance demonstrated. The device is based on eight Schottky-diode detectors which are combined with narrowband THz antennas, thereby enabling the simultaneous detection of eight frequencies in the THz range on one chip. The size of the active detector area matches the focal spot size of superradiant THz radiation utilized in bunch compression monitors of modern linear electron accelerators. The 3 dB bandwidth of the on-chip Schottky-diode detectors is less than 10% of the center frequency and allows pulse-resolved detection at up to 5 GHz repetition rates. The performance of a first prototype device is demonstrated at a repetition rate of 100 kHz at the quasi-cw SRF linear accelerator ELBE operated with electron bunch charges between a few pC and 100 pC.

Age-dependent intoxication by larkspur (Delphinium) in Angus steers.

The effect of age on larkspur poisoning of cattle is unknown. An experiment consisting of oral dosing of dried, ground, Delphinium barbeyi to ten Angus steers as yearlings, and again at two years was performed. There was a significant difference between the responses of yearling and two year old steers (P = 0.0015), with yearling steers being more susceptible. These results suggest that the adverse response of Angus cattle to larkspur is age-dependent.

Specific stereochemistry of OP-1074 disrupts estrogen receptor alpha helix 12 and confers pure antiestrogenic activity.

Complex tissue-specific and cell-specific signaling by the estrogen receptor (ER) frequently leads to the development of resistance to endocrine therapy for breast cancer. Pure ER antagonists, which completely lack tissue-specific agonist activity, hold promise for preventing and treating endocrine resistance, however an absence of structural information hinders the development of novel candidates. Here we synthesize a small panel of benzopyrans with variable side chains to identify pure antiestrogens in a uterotrophic assay. We identify OP-1074 as a pure antiestrogen and a selective ER degrader (PA-SERD) that is efficacious in shrinking tumors in a tamoxifen-resistant xenograft model. Biochemical and crystal structure analyses reveal a structure activity relationship implicating the importance of a stereospecific methyl on the pyrrolidine side chain of OP-1074, particularly on helix 12.