FAP Radioligand Linker Optimization Improves Tumor Dose and Tumor-to-Healthy Organ Ratios in 4T1 Syngeneic Model.

Fibroblast activation protein (FAP) has attracted considerable attention as a possible target for the radiotherapy of solid tumors. Unfortunately, initial efforts to treat solid tumors with FAP-targeted radionuclides have yielded only modest clinical responses, suggesting that further improvements in the molecular design of FAP-targeted radiopharmaceutical therapies (RPT) are warranted. In this study, we report several advances on the previously described FAP6 radioligand that increase tumor retention and accelerate healthy tissue clearance. Seven FAP6 derivatives with different linkers or albumin binders were synthesized, radiolabeled, and investigated for their effects on binding and cellular uptake. The radioligands were then characterized in 4T1 tumor-bearing Balb/c mice using both single-photon emission computed tomography (SPECT) and ex vivo biodistribution analyses to identify the conjugate with the best tumor retention and tumor-to-healthy organ ratios. The results reveal an optimized FAP6 radioligand that exhibits efficacy and safety properties that potentially justify its translation into the clinic.

Documenting Race and Gender Biases in Pain Assessment and a Novel Intervention Designed to Reduce Biases.

Disparities in pain care are well-documented such that women and people of color have their pain undertreated and underestimated compared to men and White people. One of the contributors of the undertreatment of pain for people of color and women may be the inaccurate assessment of pain. Understanding the pain assessment process is an important step in evaluating the magnitude of and intervening on pain disparities in care. In the current work, we focus on documenting intersectional race and gender biases in pain assessment and present the results of a novel intervention for reducing these biases. Across 3 studies (N = 532) and a mini meta-analysis using real videotaped people in pain as stimuli, we demonstrate that observers disproportionately underestimated women of color's pain compared to all other groups (men of color, White women, and White men). In study 3 (N = 232), we show that a novel intervention focused on behavioral skill building (ie, practice and immediate feedback) significantly reduced observers' pain assessment biases toward marginalized groups compared to all other types of trainings (raising awareness of societal biases, raising awareness of self-biases, and a control condition). While it is an open question as to how long this type of intervention lasts, behavioral skills building around assessing marginalized people's pain more accurately is a promising training tool for health care professionals. PERSPECTIVE: This article demonstrates the underestimation of pain among people of color and women. We also found support that a novel intervention reduced observers' pain assessment biases toward marginalized groups. This could be used in medical education or clinical care to reduce intersectional pain care disparities.

The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.

Introduction: Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers' singular positive nonverbal behaviours (NBs) on pain reports. Methods: Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups. Results: There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation. Discussion: Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream. Conclusion: No NB of caregivers is more effective in reducing pain. Caregivers' NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.

Alcohol-associated liver disease and behavioral and medical cofactors: unmet needs and opportunities.

Chronic liver disease is a leading cause of death in the US and is often preventable. Rising burden, cost, and fatality due to liver disease are driven by intensified alcohol use in the US population and the contributions of comorbid conditions. This mini-review focuses on the topic of liver health in the context of chronic, behavioral cofactors of disease, using research-based examples from the Brown University Center for Addiction and Disease Risk Exacerbation (CADRE). Our aim is to illustrate the current challenges and opportunities in clinical research addressing liver health in the context of behavioral and medical comorbidity and to highlight next steps in this crucial area of public health research and clinical care.

Reaction of Ph2C(X)(CO2H) (X = OH, NH2) with [VO(OR)3] (R = Et, nPr): structure, magnetic susceptibility and ROP capability.

Reaction of [VO(OR)3] (R = Et, nPr) with 2,2'-diphenylglycine afforded the alkoxide-bridged dimers {[VO(OR)(µ-OR)][Ph2C(NH2)(CO2)]}2, whereas use of benzilic acid, in the presence of alkali metals, afforded 16-membered metallocycles {V8(O)4M(OR)8[Ph2C(OH)(CO2)]12} (M = <1 Na, K). For the ring systems, magnetic susceptibility data is consistent with mixed-valence vanadium with an average oxidation state of 3.5. The dimer and ring systems are capable of the ring opening polymerisation (ROP) of ε-caprolactone under N2, air, or as melts affording mostly low to medium molecular weight cyclic and linear products.

Immune biomarkers in non-treatment-seeking heavy drinkers who used a probiotic supplement for 30 days: An open-label pilot study.

Alcohol use disorder (AUD) is associated with significant psychological and economic burdens, as well as physical comorbidities that can lead to death. Previous research has found that probiotics may reduce inflammatory biomarkers in persons with AUD and comorbid conditions such as cirrhosis of the liver. This relationship has not been explored in heavy drinkers without comorbid conditions. In a proof-of-concept study, individuals who were heavy drinkers without known comorbidities received a 30-day course of a daily probiotic supplement in an open-label pilot trial. Eligible participants (N = 16) met NIAAA guidelines for heavy alcohol use and did not report any preexisting medical problems. Blood samples were taken at four timepoints: prior to the probiotic course, at the midpoint, at the end, and after a washout period of at least one month. Immunoassays were conducted on plasma samples to quantify the following inflammatory biomarkers: IL-6, IL-8, IL-10, LBP, MCP-1, sCD14, sCD163, and TNF-α. Linear mixed models were used to test within-subjects changes in biomarker concentrations over the study period, with alcohol use included as a time-varying covariate. Biomarker concentrations did not change significantly. A higher number of heavy drinking days was statistically associated with higher concentrations of IL-6 (F(1,8) = 6.66, p = 0.0326) and IL-8 (F(1,17) = 6.38, p = 0.0218). Greater days since last drink was associated with a lower concentration of MCP-1 (F(1,17) = 5.77, p = 0.028). In summary, biomarker trajectories were associated with alcohol consumption variables, but not probiotic use, in this open-label pilot study. Randomized controlled trials are needed to evaluate fully the potential benefits of probiotics in heavy drinkers without known comorbidities and under conditions of non-abstinence.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Preserving privacy in the era of openness: Commentary on open science requirements for identifiable data in psychological science journals.

Psychological science journals are increasingly adopting open science (OS) policies (e.g., Transparency and Openness Promotion) requiring researchers to make all data and materials publicly available in an effort to drive research toward greater transparency and accessibility. These policies certainly have many benefits to the scientific community and public in helping ensure the quality of published research. However, the Center for Open Science has not offered any explicit guidelines regarding when exceptions to OS policies should be made, with only vague guidelines offered such as "when ethical or legal constraints prevent it." We argue that these ambiguous policies may create bias in decisions made by journal editors as to whom and what type of research is granted exceptions. When journals are too rigid in their exception policies, this may unintentionally contradict OS's goals to create a more valid and ethical science. We argue that journals should never mandate identifiable data to be posted publicly as a publication prerequisite. Maintaining participant anonymity should always come before OS policies to (a) align with psychologists' primary obligation of maintaining participant confidentiality, (b) encourage participation from the broader population and more specifically from marginalized communities, and (c) maintain unbiased, representative, and valid data. From empirical and ethical insights, we offer several solutions to ease the tensions between OS and participant privacy during the data collection and publication process. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Augmenting Virtual Reality Exposure Therapy for Social and Intergroup Anxiety With Transcranial Direct Current Stimulation.

OBJECTIVES: Exposure therapy is a cornerstone of social anxiety treatment, yet not all patients respond. Symptoms in certain social situations, including intergroup (ie, out-group) contexts, may be particularly resistant to treatment. Exposure therapy outcomes may be improved by stimulating neural areas associated with safety learning, such as the medial prefrontal cortex (mPFC). The mPFC also plays an important role in identifying others as similar to oneself. We hypothesized that targeting the mPFC during exposure therapy would reduce intergroup anxiety and social anxiety. METHODS: Participants (N = 31) with the public speaking subtype of social anxiety received active (anodal) or sham transcranial direct current stimulation (tDCS) targeting the mPFC during exposure therapy. Exposure therapy consisted of giving speeches to audiences in virtual reality. To target intergroup anxiety, half of the public speaking exposure trials were conducted with out-group audiences, defined in this study as audiences of a different ethnicity. RESULTS: Contrary to hypotheses, tDCS did not facilitate symptom reduction. Some evidence even suggested that tDCS temporarily increased in-group favoritism, although these effects dissipated at 1-month follow-up. In addition, collapsing across all participants, we found reductions across time for public speaking anxiety and intergroup anxiety. CONCLUSIONS: The data provide evidence that standard exposure therapy techniques for social anxiety can be adapted to target intergroup anxiety. Transcranial direct current stimulation targeting the mPFC may boost safety signaling, but only in contexts previously conditioned to signal safety, such as an in-group context.

Social identity and the mental health and wellbeing of male veterans.

BACKGROUND: Previous work has linked disruptions in one's social identity to increased levels of depression and suicide among veterans. This study examines the relationship between veteran social identity (as measured by the public and private regard subscales of the Warrior Identity Scale) and mental health and wellbeing among male veterans. PARTICIPANTS AND PROCEDURE: Male veterans (N = 67) completed the Warrior Identity Scale as well as various measures of mental health and wellbeing. RESULTS: The hypotheses were supported in that more positive views of one's social identity (i.e., more private regard) predicted significantly fewer post-traumatic stress disorder (PTSD) symptoms, less depression, suicidal ideation, anxiety, stress, and more perceived social support. More public regard, on the other hand, was related to more PTSD symptoms. CONCLUSIONS: This research adds to the growing work on the importance of social identity (as measured by public and private regard) in predicting mental health symptomatology among male veterans, which may act as important risk factors in clinical settings.

Exposure to the Death of Others during the COVID-19 Pandemic: Growing Mistrust in Medical Institutions as a Result of Personal Loss.

BACKGROUND AND AIMS: The prominence of death during the COVID-19 pandemic was heightened by the potential of personally knowing someone who lost their life to the virus. The terror management theory (TMT) suggests that the salient presence of death has a pronounced effect on behavior and may result in the ossification of beliefs and actions aligned with one's worldview (i.e., the mortality salience hypothesis). In this study, we evaluated how death exposure early in the COVID-19 pandemic could enact the process of firming up held beliefs and attitudes related to health and safety. Specifically, we tested the hypothesis that exposure to a personal loss during the pandemic would strengthen participants' baseline attitudes and behaviors regarding COVID-19 safety guidelines. METHOD: Data were analyzed from a prospective, regional survey administered at two time points during the pandemic, June-July 2020 and May 2021, in five United States northeastern states. Baseline and follow-up surveys were administered approximately 12 months apart, with adherence to public guidance and death exposure measured at both timepoints and other safety measures at follow-up only. FINDINGS: Our results indicated that there were significant main effects of death exposure on guideline adherence and support for COVID-related public policy. Contrary to the mortality salience hypothesis, death exposures after baseline were related to higher medical mistrust at follow-up for those high in adherence at baseline, rather than those with low adherence. CONCLUSION: Our results offer some conflicting evidence to the mortality salience hypothesis. Rather than entrench people in their worldviews, death in the context of the COVID-19 pandemic appeared to sway people away from their initial stances. This finding has important implications for TMT literature and for the COVID-19 pandemic response.

Systematic manipulation of experimenters' non-verbal behaviors for the investigation of pain reports and placebo effects.

Objective: Non-verbal behaviors (NBs) of caregivers affect pain reports and placebo effects. However, little experimental research has systematically examined the caregivers' NBs. This study protocol and preparatory study report a systematic manipulation of experimenters' NBs to investigate pain report and placebo effects. Methods: We propose an experiment in which videotaped experimenters (VEs) conduct a pain stimulation and a placebo treatment study. The VEs express one positively enhanced NB and keep the other NBs neutral. Participants will be randomized to either the positive facial expressions (+FE), tone of voice (+TV), body movement (+BM), or neutral NBs (i.e., neutral condition; NC) of the VEs. As a preparatory study for proof of concept, two groups of NB coders from Norway and the USA separately rated the degree of NBs (eye contact, body postures and movements, and tone of voice), and impressions of dominance and being in charge, positivity, and expressivity from each NB video. The NB videos had construct validity and reliability. The +BM and +FE were rated as more dominant and in charge than the +TV and the NC. The +FE and +BM were rated as the most positive and expressive NBs, respectively. Expected results: +FE will have the largest placebo effects on pain and stress levels. However, transmitting the NBs to patients by VEs is challenging. Moreover, controlling for the effects of research assistants present in the testing room is challenging. Discussion: We propose that caregivers' NBs affect pain reports and placebo effects. Moreover, different NBs elicit different impressions, and a better understanding of the role of caregiver NBs requires more rigorous investigations. Lastly, aiming to investigate the caregiver NBs, the varying degrees of micro-NBs and their effects on the formation of impressions should be considered.

Access to medication for opioid use disorder supported by telemedicine and healthcare coverage: A web-based survey during the COVID-19 pandemic.

Background and Aims: Medications for opioid use disorder (MOUD) are highly effective in improving treatment outcomes and reducing overdose. Concerns about interrupted access to critical MOUD services led to expansion of telemedicine services during the COVID-19 pandemic in the US. The current study tested the hypothesis that telemedicine usage and healthcare coverage would be significantly associated with access to MOUD in the early phase of the COVID-19 pandemic. Design: A cross-sectional online survey was administered to a non-probability sample from June 18-July 19, 2020 using the Amazon Mechanical Turk platform. Setting: Northeastern United States during the early phase of the COVID-19 pandemic. At the time of the survey, federal regulators had waived the longstanding requirement for in-office visits for MOUD prescription receipt and provided guidance on increasing third-party payer reimbursement rates for telehealth visits in order to mitigate barriers to care associated with COVID-19 safety guidelines. Participants: Individuals 18 years or older residing in Connecticut, Massachusetts, New Jersey, New York, or Rhode Island were eligible to complete the survey. The analytic sample was participants who reported using opioids not as prescribed by a physician in the past seven days. Measurements: Demographics, telemedicine usage, and healthcare coverage were assessed as explanatory variables. The primary outcome was whether participants reported ability to access MOUD in the past four weeks. Findings: In this sample of individuals who used illicit opioids in the past week (N = 191), one in two individuals who utilized telehealth or had healthcare coverage were able to access MOUD, whereas only one in five of their respective counterparts who did not have telehealth access or healthcare coverage were able to access these medications. Conclusions: Telemedicine and healthcare coverage were associated with greater MOUD access early in the COVID-19 pandemic, when barriers to care were high. Such findings speak to the importance of not only extending but also formalizing temporary policy changes instituted during the pandemic to allow MOUD prescribing via telemedicine.

"You Look Young! Are You a Doctor?" A Qualitative Content Analysis of Anesthesiology Resident Responses to Ageism in Clinical Encounters.

BACKGROUND: Healthcare trainees frequently report facing comments from their patients pertaining to their age. Exposure to ageist comments from patients may be related to greater stress and/or burnout in residents and may impact the quality of the resident-patient relationship. However, little empirical work has examined ageism expressed toward anesthesiology residents in clinical care, and therefore not much is known about how residents respond to these comments in practice. This research sought to determine how anesthesiology residents responded to ageist comments. METHODS: Anesthesiology residents (N = 60) engaged in a preoperative interaction with a standardized patient who was instructed to make an ageist comment to the resident. Resident responses were transcribed and coded using qualitative inductive content analysis to identify response themes. RESULTS: The most common resident response to the ageist comment, across gender and resident year, was to state their own experience. Some also described how they were still in training or that they were under supervision. Residents rarely reassured the patient that they would receive good care or identified the patient's anxiety as a cause of the ageist remark. CONCLUSIONS: These results provide a first step in understanding how ageism may be navigated by residents in clinical encounters. The authors discuss potential avenues for future research and education for responding to ageist remarks for both patients and clinicians.

Alcohol consumption and oral microbiome composition in a sample of healthy young adults.

The oral microbiomes of 24 healthy adults (50% female; mean age = 24.3) were examined using 16 s ribosomal RNA sequencing and compared between light and heavy drinkers. Beta diversity was related at the trend level to drinking group, and light drinkers had significantly higher abundances of key oral taxa such as Lactobacillales. These preliminary results may offer insight into early effects of heavy drinking on the composition of the oral microbiome.

Triploid Pacific oysters exhibit stress response dysregulation and elevated mortality following heatwaves.

Polyploidy has been suggested to negatively impact environmental stress tolerance, resulting in increased susceptibility to extreme climate events. In this study, we compared the genomic and physiological response of diploid (2n) and triploid (3n) Pacific oysters (Crassostrea gigas) to conditions present during an atmospheric heatwave that impacted the Pacific Northwestern region of the United States in the summer of 2021. Climate stressors were applied either singly (single stressor; elevated seawater temperature, 30°C) or in succession (multiple stressor; elevated seawater temperature followed by aerial emersion at 44°C), replicating conditions present within the intertidal over a tidal cycle during the event. Oyster mortality rate was elevated within stress treatments with respect to the control and was significantly higher in triploids than diploids following multiple stress exposure (36.4% vs. 14.8%). Triploids within the multiple stressor treatment exhibited signs of energetic limitation, including metabolic depression, a significant reduction in ctenidium Na+ /K+ ATPase activity, and the dysregulated expression of genes associated with stress response, innate immunity, glucose metabolism, and mitochondrial function. Functional enrichment analysis of ploidy-specific gene sets identified that biological processes associated with metabolism, stress tolerance, and immune function were overrepresented within triploids across stress treatments. Our results suggest that triploidy impacts the transcriptional regulation of key processes that underly the stress response of Pacific oysters, resulting in downstream shifts in physiological tolerance limits that may increase susceptibility to extreme climate events that present multiple environmental stressors. The impact of chromosome set manipulation on the climate resilience of marine organisms has important implications for domestic food security within future climate scenarios, especially as triploidy induction becomes an increasingly popular tool to elicit reproductive control across a wide range of species used within marine aquaculture.

Should I post? The relationships among social media use, emotion recognition, and mental health.

Introduction: While increased time spent on social media can be negatively related to one's overall mental health, social media research often fails to account for what behaviors users are actually engaging in while they are online. The present research helps to address this gap by measuring participants' active and passive social media behavioral styles and investigates whether and how these two social media behavioral styles are related to depression, anxiety, and stress, and the mediating role of emotion recognition ability in this relationship. Methods: A pre-study (N = 128) tested whether various social media behaviors reliably grouped into active and passive behavioral styles, and a main study (N = 139) tested the relationships between social media use style, emotion recognition, and mental health. Results: While we did not find evidence of a mediating relationship between these variables, results supported that more active social media use was related to more severe anxiety and stress as well as poorer emotion recognition skill, while passive social media use was unrelated to these outcomes. Discussion: These findings highlight that, beyond objective time spent on social media, future research must consider how users are spending their time online.

Perceived stress, mental health symptoms, and deleterious behaviors during the transition to college.

BACKGROUND: This study examined associations between different sources of chronic perceived stress and deleterious behaviors (eating disorder symptoms, insufficient sleep, and insufficient vigorous physical activity) among first-year college students. METHODS: The study used data on 885 first-year students (ages 18-20) at a large public university in North Carolina. The prevalence of deleterious behaviors was evaluated. Associations were estimated between different sources of chronic perceived stress (academic, future, peers, friendships, romantic, appearance, health, chronic illness, financial, work, family) and health behaviors after controlling for psychosocial supports and demographics. Moderating effects of gender and moderate-severe anxiety/depression symptoms were also tested. RESULTS: 19% of first-year student reported symptoms of eating disorders, 42% insufficient sleep, and 43% insufficient vigorous physical activity. Perceived chronic stress increased the odds of reporting these deleterious behaviors. These effects were not moderated by gender or moderate-severe anxiety/depression symptoms. Appearance- and health-related stress were associated with eating disorder symptoms; health- and romantic-related stress were associated with insufficient sleep; and health-related stress was associated with insufficient vigorous physical activity. LIMITATIONS: Outcomes were survey-based. The study was based on cross-sectional data from a single university, so the direction of causality cannot be determined, and more work needs to be done to determine whether this would extend to other populations.

Chimpanzees (Pan troglodytes) in U.S. Zoos, Sanctuaries, and Research Facilities: A Survey-Based Comparison of Species-Typical Behaviors.

A survey was sent to zoos, research facilities, and sanctuaries which housed chimpanzees. Data collected included information about 1122 chimpanzees' age, sex, social group-size, rearing history, and enclosure. Respondents were also asked to indicate if certain behaviors had been observed in each chimpanzee over the prior two years. Species- typical behaviors (STBs) were queried, including copulation, tool-use, nest-building, and social grooming. Tool-use was reported present for 94.3% of the sample (n = 982), active social grooming for 85.7% (n = 1121), copulation for 68.3% (n = 863) and nest-building for 58.9% (n = 982). Of the subjects for whom we had data regarding all four STBs (n = 860), 45.6% were reported to engage in all four. Logistic regression analyses using forward Wald criteria were conducted to determine the best model for each STB based on the predictors of age, sex, rearing history, group-size, facility-type, and a sex-by-rearing interaction. The best model for copulation (χ2(6) = 124.62, p < 0.001) included rearing, group-size, facility-type, and the sex-by-rearing interaction. Chimpanzees were more likely to copulate if they were mother-reared, in larger groups, living in research facilities, and, if not mother-reared (NOTMR), more likely to copulate if they were female. The best model for tool-use retained the predictors of age category, facility-type, and sex-by-rearing (χ2(5) = 55.78, p < 0.001). Chimpanzees were more likely to use tools if they were adult, living in research facilities, and if NOTMR, were female. The best model for nest-building included facility-type and rearing (χ2(3) = 205.71, p < 0.001). Chimpanzees were more likely to build nests if they were MR and if they were living in zoos or in sanctuaries. The best model for active social grooming retained the predictors of age, sex, rearing, and type of facility (χ2(6) = 102.15, p < 0.001). Chimpanzees were more likely to engage in active social grooming if they were immature, female, mother-reared, and living in zoos. This research provides a basic behavioral profile for many chimpanzees living under human care in the United States and allows us to determine potential methods for improving the welfare of these and future chimpanzees in this population.