A proteome-wide analysis unveils a core Epstein-Barr virus antibody signature of classic Hodgkin lymphoma across ethnically diverse populations.

Epstein-Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East-Asian hospital-based case-control study. We identified 16 IgG antibodies significantly elevated in EBV-positive cHL compared with controls, defining an "East-Asian antibody signature of EBV-positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case-control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East-Asian antibody signature of EBV-positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV-positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East-Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East-Asian population. This cross-comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti-EBV IgG antibodies (LMP-1, TK, BALF2, BDLF3, and BBLF1), found in both population-specific antibody signatures, represent a "core signature of EBV-positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV-positive cHL independent of population-specific factors.

Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to a role of the diet itself in increasing risk. In AD, the complement system, an arm of the immune system which normally tags redundant or damaged synapses for pruning, becomes pathologically overactivated leading to tagging of healthy synapses. While the unhealthy diet to AD link is strong, the underlying mechanisms are not well understood in part due to confounding variables associated with long-term HFD which can independently influence the brain. Therefore, we experimented with a short-term diet regimen to isolate the diet's impact on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5) in vitro microglial synaptic phagocytosis in the 3xTg-AD mouse model. Following the consumption of either standard chow or HFD, 3xTg-AD and non-Tg mice were tested for memory impairments. In a separate cohort of mice, levels of hippocampal inflammatory markers, complement proteins, AD pathology markers, and synaptic markers were measured. For the last set of experiments, BV2 microglial phagocytosis of synapses was evaluated. Synaptoneurosomes isolated from the hippocampus of 3xTg-AD mice fed chow or HFD were incubated with equal numbers of BV2 microglia. The number of BV2 microglia that phagocytosed synaptoneurosomes was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had significantly impaired long-term contextual and cued fear memory compared to non-Tg mice that was further impaired by HFD. HFD significantly increased inflammatory markers and complement expression while decreasing synaptic marker expression only in 3xTg-AD mice, without altering AD pathology markers. Synaptoneurosomes from HFD-fed 3xTg-AD mice were phagocytosed at a significantly higher rate than those from chow-fed mice, suggesting the synapses were altered by HFD. The complement receptor inhibitor blocked this effect in a dose-dependent manner, demonstrating the HFD-mediated increase in phagocytosis was complement dependent. This study indicates HFD consumption increases neuroinflammation and over-activates the complement cascade in 3xTg-AD mice, resulting in poorer memory. The in vitro data point to complement as a potential mechanistic culprit and therapeutic target underlying HFD's influence in increasing cognitive vulnerability to AD.

Loneliness Trajectories and Chronic Loneliness Around the World.

OBJECTIVES: We examine cross-national variation in (a) loneliness trajectories and (b) the association between common social risk factors and chronic loneliness in middle and older adulthood. METHODS: Using longitudinal data, we assess the country-level prevalence of loneliness trajectories (chronic, transitory, and no loneliness) and the extent of common social risk factors for loneliness (living alone, widowhood, divorce, no grandchildren, having chronic conditions, and never working) among adults 50 and older in 20 countries covering 47% of the global population in this age bracket. Additionally, we compare how the associations between social risk factors and chronic loneliness vary across countries. RESULTS: We find considerable variation in the prevalence of chronic loneliness cross-nationally, ranging between 4% (Denmark) and 15% (Greece) of adults 50 and older. Living arrangements have the most consistent association with the likelihood of chronic loneliness across countries, with those ever living alone having an 8% higher likelihood of chronic loneliness on average across countries, with a range of 2%-25%. Additionally, those who never report working and those with chronic conditions have a higher likelihood of chronic loneliness across more than a third of the countries. DISCUSSION: These results suggest that policies and interventions targeted to middle age and older adults living alone and with limited work histories or with chronic conditions are critical in reducing the public health challenges of chronic loneliness.

Sibling Availability, Sibling Sorting, and Subjective Health Among Chinese Adults.

Despite rising numbers of only children in China, little is known about their family dynamics and well-being in adulthood-for example, how often they marry other only children and whether those in siblingless families have worse or better health than others. Theoretical expectations produce opposing predictions: siblings might provide social and emotional support and reduce parental caregiving pressures, but only children might receive more support from parents and grandparents. Using the 2010 China Family Panel Study, we examine marital sorting on Chinese adults' number of siblings and test whether sibling availability and sibling sorting are associated with subjective physical and mental health. Despite general perceptions that China has an exceedingly high prevalence of adults with no siblings that might produce very small families, results demonstrate a low prevalence of siblingless couples (i.e., both spouses are only children). Married adults with no siblings or siblings-in-law have better subjective physical health but similar levels of subjective mental health relative to their counterparts with siblings. The health advantages of siblingless marital unions are greater for rural and female adults. Declining sibling prevalence in China will shape future family demographic dynamics but appears less detrimental to population health than sometimes assumed.

Building resilience in primate tourism: insights from the COVID-19 pandemic and future directions.

The coronavirus disease 2019 (COVID-19) pandemic revealed the vulnerability of the tourism industry, triggering a call for a structural shift. This study focuses on COVID-19 impacts on primate tourism sites using the resilience-based wildlife tourism study of Jones et al. (2023) as an interpretive framework. Using an online survey, we collected data on impacts, changes, and challenges experienced at primate tourism destinations in various parts of the world. Based on 33 responses, the study found that the most profound impacts were financial, compromising the ability to run facilities and facilitate tourism due mainly to limitation of access to sites for tourists and/or staff/researchers. Seventeen respondents reported that their sites did not make substantial changes in response to the pandemic. This warrants further study to elicit the reasons for the lack of response. It may indicate difficulties in adaptation or implementation due to limited resources or other factors amid COVID-19 pandemic. We suggest that the framework proposed by Jones et al. (2023) has limitations in effectively addressing rapid and extensive repercussions of a disruption such as the COVID-19 pandemic.

Relationships, race/ethnicity, gender, age, and living kidney donation evaluation willingness.

Racial/ethnic and gender disparities in living donor kidney transplantation are large and persistent but incompletely explained. One previously unexplored potential contributor to these disparities is differential willingness to donate to recipients in specific relationships such as children, parents, and friends. We collected and analyzed data from an online sample featuring an experimental vignette in which respondents were asked to rate their willingness to donate to a randomly chosen member of their family or social network. Results show very large differences in respondents' willingness to donate to recipients with different relationships to them, favoring children, spouses/partners, siblings, and parents, and disfavoring friends, aunts/uncles, and coworkers. Evidence suggesting an interactive effect between relationship, respondent race/ethnicity, respondent or recipient gender, was limited to a few cases. At the p < 0.05 level, the parent-recipient gender interaction was statistically significant, favoring mothers over fathers, as was other/multiracial respondents' greater willingness to donate to friends compared to Whites. Additionally, other interactions were significant at the p < 0.10 level, such as Hispanics' and women's higher willingness to donate to parents compared to Whites and men respectively, women's lower willingness to donate to friends compared to men, and Blacks' greater willingness to donate to coworkers than Whites. We also examined differences by age and found that older respondents were less willing to donate to recipients other than their parents. Together these results suggest that differential willingness to donate by relationship group may be a moderately important factor in understanding racial/ethnic and gender disparities in living donor kidney transplantation.

Life Events and Loneliness Transitions Among Middle-Aged and Older Adults Around the World.

OBJECTIVES: Adult loneliness is a substantial social problem and a growing point of concern for policymakers around the world. We assess whether the predictors of loneliness onset among middle-aged and older adults vary from country to country in a large array of settings across world regions. Taking a life course perspective, we focus on common life events in our focal age range, including changes in partnership, coresidence, work, and health, and we test whether changes in them have comparable prospective associations with loneliness onset in different countries. METHODS: We draw on respondent-level data from a diversity of world regions surveyed in 7 harmonized cross-national studies in 20 countries, representing 47% of the global population over the age of 50. Our innovative longitudinal approach estimates prospective transition probability models that examine how each life event predicts the transition into loneliness. RESULTS: Despite substantial variation in the prevalence of loneliness and life events across the range of countries in our sample, our results highlight consistency in the predictors of loneliness transitions. Family and household changes like divorce, coresidence, and especially widowhood are paramount predictors of loneliness transition across settings, with changes in work and health playing more minor and less universal roles. DISCUSSION: The results demonstrate the importance that family and household connections play in determining loneliness at these ages. These findings suggest that addressing late-life loneliness may require a focus on key life events, especially those concerning changes in families and households.

A Study Planning Exercise Associated with Decreased Distraction Levels among Introductory Biology Students.

Students struggle to regulate their learning during independent study sessions. In this study, we ask whether an online behavioral intervention helped introductory students decrease distraction while studying. The intervention consisted of exam 1 reflection, exam 2 planning, and exam 2 reflection exercises. During planning, students formed a goal, mentally contrasted (MC) a positive outcome of their goal to their present reality, identified an obstacle, and formed an implementation intention (II) to overcome that obstacle. During reflection, students self-reported their distraction while studying. Distraction was the most frequently reported study obstacle, and decreasing distraction was the second most frequently reported study goal. While students who aimed to decrease distraction as a goal did not follow through, students who planned for distraction obstacles did follow through on decreasing distraction levels. Only about half of students generated an II that aligned with their study goal, which may provide one reason for the opposing follow-through of distraction framed as a goal versus as an obstacle. Lastly, we examined the specificity of students' II's and found no relationship with follow-through. Overall, MC with II holds promise as a self-regulatory technique to help introductory biology students change their behaviors while studying.

Evaluating the stability of host-reference gene expression and simultaneously quantifying parasite burden and host immune responses in murine malaria.

The efficacy of pre-erythrocytic stage malaria antigens or vaccine platforms is routinely assessed in murine models challenged with Plasmodium sporozoites. Relative liver-stage parasite burden is quantified using reverse transcription quantitative PCR (RTqPCR), which relies on constitutively expressed endogenous control reference genes. However, the stability of host-reference gene expression for RTqPCR analysis following Plasmodium challenge and immunization has not been systematically evaluated. Herein, we evaluated the stability of expression of twelve common RTqPCR reference genes in a murine model of Plasmodium yoelii sporozoite challenge and DNA-adenovirus IV 'Prime-Target' immunization. Significant changes in expression for six of twelve reference genes were shown by one-way ANOVA, when comparing gene expression levels among challenge, immunized, and naïve mice groups. These changes were attributed to parasite challenge or immunization when comparing group means using post-hoc Bonferroni corrected multiple comparison testing. Succinate dehydrogenase (SDHA) and TATA-binding protein (TBP) were identified as stable host-reference genes suitable for relative RTqPCR data normalisation, using the RefFinder package. We defined a robust threshold of 'partial-protection' with these genes and developed a strategy to simultaneously quantify matched host parasite burden and cytokine responses following immunisation or challenge. This is the first report systematically identifying reliable host reference genes for RTqPCR analysis following Plasmodium sporozoite challenge. A robust RTqPCR protocol incorporating reliable reference genes which enables simultaneous analysis of host whole-liver cytokine responses and parasite burden will significantly standardise and enhance results between international malaria vaccine efficacy studies.

Lost support, lost skills: Children's cognitive outcomes following grandparental death.

OBJECTIVE: This study examines the implications of grandparental death for cognitive skills in middle childhood. METHOD: This study uses data from the Future of Families and Child Wellbeing Study (N = 2479) to estimate ordinary least squares regression models of the associations between grandparental death and subsequent cognitive skills among children in middle childhood. RESULTS: Experiencing a grandparental death between ages 5 and 9 is associated with boys' lower reading, verbal, and math scores at age 9, with associations most notable for Black and Hispanic boys; grandparental death before age 5 has minimal influence on boys' cognitive skills at age 9. There is little indication that grandparental death adversely affects girls' cognitive skills. CONCLUSION: The numerous and persistent implications of grandparental death for boys' cognitive skills merit greater recognition of grandparental death as a source of family instability, stress, and ultimately inequality in child development.

AYA-UNITE: Lessons Learned on Intervention Development Promoting Social and Physical Health of Adolescent/Young Adult Cancer Survivors.

Adolescent/young adult cancer survivors (AYACS) struggle with poor psychosocial health related to social disruptions due to cancer diagnosis, impacting long-term goal achievement and overall health. In particular, social health promotion is overlooked in AYACS' care. AYA-UNITE, a sociobehavioral exercise intervention pilot for AYACS 15-21 years of age at cancer diagnosis, was designed to foster AYACS' social and physical health. AYA-UNITE was a 12-week group-based virtual exercise program incorporating strength training and aerobic activity. In this brief report, we account AYA-UNITE's conceptual design, lessons learned through AYA-UNITE intervention development, and opportunities for improvement in implementing effective AYACS psychosocial interventions (NCT03778658).

BatTool: projecting bat populations facing multiple stressors using a demographic model.

Bats provide ecologically and agriculturally important ecosystem services but are currently experiencing population declines caused by multiple environmental stressors, including mortality from white-nose syndrome and wind energy development. Analyses of the current and future health and viability of these species may support conservation management decision making. Demographic modeling provides a quantitative tool for decision makers and conservation managers to make more informed decisions, but widespread adoption of these tools can be limited because of the complexity of the mathematical, statistical, and computational components involved in implementing these models. In this work, we provide an exposition of the BatTool R package, detailing the primary components of the matrix projection model, a publicly accessible graphical user interface ( https://rconnect.usgs.gov/battool ) facilitating user-defined scenario analyses, and its intended uses and limitations (Wiens et al., US Geol Surv Data Release 2022; Wiens et al., US Geol Surv Softw Release 2022). We present a case study involving wind energy permitting, weighing the effects of potential mortality caused by a hypothetical wind energy facility on the projected abundance of four imperiled bat species in the Midwestern United States.

Iron-sensitive protein conjugates formed with a Wittig reaction precursor in ionic liquid.

In this report, formation of protein conjugates with an iron-sensitive enamine linkage is demonstrated through the ionic liquid-based bioconjugation method.

The Care Gap in Later Life Across European Countries.

OBJECTIVES: Do adults without kin experience a care gap where they need help with activities of daily living but get no help from any source? We examine the prevalence of the care gap across Europe, and test whether those without partners or children substitute for their lack of close kin with help from broader networks, or whether they disproportionately experience care gaps. METHODS: Using data from the Survey on Health, Ageing and Retirement in Europe, we estimate the care gap in 28 European countries and Israel, how it varies, and who provides help for respondents with different family structures. RESULTS: The care gap is substantial, with 6.1% of all respondents ages 50 and above reporting a gap. It is highest in Western and Eastern Europe and lowest in Southern Europe and Israel. Respondents without partners or children are significantly more likely to have care gaps than those with close kin. However, respondents without close kin draw more often on more diverse networks of friends and relatives and use nursing home care. DISCUSSION: Our study introduces the concept of the care gap and shows that although it is most common among unpartnered adults without children it is also quite common for those with immediate family. A broader network partially but not completely substitutes for care gaps among those without immediate family. Our results offer new insights into the demand for public care services in countries with diverse welfare states.

Social network interventions to reduce race disparities in living kidney donation: Design and rationale of the friends and family of kidney transplant patients study (FFKTPS).

INTRODUCTION: Racial/ethnic disparities in living donor kidney transplantation (LDKT) are a persistent challenge. Although nearly all directed donations are from members of patients' social networks, little is known about which social network members take steps toward living kidney donation, which do not, and what mechanisms contribute to racial/ethnic LDKT disparities. METHODS: We describe the design and rationale of the Friends and Family of Kidney Transplant Patients Study, a factorial experimental fielding two interventions designed to promote LKD discussions. Participants are kidney transplant candidates at two centers who are interviewed and delivered an intervention by trained center research coordinators. The search intervention advises patients on which social network members are most likely to be LKD contraindication-free; the script intervention advises patients on how to initiate effective LKD discussions. Participants are randomized into four conditions: no intervention, search only, script only, or both search and script. Patients also complete a survey and optionally provide social network member contact information so they can be surveyed directly. This study will seek to enroll 200 transplant candidates. The primary outcome is LDKT receipt. Secondary outcomes include live donor screening and medical evaluations and outcomes. Tertiary outcomes include LDKT self-efficacy, concerns, knowledge, and willingness, measured before and after the interventions. CONCLUSION: This study will assess the effectiveness of two interventions to promote LKD and ameliorate Black-White disparities. It will also collect unprecedented information on transplant candidates' social network members, enabling future work to address network member structural barriers to LKD.

Mechanical indications for inflatable penile prosthesis revision: analysis and implications for revision surgery.

BACKGROUND: Despite technical advancements, inflatable penile prostheses (IPPs) are inherently at risk of mechanical failure given their nature as hydraulic devices. AIM: To characterize IPP component failure location at the time of device revision and stratify by manufacturer: American Medical Systems (Boston Scientific [BSCI]) and Coloplast (CP). METHODS: A retrospective review of penile prosthesis cases from July 2007 to May 2022 was conducted, identifying men who underwent revision surgery. Cases were excluded if documentation did not denote the cause of failure or the manufacturer. Mechanical indications for surgery were categorized by location (eg, tubing, cylinder, or reservoir leak; pump malfunction). Nonmechanical revisions were excluded (component herniation, erosion, or crossover). Categorical variables were assessed with Fisher exact or chi-square analysis; Student t-test and Mann-Whitney U test were used for continuous variables. OUTCOMES: Primary outcomes included specific location of IPP mechanical failure among BSCI and CP devices and time to mechanical failure. RESULTS: We identified 276 revision procedures, 68 of which met inclusion criteria (46 BSCI and 22 CP). Revised CP devices were longer than BSCI devices (median cylinder length, 20 vs 18 cm; P < .001). Log-rank analysis revealed a similar time to mechanical failure between brands (P = .096). CP devices failed most often due to tubing fracture (19/22, 83%). BSCI devices had no predominant site of failure. Between manufacturers, tubing failure was more common in CP devices (19/22 vs 15/46 for BSCI, P < .001), while cylinder failure was more common among BSCI devices (10/46 vs 0/22 for CP, P = .026). CLINICAL IMPLICATIONS: The distribution of mechanical failure is significantly different between BSCI and CP devices; this has implications regarding the approach to revision surgery. STRENGTHS AND LIMITATIONS: This is the first study to directly compare when and where mechanical failure occurs in IPPs and to compare the 2 main manufacturers head-to-head. This study would be strengthened by being repeated in a multi-institutional fashion to provide more robust and objective evaluation. CONCLUSION: CP devices commonly failed at the tubing and rarely elsewhere, while BSCI devices showed no predominant failure site; these findings may inform decision making regarding revision surgery.

Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates.

INTRODUCTION: Many studies of Black-White disparities in living donor kidney transplantation hypothesize that they were partially due to Black-White differences in candidate social network access to healthy, willing donors. This differential access hypothesis has not been tested using directly measured social network data. RESEARCH QUESTIONS: Do black kidney transplant candidates have perceived lower social network access to health and/or willing living donors than white candidates? DESIGN: A cross-sectional survey that measured the social network members was collected in 2015. Black-White differences in patient counts of perceived healthy and/or willing potential donors in social networks, and individual network members' probability of being perceived healthy and/or willing, were compared using logistic and negative binomial regression models. RESULTS: The survey included 66 kidney transplant candidates reporting on 1474 social network members at a large Southeastern US transplant center in 2015. Black and White patients had similar access to perceived healthy, likely potential donors (86% vs 87% had 1 or more, P = .92; 5.91 vs 4.13 mean counts, P = .20) and perceived healthy, agreed potential donors (56% vs 48%, P = .54; 1.77 vs 1.74, P = .97). Black patients' network members were individually more likely to be perceived healthy and likely potential donors (26% vs 21%, P = .04), and White patients' network members were more likely to have agreed (13% vs 9%, P = .03), but these differences were statistically insignificant in demographically adjusted models. CONCLUSION: Black and White transplant candidates perceived access to similar numbers of potential donors in their social networks. This result does not support the differential access hypothesis.

Gaussian process forecasts Pseudogymnoascus destructans will cover coterminous United States by 2030.

White-nose syndrome has been decimating populations of several bat species since its first occurrence in the Northeastern United States in the winter 2006-2007. The spread of the disease has been monitored across the continent through the collaboration of many organizations. Inferring the rate of spread of the disease and predicting its arrival at new locations is critical when assessing the current and predicting the future status and trends of bat species. We developed a model of disease spread that simultaneously achieves high-predictive performance, computational efficiency, and interpretability. We modeled white-nose syndrome spread using Gaussian process variations to infer the spread rate of the disease front, identify areas of anomalous time of arrival, and provide future forecasts of the expected time of arrival throughout North America. Cross-validation of model predictive performance identified a stationary Gaussian process without an additional residual error process as the best-supported model. Results indicated that white-nose syndrome is likely to spread throughout the entire continental United States by 2030. These annually updatable model predictions will be useful in determining the horizon over which disease management actions must take place as well as in status and trend assessments of disease-affected bats.

A high-throughput screening RT-qPCR assay for quantifying surrogate markers of immunity from PBMCs.

Immunoassays that quantitate cytokines and other surrogate markers of immunity from peripheral blood mononuclear cells (PBMCs), such as flow cytometry or Enzyme-Linked Immunosorbent Spot (ELIspot), allow highly sensitive measurements of immune effector function. However, those assays consume relatively high numbers of cells and expensive reagents, precluding comprehensive analyses and high-throughput screening (HTS). To address this issue, we developed a sensitive and specific reverse transcription-quantitative PCR (RT-qPCR)-based HTS assay, specifically designed to quantify surrogate markers of immunity from very low numbers of PBMCs. We systematically evaluated the volumes and concentrations of critical reagents within the RT-qPCR protocol, miniaturizing the assay and ultimately reducing the cost by almost 90% compared to current standard practice. We assessed the suitability of this cost-optimized RT-qPCR protocol as an HTS tool and determined the assay exceeds HTS uniformity and signal variance testing standards. Furthermore, we demonstrate this technique can effectively delineate a hierarchy of responses from as little as 50,000 PBMCs stimulated with CD4+ or CD8+ T cell peptide epitopes. Finally, we establish that this HTS-optimized protocol has single-cell analytical sensitivity and a diagnostic sensitivity equivalent to detecting 1:10,000 responding cells (i.e., 100 Spot Forming Cells/106 PBMCs by ELIspot) with over 90% accuracy. We anticipate this assay will have widespread applicability in preclinical and clinical studies, especially when samples are limited, and cost is an important consideration.