Simulation of early season herbivory via mechanical damage affects flower production in pumpkin (Cucurbita pepo ssp. pepo).

BACKGROUND: Damage from insect herbivores can elicit a wide range of plant responses, including reduced or compensatory growth, altered volatile profiles, or increased production of defence compounds. Specifically, herbivory can alter floral development as plants reallocate resources towards defence and regrowth functions. For pollinator-dependent species, floral quantity and quality are critical for attracting floral visitors; thus, herbivore-induced developmental effects that alter either floral abundance or attractiveness may have critical implications for plant reproductive success. Based on past work on resource trade-offs, we hypothesize that herbivore damage-induced effects are stronger in structural floral traits that require significant resource investment (e.g., flower quantity), as plants reallocate resources towards defence and regrowth, and weaker in secondary floral traits that require less structural investment (e.g., nectar rewards). SCOPE: In this study, we simulated early-season herbivore mechanical damage in the domesticated jack-o-lantern pumpkin Cucurbita pepo ssp. pepo and measured a diverse suite of floral traits over a 60-day greenhouse experiment. KEY RESULTS: We found that mechanical damage delayed the onset of male anthesis and reduced the total quantity of flowers produced. Additionally, permutational multivariate analysis of variance (PERMANOVA) indicated that mechanical damage significantly impacts overall floral volatile profile, though not output of sesquiterpenoids, a class of compounds known to recruit specialized cucumber beetle herbivores and squash bee pollinators. CONCLUSIONS: In summary, we show that C. pepo spp. pepo reduces investment in male flower production following mechanical damage, and that floral volatiles do exhibit shifts in production, indicative of damage-induced trait plasticity. Such reductions in male flower production could reduce the relative attractiveness of damaged plants to foraging pollinators in this globally relevant cultivated species.

Impact of Hypertension on the Dose-Response Association Between Physical Activity and Stroke: A Cohort Study.

BACKGROUND: Regular physical activity is associated with a reduced stroke risk. However, this relationship might be attenuated in the presence of hypertension and antihypertensive medication use. We examined the dose-response relationship between physical activity and stroke in normotensive and hypertensive individuals. METHODS: A Dutch population-based cohort including 139 930 individuals (41% men; mean age, 44±13) was performed (median follow-up, 6.75 years). Participants were stratified at baseline as hypertensive (44%) or normotensive (56%) and categorized into quartiles of the lowest (Q1) to the highest (Q4) moderate-to-vigorous, self-reported physical activity. The primary outcome was incident stroke (fatal and nonfatal). Cox regression estimated hazard ratios and 95% CIs. The main analyses were stratified on baseline blood pressure and adjusted for confounders. Hypertensives were stratified into medicated (21%) or non-medicated (79%). RESULTS: Compared with Q1, adjusted hazard ratios were 0.87 (0.69-1.10; P=0.23), 0.75 (0.59-0.95; P=0.02), and 0.94 (0.74-1.20; P=0.64) for Q2 to Q4, respectively in the total population. Hazard ratios for normotensives were 0.79 (0.50-1.25; P=0.32), 0.75 (0.48-1.18; P=0.22), 0.97 (0.62-1.51; P=0.90) for Q2 to Q4, respectively. In hypertensives, hazard ratios were 0.89 (0.68-1.17; P=0.41), 0.74 (0.56-0.98; P=0.03), 0.92 (0.69-1.23; P=0.56) for Q2 to Q4, respectively. There was no significant interaction between hypertension status for the relation between physical activity and stroke risk. The stratified analysis revealed a smaller benefit of moderate-to-vigorous physical activity in medicated hypertensives compared with nonmedicated hypertensives, but no significant interaction effect was found. CONCLUSIONS: Regular moderate-to-vigorous physical activity is beneficial for stroke risk reduction (Q3 compared with Q1), which is not affected by hypertension. Antihypertensive medication may be associated with a smaller benefit of moderate-to-vigorous physical activity on the risk of stroke, but further research is warranted.

The interaction of genetics and physical activity in the pathogenesis of metabolic dysfunction associated liver disease.

Genetic variants associated with increased liver fat and volume have been reported, but whether physical activity (PA) can attenuate the impact of genetic susceptibility to these traits is poorly understood. We aimed to investigate whether higher PA modify genetic impact on liver-related traits in the UK Biobank cohort. PA was self-reported, while magnetic resonance images were used to estimate liver fat (n = 27,243) and liver volume (n = 24,752). Metabolic dysfunction-associated liver disease (MASLD) and chronic liver disease (CLD) were diagnosed using ICD-9 and ICD-10 codes. Ten liver fat and eleven liver volume-associated genetic variants were selected and unweighted genetic-risk scores for liver fat (GRSLF) and liver volume (GRSLV) were computed. Linear regression analyses were performed to explore interactions between GRSLF/ GRSLV and PA in relation to liver-related traits. Association between GRSLF and liver fat was not different among lower (ß = 0.063, 95% CI 0.041-0.084) versus higher PA individuals (ß = 0.065, 95% CI 0.054-0.077, pinteraction = 0.62). The association between the GRSLV and liver volume was not different across different PA groups (pinteraction = 0.71). Similarly, PA did not modify the effect of GRSLF and GRSLV on MASLD or CLD. Our findings show that physical activity and genetic susceptibility to liver-related phenotypes seem to act independently, benefiting all individuals regardless of genetic risk.

Survival and transfer potential of Salmonella enterica serovar Typhimurium colonising polyethylene microplastics in contaminated agricultural soils.

Agricultural environments are becoming increasingly contaminated with plastic pollution. Plastics in the environment can also provide a unique habitat for microbial biofilm, termed the 'plastisphere', which can also support the persistence of human pathogens such as Salmonella. Human enteric Salmonella enterica serovar Typhimurium can enter agricultural environments via flooding or from irrigation with contaminated water. Using soil mesocosms we quantified the ability of S. Typhimurium to persist on microplastic beads in two agriculturally relevant soils, under ambient and repeat flood scenarios. S. Typhimurium persisted in the plastisphere for 35 days in both podzol and loamy soils; while during multiple flood events was able to survive in the plastisphere for up to 21 days. S. Typhimurium could dissociate from the plastisphere during flooding events and migrate through soil in leachate, and importantly could colonise new plastic particles in the soil, suggesting that plastic pollution in agricultural soils can aid S. Typhimurium persistence and facilitate further dissemination within the environment. The potential for increased survival of enteric human pathogens in agricultural and food production environments due to plastic contamination poses a significant public health risk, particularly in potato or root vegetable systems where there is the potential for direct contact with crops.

Elevated Salt or Angiotensin II Levels Induce CD38+ Innate Immune Cells in the Presence of Granulocyte-Macrophage Colony Stimulating Factor.

Hypertension (HTN) impacts almost half of adults, predisposing them to cardiovascular disease and renal damage. Salt-sensitive HTN (SSHTN) and angiotensin II (A2)-induced HTN (A2HTN) both involve immune system activation and renal innate immune cell infiltration. Subpopulations of activated [Cluster of differentiation 38 (CD38)] innate immune cells, such as macrophages and dendritic cells (DCs), play distinct roles in modulating renal function and blood pressure. It is unknown how these cells become CD38+ or which subtypes are pro-hypertensive. When bone marrow-derived monocytes (BMDMs) were grown in granulocyte-macrophage colony stimulating factor (GM-CSF) and treated with salt or A2, CD38+ macrophages and CD38+ DCs increased. The adoptive transfer of GM-CSF-primed BMDMs into mice with either SSHTN or A2HTN increased renal CD38+ macrophages and CD38+ DCs. Flow cytometry revealed increased renal M1 macrophages and type-2 conventional DCs (cDC2s), along with their CD38+ counterparts, in mice with either SSHTN or A2HTN. These results were replicable in vitro. Either salt or A2 treatment of GM-CSF-primed BMDMs significantly increased bone marrow-derived (BMD)-M1 macrophages, CD38+ BMD-M1 macrophages, BMD-cDC2s, and CD38+ BMD-cDC2s. Overall, these data suggest that GM-CSF is necessary for the salt or A2 induction of CD38+ innate immune cells, and that CD38 distinguishes pro-hypertensive immune cells. Further investigation of CD38+ M1 macrophages and CD38+ cDC2s could provide new therapeutic targets for both SSHTN and A2HTN.

Psychosocial implications of learning amyloid PET results in an observational cohort.

INTRODUCTION: Information on the psychosocial impact of Alzheimer's disease (AD) biomarker testing in adults at risk of AD is needed to inform best practices for communicating biomarker results. METHODS: Ninety-nine cognitively unimpaired older adults learned amyloid positron emission tomography (PET) results (mean age = 72.0 ± 4.8, 95% White, 28% elevated amyloid). Linear mixed-effects regression models were used to test the main effects and interaction of PET result × time on psychosocial outcomes up to 6 months after learning results. RESULTS: A significant interaction of PET result × time was observed for concern about AD (ß = 0.28, p = 0.02) and intrusive thoughts and avoidance (ß = -0.82, p < 0.001). A main effect of PET result was observed for AD test-related distress (ß = 12.09, p < 0.001). DISCUSSION: Cognitively unimpaired adults learning elevated-amyloid PET results reported mildly intrusive thoughts/avoidance initially following disclosure, but these symptoms decreased over time. Concern about AD dementia and AD biomarker test-related distress remained higher in elevated-amyloid compared to non-elevated-amyloid participants. HIGHLIGHTS: Longitudinal assessment of psychosocial reactions after amyloid PET disclosure was conducted. Transient highly intrusive thoughts or avoidance after learning elevated amyloid results. Persistent test result-related distress after receiving elevated-amyloid results. There is increased concern about AD dementia after receiving elevated-amyloid results. Happiness and relief are experienced after receiving non-elevated-amyloid results.

Longitudinal effects of peer victimization on adolescents' future educational and work expectations: Depressive symptoms as a mechanism.

Leveraging six waves of data, this study examined the effects of ninth-grade peer victimization on adolescents' future work and education expectations 2 years later, testing depressive symptoms as a mechanism. Participants (N = 388, Mage = 14.05; 61% female, 35% male, 3% non-binary, trans, or other gender; 46% White, 19% Black, 17% Asian, 6% AMENA, 6% Multiracial, 6% other race) completed surveys from ninth through 11th grade. Results indicated that adolescents who experienced more frequent relational, but not overt, peer victimization in ninth grade were subsequently more pessimistic about their educational and occupational prospects beyond high school; depressive symptoms mediated this link. The findings suggest that relational victimization and its psychological harm may undermine adolescents' confidence in achieving postsecondary success.

The effectiveness of the Mediterranean Diet for primary and secondary prevention of cardiovascular disease: An umbrella review.

AIMS: This study aimed to review meta-analyses of randomised controlled trials that evaluated the effectiveness of the Mediterranean Diet for the primary and secondary prevention of cardiovascular disease. METHODS: Five databases (Medline, Embase, Cochrane, CINAHL and ProQuest) were searched from inception to November 2022. Inclusion criteria were: (i) systematic review of randomised controlled studies with metanalysis; (ii) adults ≥18 years from the general population with (secondary prevention) and without (primary prevention) established cardiovascular disease; (iii) Mediterranean Diet compared with another dietary intervention or usual care. Review selection and quality assessment using AMSTAR-2 were completed in duplicate. GRADE was extracted from each review, and results were synthesised narratively. RESULTS: Eighteen meta-analyses of 238 randomised controlled trials were included, with an 8% overlap of primary studies. Compared to usual care, the Mediterranean Diet was associated with reduced cardiovascular disease mortality (n = 4 reviews, GRADE low certainty; risk ratio range: 0.35 [95% confidence interval: 0.15-0.82] to 0.90 [95% confidence interval: 0.72-1.11]). Non-fatal myocardial infarctions were reduced (n = 4 reviews, risk ratio range: 0.47 [95% confidence interval: 0.28-0.79] to 0.60 [95% confidence interval: 0.44-0.82]) when compared with another active intervention. The methodological quality of most reviews (n = 16/18; 84%) was low or critically low and strength of evidence was generally weak. CONCLUSIONS: This review showed that the Mediterranean Diet can reduce fatal cardiovascular disease outcome risk by 10%-67% and non-fatal cardiovascular disease outcome risk by 21%-70%. This preventive effect was more significant in studies that included populations with established cardiovascular disease. Better quality reviews are needed.

Negative prior aquatic experiences and children's aquatic competency: Do parent perceptions differ from reality?

ISSUE ADDRESSED: Achieving aquatic competence is recommended for preventing childhood drownings, yet many children in Victoria, Australia do not meet aquatic benchmarks despite participating in swimming and water safety programs. While few studies have explored factors influencing aquatic competency development, negative prior aquatic experiences (NPAE) have surfaced as a potential influence. Research on children's NPAE has primarily focused on parental perceptions rather than the child's actual experiences. METHODS: Parents and children (aged 10-12 years) completed reliable surveys for background information and NPAE-related data. Children also completed aquatic competency assessments against benchmark standards. Chi-square tests determined relationships between NPAE and aquatic competency, and thematic analysis categorised themes related to perceptions of the child's NPAE. RESULTS: Most parents (82.9%) indicated their child had not had NPAE, while only half (51.0%) of children did not report NPAE. Children reporting NPAE often perceived incidents as nearly drowning (41%), encompassing swimming pool environments and underwater submersion. Similarly, parents reported varied situations, noting NPAE involving open water and the child's loss of control. Parent-reported NPAE was associated with children less likely to achieve knowledge, continuous swimming, and survival competency benchmarks (p < .05). Children reporting NPAE were less likely to achieve underwater competencies (p < .05). CONCLUSIONS: The disparity between parent and child perspectives of NPAE demonstrates the importance of considering both perspectives. This should assist in providing appropriate support for children to develop aquatic competencies. SO WHAT?: Using NPAE data, practitioners can customise swim teaching approaches to address and prevent NPAE, particularly as many children associate their NPAE with pools, the common setting for aquatic education.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Implementing early feeding after liver transplant using implementation frameworks: A multimethod study.

BACKGROUND: Evidence-based guidelines (EBGs) in the nutrition management of advanced liver disease and enhanced recovery after surgery recommendations state that normal diet should recommence 12-24 h following liver transplantation. This study aimed to compare postoperative nutrition practices to guideline recommendations, explore clinician perceptions regarding feeding after transplant surgery, and implement and evaluate strategies to improve postoperative nutrition practices. METHODS: A pre-post multimethod implementation study was undertaken, guided by the knowledge-to-action framework. A retrospective chart audit of postoperative dietary practice and semistructured interviews with clinicians were undertaken. Implementation strategies were informed by the Consolidated Framework for Implementation Research-Expert Recommendations for Implementing Change matching tool and then evaluated. RESULTS: An evidence-practice gap was identified, with the median day to initiation of nutrition (free-fluid or full diet) on postoperative day (POD) 2 and only 25% of patients aligning with the EBGs. Clinician interviews identified belief in the importance of nutrition, with variation in surgical practice in relation to early nutrition, competing clinical priorities, and vulnerabilities in communication contributing to delays in returning to feeding. An endorsed postoperative nutrition protocol was implemented along with a suite of theory- and stakeholder-informed intervention strategies. Following implementation, the median time to initiate nutrition reduced to POD1 and alignment with EBGs improved to 60%. CONCLUSION: This study used implementation frameworks and strategies to understand, implement, and improve early feeding practices in line with EBGs after liver transplant. Ongoing sustainability of practice change as well as the impact on clinical outcomes have yet to be determined.

Brain abscesses, neutropenia, and B-ALL: Multiple testing modalities required to confirm PDCD10 and ETV6 dual diagnoses.

Recognition of patients with multiple diagnoses, and the unique challenges they pose to clinicians and laboratorians, is increasing rapidly as genome-wide genetic testing grows in prevalence. We describe a unique patient with dual diagnoses of PDCD10-related cerebral cavernous malformations and ETV6-related thrombocytopenia with associated neutropenia. She presented with brain abscesses as an infant, which is highly atypical for these disorders in isolation. Confirming her diagnoses depended on thorough phenotyping both during and after her acute illness. Furthermore, the causative variant in ETV6 is a novel single-exon deletion that required multiple modalities with manual review to confirm, including unique use of polymorphic nucleotides in trio exome data. She illustrates the special challenges of patients with multiple diagnoses, and the multiple tools clinicians and laboratorians must use to treat them.

Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation.

OBJECTIVES: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with MASH. Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARγ on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation. METHODS: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre + Cc1fl/fl mutants with conditional Ceacam1 deletion in HSCs and characterized their MASH phenotype. Media transfer experiments were employed to examine whether media from mutant human and murine HSCs activate their wild-type counterparts. RESULTS: LratCre + Cc1fl/fl mutants displayed hepatic inflammation and fibrosis but without insulin resistance or hepatic steatosis. Their HSCs, like KD-LX2 cells, underwent myofibroblastic transformation and their media activated wild-type HSCs. This was inhibited by nicotinic acid treatment which blunted the release of IL-6 and fatty acids, both of which activate the epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib inhibition of EGFR and its downstream NF-κB/IL-6/STAT3 inflammatory and MAPK-proliferation pathways also blunted HSCs activation in the absence of CEACAM1. CONCLUSIONS: Loss of CEACAM1 in HSCs provoked their myofibroblastic transformation in the absence of insulin resistance and hepatic steatosis. This response is mediated by autocrine HSCs activation of the EGFR pathway that amplifies inflammation and proliferation.

Public Willingness to Mask and Vaccinate in the Future: Results From a 2023 Nationally Representative Survey of US Adults.

The enduring spread of COVID-19 and other respiratory viruses highlights a need for greater focus on long-term public willingness to perform protective behaviors. Although COVID-19 is no longer considered a public health emergency of international concern, it is unknown whether people in the United States plan to continue protective behaviors to protect themselves and others against infection. To inform planning and communications, we used a nationally representative survey of 1,936 US adults to examine attitudes and intentions toward future vaccination and mask-wearing. A majority believed COVID-19 vaccines were safe (73%) and effective in protecting against serious illness (72%). One-third (33%) had strong intentions to get an updated COVID-19 vaccine most years in the future. Among those with weaker intentions (n=1,287), many cited concerns about safety (71%) and efficacy (64%), lack of trust in institutions (64%), or beliefs that prior vaccination or infection protected them (62%). Approximately two-thirds (69%) of respondents believed masks were effective in protecting the wearer from getting COVID-19, and a majority appeared moderately receptive to future public mask-wearing, particularly when there was proximate risk of infection from COVID-19 (67%) or other respiratory viruses (59%). Men, non-Hispanic White adults, younger adults, rural residents, and adults with higher incomes, without college degrees, and without serious medical conditions or physical limitations were more likely to indicate resistance toward future COVID-19 vaccination and/or mask-wearing. Findings support tailored messaging to address concerns and opportunities among different populations, as well as support for communications programs and community engagement to motivate future uptake.

Delta-8 Tetrahydrocannabinol Exposures Reported to US Poison Centers: Variations Among US States and Regions and Associations with Public Policy.

INTRODUCTION: This study investigated exposures involving ∆8-tetrahydrocannabinol (∆8-THC) reported to US poison centers (PCs), including variation among states and regions. It evaluated whether the ∆8-THC exposure rate was lower among states with ∆8-THC regulations and states where cannabis (∆9-THC) use was legal. METHODS: National Poison Data System data for ∆8-THC exposures in 2021-2022 were analyzed, including comparisons of state and regional population-based exposure rates. RESULTS: There were 4,925 exposures involving ∆8-THC as the primary substance reported to US PCs from January 1, 2021, to December 31, 2022, with 69.8% of these reported in the US South. The rate of exposure per 100,000 US population increased by 79.2% from 0.53 in 2021 to 0.95 in 2022. In 2022, the mean rate of ∆8-THC exposures in states where cannabis use was illegal was 1.64 per 100,000 population (95% CI: 1.08-2.20) compared with 0.52 (95% CI: 0.29-0.76) in states where cannabis use was legal (P = 0.0010). In 2022, the mean rate of ∆8-THC exposures in states where ∆8-THC was unregulated was 1.36 per 100,000 population (95% CI: 0.95-1.77) compared with 0.17 (95% CI: 0.06-0.27) in states where ∆8-THC was banned (P < 0.0001). CONCLUSIONS: The rate of ∆8-THC exposures reported to US PCs increased by 79% from 2021 to 2022, with the US South accounting for more than two-thirds of exposures. The rate of ∆8-THC exposures reported to PCs was significantly lower among states where ∆8-THC was banned and among states where cannabis use was legal. Consistent regulation of ∆8-THC across all states should be adopted.

Developing Infectious Disease Outbreak Emergency Communications for Populations With Limited English Proficiency: Insights to Sustain Collaborations Between Local Health Departments and Community-Based Organizations.

PURPOSE: State and local public health departments (LHDs) are encouraged to collaborate with community-based organizations (CBOs) to enhance communication and promote protective practices with communities made vulnerable during emergencies, but there is little evidence-based understanding of practical approaches to fostering collaboration in this context. This research focuses on how collaboration enhances LHD capacity for effective communication for people with limited English proficiency (LEP) during infectious disease outbreaks specifically and strategies to facilitate productive LHD-CBO collaboration. DESIGN: Qualitative, telephone interviews, conducted March-October 2021. SETTING: Rural and urban jurisdictions with Chinese-speaking or Spanish-speaking populations across the United States. PARTICIPANTS: 36 LHD and 31 CBO staff working on outreach to Chinese and Spanish speakers during COVID-19. METHOD: Interviews were audio-recorded, transcribed verbatim, and analyzed using a team-based, codebook approach to thematic analysis. RESULTS: During COVID-19, CBOs extended LHD capacity to develop and disseminate effective communication, meaning communication that is rapidly in-language, culturally resonant, locally relevant, and trusted. Practical strategies to enable and sustain effective collaboration were needed to address operational dimensions (eg, material and administrative) and relational dimensions (eg, promoting trust and respect). CONCLUSION: Policies and financing to support LHD-CBO collaborations are critical to improving communication with people with LEP and addressing long-standing inequities in outcomes during outbreaks.

School knowledge of infectious diseases in schools: conducting surveillance and on-demand, symptomatic respiratory viral testing in a large pre-kindergarten-12th grade school district.

Background: Limited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS). Methods: School KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten-12th grade) in Kansas City, Missouri. During the 2022-2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs. Results: From 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys. Conclusion: Respiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures.

The current landscape of spatial biomarkers for prediction of response to immune checkpoint inhibition.

Enabling the examination of cell-cell relationships in tissue, spatially resolved omics technologies have revolutionised our perspectives on cancer biology. Clinically, the development of immune checkpoint inhibitors (ICI) has advanced cancer therapeutics. However, a major challenge of effective implementation is the identification of predictive biomarkers of response. In this review we examine the potential added predictive value of spatial biomarkers of response to ICI beyond current clinical benchmarks.

Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers.

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts neurite-mediated cellular communication in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to docetaxel therapies. Moreover, t-NEPC-specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.