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Background: At the onset of the COVID-19 pandemic, schools closed across the United States. Given the impact of virtual learning and lost access to school resources, schools eventually reopened with COVID-19 mitigation protocols in place. This qualitative study sought to understand parental perceptions of school-based COVID-19 mitigation strategies. Methods: Using a phenomenology approach, nine focus groups were completed with 40 parents of children in grades K-8 representing eight Maryland counties. Based on acceptance of masking policies (as indicated on a survey), parents were sorted into 2 groups--lower and higher masking acceptance. A thematic analysis was conducted for each group and themes were compared between the 2 groups. Results: The main themes were related to parents' general sentiments regarding COVID-19, compliance, pandemic-related changes over time, changes in personal opinions, and in-person learning. Both groups described challenges related to inconsistent COVID-19 mitigation policies and practices, the challenges of rapid and frequent changes in guidelines during the pandemic, and the benefits of in-person learning. Conclusions: Parents of elementary and middle school children, regardless of general acceptance of masking policies, shared concerns about implementation and guidance regarding school-based mitigation strategies.

Background: The COVID-19 pandemic disrupted routine school operations, including school health programs. This study aims to describe the pandemic's impact on school health service delivery from the perspective of Maryland school health partners. Methods: We conducted semi-structured interviews with health service representatives from public schools (K-12) between July and December 2021. Interviews were recorded, transcribed, and coded through an iterative process to develop analytic themes. Results: Twenty school health partners from 15 Maryland school districts participated. Participants identified key impacts of COVID-19 on school health: (1) COVID-19 disrupted delivery of services such as dental, mental health, and preventative care, (2) COVID-19 necessitated changes in service delivery platforms, (3) COVID-19 affected school health staff through increased responsibilities and staffing shortages, and (4) COVID-19 prompted schools to become hubs for community outreach and health education. Implications for School Health Policy, Practice, and Equity: Consideration of school health service disruptions and the increased demands on service providers may inform future priorities for school administrators, health departments, and policymakers. Conclusions: COVID-19 impacted the timing and method of service delivery as well as the roles of school health staff and schools themselves in public health and education.

Childhood adversity can have detrimental impacts on life course mental and physical health. Timing, nature, severity, and chronicity of adversity are thought to explain much of the variability in health and developmental outcomes among exposed individuals. The current study seeks to characterize heterogeneity in adverse experiences over time at the individual, family, and neighborhood domains in a cohort of predominantly Black children (85% Black and 15% White, 46.2% girls, 67.2% free/reduced lunch in first grade), and to examine associations with mental health from sixth grade to age 26. Participants were part of a randomized universal preventive interventions trial in first grade with prospective follow-up through early adulthood. Separate models characterized heterogeneity in adversity in elementary, middle, and high schools. Changes in adversity over time and relationships with mental health (anxiety, depression, suicidal behaviors) were investigated using a random-intercept latent transition analysis (RI-LTA). We identified three-class solutions in early childhood, middle school, and high school. Generally, both a higher and a lower poly-adversity class were observed at each time point, with varying nature of adversity characterized by the third class. RI-LTA indicated prevalent within-individual changes in adverse exposure over time and differential associations with mental health and suicidal behaviors. Results suggest that treating adverse exposures as a static construct may limit the ability to characterize salientvariation over time. Identifying complexity in adverse experiences and their relation to health and well-being is key for developing and implementing effective prevention and early intervention efforts to mitigate negative effects through the life course.

Coarse mineral dust particles have been observed much further from the Sahara than expected based on theory. They have impacts different to finer particles on Earth's radiative budget, as well as carbon and hydrological cycles, though they tend to be under-represented in climate models. We use measurements of the full dust size distribution from aircraft campaigns over the Sahara, Canaries, Cabo Verde and Caribbean. We assess the observed and modelled dust size distribution over long-range transport at high vertical resolution using the Met Office Unified Model, which represents dust up to 63.2 µm diameter, greater than most climate models. We show that the model generally replicates the vertical distribution of the total dust mass but transports larger dust particles too low in the atmosphere. Importantly, coarse particles in the model are deposited too quickly, resulting in an underestimation of dust mass that is exacerbated with westwards transport; the 20–63 µm dust mass contribution between 2 and 3.7 km altitude is underestimated by factors of up to 11 in the Sahara, 140 in the Canaries and 240 in Cabo Verde. In the Caribbean, there is negligible modelled contribution of d > 20 µm particles to total mass, compared to 10 % in the observations. This work adds to the growing body of research that demonstrates the need for a process-based evaluation of climate model dust simulations to identify where improvements could be implemented.

Abstract Post marketing safety surveillance depends in part on the ability to detect concerning clinical events at scale. Spontaneous reporting might be an effective component of safety surveillance, but it requires awareness and understanding among healthcare professionals to achieve its potential. Reliance on readily available structured data such as diagnostic codes risks under-coding and imprecision. Clinical textual data might bridge these gaps, and natural language processing (NLP) has been shown to aid in scalable phenotyping across healthcare records in multiple clinical domains. In this study, we developed and validated a novel incident phenotyping approach using unstructured clinical textual data agnostic to Electronic Health Record (EHR) and note type. It’s based on a published, validated approach (PheRe) used to ascertain social determinants of health and suicidality across entire healthcare records. To demonstrate generalizability, we validated this approach on two separate phenotypes that share common challenges with respect to accurate ascertainment: (1) suicide attempt; (2) sleep-related behaviors. With samples of 89,428 records and 35,863 records for suicide attempt and sleep-related behaviors, respectively, we conducted silver standard (diagnostic coding) and gold standard (manual chart review) validation. We showed Area Under the Precision-Recall Curve of ~ 0.77 (95% CI 0.75–0.78) for suicide attempt and AUPR ~ 0.31 (95% CI 0.28–0.34) for sleep-related behaviors. We also evaluated performance by coded race and demonstrated differences in performance by race differed across phenotypes. Scalable phenotyping models, like most healthcare AI, require algorithmovigilance and debiasing prior to implementation.

The addition of methane-reducing compounds (MRCs) to livestock drinking water presents an alternative method for enteric methane mitigation in extensive systems where these compounds cannot be fed through the diet. This work evaluated several such compounds with the potential to be deployed in this manner. Methane-reducing compounds were selected based on the existing literature and likelihood of dissolution when combined with a commercially available water-based nutrient supplement (uPRO) (uPRO ORANGE®, DIT AgTech, QLD, Australia). This, in turn, would demonstrate the capacity for MRCs to be administered through animal drinking water when such supplements are in use. This technique requires the analysis of MRC solubility and stability in solution, which was completed via Fourier transform infrared-attenuated total reflectance spectroscopy. The uPRO supplement is comprised of urea, urea phosphate, and ammonium sulfate, providing nitrogen, phosphorus, and sulfur—limiting nutrients for ruminants grazing extensive systems during drier periods of the year. Accordingly, medium-quality Rhodes grass hay was used in fermentation runs to simulate a basal diet during the dry season. Methane-reducing compounds were assessed in accordance with each variable measured (gas/methane production, dry matter digestibility, stability under different environmental conditions) along with existing research in the field to determine the most suitable compound for co-administration. Whilst most compounds examined in this study appeared to retain their structure in solution with uPRO, fermentation results varied in terms of successful methane mitigation. The additive Agolin Ruminant L emerged as the most promising compound for further in vivo investigation.

Background and objective: Visceral metastatic disease in prostate cancer patients conveys a poor prognosis. Using advanced imaging techniques, studies have demonstrated increasing detection rates of visceral metastasis. Visceral metastases are now seen in up to 30–60% of prostate cancer patients. Survival patterns of site-specific visceral metastasis are described poorly in the literature. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. Methods: Retrospectively, we identified 203 prostate cancer patients with visceral metastases from the Mayo Clinic Advanced Prostate Cancer Registry. Patients were divided into three groups according to the first site of visceral metastases detected: lung, brain, or liver. Visceral metastases were detected primarily on either metabolic imaging (C-11 choline) or prostate-specific membrane antigen positron emission tomography computed tomography (CT) scan. Confirmation of visceral metastasis diagnosis was established with either biopsy when feasible or focused conventional imaging, including focused CT or magnetic resonance imaging. Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression model was conducted to assess different variables that affect overall and cancer-specific survival. Key findings and limitations: Over a median (interquartile range) follow-up duration of 16.2 (3.9–49.8) mo, the overall and cancer-specific survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases than in patients with first-site brain or liver metastases (p

Nigella sativa, also known as black cumin, is esteemed for its rich reservoir of health-benefitting phytoconstituents nestled within its seeds. The composition of its seeds can be influenced by factors such as genotype diversity and agricultural practices. Understanding these dynamics is important for maximizing the nutritional and medicinal attributes of the seeds. This study investigated how different genotypes, growing densities, and sowing times affect oil yield and phytoconstituents of Nigella seeds in Northern Australia. The aim was to find the optimal combination of these factors to maximize desirable compounds. Our findings revealed variability in oil yield and phytoconstituents among different genotypes, growing densities, and sowing times. No single genotype stood out as having elevated levels of all desired compounds. For instance, genotype AVTKS#5 had high total phenolic content (TPC) and antioxidant capacity, while AVTKS#8 and AVTKS#7 excelled in thymoquinone (TQ) and polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs), respectively. Planting density had a nuanced impact, with no significant effect on oil yield and CUPRAC values, but higher densities decreased TPC, FRAP, and TQ. Interestingly, seeds cultivated at 20 and 30 plants/m2 had higher ratios of MUFAs/SFAs, PUFAs/SFAs, and (MUFAs + PUFAs)/SFAs, indicating the importance of planting density in shaping fatty acid profiles. Sowing times also had a noticeable effect, with late sowing leading to a decrease in oil yield from 19% to 14%. May-sown seeds had higher TPC, FRAP, CUPRAC, and fatty acid ratios, while TQ levels peaked in June-sown seeds. Our study highlighted positive correlations among TPC, FRAP, CUPRAC, and TQ, emphasizing their collective contribution to the nutritional and medicinal potency of Nigella seeds. Fatty acids, on the other hand, showed no significant correlation with these parameters, indicating independent regulation. In summary, our comprehensive analysis provides insights into the factors (genotype and agronomic practice) that shape the phytochemical profile of Nigella seeds, and suggests better genotype, planting density, and time of sowing for the cultivation and quality production.

Throughout history, Black women have taken their unique lived experiences to make changes through civic behaviors. At the same time, they hold a complex position in society, located at the intersection of multiple marginalizing identities that put them at risk of experiencing distinct forms of discrimination. To date, little research has examined the patterns of Black women’s civic behaviors and associations with discrimination experiences and well-being. This may be particularly salient during emerging adulthood, a key period of sociopolitical development and increasing mental health problems. The current study seeks to address this gap, drawing from theories of intersectionality and sociopolitical development. Participants included 103 emerging adult Black women (Mage = 24.27, SD = 2.76) with a range of civic experiences. Overall, anti-racist action was the most prevalent domain of civic behavior. Participants were about twice as likely to engage in traditional political behaviors (e.g., signing petitions, giving money) than political protest. Latent class analysis was used to identify three unique subgroups of civic behaviors: Stably Committed, Traditionally Engaged, or Low Engagement. Findings also showed that emerging adult Black women classified as Stably Committed experienced more discrimination and higher depressive symptoms. The current findings inform the creation of safe spaces for emerging adult Black women to be civically engaged as they navigate racism and sexism and take action to seek racial justice.

Abstract Metabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types. By combining post-resuspension stable isotope addition and enzyme inhibitors, we demonstrate in-extract metabolite interconversions due to residual transaminase activity. We extend these findings with untargeted metabolomics where we observe extensive protein-mediated metabolite changes, including in-extract formation of glutamate dipeptide and depletion of total glutathione. Finally, we present a simple extraction workflow that integrates 3 kDa filtration for protein removal as a superior method for polar metabolomics. In this work, we uncover a previously unrecognized, protein-mediated source of observer effects in metabolomics experiments with broad-reaching implications across all research fields using metabolomics and molecular metabolism.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case–control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. Limitations: A retrospective study. Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

The foodborne pathogen Listeria monocytogenes can persist in produce processing environments, which increases the risk for food contamination. Increased resistance to antimicrobials commonly used in cleaning and sanitizing procedures may contribute to L. monocytogenes’ persistence in these environments. This study aimed to evaluate sanitizer resistance in L. monocytogenes isolates collected from three tree fruit packing facilities (F1, F2, and F3) during packing seasons 2020–2021 (Y1) and 2021–2022 (Y2), and to assess evidence of persistence based on the genomic similarity of isolates to historical isolates collected in previous years. L. monocytogenes isolates collected in 2020–2022 (n = 44) were tested for resistance to peroxyacetic acid (PAA) and a proprietary biofilm−removing agent using a broth microdilution assay. Further, L. monocytogenes isolates were whole genome sequenced and screened for the presence of antimicrobial resistance and virulence genes, as well as to assess the genomic similarity of isolates using the CFSAN SNP bioinformatic pipeline. Over half (57%) of the tested isolates had a PAA minimum inhibitory concentration (MIC) of 250 ppm, which was similar to the applied concentration of the PAA sanitizer in the three facilities (230 ppm). In contrast, 80% of tested isolates had a biofilm remover MIC of 0.13 ppm, which was substantially below the concentration applied in the facilities (137 ppm). Genomes of all tested isolates carried antimicrobial resistance (fosX, lin, mdrL, mprF, and norB) and virulence (inlA, inlB, plcA, plcB, prfA, hly, mpl, and iap) genes. L. monocytogenes isolates collected between 2020 and 2022 belonged to three distinct lineages, with 22 multilocus sequence types (MLSTs) belonging to 22 different clonal complexes. Genomic similarity analysis with historical isolates collected from the same facilities in 2016–2017 demonstrated a 5-year persistence of the genotypes ST 1003 and ST 554 in F2, which were no longer detected in 2022. Overall, our results highlight the need to re-evaluate sanitizer concentrations to effectively control persistent L. monocytogenes strains in tree fruit packing facilities.

Objectives: Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to assess the tolerability and safety of KE ingestion in a cohort of older adults. Design: Randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762). Setting: General community, Northern California, USA. Participants: Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n = 30; M = 15, F = 15; age = 76 y, range 65–90 y) were randomized and n = 23 (M = 14, F = 9) completed the protocol. Intervention: Participants were randomly allocated to consume either KE (25 g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily for 12 weeks. Measurements: Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events. Results: There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n = 2 (14.3% [90% CI = 2.6–38.5]); PLA n = 1 (7.1% [90% CI = 0.4–29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 and 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group. Conclusions: This KE was safe and well-tolerated in this study of healthy older adults. These results provide an initial foundation for use of KEs in clinical research with older adults.

Rice cultivation in Madurai district, Tamil Nadu, spans distinct cropping seasons: Kar (May – Jun), Semi-dry (Jul – Aug), Samba/ Late Samba (Aug – Sep), and Navarai (Dec – Jan), each with unique weather conditions and rice varieties. This study explores the correlation between weather parameters temperature, rainfall, humidity, sunshine hours, and wind speed and rice blast disease severity from 2021 to 2023. Using multiple linear regression with ordinary least squares (OLS), the analysis achieves high predictive accuracy (R² = 0.98). Results show that the maximum temperatures correlated negatively with disease severity (r = -0.869 to -0.892), while rainfall (r = 0.768 to 0.804) and wind speed (r = 0.766 to 0.938) correlated positively during the semi-dry season. Relative humidity exhibits varying impacts across seasons. These findings underscore the importance of tailored disease management strategies, such as targeted fungicidal applications during warmer seasons and optimized water management in others. By elucidating these dynamics, the study enhances understanding of weather-disease interactions, providing actionable insights to optimize disease management and enhance crop resilience in Madurai district.

Abstract CSMD1 (Cub and Sushi Multiple Domains 1) is a well-recognized regulator of the complement cascade, an important component of the innate immune response. CSMD1 is highly expressed in the central nervous system (CNS) where emergent functions of the complement pathway modulate neural development and synaptic activity. While a genetic risk factor for neuropsychiatric disorders, the role of CSMD1 in neurodevelopmental disorders is unclear. Through international variant sharing, we identified inherited biallelic CSMD1 variants in eight individuals from six families of diverse ancestry who present with global developmental delay, intellectual disability, microcephaly, and polymicrogyria. We modeled CSMD1 loss-of-function (LOF) pathogenesis in early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells (hESCs). We show that CSMD1 is necessary for neuroepithelial cytoarchitecture and synchronous differentiation. In summary, we identified a critical role for CSMD1 in brain development and biallelic CSMD1 variants as the molecular basis of a previously undefined neurodevelopmental disorder.

Abstract Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Objective: Cancer treatment misinformation (CTM) is pervasive and impacts patient health outcomes. Cancer clinicians play an essential role in addressing CTM. We previously identified four self-reported responses that characterize the communication process clinicians engage in to address CTM. Clinicians 1) work to understand the misinformation; 2) correct the misinformation through education; 3) advise about future online searches; and 4) preserve the clinician-patient relationship. We sought to confirm and expand on the model we developed by observing cancer clinicians' communication while addressing CTM with a standardized patient (SP). Methods: 17 cancer clinicians were audio recorded in a SP encounter, in which a breast cancer SP asked three questions based on CTM. We thematically analyzed transcriptions of the recordings. Results: Clinicians used four responses with associated strategies and skills to address CTM in a standardized clinical encounter, confirming the previously developed model. The four responses were: (1) work to understand the misinformation; (2) correct the misinformation through education; (3) advise about future online searches; and (4) preserve the clinician-patient relationship. This observational approach allowed us to refine strategies within each response and identify communication skills clinicians enact to address CTM. Conclusion: These findings provide a strong foundation for the Misinformation Response Model for cancer clinicians. Future research should examine which components of the model are most effective in improving patient outcomes. Innovation: This is the first study observing clinicians' communication through simulated practice with SPs about CTM.

ABSTRACTAdverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10/SGCE, NNAT, IGF2, H19, PLAGL1, PEG3, MEG3-IG, and DLK1/MEG3 regulatory sequences using pyrosequencing. Using multivariable linear regression models, we found evidence to suggest that financial stress was associated with hypermethylation of MEG3-IG in non-Hispanic White newborns; discrimination was associated with hypermethylation of IGF2 and NNAT in Hispanic newborns, and with hypomethylation of PEG3 in non-Hispanic Black newborns. We also found evidence that maternal ACEs interacted with discrimination to predict offspring PLAGL1 altered DMR methylation, in addition to interactions between maternal ACEs score and discrimination predicting H19 and SGCE/PEG10 altered methylation in non-Hispanic White newborns. However, these interactions were not statistically significant after multiple testing corrections. Findings from this study suggest that maternal ACEs, discrimination, and financial stress are associated with newborn aberrant methylation in imprinted gene regions.

Light and nitrogen availability are basic requirements for photosynthesis. Changing in light intensity and nitrogen concentration may require adaptive physiological and life process changes in phytoplankton cells. Our previous study demonstrated that two Thalassiosira species exhibited, respectively, distinctive physiological responses to light and nitrogen stresses. Transcriptomic analyses were employed to investigate the mechanisms behind the different physiological responses observed in two diatom species of the genus Thalassiosira. The results indicate that the congeneric species are different in their cellular responses to the same shifting light and nitrogen conditions. When conditions changed to high light with low nitrate (HLLN), the large-celled T. punctigera was photodamaged. Thus, the photosynthesis pathway and carbon fixation related genes were significantly down-regulated. In contrast, the small-celled T. pseudonana sacrificed cellular processes, especially amino acid metabolisms, to overcome the photodamage. When changing to high light with high nitrate (HLHN) conditions, the additional nitrogen appeared to compensate for the photodamage in the large-celled T. punctigera, with the tricarboxylic acid cycle (TCA cycle) and carbon fixation significantly boosted. Consequently, the growth rate of T. punctigera increased, which suggest that the larger-celled species is adapted for forming post-storm algal blooms. The impact of high light stress on the small-celled T. pseudonana was not mitigated by elevated nitrate levels, and photodamage persisted.

BackgroundMany patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information.PurposeTo evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel 177Lu-PSMA-617 therapy for prostate cancer.Materials and methodsTwo experts listed the 12 most commonly asked questions by patients on 177Lu-PSMA-617 therapy. These twelve questions were prompted to OpenAI ChatGPT-4 and Google Bard. AI-generated responses were distributed using an online survey platform (Qualtrics) and blindly rated by eight experts. The performances of the AI chatbots were evaluated and compared across three domains: accuracy, conciseness, and readability. Additionally, potential safety concerns associated with AI-generated answers were also examined. The Mann-Whitney U and chi-square tests were utilized to compare the performances of AI chatbots.ResultsEight experts participated in the survey, evaluating 12 AI-generated responses across the three domains of accuracy, conciseness, and readability, resulting in 96 assessments (12 responses x 8 experts) for each domain per chatbot. ChatGPT-4 provided more accurate answers than Bard (2.95 ± 0.671 vs 2.73 ± 0.732, p=0.027). Bard’s responses had better readability than ChatGPT-4 (2.79 ± 0.408 vs 2.94 ± 0.243, p=0.003). Both ChatGPT-4 and Bard achieved comparable conciseness scores (3.14 ± 0.659 vs 3.11 ± 0.679, p=0.798). Experts categorized the AI-generated responses as incorrect or partially correct at a rate of 16.6% for ChatGPT-4 and 29.1% for Bard. Bard’s answers contained significantly more misleading information than those of ChatGPT-4 (p = 0.039).ConclusionAI chatbots have gained significant attention, and their performance is continuously improving. Nonetheless, these technologies still need further improvements to be considered reliable and credible sources for patients seeking medical information on 177Lu-PSMA-617 therapy.

Aim: Nusinersen, administered by intrathecal injection at a dose of 12 mg, is indicated across all ages for the treatment of spinal muscular atrophy (SMA). Evidence on real-world healthcare resource use (HRU) and costs among patients taking nusinersen remains limited. This study aimed to evaluate real-world HRU and costs associated with nusinersen use through US claims databases. Patients & methods: Using the Merative™ MarketScan Research Databases, patients with SMA receiving nusinersen were identified from commercial (January 2017 to June 2020) and Medicaid claims (January 2017 to December 2019). Those likely to have complete information on the date of nusinersen initiation and continuous enrollment 12 months pre- and post-index (first record of nusinersen treatment) were retained. Number and costs (US$ 2020) of inpatient admissions and emergency department (ED) visits, unrelated to nusinersen administration, were evaluated for 12 months pre- and post-nusinersen initiation and stratified by age: pediatric (

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, improving outcomes for many patients. However, toxicities termed immune-related adverse events (irAEs) are limitations of these revolutionary treatments. These irAEs may resolve with treatment or ICI cessation (acute) or persist many months beyond therapy cessation (chronic). Acute irAEs were the first to be recognized and are thus more well studied. However, chronic irAEs have been highlighted in recent years and are becoming a topic of more intensive investigation. These chronic irAEs have been noted to affect many different organ systems, including endocrine, rheumatologic, gastrointestinal, dermatologic, neurologic, and cardiovascular systems. In this review, we discuss current knowledge surrounding the frequency, time course, and risk factors associated with chronic irAEs affecting various organ systems, treatment approaches, and future directions.

Abstract Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor‐predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1+/ex42del miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1+/ex42del and wild‐type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1+/ex42del miniswine demonstrated slower and shorter steps, indicative of a balance‐preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1+/ex42del miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.

Background Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.Patients and methods Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed.Results 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing.Conclusions This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.

BackgroundImmune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%–46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with intensified patient management.MethodsPatients with cardiac irAEs from the SERIO registry (www.serio-registry.org) were analyzed for demographics, ICI-related information (type of ICI, therapy line, combination with other drugs, onset of irAE, and tumor response), examination results, irAE treatment and outcome, as well as oncological endpoints. Cardiac biopsies of irMyocarditis cases (n = 12) were analyzed by Nanostring and compared to healthy heart muscle (n = 5) and longitudinal blood sampling was performed for immunophenotyping of irMyocarditis-patients (n = 4 baseline and n = 8 during irAE) in comparison to patients without toxicity under ICI-therapy (n = 4 baseline and n = 7 during ICI-therapy) using flow cytometry.ResultsA total of 51 patients with 53 cardiac irAEs induced by 4 different ICIs (anti-PD1, anti-PD-L1, anti-CTLA4) were included from 12 centers in 3 countries. Altogether, 83.0% of cardiac irAEs were graded as severe or life-threatening, and 11.3% were fatal (6/53). Thus, in centers with established consequent troponin monitoring, work-up upon the rise in troponin and consequent treatment of irMyocarditis with corticosteroids and –if required–second-line therapy mortality rate is much lower than previously reported. The median time to irMyocarditis was 36 days (range 4–1,074 days) after ICI initiation, whereas other cardiotoxicities, e.g. asystolia or myocardiopathy, occurred much later. The cytokine-mediated signaling pathway was differentially regulated in myocardial biopsies as compared to healthy heart based on enrichment Gene Ontology analysis. Additionally, longitudinal peripheral blood mononuclear cell (PBMC) samples from irMyocarditis-patients indicated ICI-driven enhanced CD4+ Treg cells and reduced CD4+ T cells. Immunophenotypes, particularly effector memory T cells of irMyocarditis-patients differed from those of ICI-treated patients without side effects. LAG3 expression on T cells and PD-L1 expression on dendritic cells could serve as predictive indicators for the development of irMyocarditis.ConclusionInterestingly, our cohort shows a very low mortality rate of irMyocarditis-patients. Our data indicate so far unknown local and systemic immunological patterns in cardiotoxicity.

The plant hormone indole-3-acetic acid (IAA), also known as auxin, plays important roles in plant growth and development, as well as in several plant–microbe interactions. IAA also acts as a microbial signal and in many bacteria regulates metabolism, stress responses, and virulence. In the bacterial plant pathogen Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000), exposure to IAA results in large-scale transcriptional reprogramming, including the differential expression of several known virulence genes. However, how PtoDC3000 senses and responds to IAA and what aspects of its biology are regulated by IAA is not understood. To investigate the mechanisms involved in perceiving and responding to IAA, we carried out a genetic screen for mutants with altered responses to IAA. One group of mutants of particular interest carried disruptions in the aefR gene encoding a TetR family transcriptional regulator. Gene expression analysis confirmed that the aefR mutants have altered responses to IAA. Thus, AefR is the first demonstrated auxin response regulator in PtoDC3000. We also investigated several aspects of PtoDC3000 biology that are regulated by both AefR and IAA, including antibiotic resistance, motility, and virulence. The observation that the aefR mutant has altered virulence on Arabidopsis, suggests that the sector of the IAA response regulated by aefR is important during pathogenesis. Our findings also provide evidence that AefR plays a role in coordinating changes in gene expression during the transition from early to late stages of infection. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate‐specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C‐11 choline positron emission tomography (PET) imaging in patients achieving ultra‐low PSA values and to evaluate clinical outcomes in this patient population. Methods In a single institution study, we reviewed the prospectively maintained Mayo Clinic C‐11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C‐11 choline PET scan while the PSA value was less than 0.5 ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan–Meier method. Intergroup differences were assessed using the log‐rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. Results A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7–106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration‐resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small‐cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow‐up of 49.4 (21.3–95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value

Abstract Background Drowning is the leading cause of death for toddlers. When caregivers are knowledgeable about water safety, they can provide the best protection against drowning. The aim of this study is to survey caregivers of toddlers to better understand factors associated with water safety knowledge, attitudes about pool supervision, and toddler water competency skills. Methods An online survey of 650 parents/caregivers of 1–4-year-old toddlers asked about the caregiver’s water safety and swimming background and views on pool supervision. Surveys included a true/false section of ten basic water safety knowledge questions. Caregivers also reported on toddler swim lesson history and whether their toddler could perform six standard water competency skills. Linear regression identified factors predictive of water safety knowledge. Results On average, caregivers selected the correct answer on six out of ten water safety knowledge questions. Water safety knowledge was predicted by the relationship of the caregiver to the toddler, gender, race, education, prior CPR training, caregiver swim capability, and reported pool supervision style. On average, caregivers reported that their toddler could perform half of the water competency skills. The majority of the toddlers had taken swimming lessons. One third of caregivers believed that after a toddler has had swimming lessons, they don’t need to be watched as closely when they are in a pool. Conclusions Findings suggest that water safety knowledge is poor and that there are misconceptions about toddler supervision needs. Efforts are needed to improve water safety knowledge and to change perceptions about supervision among caregivers of toddlers.

Background: Providencia is a G ram-negative bacillus that most frequently colonizes the urinary tract and is often resistant to many antimicrobials. This study aimed to evaluate the resistance patterns of Providencia spp. and clinical outcomes due to the paucity of data. Methods: A multi-center, descriptive, retrospective chart review of adult patients with Providencia spp. infections was conducted from 1 January 2020 to 31 May 2022. The primary outcome was to describe the drug resistance patterns of Providencia spp. isolates. This study’s secondary outcome was to evaluate the clinical outcomes of patients with Providencia spp. infections. Results: Of the 312 patients screened, 244 were excluded primarily for polymicrobial infections. The mean age was 70 years, and 39 (56.5%) were males. Of the 68 included cases, 46 (67.6%) were P. stuartii, 20 (29.4%) were P. rettgeri, and 2 (2.9%) were P. alcalifaciens. The most common infections were bacteremia 38 (55.8%), followed by 27 (39.7%) urinary tract infections and 3 (4.4%) wound infections. In this study, 45 patients (65.2%) had urinary catheters. The primary antibiotics used for treatment consisted of ceftriaxone (25 (36.2%)), cefepime (20 (29%)), and meropenem (10 (14.5%)). Only 5 of 68 (7.2%) cases were multidrug- resistant and required meropenem. In total, 19 patients (27.1%) died during their admission, but none were related to Providencia infections. A total of 10 of the 68 patients (14.5%) were readmitted within 30 days for reasons unrelated to the progression or recurrence of Providencia infections. Conclusions:Providencia bacteremia is predominantly seen in elderly patients. Third- generation cephalosporins remain an appropriate choice of antibiotics for Providencia spp. Providencia stuartii was the only species with multidrug resistance.

The optimum germination conditions for foxtail millet sprouts enriched with γ-aminobutyric acid (GABA) and antioxidant polyphenols were investigated. From single-factor experimental results, both the GABA level and total phenolic content (TPC) were more significantly affected by soaking temperature and time, and concentration of sucrose culture solution. Response surface methodology (RSE) was used to optimize the germination conditions of foxtail millet sprouts, where the interaction between soaking temperature and sucrose concentration exhibited a significant (p < 0.05) effect on TPC, and the interaction between soaking time and sucrose concentration displayed a significant (p < 0.05) effect on GABA content. The optimal germination conditions for TPC and GABA enrichment of foxtail millet sprouts were soaking at 31 °C for 4.5 h and germinating at 35 °C with 4.5 g/L sucrose solution for 5 days. Under the optimized conditions, the TPC and GABA content of foxtail millet sprouts were 926.53 milligrams of ferulic acid equivalents per 100 g dry weight (mg FAE/100 g DW) and 259.13 mg/kg, separately, with less difference from the predicted values of 929.44 mg FAE/100 g DW and 263.60 mg/kg, respectively. Collectively, all the individual phenolic compounds increased significantly (p < 0.05) by optimization, except for cis-p-coumaric acid and cis-ferulic acid in bound. The results provide a practical technology for suitable germination conditions to improve the health components of foxtail millet sprouts and increase their added value.

Dragon fruit (Hylocereus spp.), renowned for its aesthetic appeal and rich antioxidant content, has gained global popularity due to its numerous health benefits. In Australia, despite growing commercial interest in cultivating dragon fruit, there is uncertainty for local growers stemming from competition with imported varieties. Notably, there is a lack of comparative research on the shelf-life, antioxidant activity, and phytochemical contents of Australian-grown versus imported dragon fruit, which is crucial for enhancing market competitiveness and consumer perception. This study compares the shelf-life, antioxidant activity, and phytochemical content of Australian-grown and imported dragon fruits under ambient conditions, addressing the competitive challenges faced by local growers. Freshly harvested white-flesh (Hylocereus undatus) and red-flesh (H. polyrhizus) dragon fruit were sourced from Queensland and the Northern Territory and imported fruit were sourced from an importer in Queensland. All fruit were assessed for key quality parameters including peel color, firmness, weight loss, total soluble solids (TSS), pH, titratable acidity (TA), total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total betalain content (TBC), and total anthocyanin content (TAC). The results indicate that Australian-grown white dragon fruits exhibited average one day longer shelf-life with less color degradation, better firmness retention, and less decline in weight loss, TSS, and acidity compared to imported fruits. Australian-grown red dragon fruits showed similar shelf-life compared to fruits from overseas. Antioxidant activities and phytochemicals were consistently higher in Australian-grown fruits throughout their shelf-life. These findings indicate that Australian-grown dragon fruits offer better physical quality and retain more nutritional value, which could enhance their marketability.

Understanding the extraction process of Nigella oil is crucial due to its significant impact on yield, quality, and therapeutic effectiveness. This study explored the effects of various screw press temperatures (40 °C, 50 °C, 60 °C, 70 °C, and 80 °C) on the quantity and quality of Nigella oil to optimize conditions that maximize yield while maintaining its nutritional and therapeutic attributes. Our findings indicate a linear increase in oil yield as screw press temperatures rose from 40 °C to 80 °C. There were no significant differences observed in total phenolic content (TPC), cupric reducing antioxidant capacity (CUPRAC), or the composition and ratio of fatty acids across oils extracted at different temperatures. However, the ferric-reducing antioxidant power (FRAP) was highest in oils extracted at 60 °C, while the thymoquinone (TQ) content peaked between 40 °C and 60 °C. These results underscore the importance of optimizing screw press temperatures to strike a balance between maximizing oil yield and preserving its valuable therapeutic and nutritional properties

Background Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined.Methods We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared.Results Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p

With an increasing number of patients eligible for immune checkpoint inhibitors, the incidence of immune-related adverse events (irAEs) is on the rise. Dermatologic immune-related adverse events (D-irAEs) are the most common and earliest to manifest, often with important downstream consequences for the patient. Current guidelines lack clarity in terms of diagnostic criteria for D-irAEs. The goal of this project is to better define D-irAE for the purposes of identification, diagnosis, and future study of this important group of diseases.The objectives of this project were to develop consensus guidance for an approach to D-irAEs including disease definitions and severity grading. Knowing that consensus among oncologists, dermatologists, and irAE subspecialists would be critical for usability, we formed a Dermatologic irAE Disease Definition Panel. The panel was composed of 34 experts, including oncologists, dermatologists, a rheumatologist, and an allergist/immunologist from 22 institutions across the USA and internationally. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two virtual meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness, and accuracy on 9-point scales in electronic surveys and provided free text comments. A working group aggregated survey responses and incorporated them into revised definitions. Consensus was based on numeric ratings using the RAND/UCLA Appropriateness Method with prespecified definitions.Following revisions based on panelist feedback, all items received consensus in the second round of ratings. Consensus definitions were achieved for 10 core D-irAE diagnoses: ICI-vitiligo, ICI-lichen planus, ICI-psoriasis, ICI-exanthem, ICI-bullous pemphigoid, ICI-Grover’s, ICI-eczematous, ICI-eruptive atypical squamous proliferation, ICI-pruritus without rash, and ICI-erosive mucocutaneous. A standard evaluation for D-irAE was also found to reach consensus, with disease-specific exceptions detailed when necessary. Each disorder’s description includes further details on disease subtypes, symptoms, supportive exam findings, and three levels of diagnostic certainty (definite, probable, and possible).These consensus-driven disease definitions standardize D-irAE classification in a useable framework for multiple disciplines and will be the foundation for future work. Given consensus on their accuracy and usability from a representative panel group, we anticipate that they can be used broadly across clinical and research settings.

ObjectivesSeveral studies have reported risk factors for severe disease and mortality in hospitalized adults with RSV infections. There is limited information available regarding the factors that affect the duration of a patient’s hospital length of stay (LOS).MethodsThis was a multicenter historical cohort study of adult patients hospitalized for laboratory-confirmed RSV in Southeast Michigan between January 2017 and December 2021. Hospitalized patients were identified using the International Classification of Diseases, Tenth Revision 10 codes for RSV infection. Mean LOS was computed; prolonged LOS was defined as greater than the mean.ResultsWe included 360 patients with a mean age (SD) of 69.9 ± 14.7 years, 63.6% (229) were female and 63.3% (228) of white race. The mean hospital LOS was 7.1 ± 5.4 days. Factors associated with prolonged LOS in univariable analysis were old age, body mass index (BMI), smoking status, Charlson Weighted Index of Comorbidity (CWIC), home oxygen, abnormal chest x-ray (CXR), presence of sepsis, use of oxygen, and antibiotics at the time of presentation. Predictors for prolonged LOS on admission in multivariable analysis were age on admission (p

Abstract Drowning is a major public health issue internationally. In August 2022, a report was released by members of the Central Texas Drowning Prevention Action Team that provided data on drowning fatalities in Texas between 2006 and 2020 and offered recommendations for drowning prevention actions. The information in the Texas drowning report is an important contribution to the field of injury prevention. The aim of this editorial is to allow the information in the report to be available to a wider audience and potentially used as a model for other states.

Abstract Background While many studies have reported that the structure of the gut and skin microbiota is driven by both species-specific and habitat-specific factors, the relative importance of host-specific versus environmental factors in wild vertebrates remains poorly understood. The aim of this study was to determine the diversity and composition of fish skin, gut, and surrounding water bacterial communities (hereafter referred to as microbiota) and assess the extent to which host habitat and phylogeny predict microbiota similarity. Skin swabs and gut samples from 334 fish belonging to 17 species were sampled in three Laurentian Great Lakes (LGLs) habitats (Detroit River, Lake Erie, Lake Ontario). We also collected and filtered water samples at the time of fish collection. We analyzed bacterial community composition using 16S metabarcoding and tested for community variation. Results We found that the water microbiota was distinct from the fish microbiota, although the skin microbiota more closely resembled the water microbiota. We also found that environmental (sample location), habitat, fish diet, and host species factors shape and promote divergence or convergence of the fish microbiota. Since host species significantly affected both gut and skin microbiota (separately from host species effects), we tested for phylosymbiosis using pairwise host species phylogenetic distance versus bacterial community dissimilarity. We found significant phylogenetic effects on bacterial community dissimilarity, consistent with phylosymbiosis for both the fish skin and gut microbiota, perhaps reflecting the longstanding co-evolutionary relationship between the host species and their microbiomes. Conclusions Analyzing the gut and skin mucus microbiota across diverse fish species in complex natural ecosystems such as the LGLs provides insights into the potential for habitat and species-specific effects on the microbiome, and ultimately the health, of the host. Video Abstract

Abstract Seismic ground motion creates low-frequency atmospheric sound (infrasound) that is detectable at remote sensor arrays. However, earthquake infrasound signal analysis is complicated by interference between multiple waves arriving at sensors simultaneously, reducing the accuracy and detail of ground motion detection. Here we show that individual waves in complicated wavefields can be resolved by recording infrasound on large-N arrays and processing with CLEAN beamforming. Examining both a local (ML3.5, purely tropospheric infrasound propagation) and regional earthquake (ML6.5, upper-atmospheric returns), we detect infrasound from tens of km away and up to several hundred km away respectively. Source regions span arcs of approximately 90°, indicating that although detection bias does occur (most likely from atmospheric winds) the recorded infrasound sources are widely dispersed and not simply epicentral. Infrasound-based remote detection of ground motion over wide areas can complement point measurements by seismometers and spur innovations in earthquake research and real-time hazard monitoring.

This study explored the performance and physiological responses of three commercially used peanut cultivars in Australian farming systems under ambient and elevated CO2 conditions, aiming to identify the most suitable genotype for dual-purpose (grain and graze) cropping experiments. The experiment utilized an open-top chamber (OTC) facility to regulate CO2 concentrations. The elevated CO2 (EC) treatment targeted approximately 650 ± 50 µmol mol−1, while both ambient CO2 (AC) and control plots operated at a concentration of approximately 400 µmol mol−1. Notably, control plots without chambers served as a reference for current CO2 and environmental conditions. In contrast, despite having the same ambient CO2 concentration, AC plots were enclosed in chambers, allowing for plant growth comparisons with EC plots with the same environmental conditions aside from CO2 levels. The analyses revealed significant effects of CO2 enrichment on peanut plants. In particular, the EC treatment led to enhanced photosynthetic rates (20% in Kairi, 31% in Holt, and 19% in Alloway), alongside reduced stomatal conductance (−55% in Kairi, −32% in Holt, and −40% in Alloway), transpiration, and increased water use efficiency compared to AC conditions. Elevated CO2 levels positively influenced pod yields in Kairi (+41%) and Alloway (+36%). However, CO2 enrichment did not significantly alter the protein content, total phenolic content, cupric-reducing antioxidant capacity, and ferric-reducing antioxidant power of peanut plant material. Furthermore, no significant differences were observed in the phytochemical composition among the three cultivars under ambient or elevated CO2 conditions. On the other hand, analysis of the fibre structure conducted on peanut stover harvested at plant maturity suggested potential declines in feedstock quality. Based on the findings of this research, further investigations and testing, including simulated grazing trials, will be carried out to identify a single breed line suitable for dual-purpose management under future elevated CO2 conditions.

Cuticular hydrocarbon (CHC) profiling shows promise as a chemotaxonomic tool for identifying and discriminating between closely related insect species. However, there have been limited studies using CHC profiling to differentiate between weevil species (Coleoptera: Curculionidae). This proof-of-concept study investigated the use of CHC and volatile profiling to discriminate between five weevil species from three genera in the Gonipterini tribe. A total of 56 CHCs and 41 other volatile compounds were found across the five species, with 83 of the compounds being identified through their mass fragmentation patterns. The number of CHCs from each species ranged from 20 to 43, while the proportion of CHCs unique to each species varied between 0% and 19%. The most abundant CHCs were nonacosane, 7-methylheptacosane, heptacosane, and hexacosane. Principal component analysis of the centred log-ratio transformed data revealed broad differences in CHC profiles between the two Oxyops species, with Bryachus squamicollis demonstrating the greatest divergence from the other Gonipterini species. The results suggest that CHC analysis could be used to support established taxonomic methods, including morphological features and genetic sequencing results.

Abstract The discovery and development of novel treatments that harness the patient’s immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. These new approaches are focused on patients with an inadequate response to current treatments, with emerging evidence of improved responses in various cancers with new immunotherapy agents, often in combinations with existing agents. The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th–December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer.

Abstract Background Despite being twice as likely to get Alzheimer’s disease (AD), African Americans have been grossly underrepresented in AD research. While emerging evidence indicates that African Americans with AD have lower cerebrospinal fluid (CSF) levels of Tau compared to Caucasians, other differences in AD CSF biomarkers have not been fully elucidated. Here, we performed unbiased proteomic profiling of CSF from African Americans and Caucasians with and without AD to identify both common and divergent AD CSF biomarkers. Methods Multiplex tandem mass tag-based mass spectrometry (TMT-MS) quantified 1,840 proteins from 105 control and 98 AD patients of which 100 identified as Caucasian while 103 identified as African American. We used differential protein expression and co-expression approaches to assess how changes in the CSF proteome are related to race and AD. Co-expression network analysis organized the CSF proteome into 14 modules associated with brain cell-types and biological pathways. A targeted mass spectrometry method, selected reaction monitoring (SRM), with heavy labeled internal standards was used to measure a panel of CSF module proteins across a subset of African Americans and Caucasians with or without AD. A receiver operating characteristic (ROC) curve analysis assessed the performance of each protein biomarker in differentiating controls and AD by race. Results Consistent with previous findings, the increase of Tau levels in AD was greater in Caucasians than in African Americans by both immunoassay and TMT-MS measurements. CSF modules which included 14–3-3 proteins (YWHAZ and YWHAG) demonstrated equivalent disease-related elevations in both African Americans and Caucasians with AD, whereas other modules demonstrated more profound disease changes within race. Modules enriched with proteins involved with glycolysis and neuronal/cytoskeletal proteins, including Tau, were more increased in Caucasians than in African Americans with AD. In contrast, a module enriched with synaptic proteins including VGF, SCG2, and NPTX2 was significantly lower in African Americans than Caucasians with AD. Following SRM and ROC analysis, VGF, SCG2, and NPTX2 were significantly better at classifying African Americans than Caucasians with AD. Conclusions Our findings provide insight into additional protein biomarkers and pathways reflecting underlying brain pathology that are shared or differ by race.

Abstract Background A haplotype is a set of DNA variants inherited together from one parent or chromosome. Haplotype information is useful for studying genetic variation and disease association. Haplotype assembly (HA) is a process of obtaining haplotypes using DNA sequencing data. Currently, there are many HA methods with their own strengths and weaknesses. This study focused on comparing six HA methods or algorithms: HapCUT2, MixSIH, PEATH, WhatsHap, SDhaP, and MAtCHap using two NA12878 datasets named hg19 and hg38. The 6 HA algorithms were run on chromosome 10 of these two datasets, each with 3 filtering levels based on sequencing depth (DP1, DP15, and DP30). Their outputs were then compared. Result Run time (CPU time) was compared to assess the efficiency of 6 HA methods. HapCUT2 was the fastest HA for 6 datasets, with run time consistently under 2 min. In addition, WhatsHap was relatively fast, and its run time was 21 min or less for all 6 datasets. The other 4 HA algorithms’ run time varied across different datasets and coverage levels. To assess their accuracy, pairwise comparisons were conducted for each pair of the six packages by generating their disagreement rates for both haplotype blocks and Single Nucleotide Variants (SNVs). The authors also compared them using switch distance (error), i.e., the number of positions where two chromosomes of a certain phase must be switched to match with the known haplotype. HapCUT2, PEATH, MixSIH, and MAtCHap generated output files with similar numbers of blocks and SNVs, and they had relatively similar performance. WhatsHap generated a much larger number of SNVs in the hg19 DP1 output, which caused it to have high disagreement percentages with other methods. However, for the hg38 data, WhatsHap had similar performance as the other 4 algorithms, except SDhaP. The comparison analysis showed that SDhaP had a much larger disagreement rate when it was compared with the other algorithms in all 6 datasets. Conclusion The comparative analysis is important because each algorithm is different. The findings of this study provide a deeper understanding of the performance of currently available HA algorithms and useful input for other users.