Search

Hippocampal dentate gyral dysplasia is well-described in temporal lobe epilepsy and may be a risk factor for sudden, unexpected death in several populations: infants (sudden infant death syndrome [SIDS], sudden unexpected infant death [SUID]), toddlers (sudden unexpected death of a child [SUDC]), and epileptics (sudden unexpected death in epilepsy [SUDEP]). We examined reports and histopathological slides from autopsies performed at our institution from 2008 through 2016 to determine whether the presence or absence of any of the described forms of such dysplasias (duplications, hyperconvolutions, and granule cell dispersion, including bilamination), correlated with the causes of death. From well over 4000 autopsies, we identified 949 autopsies with a neuropathology examination by a neuropathologist. Of these, 205 cases (21.6%) had 1 or more of the described abnormalities of 1 or both dentate gyri; 87 (42.4%) of the individuals in this group of 205 autopsies had died suddenly and unexpectedly, including 29/90 (32.2%) cases of SUDEP, 17/31 (54.8%) cases of SUDC, and 51/104 (49.0%) cases of infants with SIDS or SUID. We conclude that these changes are readily recognizable by experienced neuropathologists and that because they are overrepresented in an autopsy population that died suddenly and unexpectedly, they may represent a risk factor for such outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: Recent attention has focused on understanding later-life caregiving networks, emphasizing how multiple adult children within the same family navigate parental care. However, families with one child are increasingly common, and we know little about how adult only children experience caregiving and whether their experiences differ from those with siblings. Therefore, this study assessed differences in caregiving experiences between adult child caregivers with and without siblings and whether associations between caregiving experiences and mental health (i.e., psychological well-being and distress) vary by sibling presence., Research Design and Methods: We used cross-sectional data from 1,773 adult child caregivers (12% without siblings; Mage = 56.75 [9.23]) in the National Health and Aging Trends Study and National Study of Caregiving. We conducted t-tests and a series of multivariate regressions with interactions to test hypotheses., Results: Adult only child caregivers reported more financial difficulty with care than respondents with siblings. The negative association between emotional difficulty of care and psychological well-being was stronger among adult children without siblings. Informal support was positively associated with psychological well-being only for adult children with siblings, although this may be accounted for by race and ethnicity., Discussion and Implications: Findings suggest that adult only children may be at elevated risks of the financial difficulties and the emotional consequences of parental care provision. Further, informal support may be less protective for adult only children's well-being. Given the increasing prevalence of single-child families, more research is needed to better understand and support adult only children caring for parents., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Objectives: Research and theory suggest that older adults' self-perceptions of aging (SPA) are associated with their health behavior engagement. Likewise, romantic partners often play a key role in shaping each other's health behaviors. This study aims to explore the longitudinal dyadic associations between SPA and health behaviors among couples in midlife and older adulthood., Research Design and Methods: Data were drawn from 3,330 couples ages 50-96 (Mmen = 67.22 [9.43]; Mwomen = 65.42 [8.96]) from the Health and Retirement Study, using pooled samples from 2010/2012 to 2012/2014. We estimated actor-partner interdependence models with moderation to assess whether and to what extent a partner's SPA moderated the links between positive and negative SPA and engagement in preventive and risky health behaviors two years later., Results: Women's SPA moderated the association between men's SPA and men's risky health behaviors only when women reported extreme levels of negative or positive SPA. In contrast, men's SPA did not moderate the associations between women's SPA and women's health behaviors., Discussion and Implications: This study's findings emphasize that links between SPA and health behaviors operate within the broader social environment and in the context of romantic relationships. The results highlight how couples' perceptions of aging relate to their own and their partners' health behaviors. This work contributes to the literature on the gendered and social nature of health behaviors and has implications for designing interventions targeting SPA., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This ancillary study's purpose is to describe the relationship between dose of treatment and body mass index (BMI) outcomes in a tele-behavioral health program delivered in the IDeA States Pediatric Clinical Trials Network to children and their families living in rural communities., Methods: Participants randomized to the intervention were able to receive 26 contact hours (15 hr of group sessions and 11 hr of individual sessions) of material focused on nutrition, physical activity, and behavioral caregiver training delivered via interactive televideo. Dose of the intervention received by child/caregiver dyads (n = 52) from rural areas was measured as contact hours. The total doses of group, individual, and total contact hours were analyzed, and generalized linear mixed models were utilized to determine how dose received impacted BMI outcomes., Results: The majority (64.4%) of participants received the target of at least 80% (20.8 hr) of the total intervention dose. Older children (9-11 years) achieved significantly less intervention dose than targeted (M = 19.7; p = .031); as did males (M = 17.2; p < .001), children who identified as Black (M = 17.8; p < .001), and children from Site 3 (M = 18.0; p < .001). Dose was not significantly related to BMI outcomes in children or caregivers., Conclusions: As this study is underpowered and took place during the early stages of the COVID-19 pandemic, results should be interpreted with caution, but contact hours did not predict health outcomes for families living in rural communities., (Published by Oxford University Press on behalf of the Society of Pediatric Psychology 2025.)

G-quadruplex (G4) structure is a nucleic acid secondary structure formed by guanine-rich sequences, playing essential roles in various biological processes such as gene regulation and environmental stress adaptation. Although prokaryotes growing at high temperatures have higher GC contents, the pattern of G4 structure associated with GC content variation in thermal adaptation remains elusive. This study analyzed 681 bacterial genomes to explore the role of G4 structures in thermal adaptation. Our findings revealed a strong positive correlation between G4 patterns in the region encoding 16S rRNA genes and optimal growth temperatures (Topt), whereas genomic GC content and G4 patterns did not show significant correlations with Topt. Evolutionary analysis showed distinctive differences in G4 stability between Thermotoga (Topt ≥ 80°C) and Pseudothermotoga (60°C ≤ Topt < 80°C) species, with Thermotoga species exhibiting higher G4 stability, indicating stronger selective pressure for G4 structures. In vitro spectroscopy analysis showed that base mutations at key sites resulted in the absence of G4 structural stability and integrity in Thermotoga compared to Pseudothermotoga. Collectively, this study suggests that the G4 structures in 16S rRNA regions emerged as key indicators of thermal adaptation in prokaryotes and contributes to our understanding of the molecular basis of evolutionary adaptation., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: This study aimed to explore the utilization of a fine-tuned language model to extract expressions related to the Age-Friendly Health Systems 4M Framework (What Matters, Medication, Mentation, and Mobility) from nursing home worker text messages, deploy automated mapping of these expressions to a taxonomy, and explore the created expressions and relationships., Materials and Methods: The dataset included 21 357 text messages from healthcare workers in 12 Missouri nursing homes. A sample of 860 messages was annotated by clinical experts to form a "Gold Standard" dataset. Model performance was evaluated using classification metrics including Cohen's Kappa (κ), with κ ≥ 0.60 as the performance threshold. The selected model was fine-tuned. Extractions were clustered, labeled, and arranged into a structured taxonomy for exploration., Results: The fine-tuned model demonstrated improved extraction of 4M content (κ = 0.73). Extractions were clustered and labeled, revealing large groups of expressions related to care preferences, medication adjustments, cognitive changes, and mobility issues., Discussion: The preliminary development of the 4M model and 4M taxonomy enables knowledge extraction from clinical text messages and aids future development of a 4M ontology. Results compliment themes and findings in other 4M research., Conclusion: This research underscores the need for consensus building in ontology creation and the role of language models in developing ontologies, while acknowledging their limitations in logical reasoning and ontological commitments. Further development and context expansion with expert involvement of a 4M ontology are necessary., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

As with phenotyping of any microscopic appendages, such as cilia or antennae, phenotyping of root hairs has been a challenge due to their complex intersecting arrangements in two-dimensional images and the technical limitations of automated measurements. Digital Imaging of Root Traits at Microscale (DIRT/μ) is a newly developed algorithm that addresses this issue by computationally resolving intersections and extracting individual root hairs from two-dimensional microscopy images. This solution enables automatic and precise trait measurements of individual root hairs. DIRT/μ rigorously defines a set of rules to resolve intersecting root hairs and minimizes a newly designed cost function to combinatorically identify each root hair in the microscopy image. As a result, DIRT/μ accurately measures traits such as root hair length distribution and root hair density, which are impractical for manual assessment. We tested DIRT/μ on three datasets to validate its performance and showcase potential applications. By measuring root hair traits in a fraction of the time manual methods require, DIRT/μ eliminates subjective biases from manual measurements. Automating individual root hair extraction accelerates phenotyping and quantifies trait variability within and among plants, creating new possibilities to characterize root hair function and their underlying genetics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

As human complex diseases are influenced by the interaction between genetics and the environment, identifying gene-environment interactions (G×E) is crucial for understanding disease mechanisms and predicting risk. Developing robust quantitative tools for G×E analysis can enhance the study of complex diseases. However, many existing methods that explore G×E focus on the interplay between an environmental factor and genetic variants, exclusively for common or rare variants. In this study, we developed MAGEIT&#95;RAN and MAGEIT&#95;FIX to identify interactions between an environmental factor and a set of genetic markers, including both rare and common variants, based on the MinQue for Summary statistics. The genetic main effects in MAGEIT&#95;RAN and MAGEIT&#95;FIX are modeled as random and fixed effects, respectively. Simulation studies showed that both tests had type I error under control, with MAGEIT&#95;RAN being the most powerful test. Applying MAGEIT to a genome-wide analysis of gene-alcohol interactions on hypertension and seated systolic blood pressure in the Multiethnic Study of Atherosclerosis revealed genes like EIF2AK2, CCNDBP1, and EPB42 influencing blood pressure through alcohol interaction. Pathway analysis identified 1 apoptosis and survival pathway involving PKR and 2 signal transduction pathways associated with hypertension and alcohol intake, demonstrating MAGEIT&#95;RAN's ability to detect biologically relevant gene-environment interactions., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The 1918-1920 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I) using information from Alaska death certificates dating between 1915 and 1921 (n = 7147). Goals include a reassessment of pandemic death numbers, analysis of P&I deaths beyond 1919, estimates of excess mortality patterns overall and by age using intercensal population estimates based on Alaska's demographic history, and comparisons between Alaska Native (AN) and non-AN residents. Results indicate that ANs experienced 83% of all P&I deaths and 87% of all-cause excess deaths during the pandemic. Alaska Native mortality was 8.1 times higher than non-AN mortality. Analyses also uncovered previously unknown mortality peaks in 1920. Both subpopulations showed characteristically high mortality of young adults, possibly due to imprinting with the 1889-1890 pandemic virus, but their age-specific mortality patterns were different: non-AN mortality declined after age 25-29 and stayed relatively low for the elderly, while AN mortality increased after age 25-29, peaked at age 40-44, and remained high up to age 64. This suggests a relative lack of exposure to H1-type viruses pre-1889 among AN persons. In contrast, non-AN persons, often temporary residents, may have gained immunity before moving to Alaska., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest: The author(s) declare no conflict of interest.

The bovine conceptus elongates near Day 16 of development and releases interferon-tau (IFNT), disrupting the endometrial luteolytic mechanism to sustain luteal P4 and pregnancy. Conceptus factors other than IFNT modify local endometrial activities to support pregnancy; however, the microenvironment is largely uncharacterized. We utilized a bovine conceptus-endometrial culture system to elucidate the microenvironment in the form of RNA and protein. Estrus synchronized heifers remained cyclic (13) or were inseminated (9) to produce Day 16 cyclic endometrium and elongating conceptuses, respectively. Conceptus sections and endometrium were then used to generate tissue cultures in 1 mL of medium: (1) no tissue (Control Med; n = 7), (2) mono-cultured conceptus (Conceptus; n = 9, 3) mono-cultured endometrium (Endo; n = 13), or (4) Endo-Conceptus Co-culture (n = 15). After 12 h, tissue RNA was sequenced (RNA-Seq) and media underwent proteomic analysis (LC-MS/MS). Compared to Conceptus and Endo, co-cultured conceptus and endometrial tissue contained 3400 and 4575 differentially expressed genes (DEG), respectively (P ≤ 0.01). More abundantly expressed endometrial DEG were associated with interferon signaling whereas more abundantly expressed conceptus DEG were associated with protein homeostasis and metabolism (FDR < 0.001). When Co-culture media where compared to Endo media, 288 more abundant protiens were identified (P < 0.05). Biological processes related to these proteins included antigen presentation via MHC Class Ib and keratinization (FDR < 0.001). Within the mono-cultured conceptus and endometrial media, folate receptor alpha (FOLR1) (P < 0.001) was identified as the most abundant secreted protein suggesting the reproductive tissues elicit a microenvironment supportive of conceptus growth involving folate metabolism., (© The Author(s) 2025. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The scientific community has long benefited from the opportunities provided by data reuse. Recognizing the need to identify the challenges and bottlenecks to reuse in the agricultural research community and propose solutions for them, the data reuse working group was started within the AgBioData consortium framework. Here, we identify the limitations of data standards, metadata deficiencies, data interoperability, data ownership, data availability, user skill level, resource availability, and equity issues, with a specific focus on agricultural genomics research. We propose possible solutions stakeholders could implement to mitigate and overcome these challenges and provide an optimistic perspective on the future of genomics and transcriptomics data reuse., (© The Author(s) 2025. Published by Oxford University Press GigaScience.)

The Natural Products Magnetic Resonance Database (NP-MRD; https://np-mrd.org) is a comprehensive, freely accessible, web-based resource for the deposition, distribution, extraction, and retrieval of nuclear magnetic resonance (NMR) data on natural products (NPs). The NP-MRD was initially established to support compound de-replication and data dissemination for the NP community. However, that community has now grown to include many users from the metabolomics, microbiomics, foodomics, and nutrition science fields. Indeed, since its launch in 2022, the NP-MRD has expanded enormously in size, scope, and popularity. The current version of NP-MRD now contains nearly 7× more compounds (281 859 versus 40 908) and 7× more NMR spectra (5.5 million versus 817 278) than the first release. More specifically, an additional 4.6 million predicted spectra and another 11 000 spectra simulated from experimental chemical shifts were deposited into the database. Likewise, the number of NMR raw spectral data depositions has grown from 165 spectra per year to >10 000 per year. As a result of this expansion, the number of monthly webpage views has grown from 55 to 20 000 and the number of monthly visitors has increased from 7 to 2500. To address this growth and to better support the expanding needs of its diverse community of users, many additional improvements to the NP-MRD have been made. These include significant enhancements to the data submission process, notable updates to the database's spectral search utilities and useful additions to support better NMR spectral analysis/prediction. Significant efforts have also been undertaken to remediate and update many of NP-MRD's database entries. This manuscript describes these database improvements and expansion efforts, along with how they have been implemented and what future upgrades to the NP-MRD are planned., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Dysphagia is a common gastrointestinal complaint in the pediatric population and should raise concern for oropharyngeal as well as esophageal disorders. We describe a 7-year old patient who was admitted to the hospital for sudden onset dysphagia, abdominal pain, and decreased oral intake. Extensive evaluations including endoscopy eventually revealed herpes simplex esophagitis as well as eosinophilic esophagitis. Herpes simplex esophagitis is a rare condition in the immunocompetent population and is typically self-resolving. Eosinophilic esophagitis is a chronic, inflammatory condition characterized by esophageal eosinophilia and signs of esophageal dysfunction. The concurrent presentation of both conditions in the pediatric population has rarely been described., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This work explored whether bovine embryo development relies on signaling from the interleukin-6 (IL6) cytokine family. This was accomplished by interrupting IL6 signal transducer (IL6ST), the common beta-subunit receptor used by the IL6 family. One series of studies cultured in vitro-produced (IVP) embryos with SC144, a pharmacological IL6ST inhibitor. Providing the inhibitor at a concentration that partially diminished IL6ST signaling reduced development to the 16-cell and blastocyst stages and reduced inner cell mass (ICM) cell numbers. Inhibitor concentrations that completely blocked IL6ST signaling prevented blastocyst development. Another series of studies used CRISPR-Cas9 to disrupt IL6ST. Two electroporation approaches were used to introduce guide RNAs and Cas9 protein into one-cell IVP embryos. Editing efficiency was ≥82%. Targeting IL6ST did not affect cleavage but reduced development to the 16-cell and blastocyst stages. A reduction in ICM cell numbers was detected, and a disorganization of the ICM was observed in approximately one-half of the IL6ST-targeted blastocysts. These observations indicate that embryo-derived IL6 family members that signal through IL6ST are needed to support normal in vitro bovine embryo development. These signals are needed by the 16-cell stage and for ICM cell development at the blastocyst stage. There also is evidence that these signals support the overall cellular organization of the blastocyst., (© The Author(s) 2025. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introgressive hybridization may lead to contrasting evolutionary outcomes that are difficult to predict since they depend on the fitness effects of endogenous genomic interactions and environmental factors. Conservation of endemic biodiversity may be more effective with require direct measurement of introgressed ancestry and fitness in wild populations, especially for keystone taxa at risk of hybridization following species introductions. We assessed the relationship of non-native ancestry with growth and body condition in the basin-restricted Neosho Bass (Micropterus velox; NB), focussing on two streams in the NB native range that are admixed extensively with non-native Smallmouth Bass (M. dolomieu; SMB). We quantified the genetic composition of 116 fish from Big Sugar Creek (N = 46) and Elk River (N = 70) at 14 microsatellite loci. Using back-calculated total length-at-age estimated from sagittal otoliths, we assessed whether genetic ancestry explained variation in von Bertalanffy growth model parameters, accounting for sex and stream effects. We then assessed the relationship between ancestry and body condition. We found no differences in growth parameters by sex, stream, or ancestry, suggesting phenotypic homogenization which could be mediated by selection on body size. We found a negative correlation between SMB ancestry and condition, including lower condition in Big Sugar Creek, possibly reflecting a trade-off between maximum length and condition with respect to overall fitness. We show that ongoing non-native introgression, which may be augmented by anthropogenic SMB introductions, may attenuate evolutionary differentiation between species and directly influence fitness, possibly having critical implications for long-term persistence and management of adaptive potential in a popular and ecologically important endemic sportfish., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. Elements of the work have been written by employees of the US Government.)

Background: Metagenomic next-generation sequencing (mNGS) for pathogen detection offers the potential for broad pathogen detection directly from clinical specimens. However, the yield and impact of testing is variable, financial cost is high, and questions surrounding its optimal use remain. Our pediatric institution used a clinical committee-based approach to discuss and approve or deny mNGS test requests. In this study, we evaluate the patient characteristics for which mNGS testing was considered, test yield, and clinical impact of mNGS results when employing this model of diagnostic stewardship., Methods: Patients for which plasma cell-free DNA mNGS testing was requested and assessed by the clinical committee between August 1, 2018, and April 30, 2021, were included. The committee discussion emails were used to evaluate reasons for making the test request and treatment plans. Patient characteristics and additional clinical information were gathered by chart review. For approved cases, the clinical impact of the mNGS results were retrospectively adjudicated by infectious disease and clinical microbiology experts., Results: Twelve requests for plasma cell-free DNA mNGS were evaluated and 9 were approved. mNGS results led to a positive clinical management change in 55% of approved requests. Negative clinical impact of mNGS testing did not occur during the study. The patients for which testing requests were denied had resolution of symptoms without further intervention., Conclusions: This committee-based test request approval diagnostic stewardship model has the potential to support high-yield mNGS testing while using healthcare resources responsibly., (© Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging., Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes., Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023. Outcomes assessed included comorbidities, presenting features, preoperative endocrine evaluations, perioperative characteristics, postoperative endocrine laboratory values, and complications., Results: Of the 608 patients evaluated, 496 (81.6%) were female; median age at surgery was 44 years (range, 10-78). Increasing age was associated with increasing comorbidities, frailty, rates of postoperative thromboembolic disease, Knosp grade, tumor size, and postoperative cortisol and ACTH nadirs. Conversely, increasing age was associated with decreased hallmark CD features, preoperative 24-hour urinary free cortisol, Ki-67 indices, and arginine vasopressin deficiency. Younger patients presented more frequently with weight gain, facial rounding/plethora, abdominal striae, hirsutism, menstrual irregularities, dorsocervical fat pad, and acne. Obstructive sleep apnea and infections were more common with increasing age., Conclusions: There are age-dependent differences in clinical presentation, tumor behavior, and postoperative outcomes in patients with CD. Compared to younger patients, older patients present with a less classical phenotype characterized by fewer hallmark features, more medical comorbidities, and larger tumors. Notably, age-related differences suggest a more indolent tumor behavior in older patients, potentially contributing to delayed diagnosis and increased perioperative risk. These findings underscore the need for tailored diagnostic and therapeutic approaches across age groups, with a focus on managing long-term comorbidities and optimizing surgical outcomes., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objective: The American Medical Informatics Association (AMIA) Task Force on Diversity, Equity, and Inclusion (DEI) was established to address systemic racism and health disparities in biomedical and health informatics, aligning with AMIA's mission to transform healthcare. AMIA's DEI initiatives were spurred by member voices responding to police brutality and COVID-19's impact on Black/African American communities., Materials and Methods: The Task Force, consisting of 20 members across 3 groups aligned with AMIA's 2020-2025 Strategic Plan, met biweekly to develop DEI recommendations with the help of 16 additional volunteers. These recommendations were reviewed, prioritized, and presented to the AMIA Board of Directors for approval., Results: In 9 months, the Task Force (1) created a logic model to support workforce diversity and raise AMIA's DEI awareness, (2) conducted an environmental scan of other associations' DEI activities, (3) developed a DEI framework for AMIA meetings, (4) gathered member feedback, (5) cultivated DEI educational resources, (6) created a Board nominations and diversity session, (7) reviewed the Board's Strategic Planning for DEI alignment, (8) led a program to increase diversity at the 2020 AMIA Virtual Annual Symposium, and (9) standardized socially-assigned race and ethnicity data collection., Discussion: The Task Force proposed actionable recommendations that focused on AMIA's role in addressing systemic racism and health equity, helping the organization understand its member diversity., Conclusion: This work supported marginalized groups, broadened the research agenda, and positioned AMIA as a DEI leader while reinforcing the need for ongoing transformation within informatics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

During their lifespan, plants are often exposed to a broad range of stresses that change their redox balance and lead to accumulation of reactive oxygen species (ROS). The traditional view is that this comes with negative consequences to cells structural integrity and metabolism and, to prevent this, plants evolved a complex and well-coordinated antioxidant defence system that relies on the operation of a range of enzymatic and non-enzymatic antioxidants (AO). Due to the simplicity of measuring their activity, and in the light of the persistent dogma that stress-induced ROS accumulation is detrimental for plants, it is not surprising that enzymatic AO have often been advocated as suitable proxies for stress tolerance, as well as potential targets for improving tolerance traits. However, there is a growing number of reports showing either no changes or even downregulation of AO systems in stressed plants. Moreover, ROS are recognised now as important second messengers operating in both local and systemic signalling, synergistically interacting with the primary stressor, to regulate gene expression needed for optimal acclimatization. This work critically assesses the suitability of using enzymatic AO as a proxy for stress tolerance, or as a target for crop genetic improvement. It is concluded that constitutively higher AO activity may interfere with stress-induced ROS signalling and be of disadvantage to plant stress tolerance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Reproductive phasiRNAs (phased, secondary, small interfering RNAs), produced from numerous PHAS loci, are essential for plant anther development. PHAS transcripts are enriched on endoplasmic reticulum-bound ribosomes in maize (Zea mays), but the impact of ribosome binding on phasiRNA biogenesis remains elusive. Through ribosome profiling of maize anthers at 10 developmental stages, we demonstrated that 24-PHAS transcripts are bound by ribosomes, with patterns corresponding to the timing and abundance of 24-PHAS transcripts. Ribosome binding to 24-PHAS transcripts is conserved among different maize inbred lines, with ribosomes enriched upstream of the miR2275 target sites. We detected short open reading frames (sORFs) in the ribosome-binding regions of some 24-PHAS transcripts and observed a 3-nt periodicity in most sORFs, but mass spectrometry failed to detect peptides corresponding to the sORFs. Deletion of the entire ribosome-binding region of 24PHAS&#95;NO296 locus eliminated ribosome binding and decreased 24-nt phasiRNA production, without affecting 24PHAS&#95;NO296 transcript levels. In contrast, disrupting only the sORFs in 24PHAS&#95;NO296 did not substantially affect the generation of 24-nt phasiRNAs. A newly formed sORF in these mutants may have re-directed ribosome binding to its transcripts. Overall, these findings demonstrate that sORFs facilitate ribosome binding to 24-PHAS transcripts, thereby promoting phasiRNA biogenesis in meiotic anthers., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Phased, small interfering RNAs (PhasiRNAs) play a crucial role in supporting male fertility in grasses. Earlier work in maize (Zea mays) and rice (Oryza sativa)-and subsequently many other plant species-identified premeiotic 21-nucleotide (nt) and meiotic 24-nt phasiRNAs. More recently, a group of premeiotic 24-nt phasiRNAs was discovered in the anthers of 2 Pooideae species, barley (Hordeum vulgare) and bread wheat (Triticum aestivum). Whether premeiotic 24-nt phasiRNAs and other classes of reproductive phasiRNAs are conserved across Pooideae species remains unclear. We conducted comparative RNA profiling of 3 anther stages in 6 Pooideae species and 1 Bambusoideae species. We observed complex temporal accumulation patterns of 21-nt and 24-nt phasiRNAs in Pooideae and Bambusoideae grasses. In Bambusoideae, 21-nt phasiRNAs accumulated during meiosis, whereas 24-nt phasiRNAs were present in both premeiotic and postmeiotic stages. We identified premeiotic 24-nt phasiRNAs in all 7 species examined. These phasiRNAs exhibit distinct biogenesis mechanisms and potential Argonaute effectors compared to meiotic 24-nt phasiRNAs. We show that specific Argonaute genes coexpressed with stage-specific phasiRNAs are conserved across Bambusoideae and Pooideae species. Our degradome analysis identified a set of conserved miRNA target genes across species, while 21-nt phasiRNA targets were species-specific. Cleavage of few targets was observed for 24-nt phasiRNAs. In summary, this study demonstrates that premeiotic 24-nt phasiRNAs are present across Bambusoideae and Pooideae families, and the temporal accumulation of other classes of 21-nt and 24-nt phasiRNA differs between bamboo and Pooideae species. Furthermore, targets of the 3 classes of phasiRNAs may be rapidly evolving or undetectable., Competing Interests: Conflict of interest statement. The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The basal endosperm transfer layer (BETL) of the maize (Zea mays L.) kernel is composed of transfer cells for nutrient transport to nourish the developing kernel. To understand the spatiotemporal processes required for BETL development, we characterized 2 unstable factor for orange1 (Zmufo1) mutant alleles. The BETL defects in these mutants were associated with high levels of reactive oxygen species, oxidative DNA damage, and cell death. Interestingly, antioxidant supplementation in in vitro cultured kernels alleviated the cellular defects in mutants. Transcriptome analysis of the loss-of-function Zmufo1 allele showed differential expression of tricarboxylic acid cycle, redox homeostasis, and BETL-related genes. The basal endosperms of the mutant alleles had high levels of acetyl-CoA and elevated histone acetyltransferase activity. The BETL cell nuclei showed reduced electron-dense regions, indicating sparse heterochromatin distribution in the mutants compared with wild-type. Zmufo1 overexpression further reduced histone methylation marks in the enhancer and gene body regions of the pericarp color1 (Zmp1) reporter gene. Zmufo1 encodes an intrinsically disordered nuclear protein with very low sequence similarity to known proteins. Yeast two-hybrid and luciferase complementation assays established that ZmUFO1 interacts with proteins that play a role in chromatin remodeling, nuclear transport, and transcriptional regulation. This study establishes the critical function of Zmufo1 during basal endosperm development in maize kernels., Competing Interests: Conflict of interest statement: The authors declare no competing financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), and is associated with increased cardiovascular mortality that may not be reduced by standard therapies. Inappropriate activation of the renin-angiotensin-aldosterone system occurs in IH, and mineralocorticoid receptor (MR) blockade has been shown to improve vascular outcomes in cardiovascular disease. Thus, we hypothesized that MR inhibition prevents coronary and renal vascular dysfunction in mice exposed to chronic IH., Methods: Human and mouse coronary vascular cells and male C57BL/6J mice were exposed to IH or room air (RA) for 12 hours/day for 3 days (in vitro) and 6 weeks with or without treatments with spironolactone (SPL) or hydrochlorothiazide (HTZ)., Results: In vitro studies demonstrated that IH increased MR gene expression in human and mouse coronary artery endothelial and smooth muscle cells. Exposure to IH in mice increased blood pressure, reduced coronary flow velocity reserve (CFVR), and attenuated endothelium-dependent dilation and enhanced vasoconstrictor responsiveness in coronary, but not renal arteries. Importantly, SPL treatment prevented altered coronary vascular function independent of blood pressure as normalization of BP with HTZ did not improve CFVR or coronary vasomotor function., Conclusions: These data demonstrate that chronic IH, which mimics the hypoxia-reoxygenation cycles of moderate-to-severe OSA, increases coronary vascular MR expression in vitro. It also selectively promotes coronary vascular dysfunction in mice. Importantly, this dysfunction is sensitive to MR antagonism by SPL, independent of blood pressure. These findings suggest that MR blockade could serve as an adjuvant therapy to improve long-term cardiovascular outcomes in patients with OSA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children., Methods: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with antiviral receipt., Results: A total of 1213 children with laboratory-confirmed influenza were included. Overall, 652 children (53.8%) received an antiviral. Roughly 63.0% of children received clinical influenza testing. Among those with clinical testing, 67.4% received an antiviral. Factors associated with higher odds of antiviral receipt included hematologic (aOR = 1.76; 95% CI = 1.03-3.02) or oncologic/immunocompromising (aOR = 2.41; 95% CI = 1.13-5.11) disorders, prehospitalization antiviral receipt (aOR = 2.34; 95% CI = 1.49-3.67), clinical influenza testing (aOR = 3.07; 95% CI = 2.28-4.14), and intensive care unit admission (aOR = 1.53; 95% CI = 1.02-2.29). Symptom duration >2 days was associated with lower odds of antiviral treatment (aOR = 0.40; 95% CI = .30-.52). Antiviral receipt varied by site with a 5-fold difference across sites., Conclusions: Almost half of children hospitalized with influenza did not receive antivirals. Additional efforts to understand barriers to guideline adherence are crucial for optimizing care in children hospitalized with influenza., Competing Interests: Potential conflicts of interest. J. W. A. previously served as a member of the AstraZeneca Scientific Advisory Board. G. A. W. has received honoraria from Merck & Company for writing and revising chapters in the Merck Manual Electrophysiologic Studies. M. A. S. has received research funding from Pfizer and honoraria from Sanofi Pasteur for vaccine consultation. J. A. E. reports work as a consultant to AbbVie, AstraZeneca, Meissa Vaccines, Pfizer, Moderna, and Sanofi Pasteur and research to support their university from AstraZeneca, GSK, Merck, and Pfizer. M. G. M. reports research to support their university from Merk Sharpe & Dohme and a nonfinancial research grant from Viracor. F. M. M. reports work as a consultant for Moderna, GSK, AstraZeneca, Sanofi, Novavax, and Merck; serving on the data and safety monitoring boards for Pfizer, Moderna, the National Institutes of Health (NIH), Meissa, and Dynavax; and grant and research support from Pfizer, Gilead, NIH, and CDC. J. E. S. reports work as a consultant at the Association of American Medical Colleges. J. V. W. previously served as a member of the Quidel Scientific Advisory Board and on an independent data monitoring committee for GSK. S. M. O. reports travel support from the Gates Foundation. N. B. H. received grant support from Sanofi and Quidel, receives current grant support from Merck, and served on an advisory board for CSL Seqirus. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Gastrointestinal nematode (GIN) infection adversely affects the performance and well-being of forage-based sheep throughout the world. The study objectives were to estimate longitudinal differences between birth seasons and production systems for lamb postweaning growth and indicators of GIN infection. Data were collected on Katahdin lambs within a single flock from 2006 to 2022. Lambs were born in either the winter or fall and reared in conventional or certified organic production systems. Four sub-flocks were defined as the combination of birth season and production system (winter-conventional = W-C, n  = 1766; winter-organic = W-O, n  = 190; fall-conventional = F-C, n  = 846; and fall-organic = F-O, n  = 189). All lambs were naturally infected with GIN from previously grazed pastures, weaned at approximately 60 d of age, and remained on pasture throughout the postweaning phase. At approximately 90, 120, and 150 d of age lamb body weight (BW) was recorded, and fecal egg count and blood packed cell volume (PCV) were quantified. Fecal egg count was log-transformed (LFEC) prior to analyses. Traits were initially analyzed within collection timepoint to compare all 4 sub-flocks. Final BW at 150 d and LFEC and PCV throughout the postweaning phase were similar between conventional and organic lambs born in the same season. Repeated measures models were then used to analyze records from W-C and F-C lambs over time. The collection timepoint × deworming treatment × sub-flock interaction effect was significant for all traits ( P  < 0.01). Within lambs that did not require deworming, no difference in BW between birth seasons was observed. However, LFEC trends for untreated F-C and W-C lambs were nearly exact opposite of one another, being greater for F-C at 90 d, ( P  < 0.01) not different at 120 d, and greater for W-C at 150 d ( P  < 0.01). Additionally, PCV of untreated F-C lambs was lower at 90 d but greater at 120 and 150 d than untreated W-C lambs ( P  ≤ 0.04). This was the first study conducted in the U.S. to compare longitudinal performance between lambs born in different seasons and reared in different production systems. Under the conditions of this study, organically managed lambs had similar performance to their conventionally managed counterparts. However, large differences in GIN infection risk over time existed between birth seasons and deworming regimens which have important implications for producer management decisions and genetic improvement programs., Competing Interests: The authors declare no real or perceived conflicts of interest., (Published by Oxford University Press for the American Society of Animal Science 2024.)

In cattle, oviductal function is controlled by the ovarian sex-steroids estradiol and progesterone. Here, we tested the hypothesis that the exposure to contrasting sex-steroid milieus differentially impacts the oviductal fluid composition. Estrous cycles of non-lactating, multiparous Nelore cows were pre-synchronized and then synchronized with a protocol designed two induce ovulation of large or small follciles. Larger preovulatory follicle (day 0) and corpora lutea (day 4) and greater estradiol (day 0) and progesterone (day 4) concentrations were observed in the large follciles group. Four days after induced ovulation, oviductal fluid was collected post-mortem. Quantitative mass spectrometry was used to determine the concentration of amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, hexoses, prostaglandins, and related compounds. Multivariate analyses (orthogonal projections to latent structures discriminant analysis) were conducted to compare the metabolomic signatures of oviductal fluids. Correlation network analysis was conducted to measure the strength and hierarchy of associations among metabolites. Of the 205 metabolites quantified, 171 were detected in at least 50% of the samples and were included in further data analysis. After orthogonal projections to latent structures discriminant analysis analysis, samples of the large follciles and small follciles were divided clearly into two non-overlapping clusters. Twenty metabolites had different or tended to have different concentrations in the oviductal fluid when comparing groups. Seven of these 20 analytes had greater concentrations in large follciles cows. Moreover, total sum of biogenic amines, phosphatidylcholines, and prostaglandins were higher in the small follciles group. The correlation network showed that the large follciles group metabolites' concentrations were highly intercorrelated, which was not observed in the small follciles group. We concluded that the periovulatory endocrine milieu regulates the composition of the oviductal fluid., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. Within seven genes (CHRNA3, CHRNA5, CHRNB2, CHRNB4, DRD2, DBH and CYP2A6) influencing biological mechanisms relevant to smoking, this study aimed to identify single nucleotide polymorphisms (SNPs) associated with smoking cessation throughout up to 38-years of follow-up., Methods: Participants were from two all-female cohort studies, Nurses' Health Study (NHS) (n = 10,017) and NHS-2 (n = 2,793). For 132 SNPs providing coverage of these genes, genotype associations with the probability of quitting smoking over time were evaluated using generalized estimating equations models. For SNPs reaching nominal statistical significance (p < 0.05) within NHS, NHS-2 was used as the replication cohort to control for multiple testing (false discovery rate (FDR) < 0.05). SNP genotype by smoking intensity (lifetime light versus non-light smoking) interactions were also evaluated., Results: Five SNPs identified in NHS were replicated in NHS-2 with FDR < 0.05. Women with the minor alleles of CHRNA5 SNPs rs637137 [OR = 1.21] and rs503464 [OR = 1.24] had increased odds of cessation. Women with the minor alleles of CYP2A6 SNPs rs56113850 [OR = 0.81] and rs56267346 [OR = 0.82] and DBH SNP rs6479643 [OR = 0.78] had lower odds of cessation throughout adulthood. An interaction with smoking intensity was indicated for three SNPs, CHRNB4 rs4887074, CHRNA3 SNP rs77438700, and CHRNA5 SNP rs76474922., Conclusion: Genetic associations with smoking cessation over decades of follow-up were observed and may guide targeted approaches for smokers most at risk for long-term relapse., Implications: This study identified single nucleotide polymorphisms (SNPs) within CHRNA5-A3-B4, CYP2A6, and DBH that were associated with smoking cessation in women over decades of follow-up. This study is the first to examine these genetic associations over years of follow-up. Some associations were novel while others replicated previous findings from short-term studies for the first time. Potential differences in some associations between light and non-light smokers were also observed. Genetic factors associated with long-term smoking behavior may help inform interventions modeled on long-term chronic disease management approaches; specifically, targeted maintenance interventions to sustain abstinence could be implemented among high-risk smokers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Across the tree of life, species have repeatedly evolved similar phenotypes. While well-studied for ecological traits, there is also evidence for recurrent evolution of sexually selected traits. Swordtail fish (Xiphophorus) is a classic model system for studying sexual selection, and female Xiphophorus exhibit strong mate preferences for large male body sizes and a range of sexually dimorphic ornaments. Interestingly, sexually selected traits have also been lost multiple times in the genus. However, there has been uncertainty over the number of losses of ornamentation and large body size because phylogenetic relationships between species in this group have historically been controversial, partially due to prevalent gene flow. Here, we use whole-genome sequencing approaches to reexamine phylogenetic relationships within a Xiphophorus clade that varies in the presence and absence of sexually selected traits. Using wild-caught individuals, we determine the phylogenetic placement of a small, unornamented species, X. continens, confirming an additional loss of ornamentation and large body size in the clade. With these revised phylogenetic relationships, we analyze evidence for coevolution between body size and other sexually selected traits using phylogenetic comparative methods. These results provide insights into the evolutionary pressures driving the recurrent loss of suites of sexually selected traits., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE).)

Background and Objectives: This paper aims to extend research on the association between mother-child contact and adult children's psychological well-being in later-life families by differentiating between in-person, virtual, and written digital contact, examining the moderating role of children's gender, and exploring the processes that underlie these associations., Research Design and Methods: Mixed-methods data were collected from 250 adult children nested within 131 families as part of the third wave of the Within-Family Differences Study. On average, adult children were 59 and mothers were 88 years of age., Results: Multilevel analyses revealed that interacting with mothers through written digital media was associated with higher depressive symptoms among adult children, whereas mother-child in-person and virtual digital contact were not associated with children's depressive symptoms. When stratifying the sample by children's gender, we found that mother-child written digital contact was associated with higher depressive symptoms among daughters, but not sons. Qualitative analyses suggested that adult daughters' psychological well-being was negatively associated with written digital contact with their mothers because this medium of interaction typically fell short of daughters' expectations for emotionally enriching exchanges., Discussion and Implications: This study revealed differences in how virtual and written digital contact are associated with psychological well-being among adult daughters, but not sons, suggesting that it is important to consider type of contact, gender of interactants, and content of exchanges when studying the associations between digital communication and relational and psychological well-being and designing intervention programs and digital communication technologies., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM)., Methods: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS., Results: Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores., Conclusion: The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival., Competing Interests: V.T.Y.C., D.M., K.P., and M.F.B. developed the software through Voronoi Health Analytics, Inc. that was used for this study. This had no influence on the data analysis, data interpretation, or manuscript preparation and submission at any point., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Psychedelics (e.g., 3,4-Methylenedioxymethamphetamine [MDMA], lysergic acid diethylamide [LSD], psilocybin) are molecules that have the potential to produce rapid therapeutic effects when paired with psychotherapy. Randomized clinical trials of psychedelic-assisted psychotherapy (PAT) have shown promising results for post-traumatic stress disorder (PTSD), depression, and substance use disorders. The U.S. Food and Drug Administration has acknowledged the promise of PAT, signaling potential approval of psilocybin-assisted therapy for depression by 2026. Given this timeline, implementation scientists must engage with PAT researchers, policymakers, and practitioners to think critically about bringing these promising new treatments into routine practice settings while maintaining quality and safety. This commentary aims to initiate a dialogue between implementation scientists and PAT researchers and practitioners on addressing these questions with a lens toward equity. Specifically, we discuss how the field of implementation science can support PAT stakeholders to accelerate the translational process from research into practice, focusing specifically on safety-net settings (i.e., Federally Qualified Health Centers and Veterans Affairs health systems) that serve historically marginalized populations. We use the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework to illustrate five critical areas where implementation science can help move PAT from research into real-world practice. For each RE-AIM dimension, we highlight ways the field of implementation science can contribute tools (e.g., implementation strategies), methodologies (e.g., pragmatic hybrid implementation-effectiveness trials), and approaches (community-based participatory research) for establishing the safety, effectiveness, and accessibility of PAT for historically underserved communities., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of high-resolution 3-Dimensional (3D) structures of large biological macromolecules. Protein particle picking, the process of identifying individual protein particles in cryo-EM micrographs for building protein structures, has progressed from manual and template-based methods to sophisticated artificial intelligence (AI)-driven approaches in recent years. This review critically examines the evolution and current state of cryo-EM particle picking methods, with an emphasis on the impact of AI. We conducted a comparative evaluation of popular AI-based particle picking methods, using both general machine learning metrics and specific cryo-EM structure determination metrics. This analysis involved constructing the 3D density map from the picked protein particles and assessing the obtained resolution and particle orientation diversity, underscoring the significant impact of AI on cryo-EM particle picking. Despite the advancements, we also identified key obstacles, such as handling complex micrographs with small proteins. The analysis provides insights into the future development of more sophisticated and fully automated AI methods in cryo-EM particle recognition., (© The Author(s) 2025. Published by Oxford University Press.)

The Green Revolution more than doubled crop yields and food production in crop species such as wheat and rice. This was primarily accomplished by altering the gibberellin (GA) signaling pathway to reduce plant height and prevent plants from falling over when growth was promoted with fertilizer application. Similar approaches have not been successfully accomplished in other grass crops species, such as maize, due to pleiotropic deleterious traits that arise from altering the GA pathway. This review highlights new findings in GA research across grass crop species. We have primarily focused on the developmental role of GAs in plant architecture and growth. We discuss how alteration of GA effects could be used to alter plant morphology and development of ideal plant ideotypes for grass crop species. To further extend the Green Revolution and improve food production from cereal crop species, targeted and tissue specific regulation of the GA pathway will have to be undertaken., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9 KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9 leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mechanisms controlling trophoblast (TB) proliferation and differentiation during embryo implantation are poorly understood. Human trophoblast stem cells (TSC) and BMP4/A83-01/PD173074-treated pluripotent stem cell-derived trophoblast cells (BAP) are two widely employed, contemporary models to study TB development and function, but how faithfully they mimic early TB cells has not been fully examined. We evaluated the transcriptomes of TB cells from BAP and TSC and directly compared them with those from peri-implantation human embryos during extended embryo culture (EEC) between embryonic days 8 to 12. The BAP and TSC grouped closely with TB cells from EEC within each TB sublineage following dimensional analysis and unsupervised hierarchical clustering. However, subtle differences in transcriptional programs existed within each TB sublineage. We also validated the presence of six genes in peri-implantation human embryos by immunolocalization. Our analysis reveals that both BAP and TSC models have features of peri-implantation TB s, while maintaining minor transcriptomic differences, and thus serve as valuable tools for studying implantation in lieu of human embryos., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The National Cancer Institute (NCI) issued a 2021 memorandum adopting the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) task force recommendations to broaden clinical study eligibility criteria. They recommended that washout periods be eliminated for most prior cancer therapy and when required to utilize evidence- and/or rationale-based criteria. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium responded to this guidance., Methods: A TACL task force reviewed the consortium's research portfolio, the relevant literature and guidance documents from ASCO-Friends, NCI, and US Food and Drug Administration to make expert consensus and evidence-based recommendations for modernizing, broadening, and codifying TACL-study washout periods while ensuring consistency with pediatric ethics, and federal regulations. TACL's screening log was reviewed to estimate the impact that updated washout periods would have on patient inclusivity and recruitment., Results: Over a 19-year period, 42 (14.6% of all screened ineligible patients [n = 287]) patients were identified as excluded from TACL early phase studies exclusively because of not meeting washout criteria. An additional 6 (2.1%) did not meet washout and at least 1 other exclusion criterion. A new TACL washout guidance document was developed and then adopted for use. Where washout criteria were not eliminated, rationale- and/or evidenced-based criteria were established with citation., Conclusion: In an effort to reduce unnecessary exclusion from clinical trials, TACL created rationale- and/or evidenced-based washout period standards largely following guidance from the NCI and ASCO-Friends recommendations. These new, expanded eligibility criteria are expected to increase access to TACL clinical trials while maintaining safety and scientific excellence., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery. By isolating and extending the ELD, we created a novel shuttle peptide, termed S237. While S237 achieved lower delivery of green fluorescent protein, it outperformed S10 at Cas9 RNP delivery to cultured human airway epithelial cells and to pig airway epithelia in vivo, possibly due to its lower net charge. In well-differentiated primary human airway epithelial cell cultures, S237 achieved a 4.6-fold increase in base editor RNP delivery, correcting up to 9.4% of the cystic fibrosis transmembrane conductance regulator (CFTR) R553X allele and restoring CFTR channel function close to non-CF levels. These findings deepen the understanding of peptide-mediated delivery and offer a translational approach for base editor RNP delivery for CF airway disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

The impact of vaccine-induced immune responses on host metabolite availability has not been well studied. Here we show that prior vaccination alters the metabolic profile of mice challenged with Brucella melitensis. In particular, glucose levels were reduced in vaccinated mice in an antibody-dependent manner. We also found the glucose transporter gene gluP plays a lesser role in B melitensis virulence in vaccinated wild type mice relative to vaccinated mice unable to secrete antibodies. These data indicate that vaccine-elicited antibodies protect the host in part by restricting glucose availability. Moreover, Brucella and other pathogens may need to employ different metabolic strategies in vaccinated hosts., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)