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In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22-1.2 μm), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms.

For most graduate writers, acclimating to doctoral-level inquiry is fraught with numerous tensions, whether regarding the development of scholarly identity (Gardner et al., 2014), navigating graduate school's newly decentralized sources for support (Simpson, 2012), or mastering the writing and research conventions that govern disciplinary practice. Using a Cultural Historical Activity Theory (CHAT) framework, this case study analyzes the first-term experiences of Miranda, a first-year PhD student from the field of gerontology (who is also a co-author), and the tensions she feels around the drafting and revision of a single paper. Drawing from Engeström (1987), we theorize Miranda's challenges around motive, authority, and expert feedback as comprising three "contradictions" engendered by the contemporary activity system of doctoral-level learning-to-write, contradictions that at once challenge the writer's going presumptions about writing even while they enable new concepts and solutions to emerge. This analysis finally encourages researchers to take a wide, cultural-historical view of the many contexts in which doctoral students write during their first terms, including the instructor-led classroom, the larger culture of the program and institution, and the current high-pressure realities of doctoral-level academic study in the United States.

Abstract Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (encoded by IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKε. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a regulatory pathway involving rs2297550, Ikaros, and IKKε implicated by human genetics in risk for SLE.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Microglia are central to pathogenesis in many neurological conditions. Drugs targeting colony-stimulating factor-1 receptor (CSF1R) to block microglial proliferation in preclinical disease models have shown mixed outcomes, thus the therapeutic potential of this approach remains unclear. Here, we show that CSF1R inhibitors given by multiple dosing paradigms in the Tg2541 tauopathy mouse model cause a sex-independent reduction in pathogenic tau and reversion of non-microglial gene expression patterns toward a normal wild type signature. Despite greater drug exposure in male mice, only female mice have functional rescue and extended survival. A dose-dependent upregulation of immediate early genes and neurotransmitter dysregulation are observed in the brains of male mice only, indicating that excitotoxicity may preclude functional benefits. Drug-resilient microglia in male mice exhibit morphological and gene expression patterns consistent with increased neuroinflammatory signaling, suggesting a mechanistic basis for sex-specific excitotoxicity. Complete microglial ablation is neither required nor desirable for neuroprotection and therapeutics targeting microglia must consider sex-dependent effects.

This paper describes the development and implementation of a yearlong integrated English Language Arts (ELA) and computational thinking (CT) curriculum that has been adapted to meet the needs of multilingual students. The integration of computational thinking into K-12 literacy instruction has only been examined in a handful of studies, and little is known about how such integration supports the development of CT for multilingual students. We conducted a qualitative case study on curricular implementation in a general education classroom with large numbers of students designated as English learners. Results from detailed field notes revealed that the strategic application of instructional practices was implemented in the service of building on students' existing literacy skills to teach CT concepts and dispositions. The CT and literacy framework put forth in this study can be used as an analytic framework to highlight how instructional strategies mobilize the existing literacy and CT resources of linguistically diverse students. Based on our findings, we discuss recommendations for future integrated ELA-CT curricula.

PurposeQuantitative in vivo [18F]-(2S,4R)4-fluoroglutamine ([18F]4-FGln or more simply [18F]FGln) metabolic kinetic parameters are compared with activity levels of glutamine metabolism in different types of hepatocellular carcinoma (HCC).MethodsFor this study, we used two transgenic mouse models of HCC induced by protooncogenes, MYC, and MET. Biochemical data have shown that tumors induced by MYC have increased levels of glutamine metabolism compared to those induced by MET. One-hour dynamic [18F]FGln PET data were acquired and reconstructed for fasted MYC mice (n = 11 tumors from 7 animals), fasted MET mice (n = 8 tumors from 6 animals), fasted FVBN controls (n = 8 normal liver regions from 6 animals), nonfasted MYC mice (n = 16 tumors from 6 animals), and nonfasted FVBN controls (n = 8 normal liver regions from 3 animals). The influx rate constants (K 1) using the one-tissue compartment model were derived for each tumor with the left ventricular blood pool input function.ResultsInflux rate constants were significantly higher for MYC tumors (K 1 = 0.374 ± 0.133) than for MET tumors (K 1 = 0.141 ± 0.058) under fasting conditions (P = 0.0002). Rate constants were also significantly lower for MET tumors (K 1 = 0.141 ± 0.135) than normal livers (K 1 = 0.332 ± 0.179) under fasting conditions (P = 0.0123). Fasting conditions tested for MYC tumors and normal livers did not result in any significant difference with P values > 0.005.ConclusionHigher influx rate constants corresponded to elevated levels of glutamine metabolism as determined by biochemical assays. The data showed that there is a distinctive difference in glutamine metabolism between MYC and MET tumors. Our study has demonstrated the potential of [18F]FGln PET imaging as a tool to assess glutamine metabolism in HCC tumors in vivo with a caution that it may not be able to clearly distinguish HCC tumors from normal liver tissue.

Coastal observations along the Texas coast are valuable for many stakeholders in diverse domains. However, the management of the collected data has been limited, creating gaps in hydrological and atmospheric datasets. Among these, water and air temperature measurements are particularly crucial for water temperature predictions, especially during freeze events. These events can pose a serious threat to endangered sea turtles and economically valuable fish, which can succumb to hypothermic stunning, making them vulnerable to cold-related illness or death. Reliable and complete water and air temperature measurements are needed to provide accurate predictions of when cold-stunning events occur. To address these concerns, the focus of this paper is to describe the method used to create a complete 10-year dataset that is representative of the upper Laguna Madre, TX using multiple stations and various gap-filling methods. The raw datasets consist of a decade's worth of air and water temperature measurements within the Upper Laguna Madre from 2012 to 2022 extracted from the archives of the Texas Coastal Ocean Observation Network and the National Park Service. Large portions of data from the multiple stations were missing from the raw datasets, therefore a systematic gap-filling approach was designed and applied to create a near-continuous dataset. The proposed imputation method consists of three steps, starting with a short gap interpolation method, followed by a long gap-filling process using nearby stations, and finalized by a second short gap interpolation method. This systematic data imputation approach was evaluated by creating random artificial gaps within the original datasets, filling them using the proposed data imputation method, and assessing the viability of the proposed methods using various performance metrics. The evaluation results help to ensure the reliability of the newly imputed dataset and the effectiveness of the data imputation method. The newly created dataset is a valuable resource that transcends the local cold-stunning issue, offering viable utility for analyzing temporal variability of air and water temperatures, exploring temperature interdependencies, reducing forecasting uncertainties, and refining natural resource and weather advisory decision-making processes. The cleaned dataset with minimal gaps (

Abstract Background Adolescents and young adults (AYAs) with cancer are at high risk of poor psychosocial outcomes, and evidence-based interventions designed to meet their psychosocial and communication needs are lacking. The main objective of this project is to test the efficacy of a new adaptation of the Promoting Resilience in Stress Management intervention for AYAs with Advanced Cancer (PRISM-AC). Methods/design The PRISM-AC trial is a 2-arm, parallel, non-blinded, multisite, randomized controlled trial. 144 participants with advanced cancer will be enrolled and randomized to either usual, non-directive, supportive care without PRISM-AC (“control” arm) or with PRISM-AC (“experimental” arm). PRISM is a manualized, skills-based training program comprised of four 30–60 min, one-on-one sessions targeting AYA-endorsed resilience resources (stress-management, goal-setting, cognitive-reframing, and meaning-making). It also includes a facilitated family meeting and a fully equipped smartphone app. The current adaptation includes an embedded advance care planning module. English- or Spanish-speaking individuals 12–24 years old with advanced cancer (defined as progressive, recurrent, or refractory disease, or any diagnosis associated with

Abstract Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology.

BACKGROUND: A low prevalence of HIV in sickle cell disease (SCD) patients has been reported in the literature though mechanisms for this are not understood. METHODS: HIV risk behaviors were compared between SCD cases and non-SCD controls using a self-administered audio computer-assisted self-interview. SCD cases were recruited from a multi-center SCD cohort established in Brazil; controls were recruited from SCD social contacts. Categorical variables were analyzed using Chi-Square or Fisher exact test. Continuous variables were compared using the Mann-Whitney U test. RESULTS: There were 152 SCD cases and 154 age/location matched controls enrolled at three participating Brazilian centers during 2016-17. No significant differences in number of sexual partners (lifetime or previous 12 months), male-to-male sex partners or intravenous drug use were observed. Cases received more transfusions, surgeries, and acupuncture treatment. CONCLUSIONS: Besides the risk of transfusion-transmitted HIV, which is now exceedingly rare, SCD and non-SCD participants demonstrated similar HIV risk behaviors. Causes other than risk behaviors such as factors inherent to SCD pathophysiology may explain the reported low prevalence of HIV in SCD.

Tau-mediated neurodegeneration is driven by disease-activated microglia and suppressed by their pharmacological blockade. The authors identified drug dose- and sex-dependent residual microglial phenotypes, neuronal excitotoxicity, and animal survival.

We propose a novel machine learning method for sampling from the high-dimensional probability distributions of Lattice Field Theories, which is based on a single neural ODE layer and incorporates the full symmetries of the problem. We test our model on the $\phi^4$ theory, showing that it systematically outperforms previously proposed flow-based methods in sampling efficiency, and the improvement is especially pronounced for larger lattices. Furthermore, we demonstrate that our model can learn a continuous family of theories at once, and the results of learning can be transferred to larger lattices. Such generalizations further accentuate the advantages of machine learning methods.

While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (±4% SD) under low emissions and 17% (±11% SD) under high emissions by 2100, with an average 5% decline for every 1 °C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends.

Verbal repetition requires the coordination of auditory, memory, linguistic, and motor systems. To date, the basic dynamics of neural information processing in this deceptively simple behavior are largely unknown. Here, we examined the neural processes underlying verbal repetition using focal interruption (electrocortical stimulation) in 58 patients undergoing awake craniotomies, and neurophysiological recordings (electrocorticography) in 8 patients while they performed a single word repetition task. Electrocortical stimulation revealed that sub-components of the left peri-Sylvian network involved in single word repetition could be differentially interrupted, producing transient perceptual deficits, paraphasic errors, or speech arrest. Electrocorticography revealed the detailed spatio-temporal dynamics of cortical activation, involving a highly-ordered, but overlapping temporal progression of cortical high gamma (75-150Hz) activity throughout the peri-Sylvian cortex. We observed functionally distinct serial and parallel cortical processing corresponding to successive stages of general auditory processing (posterior superior temporal gyrus), speech-specific auditory processing (middle and posterior superior temporal gyrus), working memory (inferior frontal cortex), and motor articulation (sensorimotor cortex). Together, these methods reveal the dynamics of coordinated activity across peri-Sylvian cortex during verbal repetition.

Abstract Background Effective systemic treatments have revolutionized the management of patients with metastatic melanoma, including those with brain metastases. The extent to which these treatments influence disease trajectories close to death is unknown. Therefore, this study aimed to gain insight into provided treatments and healthcare consumption during the last 3 months of life in patients with melanoma brain metastases. Methods Retrospective, single-center study, including consecutive patients with melanoma brain metastases diagnosed between June-2015 and June-2018, referred to the medical oncologist, and died before November-2019. Patient and tumor characteristics, anti-tumor treatments, healthcare consumption, presence of neurological symptoms, and do-not-resuscitate status were extracted from medical charts. Results 100 patients were included. A BRAF-mutation was present in 66 patients. Systemic anti-tumor therapy was given to 72% of patients during the last 3 months of life, 34% in the last month, and 6% in the last week. Patients with a BRAF-mutation more frequently received systemic treatment during the last 3 (85% vs. 47%) and last month (42% vs. 18%) of life than patients without a BRAF-mutation. Furthermore, patients receiving systemic treatment were more likely to visit the emergency room (ER, 75% vs. 36%) and be hospitalized (75% vs. 36%) than those who did not. Conclusion The majority of patients with melanoma brain metastases received anti-tumor treatment during the last 3 months of life. ER visits and hospitalizations occurred more often in patients on anti-tumor treatment. Further research is warranted to examine the impact of anti-tumor treatments close to death on symptom burden and care satisfaction.