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Abstract High‐sulfur, low‐oxygen environments formed by underwater sinkholes and springs create unique habitats populated by microbial mat communities. To explore the diversity and biogeography of these mats, samples were collected from three sites in Alpena, Michigan, one site in Monroe, Michigan, and one site in Palm Coast, Florida. Our study investigated previously undescribed eukaryotic diversity in these habitats and further explored their bacterial communities. Mat samples and water parameters were collected from sulfur spring sites during the spring, summer, and fall of 2022. Cyanobacteria and diatoms were cultured from mat subsamples to create a culture‐based DNA reference library. Remaining mat samples were used for metabarcoding of the 16S and rbcL regions to explore bacterial and diatom diversity, respectively. Analyses of water chemistry, alpha diversity, and beta diversity articulated a range of high‐sulfur, low‐oxygen habitats, each with distinct microbial communities. Conductivity, pH, dissolved oxygen, temperature, sulfate, and chloride had significant influences on community composition but did not describe the differences between communities well. Chloride concentration had the strongest correlation with microbial community structure. Mantel tests revealed that biogeography contributed to differences between communities as well. Our results provide novel information on microbial mat composition and present evidence that both local conditions and biogeography influence these unique communities.

The "RNA world" represents a novel frontier for the study of fundamental biological processes and human diseases and is paving the way for the development of new drugs tailored to each patient's biomolecular characteristics. Although scientific data about coding and non-coding RNA molecules are constantly produced and available from public repositories, they are scattered across different databases and a centralized, uniform, and semantically consistent representation of the "RNA world" is still lacking. We propose RNA-KG, a knowledge graph (KG) encompassing biological knowledge about RNAs gathered from more than 60 public databases, integrating functional relationships with genes, proteins, and chemicals and ontologically grounded biomedical concepts. To develop RNA-KG, we first identified, pre-processed, and characterized each data source; next, we built a meta-graph that provides an ontological description of the KG by representing all the bio-molecular entities and medical concepts of interest in this domain, as well as the types of interactions connecting them. Finally, we leveraged an instance-based semantically abstracted knowledge model to specify the ontological alignment according to which RNA-KG was generated. RNA-KG can be downloaded in different formats and also queried by a SPARQL endpoint. A thorough topological analysis of the resulting heterogeneous graph provides further insights into the characteristics of the "RNA world". RNA-KG can be both directly explored and visualized, and/or analyzed by applying computational methods to infer bio-medical knowledge from its heterogeneous nodes and edges. The resource can be easily updated with new experimental data, and specific views of the overall KG can be extracted according to the bio-medical problem to be studied.

Pacing guides are commonplace yet controversial in American public schools. For teachers who question their usefulness, one means to circumvent them is to exercise autonomy in pedagogical decision-making, though doing so comes with challenges. Through interviews, we examined how 87 gifted and general education 4th and 5th grade math and reading/language arts teachers in one large, diverse public school district expressed their autonomy and reported enacting it in their classrooms. Findings indicated teachers' perceptions of autonomy differed, and their reported pacing guide deviations also differed accordingly. We discuss implications for those in environments where use of pacing guides is mandated.

Abstract: Quantifying evapotranspiration (ET) is critical to accurately predict vegetation health, groundwater recharge, and streamflow generation. Hillslope aspect, the direction a hillslope faces, results in variable incoming solar radiation and subsequent vegetation water use that drive ET. Previous work in watersheds with a single dominant vegetation type (e.g., trees) have shown that equator‐facing slopes (EFS) have higher ET compared to pole‐facing slopes (PFS) due to higher evaporative demand. However, it remains unclear how differences in vegetation type (i.e., grasses and trees) influence ET and water partitioning between hillslopes with opposing aspects. Here, we quantified ET and root‐zone water storage deficits between a PFS and EFS with contrasting vegetation types within central coastal California. Our results suggest that the cooler PFS with oak trees has higher ET than the warmer EFS with grasses, which is counter to previous work in landscapes with a singule dominant vegetation type. Our root‐zone water storage deficit calculations indicate that the PFS has a higher subsurface storage deficit and a larger seasonal dry down than the EFS. This aspect difference in subsurface water storage deficits may influence the subsequent replenishment of dynamic water storage, groundwater recharge and streamflow generation. In addition, larger subsurface water deficits on PFS may reduce their ability to serve as hydrologic refugia for oaks during multi‐year droughts. This research provides a novel integration of field‐based and remotely‐sensed estimates of ET required to properly quantify hillslope‐scale water balances. These findings emphasize the importance of resolving hillslope‐scale vegetation structure within Earth system models, especially in landscapes with diverse vegetation types.

BACKGROUND: Recovery following total joint arthroplasty is patient-specific, yet groups of patients tend to fall into certain similar patterns of recovery. The purpose of this study was to identify and characterize recovery patterns following total hip arthroplasty (THA) and total knee arthroplasty (TKA) using patient-reported outcomes that represent distinct health domains. We hypothesized that recovery patterns could be defined and predicted using preoperative data. METHODS: Adult patients were recruited from a large, urban academic center. To model postoperative responses to THA and TKA across domains such as physical health, mental health, and joint-specific measures, we employed a longitudinal clustering algorithm that incorporates each of these health domains. The clustering algorithm from multiple health domains allows the ability to define distinct recovery trajectories, which could then be predicted from preoperative and perioperative factors using a multinomial regression. RESULTS: Four hundred forty-one of 1134 patients undergoing THA and 346 of 921 undergoing TKA met eligibility criteria and were used to define distinct patterns of recovery. The clustering algorithm was optimized for 3 distinct patterns of recovery that were observed in THA and TKA patients. Patients recovering from THA were divided into 3 groups: standard responders (50.8%), late mental responders (13.2%), and substandard responders (36.1%). Multivariable, multinomial regression suggested that these 3 groups had defined characteristics. Late mental responders tended to be obese (P = .05) and use more opioids (P = .01). Substandard responders had a larger number of comorbidities (P = .02) and used more opioids (P = .001). Patients recovering from TKA were divided among standard responders (55.8%), poor mental responders (24%), and poor physical responders (20.2%). Poor mental responders were more likely to be female (P = .04) and American Society of Anesthesiologists class III/IV (P = .004). Poor physical responders were more likely to be female (P = .03), younger (P = .04), American Society of Anesthesiologists III/IV (P = .04), use more opioids (P = .02), and be discharged to a nursing facility (P = .001). The THA and TKA models demonstrated areas under the curve of 0.67 and 0.72. CONCLUSIONS: This multidomain, longitudinal clustering analysis defines 3 distinct patterns in the recovery of THA and TKA patients, with most patients in both cohorts experiencing robust improvement, while others had equally well defined yet less optimal recovery trajectories that were either delayed in recovery or failed to achieve a desired outcome. Patients in the delayed recovery and poor outcome groups were slightly different between THA and TKA. These groups of patients with similar recovery patterns were defined by patient characteristics that include potentially modifiable comorbid factors. This research suggests that there are multiple defined recovery trajectories after THA and TKA, which provides a new perspective on THA and TKA recovery. LEVEL OF EVIDENCE: III.

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.

Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoint resources and abstraction algorithms), and benchmarks (e.g., prebuilt KGs). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 different large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

IntroductionAssociations of cerebellar atrophy with specific neuropathologies in Alzheimer's disease and related dementias (ADRD) have not been systematically analyzed. This study examined cerebellar gray matter volume across major pathological subtypes of ADRD.MethodsCerebellar gray matter volume was examined using voxel-based morphometry in 309 autopsy-proven ADRD cases and 80 healthy controls. ADRD subtypes included AD, mixed Lewy body disease and AD (LBD-AD), and frontotemporal lobar degeneration (FTLD). Clinical function was assessed using the Clinical Dementia Rating (CDR) scale.ResultsDistinct patterns of cerebellar atrophy were observed in all ADRD subtypes. Significant cerebellar gray matter changes appeared in the early stages of most subtypes and the very early stages of AD, LBD-AD, FTLD-TDP type A, and progressive supranuclear palsy. Cortical atrophy positively predicted cerebellar atrophy across all subtypes.DiscussionOur findings establish pathology-specific profiles of cerebellar atrophy in ADRD and propose cerebellar neuroimaging as a non-invasive biomarker for differential diagnosis and disease monitoring.HighlightsCerebellar atrophy was examined in 309 patients with autopsy-proven neurodegeneration. Distinct patterns of cerebellar atrophy are found in all pathological subtypes of Alzheimer's disease and related dementias (ADRD). Cerebellar atrophy is seen in early-stage (Clinical Dementia Rating [CDR] ≤1) AD, Lewy body dementia (LBD), frontotemporal lobar degeneration with tau-positive inclusion (FTLD-tau), and FTLD-transactive response DNA binding protein (FTLD-TDP). Cortical atrophy positively predicts cerebellar atrophy across all neuropathologies.

Background or Context: Public school library book challenges have garnered ample media attention in recent years as many school districts and advocacy organizations have reported record numbers of book challenges. Book challenges are not a new phenomenon, historically speaking, but they have often illuminated values clashes in communities and raise questions about the rights and freedoms of public school students. Judicial rulings and school district policies that address book challenges could provide insights for many members of school communities (including, but not limited to, school board members, students, parents, and teachers) as they experience challenges, but these aspects of the legal record and their influence on responses to book challenges remains underexamined in scholarship. Purpose, Objective, Research Question, or Focus of Study: The 1982 Supreme Court case "Island Trees School District v. Pico" remains the lasting judicial precedent for interpreting public school students' First Amendment rights as they interact with school library books. We examine the extent to which school district book challenge policies align with court precedent set in "Pico" (1982) and the implications for students' rights and democratic participation during book challenges. Research Design: Drawing on elements of the law and society framework as well as political analysis categories, this study uses qualitative methods to illuminate specific elements of district policies that govern book challenges. Specifically, we examine 29 policies in school districts that experienced a publicly reported book challenge between 2017 and 2021 to understand relationships between school district book challenge policies and the "Pico" (1982) precedent. Conclusions or Recommendations: Our findings reveal ample space between judicial rulings and school district policies we examine. In fact, we find a broader array of relevant actors in book challenge processes than conceived by the courts and raise implications for students' constitutional rights and protections related to who policies indicate may or must be involved in these processes, the settings in which book challenge decisions are made, and the limited roles for public involvement during school library book challenges.

Theological education faces the task of forming leaders and scholars with the capacity for personal and social transformation. This effort requires a deeper understanding of habit formation as both problem and potential. Utilizing the example of how racism functions through embodied habits, this article emphasizes bodily awareness and repeated practice as necessary components for theological formation. In doing so, this approach integrates contemplative and embodied pedagogies and suggests ways to address the research gap in these areas, especially regarding the study and teaching of religion. The tools and resources of somatic abolitionism offer a way to rewire bodily perceptions with theological classrooms.

Lyme disease, caused by infection with the bacterium Borrelia burgdorferi, is the most common vectorborne illness in the United States and is steadily affecting an expanding area of the country [...]

The purpose of this pilot study was to define what changes were experienced in the Fall 2020 semester by students in an undergraduate anatomy and physiology of speech and hearing course and highlight any differences in the experience of first-generation college students (FGCS). An online survey was administered to a single class of undergraduate students. Results indicated that students experienced a variety of challenges related to the pandemic and virtual learning. Differences in the experiences of FGCS compared to traditional students included increased hours worked and feelings of being overwhelmed and spending less time on course content each week. Future research is warranted to investigate these trends within a more representative population and identify ways that academic support can be utilized to improve student success.

Is underrepresentation of Black students, Latinx students, English learners (EL), and students from economically challenging communities in gifted programs due to inequality in early academic achievement or bias in the gifted identification process? Using three-level multilevel logistic models, we examine the degree to which the disparities in gifted identification are due to disparities in early achievement. Our datasets include 3rd-, 4th-, and 5th-grade achievement scores and demographic variables from all students in a 3rd-grade, 2011-2012 cohort across three states. Students who qualified for free/reduced-price lunch (FRPL), EL, and Black or Latinx students were between two to eight times less likely to be identified as gifted compared to non-free/reduced-price lunch, non-EL, and White or Asian students. However, between 50% and 100% of gifted identification disparities could be explained by student-level differences in early academic achievement, which is consistent with an opportunity gap explanation of underrepresentation.

In this column we describe the actions taken by the University of California, Davis Library to support and to communicate with the campus research community after the suspension of access to Elsevier's ScienceDirect platform.

BACKGROUND: The mare-foal relationship is essential for the well-being and growth of a foal. Mares milk provides a foal with nutrients, protective immunity, and microbes. Within the first two weeks of life, there is a risk for a foal to suffer from diarrhea, particularly foal heat diarrhea which happens at about the time of a mares estrus cycle but is more likely due to transitions in the microbiota in the foals gastrointestinal (GI) tract. We hypothesized that this GI microbiota transition could be caused by changes in lysozyme and microbial populations in the mares milk. To test this hypothesis, fifteen mare-foal pairs were followed in the first 15 days post-foaling. Every other day milk was collected from mares and rectal swabs were collected from foals. Lysozyme activity in the mares milk was measured using a fluorescence assay. Microbial DNA was isolated from the milk and swabs and the V4 domain of 16 S rRNA genes were PCR amplified and sequenced using Illumina MiSeq technology. Microbial populations were analyzed using DADA2 and phyloseq within R. RESULTS: Mares milk lysozyme activity peaked for samples at Day 1 and levels dropped to 72.5% of Day 1 activity by Day 15; however, microbial populations in the mares milk did not vary significantly over the two weeks. Furthermore, levels of microbial diversity found in foal rectal swabs were initially similar to microbial diversity seen in mares milk; however, over the first fifteen days, diversity increased for the foal rectal swab microbiota and swab microbial populations differed from milk microbes. A transition occurred shifting from microbes from the phylum Proteobacteria early in rectal swabs to those primarily from the phyla Firmicutes and Bacteroidota after the first few days post-foaling. These phyla contained several families and genera of microbes that promote utilization of milk components in healthy gut transition. Microbial abundance levels correlated more with days post-parturition than with lysozyme activity and mares milk microbial populations. CONCLUSIONS: The findings suggest that much of the microbial populations responsible for the transition of the foals gut comes from sources outside of mares milk species and levels of lysozyme activity.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate cook loss, drip loss, histopathology scores, and the gene expression of CCR7, LECT2, CD36, PPARG, and PTGS2. There were no significant differences between the broiler weights, thus chitosan did not appear to compromise the overall growth of the broilers. Female broilers fed 0.4% chitosan had the lowest WS incidence, while male broiler fed 0.4% chitosan had the least cook loss. However, gene expression analyses did not offer insight into any grossly or histologically visualized differences in the muscles. Thus, while we can postulate that chitosan could have some positive effect in reducing WS incidence and improving meat quality, further studies are required to better scrutinize the mechanisms by which chitosan affects WS and other such myopathies in fast-growing broilers.

INTRODUCTION: Cognition often remains unassessed in primary care. To improve early diagnosis of neurocognitive disorder (NCD) in Switzerland, the tablet-based UCSF brain health assessment (BHA) and brain health survey (BHS) were validated. METHODS: The German BHA, BHS, and Montreal Cognitive Assessment (MoCA) were administered to 67 patients with mild/major NCD and 50 controls. BHA includes subtests of memory, executive, visuospatial, and language functioning, and informant-based BHS asks about behavior and motor functioning. RESULTS: The complete instrument (BHA + BHS) was most accurate at detecting mild NCD (AUC = 0.95) and NCD without amyloid pathology (AUC = 0.96), followed by the BHA. All measures were accurate (all AUCs > 0.95) at distinguishing major NCD and NCD with amyloid pathology (Alzheimers disease [AD]) from controls. DISCUSSION: The German BHA and BHS are more sensitive to mild NCD and non-AD presentations than the MoCA and thus have a high potential to identify patients with NCD in primary care earlier than currently used screens.

PURPOSE: To serve as a guide for non-operative physicians in the management of femoroacetabular impingement syndrome and provide an algorithm as to when to refer patients for potential surgical management. RECENT FINDINGS: Supervised physical therapy programs that focus on active strengthening and core strengthening are more effective than unsupervised, passive, and non-core-focused programs. There is promising evidence for the use of intra-articular hyaluronic acid and PRP as adjunct treatment options. Recent systematic reviews and meta-analyses have found that in young active patients, hip arthroscopy demonstrates improved short-term outcomes over physical therapy. The decision for the management of FAIS is complex and should be specific to each patient. Consideration of the patients age, timing to return to sport, longevity of treatment, hip morphology, and degree of cartilage degeneration is required to make an informed decision in the treatment of these patients.