Predictors of middle school students' perceptions of automated writing evaluation.

This study examined middle school students' perceptions of an automated writing evaluation (AWE) system, MI Write. We summarize students' perceptions of MI Write's usability, usefulness, and desirability both quantitatively and qualitatively. We then estimate hierarchical entry regression models that account for district context, classroom climate, demographic factors (i.e., gender, special education status, limited English proficiency status, socioeconomic status, grade), students' writing-related beliefs and affect, and students' writing proficiency as predictors of students' perceptions. Controlling for districts, students reporting more optimal classroom climate also reported higher usability, usefulness, and desirability for MI Write. Also, model results revealed that eighth graders, students with limited English proficiency, and students of lower socioeconomic status perceived MI Write relatively more useable; students with lower socioeconomic status also perceived MI Write relatively more useful and desirable. Students who liked writing more and more strongly believed that writing is a recursive process viewed MI Write as more useable, useful, and desirable. Students with greater writing proficiency viewed MI Write as less useable and useful; writing proficiency was not related to desirability perceptions. We conclude with a discussion of implications and future directions.

Rbpj deletion in hepatic progenitor cells attenuates endothelial responses in a mouse model of cholestatic liver disease.

Background and Aims: Since the role of hepatic progenitor cells (HPCs) constituting ductular reactions in pathogenesis remains ambiguous, we aimed to establish the in vivo cause-and-effect relationship between HPCs and angiogenesis, a process associated with chronic liver disease progression. We previously demonstrated that peritumoral ductules are associated with angiogenesis in liver tumors and forkhead box L1 (Foxl1)- expressing murine HPCs secrete angiogenic factors in vitro. Therefore, we hypothesized that HPCs are capable of remodeling the vascular microenvironment and this function of HPCs is dependent on recombination signal binding protein for immunoglobulin kappa J region (RBPJ), a key effector of the Notch signaling pathway. Approach and Results: We generated HPC-specific Rbpj conditional knockout mice using Foxl1-Cre and treated them with the 3,5-diethoxycarbonyl-1,4-dihydrocollidine-supplemented diet to induce cholestatic liver disease. Knockout mice displayed significant reduction of HPC proliferation and ductular reactions as well as attenuated vascular and fibrotic areas compared to control mice. Assessment of vascular endothelial growth factor A-positive areas in vivo and the effects of Rbpj shRNAs in vitro indicated that Rbpj knockout in HPCs reduces the total number of angiogenic factor-expressing cells rather than affecting angiogenic factor expression within HPCs. Single-nucleus RNA sequencing analysis indicated that conditional Rbpj knockout in HPCs induces transcriptional changes in endothelial cells and alters expression of genes involved in various functions of the endothelium. Conclusion: Our findings indicate that HPCs regulate endothelial responses to cholestatic liver disease and Rbpj deletion in HPCs attenuates these responses, identifying novel targets for modulating angiogenesis during disease progression.

Single-cell sequencing dissects the transcriptional identity of activated fibroblasts and identifies novel persistent distal tubular injury patterns in kidney fibrosis.

Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with "secretory", "contractile" and "vascular" transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8 and Vcam1, while the surviving proximal tubules (PTs) showed restored transcriptional signature. We also found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease.

d-Mon: A Transmon with Strong Anharmonicity Based on Planar c-Axis Tunneling Junction between d-Wave and s-Wave Superconductors.

We propose a novel qubit architecture based on a planar c-axis Josephson junction between a thin flake d-wave superconductor, such as a high-T_{c} cuprate Bi_{2}Sr_{2}CaCu_{2}O_{8+x}, and a conventional s-wave superconductor. When operated in the transmon regime the device-that we call "d mon"-becomes insensitive to offset charge fluctuations and, importantly, exhibits at the same time energy level spectrum with strong anharmonicity that is widely tunable through the device geometry and applied magnetic flux. Crucially, unlike previous qubit designs based on d-wave superconductors the proposed device operates in a regime where quasiparticles are fully gapped and can be therefore expected to achieve long coherence times.

Writing motivation and ability profiles and transition during a technology-based writing intervention.

Students exhibit heterogeneity in writing motivation and ability. Profiles based on measures of motivation and ability might help to describe this heterogeneity and better understand the effects of interventions aimed at improving students' writing outcomes. We aimed to identify writing motivation and ability profiles in U.S. middle-school students participating in an automated writing evaluation (AWE) intervention using MI Write, and to identify transition paths between profiles as a result of the intervention. We identified profiles and transition paths of 2,487 students using latent profile and latent transition analysis. Four motivation and ability profiles emerged from a latent transition analysis with self-reported writing self-efficacy, attitudes toward writing, and a measure of writing writing: Low, Low/Mid, Mid/High, and High. Most students started the school year in the Low/Mid (38%) and Mid/High (30%) profiles. Only 11% of students started the school year in the High profile. Between 50 and 70% of students maintained the same profile in the Spring. Approximately 30% of students were likely to move one profile higher in the Spring. Fewer than 1% of students exhibited steeper transitions (e.g., from High to Low profile). Random assignment to treatment did not significantly influence transition paths. Likewise, gender, being a member of a priority population, or receiving special education services did not significantly influence transition paths. Results provide a promising profiling strategy focused on students' attitudes, motivations, and ability and show students' likeliness to belong to each profile based on their demographic characteristics. Finally, despite previous research indicating positive effects of AWE on writing motivation, results indicate that simply providing access to AWE in schools serving priority populations is insufficient to produce meaningful changes in students' writing motivation profiles or writing outcomes. Therefore, interventions targeting writing motivation, in conjunction with AWE, could improve results.

Single-cell sequencing dissects the transcriptional identity of activated fibroblasts and identifies novel persistent distal tubular injury patterns in kidney fibrosis.

Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with "secretory", "contractile" and "vascular" transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8, while the surviving proximal tubules (PTs) showed restored transcriptional signature. Furthermore, we found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease.

Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids.

De novo mutations and copy number deletions in NRXN1 (2p16.3) pose a significant risk for schizophrenia (SCZ). It is unclear how NRXN1 deletions impact cortical development in a cell type-specific manner and disease background modulates these phenotypes. Here, we leveraged human pluripotent stem cell-derived forebrain organoid models carrying NRXN1 heterozygous deletions in isogenic and SCZ patient genetic backgrounds and conducted single-cell transcriptomic analysis over the course of brain organoid development from 3 weeks to 3.5 months. Intriguingly, while both deletions similarly impacted molecular pathways associated with ubiquitin-proteasome system, alternative splicing, and synaptic signaling in maturing glutamatergic and GABAergic neurons, SCZ-NRXN1 deletions specifically perturbed developmental trajectories of early neural progenitors and accumulated disease-specific transcriptomic signatures. Using calcium imaging, we found that both deletions led to long-lasting changes in spontaneous and synchronous neuronal networks, implicating synaptic dysfunction. Our study reveals developmental-timing- and cell-type-dependent actions of NRXN1 deletions in unique genetic contexts.

Center volume effect on acute cellular rejection and outcomes in pediatric lung transplant recipients.

BACKGROUND: Acute cellular rejection (ACR) is common after lung transplant (LTx). We sought to determine if transplant center volume affected ACR-related outcomes in children after LTx. METHODS: The United Network for Organ Sharing (UNOS) Registry was queried for patients <18-years-of-age who underwent LTx 1987-2020. Cohorts were children who survived the first-year post transplant and were treated for ACR within that first year (ACR group) and those not treated for ACR (non-ACR). LTx center volume was defined as: high volume center (HVC) (>5LTxs/year), medium volume center (MVC) (>1≤5 LTxs/year), and low volume center (LVC) (≤1LTxs/year). RESULTS: 1320 patients were enrolled into the study; 269 (20.4%) did not experience ACR. The ACR cohort was older (median 14 [11-16] vs 13 [7-16] years, p < 0.001), female (65.3% vs 57.3%, p = 0.016), had cystic fibrosis (62.3% vs 45.5%, p < 0.001), and had a higher lung allocation score (37.3 [34.6-47.8] vs 35.8 [33-42.6], p = 0.029). The ACR cohort trended (p = 0.06) towards lower survival at 5-year (37% vs 47%) and 10-year (25% vs 34%) post-LTx. Among children at HVCs, ACR occurred in 17% of recipients (n = 98/574), compared to 18.5% (n = 73/395) at MVCs and 27% (n = 100/369) at LVCs. Children treated for ACR at HVCs had higher survival than LVCs at 5-years (52% vs 29%) and 10-years (36% vs 15%) (p < 0.001) but similar survival to MVCs at 5-years (52% vs 43%) and 10-years (36% vs 24%) (p = 0.081). No survival differences were detected in MVCs vs LVCs (p = 0.14). CONCLUSIONS: ACR treated within the first post-LTx year influence survival of children. ACR incidence was lowest at higher volume centers whereas post-ACR treatment survival outcomes were also superior.

Reverse vaccinology-based identification of a novel surface lipoprotein that is an effective vaccine antigen against bovine infections caused by Pasteurella multocida.

Pasteurella multocida can infect a multitude of wild and domesticated animals, with infections in cattle resulting in hemorrhagic septicemia (HS) or contributing to bovine respiratory disease (BRD) complex. Current cattle vaccines against P. multocida consist of inactivated bacteria, which only offer limited and serogroup specific protection. Here, we describe a newly identified surface lipoprotein, PmSLP, that is present in nearly all annotated P. multocida strains isolated from cattle. Bovine associated variants span three of the four identified phylogenetic clusters, with PmSLP-1 and PmSLP-2 being restricted to BRD associated isolates and PmSLP-3 being restricted to isolates associated with HS. Recombinantly expressed, soluble PmSLP-1 (BRD-PmSLP) and PmSLP-3 (HS-PmSLP) vaccines were both able to provide full protection in a mouse sepsis model against the matched P. multocida strain, however no cross-protection and minimal serum IgG cross-reactivity was identified. Full protection against both challenge strains was achieved with a bivalent vaccine containing both BRD-PmSLP and HS-PmSLP, with serum IgG from immunized mice being highly reactive to both variants. Year-long stability studies with lyophilized antigen stored under various temperatures show no appreciable difference in biophysical properties or loss of efficacy in the mouse challenge model. PmSLP-1 and PmSLP-3 vaccines were each evaluated for immunogenicity in two independent cattle trials involving animals of different age ranges and breeds. In all four trials, vaccination with PmSLP resulted in an increase in antigen specific serum IgG over baseline. In a blinded cattle challenge study with a recently isolated HS strain, the matched HS-PmSLP vaccine showed strong efficacy (75-87.5% survival compared to 0% in the control group). Together, these data suggest that cattle vaccines composed of PmSLP antigens can be a practical and effective solution for preventing HS and BRD related P. multocida infections.

Racial and Ethnic Disparities in Hospital-Based Care Among Dual Eligibles Who Use Health Centers.

Introduction: Health center use may reduce hospital-based care among Medicare-Medicaid dual eligibles, but racial and ethnic disparities in this population have not been widely studied. We examined the extent of racial and ethnic disparities in hospital-based care among duals using health centers and the degree to which disparities occur within or between health centers. Methods: We used 2012-2018 Medicare claims and health center data to model emergency department (ED) visits, observation stays, hospitalizations, and 30-day unplanned returns as a function of race and ethnicity among dual eligibles using health centers. Results: In rural and urban counties, age-eligible Black individuals had more ED visits (7.9 [4.0, 11.7] and 13.7 [10.0, 17.4] per 100 person-years) and were more likely to experience an unplanned return (1.4 [0.4, 2.4] and 1 [0.4, 1.6] percentage points [pp]) than White individuals, but were less likely to be hospitalized (-3.3 [-3.9, -2.8] and -1.2 [-1.6, -0.9] pp). In urban counties, age-eligible Black individuals were 1.2 [0.9, 1.5] pp more likely than White individuals to have observation stays. Other racial and ethnic groups used the same or less hospital-based care than White individuals. Including state and health center fixed effects eliminated Black versus White disparities in all outcomes, except hospitalization. Results were similar among disability-eligible duals. Conclusion: Racial and ethnic disparities in hospital-based care among dual eligibles are less common within than between health centers. If health centers are to play a more central role in eliminating racial and ethnic health disparities, these differences across health centers must be understood and addressed.

IL-1/MyD88-Dependent G-CSF and IL-6 Secretion Mediates Postburn Anemia.

The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion. Our analysis of mouse and human skin samples identified the burn wound as a primary source of G-CSF and IL-6 secretion. We show that G-CSF and IL-6 are secreted independently through an IL-1/MyD88-dependent mechanism, and we ruled out TLR2 and TLR4 as critical receptors. Our results indicate that IL-1/MyD88-dependent G-CSF secretion plays a key role in impairing medullary erythropoiesis and IL-6 secretion plays a key role in limiting the access of erythroid cells to iron. Importantly, we found that IL-1α/ß neutralizing Abs broadly attenuated features of postburn ACI that could be attributed to G-CSF or IL-6 secretion and rescued deficits of circulating RBC counts, hemoglobin, and hematocrit caused by burn injury. We conclude that wound-based IL-1/MyD88 signaling mediates postburn ACI through induction of G-CSF and IL-6 secretion.

Primary care patterns among dual eligibles with Alzheimer's disease and related dementias.

BACKGROUND: Primary care is essential for persons with Alzheimer's disease and related dementias (ADRD). Prior research suggests that the propensity to provide high-quality, continuous primary care varies by provider setting, but the settings used by Medicare-Medicaid dual-eligibles with ADRD have not been described at the population level. METHODS: Using 2012-2018 Medicare data, we identified dual-eligibles with ADRD. For each person-year, we identified primary care visits occurring in six settings. We calculated descriptive statistics for beneficiaries with a majority of visits in each setting, and conducted a k-means cluster analysis to determine utilization patterns, using the standardized count of primary care visits in each setting. RESULTS: Each year from 2012 to 2018, at least 45.6% of dual-eligibles with ADRD received a majority of their primary care in nursing facilities, while at least 25.2% did so in physician offices. Over time, the share relying on nursing facilities for primary care decreased by 5.2 percentage points, offset by growth in Federally Qualified Health Centers (FQHCs) and miscellaneous settings (2.3 percentage points each). Dual-eligibles relying on nursing facilities had more annual primary care visits (16.1) than those relying on other settings (range: 6.8-10.7 visits). Interpersonal care continuity was also higher in nursing facilities (97.0%) and physician offices (87.9%) than in FQHCs (54.2%), rural health clinics (RHCs, 46.6%), or hospital-based clinics (56.8%). Among dual-eligibles without care continuity, 82.7% were assigned to a cluster with few primary care visits. CONCLUSIONS: A trend toward care in different settings likely reflects improved access to patient-centered primary care. Low rates of interpersonal care continuity in FQHCs, RHCs, and physician offices may warrant concern, unless providers in these settings function as a care team. Nonetheless, every healthcare system encounter presents an opportunity to designate a primary care provider for dual-eligibles with ADRD who use little or no primary care.

Characterizing the Uptake of Newly Opened Health Centers by Individuals Dually Enrolled in Medicare and Medicaid.

Federally qualified health centers (FQHCs) increasingly provide high-quality, cost-effective primary care to individuals dually enrolled in Medicare and Medicaid. However, not everyone can access an FQHC. We used 2012 to 2018 Medicare claims and federally collected FQHC data to examine communities where an FQHC first opened and determine which dual eligibles used it. Overall uptake was 10%, ranging from 6.6% among age-eligible urban residents to 14.8% among disability-eligible rural residents. Community-level uptake ranged from 0% to 76.4% (median = 5.5%; interquartile range = 2.8%-11.3%). Certain subpopulations of dual eligibles are significantly more likely to use FQHCs. Our findings should inform the targeting of future FQHC expansions.

Transitions in the Learnability of Global Charges from Local Measurements.

We consider monitored quantum systems with a global conserved charge, and ask how efficiently an observer ("eavesdropper") can learn the global charge of such systems from local projective measurements. We find phase transitions as a function of the measurement rate, depending on how much information about the quantum dynamics the eavesdropper has access to. For random unitary circuits with U(1) symmetry, we present an optimal classical classifier to reconstruct the global charge from local measurement outcomes only. We demonstrate the existence of phase transitions in the performance of this classifier in the thermodynamic limit. We also study numerically improved classifiers by including some knowledge about the unitary gates pattern.

Field Theory of Charge Sharpening in Symmetric Monitored Quantum Circuits.

Monitored quantum circuits (MRCs) exhibit a measurement-induced phase transition between area-law and volume-law entanglement scaling. MRCs with a conserved charge additionally exhibit two distinct volume-law entangled phases that cannot be characterized by equilibrium notions of symmetry-breaking or topological order, but rather by the nonequilibrium dynamics and steady-state distribution of charge fluctuations. These include a charge-fuzzy phase in which charge information is rapidly scrambled leading to slowly decaying spatial fluctuations of charge in the steady state, and a charge-sharp phase in which measurements collapse quantum fluctuations of charge without destroying the volume-law entanglement of neutral degrees of freedom. By taking a continuous-time, weak-measurement limit, we construct a controlled replica field theory description of these phases and their intervening charge-sharpening transition in one spatial dimension. We find that the charge fuzzy phase is a critical phase with continuously evolving critical exponents that terminates in a modified Kosterlitz-Thouless transition to the short-range correlated charge-sharp phase. We numerically corroborate these scaling predictions also hold for discrete-time projective-measurement circuit models using large-scale matrix-product state simulations, and discuss generalizations to higher dimensions.

Dynamical topological phase realized in a trapped-ion quantum simulator.

Nascent platforms for programmable quantum simulation offer unprecedented access to new regimes of far-from-equilibrium quantum many-body dynamics in almost isolated systems. Here achieving precise control over quantum many-body entanglement is an essential task for quantum sensing and computation. Extensive theoretical work indicates that these capabilities can enable dynamical phases and critical phenomena that show topologically robust methods to create, protect and manipulate quantum entanglement that self-correct against large classes of errors. However, so far, experimental realizations have been confined to classical (non-entangled) symmetry-breaking orders1-5. In this work, we demonstrate an emergent dynamical symmetry-protected topological phase6, in a quasiperiodically driven array of ten 171Yb+ hyperfine qubits in Quantinuum's System Model H1 trapped-ion quantum processor7. This phase shows edge qubits that are dynamically protected from control errors, cross-talk and stray fields. Crucially, this edge protection relies purely on emergent dynamical symmetries that are absolutely stable to generic coherent perturbations. This property is special to quasiperiodically driven systems: as we demonstrate, the analogous edge states of a periodically driven qubit array are vulnerable to symmetry-breaking errors and quickly decohere. Our work paves the way for implementation of more complex dynamical topological orders8,9 that would enable error-resilient manipulation of quantum information.

The association between primary care use and potentially-preventable hospitalization among dual eligibles age 65 and over.

BACKGROUND: Individuals dually-enrolled in Medicare and Medicaid (dual eligibles) are disproportionately sicker, have higher health care costs, and are hospitalized more often for ambulatory care sensitive conditions (ACSCs) than other Medicare beneficiaries. Primary care may reduce ACSC hospitalizations, but this has not been well studied among dual eligibles. We examined the relationship between primary care and ACSC hospitalization among dual eligibles age 65 and older. METHODS: In this observational study, we used 100% Medicare claims data for dual eligibles ages 65 and over from 2012 to 2018 to estimate the likelihood of ACSC hospitalization as a function of primary care visits and other factors. We used linear probability models stratified by rurality, with subgroup analyses for dual eligibles with diabetes or congestive heart failure. RESULTS: Each additional primary care visit was associated with an 0.05 and 0.09 percentage point decrease in the probability of ACSC hospitalization among urban (95% CI: - 0.059, - 0.044) and rural (95% CI: - 0.10, - 0.08) dual eligibles, respectively. Among dual eligibles with CHF, the relationship was even stronger with decreases of 0.09 percentage points (95% CI: - 0.10, - 0.08) and 0.15 percentage points (95% CI: - 0.17, - 0.13) among urban and rural residents, respectively. CONCLUSIONS: Increased primary care use is associated with lower rates of preventable hospitalizations for dual eligibles age 65 and older, especially for dual eligibles with diabetes and congestive heart failure. In turn, efforts to reduce preventable hospitalizations for this dual-eligible population should consider how to increase access to and use of primary care.