Understanding the relationship between social interaction patterns and cognitive engagement levels has critical implications on collaborative learning theory, pedagogy, and technology. This study used a multi-method approach to examine the relationship between students' social participatory roles and cognitive engagement levels within asynchronous online discussions. Results showed that students' social participatory role was a critical indicator of cognitive engagement level. Socially active students made more cognitive contributions to knowledge inquiry and knowledge construction. But there were exceptions: after taking leadership roles (i.e., discussion designers and facilitators), some students moved from peripheral participation to active participation. Second, there was a progressive development process: individual students' deep-level knowledge inquiry could trigger peer interaction, which could further advance group knowledge construction. Third, students had a tendency to keeping social-cognitive engagement patterns throughout discussions. Based on the result, this study proposed implications for collaborative learning theory, pedagogy support, and tool development.The relationship between social interaction and cognitive engagement is of significant importance for collaborative learning research and practice, pedagogy development and technology use (de Laat, Lally, Lipponen, & Simons, 2007). First, from the socio-cognitive constructivism perspective, there is a close relationship between social interaction and cognitive inquiry: the change and development in one have influences on the other (Liu & Matthews, 2005). Second, in practices, pedagogical strategies (eg, knowledge building pedagogy) have stressed the importance of understanding the interconnection between social interaction and cognitive inquiry to improve collaborative learning quality (van Aalst, 2009). Third, emerging tools, such as social network

A lthough most coronavirus disease 2019 (COVID-19) infections are self-limited, some develop into sepsis and multisystem organ failure (MSOF), 1 resembling lipotoxic acute pancreatitis. 2,3 Understanding underlying mechanisms may guide supportive care while clinical trials are ongoing. Unsaturated fatty acids (UFAs) generated by adipose lipolysis 2,3 cause MSOF, including acute lung injury. 2 Severe acute pancreatitis and severe COVID-19 share obesity as a risk factor, 4 along with lipase elevation, 5 hypoalbuminemia, 1 and hypocalcemia. 6 The latter 2 may progress undetected because calcium-albumin correction calculations (eg, https:// www.mdcalc.com/calcium-correction-hypoalbuminemia) can pseudonormalize calcium values (eg, uncorrected calcium of 5.9 mg/dL and albumin of 0.1 g/dL to corrected calcium of 9.0 mg/dL). Notably, calcium ameliorates MSOF, 7 and UFAs cause nonendocrine hypocalcemia. 7 The ACE2 receptor resides on adipocytes 8 containing triglycerides and adipocyte triglyceride lipase (ATGL) and on pancreatic acini expressing pancreatic triglyceride lipase (PNLIP). 2 Both oleic acid (C18:1) administration and adipose lipolysis 3 by PNLIP can cause acute lung injury and MSOF. These, and previous data showing that UFAs depolarize mitochondria, 2 inhibit complexes I and V, 3 decrease adenosine triphosphate, release intracellular calcium, 3 and increase inflammatory mediators, 3 made us explore lipotoxicity during severe COVID-19. This approach, culminating in clinical advice to keep calcium and albumin levels normal from early on in the disease, is summarized in Figure 1A and explained diagrammatically in supplementary figure 1. Methods See Supplementary Materials. Results Hypocalcemia and Hypoalbuminemia Occur Early During Severe Coronavirus Disease 2019 Seven of 15 hospitalized patients were discharged home by 3. 4 ±1.6 days. One died of hypoxemic failure after *Authors share co-first authorship.

IntroductionQuiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. Tumor specific expression of QSOX1 has been reported for numerous tumor types. In this study, we investigate QSOX1 as a marker of breast tumor progression and evaluate the role of QSOX1 as it relates to breast tumor growth and metastasis.MethodsCorrelation of QSOX1 expression with breast tumor grade, subtype and estrogen receptor (ER) status was gathered through informatic analysis using the "Gene expression based Outcome for Breast cancer Online" (GOBO) web-based tool. Expression of QSOX1 protein in breast tumors tissue microarray (TMA) and in a panel of breast cancer cell lines was used to confirm our informatics analysis. To investigate malignant cell mechanisms for which QSOX1 might play a key role, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in ER+ Luminal A-like MCF7, ER+ Luminal B-like BT474 and ER- Basal-like BT549 breast cancer cell lines.ResultsGOBO analysis revealed high levels of QSOX1 RNA expression in ER+ subtypes of breast cancer. In addition, Kaplan Meyer analyses revealed QSOX1 RNA as a highly significant predictive marker for both relapse and poor overall survival in Luminal B tumors. We confirmed this finding by evaluation of QSOX1 protein expression in breast tumors and in a panel of breast cancer cell lines. Expression of QSOX1 in breast tumors correlates with increasing tumor grade and high Ki-67 expression. Suppression of QSOX1 protein slowed cell proliferation as well as dramatic inhibition of MCF7, BT474 and BT549 breast tumor cells from invading through Matrigel™ in a modified Boyden chamber assay. Inhibition of invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin zymography indicated that QSOX1 plays an important role in the function of MMP-9, a key mediator of breast cancer invasive behavior.ConclusionsTaken together, our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor survival in Luminal B breast cancer, and has a pro-proliferative and pro-invasive role in malignant progression partly mediated through a decrease in MMP-9 functional activity.

Cardiovascular disease (CVD) is a leading cause of post-liver transplant death, and variable care patterns may affect outcomes. We aimed to describe epidemiology and outcomes of inpatient CVD care across US hospitals. Using a merged data set from the 2002-2011 Nationwide Inpatient Sample and the American Hospital Association Annual Survey, we evaluated liver transplant patients admitted primarily with myocardial infarction (MI), stroke (cerebrovascular accident [CVA]), congestive heart failure (CHF), dysrhythmias, cardiac arrest (CA), or malignant hypertension. Patient-level data include demographics, Charlson comorbidity index, and CVD diagnoses. Facility-level variables included ownership status, payer-mix, hospital resources, teaching status, and physician/nursing-to-bed ratios. We used generalized estimating equations to evaluate patient- and hospital-level factors associated with mortality. There were 4763 hospitalizations that occurred in 153 facilities (transplant hospitals, n = 80). CVD hospitalizations increased overall by 115% over the decade (P < 0.01). CVA and MI declined over time (both P < 0.05), but CHF and dysrhythmia grew significantly (both P < 0.03); a total of 19% of hospitalizations were for multiple CVD diagnoses. Transplant hospitals had lower comorbidity patients (P < 0.001) and greater resource intensity including presence of cardiac intensive care unit, interventional radiology, operating rooms, teaching status, and nursing density (all P < 0.01). Transplant and nontransplant hospitals had similar unadjusted mortality (overall, 3.9%, P = 0.55; by diagnosis, all P > 0.07). Transplant hospitals had significantly longer overall length of stay, higher total costs, and more high-cost hospitalizations (all P < 0.05). After risk adjustment, transplant hospitals were associated with higher mortality and high-cost hospitalizations. In conclusion, CVD after liver transplant is evolving and responsible for growing rates of inpatient care. Transplant hospitals are associated with poor outcomes, even after risk adjustment for patient and hospital characteristics, which may be attributable to selective referral of certain patient phenotypes but could also be related to differences in quality of care. Further study is warranted.

Objective: To understand whether reduced lengths of stay after kidney transplantation were associated with excess health care utilization in the first 90 days or long-term graft and patient survival outcomes. Background: Reducing length of stay after kidney transplant has an unknown effect on post-transplant health care utilization. We studied this association in a cohort of 1001 consecutive kidney transplants. Methods: We retrospectively reviewed 2011-2015 data from a prospectively-maintained kidney transplant database from a single center. Results: A total of 1001 patients underwent kidney transplant, and were dismissed from the hospital in 3 groups: Early [ 2 days] (19.8%), Normal [3-7 days] (79.4%) and Late [>7 days] (3.8%). 34.8% of patients had living donor transplants (Early 51%, Normal 31.4%, Late 18.4%, P < 0.001). Early patients had lower delayed graft function rates (Early 19.2%, Normal 32%, Late73.7%, P ¼ 0.001). By the hospital dismissal group, there were no differences in readmissions or emergency room visits at 30 or 90 days. Glomerular filtration rate at 12 months and rates of biopsy-proven acute rejection were also similar between groups. The timing of hospital dismissal was not associated with the risk-adjusted likelihood of readmission. Early and Normal patients had similar graft and patient survival. Late dismissal patients, who had higher rates of cardiovascular complications, had significantly higher late mortality versus Normal dismissal patients in unadjusted and riskadjusted models. Conclusion: Dismissing patients from the hospital 2 days after kidney transplant is safe, feasible, and improves value. It is not associated with excess health care utilization or worse short or long-term transplant outcomes.