Search

Student dropout is a major concern in studies investigating retention strategies in higher education. This study identifies which variables are important to predict student dropout, using academic data from 3583 first-year students on the Business Administration (BA) degree at the University of Barcelona (Spain). The results indicate that two variables, the percentage of subjects failed and not attended in the first semester, demonstrate significant predictive power. This has been corroborated with an additional sample of 10,784 students from three-degree programs (Law, BA, and Economics) at the Complutense University of Madrid (Spain), to assess the robustness of the results. Three different algorithms have also been utilized: neural networks, random forest, and logit. In the specific case of neural networks, the NeuralSens methodology has been employed, which is based on the use of sensitivities, allowing for its interpretation. The outcomes are highly consistent in all cases: both a simple model (logit) and more sophisticated ones (neural networks and random forest) exhibit high accuracy (correctly predicted values) and sensitivity (correctly predicted dropouts). In test set average values of 77% and 69% have been respectively achieved. In this regard, a noteworthy point is that only academic data from the university itself was used to develop the models. This ensures that there's no dependence on other personal or organizational variables, which can often be difficult to access.

Mitochondrial antiviral signaling protein (MAVS) is a crucial signaling adaptor in the sensing of positive-sense RNA viruses and the subsequent induction of the innate immune response. Coronaviruses have evolved multiple mechanisms to evade this response, amongst others, through their main protease (Mpro), which is responsible for the proteolytic cleavage of the largest part of the viral replicase polyproteins pp1a and pp1ab. Additionally, it can cleave cellular substrates, such as innate immune signaling factors, to dampen the immune response. Here, we show that MAVS is cleaved in cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV), but not in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This cleavage was independent of cellular negative feedback mechanisms that regulate MAVS activation. Furthermore, MERS-CoV Mpro expression induced MAVS cleavage upon overexpression and suppressed the activation of the interferon-β (IFN-β) and nuclear factor-κB (NF-κB) response. We conclude that we have uncovered a novel mechanism by which MERS-CoV downregulates the innate immune response, which is not observed among other highly pathogenic coronaviruses.

This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.

Rationale and Objectives: Thyroid nodules are a common occurrence and up to 30% are indeterminate on Fine Needle Aspiration (FNA) biopsy. Use of machine learning (ML) algorithms as computer aids, i.e., computer-aided diagnosis (CADx), may provide accessible, accurate methods of diagnosing thyroid cancer on ultrasound (US) images of thyroid nodules. We conducted a systematic review to synthesize the current knowledge and potential of ML in assisting physicians in diagnosing indeterminate thyroid nodules. Materials and Methods: We searched PubMed for studies without a year constraint. Inclusion criteria were as follows: (1) publication of the study as a full-text manuscript in a peer-reviewed journal, (2) original work (e.g., not a review). Studies were excluded if they (1) did not perform FNA biopsy, (2) excluded all indeterminate lesions, (3) focused on a non-cancer thyroid pathology, (4) described only non-diagnostic uses of their model(s) (e.g. calcification quantification), or (5) did not use grayscale ultrasound. We used the Joanna Briggs Institute Appraisal Checklist for Diagnostic Test Accuracy Studies to synthesize and present quality data and PRISMA guidelines for reporting. Results: Our search yielded only 6 articles published between 2013 and 2022. All studies used either only fine-needle aspiration (FNA) biopsy or a combination of FNA and surgery as the reference standard. Of these, one study included only indeterminate nodules, while 5 studies included other nodules in categories as well. Results varied greatly and studies were inconsistent in which performance metrics they reported. Physician performances yielded areas under the ROC curve (AUC) ranging from 0.68 to 0.83, while ML models gave AUCs from 0.666 to 0.954. One study showed that their model had a greater AUC than physicians, while another study showed no difference in AUCs of their ML model and physicians. Another study demonstrated that their ML-assisted approach had a greater AUC (0.917) than either an American College of Radiology (ACR) Thyroid Imaging Reporting & Data System (TI-RADS)-only approach (AUC 0.68) or a ML only approach (AUC 0.77). One study measured the performance of ML models without physician comparison, with AUCs ranging from 0.85 to 0.90. One study found no difference between their ML model and molecular testing (AUC 0.88 and 0.81, respectively). Conclusion: The growing field of CADx and increasing availability of commercial models suggests an increasing interest toward utilization of ML-assisted diagnosis in the clinical setting. However, there is a significant lack of research on the role of ML the diagnosis of indeterminate thyroid nodules. Funding: The source of funding for this review was institutional funds from the University of Chicago.

Although fumed silica/siloxane suspensions are commonly employed in additive manufacturing technology, the interplay between shelf life, storage conditions, and printability has yet to be explored. In this work, direct ink writing (DIW) was used to print unique three-dimensional structures that required suspensions to retain shape and form while being printed onto a substrate. Suspensions containing varying concentrations of hydrophobic and hydrophilic silica were formulated and evaluated over a time span of thirty days. Storage conditions included low (8%) and high (50%) relative humidity and temperatures ranging from 4 °C to 25 °C. The shelf life of the suspensions was examined by comparing the print quality of pristine and aged samples via rheology, optical microscopy, and mechanical testing. Results showed a significant decrease in printability over time for suspensions containing hydrophilic fumed silica, whereas the printability of suspensions containing hydrophobic fumed silica remained largely unchanged after storage. The findings in this work established the following recommendations for extending the shelf life and printability of suspensions commonly used in DIW technology: (1) higher fumed silica concentrations, (2) low humidity and low temperature storage environments, and (3) the use of hydrophobic fumed silica instead of hydrophilic fumed silica.

The central premise of this article is that synodality ought to be grounded in the Eucharist. The author explores the implications of this claim in the areas of ecclesiology and ethics. On the side of ecclesiology, the author argues that the Eucharist is the ritual and theological center of a synodal church. In the context of its own life, considered not only at an abstract theological level but at a practical and political level as well, the church cannot be synodal if it is not attentive to its Eucharistic origins. Synodality is the key in which communion is realized. The author discusses this idea in the context of the Eucharist Revival in the United States and in connection to baptism and the ecclesiology of the People of God. On the side of ethics, the author develops an account of synodality as a virtue. Synodality is the virtue that shapes the church and its members in order to realize communion. Its object is the right use of power. An ethics of synodality, the author argues, entails both reform in the church itself and a commitment on the part of the church and its members to a politics of the universal common good and the building of a just social order.

Abstract Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We investigated its relevance in breast cancer by immunophenotyping 21 normal breast and 1860 tumour samples. Nuclear SOX10 was detected in normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In tumours, nuclear SOX10 was almost exclusive to TNBC, and predicted poorer outcome amongst cross-sectional (p = 0.0015, hazard ratio 2.02, n = 224) and metaplastic (p = 0.04, n = 66) cases. To understand SOX10’s influence over the transcriptome during the transition from normal to malignant states, we performed a systems-level analysis of co-expression data, de-noising the networks with an eigen-decomposition method. This identified a core module in SOX10’s normal mammary epithelial network that becomes rewired to NCSC genes in TNBC. Crucially, this reprogramming was proportional to genome-wide promoter methylation loss, particularly at lineage-specifying CpG-island shores. We propose that the progressive, genome-wide methylation loss in TNBC simulates more primitive epigenome architecture, making cells vulnerable to SOX10-driven reprogramming. This study demonstrates potential utility for SOX10 as a prognostic biomarker in TNBC and provides new insights about developmental phenotypic mimicry—a major contributor to intratumoral heterogeneity.

A review of Lisa Allen, _A Womanist Theology of Worship: Liturgy, Justice, and Communal Righteousness_.

Extensive clinical data from liver-mediated gene therapy trials have shown that dose-dependent immune responses against the vector capsid may impair or even preclude transgene expression if not managed successfully with prompt immune suppression. The goal of this preclinical study was to generate an adeno-associated viral (AAV) vector capable of expressing therapeutic levels of B-domain deleted factor VIII (FVIII) at the lowest possible vector dose to minimize the potential Risk of a capsid-mediated immune response in the clinical setting. Here, we describe the studies that identified the investigational agent SPK-8011, currently being evaluated in a phase 1/2 study (NCT03003533) in individuals with hemophilia A. In particular, the potency of our second-generation expression cassettes was evaluated in mice and in non-human primates using two different bioengineered capsids (AAV-Spark100 and AAV-Spark200). At 2 weeks after gene transfer, primates transduced with 2 × 1012 vg/kg AAV-Spark100-FVIII or AAV-Spark200-FVIII expressed FVIII antigen levels of 13% ± 2% and 22% ± 6% of normal, respectively. Collectively, these preclinical results validate the feasibility of lowering the AAV capsid dose for a gene-based therapeutic approach for hemophilia A to a dose level orders of magnitude lower than the first-generation vectors in the clinic.

Student dropout is a major concern in studies investigating retention strategies in higher education. This study identifies which variables are important to predict student dropout, using academic data from 3583 first-year students on the Business Administration (BA) degree at the University of Barcelona (Spain). The results indicate that two variables, the percentage of subjects failed and not attended in the first semester, demonstrate significant predictive power. This has been corroborated with an additional sample of 10,784 students from three-degree programs (Law, BA, and Economics) at the Complutense University of Madrid (Spain), to assess the robustness of the results. Three different algorithms have also been utilized: neural networks, random forest, and logit. In the specific case of neural networks, the NeuralSens methodology has been employed, which is based on the use of sensitivities, allowing for its interpretation. The outcomes are highly consistent in all cases: both a simple model (logit) and more sophisticated ones (neural networks and random forest) exhibit high accuracy (correctly predicted values) and sensitivity (correctly predicted dropouts). In test set average values of 77% and 69% have been respectively achieved. In this regard, a noteworthy point is that only academic data from the university itself was used to develop the models. This ensures that there's no dependence on other personal or organizational variables, which can often be difficult to access. [ABSTRACT FROM AUTHOR]

Pompe disease is currently treated with enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase (GAA). Here, the authors show hepatic-directed gene therapy with AAV vectors enhances GAA bioavailability compared with ERT, resulting in improved rescue of the disease phenotype in mice and broad enzyme distribution in mice and non-human primates.

BackgroundTraumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.MethodsData were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.ResultsThe cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.ConclusionsPTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.