Parallels between oncogene-driven cardiac hyperplasia and heart regeneration in zebrafish.

The human heart is poorly regenerative and cardiac tumors are extremely rare. Whether the adult zebrafish myocardium is responsive to oncogene overexpression and how this condition affects its intrinsic regenerative capacity remains unknown. Here, we have established a strategy of inducible and reversible expression of HRASG12V in zebrafish cardiomyocytes. This approach stimulated a hyperplastic cardiac enlargement within 16 days. The phenotype was suppressed by rapamycin-mediated inhibition of TOR signaling. As TOR signaling is also required for heart restoration after cryoinjury, we compared transcriptomes of hyperplastic and regenerating ventricles. Both conditions were associated with upregulation of cardiomyocyte dedifferentiation and proliferation factors, as well as with similar microenvironmental responses, such as deposition of nonfibrillar Collagen XII and recruitment of immune cells. Among the differentially expressed genes, many proteasome and cell-cycle regulators were upregulated only in oncogene-expressing hearts. Preconditioning of the heart with short-term oncogene expression accelerated cardiac regeneration after cryoinjury, revealing a beneficial synergism between both programs. Identification of the molecular bases underlying the interplay between detrimental hyperplasia and advantageous regeneration provides new insights into cardiac plasticity in adult zebrafish.

Generation and characterization of Chd7-iCreERT2-tdTomato mice.

Heterozygous mutation of CHD7 gene causes a severe developmental disorder called CHARGE syndrome. In order to further explore the expression and function of Chd7 in vivo, we generated a Chd7-P2A-iCreERT2-P2A-tdTomato (in short, Chd7-CT-tdT) knockin mouse line using the CRISPR/Cas9 technology. The specificity and efficiency of two knockin genetic elements were validated. The Chd7-CT-tdT reporter gene could accurately reflect both the dynamic expression pattern of endogenous Chd7 during neurodevelopment and cell-type specific expression in the brain and eye. The recombination efficiency of Chd7-CT-tdT in postnatal cerebellum is very high. Moreover, lineage tracing experiment showed that Chd7 is expressed in intestinal stem cells. In summary, the newly constructed Chd7-CT-tdT mouse line provide a useful tool to study the function of Chd7.

Ribosomal profiling of human endogenous retroviruses in healthy tissues.

Human endogenous retroviruses (HERVs) are the germline embedded proviral fragments of ancient retroviral infections that make up roughly 8% of the human genome. Our understanding of HERVs in physiology primarily surrounds their non-coding functions, while their protein coding capacity remains virtually uncharacterized. Therefore, we applied the bioinformatic pipeline "hervQuant" to high-resolution ribosomal profiling of healthy tissues to provide a comprehensive overview of translationally active HERVs. We find that HERVs account for 0.1-0.4% of all translation in distinct tissue-specific profiles. Collectively, our study further supports claims that HERVs are actively translated throughout healthy tissues to provide sequences of retroviral origin to the human proteome.

Clinical outcomes in patients switching from agalsidase beta to migalastat: A Fabry Registry analysis.

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m2/year; postswitch: -1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.

Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.

Lysosomal storage diseases (LSDs) are multisystem inherited metabolic disorders caused by dysfunctional lysosomal activity, resulting in the accumulation of undegraded macromolecules in a variety of organs/tissues, including the central nervous system (CNS). Treatments include enzyme replacement therapy, stem/progenitor cell transplantation, and in vivo gene therapy. However, these treatments are not fully effective in treating the CNS as neither enzymes, stem cells, nor viral vectors efficiently cross the blood-brain barrier. Here, we review the latest advancements in improving delivery of different therapeutic agents to the CNS and comment upon outstanding questions in the field of neurological LSDs.

Rapid home therapy infusion of velaglucerase alfa in naïve patients with Gaucher disease.

BACKGROUND: Enzyme replacement therapy (ERT) has revolutionised the management of patients with Gaucher disease (GD). In 2018, we published the safety and efficacy of rapid 10-min infusion of velaglucerase alfa in previously treated patients, mostly on low-dose therapy. AIM: To improve quality of life (QoL) for patients needing lifelong bi-weekly infusions by introducing a 10-min infusion instead of 1 h per label in patients naive to ERT and on high-dose therapy. METHODS: Fifteen naive patients were enrolled; all received bi-weekly infusions of 60 units/kgBW velaglucerase alfa; the infusion rate was gradually reduced in the hospital, followed by home infusions. Each infusion was followed for safety. Efficacy parameters were assessed every 3 months. Patient-reported outcome questionnaires were collected at baseline and follow-up. RESULTS: Ten-minute rapid infusions were well tolerated without related severe adverse events (SAEs). Two patients experienced a non-related SAE and another a possibly related AE. In three patients, the infusion rate was increased to 30 or 60 min (two because of suboptimal response and one because of AE). Two patients dropped out because of an unwillingness to attend follow-up visits during the COVID-19 pandemic. All 13 remaining patients reached the 24-month end-point. The platelet counts increased by a median (range) of 68.38% (12.5-300%) and the lyso-Gb1 levels decreased by 62.6% (32.9-89.9%). CONCLUSION: Home therapy with rapid infusion of high-dose velaglucerase alfa was a safe, effective and preferable alternative for patients with GD naïve to treatment. We believe that shortening the infusion time improves the QoL of patients with GD who have a lifelong commitment to intravenous therapy.

Evaluation of a Ground Subsidence Zone in an Urban Area Using Geophysical Methods.

An important geological risk to which many towns in Puglia are exposed is sinking cavities in urban areas. For urban centers, studying, mapping, providing geological and speleological descriptions, classifying, and cataloging the forms and types of cavities is essential because cavities are linked to past local anthropic and natural processes at different sites. These circumstances could lead to the enhancement of existing underground cavities in urban areas through conservation and continuous monitoring. Unfortunately, in many cases, these underground cavities have been used as landfills and subsequently abandoned. In late March 2007, one of these cavities collapsed inside Gallipoli's inhabited center, causing damage to the structures but fortunately not human lives. In the area surrounding the collapsed cavity, a series of geophysical investigations were undertaken using ground penetrating radar in an attempt to delimit the area of collapse and develop possible interventions for restoration. In the same area, these measures were repeated 16 years later in December 2022 due to another collapse. The comparison between data acquired in these two periods shows that there were no strong changes apart from an increased presence of subsoil moisture in 2022.

Three-Dimensional ERT Advanced Detection Method with Source-Position Electrode Excitation for Tunnel-Boring Machines.

Tunnel-boring machines (TBMs) are widely used in urban underground tunnel construction due to their fast and efficient features. However, shield-tunnel construction faces increasingly complex geological environments and may encounter geological hazards such as faults, fracture zones, water surges, and collapses, which can cause significant property damage and casualties. Existing geophysical methods are subject to many limitations in the shield-tunnel environment, where the detection space is extremely small, and a variety of advanced detection methods are unable to meet the required detection requirements. Therefore, it is crucial to accurately detect the geological conditions in front of the tunnel face in real time during the tunnel boring process of TBM tunnels. In this paper, a 3D-ERT advanced detection method using source-position electrode excitation is proposed. First, a source-position electrode array integrated into the TBM cutterhead is designed for the shield-tunnel construction environment, which provides data security for the inverse imaging of the anomalous bodies. Secondly, a 3D finite element tunnel model containing high- and low-resistance anomalous bodies is established, and the GREIT reconstruction algorithm is utilized to reconstruct 3D images of the anomalous body in front of the tunnel face. Finally, a physical simulation experiment platform is built, and the effectiveness of the method is verified by laboratory physical modeling experiments with two different anomalous bodies. The results show that the position and shape of the anomalous body in front of the tunnel face can be well reconstructed, and the method provides a new idea for the continuous detection of shield construction tunnels with boring.

Stress-induced deeper rooting introgression enhances wheat yield under terminal drought.

Water scarcity is the primary environmental constraint affecting wheat growth and production and is increasingly exacerbated due to climatic fluctuation, which jeopardizes future food security. Most breeding efforts to improve wheat yields under drought have focused on above-ground traits. Root traits are closely associated with various drought adaptability mechanisms, but the genetic variation underlying these traits remains untapped, even though it holds tremendous potential for improving crop resilience. Here, we examined this potential by re-introducing ancestral alleles from wild emmer wheat (Triticum turgidum ssp. dicoccoides) and studied their impact on root architecture diversity under terminal drought stress. We applied an active sensing electrical resistivity tomography approach to compare a wild emmer introgression line (IL20) and its drought-sensitive recurrent parent (Svevo) under field conditions. IL20 exhibited greater root elongation under drought, which resulted in higher root water uptake from deeper soil layers. This advantage initiated at the pseudo-stem stage and increased during the transition to the reproductive stage. The increased water uptake promoted higher gas exchange rates and enhanced grain yield under drought. Overall, we show that this presumably 'lost' drought-induced mechanism of deeper rooting profile can serve as a breeding target to improve wheat productiveness under changing climate.

Interpretation of GFR slope in untreated and treated adult Fabry patients.

Nephropathy is one of the main features of Fabry disease (FD) that leads, in untreated patients with classical mutations, to end-stage renal disease (ESRD) from the third to the fifth decade of life. The availability of a specific treatment modified the natural history of FD; in particular, it was widely reported that enzyme replacement therapy (ERT) is able to slow the progression of the disease. Regarding Fabry nephropathy, several reports have documented an elevated estimated glomerular filtration rate (eGFR) slope in untreated patients as expression of a rapid disease progression towards ESRD. Otherwise, the prompt start of treatment may be beneficial in stabilizing renal function or slowing its decline. Therefore, based on data in the literature about the effects of ERT on eGFR decline and on the evidence supporting the role of eGFR slope as a surrogate endpoint for chronic kidney disease progression, we suggest, in this 'Expert Opinion', that a treatment should be defined effective when eGFR decline is <1 ml/min/1.73 m2/year and not effective when eGFR loss remains ≥3 ml/min/1.73 m2/year (≥2.5 ml/min/1.73 m2/year in females). Moreover, practical clinical recommendations and guidance for Fabry patients suggests that a change in treatment may be appropriate if individualized therapeutic goals are not achieved. Since a dose-dependent efficacy has been demonstrated for ERT, we suggest considering a switch to a higher dose of ERT in symptomatic adult Fabry patients (ages 18-60 years) with an eGFR of 45-90 ml/min/1.73 m2 and treated with a stable dose of ERT for at least 1 year, in which a linear negative slope of eGFR of 3 ml/min/1.73 m2/year for males (2.5 ml/min/1.73 m2/year for females) was observed.

Association between changes in pulmonary function and in patient reported outcomes during enzyme therapy of adult patients with late-onset Pompe disease.

Pompe disease is a rare, progressive, and metabolic myopathy. Reduced pulmonary function is one of the main problems seen in adult patients with late-onset Pompe disease (LOPD). We aimed to explore the association between changes over time in pulmonary function and in patient-reported outcome measures (PROMs), in these patients treated with enzyme replacement therapy (ERT). This is a post hoc analysis of two cohort studies. Pulmonary function was assessed as forced vital capacity in the upright position (FVCup ). As PROMs, we assessed the physical component summary score (PCS) of the Medical Outcome Study 36-item Short-Form Health Survey (SF-36) and daily life activities (Rasch-Built Pompe-Specific Activity [R-PACT] scale). We fitted Bayesian multivariate mixed-effects models. In the models of PROMs, we assumed a linear association with FVCup , and adjusted for time (nonlinear), sex, and age and disease duration at the start of ERT. One hundred and one patients were eligible for analysis. PCS and R-PAct were positively associated with FVCup , while their relation with time was nonlinear (initial increase then decrease). A 1%-point increase in FVCup is expected to increase PCS by 0.14 points (95% Credible Interval: [0.09;0.19]) and R-PACT by 0.41 points [0.33;0.49] at the same time point. In the first year of ERT, we expect a change of PCS and R-PAct scores by +0.42 and +0.80 points, and in the 5th year of +0.16 and +0.45, respectively. We conclude that the physical domain of quality of life and daily life activities improve when FVCup increases during ERT.

Comprehensive and long-term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3.

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%-70% of the Asian affected population. METHODS: We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3). RESULTS: Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6-18 months and the age at HSCT was 3.8-15 years in the patients with GD3. The latest age at follow-up was 8-22 years, with a post-HSCT duration of 3-14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment. CONCLUSIONS: ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression.

The summer heatwave in 2022 and its role in changing permafrost and periglacial conditions at a historic mountain pass in the Eastern Alps (Hochtor, Hohe Tauern Range, Austria).

Air temperatures in Europe in 2022 had been the highest on record for the meteorological summer season [June, July and August (JJA)], with +1.3°C above the 1991-2020 average. We studied the effects of recent warming on permafrost and periglacial conditions at a historical mountain pass in the Eastern Alps (Hochtor, 2,576 m asl, 47.08°N, 12.84°E). We used ground temperature data (2010-2022), repeated electrical resistivity tomography measurements (2019, 2022) and auxiliary data dating back to Roman times. We quantified permafrost conditions, evaluated frost-related weathering and slope processes and assessed the impact of atmospheric warming on it. Results show that summer ground surface temperatures increased by 2.5°C between 1891-1920 and 1991-2020, whereas frost-related weathering and periglacial processes decreased. The summers of 2003, 2015, 2019 and 2022 were the four warmest ones in 1887-2022. Hochtor changed in 2010-2022 from an active permafrost site to an inactive one with supra-permafrost talik. A general three-layer structure was quantified for all three ERT profiles measured. The middle, 5-10 m thick layer is ice-poor permafrost detected in 2019, whose existence, although smaller, was confirmed in 2022. Resistivity decreased at the three profiles by 3.9% to 5.2% per year, suggesting permafrost degradation. We interpret the resistivity changes between the summers of 2019 and 2022 as a long-term signal of permafrost degradation and not as the single effect of the summer heatwave in 2022. As our data show how rapidly permafrost degrades and as we face an even warmer climate for the remaining part of the 21st century, we expect that near-surface permafrost at the Hochtor site will soon be history.

Toxicology Certification: The Need, the Value, and an Evolving Landscape.

Certification in toxicology remains a subject of interest to those in the field, as evidenced by the number of presentations at major meetings and publications in the past decade. In 2009, Brock and colleagues summarized the certifications available in the field of toxicology and provided an international perspective of the pros and cons of gaining certification. Though that article has been viewed thousands of times, the certification processes have evolved over the past decade. Therefore, the purpose of the article is to build upon the prior work and present current information for toxicologists seeking certification with the American Board of Toxicology (DABT), Academy of Toxicological Sciences (ATS), as a European Registered Toxicologist (ERT), as a Diplomate, Japanese Society of Toxicology (DJSOT), and as a Diplomate of the Chinese Society of Toxicology (DCST). In addition, other certifications are presented, but available details are limited.

Designing for digital transformation of residency education - a post-pandemic pedagogical response.

BACKGROUND: The forced transition to emergency remote teaching (ERT) during the COVID-19 pandemic has significantly impacted health professions education worldwide. In Sweden, the need for alternative solutions for the training of junior doctors became urgent, as many of the mandatory onsite courses required for residents to qualify as specialists were canceled. The purpose of this study was to understand course leaders' perceptions and experiences of using digital technologies, such as video conferencing, to teach medical residents (ST) during the pandemic and beyond. METHODS: A qualitative study using semi-structured interviews was conducted with seven course leaders responsible for residency courses during the first year of the pandemic to capture their perceptions and experiences. The interviews were transcribed verbatim and analyzed using thematic analysis, drawing on the technology affordances and constraints theory (TACT) as a framework to explore pedagogical strategies and new teaching practices emerging from the forced use of digital technologies for remote teaching. RESULTS: The data analysis revealed affordances of, as well as constraints to, teaching specialist medical training during the pandemic. The findings show that the use of digital conference technologies for ERT can both enable and inhibit social interactions, the interactive learning environment and the utilization of technological features, depending on the individual course leaders' goals of using the technology and the situated context of the teaching. CONCLUSIONS: The study reflects the course leaders' pedagogical response to the pandemic, as remote teaching became the only way to provide residency education. Initially, the sudden shift was perceived as constraining, but over time they found new affordances through the enforced use of digital technology that helped them not only to cope with the transition but also to innovate their pedagogical methods. After a rapid, forced shift from on-site to digital courses, it is crucial to utilize experiences to create better preconditions for digital technology to facilitate learning in the future.

Contribution of Glucosylsphingosine (Lyso-Gb1) to Treatment Decisions in Patients with Gaucher Disease.

Glucosylsphingosine (lyso-Gb1), the deacylated form of glucocerebroside, was shown to be the most specific and sensitive biomarker for diagnosing Gaucher disease (GD). The aim of this study is to assess the contribution of lyso-Gb1 at the time of diagnosis for treatment decisions in naïve patients with GD. Newly diagnosed patients from July 2014 to November 2022 were included in this retrospective cohort study. The diagnosis was done by sending a dry blood spot (DBS) sample for GBA1 molecular sequencing and lyso-Gb1 quantification. Treatment decisions were based on symptoms, signs, and routine laboratory tests. We diagnosed 97 patients (41 males), both type 1 (n = 87), and neuronopathic (n = 10). The median (range) age at diagnosis was 22 (1-78), with 36 children. In 65 patients, GD-specific therapy was started with a median (range) lyso-Gb1, 337 (60-1340) ng/mL, significantly higher than in patients who did not go on to treatment, 153.5 (9-442) ng/mL. Using a receiver operating characteristic (ROC) analysis, a cutoff of lyso-Gb1 > 250 ng/mL was associated with treatment with a sensitivity of 71% and specificity of 87.5%. Predictors of treatment were thrombocytopenia, anemia, and elevated lyso-Gb1 (>250 ng/mL). In conclusion, lyso-Gb1 levels contribute to the medical decision related to the initiation of treatment, mainly among mildly affected newly diagnosed patients. For patients with a severe phenotype, as for all patients, the main value of lyso-Gb1 would be to monitor response to therapy. The variable methodology and differences in the units of lyso-Gb1 measurements between laboratories prevent the adaptation of the exact cut-off we found in general practice. However, the concept is that a significant elevation, i.e., a several-fold increase from the diagnostic lyso-Gb1 cutoff, is related to a more severe phenotype and, accordingly, to the decision regarding the initiation of GD-specific therapy.

High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy.

Ambroxol hydrochloride (ABX), an oral mucolytic drug available over the counter for many years, acts as a pharmacological chaperone for mutant glucocerebrosidase, albeit at higher doses. Proof-of-concept reports have been published over the past decade on all three types of Gaucher disease (GD). Here, we assess the safety and efficacy of 12 months of 600 mg ambroxol per day in three groups of Type 1 GD patients with a suboptimal response to enzyme replacement therapy (ERT) or substrate reduction therapy (SRT), defined as platelet count < 100 × 103/L, lumbar spine bone density T-score < -2.0, and/or LysoGb1 > 200 ng/mL, and for a group of naïve patients who had abnormal values in two of these three parameters. We enrolled 40 patients: 28 ERT- or SRT-treated, and 12 naïve. There were no severe adverse effects (AEs). There were 24 dropouts, mostly due to AEs (n = 12), all transient, and COVID-19 (n = 7). Among the 16 completers, 5 (31.2%) had a >20% increase in platelet count, 6 (37.5%) had a >0.2 increase in T-score, and 3 (18.7%) had a >20% decrease in Lyso-Gb1. This study expands the number of patients exposed to high-dose ABX, showing good safety and satisfactory efficacy, and provides an additional rationale for adding off-label ABX to the arsenal of therapies that could be offered to patients with GD1 and a suboptimal response or those unable to receive ERT or SRT.

Protective and risk social dimensions of emergency remote teaching during COVID-19 pandemic: A multiple mediation study.

The changes in teaching due to COVID-19-related restraints generated distress among teachers, putting their job-related efficacy and satisfaction at risk. This study deepens the community-related protective and risk factors in teachers' experience. An online questionnaire detecting social distancing burnout, job-related distress experience, efficacy and satisfaction, and Sense of Community (SoC) was administered to 307 Italian teachers. A multiple mediation model was tested with Structural Equation Modeling. Evidence showed that social distancing burnout could increase teachers' distress rates and, through them, impact their job-related efficacy and satisfaction; however, its effects on the latter depended on the kind of distress mediating. Conversely, SoC could support their job-related efficacy and satisfaction, yet no association with their distress rates emerged. The role of social distancing and Information and Communication Technologies (ICTs)-related distress as the main threats for teachers stems, along with the one of job distress and the community of belonging as assets on which teachers relied.

Comparing Student Performance in Emergency Remote and Face-to-Face Collaborative Learning Courses.

The start of the COVID-19 pandemic forced an unprecedented shift from face-to-face (F2F) instruction to emergency remote teaching (ERT) for over one billion learners worldwide. Studies from K-12 and higher education have begun to address the impact of ERT on student learning and well-being. The lessons learned from ERT will likely shape the response to future public health emergencies and inform the design and implementation of remote courses. As such, it will be important to identify teaching practices in ERT that promoted student engagement and learning. Here, we address whether undergraduate collaborative learning courses were able to support student content knowledge outcomes at similar levels in ERT as compared to F2F classroom environments. Specifically, we tracked student performance in three different team-based undergraduate neuroscience courses. These courses were all taught by the same instructor during the academic years 2020-2021 and 2021-2022. Importantly, we found that student scores on individual and team assessments as well as measures of course satisfaction were similar between ERT and F2F. Taken together, our data suggest that the virtual collaborative learning environment in these courses was not associated with a decrease in student or team performance when compared to a traditional F2F classroom.

A multi-criteria decision-making (MCDM) approach for data-driven distance learning recommendations.

Distance learning has been adopted as an alternative learning strategy to the face-to-face teaching methodology. It has been largely implemented by many governments worldwide due to the spread of the COVID-19 pandemic and the implication in enforcing lockdown and social distancing. In emergency situations distance learning is referred to as Emergency Remote Teaching (ERT). Due to this dynamic, sudden shift, and scaling demand in distance learning, many challenges have been accentuated. These include technological adoption, student commitments, parent involvement, and teacher extra burden management, changes in the organization methodology, in addition to government development of new guidelines and regulations to assess, manage, and control the outcomes of distance learning. The objective of this paper is to analyze the alternatives of distance learning and discuss how these alternatives reflect on student academic performance and retention in distance learning education. We first, examine how different stakeholders make use of distance learning to achieve the learning objectives. Then, we evaluate various alternatives and criteria that influence distance learning, we study the correlation between them and extract the best alternatives. The model we propose is a multi-criteria decision-making model that assigns various scores of weights to alternatives, then the best-scored alternative is passed through a recommendation model. Finally, our system proposes customized recommendations to students, and teachers which will lead to enhancing student academic performance. We believe that this study will serve the education system and provides valuable insights and understanding of the use of distance learning and its effectiveness.