Graft-versus-host-disease prophylaxis with ATG or PTCY in patients with lymphoproliferative disorders undergoing reduced intensity conditioning regimen HCT from one antigen mismatched unrelated donor.

Post-transplant cyclophosphamide (PTCY) has been introduced as graft-versus-host disease (GvHD) prophylaxis in mismatched and matched unrelated hematopoietic cell transplant (HCT). However, data comparing outcomes of PTCY or ATG in patients undergoing a 1 antigen mismatched HCT for lymphoproliferative disease are limited. We compared PTCY versus ATG in adult patients with lymphoproliferative disease undergoing a first 9/10 MMUD HCT with a reduced intensity conditioning regimen from 2010 to 2021. Patients receiving PTCY were matched to patients receiving ATG according to: age, disease status at transplant, female to male matching, stem cell source and CMV serology. Grade II-IV acute GvHD at 100 day was 26% and 41% for the ATG and PTCY group, respectively (p = 0.08). Grade III-IV acute GvHD was not significantly different between the two groups. No differences were observed in relapse incidence, non-relapse mortality, progression-free survival, overall survival and GvHD-relapse-free survival at 1 year. The cumulative incidence of 1-year extensive chronic GvHD was 18% in the ATG and 5% in the PTCY group, respectively (p = 0.06). In patients with lymphoproliferative diseases undergoing 9/10 MMUD HCT, PTCY might be a safe option providing similar results to ATG prophylaxis. Due to the limited number of patients, prospective randomized trials are needed.

A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis.

Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence by health care professionals. We propose a family of fast and easy-to-use graphical representations in which the impact of a variant is considered relative to other pathogenic and benign variants. To illustrate their value, the representations are applied to three problems in variant interpretation. The assessment of computational pathogenicity predictions showed that the graphics provide an intuitive view of prediction reliability, complementing and extending conventional numerical reliability indexes. When applied to variant of unknown significance populations, the representations shed light on the nature of these variants and can be used to prioritize variants of unknown significance for further studies. In a third application, the graphics were used to compare the two versions of the ATM-adapted American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines, obtaining valuable information on their relative virtues and weaknesses. Finally, a server [ATMision (ATM missense in silico interpretation online)] was generated for users to apply these representations in their variant interpretation problems, to check the ATM-adapted guidelines' criteria for computational evidence on their variant(s) and access different sources of information.

Cognitive and functional evolution in older adults with and without intellectual disability using a multicomponent intervention: A prospective longitudinal study.

BACKGROUND: The global population is experiencing accelerated biopsychosocial aging. Cognitive impairment is frequently associated with functional impairment in basic and instrumental daily living activities. To maintain optimal cognitive and functional functioning, health professionals recommend that older adults participate in cognitive training. AIMS: This study examines the cognitive and functional evolution of older adults with and without Intellectual Disability and the factors associated with favourable evolution following the intervention of a multicomponent programme based on the human occupational model and the person-centred care model. METHODS AND PROCEDURES: 247 people participated. Descriptive and univariate analyses were performed to examine baseline data. The Wilcoxon paired samples test was used to compare cognitive and functional evolution one year after the intervention. Linear regression was used to detect factors predicting favourable evolution. OUTCOMES AND RESULTS: Both populations improved cognitively. There was no change in basic activities of daily living. There was an improvement in instrumental activities of daily living in the group with Intellectual Disability. None of the variables collected was a predictor of greater improvement. CONCLUSIONS AND IMPLICATIONS: This study demonstrated that older people with Intellectual Disability who have supports to cope with this life stage can improve their cognitive and functional abilities.

The Cantabria Cohort, a protocol for a population-based cohort in northern Spain.

Cantabria Cohort stems from a research and action initiative lead by researchers from Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital and University of Cantabria, supported by the regional Goverment. Its aim is to identify and follow up a cohort that would provide information to improve the understanding of the etiology and prognosis of different acute and chronic diseases. The Cantabria Cohort will recruit between 40,000-50,000 residents aged 40-69 years at baseline, representing 10-20% of the target population. Currently, more than 30,000 volunteers have been enrolled. All participants will be invited for a re-assessment every three years, while the overall duration is planned for twenty years. The repeated collection of biomaterials combined with broad information from participant questionnaires, medical examinations, actual health system records and other secondary public data sources is a major strength of its design, which will make it possible to address biological pathways of disease development, identify new factors involved in health and disease, design new strategies for disease prevention, and advance precision medicine. It is conceived to allow access to a large number of researchers worldwide to boost collaboration and medical research.

Amelogenin peptide analyses reveal female leadership in Copper Age Iberia (c. 2900-2650 BC).

Given the absence of written records, the main source of information available to analyze gender inequalities in early complex societies is the human body itself. And yet, for decades, archaeologists have struggled with the sex estimation of poorly preserved human remains. Here we present an exceptional case study that shows how ground-breaking new scientific methods may address this problem. Through the analysis of sexually dimorphic amelogenin peptides in tooth enamel, we establish that the most socially prominent person of the Iberian Copper Age (c. 3200-2200 BC) was not male, as previously thought, but female. The analysis of this woman, discovered in 2008 at Valencina, Spain, reveals that she was a leading social figure at a time where no male attained a remotely comparable social position. Only other women buried a short time after in the Montelirio tholos, part of the same burial area, appear to have enjoyed a similarly high social position. Our results invite to reconsider established interpretations about the political role of women at the onset of early social complexity, and question traditionally held views of the past. Furthermore, this study anticipates the changes that newly developed scientific methods may bring to prehistoric archaeology and the study of human social evolution.

Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.

Clinical simulation in health education: a systematic review / La simulación clínica en la enseñanza sanitaria: una revisión sistemática / Simulação clínica na educação em saúde: uma revisão sistemática

Objective. To summarize the most recent scientific evidence on the usefulness and implementation of simulation training programs for health science students. Methods. A search and systematic review were conducted of the literature through the use of the PRISMA guidelines using the terms MESH Simulation AND healthcare AND Professional Training, including 42 articles. Results. The bibliometric analysis revealed that most of the studies were local in nature, that is, conducted in a single center, or in a few centers in the same region, from the English-speaking world, and using a mixed methodology with pre/post-test measurements. As for the educational aspects, most of the studies were conducted at universities or in the area of continuous education, used multidisciplinary teams as the student target, and used role-playing games as the simulation method. Also, these programs were especially successful in the acquisition of competencies, such as teamwork, communication, and trust. Conclusion. Clinical simulation is a teaching methodology implemented in the last twenty years, mainly in English-speaking countries; it utilizes techniques for its execution and assessment that have been validated in contrasted in many scientific studies, and lastly, it was also observed that it is useful for providing training on general competencies for multidisciplinary groups.

Objetivo. Resumir la evidencia científica más reciente sobre la utilidad e implementación de programas de formación mediante simulación en estudiantes de ciencias de la salud. Métodos. Se ha desarrollado una búsqueda y revisión sistemática de la literatura mediante la guía PRISMA empleando los términos MESH Simulation AND healthcare AND Professional Training, incluyéndose 42 artículos. Resultados. El análisis bibliométrico reveló que la mayoría de estudios eran de ámbito local, es decir, desarrollados en un único centro o en unos pocos centros de una misma localidad, procedentes del mundo anglosajón, y utilizaban una metodología mixta con pre/post-test. En cuanto a los aspectos educativos, la mayoría de estudios se desarrollaron a nivel universitario o en el ámbito de la formación continua, tuvieron como alumnado objetivo equipos multidisciplinares y utilizaron el juego de rol como método de simulación. Además, estos programas fueron especialmente exitosos en la adquisición de competencias como el trabajo en equipo, la comunicación y la confianza. Conclusión. La simulación clínica es una metodología docente que se ha ido implantando progresivamente durante las últimas dos décadas, mayoritariamente en países anglosajones, que utiliza técnicas para su ejecución y evaluación validadas y contrastadas en múltiples estudios científicos, y que resulta útil para el entrenamiento de competencias genéricas y equipos multidisciplinares.

Objetivo. Resumir as evidências científicas mais recentes sobre a utilidade e implementação de programas de treinamento de simulação em estudantes de ciências da saúde. Métodos. Uma busca sistemática e revisão da literatura foi realizada usando o guia PRISMA usando os termos MESH Simulation AND Healthcare AND Professional Training, incluindo 42 artigos. Resultados. A análise bibliométrica revelou que a maioria dos estudos foram locais, ou seja, desenvolvidos num único centro ou em alguns centros de uma mesma cidade, do mundo anglo-saxão, e utilizaram uma metodologia mista com pré/pós- teste. Quanto aos aspectos educacionais, a maioria dos estudos foi realizada no nível universitário ou no campo da formação contínua, os alunos-alvo eram equipes multidisciplinares e usaram a dramatização como método de simulação. Além disso, esses programas foram especialmente bem-sucedidos na aquisição de habilidades como trabalho em equipe, comunicação e confiança. Conclusão. A simulação clínica é uma metodologia de ensino que tem vindo a ser progressivamente implementada ao longo das duas últimas décadas, maioritariamente em países anglo-saxões, que utiliza técnicas para a sua execução e avaliação validadas e contrastadas em múltiplos estudos científicos, e que é útil para o treino de competências genéricas. equipes multidisciplinares.

Clinical simulation in health education: a systematic review.

Objective: To summarize the most recent scientific evidence on the usefulness and implementation of simulation training programs for health science students. Methods: A search and systematic review were conducted of the literature through the use of the PRISMA guidelines using the terms MESH Simulation AND healthcare AND Professional Training, including 42 articles. Results: The bibliometric analysis revealed that most of the studies were local in nature, that is, conducted in a single center, or in a few centers in the same region, from the English-speaking world, and using a mixed methodology with pre/post-test measurements. As for the educational aspects, most of the studies were conducted at universities or in the area of continuous education, used multidisciplinary teams as the student target, and used role-playing games as the simulation method. Also, these programs were especially successful in the acquisition of competencies, such as teamwork, communication, and trust. Conclusion: Clinical simulation is a teaching methodology implemented in the last twenty years, mainly in English-speaking countries; it utilizes techniques for its execution and assessment that have been validated in contrasted in many scientific studies, and lastly, it was also observed that it is useful for providing training on general competencies for multidisciplinary groups.

Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation.

Bile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Impact of the Pandemic on the Teaching and Research Staff at a Technological University in Spain: Deepening the Gender Gap.

The alteration of the educational model caused by the COVID-19 pandemic has not affected all university faculty equally. This work explores the academic, digital and gender inequalities caused by the pandemic on the teaching and research staff of a technological university for STEM (Science, Technology, Engineering and Mathematics) disciplines in Spain, the Universitat Politècnica de Catalunya-BarcelonaTech (UPC). The study considers an anonymous survey with a non-probabilistic voluntary sample (n = 355). The results of the survey reveal that, over these months, the teaching and research staff of the university, regardless of gender, has significantly increased its academic activity due especially to the number of hours devoted to virtual teaching compared to its teaching dedication in a situation of normalcy. This study shows that the lockdown has strongly affected women who are more vulnerable to crisis. In particular, the negative impact on research has been higher in female faculty staff from the UPC, who already face disparities regarding promotion and, during lockdown, stated more difficulties with household work reconciliation. From the results of this study, it is possible to conclude that the COVID-19 pandemic has deepened the gender gap in the academic field.

Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia.

BACKGROUND AND AIMS: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3α,7α,12α-trihydroxy-5ß-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. METHODS AND RESULTS: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAXα expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. CONCLUSIONS: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.

Corrosion Behavior of Titanium Dental Implants with Implantoplasty.

The procedure generally used to remove bacterial biofilm adhering to the surface of titanium on dental implants is implantoplasty. This treatment is based on the machining of the titanium surface to remove bacterial plaque. In this study, we used 60 grade 4 titanium implants and performed the implantoplasty protocol. Using X-ray diffraction, we determined the stresses accumulated in each of the as-received, machined and debris implants. The resistance to corrosion in open circuit and potentiodynamically in physiological medium has been determined, and the corrosion potentials and intensities have been determined. Tests have been carried out to determine ion release by ICP-MS at different immersion times. The results show that the corrosion resistance and the release of titanium ions into the medium are related to the accumulated energy or the degree of deformation. The titanium debris exhibit compressive residual stresses of -202 MPa, the implant treated with implantoplasty -120 MPa, and as-received -77 MPa, with their corrosion behavior resulting in corrosion rates of 0.501, 0.77, and 0.444 mm/year, respectively. Debris is the material with the worst corrosion resistance and the one that releases the most titanium ions to the physiological medium (15.3 ppb after 21 days vs. 7 ppb for as-received samples). Pitting has been observed on the surface of the debris released into the physiological environment. This behavior should be taken into account by clinicians for the good long-term behavior of implants with implantoplasty.

Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation.

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

Immune Assessment of BNT162b2 m-RNA-Spike Based Vaccine Response in Adults.

Vaccine efficacy is based on clinical data. Currently, the assessment of immune response after SARS-CoV-2 vaccination is scarce. A total of 52 healthcare workers were immunized with the same lot of BNT162b2 vaccine. The immunological response against the vaccine was tested using a T-specific assay based on the expression of CD25 and CD134 after stimulation with anti-N, -S, and -M specific peptides of SARS-CoV-2. Moreover, IgG anti-S2 and -RBD antibodies were detected using ELISA. Furthermore, the cell subsets involved in the response to the vaccine were measured in peripheral blood by flow cytometry. Humoral-specific responses against the vaccine were detected in 94% and 100% after the first and second doses, respectively. Therefore, anti-S T-specific responses were observed in 57% and 90% of the subjects after the first and second doses of the vaccine, respectively. Thirty days after the second dose, significant increases in T helper 1 memory cells (p < 0.001), peripheral memory T follicular helper (pTFH) cells (p < 0.032), and switched memory (p = 0.005) were observed. This study describes the specific humoral and cellular immune responses after vaccination with the new mRNA-based BNT162b2 vaccine. A mobilization of TFH into the circulation occurs, reflecting a specific activation of the immune system.

Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients.

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27-CD28-, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27-CD28-, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease.

Academic and emotional effects of online learning during the COVID-19 pandemic on engineering students.

The unprecedented situation of the COVID-19 pandemic has caused the closure of universities worldwide and has forced the transition to online learning. This exceptional context compels us to understand students' experience with online learning. Previous literature identifies relevant factors that intervene in the online education experience and can affect students' academic development. One of the main concerns is the students' mental health, given the lockdown restrictions under which classes have been conducted. Furthermore, the impact of the prolonged lockdown and the pandemic fatigue on university students and their academic experience is still unclear. This study delves into engineering undergraduate students' online education experience during the COVID-19 pandemic and its emotional impact across time. With this aim, a questionnaire was distributed to second, third, and fourth-year engineering undergraduate students at two time points, approximately six months apart. The results show significant differences in students' connection with other students and teachers, workspace conditions, and boredom between time points. Besides, the findings indicate significant correlations between academic development and quality of online classes, adaptation of the course, workspace conditions, and connection with other students and teachers, and also between students' emotions and connection with other students and teachers. Finally, the study identifies best practices carried out during online teaching that will be of value for future courses and engineering education beyond the pandemic situation, amongst which those related to effective communication with teachers stand out.

Dose intensity and treatment duration of bortezomib in transplant-ineligible newly diagnosed multiple myeloma.

BACKGROUND: Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy. PATIENTS AND METHODS: We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib. RESULTS: Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m2 (2.6-67.6) and median dose intensity was 1.0 mg/m2 /wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed <60 days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6 mg/m2 than the remaining individuals, 45.5 (P = .023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P = .00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P = .00002), patients with at least 50 weeks of treatment (P = .02) and patients receiving a cumulative dose of at least 49 mg/m2 (P = .05). Achievement of a VGPR (HR 0.23; 95%CI 0.12-0.46; P = .00002) and a cumulative dose of 49 mg/m2 (HR 0.46, 95%CI 0.27-0.78; P = .003) were statistically independent prognostic factors for PFS. Toxicity-related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN. CONCLUSIONS: Biweekly full-dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.

Innate and Adaptive Immunity Alterations in Metabolic Associated Fatty Liver Disease and Its Implication in COVID-19 Severity.

The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.