A machine learning tool for the diagnosis of SARS-CoV-2 infection from hemogram parameters.

Monocytes and neutrophils play key roles in the cytokine storm triggered by SARS-CoV-2 infection, which changes their conformation and function. These changes are detectable at the cellular and molecular level and may be different to what is observed in other respiratory infections. Here, we applied machine learning (ML) to develop and validate an algorithm to diagnose COVID-19 using blood parameters. In this retrospective single-center study, 49 hemogram parameters from 12,321 patients with clinical suspicion of COVID-19 and tested by RT-PCR (4239 positive and 8082 negative) were analysed. The dataset was randomly divided into training and validation sets. Blood cell parameters and patient age were used to construct the predictive model with the support vector machine (SVM) tool. The model constructed from the training set (5936 patients) achieved an accuracy for diagnosis of SARS-CoV-2 infection of 0.952 (95% CI: 0.875-0.892). Test sensitivity and specificity was 0.868 and 0.899, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.896 and 0.872, respectively (prevalence 0.50). The validation set model (4964 patients) achieved an accuracy of 0.894 (95% CI: 0.883-0.903). Test sensitivity and specificity was 0.8922 and 0.8951, respectively, with a positive (PPV) and negative (NPV) predictive value of 0.817 and 0.94, respectively (prevalence 0.34). The area under the receiver operating characteristic curve was 0.952 for the algorithm performance. This algorithm may allow to rule out COVID-19 diagnosis with 94% of probability. This represents a great advance for early diagnostic orientation and guiding clinical decisions.

Particle Tracking and Micromixing Performance Characterization with a Mobile Device.

Strategies to stir and mix reagents in microfluid devices have evolved concomitantly with advancements in manufacturing techniques and sensing. While there is a large array of reported designs to combine and homogenize liquids, most of the characterization has been focused on setups with two inlets and one outlet. While this configuration is helpful to directly evaluate the effects of features and parameters on the mixing degree, it does not portray the conditions for experiments that involve more than two substances required to be subsequently combined. In this work, we present a mixing characterization methodology based on particle tracking as an alternative to the most common approach to measure homogeneity using the standard deviation of pixel intensities from a grayscale image. The proposed algorithm is implemented on a free and open-source mobile application (MIQUOD) for Android devices, numerically tested on COMSOL Multiphysics, and experimentally tested on a bidimensional split and recombine micromixer and a three-dimensional micromixer with sinusoidal grooves for different Reynolds numbers and geometrical features for samples with fluids seeded with red, blue, and green microparticles. The application uses concentration field data and particle track data to evaluate up to eleven performance metrics. Furthermore, with the insights from the experimental and numerical data, a mixing index for particles (mp) is proposed to characterize mixing performance for scenarios with multiple input reagents.

Psychiatric beds and prison populations in 17 Latin American countries between 1991 and 2017: rates, trends and an inverse relationship between the two indicators.

BACKGROUND: In 1990, Latin American countries committed to psychiatric reforms including psychiatric bed removals. Aim of the study was to quantify changes in psychiatric bed numbers and prison population rates after the initiation of psychiatric reforms in Latin America. METHODS: We searched primary sources to collect numbers of psychiatric beds and prison population rates across Latin America between the years 1991 and 2017. Changes of psychiatric bed numbers were compared against trends of incarceration rates and tested for associations using fixed-effects regression of panel data. Economic variables were used as covariates. Reliable data were obtained from 17 Latin American countries: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Guatemala, Mexico, Nicaragua, Panama, Paraguay, Peru, El Salvador, Uruguay and Venezuela. RESULTS: The number of psychiatric beds decreased in 15 out of 17 Latin American countries (median -35%) since 1991. Our findings indicate the total removal of 69 415 psychiatric beds. The prison population increased in all countries (median +181%). Panel data regression analyses showed a significant inverse relationship -2.70 (95% CI -4.28 to -1.11; p = 0.002) indicating that prison populations increased more when and where more psychiatric beds were removed. This relationship held up when introducing per capita income and income inequality as covariates -2.37 (95% CI -3.95 to -0.8; p = 0.006). CONCLUSIONS: Important numbers of psychiatric beds have been removed in Latin America. Removals of psychiatric beds were related to increasing incarceration rates. Minimum numbers of psychiatric beds need to be defined and addressed in national policies.

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Legal and Policy Implications in Mexico of Changes in ICD-11 Paraphilic Disorders.

INTRODUCTION: The World Health Organization (WHO) has made substantial changes to the classification of paraphilic disorders for the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11), recently approved by the World Health Assembly. The most important is to limit paraphilic disorders primarily to persistent and intense patterns of atypical sexual arousal involving non-consenting individuals, manifested through persistent sexual thoughts, fantasies, urges, or behaviors, that have resulted in action or significant distress. AIM: To analyze the legal, regulatory, and policy implications of the changes in the ICD-11 classification of paraphilic disorders for forensic practice, health systems, adjudication of sex offenders, and the provision of treatment in Mexico. METHODS: An expert Mexican advisory group was appointed to conduct this evaluation following an assessment guide provided by the WHO. MAIN OUTCOME MEASURES: The WHO assessment guide covered (i) laws related to sexual behaviors; (ii) the relationship between legal and clinical issues for non-forensic health professionals; (iii) implications of mental disorder classification for forensic practice; (iv) other implications of ICD-11 paraphilic disorders proposals; and (v) contextual issues. RESULTS: A variety of factors in Mexico make it highly unlikely that appropriate, evidence-based treatments for paraphilic disorders will be provided to those who need them, even if they seek treatment voluntarily and have not committed a crime. Mexican law focuses on the punishment of specific sexual behaviors rather than on underlying disorders. A paraphilic disorder would not be considered sufficient grounds for exemption from criminal responsibility. The application and scope of mental health evaluations in Mexican legal proceedings are quite limited, and individuals who commit sexual crimes almost never undergo forensic evaluations to establish the presence of paraphilic disorders. Psychiatric services may be mandated for sex offenders in highly specific circumstances but cannot exceed the duration of the criminal sentence. CLINICAL IMPLICATIONS: Evaluation and treatment guidelines should be developed based on international evidence and standards and promulgated for use with individuals with paraphilic disorders in forensic and non-forensic poopulations. The much greater specificity and operationalization of the ICD-11 guidelines as compared with the ICD-10 guidelines provide a better basis for identification and case formulation. STRENGTHS & LIMITATIONS: Major strengths of this analyses were that it was conducted to facilitate international comparability across several participating countries and the fact that it was conducted by a diverse multidisciplinary group representing various relevant legal, forensic and and clinical sectors. A limitation was that it was only possible to examine relevant federal laws and those of Mexico City rather than those of all 32 Mexican states. CONCLUSION: The descriptions of paraphilic disorders in the ICD-11 could support substantial improvements in the treatment of individuals with paraphilic disorders and the adjudication of sex offenders in Mexico, but specific changes in Mexican law would be required. Martínez-López JNI, Robles R, Fresán A, et al. Legal and Policy Implications in Mexico of Changes in ICD-11 Paraphilic Disorders. J Sex Med 2019;16:1623-1637.

Papain-treated panels are a simple method for the identification of alloantibodies in multiple myeloma patients treated with anti-CD38-based therapies.

OBJECTIVES: To report our 2 years of experience navigating the interference of anti-CD38 monoclonal antibodies (MAs) in 33 patients and describe papain-treated panels as a complementary method to dithiothreitol (DTT). BACKGROUND: Novel anti-CD38 MAs are now approved or undergoing clinical trials to evaluate their activity in patients with multiple myeloma. A concern with the use of these drugs is that they interfere with blood bank tests in a group of patients who often require blood transfusions. METHODS: Clinical data and whole blood samples were collected from patients receiving daratumumab or isatuximab. Routine blood bank serological tests were performed. RESULTS: A total of 9·1% of patients presented with alloantibodies prior to treatment. All patients exhibited nonspecific reactivity in indirect antiglobulin tests, and 26% had positive direct antiglobulin tests after beginning treatment. This interference disappeared in all patients after discontinuing treatment. Papain panels avoided this reactivity and allowed us to identify alloantibodies. Phenotyped blood units were transfused, and no patient suffered any transfusion-related complications. CONCLUSION: Anti-CD38 MAs produce nonspecific interference in blood bank tests. This interference can be overcome by various methods, including DTT or papain treatment as proposed here. These methods have limitations that can be resolved using phenotyped blood units.

Prognostic factors and predictive model for in-hospital mortality following hip fractures in the elderly.

PURPOSE: The incidence of hip fractures is increasing within the aging population. Our objective was to identify and quantify the risk factors and develop a predictive model for the in-hospital mortality among hip fracture patients older than 65 years. METHODS: This is a prospective study conducted on 331 hip fracture patients older than 65 years admitted to our hospital from 2011 to 2014. Patients' demographics, prehospitalization residential status, prefracture comorbidity data, anti-aggregant and anticoagulant medication, preoperative hemoglobin value, type of fractures, type of treatments, time to surgery, and complications were recorded. RESULTS: The average age was 83 years, 73% female, and 57% of them sustained a femoral neck fracture. In 62.8% of patients, the number of pre-fracture baseline comorbidities was ≥2. The in-hospital mortality rate was 11.4%. In multivariate analysis, age over 90 years, congestive heart failure, asthma, rheumatologic disease, lung cancer, and not taking antiaggregant medication were independently associated with in-hospital mortality. A formula and risk stratification scoring for predicting the risk for in-hospital mortality was developed. Risk-adjustment model based on these variables had acceptable accuracy for predicting in-hospital mortality (c-statistic 0.77). CONCLUSION: Advanced age, and five prefracture comorbidities have a strong association with in-hospital mortality in a hip fracture patient older than 65 years old. Our predictive model was specifically designed for the old hip fracture population. It has an accuracy similar to other risk models. The specificity, positive predictive value, and negative predictive value are high. In addition, it could discriminate a high risk patient from a low risk patient for in-hospital mortality.

Current opinion and consensus statement regarding the diagnosis, prognosis, and treatment of patients with essential thrombocythemia: a survey of the Spanish Group of Ph-negative Myeloproliferative Neoplasms (GEMFIN) using the Delphi method.

The current consensus on the diagnosis, prognosis, and treatment of essential thrombocythemia (ET) is based on experts' recommendations. However, several aspects of the diagnosis of, prognosis of, and therapy for ET are still controversial. The Delphi method was employed with an expert panel of members of the Spanish Group of Ph-negative Myeloproliferative Neoplasms in order to identify the degree of agreement on the diagnosis, prognosis, and treatment of ET. Nine leading experts selected a total of 41 clinical hematologists with well-known expertise in ET. An electronic questionnaire was used to collect the questions rated in a four-step scale. The questions were grouped into four blocks: diagnosis, risk stratification, goals of therapy, and treatment strategy. After the first round consisting of 80 questions, a second round including 14 additional questions focused on the recommendations advocated by experts of the European LeukemiaNet in 2011 was analyzed. The median and mean values for the first and second rounds were calculated. A summary of the conclusions considered as the most representative of each block of questions is presented. The Delphi method is a powerful instrument to address the current approaches and controversies surrounding ET.

Xurography as a Rapid Fabrication Alternative for Point-of-Care Devices: Assessment of Passive Micromixers.

Despite the copious amount of research on the design and operation of micromixers, there are few works regarding manufacture technology aimed at implementation beyond academic environments. This work evaluates the viability of xurography as a rapid fabrication tool for the development of ultra-low cost microfluidic technology for extreme Point-of-Care (POC) micromixing devices. By eschewing photolithographic processes and the bulkiness of pumping and enclosure systems for rapid fabrication and passively driven operation, xurography is introduced as a manufacturing alternative for asymmetric split and recombine (ASAR) micromixers. A T-micromixer design was used as a reference to assess the effects of different cutting conditions and materials on the geometric features of the resulting microdevices. Inspection by stereographic and confocal microscopy showed that it is possible to manufacture devices with less than 8% absolute dimensional error. Implementation of the manufacturing methodology in modified circular shape- based SAR microdevices (balanced and unbalanced configurations) showed that, despite the precision limitations of the xurographic process, it is possible to implement this methodology to produce functional micromixing devices. Mixing efficiency was evaluated numerically and experimentally at the outlet of the microdevices with performances up to 40%. Overall, the assessment encourages further research of xurography for the development of POC micromixers.

Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors.

Lynch syndrome (LS) is an autosomal dominant cancer-susceptibility disease caused by inactivating germline mutations in mismatch repair (MMR) genes. Variants of unknown significance (VUS) are often detected in mutational analysis of MMR genes. Here we describe a large family fulfilling Amsterdam I criteria carrying two rare VUS in the MLH1 gene: c.121G > C (p.D41H) and c.2128A > G (p.N710D). Collection of clinico-pathological data, multifactorial analysis, in silico predictions, and functional analyses were used to elucidate the clinical significance of the identified MLH1 VUS. Only the c.121G > C variant cosegregated with LS-associated tumors in the family. Diagnosed colorectal tumors were microsatellite unstable although immunohistochemical staining revealed no loss of MMR proteins expression. Multifactorial likelihood analysis classified c.2128A > G as a non-pathogenic variant and c.121G > C as pathogenic. In vitro functional tests revealed impaired MMR activity and diminished expression of c.121G > C. Accordingly, the N710 residue is located in the unconserved MLH1 C-terminal domain, whereas D41 is highly conserved and located in the ATPase domain. The obtained results will enable adequate genetic counseling of c.121G > C and c.2128A > G variant carriers and their families. Furthermore, they exemplify how cumulative data and comprehensive analyses are mandatory to refine the classification of MMR variants.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Impaired FADD/BID signaling mediates cross-resistance to immunotherapy in Multiple Myeloma.

The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM. Here, we describe impaired death receptor signaling as a novel mechanism of resistance to T-cell mediated immunotherapies in MM. This resistance seems exclusive to novel immunotherapies while sensitivity to conventional anti-tumor therapies being preserved in vitro. As a proof of concept, we present a confirmatory clinical case indicating that the FADD/BID axis is required for meaningful responses to novel immunotherapies thus we report impaired death receptor signaling as a novel resistance mechanism to T-cell mediated immunotherapy in MM.

Predictive Modeling of Soft Stretchable Nanocomposites Using Recurrent Neural Networks.

Human skin is characterized by rough, elastic, and uneven features that are difficult to recreate using conventional manufacturing technologies and rigid materials. The use of soft materials is a promising alternative to produce devices that mimic the tactile capabilities of biological tissues. Although previous studies have revealed the potential of fillers to modify the properties of composite materials, there is still a gap in modeling the conductivity and mechanical properties of these types of materials. While traditional Finite Element approximations can be used, these methodologies tend to be highly demanding of time and processing power. Instead of this approach, a data-driven learning-based approximation strategy can be used to generate prediction models via neural networks. This paper explores the fabrication of flexible nanocomposites using polydimethylsiloxane (PDMS) with different single-walled carbon nanotubes (SWCNTs) loadings (0.5, 1, and 1.5 wt.%). Simple Recurrent Neural Networks (SRNN), Long Short-Term Memory (LSTM), and Gated Recurrent Units (GRU) models were formulated, trained, and tested to obtain the predictive sequence data of out-of-plane quasistatic mechanical tests. Finally, the model learned is applied to a dynamic system using the Kelvin-Voight model and the phenomenon known as the bouncing ball. The best predictive results were achieved using a nonlinear activation function in the SRNN model implementing two units and 4000 epochs. These results suggest the feasibility of a hybrid approach of analogy-based learning and data-driven learning for the design and computational analysis of soft and stretchable nanocomposite materials.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Low-Cost Light-Based GelMA 3D Bioprinting via Retrofitting: Manufacturability Test and Cell Culture Assessment.

Light-based bioprinter manufacturing technology is still prohibitively expensive for organizations that rely on accessing three-dimensional biological constructs for research and tissue engineering endeavors. Currently, most of the bioprinting systems are based on commercial-grade-based systems or modified DIY (do it yourself) extrusion apparatuses. However, to date, few examples of the adoption of low-cost equipment have been found for light-based bioprinters. The requirement of large volumes of bioinks, their associated cost, and the lack of information regarding the parameter selection have undermined the adoption of this technology. This paper showcases the retrofitting and assessing of a low-cost Light-Based 3D printing system for tissue engineering. To evaluate the potential of a proposed design, a manufacturability test for different features, machine parameters, and Gelatin Methacryloyl (GelMA) concentrations for 7.5% and 10% was performed. Furthermore, a case study of a previously seeded hydrogel with C2C12 cells was successfully implemented as a proof of concept. On the manufacturability test, deviational errors were found between 0.7% to 13.3% for layer exposure times of 15 and 20 s. Live/Dead and Actin-Dapi fluorescence assays after 5 days of culture showed promising results in the cell viability, elongation, and alignment of 3D bioprinted structures. The retrofitting of low-cost equipment has the potential to enable researchers to create high-resolution structures and three-dimensional in vitro models.

E-Skin Development and Prototyping via Soft Tooling and Composites with Silicone Rubber and Carbon Nanotubes.

The strategy of embedding conductive materials on polymeric matrices has produced functional and wearable artificial electronic skin prototypes capable of transduction signals, such as pressure, force, humidity, or temperature. However, these prototypes are expensive and cover small areas. This study proposes a more affordable manufacturing strategy for manufacturing conductive layers with 6 × 6 matrix micropatterns of RTV-2 silicone rubber and Single-Walled Carbon Nanotubes (SWCNT). A novel mold with two cavities and two different micropatterns was designed and tested as a proof-of-concept using Low-Force Stereolithography-based additive manufacturing (AM). The effect SWCNT concentrations (3 wt.%, 4 wt.%, and 5 wt.%) on the mechanical properties were characterized by quasi-static axial deformation tests, which allowed them to stretch up to ~160%. The elastomeric soft material's hysteresis energy (Mullin's effect) was fitted using the Ogden-Roxburgh model and the Nelder-Mead algorithm. The assessment showed that the resulting multilayer material exhibits high flexibility and high conductivity (surface resistivity ~7.97 × 104 Ω/sq) and that robust soft tooling can be used for other devices.

SCRT1 is a novel beta cell transcription factor with insulin regulatory properties.

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3ß-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.