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BackgroundThe Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase 1 clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).MethodsWe performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 mcg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 mcg d-RBD (three doses); 3) FINLAY-FR-1A-25 mcg d-RDB (three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or of FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction.ResultsMost adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules.ConclusionsVaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant.Trial registryhttps://rpcec.sld.cu/en/trials/RPCEC00000338-En

For more than a century, scholars and policymakers have commented and debated on the purposes of higher education. These conversations reflect a combination of public and private goals, with an inc...

Background: Besides biological factors, abdominal aortic aneurysm rupture is also caused by mechanical parameters, which are constantly affecting the wall’s tissue due to their abnormal values. The ability to evaluate these parameters could vastly improve the clinical treatment of patients with abdominal aortic aneurysms. The objective of this study was to develop and demonstrate a methodology to analyze the fluid dynamics that cause the wall stress distribution in abdominal aortic aneurysms, using accurate 3D geometry and a realistic, nonlinear, elastic biomechanical model using a computer-aided software. Methods: The geometry of the abdominal aortic aneurysm; was constructed on a 3D scale using computer-aided software SolidWorks (Dassault Systems SolidWorksCorp., Waltham MA). Due to the complex nature of the abdominal aortic aneurysm geometry, the physiological forces and constraints acting on the abdominal aortic aneurysm wall were measured by using a simulation setup using boundary conditions and initial conditions for different studies such as finite element analysis or computational fluid dynamics. Results: The flow pattern showed an increase velocity at the angular neck, followed by a stagnated flow inside the aneurysm sack. Furthermore, the wall shear stress analysis showed to focalized points of higher stress, the top and bottom of the aneurysm sack, where the flow collides against the wall. An increase of the viscosity showed no significant velocity changed but results in a slight increase in overall pressure and wall shear stress. Conclusions: Conducting computational fluid dynamics modeling of the abdominal aortic aneurysm using computer-aided software SolidWorks (Dassault Systems SolidWorksCorp., Waltham MA) proves to be an insightful approach for the clinical setting. The careful consideration of the biomechanics of the abdominal aortic aneurysm may lead to an improved, case-specific prediction of the abdominal aortic aneurysm rupture potential, which could significantly improve the clinical management of these patients.

Evaluation of immunoprofile as predictive and prognostic biomarker are essential to follow up patients in Multiple Myeloma after autologous hematopoietic stem cells transplantation (AHSCT). It can be defining the engraftment and predicts complications. An AHSCT was performed for the first time in the United Arab Emirates to treat a patient with multiple myeloma. We apply the evaluation of the patient's immune status before and during the early follow-up by flow and mass cytometry. The analysis revealed a decrease in all leukocyte populations in blood seven days after transplantation, mainly of B and T helper lymphocytes. The patients showed diarrhea and cellulitis as complications. An increase in regulatory T and NK lymphocytes was evidenced at the same time. 28 days’ post-transplantation, all lymphocyte populations were recovered, except for B lymphocytes, a high level of T regulatory and NK was maintained. The early immune restoration coincided with the recovery of the complications presented by the patient. the leukocyte composition of apheresis was similar to that found in blood at baseline time. Our study evidenced that the extended immunoprofile by mass cytometry could be useful to predict the outcome and response to transplantation.

La efectividad de los procesos hoteleros, así como su calidad dependen en gran medida de la participación de los trabajadores en las acciones y toma de decisiones de la empresa. También inciden en gran medida el clima organizacional; donde un ambiente de trabajo confortable y cálido y mantener una buena relación entre directivos y subordinados inciden en la productividad de una empresa y por consiguiente en su éxito en el mercado. En el marco anterior, la comunicación juega un papel primordial en el establecimiento de las relaciones humanas y de producción; además es la pieza clave en los procesos de una entidad como factor transformador. En varias investigaciones del contexto hotelero la comunicación es una herramienta de gestión para la solución de problemas. Es así que la presente investigación propone el diagnóstico de la comunicación interna en el Hotel Comodoro. Los resultados de esta investigación permiten conocer las principales características del Hotel Comodoro y la percepción de trabajadores y directivos sobre la comunicación interna en el hotel.

Introducción: la lesión renal diabética es la complicación microvascular más frecuente de la diabetes mellitus, presente en el 20 al 40% de los casos, considerada la principal causa de enfermedad renal terminal. Objetivo: identificar si la funcionalidad familiar influye en la aparición de enfermedad renal en diabéticos de 40 a 79 años de edad de la ciudad de Loja. Metodología: fue un estudio de casos y controles, realizado en el área urbana, elegidos según muestreo probabilístico estratificado de tipo sistemático. Se evaluó la funcionalidad familiar con el test (FFSIL); se utilizó un cuestionario para datos sociodemográficos, valoración de datos antropométricos y elementos de control clínico; glucosa, hemoglobina glicosilada, triglicéridos, colesterol, lipoproteínas de alta y baja densidad, determinación de albumina con la utilización de tira reactiva y cálculo del filtrado glomerular utilizando la fórmula de CKD EPI. Resultados: se estudiaron 500 pacientes, 339 (67,8%) de género femenino y 161 (32,2%) del género masculino, con edad media de 61,37 años; tiempo de evolución de la diabetes con una media 3,52 años. En cuanto a la escolaridad, 162 (32,4%) con primaria completa y 38 (7,6%) analfabetos; al indagar correspondencia entre funcionalidad familiar utilizando el test FFSSIL y lesión renal diabética, no hubo asociación estadísticamente significativa (54; 10,8%), con valor de X2 de asociación de 1,021 con p=0,045. Conclusión: se encontró que la percepción de la funcionalidad familiar y el desarrollo de lesión renal diabética no guardan asociación estadísticamente significativa en este tipo de pacientes y en este grupo de edades.

The objective was to analyze the social responsibility construct through the Boston College method in a company of the automotive chain in Chihuahua from June to November 2018. The hypothesis to contrast was this: the company of the automotive chain is in its transformation stage to social responsibility. The methodological approach was qualitative, based on the inductive method and the design was transectional, descriptive and not experimental. The sampling frame and units of analysis were based on the list of personnel provided by HR; a structured interview of open questions was applied to seven hierarchical levels of the organization. The main strategic finding is that only 20% of respondents consider that social responsibility is present in the organization; this shows that the personnel is not involved and ignores that the company has social responsibility practices.

Introduction: Early pregnancy has been shown to decrease the life-time risk of mammary cancer. Further, systemic alterations in circulating levels of growth hormone (GH) and prolactin (PRL) have been associated with the decreased risk. GH and PRL have been shown to affect the mammary stroma and epithelium. Carcinogenesis is a multistep process and there are several ways in which the host environment can affect progression of initiated cells to neoplasia. During normal and tumor development complex interactions occur between epithelial cells and stromal cells in the tissue microenvironment. These epithelial-stromal interactions in the microenvironment play a crucial role in the progression of mammary tumors. Determining the epithelial-stromal regulation by GH and PRL in the mammary gland of early parous rats is expected to improve our understanding of the dynamics of the epithelium and stromal interactions in mammary carcinogenesis. Materials and Methods: The inguinal mammary fat pad was cleared of the host mammary gland in 3-4-week-old female Lewis rats. One group (n=20) of rats were exposed to MNU at 7 weeks of age, and another group (n=20) of rats were not exposed to MNU. A subset (n=10) of rats from each of these experimental groups were mated at 9 weeks and allowed to go through a full-term pregnancy. The mothers were allowed to lactate for 3 weeks and weaned. All animals were terminated 6 weeks post-weaning. Mammary epithelial cells (MECs) were isolated using a standard collagenase cell dissociation procedure. The isolated MECs (5 × 105) were transplanted into the gland-free fat pads of respective hosts (n=30). MECs isolated from control and carcinogen treated age-matched nulliparous (AMNP) rats were transplanted into the gland-free fat pads of parous hosts and similarly MECs from control and carcinogen treated parous were transplanted into gland-free fats pads of AMNP hosts. In brief, we studied the following groups to understand the influence of early parity on epithelial-stromal interactions involved in mammary carcinogenesis: 1) carcinogen treated MECs from AMNP rats was transplanted into untreated parous rats; 2) carcinogen treated MECs from parous rats was transplanted into untreated AMNP rats; 3) untreated MECs from AMNP rats was transplanted into carcinogen treated parous rats and 4) untreated MECs from parous rats was transplanted into carcinogen treated AMNP rats. In another experiment, we treated a subset of the above mentioned groups with GH or PRL (n=10). Mammary carcinogenesis was monitored weekly for incidence, multiplicity, and latency. The cancerous nature of the palpable tumors was confirmed by histopathological analysis. Results: Our results demonstrate that when MECs from AMNP rats were transplanted to parous hosts they did not grow further to make palpable cancers. In contrast when MECs from parous rats were transplanted to AMNP they formed palpable cancers. Further, administration of GH or PRL increased carcinogenesis in parous rats. Conclusion: These findings indicate that the epithelial stromal interactions are important for mammary carcinogenesis and they are influenced significantly by GH and PRL. Citation Format: Ramadevi Subramani, Adriana Galvez, Diego Pedroza, Alejandro Bencomo, Madeline Dixon, Rajkumar Lakshmanaswamy. Growth hormone and prolactin influences mammary epithelial and stromal interactions in early parity induced protection against breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-12-02.

BackgroundSOBERANA 02 is a COVID-19 conjugate vaccine candidate based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid. SOBERANA Plus antigen is dimeric-RBD. Here we report safety, reactogenicity and immunogenicity from phase I and IIa clinical trials using two-doses SOBERANA 02 (homologous protocol) and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols.MethodWe performed an open-label, monocentric, sequential and adaptive phase I for evaluating safety, reactogenicity and exploring immunogenicity of SOBERANA 02 in two formulations (15 and 25 μg) in 40 subjects, 19–59 years old. Phase IIa was open-label including 100 volunteers 19–80 years, receiving two doses of SOBERANA 02-25 μg. In both trials, half of volunteers received a third dose of SOBERANA 02, half received a heterologous dose of SOBERANA Plus-50 μg. Primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization test of RBD:hACE2 interaction, live-virus neutralization test and specific T-cells response.ResultsThe most frequent AE was local pain, other AEs had frequencies ≤ 5%. No serious related AEs were reported. Phase IIa confirmed the safety results in 60–80 years subjects. In phase-I SOBERANA 02-25µg elicited higher immune response than SOBERANA 02-15 µg; in consequence, the higher dose progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 μg even in 60–80 age range. Two doses of SOBERANA02-25 μg elicited an immune response similar to that of the Cuban Convalescent Serum Panel; it was higher after both the homologous and heterologous third doses; the heterologous scheme showing a higher immunological response.ConclusionsSOBERANA 02 was safe and immunogenic in persons aged 19–80 years, eliciting neutralizing antibodies and specific T cell response. Highest immune responses were obtained in the heterologous three doses protocol. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000340 and https://rpcec.sld.cu/trials/RPCEC00000347

Inter-agency guidelines recommend that survivors of intimate partner violence in humanitarian settings receive multisectoral services consistent with a survivor-centered approach. Providing integrated services across sectors is challenging, and aspirations often fall short in practice. In this study, we explore factors that influence the implementation of a multisectoral, integrated intervention intended to reduce psychological distress and intimate partner violence in Nyarugusu Refugee Camp, Tanzania. We analyzed data from a desk review of donor, legal, and policy documents; a gender-based violence services mapping conducted through 15 interviews and 6 focus group discussions; and a qualitative process evaluation with 29 stakeholders involved in the implementation of the integrated psychosocial program. We identified the challenges of implementing a multisectoral, integrated intervention for refugee survivors of intimate partner violence at the structural, inter-institutional, intra-institutional, and in social and interpersonal levels. Key determinants of successful implementation included the legal context, financing, inter-agency coordination, engagement and ownership, and the ability to manage competing priorities. Implementing a multisectoral, integrated response for survivors of intimate partner violence is complex and influenced by interrelated factors from policy and financing to institutional and stakeholder engagement. Further investment in identifying strategies to overcome the existing challenges of implementing multisectoral approaches that align with global guidelines is needed to effectively address the burden of intimate partner violence in humanitarian settings.

SUMMARYBackgroundSOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralizing antibodies.MethodsFrom March 8th to September 30th, 2021 we conducted in Havana, Cuba a multicentre randomized, double-blind, placebo-controlled, phase-3 trial evaluating two doses of SOBERANA-02 and a heterologous scheme with one dose SOBERANA-Plus added to it. Participants 19–80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 occurring at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose.FindingWe included 44·031 participants in a context of Beta VOC predominance, with this variant being gradually replaced by Delta near the trial end. Vaccine efficacy in the heterologous combination was 92·0% (95%CI 80·4–96·7) against symptomatic and 100% against severe COVID-19. Two doses of SOBERANA-02 was 69·7% (95%CI 56·5-78·9) and 74·9% (95%CI 33·7-90·5) efficacious to protect against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe AEs was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.InterpretationOur results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC dominance and that they constitute an attractive, feasible option for low- and middle-income countries, where besides financial constraints ease of vaccine storage and distribution is of concern.FundingThis study received funds from Finlay Vaccine Institute and National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020–20). of Ministry of Science, Technology and the Environment (Contract Project-2020-20) in Cuba.

Welcome to the Eigth International Workshop on Artificial Intelligence and Requirements Engineering (AIRE’21). The purpose of this workshop is to explore synergies between Artificial Intelligence (AI) and Requirements Engineering (RE). AIRE aims to strengthen the links in the community, including those between industry and academia. As such, we welcome submissions in the intersection between RE and AI. An important goal is to inspire a new and broad community for interdisciplinary discussions concerning novel research directions for Requirements Engineering and Artificial Intelligence. The edition of the workshop in 2021 received 18 submissions, which were independently reviewed by at least three program committee members. In the end, 12 long papers were accepted. All the conflicts of interest were treated seriously and independently. The high quality of submissions are a sign of a healthy research community and the selected papers will lead to a stimulating program, which also includes technical presentations and the Panel. We hope that you enjoy the AIRE’21 workshop and its proceedings. We consider that in the days when AI is gaining prominence in our daily lives, the RE community cannot neglect the benefit that AI techniques can deliver to the practice of requirements engineering. We look forward to seeing you all at this workshop and the future editions. We are very grateful to the Program Committee members and authors of the submissions for their hard work and dedication in putting together this program. We would like to thank you all for your participation in AIRE’21. We hope that you find this workshop fruitful and inspiring!Nelly, Rachel, and Daniel

Context: With the growing importance and complexity of software-based systems in relevant domain areas such as healthcare, education and e-government, acceptance of software products is essential.Problem / Motivation: We require to understand, model, and predict decisions taken by end users regarding the adoption and utilization of software products, where soft factors (such as human values, motivations and attitudes) need to be taken into account.Idea: In this paper, we address this need by using a novel probabilistic approach that allows the prediction of end users’ decisions and ranks soft factors importance in taking these decisions.Solution and Early Results: We implement a computational Bayesian network to model hidden states and their relationships to the dynamics of technology acceptance. The model has been applied in the healthcare domain using the NHS COVID-19 Test and Trace app (COVID-19 app). We found that soft factors such as Fear of infection and Altruism were important for the COVID-19 app acceptance. The results are reported as part of a two stage-validation of the model.

ObjectiveA weak and politicised COVID-19 pandemic response in the United States (US) that failed to prioritise sexual and reproductive health and rights (SRHR) overlaid longstanding SRHR inequities. In this study we investigated how COVID-19 affected SRHR service provision in the US during the first 6 months of the pandemic.MethodsWe used a multiphase, three-part, mixed method approach incorporating: (1) a comprehensive review of state-by-state emergency response policies that mapped state-level actions to protect or suspend SRHR services including abortion, (2) a survey of SRHR service providers (n=40) in a sample of 10 states that either protected or suspended services and (3) in-depth interviews (n=15) with SRHR service providers and advocacy organisations.ResultsTwenty-one states designated some or all SRHR services as essential and therefore exempt from emergency restrictions. Protections, however, varied by state and were not always comprehensive. Fourteen states acted to suspend abortion. Five cross-cutting themes surrounding COVID-19’s impact on SRHR services emerged across the survey and interviews: reductions in SRHR service provision; shifts in service utilisation; infrastructural impacts; the critical role of state and local governments; and exacerbation of SRHR inequities for certain groups.ConclusionsThis study demonstrates serious disruptions to the provision of SRHR care that exacerbated existing SRHR inequities. The presence or absence of policy protections for SRHR services had critical implications for providers and patients. Policymakers and service providers must prioritise and integrate SRHR into emergency preparedness planning and implementation, with earmarked funding and tailored service delivery for historically oppressed groups.

In recent times, the importance of the responsibility of universities has been highlighted. The objectives of the research focused on making a diagnosis of the progress in the transversal management of University Social Responsibility (RSU) in Higher Education Institutions (IES), 2 public ones, the Autonomous University of Chihuahua (UACH), and University of Colima (UCol); and 2 private ones, the Universidad de Monterrey (UDEM); and the Instituto Tecnologico y de Estudios Superiores de Monterrey (ITESM), Monterrey campus, to compare the performance in RSU of the same and to identify good practices of RSU. The nature of the research was quantitative, descriptive, non-experimental and transectional. The method was based on a 2019 random survey of 201 university executives. A measurement instrument was applied that divides the RSU macrovariable into 4 areas of action and 12 compliance goals. The stated objectives were met and it was found that the level of RSU progress in ITESM was 3.27, in UDEM it was 4.24, in UCol it was 3.52, and in UACH it was 2.78.

Despite significant advances in the treatment of myeloid malignancies, many patients become resistant to therapy and ultimately succumb to their disease. Accumulating evidence over the past several years has suggested that the inadequacy of many leukaemia therapies results from their failure to target the leukaemic stem cell (LSC). For this reason, the LSC population currently represents the most critical target in the treatment of myeloid malignancies. However, while LSCs are ideal targets in the treatment of these diseases, they are also the most difficult population to target. This is due to both their heterogeneity within the LSC population, and also their phenotypic similarities with normal haematopoietic stem cells. This review will highlight the current landscape surrounding LSC biology in myeloid malignancies, with a focus on altered energy metabolism, and how that knowledge is being translated into clinical advances for the treatment of chronic and acute myeloid leukaemia and myelodysplastic syndromes.

The mobility of people is at the center of transportation planning and decision-making of the cities of the future. In order to accelerate the transition to zero-emissions and to maximize air quality benefits, smart cities are prioritizing walking, cycling, shared mobility services and public transport over the use of private cars. Extensive progress has been made in autonomous and electric cars. Autonomous Vehicles (AV) are increasingly capable of moving without full control of humans, automating some aspects of driving, such as steering or braking. For these reasons, cities are investing in the infrastructure and technology needed to support connected, multi-modal transit networks that include shared electric Autonomous Vehicles (AV). The relationship between traditional public transport and new mobility services is in the spotlight and need to be rethought. This paper proposes an agent-based simulation framework that allows for the creation and simulation of mobility scenarios to investigate the impact of new mobility modes on a city daily life. It lets traffic planners explore the cooperative integration of AV using a decentralized control approach. A prototype has been implemented and validated with data of the city of Trento., Comment: 13 pages, 10 Figures, Early Access Article published at the IEEE Transactions on Intelligent Transportation Systems

Background The novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed. Method An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first. Results The study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56–1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56–0.88). Conclusions Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. Trial registration ClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

Background: Human papillomavirus (HPV) is recognized as the most important cofactor in the etiology of cancers of the cervix, esophagus, larynx, and nasopharynx. Experimental evidence suggests that HPV could have an oncogenic influence on thyroid follicular cells; however, to the best of our knowledge, there is no record of its role in human thyroid gland neoplasms. Objective: The purpose of this study is to describe the frequency and the types of HPV present in neoplastic thyroid tissue by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Methods: Over 157 samples were analyzed of paraffin-embedded tissue from malignant and benign thyroid tumors. All the paraffin blocks were selected consecutively from the Pathology Tissue Bank archive of the Western Medical Center. The molecular detection and typing were performed at the Molecular Microbiology Laboratory of the Biomedical Research Center, Mexican Institute of Social Security. Results: The frequency of HPV findings was 2.5% (four cases). HPV-6 was found in two cases of thyroid hyperplasia (2.5%), and HPV-33 in two cases of papillary cancer (4.6%). Conclusion: The presence of HPV is not frequent in thyroid neoplasms, at least in the studied population. Due to the low prevalence of this virus in our sample, it is not possible to reach conclusions. Further research is needed.

Motivational digital systems offer capabilities to engage and motivate end-users to foster behavioral changes towards a common goal. In general these systems use gamification principles in non-games contexts. Over the years, gamification has gained consensus among researchers and practitioners as a tool to motivate people to perform activities with the ultimate goal of promoting behavioural change, or engaging the users to perform activities that can offer relevant benefits but which can be seen as unrewarding and even tedious. There exists a plethora of heterogeneous application scenarios towards reaching the common good that can benefit from gamification. However, an open problem is how to effectively combine multiple motivational campaigns to maximise the degree of participation without exposing the system to counterproductive behaviours. We conceive motivational digital systems as multi-agent systems: self-adaptation is a feature of the overall system, while individual agents may self-adapt in order to leverage other agents' resources, functionalities and capabilities to perform tasks more efficiently and effectively. Consequently, multiple campaigns can be run and adapted to reach common good. At the same time, agents are grouped into micro-communities in which agents contribute with their own social capital and leverage others' capabilities to balance their weaknesses. In this paper we propose our vision on how the principles at the base of the autonomous and multi-agent systems can be exploited to design multi-challenge motivational systems to engage smart communities towards common goals. We present an initial version of a general framework based on the MAPE-K loop and a set of research challenges that characterise our research roadmap for the implementation of our vision., 7 pages, 1 figure

Software is becoming more complex as it needs to deal with an increasing number of aspects in volatile environments. This complexity may cause behaviors that violate the imposed constraints. A goal of runtime service monitoring is to determine whether the service behaves as intended to potentially allow the correction of the behavior. It may be set up in advance the infrastructure to allow the detections of suspicious situations. However, there may also be unexpected situations to look for as they only become evident during data stream monitoring at runtime produced by te system. The access to historic data may be key to detect relevant situations in the monitoring infrastructure. Available technologies used for monitoring offer different trade-offs, e.g. in cost and flexibility to store historic information. For instance, Temporal Graphs (TGs) can store the long-term history of an evolving system for future querying, at the expense of disk space and processing time. In contrast, Complex Event Processing (CEP) can quickly react to incoming situations efficiently, as long as the appropriate event patterns have been set up in advance. This paper presents an architecture that integrates CEP and TGs for service monitoring through the data stream produced at runtime by a system. The pros and cons of the proposed architecture for extracting and treating the monitored data are analyzed. The approach is applied on the monitoring of Quality of Service (QoS) of a data-management network case study. It is demonstrated how the architecture provides rapid detection of issues, as well as the ability to access to historical data about the state of the system to allow for a comprehensive monitoring solution.

Herein we describe the modular design and manufacturing of an emergency ventilator based on cyclical compression of a resuscitation bag to face the COVID-19 pandemic. This was done to mitigate the staggering conditions to supply these medical devices under challenging scenarios of need and logistics. The design is based on international standards and commissions for medical electrical equipment, particular requirements for basic safety, electromagnetic compatibility, and essential performance of critical care and emergency ventilators. The modular design is capable of providing four ventilation modes: volume/pressure mandatory ventilation and volume/pressure assisted ventilation. After testing with artificial lungs, calibration, and validation instruments it was found that the main ventilation parameters achieved are: maximum tidal volume of 700 mL, maximum pressure of 50 cmH2O, inspiration/expiration ratio up to 1:4 at 30 breaths per minute. The MEDIIK designation is derived from the mayan word ik’ which means wind.

We evaluated response to a single dose of the FINLAY-FR-1A recombinant dimeric-RBD base vaccine during a phase I clinical trial with 30 COVID-19 convalescents, to test its capacity for boosting natural immunity. This short report shows: a) an excellent safety profile one month after vaccination for all participants, similar to that previously found during vaccination of naïve individuals; b) a single dose of vaccine induces a >20 fold increase in antibody response one week after vaccination and remarkably 4-fold higher virus neutralization compared to the median obtained for Cuban convalescent serum panel. These preliminary results prompt initiation of a phase II trial in order to establish a general vaccination protocol for convalescents.

The models and data framework demystifies the different roles that models and data play in software development and operation and clarifies where machine learning and artificial intelligence techniques could be used.

This paper describes an investigation into value-based software engineering and proposes a comprehensive value taxonomy with an interpretation of design feature implications. The value taxonomy is used to assess the design of Covid19 symptom tracker applications., Comment: ICSE SEIS 2021

BackgroundThe COVID-19 pandemic presented an unprecedented challenge to identify effective drugs for prevention and treatment.ObjectiveTo characterize acute renal injury (AKI) in patients with COVID-19 and their relation with clinical outcomes within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center.MethodsAbu Dhabi Stem Cell Center (ADSCC) proposed a prospective clinical trial nebulization treatment with autologous stem cells (Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC)), at Abu Dhabi hospitals.Participants20 treated patients were compared with 23 not treated patients. Both groups received COVID 19 standard treatment.OutcomesAfter the results were collected, this study was created to determine the impact of the disease on the renal function and the efficacy of the therapy on patient’s outcomes.ResultsOne third of the critical patients studied suffered kidney failure. Patients in the treated group showed a favorable tendency to improve in contrast to those in the control group. Less patients from group A suffered from sepsis in comparison with the group B (25% vs 65%), HR=0.38, (95% Confidence Interval: 0.16 – 0.86), *p=0.0212. These results suggested a NNT=2.5. An improvement in lymphocyte count, CRP, and shorter hospital stay after treatment was evidenced, which led to less superinfection and sepsis in the treated group.ConclusionsThe proposed anti-inflammatory effect of the stem cells, offers a great promise for managing the illness, emerging as a crucial adjuvant tool in promoting healing and early recovery in severe COVID-19 infections and other supportive treatments.ARTICLE SUMMARYOur study had several strengths and limitation: It was a randomized trial.The treatment showed a positive result, providing evidence that this intervention is effective in routine practice.We found fewer complications related to prolonged hospital stay in the treated group.The is the small number of participants.It was carried out in 4 different hospitals, each with different criteria for the selection of the initial empirical antimicrobials, which can cause multiple resistant germs.

OBJECTIVE Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with males more commonly affected than females(1.6:1). Despite advancements in treatments, prognosis is dismal with a median overall survival of 15 months. Our aim was to investigate sex as a variable in GBM patient survival after receiving incremental levels of standard-of-care treatment regimens – different extents of surgical resection and different numbers of cycles of adjuvant temozolomide chemotherapy. METHODS Drawing from our extensive multi-institutional brain tumor repository, we investigated GBM subjects with overall survival (OS), extent of resection (EOR), number of temozolomide (TMZ) cycles, and sex data (n=620, males: n=387, females: n=233). Cox proportional hazard ratios were computed to investigate the multivariable predictive value of the patient variables with OS. Patients were then divided into groups based on their sex, EOR (either biopsy, subtotal resection (STR) or gross total resection (GTR)), and TMZ cycles (I: < 6 cycles, II: 7-11 cycles and III: >12 cycles). RESULTS We observed that STR was beneficial for females (HR=0.52; CI=0.33-0.83; p-value=0.013), while for males the benefit was not detected (HR=0.73; CI=0.46-1.15; p-value=0.173) for STR but was detectable for GTR (HR=0.58, CI=0.37-0.90; p-value=0.014). Females receiving 7-11 cycles of TMZ showed a survival benefit (HR=0.52; CI=0.12-0.53; p-value=0.048) while males in the same group did not (HR=0.74; CI=0.46-1.19; p-value=0.21), in comparison to those in group I of TMZ cycles. No sex differences were identified in patients receiving < =6 cycles or >=12 cycles. CONCLUSION Together, our results contribute to the growing literature that sex differences exist in GBM patients, even in response to standard-of-care therapies. This should be accounted for when designing clinical trials for GBM so that we may advance our pursuit to deliver personalized medicine.

BACKGROUND The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

International audience; The ever-growing complexity of systems, the growing number of stakeholders, and the corresponding continuous emergence of new domain-specific modeling abstractions has led to significantly higher cognitive load on modelers. There is an urgent need to provide modelers with better, more Intelligent Modeling Assistants (IMAs). An important factor to consider is the ability to assess and compare, to learn from existing and inform future IMAs, while potentially combining them. Recently, a conceptual Reference Framework for Intelligent Modeling Assistance (RF-IMA) was proposed. RF-IMA defines the main required components and high-level properties of IMAs. In this paper, we present a detailed, level-wise definition for the properties of RF-IMA to enable a better understanding, comparison, and selection of existing and future IMAs. The proposed levels are a first step towards a comprehensive assessment grid for intelligent modeling assistance. For an initial validation of the proposed levels, we assess the existing landscape of intelligent modeling assistance and three future scenarios of intelligent modeling assistance against these levels. • General and reference → Evaluation; • Software and its engineering → Model-driven software engineering; Abstraction , modeling and modularity; Integrated and visual development environments; Application specific development environments .

Software systems are increasingly making decisions autonomously by incorporating AI and machine learning capabilities. These systems are known as self-adaptive and autonomous systems (SAS). Some of these decisions can have a life-changing impact on the people involved and therefore, they need to be appropriately tracked and justified: the system should not be taken as a black box. It is required to be able to have knowledge about past events and records of history of the decision making. However, tracking everything that was going on in the system at the time a decision was made may be unfeasible, due to resource constraints and complexity. In this paper, we propose an approach that combines the abstraction and reasoning support offered by models used at runtime with provenance graphs that capture the key decisions made by a system through its execution. Provenance graphs relate the entities, actors and activities that take place in the system over time, allowing for tracing the reasons why the system reached its current state. We introduce activity scopes, which highlight the high-level activities taking place for each decision, and reduce the cost of instrumenting a system to automatically produce provenance graphs of these decisions. We demonstrate a proof of concept implementation of our proposal across two case studies, and present a roadmap towards a reusable provenance layer based on the experiments.

The term gamification has been introduced in the early 2000s [13] and has as central idea the usage of game elements in non-entertainment application domains to foster motivation [8], [15], [6]. There is a considerable amount of literature concerning gamification concepts [5], [16], related taxonomies [18], [17], and literature reviews [10].

The COVID-19 pandemic has called attention to the contribution of comorbidities, including cancer and brought additional challenges to previously existing programs for cancer treatment and control. The COVID-19 pandemic in Cuba was addressed through an integrated all-society action plan that to date has been largely successful with a low incidence of COVID-19 and mortality rates several-fold lower than worldwide averages. Despite downsizing many other health components all oncology services were maintained. Between March 11, when the first case was detected, until July 23, Cuba reported 2,449 cases of COVID-19 that included 28 (1.14%) with a diagnosis of cancer. Distribution among cancer diagnoses did not deviate from that expected according to cancer epidemiology in Cuba. However, although the probability of getting infected with the coronavirus for a cancer patient (0.012%), was not higher than that of the general population (0.020%), 9 of the 28 (32.1%) died, a lethality higher than that of COVID-19 patients without cancer (3.5%) a difference that is statistically significant (P< .001). We argue that going forward scientific research on the relationship of aging, inflammation and cancer, including identification of biomarkers and the development of novel therapeutic interventions, should become one of the priorities in the post-COVID agenda of both oncologists and infectious disease scientists.

Distinction between infection and flare in patients with systemic lupus erythematosus (SLE) is a challenge in clinical practice. Objective To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE. Methods A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%. Conclusion In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.

Background Nasopharyngeal colonisation (CNF) is considered a “major point” in the evaluation of pneumococal conjugate vaccines (PCVs). A year after the administration of PCVs in Cienfuegos, Cuba, we described the changes in CNF due to Streptococcus pneumoniae in children between 1 and 5 years included in a clinical trial of the new Cuban vaccine candidate PCV7-TT compared to PCV13. Method A pre–post vaccination evaluation study was conducted based on two cross-sectional surveys. The first pre vaccination survey (2014–2015) included 1135 children. A subsample (n2 = 555) of vaccinated children was selected through a simple random sample in 2016. The proportions and percentage differences of global CNF and serotypes and for each age group were estimated and compared before and after vaccination. Results The overall proportion of CNF in preschool children ranged from 34.0% to 26.7%, one year after vaccination (p = .00878). The greatest reduction was observed in the group between 2 and 5 years (from 45.8% to 17.6; [p Conclusions Despite the limitations of the study due to not having a concurrent control group of unvaccinated, the reduction in CNF by vaccine serotypes suggests that the introduction of the PCV7-TT could significantly impact the burden of CNF in children and consequently reduce the rates of disease associated with pneumococcal infection. Subsequent studies would be necessary to evaluate the phenomenon of serotype replacement and its influence on the reduction of effectiveness over pneumococcal disease.

Drinking water supply through desalination processes based on reverse osmosis is a technology widely used in the Canary Islands due to its modular capacity and lower specific energy consumption compared to distillation technologies. The first energy recovery devices were based in centrifugal devices like the Francis Turbine. Later these devices were replaced by Pelton Turbines until the eighties when engineers developed positive-displacement devices called isobaric chambers for seawater reverse osmosis. Due to the importance of these devices in the reverse osmosis desalination process, this work analyzes, through several interviews and surveys, the main commercial isobaric chambers installed and their behavior based upon the experience of >50 years of the managers of several seawater reverse osmosis desalination plants, which are currently in operation in the Canary Islands. The purpose is to establish which of the energy recovery devices is the most suitable for installing in the future in medium and large capacity desalination plants. These results indicate the value of the factors studied: operational data, maintenance, troubleshooting and specific energy consumption of each device studied.

The goal of the present research was to compare the profiles of old age prejudice in male and female students from the area of physical activity. The study was conducted from January to October 2016. Participants were recruited from different semesters of the Physical Education and Human Motricity bachelor’s degrees offered at the Faculty of Physical Culture Sciences of the Autonomous University of Chihuahua, Mexico. The sample was obtained through convenience sampling, and included 1652 participants; 828 women and 824 men, mean age was 20.51 ± 1.83 years 20.90 ± 2.03 years respectively. The approach of the study was quantitative with a descriptive survey-like design. All participants completed the Questionnaire on Negative Stereotypes towards Old Age. Results from the Multivariate Analyses of Variance, and the follow-up Univariate Analyses of Variance, show that men report greater levels of prejudice towards old age on the sociomotivational (F = 31.657, p

Objective Compare the concordance degree between plasma glucose and glucose measurements on Dried Blood Spots (DBS) during pregnancy. Subjects and methods Glucose measurement was performed in pregnant women after a fast of 8-12 hours. Venous blood was collected with sodium fluoride, the plasma was separated, and glucose measured by the enzymatic oxidase glucose method. Capillary blood samples were collected and analyzed by DBS. For statistics, the paired Student’s t test, interclass correlation coefficient (ICC), graphic approach of Altman and Bland, and survival – concordance plot were used. Results 307 pregnant women were evaluated, 88.6% without diabetes and 11.4% with previous diabetes. The glucose ranged from 66 to 190 mg/dL [3.66 to 10.55 mmol/L] in plasma and from 53 to 166 mg/dL [2.94 to 9.21 mmol/L] in DBS. The glucose average values were 88.1 ± 12 mg/dL [4.98 ± 0.67 mmol/L] in plasma and 89.2 ±11,5 mg/dL, [4.95 ± 0.64 mmol/L] in DBS – p-value = 0.084. The ICC value was moderate (0.510), and Pearson’s correlation coefficient was r = 0.507 p < 0.001. Altman and Bland’s graph showed that difference between the values obtained by both methods is -24.62 to 22.3 mg/dL [-1.37 to 1.24 mmol/L]. Significant fixed bias (-1,16 average difference) and proportional bias (r = 0.056; p = 0.33) were not observed. Anemia was associated with differences between plasma glucose and DBS measurements (p = 0.031). Conclusion Capillary glucose in DBS correlates with plasma glucose; however, the methods do not present good concordance. The presence of anemia worsens this result.

International audience; Sustainability has emerged as a concern of central relevance. As a wicked problem, it poses challenges to business-as-usual in many areas, including that of modeling. This article addresses a question at the intersection of model-driven engineering and sustainability research: "How can we better support sustainability by bringing together model-driven engineering, data, visualization and self-adaptive systems, to facilitate engagement, exploration, and understanding of the effects that individual and organizational choices have on sustainability?" We explore this question via an idealized vision of an evaluation environment that facilitates integration and mapping of models from multiple diverse sources, visual exploration, and evaluation of what-if scenarios, for stakeholders with divergent perspectives. The article identifies research challenges to be addressed to enable decision making to support sustainability and provides a map of sustainability modeling issues across disciplines.

One of the basic principles in product lines is to delay design decisions related to offered functionality and quality to later phases of the life cycle [25]. Instead of deciding on what system to develop in advance, a set of assets and a common reference architecture are specified and implemented during the Domain Engineering process. Later on, during Application Engineering, specific systems are developed to satisfy the requirements reusing the assets and architecture [16]. Traditionally, this is during the Application Engineering when delayed design decisions are solved. The realization of this delay relies heavily on the use of variability in the development of product lines and systems. However, as systems become more interconnected and diverse, software architects cannot easily foresee the software variants and the interconnections between components. Consequently, a generic a priori model is conceived to specify the system's dynamic behaviour and architecture. The corresponding design decisions are left to be solved at runtime [13].Surprisingly, few research initiatives have investigated variability models at runtime [9]. Further, they have been applied only at the level of goals and architecture, which contrasts to the needs claimed by the variability community, i.e., Software Product Lines (SPLC) and Dynamic Software Product Lines (DSPL) [2, 10, 14, 22]. Especially, the vision of DSPL with their ability to support runtime updates with virtually zero downtime for products of a software product line, denotes the obvious need of variability models being used at runtime to adapt the corresponding programs. A main challenge for dealing with runtime variability is that it should support a wide range of product customizations under various scenarios that might be unknown until the execution time, as new product variants can be identified only at runtime [10, 11]. Contemporary variability models face the challenge of representing runtime variability to therefore allow the modification of variation points during the system's execution, and underpin the automation of the system's reconfiguration [15]. The runtime representation of feature models (i.e. the runtime model of features) is required to automate the decision making [9].Software automation and adaptation techniques have traditionally required a priori models for the dynamic behaviour of systems [17]. With the uncertainty present in the scenarios involved, the a priori model is difficult to define [20, 23, 26]. Even if foreseen, its maintenance is labour-intensive and, due to architecture decay, it is also prone to get out-of-date. However, the use of models@runtime does not necessarily require defining the system's behaviour model beforehand. Instead, different techniques such as machine learning, or mining software component interactions from system execution traces can be used to build a model which is in turn used to analyze, plan, and execute adaptations [18], and synthesize emergent software on the fly [7].Another well-known problem posed by the uncertainty that characterize autonomous systems is that different stakeholders (e.g. end users, operators and even developers) may not understand them due to the emergent behaviour. In other words, the running system may surprise its customers and/or developers [4]. The lack of support for explanation in these cases may compromise the trust to stakeholders, who may eventually stop using a system [12, 24]. I speculate that variability models can offer great support for (i) explanation to understand the diversity of the causes and triggers of decisions during execution and their corresponding effects using traceability [5], and (ii) better understand the behaviour of the system and its environment.Further, an extension and potentially reframing of the techniques associated with variability management may be needed to help taming uncertainty and support explanation and understanding of the systems. The use of new techniques such as machine learning exacerbates the current situation. However, at the same time machine learning techniques can also help and be used, for example, to explore the variability space [1]. What can the community do to face the challenges associated?We need to meaningfully incorporate techniques from areas such as artificial intelligence, machine learning, optimization, planning, decision theory, and bio-inspired computing into our variability management techniques to provide explanation and management of the diversity of decisions, their causes and the effects associated. My own previous work has progressed [3, 5, 6, 8, 11, 12, 19, 21] to reflect what was discussed above.

Developing new distillation strategies can help the spirits industry to improve quality, safety and process efficiency. Batch stills equipped with a packed column and an internal partial condenser are an innovative experimental system, allowing a fast and flexible management of the rectification. In this study, the impact of four factors (heart-cut volume, head-cut volume, pH and cooling flow rate of the internal partial condenser during the head-cut fraction) on 18 major volatile compounds of Muscat spirits was optimized using response surface methodology and desirability function approaches. Results have shown that high rectification at the beginning of the heart-cut enhances the overall positive aroma compounds of the product, reducing off-flavor compounds. In contrast, optimum levels of heart-cut volume, head-cut volume and pH factors varied depending on the process goal. Finally, three optimal operational conditions (head off-flavors reduction, flowery terpenic enhancement and fruity ester enhancement) were evaluated by chemical and sensory analysis.

Background: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. Methods: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Findings: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-I³ and TNF-α. Interpretation: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. Funding: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. Antecedentes: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfeccion, evaluamos la vacuna FINLAY-FR-1A en un ensayo clinico. Metodos: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 anos: convalecientes de COVID-19 leve y convalecientes asintomaticos, ambos con prueba PCR positiva al momento del diagnostico; e individuos con infeccion subclinica detectada por IgG especifica viral. Los participantes recibieron una dosis unica por via intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de union al receptor recombinante dimerico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 dias despues de la vacunacion. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y despues de la vacunacion, se evaluo por ELISA y mediante la prueba de neutralizacion del virus vivo. Tambien se evaluo la respuesta de celulas T efectoras. Registro Publico Cubano de Ensayos Clinicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Resultados: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los mas comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimulo un incremento >21 veces de los anticuerpos IgG anti-RBD 28 dias despues de la vacunacion. La mediana de los titulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron titulos de neutralizacion viral superiores a 1:160 en 24 (80%) de los participantes. Tambien hubo un aumento en las celulas T especificas de RBD que producen IFN-I³ y TNF-α. Interpretacion: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzo eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. Financiamiento: Se recibio un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministerio de Ciencia, Tecnologia y Medio Ambiente, Cuba.

Deep learning has become one of the most promising approaches in recent years. One of the main applications of deep learning is the automatic feature extraction with auto-encoders (AEs). Feature extraction, one of the most important stages in machine learning, that can reduce drastically the dimensionality of the problem, making easier any subsequent process such as classification. The main contribution of this research is to evaluate the use of AEs for automatic feature extraction in massive thermonuclear fusion databases. In order to show the performance of AEs in a practical way, the problem of image classification of the TJ-II Thomson Scattering diagnostic has been selected. The classification has been performed by the algorithm of support vector machines and conformal predictors. The results show that the use of AEs produces the predictions faster, with more reliable models, and with higher success rates in comparison to the performance without using the deep learning approach.

Ever since the ubiquitin proteasome system was characterized, efforts have been made to manipulate its function to abrogate the progression of cancer. As a result, the anti-cancer drugs bortezomib, carfilzomib, and ixazomib targeting the 26S proteasome were developed to treat multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, among others. Despite success, adverse side effects and drug resistance are prominent, raising the need for alternative therapeutic options. We recently demonstrated that knockdown of the 19S regulatory components, 26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3), resulted in increased apoptosis of chronic myeloid leukemia (CML) cells, but had no effect on normal controls, suggesting they may be good targets for therapy. Therefore, we hypothesized that PSMD1 and PSMD3 are potential targets for anti-cancer therapeutics and that their relevance stretches beyond CML to other types of cancers. In the present study, we analyzed PSMD1 and PSMD3 mRNA and protein expression in cancerous tissue versus normal controls using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), comparing expression with overall survival. Altogether, our data suggest that PSMD1 and PSMD3 may be novel putative targets for cancer prognosis and therapy that are worthy of future investigation.

A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.

Bat acoustic libraries are important tools that assemble echolocation calls to allow the comparison and discrimination to confirm species identifications. The Sonozotz project represents the first nation‐wide library of bat echolocation calls for a megadiverse country. It was assembled following a standardized recording protocol that aimed to cover different recording habitats, recording techniques, and call variation inherent to individuals. The Sonozotz project included 69 species of echolocating bats, a high species richness that represents 50% of bat species found in the country. We include recommendations on how the database can be used and how the sampling methods can be potentially replicated in countries with similar environmental and geographic conditions. To our knowledge, this represents the most exhaustive effort to date to document and compile the diversity of bat echolocation calls for a megadiverse country. This database will be useful to address a range of ecological questions including the effects of anthropogenic activities on bat communities through the analysis of bat sound., The Sonozotz project represents the first nation‐wide library of bat echolocation calls for a megadiverse country.