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Abstract Lysine-specific histone demethylase 1 (LSD1) is a histone demethylase that plays a critical role in epigenetic regulation by removing the methyl group from mono- and di-methylated lysine 4 on histone H3 (H3K4me1/2), acting as a repressor of gene expression. Recently, catalytically independent functions of LSD1, serving as a scaffold for assembling chromatin-regulator and transcription factor complexes, have been identified. Herein, we show for the first time that LSD1 interacts with chromodomain-helicase-DNA-binding protein 7 (CHD7) in mouse embryonic stem cells (ESCs). To further investigate the CHD7–LSD1 crosstalk, we engineered Chd7 and Chd7/Lsd1 knockout (KO) mouse ESCs. We show that CHD7 is dispensable for ESC self-renewal and survival, while Chd7 KO ESCs can differentiate towards embryoid bodies (EBs) with defective expression of ectodermal markers. Intriguingly, Chd7/Lsd1 double KO mouse ESCs exhibit proliferation defects similar to Lsd1 KO ESCs and have lost the capacity to differentiate properly. Furthermore, the increased co-occupancy of H3K4me1 and CHD7 on chromatin following Lsd1 deletion suggests that LSD1 is required for facilitating the proper binding of CHD7 to chromatin and regulating differentiation. Collectively, our results suggest that LSD1 and CHD7 work in concert to modulate gene expression and influence proper cell fate determination.

Abstract Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but not LSD1MUT results in decreased DNMT1 and UHRF1 proteins coupled to global hypomethylation. We show that both LSD1 and LSD1MUT control protein stability of UHRF1 and DNMT1 through interaction with HDAC1 and the ubiquitin-specific peptidase 7 (USP7), consequently, facilitating the deacetylation and deubiquitination of DNMT1 and UHRF1. Our studies elucidate a mechanism by which LSD1 controls DNA methylation in mouse ESCs, independently of its lysine demethylase activity.

The paper studies packing polygons of variable shapes, regarding the stretching coefficient, in a rectangular target domain of minimum height. Packing objects of a variable shape have a wide spectrum of applications, e.g, in biology, materials science, mechanics, land allocation, and logistics. Interest in these problems is also due to the modeling of the structures of porous media under pressure, e.g., for creating test models of artificial digital cores. Elements of porous media can be deformed under the influence of an external force, but the mass of each particle remains unchanged. This corresponds to conservation of area for the two-dimensional case. Polygonal objects must be completely contained within the target domain (containment constraint) and do not overlap (non-overlapping constraint), provided they have free translations, continuous rotations, stretch transformations, and conserve their area. The phi-function technique is used for an analytical description of the placement constraints for variable shape polygons. Quasi-phi-functions for describing non-overlapping constraints and phi-functions for describing containment constraints are defined. The packing problem is presented in the form of a nonlinear programming model. A solution strategy is proposed, which consists of the following stages: generation of feasible starting points; search for local minima of the problem of packing soft polygons for each starting point using the decomposition algorithm; choosing the best local minimum found at the previous stage. To search for smart starting arrangements, an optimization algorithm for packing original polygons using their homothetic transformations is applied. Decomposition of the problem of packing polygons of variable shapes is based on an iterative procedure that allows reducing a large-scale problem to a sequence of smaller nonlinear programming problems (linear to the number of objects). Numerical examples are provided for oriented rectangles and non-oriented regular polygons.

IntroductionSerine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.MethodsTo evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity).ResultsAccording to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02).DiscussionOur data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Background and purposeImage-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy.Materials and methodsWe included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT.ResultsNinety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4).ConclusionHR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

Background/purpose(s): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. Methods: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. Results: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04–3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02–2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04–3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21–4.9) with deceased outcomes. Conclusion: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

This article provides a detailed analysis of China’s ongoing struggle against poverty. In addition to discussing the recently concluded targeted poverty alleviation program, in which the CPC-led government achieved its goal of ending extreme poverty, the author discusses the anti-poverty measures taken during the various phases of the Chinese Revolution, including land reform in the liberated areas in the 1930s and 1940s; the period of initial socialist construction from 1949; reform and opening up from 1978; and the more recent measures aimed at building common prosperity. He concludes that poverty alleviation, and more broadly the improvement of people’s living standards, has been foundational to the entire Chinese socialist project and constitutes a key theme of each of its stages.

Abstract Background Ultrasound‐determined gallbladder wall thickness is widely used to aid in the diagnosis of gallbladder disease, but no reference values supported by published measurement data are available in dogs. Hypothesis/Objective Establish normal thickness of the gallbladder wall in dogs. Animals Fifty‐three dogs presented to a referral hospital and required abdominal ultrasound examination for reasons unrelated to primary hepatobiliary disease. Methods Cross‐sectional observational study recruiting dogs requiring abdominal ultrasound examination. A standard sequence of gallbladder wall images was recorded for later review. Inclusion criteria were normal ultrasonographic hepatobiliary, pancreatic, and small intestinal findings. Exclusion was determined by 2 European College of Veterinary Internal Medicine (ECVIM)‐certified veterinary internists blinded to gallbladder wall thickness data. Dogs were excluded if they had inadequate medical records, a previous history of hepatobiliary, gastrointestinal, or pancreatic disease likely to impact the biliary system (eg, chronic vomiting, nausea, jaundice, diarrhea), unexplained increases in liver enzyme activities, hypoalbuminemia, or ascites. Gallbladder wall thickness was determined by 2 European College of Veterinary Diagnostic Imaging (ECVDI)‐certified veterinary radiologists working together to generate a consensus for each dog. The final output was the maximum normal wall thickness for this population of dogs. Results The upper limit for gallbladder wall thickness in 53 fasted (8 hours) dogs

Drawing on ethnographic fieldwork among homeless deportees living in the Tijuana River canal, I examine how the ‘rehabilitation’ of toxic terrains can have corporeal and social consequences for those inhabiting such spaces. For decades, the Tijuana River basin traversing the U.S.–Mexico border has been perceived by officials from both countries as an unruly body of water. Prone to persistent flooding, the canal also experiences flows of toxic sewage from Tijuana’s maquiladora industry. In recent years, the riverbed in Tijuana has been inhabited by homeless and drug using communities, many of whom have been deported from the U.S. In response, rehabilitation of the canal and forced drug rehabilitation have been conjoined and promoted by the state as solutions for managing this unruly terrain and its residents. I take the deployment of the term ‘rehabilitation’ targeting both homeless deportees and the canal as an opportunity to consider how the concurrent disciplining of landscapes and human populations has been a central and evolving feature of the Anthropocene. I examine how my homeless interlocutors have experienced ‘rehabilitation’ as a violent process of abjection, dispossession, and captivity, which has converted this transborder landscape structure into a carceral zone under the guise of urban sanitation and health promotion.

Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: β1, β2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.

In recent years, the US government has implemented several bureaucratic changes aimed at stalling the influx of asylum seekers. From the “metering” system initiated under the Obama administration to the Migrant Protection Protocols (MPP) implemented by the Trump administration, these measures have erected a bureaucratic wall against asylum seekers that has kept them captive in Mexican border cities. Drawing on ethnographic fieldwork conducted in Tijuana, Mexico, I examine how these policies have produced deadly conditions for asylum seekers by calibrating time and space in such a way that increases their exposure and vulnerability to highly precarious environments and predatory bureaucracies.

Abstract Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced pluripotent stem cell-derived motor neurons (iPSMNs) offer a solution; however, studies have typically been limited to underpowered cohorts. Here, we present a comprehensive compendium of 429 iPSMNs from 15 datasets, and 271 post-mortem spinal cord samples. Using reproducible bioinformatic workflows, we identify robust upregulation of p53 signalling in ALS in both iPSMNs and post-mortem spinal cord. p53 activation is greatest with C9orf72 repeat expansions but is weakest with SOD1 and FUS mutations. TDP-43 depletion potentiates p53 activation in both post-mortem neuronal nuclei and cell culture, thereby functionally linking p53 activation with TDP-43 depletion. ALS iPSMNs and post-mortem tissue display enrichment of splicing alterations, somatic mutations, and gene fusions, possibly contributing to the DNA damage response.

The stability and reliability of the global Internet infrastructure heavily rely on the Border Gateway Protocol (BGP), a crucial protocol that facilitates the exchange of routing information among various Autonomous Systems, ensuring seamless connectivity worldwide. However, BGP inherently possesses a susceptibility to abnormal routing behaviors, potentially leading to significant connectivity disruptions. Despite extensive efforts, accurately detecting and effectively mitigating such abnormalities persist as tough challenges. To tackle these, this article proposes a novel statistical approach employing the median absolute deviation under certain constraints to proactively detect anomalies in BGP. By applying advanced analysis techniques, this research offers a robust method for the early detection of anomalies, such as Internet worms, configuration errors, and link failures. This innovative approach has been empirically validated, achieving an accuracy rate of 90% and a precision of 95% in identifying these disruptions. This high level of precision and accuracy not only confirms the effectiveness of the statistical method employed but also marks a significant step forward for enhancing the stability and reliability of the global Internet infrastructure.

Slow-read Distributed Denial of Service (DDoS) attacks are complex to detect and mitigate. Although existing tools allow one to identify these attacks, these tools mainly generate alerts. However, in real scenarios, a large number of attack detection alerts will put the security workforce in a bottleneck, as they will not be able to implement mitigation actions in a complete and timely manner. Furthermore, since most existing security solutions for DDoS attack mitigation are tested using datasets and simulated scenarios, their applicability to production networks could be unfeasible or ineffective due to possibly incomplete assumptions in their design. Therefore, automated security solutions against DDoS attacks are needed not only to be designed but also to be implemented and evaluated in real scenarios. This study presents a Software-Defined Networking (SDN)-based security framework, which automates the monitoring, detection, and mitigation of slow-rate DDoS attacks. The framework is implemented in a physical network that uses equipment from the European Experimental Facility Smart Networks for Industry (SN4I). The results demonstrate that the framework effectively mitigates malicious connections, with a mitigation efficiency between 91.66%– 100% for different conditions of the number of attackers and victims. In addition, the SDN-SlowRate-DDoS dataset is presented, which contains multiple experiments of slow-rate DDoS attacks performed on the real testbed. The resources provided in this security dataset are useful to the scientific and industry communities in designing and testing realistic solutions for intrusion detection systems.

This single-center study aimed to retrospectively evaluate the survival outcomes of patients with FIGO stage I clear cell and serous uterine carcinoma according to the type of adjuvant treatment received. The data were collected between 2003 and 2020 and only patients with stage I clear cell or serous uterine carcinoma treated with primary surgery were included. These were classified into three groups: No treatment or brachytherapy only (G1), radiotherapy +/− brachytherapy (G2), chemotherapy +/− radiotherapy +/− brachytherapy (G3). In total, we included 52 patients: 18 patients in G1, 16 in G2, and 18 in G3. Patients in the G3 group presented with poorer prognostic factors: 83.3% had serous histology, 27.8% LVSI, and 27.8% were FIGO stage IB. Patients treated with adjuvant radiotherapy showed an improved 5-year overall survival (OS) (p = 0.02) and a trend towards an enhanced 5-year progression-free survival (PFS) (p = 0.056). In contrast, OS (p = 0.97) and PFS (p = 0.84) in the chemotherapy group with poorer prognostic factors, were similar with increased toxicity (83.3%). Radiotherapy is associated with improved 5-year OS and tends to improve 5-year PFS in women with stage I clear cell and serous uterine carcinoma. Additional chemotherapy should be cautiously considered in serous carcinoma cases presenting poor histological prognostic factors.

Abstract A large group of countries constitute Latin American (LATAM) countries, where hemophilia care is as varied as the landscape of this region. To better understand the care provided to persons with bleeding disorders, especially hemophilia, a symposium was organized as part of the CLAHT Congress 2021 in Colombia to highlight the issues of hemophilia care and challenges faced by persons with hemophilia in four LATAM countries, Colombia, Peru, Argentina, and Mexico. A summary of the symposium is provided. Four clinicians highlighted the issues in their own country, the status, and the path forward to bring the standard of care to the international level in each of these countries. The geography of the country, the health infrastructure, and the resources available are obstacles in these countries to provide state‐of‐the‐art care to the bleeding disorder community. However, depending on the country, its infrastructure and the resources available, progress is being made to upend the care provided. Indeed, the care of persons with hemophilia has been greatly improved, including personalized prophylaxis. The information summarized here first emphasizes how the geography of a country and the different healthcare infrastructures play a major role in how care is offered. It also provides a path for other countries to evaluate these issues in their own realities. In parallel, these data provide hope to many developing countries; despite obstacles, strides can be made in the care of the bleeding disorder community.

Abstract Research software is a fundamental and vital part of research, yet significant challenges to discoverability, productivity, quality, reproducibility, and sustainability exist. Improving the practice of scholarship is a common goal of the open science, open source, and FAIR (Findable, Accessible, Interoperable and Reusable) communities and research software is now being understood as a type of digital object to which FAIR should be applied. This emergence reflects a maturation of the research community to better understand the crucial role of FAIR research software in maximising research value. The FAIR for Research Software (FAIR4RS) Working Group has adapted the FAIR Guiding Principles to create the FAIR Principles for Research Software (FAIR4RS Principles). The contents and context of the FAIR4RS Principles are summarised here to provide the basis for discussion of their adoption. Examples of implementation by organisations are provided to share information on how to maximise the value of research outputs, and to encourage others to amplify the importance and impact of this work.

RESUMEN Antecedentes: La cirrosis es la etapa final de una alteración crónica presentada a nivel del hígado, cuya supervivencia es menor a los 3 años una vez que esta se encuentre descompensada, es la consecuencia de múltiples factores, entre los más comunes se presenta: ingestión de alcohol, hígado graso no alcohólico, hemocromatosis, hepatitis crónica B o C y obstrucción biliar. Objetivo: Exponer información sobre la cirrosis en niños y adolescentes. Materiales y métodos: Para la presente revisión bibliográfica, se consultaron las siguientes bases de datos: Springer, Scopus, Web of Science y Science direct. Además, en buscadores como Google académico y PUBMed, así también algunas bases de datos regionales, como: Scielo, Redalyc, Medline y Latindex. Para la estrategia de búsqueda es necesario la aplicación del PICO process, utilizamos palabras claves como: ADOLESCENTES Y NIÑOS, ENFERMEDAD, HEPÁTICA, pudiendo ser éstas tanto en inglés como en español con la palabra clave CIRROSIS. Resultados: Los resultados indicaron que la cirrosis en niños y adolescentes tiene diferentes estadios, repercutiendo de diferentes maneras, dejando distintas secuelas a nivel cognitivo, funcionamiento del hígado y fenotípicamente. Conclusiones: Controlar o mantener vigiladas las diferentes enfermedades desencadenantes de la cirrosis, así evitar ciertas complicaciones asociadas a la patología como la hipertensión portal y miocardiopatía cirrótica. Palabras clave: adolescentes, cirrosis, enfermedad, hepática.

Abstract Mitochondrial activation and the production of mitochondrial reactive oxygen species (mROS) are crucial for CD4+ T cell responses and have a role in naïve cell signaling after TCR activation. However, little is known about mROS role in TCR-independent signaling and in recall responses. Here, we found that mROS are required for IL-12 plus IL-18-driven production of IFN-γ, an essential cytokine for inflammatory and autoimmune disease development. Compared to TCR stimulation, which induced similar levels of mROS in naïve and memory-like cells, IL-12/IL-18 showed faster and augmented mROS production in memory-like cells. mROS inhibition significantly downregulated IFN-γ and CD44 expression, suggesting a direct mROS effect on memory-like T cell function. The mechanism that promotes IFN-γ production after IL-12/IL-18 challenge depended on the effect of mROS on optimal activation of downstream signaling pathways, leading to STAT4 and NF-κB activation. To relate our findings to IFN-γ-driven lupus-like disease, we used Fas-deficient memory-like CD4+ T cells from lpr mice. Importantly, we found significantly increased IFN-γ and mROS production in lpr compared with parental cells. Treatment of WT cells with FasL significantly reduced mROS production and the activation of signaling events leading to IFN-γ. Moreover, Fas deficiency was associated with increased mitochondrial levels of cytochrome C and caspase-3 compared with WT memory-like cells. mROS inhibition significantly reduced the population of disease-associated lpr CD44hiCD62LloCD4+ T cells and their IFN-γ production. Overall, these findings uncovered a previously unidentified role of Fas/FasL interaction in regulating mROS production by memory-like T cells. This apoptosis-independent Fas activity might contribute to the accumulation of CD44hiCD62LloCD4+ T cells that produce increased IFN-γ levels in lpr mice. Overall, our findings pinpoint mROS as central regulators of TCR-independent signaling, and support mROS pharmacological targeting to control aberrant immune responses in autoimmune-like disease.

Introduction and Objectives: Liver transplant patients require a vast and complex evaluation prior to transplant surgery. Hemodynamic evaluation by Doppler echocardiography is important in the identification of systolic/diastolic alterations as a predictor of post-liver transplant outcomes, from cardiovascular alterations to graft dysfunction and mortality. This study aimed to describe the relationship between the hemodynamic variables evaluated by Doppler echocardiography and post-transplant liver outcomes in patients diagnosed with cirrhosis at LaCardio hospital. We describe the demographic variables of our cohort and outcomes such as mortality, acute kidney injury, need for dialysis and hospital admission for acute heart failure in the post-transplant period up to one year of follow-up. Materials and Methods: Retrospective cohort study. Patient with liver transplant at LaCardio hospital, in Bogotá, Colombia, between January 2005 and July 2021. Analysis of sociodemographic variables, comorbidities, echocardiography and intraoperative variables, with primary outcomes such as early graft dysfunction, acute kidney injury and intraoperative mortality. A classification and regression tree (CART) was performed. Results: 397 patients were analyzed, with 54.4% men. The median of age was 56 years and the most common etiology of cirrhosis was alcoholic. The most common comorbidities were hypertension (54%) and type 2 diabetes mellitus (24%). In 71% of patients, there was some degree of diastolic dysfunction and left ventricular hypertrophy (30.9%). The presence of graft dysfunction was present in up to 8% of patients and was associated with acute kidney injury (AKI) in 21%, requirement of multiple transfusions during surgery and renal replacement therapy with a mortality of 15% during study follow-up. In the CART model for mortality and graft dysfunction outcomes, it was related to the presence of BMI

Abstract Emissivity as a function of wavelength, direction, and temperature correlates to a material's efficiency in radiating thermal energy. Knowledge of emissivity is essential for designing and developing radiation‐cooled thermal protective systems for hypersonic applications. It is desirable to achieve a high emissivity (with a value close to 1) to maximize heat radiation from a hot surface of a hypersonic vehicle's leading edge during atmospheric re‐entry. With the goal of providing the hypersonic materials community with this necessary knowledge, this article offers a basic understanding of thermal radiation, methods for measuring emissivity at high temperatures, and a comprehensive overview of the emissivity of ultra‐high temperature ceramics.

In academic research virtually every field has increased its use of digital and computational technology, leading to new scientific discoveries, and this trend is likely to continue. Reliable and efficient scholarly research requires researchers to be able to validate and extend previously generated research results. In the digital era, this implies that digital objectsKahn and Wilensky 2006 used in research should be Findable, Accessible, Interoperable and Reusable (FAIR). These objects include (but are not limited to) data, software, models (for example, machine learning), representations of physical objects, virtual research environments, workflows, etc. Leaving any of these digital objects out of the FAIR process may result in a loss of academic rigor and may have severe consequences in the long term for the field, such as a reproducibility crisis. In this extended abstract, we focus on research software as a FAIR digital object (FDO).The FDO framework De Smedt et al. 2020 describes FDOs as being actionable units of knowledge, which can be aggregated, analyzed, and processed by different types of algorithms. Such algorithms must be implemented by software in one form or another. The framework also describes large software stacks supporting FDOs enabling responsible data science and increasing reproducibility. This implies that software is a key ingredient of the FDO framework, and should adhere to the FAIR principles. Software plays multiple roles: it is a DO itself, it is responsible for creating new FDOs (e.g., data) and it helps to make them available to the public (e.g., via repositories and registries). However there is a need to specify in more detail how non-data DOs, in particular software, fit in this framework.Different classes of digital objects have different intrinsic properties and ways to relate to other DOs. This means that while they, in principle, are subject to the high-level FAIR principles, there are also differences depending on their type and properties, requiring an adaptation so FAIR implementations are more aligned to the digital object itself. This holds true in particular to software. Software has intrinsic properties (executability, composite nature, development practices, continuous evolution and versioning, and packaging and distribution) and specific needs that must be considered by the FDO framework. For example, open source software is typically developed in the open on social coding platforms, where releases are distributed through package management systems, unlike data that is typically published in archival repositories. These social coding platforms do not provide long term archiving, permanent identifiers, or metadata, and package management systems, while somewhat better, similarly do not make a commitment to long term archiving, do not use identifiers that fit the scholarly publication system well, and provide metadata that may be missing key elements. The FAIR for research software (FAIR4RS, Chue Hong et al. 2021) working group has dedicated significant effort in building a community consensus around developing FAIR principles that are customized for research software, providing methods for researchers to understand and address these gaps.In this presentation we will highlight the importance of software for the FAIR landscape and why different (but related) FAIR principles are needed for software (vs those originally developed for data). Our goal here is to contribute to building an FDO landscape together, where we consider all different types of digital objects that are essential in today's research, and we are enthusiastic about contributing our expertise on research software in helping shape this landscape.

Bacterial adhesion to the surface of materials is the first step in biofilm formation, which will lead to conditions that may compromise the health status of patients. Recently, polydopamine (PDA) has been proposed as an antibacterial material. Therefore, the objective of the current work was to assess and compare the adhesion of Streptococcus mutans to the surface of poly(methyl methacrylate) (PMMA) discs that were modified using PDA following a biomimetic approach versus smooth PDA-coated PMMA surfaces. In addition, an assessment of the growth inhibition by PDA was performed. PMMA discs were manufactured and polished; soft lithography, using the topography from the Crocosmia aurea leaf, was used to modify their surface. PDA was used to smooth-coat PMMA discs by dip-coating. The growth inhibition was measured using an inhibition halo. The surfaces were characterized by means of atomic force microscopy (AFM), the contact angle (CA), and Fourier-transform infrared spectroscopy (FTIR). Polydopamine exhibited a significant antibacterial effect when used directly on the S. mutans planktonic cells, but such an effect was not as strong when modifying the PMMA surfaces. These results open the possibility of using polydopamine to reduce the adhesion and growth of S. mutans, which might have important consequences in the dental field.

Recent research has advanced two degree-of-freedom (DoF), simultaneous, independent and proportional control of hand-wrist prostheses using surface electromyogram signals from remnant muscles as the control input. We evaluated two such regression-based controllers, along with conventional, sequential two-site control with co-contraction mode switching (SeqCon), in box-block, refined-clothespin and door-knob tasks, on 10 able-bodied and 4 limb-absent subjects. Subjects operated a commercial hand and wrist using a socket bypass harness. One 2-DoF controller (DirCon) related the intuitive hand actions of open-close and pronation-supination to the associated prosthesis hand-wrist actions, respectively. The other (MapCon) mapped myoelectrically more distinct, but less intuitive, actions of wrist flexion-extension and ulnar-radial deviation. Each 2-DoF controller was calibrated from separate 90 s calibration contractions. SeqCon performed better statistically than MapCon in the predominantly 1-DoF box-block task (>20 blocks/minute vs. 8–18 blocks/minute, on average). In this task, SeqCon likely benefited from an ability to easily focus on 1-DoF and not inadvertently trigger co-contraction for mode switching. The remaining two tasks require 2-DoFs, and both 2-DoF controllers each performed better (factor of 2–4) than SeqCon. We also compared the use of 12 vs. 6 optimally-selected EMG electrodes as inputs, finding no statistical difference. Overall, we provide further evidence of the benefits of regression-based EMG prosthesis control of 2-DoFs in the hand-wrist.

Abstract Understanding the ecological consequences of supplemental feeding to both hummingbirds and the plants they pollinate is complicated by logistical challenges associated with assessing relative dietary resource use with commonly applied observational methods. Here, we describe the results of research conducted to assess the relative use of feeder and flower nectar by Broad‐tailed (Selasphorus platycercus) and Rufous hummingbirds (Selasphorus rufus) using two distinct methodological variations to measure the δ13C values of exhaled CO2. Because of the relatively quick time in which both species switch from exogenous to endogenous resources to fuel metabolism, our experiment allowed us to assess resource use at two timescales. Our results suggest variability in the relative contributions of the two dietary sources within and among species and timescales, with most birds employing a mixture of feeder and flower sugars as fuel sources. This diversity in relative resource use may mitigate potential negative effects of supplemental feeding on hummingbirds and their plant symbionts.

The value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the detection of prostate cancer is controversial. There are currently insufficient peer reviewed published data or expert consensus to support routine adoption of DCE-MRI for clinical use. Thus, the objective of this study was to explore the optimal temporal resolution and measurement length for DCE-MRI to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate by non-parametric MRI analysis and to compare with a quantitative MRI analysis. Predictors of interest were onset time, relative signal intensity (RSI), wash-in slope, peak enhancement, wash-out and wash-out slope determined from non-parametric characterisation of DCE-MRI intensity-time profiles. The discriminatory power was estimated from C-statistics based on cross validation. We analyzed 54 patients with 97 prostate tissue specimens (47 prostate cancer, 50 normal prostate tissue) of the peripheral zone, mean age 63.8 years, mean prostate-specific antigen 18.9 ng/mL and mean of 10.5 days between MRI and total prostatectomy. When comparing prostate cancer tissue with normal prostate tissue, median RSI was 422% vs 330%, and wash-in slope 0.870 vs 0.539. The peak enhancement of 67 vs 42 was higher with prostate cancer tissue, while wash-out (-30% vs -23%) and wash-out slope (-0.037 vs -0.029) were lower, and the onset time (32 seconds) was comparable. The optimal C-statistics was 0.743 for temporal resolution of 8.0 seconds and measurement length of 2.5 minutes compared with 0.656 derived from a quantitative MRI analysis. This study provides evidence that the use of a non-parametric approach instead of a more established parametric approach resulted in greater precision to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate.

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work.

Agri-environment schemes (AES) are expected to counteract the negative impacts of intensive agriculture on biodiversity. These schemes were specifically designed to target farmland biodiversity and included, for instance, ecological focus areas (EFAs). In Switzerland, in order to qualify for direct payments, farmers must manage 7% or more of their land as biodiversity promotion areas (BPAs). BPAs encompass extensively managed and low intensity hay meadows, fallows (wildflower strips), traditional orchards with high-stem trees and hedgerows. Evaluation of AES delivery for biodiversity is of crucial importance but must be performed across several years and considering the various components of species diversity to avoid incomplete or wrong conclusions. From a complex study design comprising 478 fields in three regions and sampling over 7 years with four sampling times, spider assemblages of BPA habitats were compared to corresponding conventionally managed fields. A battery of investigations was performed including alpha- and beta-diversity analysis, multivariate dispersion, indicator species and species specificity to understand what BPAs deliver for spiders in the habitat scale and farming landscape. Results showed that alpha-diversity (average number of species) was usually higher in BPA habitats than in conventionally managed fields but the species composition (beta-diversity) had more power to perceive AES impact. Furthermore, the various environmental conditions of BPAs in the farming landscape led to highly diverse spider assemblages (multivariate dispersion) emphasizing that not only the agricultural management plays a role in determining species diversity but the environmental heterogeneity. Indicator (and rare) species were mostly found in woody BPAs (hedges and high-stem tree orchards) revealing the high importance of these BPA habitats for spider conservation. At regional scale, BPA hedges contributed most to the regional diversity of spiders in grassland and mixed regions while BPA meadows and wildflower strip BPAs were first delivering in the region of arable crops. Recommendations highlight the role of the woody habitats and of the environmental heterogeneity in the farming landscape as well as of regional planning to make AES effective.

Anthropogenic activities continue to pose the greatest challenges to freshwater ecosystems. Therefore, long-term monitoring is essential for the management and conservation of these resources. Monitoring programs for freshwater bodies often use a range of indicators, including biological elements such as fish. Existing European standard provides a depth-stratified gillnet sampling approach mainly in benthic habitats and at the deepest part of lakes to account for the uneven distribution of fish. However, the commonly used CEN (European Committee for Standardization) protocol does not weight sufficiently habitat volumes and underrepresent pelagic habitats to calculate whole-lake catch and biomass per unit effort (CPUE and BPUE, respectively). Extended European standard gillnet (4 larger mesh-sizes added in the geometric series) catch data collected over 18 years (2004–2021) in Římov Reservoir (Czech Republic) were used for a method comparison on indices for relative abundance and biomass of fish: CEN protocol without volume-weighting and two volume-weighted approaches. We also evaluated changes in species composition and trends in these fish population over time. Results indicated interannual changes in species composition, relative abundance, and biomass of fish community. The CEN protocol tended to put greater emphasis on benthic habitats which generally have larger CPUE and BPUE. Consequently, the two volume-weighting approaches produced lower estimates of the two parameters, with the exception of the most dominant pelagic bleak Alburnus alburnus (L.). All approaches consistently showed an increasing trend in whole-reservoir fish abundance and a decreasing trend in biomass over the study period. Following our assessment, we put forward the volume-weighting approach that considers the Volume of the depth Stratum (VOST) for weighting as the most realistic approximation of fish populations and therefore recommend its use.

ObjectivePelvic magnetic resonance imaging (MRI) is a key exam used for the initial assessment of loco-regional involvement of cervical cancer. In patients with locally advanced cervical cancer, MRI is used to evaluate the early response to radiochemotherapy before image-guided brachytherapy, the prognostic impact of which we aimed to study.MethodsPatients with locally advanced cervical cancer treated using concomitant radiochemotherapy followed by closure treatment between January 2010 and December 2015 were included in this study. Clinical, anatomopathological, radiological, therapeutic, and follow-up data were evaluated.ResultsAfter applying the inclusion and exclusion criteria to the initially chosen 310 patients, 232 were included for evaluation (median follow-up period, 5.3 years). The median age was 50 years (range, 25–83 years), and the median tumor size was 47.5 mm (range, 0–105 mm). Based on the International Federation of Gynaecology and Obstetrics classification system, 9 patients were in stage IB2; 20, IB3; 2, IIA; 63, IIB; 4, IIIA; 7, IIIB; and 127, IIIC1 or higher. The re-evaluation MRI was performed at the median dose of 55.5 Gy, and median reduction in tumor size was 55.2% (range, −20–100%). There was a difference between the disease-free and overall survival rates of the patients with a tumor response greater or lesser than 50%. The risk of recurrence or death reduced by 39% in patients with a tumor size reduction >50%. The overall 5-year survival rate of patients with a response greater and lesser than 50% were 77.7% and 61.5%, respectively. The 5-year disease-free survival rate for these two groups of patients were 68.8% and 51.5%, respectively.ConclusionOur study confirms the prognostic impact of tumor size reduction using MRI data obtained after radiochemotherapy in patients with locally advanced cervical cancer.

BackgroundThe use of e-cigarettes is proliferating globally, especially among youth and even children. Marketing is a known risk factor for e-cigarette initiation, yet little is known of e-cigarette marketing on social media in low- and middle-income countries. This study compares e-cigarette social media marketing in India, Indonesia, and Mexico, three such countries with different regulatory environments.MethodsInstances of e-cigarette marketing on social media platforms were identified via the Tobacco Enforcement and Reporting Movement (TERM), a digital tobacco marketing monitoring system. Through systematic keyword-based searches, all tobacco marketing posts observed between 15 December 2021 and 16 March 2022 were included in the analysis. The final sample included 1,437 e-cigarette-related posts on Instagram, Facebook, Twitter, YouTube, and TikTok, which were systematically content analyzed by independent coders after inter-reliability (Cohen's Kappa K > 0.79) was established using a theory-derived codebook. The final data is represented in percentages and frequencies for ease of presentation.ResultsWe observed e-cigarette marketing online in all countries studied, yet there was variation in the volume of marketing and types of accounts identified. In India, where e-cigarettes were comprehensively banned, we identified 90 (6%) posts; in Mexico, where e-cigarettes were partially restricted, 318 (22%) posts were observed; and in Indonesia, where there were no restrictions, 1,029 (72%) posts were observed. In both India and Mexico, marketing originated from retailer accounts (100%), whereas in Indonesia, it was primarily product brand accounts (86%). Across countries, e-cigarettes were mostly marketed directly to sell products (India: 99%, Indonesia: 69% and Mexico: 93%), though the sales channels varied. Product features, including e-liquid flavors, device colors and technical specifications, was the most prominent message framing (India: 86%; Mexico: 73%; Indonesia: 58%). Harm reduction messaging was most popular in Mexico (8%) and was not common in Indonesia (0.3%) or India (0%).ConclusionOur study provides important insights for tobacco control stakeholders on the evolving nature of e-cigarette marketing in low- and middle-income countries. It underscores the presence of e-cigarette marketing, including in countries where comprehensive regulations exist, and suggests the importance of continuous monitoring to keep up with industry practices and strengthen tobacco control stakeholder efforts to counter them.

Se realizó un estudio para determinar el costo exergético de la producción de biocarbón a base de cuesco de palma de aceite mediante pirolisis lenta en un horno de experimental y uno piloto. Inicialmente se evaluaron flujos másicos, energéticos y exergéticos aplicando la metodología de escalamiento de Costo Exergético Específico (CEE), basada en el concepto recurso-producto. Se determinaron las eficiencias energéticas y exergéticas de los equipos y se calculó el costo exergético. El costo exergético de 1 kg de biocarbón es de 38990 $-kJ/kJ para el horno experimental y 206 $-kJ/kJ para el horno piloto. En conclusión, el costo exergético del biocarbón puede variar dependiendo de los equipos, las condiciones de operación y el lugar en donde se produzca. Se recomienda realizar el aprovechamiento del calor y de la energía que contienen los gases para optimizar los procesos.

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

Rainfall in the Caribbean is an important resource for numerous stakeholders in the region. Based on previous work, which identified several variables that could provide predictive skill of rainfall in the region, canonical correlation analysis is applied to assess forecast skill for station-averaged sub-regional frequency and intensity of the Early-Rainy Season (ERS) and Late-Rainy Season (LRS) wet days, and magnitude of the Mid-Summer Drought (MSD). Predictor fields are explored from the ERA-Interim and North American Multi-Model Ensemble (NMME). The use of sea-level pressure (SLP), 850 hPa zonal winds (u850), vertically integrated zonal (UQ), and meridional (VQ) moisture fluxes show comparable, if not better, forecast skill than sea-surface temperatures (SSTs), which is generally the commonly-used predictor in a given region’s seasonal climate forecasts. Generally, the highest predictive skill is found for the frequency of wet days. Rainfall characteristics in the Central and Eastern Caribbean have significant predictive skill. Forecast skill of rainfall characteristics in the Northwestern and Western Caribbean are lower and less consistent. The sub-regional differences and consistently significant skill across lead times up to at least two months can be attributed to persistent SST/SLP anomalies during the ERS that resemble the North Atlantic Oscillation, and that resembles the summer-time onset of the El Niño-Southern Oscillation during the LRS. The anomalous spatial patterns during the MSD bear resemblance to both the ERS and LRS signals. The results provide additional variables that can be used to forecast rainfall characteristics in the Caribbean and a way to tailor seasonal forecasts for each sub-region.

IntroductionSevere acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization–triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Abstract Background Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT. Methods Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS. Results Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E−14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E−08). This association was not observed in low TMB patients. Conclusions We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.

Background and purpose: Prostate radiotherapy relies on the delivery of high doses that can be obstructed when a small bowel loop descends in the pelvis. We present a laparoscopic minimally invasive prosthetic-free technique closing the Douglas’ pouch with a peritoneal running suture to cordon off the bowel from the pelvis and hence allow optimal irradiation. Materials and methods: Prostate cancer patients referred for radiotherapy and whose planning-CT revealed a bowel loop trapped in the pelvis were proposed the procedure, followed by a new planning-CT. This proof-of-concept study reports postoperative follow-up and dosimetric benefits. Results: The procedure was performed in ten patients (2016–2020) as a same-day surgery for nine. Median operative time was 34 min (range 22–50) and no relevant intraoperative complication occurred. The third patient of the series presented a small bowel hernia through the peritoneal suture at the 15th postoperative day requiring a laparotomic desincarceration without major consequences. Regarding the small bowel, median D1cc (dose to 1 cc) was 65.5 Gy and 55.5 Gy (p = 0.005) before and after procedure. Median V60 (volume receiving ≥60 Gy) was 10.2 cc and 0.0 cc (p = 0.005). In the immediate vicinity of the small bowel (5 mm), median D1cc was 68.3 Gy and 57.7 Gy (p = 0.005). Radiotherapy was safely delivered to all patients. Conclusion: Laparoscopic closure of the Douglas’ pouch by a peritoneal suture is an efficient technique to cordon off inconvenient ectopic small bowel loops. It prevents excessive bowel irradiation and hence facilitates curative prostate radiotherapy. The technique could be applied to other pelvic malignancies.

Small molecules stabilising a distorted TNF trimer can inhibit TNF signaling, but the underlying mechanism is unclear. Here, the authors characterize the inhibitor-bound TNF-receptor complex structurally and biochemically, showing that the inhibitors alter TNF-receptor binding stoichiometry and cluster formation.

The Research Software Encyclopedia is a community driven, open source strategy to define the term “research software” in different contexts. It consists of several elements: a base library to manage a database of software, criteria and taxonomy items that can be used to answer questions about the software in the database, and several ways for an interested party to interact. A community database is stored in version control (GitHub), and by way of providing and updating this database, the Research Software Encyclopedia takes a strategy of small contributions over time to grow a valuable resource. Using a community-driven open source approach offers a number of advantages over attempting to derive a single, holistic definition for research software. First, it takes into account the context under which the definition is considered. Second, community and scoped contributions to specific components of the task are easy. Third, it provides a resource that can be extended to other use cases. Finally, this initiative creates a solution that requires no grants or other funding to maintain, increasing its ability to grow, adapt, and evolve over time.

It was widely assumed in the West following the collapse of European socialism that China would undergo a similar process of counter-revolution. This article seeks to understand why, three decades later, this hasn't happened, and whether it is likely to happen in the foreseeable future. The article contrasts China's “reform and opening up” process, pursued since 1978, with the “perestroika” and “glasnost” policies taken up in the Soviet Union under the Gorbachev leadership. A close analysis of the available data makes it clear that China's reform has been far more successful than the Soviet reform; that, in contrast to the Soviet Union in the 1980s, all the key quality of life indicators in China have undergone significant improvement in the last 40 years, and China is emerging as a global leader in science, technological innovation and environmental preservation. The article argues that the disparate outcomes in China and the Soviet Union are the result primarily of the far more effective economic strategy pursued by the Chinese government, along with the continued strengthening of the Communist Party of China's leadership.

Abstract Cardiovascular diseases are associated to risk factors as obesity, hypertension and diabetes. The transforming growth factor-β1 receptors ALK1 and endoglin regulate blood pressure and vascular homeostasis. However, no studies relate the association of ALK1 and endoglin polymorphisms with cardiovascular risk factors. We analysed the predictive value of the ALK1 and endoglin polymorphisms on cardiovascular target organ damage in hypertensive and diabetic patients in 379 subjects with or without hypertension and diabetes in a Primary Care setting. The ALK1 rs2071219 polymorphism (AA genotype) is associated with a lower presence of diabetic retinopathy and with the absence of altered basal glycaemia. Being carrier of the ALK1 rs3847859 polymorphism (G allele) is associated with lower basal heart rate and with higher LDL-cholesterol levels. The endoglin rs3739817 polymorphism (AA genotype) is associated with higher levels of LDL-cholesterol, and being carrier of the endoglin rs10987759 polymorphism (C allele) is associated with higher haemoglobin levels and with an increased heart rate. Summarizing, several ALK1 and endoglin gene polymorphisms increase the risk of cardiovascular events. The analysis of these polymorphisms in populations at risk, in combination with the determination of other parameters and biomarkers, could implement the diagnosis and prognosis of susceptibility to cardiovascular damage.

Abstract Background High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability normally preclude processing samples across multiple technologies, making it challenging to directly evaluate performance and whether data from different platforms can be reliably compared or integrated. Methods This study describes our experiences of nine new and established mRNA profiling techniques including Lexogen QuantSeq, Qiagen QiaSeq, BioSpyder TempO-Seq, Ion AmpliSeq, Nanostring, Affymetrix Clariom S or U133A, Illumina BeadChip and RNA-seq of formalin-fixed paraffin embedded (FFPE) and fresh frozen (FF) sequential patient-matched breast tumour samples. Results The number of genes represented and reliability varied between the platforms, but overall all methods provided data which were largely comparable. Crucially we found that it is possible to integrate data for combined analyses across FFPE/FF and platforms using established batch correction methods as required to increase cohort sizes. However, some platforms appear to be better suited to FFPE samples, particularly archival material. Conclusions Overall, we illustrate that technology selection is a balance between required resolution, sample quality, availability and cost.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.