Unravelling glioblastoma heterogeneity by means of single-cell RNA sequencing.

Glioblastoma (GBM) is the most invasive and deadliest brain cancer in adults. Its inherent heterogeneity has been designated as the main cause of treatment failure. Thus, a deeper understanding of the diversity that shapes GBM pathobiology is of utmost importance. Single-cell RNA sequencing (scRNA-seq) technologies have begun to uncover the hidden composition of complex tumor ecosystems. Herein, a semi-systematic search of reference literature databases provided all existing publications using scRNA-seq for the investigation of human GBM. We compared and discussed findings from these works to build a more robust and unified knowledge base. All aspects ranging from inter-patient heterogeneity to intra-tumoral organization, cancer stem cell diversity, clonal mosaicism, and the tumor microenvironment (TME) are comprehensively covered in this report. Tumor composition not only differs across patients but also involves a great extent of heterogeneity within itself. Spatial and cellular heterogeneity can reveal tumor evolution dynamics. In addition, the discovery of distinct cell phenotypes might lead to the development of targeted treatment approaches. In conclusion, scRNA-seq expands our knowledge of GBM heterogeneity and helps to unravel putative therapeutic targets.post-print4967 K

Medical and Surgical Treatment for Overactive Bladder

In this chapter, we focus on the medical treatment of overactive bladder (OAB) syndrome. The treatment of choice of the OAB syndrome is still the anticholinergic therapy, although we must consider β3‐agonists with almost the same evidence. No drug has been shown to be clearly superior to the rest. The use of oxybutynin transdermal should be considered when the side effects due to the oral administration are intolerable. In elderly patients, first efforts should be directed to use non‐drug therapies, such as behavioural therapy. In patients suffering from cognitive dysfunctions, the use of antimuscarinic with caution is recommended. Mirabegron, a β3‐agonist, can be offered, although it should be noted that the long‐term effects are still unknown. The logical second‐line treatment is the intravesical injection of botulinum toxin A, considering its temporary effectiveness and the possibility of retention. In some centres, sacral nerve stimulation may be an option. Surgical treatment should be reserved when conservative therapies fail

Application of pelvic floor ultrasound during pregnancy to detect patients at risk of cesarean section due to failure of labor progression in a Spanish population.

Objective: Our study is aimed at evaluating the characteristics of the pelvic floor, assessed through transperineal ultrasound, since it may influence or increase the possibility of having a cesarean delivery, with the objective of acting on those variables that can be modified during pregnancy. Study Design: Transperineal ultrasound was performed on 109 primiparous pregnant women in their first trimester of pregnancy, recruited between May 2018 and February 2019, with the purpose of studying the hiatus area at rest, retention and Valsalva. We have reassessed them at the end of pregnancy and delivery data were recorded. We selected 8 patients as case-study, who had cesarean section delivery due to failure of labor progression. We selected 4 control-cases for each, reaching the total of 32 controls, with similar age and body mass index, to avoid obtaining a biased result from these data. Results: In the study of hiatal areas, patients who delivered by cesarean section had a smaller hiatal area at rest, during levator ani muscle contraction and during Valsalva maneuver, at all visits. In early pregnancy, the range of the resting hiatal area was 13.8 ± 2.0 cm2 for cesarean sections, compared to 16.2 ± 2.7 cm2 for vaginal deliveries with an OR of 0.57 (0.34–0.95, 95% CI). For hiatal area on Valsalva, the OR was 0.55 (0.35–0.88, 95% CI). Therefore, the smaller the hiatal area, the greater the possibility of cesarean section. At the end of pregnancy, between 34 and 36 weeks of gestation, the OR of hiatal area on Valsalva was 0.78 (0.60–1.00, 95% CI). Conclusion: The hiatus area measured by transperineal ultrasonography at the beginning and at the end of the pregnancy may be useful to identify the patients who are at a higher risk of cesarean delivery due to failure of labor progression.post-print798 K

Material properties of evolutionary diverse spider silks described by variation in a single structural parameter

Spider major ampullate gland silks (MAS) vary greatly in material properties among species but, this variation is shown here to be confined to evolutionary shifts along a single universal performance trajectory. This reveals an underlying design principle that is maintained across large changes in both spider ecology and silk chemistry. Persistence of this design principle becomes apparent after the material properties are defined relative to the true alignment parameter, which describes the orientation and stretching of the protein chains in the silk fiber. Our results show that the mechanical behavior of all Entelegynae major ampullate silk fibers, under any conditions, are described by this single parameter that connects the sequential action of three deformation micromechanisms during stretching: stressing of protein-protein hydrogen bonds, rotation of the ?-nanocrystals and growth of the ordered fraction. Conservation of these traits for over 230 million years is an indication of the optimal design of the material and gives valuable clues for the production of biomimetic counterparts based on major ampullate spider silk

Kinetics of anti-SARS-CoV-2 antibodies over time. Results of 10 month follow up in over 300 seropositive Health Care Workers.

Background The kinetics of the antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated since long-term duration of antibody remains largely unknown, particularly in infected healthcare workers (HCW). Methods Prospective study, evaluating the longitudinal profile of anti-SARS-CoV-2 antibody titers in a random sample of 331 seropositive healthcare workers (HCW) of Spanish Hospitals Group. Serial measurements of serum IgG-anti-SARS-CoV-2 were obtained at baseline (April-May,2020), and in 2 follow-up visits. Linear mixed models were used to investigate antibody kinetics and associated factors. Results A total of 306 seropositive subjects (median age: 44.7years;69.9% female) were included in the final analysis. After a median follow-up of 274 days between baseline and final measurement, 235(76.8%) maintained seropositivity. Antibody titers decreased in 82.0%, while remained stable in 13.1%. Factors associated with stability of antibodies over time included age≥45 years, higher baseline titers, severe/moderate infection and high-grade exposure to COVID-19 patients. In declining profile, estimated mean antibody half-life was 146.3 days(95%CI:138.6–154.9) from baseline. Multivariate models show independent longer durability of antibodies in HCW with high-risk exposure to COVID-19 patients (+14.1 days;95%CI:0.6–40.2) and with symptomatic COVID-19 (+14.1 days;95%CI:0.9–43.0). The estimated mean time to loss antibodies was 375(95% CI:342–408) days from baseline. Conclusions We present the first study measuring the kinetics of antibody response against SARS-CoV-2 in HCW beyond 6 months. Most participants remained seropositive after 9 months but presented a significant decline in antibody-titers. Two distinct antibody dynamic profiles were observed (declining vs. stable). Independent factors associated with longer durability of antibodies were symptomatic infection and higher exposure to COVID-19 patients.post-print1262 K

Emergence of supercontraction in regenerated silkworm (Bombyx mori) silk fibers

The conditions required for the emergence of supercontraction in regenerated silkworm (Bombyx mori) silk fibers are assessed through an experimental approach that combines the spinning of regenerated fibers with controlled properties and their characterization by 13 C solid-state nuclear magnetic resonance (NMR). Both supercontracting and non-supercontracting regenerated fibers are produced using the straining flow spinning (SFS) technique from 13 C labeled cocoons. The short-range microstructure of the fibers is assessed through 13 C CP/MAS in air and 13 C DD/MAS in water, and the main microstructural features are identified and quantified. The mechanical properties of the regenerated fibers and their microstructures are compared with those of natural silkworm silk. The combined analysis highlights two possible key elements as responsible for the emergence of supercontraction: (1) the existence of an upper and a lower limit of the amorphous phase compatible with supercontraction, and (2) the existence of two ordered phases, ß-sheet A and B, which correspond to different packing arrangements of the protein chains

Emergence of supercontraction in regenerated silkworm (Bombyx mori) silk fibers

The conditions required for the emergence of supercontraction in regenerated silkworm (Bombyx mori) silk fibers are assessed through an experimental approach that combines the spinning of regenerated fibers with controlled properties and their characterization by 13C solid-state nuclear magnetic resonance (NMR). Both supercontracting and non-supercontracting regenerated fibers are produced using the straining flow spinning (SFS) technique from 13C labeled cocoons. The short-range microstructure of the fibers is assessed through 13C CP/MAS in air and 13C DD/MAS in water, and the main microstructural features are identified and quantified. The mechanical properties of the regenerated fibers and their microstructures are compared with those of natural silkworm silk. The combined analysis highlights two possible key elements as responsible for the emergence of supercontraction: (1) the existence of an upper and a lower limit of the amorphous phase compatible with supercontraction, and (2) the existence of two ordered phases, β-sheet A and B, which correspond to different packing arrangements of the protein chains.Ministerio de Economía y Competitividad MAT2016-75544- C2-1-RMinisterio de Economía y Competitividad MAT2016-79832-RMinisterio de Economía y Competitividad DPI2016-78887-C3-1-RConsejería de Educación Comunidad de Madrid NEUROCENTRO-B2017/BMD-3760Ministerio de Educación, Ciencia y Cultura JP26248050Ministerio de Economía y Competitividad DPI2016-78887-C3-1-

Hemogram as marker of in-hospital mortality in COVID-19.

The clinical impact of COVID-19 disease calls for the identification of routine variables to identify patients at increased risk of death. Current understanding of moderate-to-severe COVID-19 pathophysiology points toward an underlying cytokine release driving a hyperinflammatory and procoagulant state. In this scenario, white blood cells and platelets play a direct role as effectors of such inflammation and thrombotic response. We investigate whether hemogram-derived ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and the systemic immune-inflammation index may help to identify patients at risk of fatal outcomes. Activated platelets and neutrophils may be playing a decisive role during the thromboinflammatory phase of COVID-19 so, in addition, we introduce and validate a novel marker, the neutrophil-to-platelet ratio (NPR). Two thousand and eighty-eight hospitalized patients with COVID-19 admitted at any of the hospitals of HM Hospitales group in Spain, from March 1 to June 10, 2020, were categorized according to the primary outcome of in-hospital death. Baseline values, as well as the rate of increase of the four ratios analyzed were significantly higher at hospital admission in patients who died than in those who were discharged (p<0.0001). In multivariable logistic regression models, NLR (OR 1.05; 95% CI 1.02 to 1.08, p=0.00035) and NPR (OR 1.23; 95% CI 1.12 to 1.36, p<0.0001) were significantly and independently associated with in-hospital mortality. According to our results, hemogram-derived ratios obtained at hospital admission, as well as the rate of change during hospitalization, may easily detect, primarily using NLR and the novel NPR, patients with COVID-19 at high risk of in-hospital mortality.pre-print300 K

Persistence and variation in microstructural design during the evolution of spider silk

The extraordinary mechanical performance of spider dragline silk is explained by its highly ordered microstructure and results from the sequences of its constituent proteins. This optimized microstructural organization simultaneously achieves high tensile strength and strain at breaking by taking advantage of weak molecular interactions. However, elucidating how the original design evolved over the 400 million year history of spider silk, and identifying the basic relationships between microstructural details and performance have proven difficult tasks. Here we show that the analysis of maximum supercontracted single spider silk fibers using X ray diffraction shows a complex picture of silk evolution where some key microstructural features are conserved phylogenetically while others show substantial variation even among closely related species. This new understanding helps elucidate which microstructural features need to be copied in order to produce the next generation of biomimetic silk fibers

Straining Flow Spinning of Artificial Silk Fibers: A Review

This work summarizes the main principles and some of the most significant results of straining flow spinning (SFS), a technology developed originally by the authors of this work. The principles on which the technology is based, inspired by the natural spinning system of silkworms and spiders, are presented, as well as some of the main achievements of the technique. Among these achievements, spinning under environmentally friendly conditions, obtaining high-performance fibers, and imparting the fibers with emerging properties such as supercontraction are discussed. Consequently, SFS appears as an efficient process that may represent one of the first realizations of a biomimetic technology with a significant impact at the production level.Ministerio de Economía y Competitividad MAT2016-75544-C2-1-RMinisterio de Economía y Competitividad MAT2016-79832-RMinisterio de Economía y Competitividad CPI2016-78887-C3-1-RComunidad de Madrid NEUROCENTRO-B2017Comunidad de Madrid BMD-376