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If human action cannot be understood separately from subjectivity, as the phenomenological tradition has shown, with this article I seek to explore the relationship between subjectivity and community, in what can be taken as an intersubjective consciousness constituted by the phenomenological totality of a particular way of being human -an anthropical image-. Thus, if such consciousness is intersubjective, it is precisely because it implies the same way of being and acting in others. This way of being and acting is the expression of a certain power, not only that of persisting in the actualisation of this anthropical image, but also that of incarnating it in progressive degrees of perfection. This power, therefore, although it is to a greater degree in those subjects who incarnate it more perfectly, whom we can call elites, it is also to an essential degree in the other co-subjects. Acting in a certain way implies a meaning and an interest, both of which are particularly vested in the community’s elites.

La presente investigación tuvo como objetivo de estudio el desarrollo de una propuesta de marketing relacional enfocada en la fidelización de los clientes. Para efectos de estudio la metodología usada es de enfoque cualitativo descriptivo simple ya que admitió obtener, evaluar e interpretar información que se recolectó, al igual que posibilitó describir las situaciones de cómo se manifiesta el fenómeno de estudio. Para esta investigación se utilizó el software Excel para la determinación de comprobación de las hipótesis y la realización de gráficos. El instrumento que se aplicó fue el cuestionario, que permitió recolectar los datos de manera más económica y flexible, teniendo los resultados más precisos sobre la situación actual de la empresa, así como también el servicio que brinda y la factibilidad para la elaboración de estrategias de marketing relacional. Se llegó a la conclusión en base a un análisis cualitativo de la fidelidad y la interacción de los clientes, que es fundamental el establecer una interacción más biunívoca con el cliente ya que de esta manera se logra mantener un contacto permanente con él, con el fin de generar relaciones rentables y a largo plazo. Además, se determinó que los clientes buscan un servicio con atención personalizada, de calidad e incentivos que los motiven a realizar compras de forma periódica y permanente.

Supercapacitors are fast-charging energy storage devices of great importance for the development of robust and climate-friendly energy infrastructures for the future. Research in this field has seen rapid growth in recent years, hence consistent reporting practices must be implemented to enable reliable comparison of device performance. Although several studies have highlighted the best practices for analysing and reporting data from such energy storage devices, there is yet to be an empirical study that investigates whether researchers in the field are correctly implementing these recommendations, and which assesses the variation in reporting between different laboratories. Here, we address this deficit by carrying out the first interlaboratory study of the analysis of supercapacitor electrochemistry data. We find that the use of incorrect formulae and researchers having different interpretations of key terminologies are the primary causes of variability in data reporting. Furthermore, we highlight the more significant variation in reported results for electrochemical profiles showing non-ideal capacitive behaviour. From the insights gained through this study, we make additional recommendations to the community to help ensure consistent reporting of performance metrics moving forward.

BACKGROUND & AIMS: Constitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair variants. Constitutional microsatellite instability (cMSI) is a CMMRD diagnostic hallmark and may associate with cancer risk. We quantified cMSI in a large CMMRD patient cohort to explore genotype-phenotype correlations using novel MSI markers selected for instability in blood.METHODS: Three CMMRD, 1 Lynch syndrome, and 2 control blood samples were genome sequenced to >120× depth. A pilot cohort of 8 CMMRD and 38 control blood samples and a blinded cohort of 56 CMMRD, 8 suspected CMMRD, 40 Lynch syndrome, and 43 control blood samples were amplicon sequenced to 5000× depth. Sample cMSI score was calculated using a published method comparing microsatellite reference allele frequencies with 80 controls.RESULTS: Thirty-two mononucleotide repeats were selected from blood genome and pilot amplicon sequencing data. cMSI scoring using these MSI markers achieved 100% sensitivity (95% CI, 93.6%-100.0%) and specificity (95% CI 97.9%-100.0%), was reproducible, and was superior to an established tumor MSI marker panel. Lower cMSI scores were found in patients with CMMRD with MSH6 deficiency and patients with at least 1 mismatch repair missense variant, and patients with biallelic truncating/copy number variants had higher scores. cMSI score did not correlate with age at first tumor.CONCLUSIONS: We present an inexpensive and scalable cMSI assay that enhances CMMRD detection relative to existing methods. cMSI score is associated with mismatch repair genotype but not phenotype, suggesting it is not a useful predictor of cancer risk.

This article provides a renovation of Ernesto Laclau’s theories of political competition and collective identity-building for their better application at an empirical level. It does so not as a critique but as a way to make the Laclauian approach more operational and rigorous from a methodological perspective. The key goal is to make available a form of discourse analysis that centers on the political sphere and has two key characteristics. The first is an emphasis on the role of what Antonio Gramsci called “organic ideologies” in political identity-building. The second is the differentiation between a descriptive and a subjective level of analysis. The article intends to initiate a debate on the prospects of the Laclauian approach both with its advocates and its detractors.

Congenital transmission ofTrypanosoma cruzi, the causative agent of Chagas disease, is an important source of new infections worldwide. The mechanisms of congenital transmission remain poorly understood, but there is evidence that parasite factors could play a role.Investigating changes in parasite strain diversity during transmission could provide insight into the parasite factors that influence the process. Here we use deep amplicon sequencing of a single copy gene in theT. cruzigenome to evaluate the diversity of infection in a collection of clinical blood samples from Chagas positive mothers and their infected infants. We found several infants and mothers infected with more than two parasite haplotypes, indicating infection with multiple parasite strains. Two haplotypes were detected exclusively in infant samples, while one haplotype was never found in infants, suggesting a relationship between the probability of transmission and parasite genotype. Finally, we found an increase in parasite population diversity in children after birth compared to their mothers, suggesting that there is no transmission bottleneck during congenital infection and that multiple parasites breach the placenta in the course of congenital transmission.

Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1 , encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias. Functional studies demonstrated lack of full-length protein and deficient SAC response, resulting in ~30 to 40% of aneuploid blood cells. Single-cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFκB signaling both in aneuploid and euploid cells, suggesting a non–cell autonomous response. MAD1L1 mutations resulted in specific clonal expansions of γδ T cells with chromosome 18 gains and enhanced cytotoxic profile as well as intermediate B cells with chromosome 12 gains and transcriptomic signatures characteristic of leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy with systemic inflammation and unprecedented tumor susceptibility.

Aneuploidy is a frequent feature of human tumors. Germline mutations leading to aneuploidy are very rare in humans, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, the gene encoding the Spindle Assembly Checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias, including five malignant tumors. Functional studies in peripheral blood cells demonstrated lack of full-length protein and deficient SAC response, resulting in ∼30-40% of aneuploid cells as detected by cytogenetic and single-cell (sc) DNA analysis. scRNA-seq analysis of patient blood cells identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFkB signaling. The inference of chromosomal aberrations from scRNA-seq analysis detected inflammatory signals both in aneuploid and euploid cells, suggesting a non-cell autonomous response to aneuploidy. In addition to random aneuploidies, MAD1L1 mutations resulted in specific clonal expansions of γδ T-cells with chromosome 18 gains and enhanced cytotoxic profile, as well as intermediate B-cells with chromosome 12 gains and transcriptomic signatures characteristic of chronic lymphocytic leukemia cells. These data point to MAD1L1 mutations as the cause of a new aneuploidy syndrome with systemic inflammation and unprecedented tumor susceptibility.

With this article, I seek to examine Krause’s analysis of the self in Analitische Philosophie, and in particular in Vorlesungen über die Psychische Anthropologie (1836/1848). But I do so through the texts that the Spanish Krausists devoted either to translating or to discussing and disseminating Krause’s ideas in dialogue with the philosophies of the time. In my exposition and examination of the doctrine of the self, I focus on its embedding in a particular existence through embodiment, and argue that these are aspects with which Krausism can still illuminate the debate about human subjectivity.

The purpose of this article is to analyse critically the idea of ethnopluralism (also known as ethno-differentialism and droit a la difference) as formulated by Alain de Benoist, one of the foundin...

Mutational signatures are imprints of pathophysiological processes arising through tumorigenesis. We generated isogenic CRISPR-Cas9 knockouts (Δ) of 43 genes in human induced pluripotent stem cells, cultured them in the absence of added DNA damage, and performed whole-genome sequencing of 173 subclones. ΔOGG1, ΔUNG, ΔEXO1, ΔRNF168, ΔMLH1, ΔMSH2, ΔMSH6, ΔPMS1, and ΔPMS2 produced marked mutational signatures indicative of being critical mitigators of endogenous DNA modifications. Detailed analyses revealed mutational mechanistic insights, including how 8-oxo-dG elimination is sequence-context-specific while uracil clearance is sequence-context-independent. Mismatch repair (MMR) deficiency signatures are engendered by oxidative damage (C>A transversions), differential misincorporation by replicative polymerases (T>C and C>T transitions), and we propose a ‘reverse template slippage’ model for T>A transversions. ΔMLH1, ΔMSH6, and ΔMSH2 signatures were similar to each other but distinct from ΔPMS2. Finally, we developed a classifier, MMRDetect, where application to 7,695 WGS cancers showed enhanced detection of MMR-deficient tumors, with implications for responsiveness to immunotherapies.

Background - SCLC is the most aggressive lung cancer type and with the worst prognosis. There are four molecular subtypes based on the high expression of distinct transcription factors and with different therapeutic vulnerabilities. However, all share transcriptional addiction as pathogenic mechanism. Lurbinectedin is a novel oncogenic transcription inhibitor, approved in the United States and other countries for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The aim of this study was to analyze the activity of lurbinectedin in the different SCLC molecular subtypes and to investigate new biomarkers of response. Methods and Results - We have characterized a panel of 20 SCLC human cell lines based on the expression of ASCL1, NEUROD1, YAP1 and POU2F3, where lurbinectedin yielded a mean IC50 value of 6.52 nM, which is considerable greater than the activity exerted by topotecan, irinotecan, carboplatin, etoposide, olaparib, alisertib and navitoclax (IC50 100 µM-100 nM). Lurbinectedin potency is high in the four molecular subtypes, with IC50 values of 4.1, 14.9, 7.2, and 0.2 nM for SCLC-A, -N, -I and -P, respectively. However, high expression of POU2F3 correlated with better responses. In fact, mean IC50 was 0.28 nM for POU2F3high cells versus 12.1 nM for all POU2F3low cells (p=0.0443). Additionally, basal SLFN11 levels were evaluated, observing that SLFN11high cells responded better to lurbinectedin, with IC50 values of 1.1 nM versus 11.8 nM for SLFN11low (p=0.05). Likewise, lurbinectedin treatment induced greater antitumor activity in SLFN11high tumor-bearing mice (H526: T/C, 18% on day 11) than in SLFN11low tumor-bearing mice (H82: T/C, 65% on day 7) after intravenous treatment at 0.18 mg/kg (on days 0, 7 and 14). Finally, SLFN11 expression was evaluated by IHC in FFPE tumor samples from SCLC patients participating in a multicenter phase II clinical trial in advanced solid tumors (NCT02454972), which allowed lurbinectedin accelerated approval in this indication by FDA. Patients with higher expression of SLFN11 had a slightly better overall survival (OS at 6 months: 68.4% ( Conclusions - Lurbinectedin is highly effective in all molecular subtypes of SCLC in vitro and in vivo, with IC50 values at least two logs more potent than for other antitumoral agents and its activity is even greater in tumors with high POU2F3 expression and/or high SLFN11 expression. Citation Format: Marta Martínez Diez, Gema Santamaría Nuñez, María José Guillén, Daniel Rueda, Eva Maria Garrido-Martin, Pablo Avilés, Carmen Cuevas. Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SLFN11 are biomarkers for a better response. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6247.

Copy neutral loss of heterozygosity (cnLOH) is a common event in several human malignancies—positing this as a mechanism of carcinogenesis. However, the role of cnLOH in synchronous colorectal cancer (SCRC), a unique CRC subtype, is not well understood. The aim of this study was to establish a cnLOH profile of SCRC using a single-nucleotide polymorphism array (SNP-A), and to explore associations between cnLOH and the genomic landscape of frequently mutated genes in SCRC. Among 74 paired SCRC cases, the most frequently altered regions were 16p11.2–p11.1 (59.5%) and 11p11.2–p11.12 (28.4%). Notably, the 6q11.21–q11.22 region altered by cnLOH was uniquely associated with polyclonal SCRCs (p = 0.038). Together, our analysis suggests that inactivation of tumor suppressor genes and cnLOH are rare events among SCRC cases. This study defines distinct patterns of cnLOH in SCRC, and provides initial evidence of a role for cnLOH in SCRC etiology., This work was funded by Projects PI16/01650 to JP, and PI16/01920 to RG-S, from the Spanish Ministry of Health and Consumer Affairs and FEDER, by Project 2012-0036 from the Mutua Madrileña Foundation. ANH was supported by the National Institutes of Health K12 HD043483 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The political-strategic approach is one of the most employed frameworks within the methodologically heterogeneous subfield of populism studies. In the last two decades, it has contributed to the analysis of populism both in Latin America and the United States and, more recently, in Western and Eastern Europe. That being said, a close inspection of its axioms and its conceptualization of the phenomenon shows that it is built on ill-conceived premises. This article intends to be a comprehensive critique of the approach that can contribute to the methodological progress of the field. It criticizes the three main dysfunctions of the approach: selective rationalism, leader-centrism, and normative bias.

Simple Summary Few metastatic urothelial cancer patients achieve durable clinical benefit with vinflunine. Predictive biomarkers to help to identify better treatment strategies are extremely needed. The objective of this study was to identify molecular differences between extreme responders to vinflunine in urothelial cancer. Genomic and immune markers are potentially useful identifying patients that may achieve greater benefit with vinflunine. Abstract Background and Aims: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing. In this study, we aimed to identify potential genomic biomarkers of vinflunine response in mUC patient samples and potential management alternatives. Methods: Formalin-fixed paraffin-embedded samples of mUC patients (n = 23) from three university hospitals in Spain were used for genomic targeted-sequencing and transcriptome (using the Immune Profile panel by NanoString) analyses. Patients who received vinflunine after platinum-based chemotherapy failure were classified in non-responders (NR: progressive disease ≤ 3 months; n= 11) or responders (R: response ≥ 6 months; n = 12). Results: Genomic characterization revealed that the most common alteration, TP53 mutations, had comparable frequency in R (6/12; 50%) and NR (4/11; 36%). Non-synonymous mutations in KTM2C (4/12; 33.3%), PIK3CA (3/12; 25%) and ARID2 (3/12; 25%) were predominantly associated with response. No significant difference was observed in tumour mutational burden (TMB) between R and NR patients. The NR tumours showed increased expression of diverse immune-related genes and pathways, including various interferon gamma-related genes. We also identified increased MAGEA4 expression as a potential biomarker of non-responding tumours to vinflunine treatment. Conclusions: Our data may help to identify potential genomic biomarkers of response to vinflunine. Moreover, tumours refractory to vinflunine showed immune signatures potentially associated with response to ICB. Extensive validation studies, including longitudinal series, are needed to corroborate these findings.

Hydrogen, generated from water splitting, is postulated as one of the most promising alternatives to fossil fuels. In this context, direct hydrogen generation by electrolysis and fixation to graphene oxide in an aqueous suspension could overcome storage and distribution problems of gaseous hydrogen. This study presents time-resolved determination of the electrochemical hydrogenation of GO by in-situ Raman spectroscopy, simultaneous to original functional groups elimination. Hydrogenation is found favoured by dynamic modulation of the electrochemical environment compared to fixed applied potentials, with a 160% increase of C–H bond formation. Epoxide groups suppression and generated hydroxide groups point at these epoxide groups being one of the key sites where hydrogenation was possible. FTIR revealed characteristic symmetric and asymmetric stretching vibrations of C–H bonds in CH2 and CH3 groups. This shows that hydrogenation is significantly also occurring in defective sites and edges of the graphene basal plane, rather than H-Csp3 groups as graphane. We also determined a −0.05 VRHE reduction starting potential in alkaline electrolytes and a 150 mV cathodic delay in acid electrolytes. The identified key parameters role, together with observed diverse C-Hx groups formation, points at future research directions for large-scale hydrogen storage in graphene., ICFO and IREC acknowledge financial support from LESGO project (Code: 952068. H2020-EU.1.2.2. funded), BIST Master Program and Severo Ochoa Program. This work was partially funded by CEX2019-000910-S (MCIN/AEI/10.13039/501100011033), Fundació Cellex, Fundació Mir-Puig, and Generalitat de Catalunya through CERCA. ICN2 acknowledge support from Severo Ochoa program, the Spanish Research Agency (AEI, grant no. SEV-2017-0706) and the CERCA Programme/Generalitat de Catalunya. E.C.-A., P.X. and C.M.S.T acknowledge support from Spanish MICINN project SIP (PGC2018-101743-B-I00). P.X. acknowledges support by Ph.D. fellowship from the EU Marie Sklodowska-Curie COFUND PREBIST (Grant Agreement 754558). C.R. acknowledges support from the MCIN/AEI (FJC2020-043223-I) and the Severo Ochoa Excellence Post-doctoral Fellowship (CEX2019-000910-S).

Krausists followed a dialectical method in all their activities. It is an action plan in which theory and practice are established on a continuum. Since it summarizes all human activity, this dialectic implies a philosophy of action. The originality of this article lies precisely in offering an account of the philosophy of action implicit in the work of Krause, which has never before been made explicit. Therefore, the goal of this article is, on the one hand, to isolate this dialectic in the texts of the Spanish Krausists, and, on the other hand, to demonstrate the traditional affirmation about the practical meaning of Krause’s philosophy, as shown in its Spanish version. This practical orientation of his thought was channelled through several disciplines and, especially, through the modern pedagogy known as active education. Throughout the article, I also show how to relate Krause’s philosophy to contemporary philosophical debates.

The uses of quinones in Redox Flow Batteries (RFBs) has been mainly circumscribed to aqueous solutions (of derivatives with polar groups) despite a larger solubility and wider electrochemical window provided by organic media. The redox mechanism of quinones in protic media is simpler and better known than in aprotic media, where radical species are involved. This paper reports the behaviour of methyl-p-benzoquinone (MBQ) under electrochemical reduction conditions in a LiClO[sbnd]CHCN electrolyte and various working electrodes. We detected the reversible generation of a bright green coating on the working electrode and the subsequent formation of a polymer (the nature of which depends on the presence or absence of oxygen). These coatings prevent the regular redox process of methyl-p-benzoquinone from taking place on the surface of the electrode and is generated regardless of the electrode material used or the presence of O in solution. In addition to MBQ, the green passivating layer was also found for less sterically hindered quinones such as p-benzoquinone or 1,4-naphthoquinone, but not for anthraquinone. We have also shown the central role of Li in the formation of this green layer. This work provides important guidelines for the final use of quinones in RFBs with organic electrolytes., Partial funding from Miisterio de Economía y Competitividad through Fondo Europeo de Desarrollo Regional (Grant MAT2015-68394-R, MINECO/FEDER) is acknowledged. ICN2 acknowledges support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program under Grant SEV-2013-0295. Finally, the award to DPD of a Marie-Curie Fellowship through Beatriu de Pinos Program (BP-DGR-2013) from the Catalan system of science and technology, Spain, is gratefully acknowledged.

This article belongs to the Special Issue Selected papers of the "1st International Conference on Nanofluids (ICNf)"., Here, we describe selected work on the development and study of nanofluids based on graphene and reduced graphene oxide both in aqueous and organic electrolytes. A thorough study of thermal properties of graphene in amide organic solvents (N,N-dimethylformamide, N,N-dimethylacetamide, and N-methyl-2-pyrrolidone) showed a substantial increase of thermal conductivity and specific heat upon graphene integration in those solvents. In addition to these thermal studies, our group has also pioneered a distinct line of work on electroactive nanofluids for energy storage. In this case, reduced graphene oxide (rGO) nanofluids in aqueous electrolytes were studied and characterized by cyclic voltammetry and charge-discharge cycles (i.e., in new flow cells). In addition, hybrid configurations (both hybrid nanofluid materials and hybrid cells combining faradaic and capacitive activities) were studied and are summarized here., ICN2 acknowledges support from the Severo Ochoa Program (MINECO, grant SEV-2017-0706) and funding from the CERCA Programme/Generalitat de Catalunya. Funding from the Spanish Ministry (MAT2015-68394-R and RTI2018-099826-B-I00, MCIU/AEI/FEDER, UE) is also acknowledged.

The rising amount of patients suffering for diabetes mellitus increases the requirements for effective insulin sensors. Carbon materials are a suitable choice for the development of insulin sensors due to their electrochemical characteristics. Pencil graphite electrodes (PGE) represent the trade‐off between price and excellent conductive properties. The modification of PGE by NiO and Ni nanoparticles fixed by chitosan results in surface area enlargement and improved electrocatalytic properties. This paper is focused on the comparison of different properties of Ni and NiO nanoparticles and their effect on redox reaction mechanism of insulin and detection characteristics. The electrode modified by Ni nanoparticles displays linear range of 1 μM–5 μM (R2 0.80), limit of detection (LOD) of 4.34 μM and sensitivity of 0.12 μA/μM. On the other hand, the electrode modified by NiO nanoparticles displays enhanced electrochemical characteristics such as linear range of 0.05 μM–5 μM (R2 0.99), limit of detection of 260 nM and sensitivity of 0.64 μA/μM. These properties make the NiO nanoparticles modified PGE the appropriate candidate for insulin determination., This work was supported by the Projects APVV‐16‐0029 of the Slovak Research and Development Agency, VEGA 1/0074/17 of the Slovak Scientific Grant Agency, VVGS‐PF‐2018‐795 and VVGS‐PF‐2018‐794 of Pavol Jozef Šafárik University in Košice.