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Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5–94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49–47.11); no chronic illness, aOR = 2.81 (95% CI 1.28–6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42–6.85); younger age, aOR = 0.97 (95% CI 0.94–0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97–0.99). To improve the surveillance of future epidemics, new approaches are recommended.

Biliary tract cancers (BTCs) are rare and aggressive malignancies with an increasing incidence and poor prognosis. The standard systemic treatment for BTCs has evolved to include immune checkpoint inhibitors associated with gemcitabine–cisplatin as first-line therapies. However, survival rates remain low, highlighting the critical need for personalized treatment strategies based on molecular profiling. Currently, significant advancements have been made in the molecular characterization of BTCs, where genetic alterations, such as IDH1 mutations and FGFR2 fusions, provide targets for therapy. Molecular profiling is crucial early in the management process to identify potential candidates for clinical trials and guide treatment strategy. The integration of these molecular insights into clinical practice has allowed for the development of targeted therapies, although many of them are still in the phase 2 trial stage without definitive survival benefits demonstrated in phase 3 trials. This integration of comprehensive molecular profile insights with traditional treatment approaches offers a new horizon in the personalized medicine landscape for BTCs, with the aim of significantly improving patient outcomes through precision oncology.

This article explores the intersectional relationship between domestic and medical gender-based violence, focusing specifically on the discursive aspect of medical practices. This research is based on the systemic disregard of female narratives in medical environments —particularly during screening and diagnostic processes— and the ex-treme technicality and personal distancing that certain medical discourses have acquired in the last few years. To this end, this article presents a close reading of Anne Carson’s poem “The Glass Essay”, included in Glass, Irony and God (1995), to advocate for the inclusion of more creative and freer narratives during psychological assessments and treatments to overcome those gendered discriminations that have been present in medical practices and have dismissed female narratives of illness and abuse as overly emotional and subjective. To ground this work, Rita Charon’s studies in Narrative Medicine, together with a close reading of Carson’s unique construction of the autobiographical self, will serve as a methodological basis to understand the relevance of gender exclusion in psychotherapeutic practices and the importance of using creative writing methods to allow victims of abuse to express themselves without the constraints of technicalities and gender-based stigmas.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Summary: Triple negative breast cancer (TNBC) is an aggressive type of breast cancer. While most TNBCs are initially sensitive to chemotherapy, a substantial fraction acquires resistance to treatments and progresses to more advanced stages. Here, we identify the spliceosome U2 small nuclear ribonucleoprotein particle (snRNP) complex as a modulator of chemotherapy efficacy in TNBC. Transient U2 snRNP inhibition induces persistent DNA damage in TNBC cells and organoids, regardless of their homologous recombination proficiency. U2 snRNP inhibition pervasively deregulates genes involved in the DNA damage response (DDR), an effect relying on their genomic structure characterized by a high number of small exons. Furthermore, a pulse of splicing inhibition elicits long-lasting repression of DDR proteins and enhances the cytotoxic effect of platinum-based drugs and poly(ADP-ribose) polymerase inhibitors (PARPis) in multiple TNBC models. These findings identify the U2 snRNP as an actionable target that can be exploited to enhance chemotherapy efficacy in TNBCs.

The aim of this paper is to analyze the differences and similarities between the latest volume of stories published by the Romanian writer Mircea Cărtărescu (Melancolia, 2019, Bucharest, Humanitas) and his previous literary production. Although Melancolia has been associated with Nostalgia and indeed exhibits many parallels with the first volume of short novels published by Cartarescu, the truth is that the 2019 volume refers to the literary universe created from other texts as well. By comparing and contrasting Melancolia with some of his main works, from novels such as the three volumes of the Orbitor trilogy (Aripa stângă, Corpul, Aripa dreaptă), Travesti or Solenoid to his poetry, through the stories of Nostalgia, the essay aims to demonstrate how this volume dialogues, more or less explicitly, with all the previous ones while distancing itself from them in some narrative and stylistic aspects. After examining elements such as characters, motifs, symbols, metaphors, subjects, intertextuality, and metafiction, the work focuses on space and time as the two main categories in which the most significant changes take place as they move away from their usual context, communist Bucharest (more precisely, from the late 1950s to the end of Nicolae Ceaușescu’s regime in the late 1980s). This temporal and spatial framework is one of the fundamental axes of all Cărtărescu’s literary texts, which gives them unity, stability, and continuity. However, as the article tries to demonstrate, the change is not total, but Mircea Cărtărescu, through his usual intertextual play, refers indirectly to this space well known by his readers and, consequently, perhaps also to that historical period. To argue this issue, this article outlines the direct allusion to a specific space mentioned in some of the author’s earlier texts. This is the factory where one of the most important episodes of the first story (Punțile) takes place. The spatial descriptions of the first and third stories are also analyzed to check the parallels between them and some settings of Nostalgia, Orbitor or Solenoid. The work also investigates the possible objectives of these changes and similarities. On the one hand, it is possible to identify some of Cărtărescu’s characteristic elements in Melancholy due to its thematic and stylistic permanence (child and adolescent characters, the games as creation and as a gateway to a magical universe, the mother, rites of passage, onirism, the use of polysemic symbols such as the butterfly, duality, symmetry and twins, fractal images, anti-mimetic references, etc.), as well as the allusions (explicit or implicit) to his previous works. On the other hand, by neglecting (at least unequivocally) the preferred space-time frame of his previous works, Melancolia can be universalized, and the fictitious components can prevail over any possible reference to extra-literary reality. In this way, the Romanian writer achieves a work that is both very similar to and very different from his broader literary corpus, from everything he had written until the moment of the publication of Melancolia.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case–control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry–based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Abstract Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.

From a large-scale sampling of limnoterrestrial tardigrades in the Valley of Mexico Basin, in the Huasteca Potosina, and Monarch Butterfly Sanctuary, Mexico, we develop an initial species list and determine the type of vegetation and substrates for most sampled species. In total 160 moss samples and over 2000 tardigrades were obtained, belonging to 17 genera, 35 putative species, one subspecies, of which eight could be accurately identified to species or subspecies, three to affinity, and 15 as morpho-species; the remaining samples were identified to genus, mainly due to the few specimens available and their preservation was not optimal. We provide novel records for one genus and two species from the country. Our estimates on five vegetation types and three substrate types indicates that our inventory is incomplete, and as many as twice the number of species may still be found in these ecosystems.