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This essay introduces our call for an intertwined history-of-emotions/history-of science perspective. We argue that the history of science can greatly extend the history of emotions by proffering science qua science as a new resource for the study of emotions. We present and read science, in its multiple diversities and locations, and in its variegated activities, products, theories, and emotions, as constitutive of the norms, experiences, expressions, and regimes of emotions. Reciprocally, we call for a new reading of science in terms of emotions as an analytical category. Assuming emotions are intelligible and culturally learned, we extend the notion of emotion to include a nonintentional and noncausal “emotional style,” which is inscribed into (and can reciprocally be generated by) technologies, disease entities, laboratory models, and scientific texts. Ultimately, we argue that emotional styles interrelate with broader emotional cultures and thus can contribute to and/or challenge grand historical narratives.

Abstract Aboveground biomass density (AGBD) estimates from Earth Observation (EO) can be presented with the consistency standards mandated by United Nations Framework Convention on Climate Change (UNFCCC). This article delivers AGBD estimates, in the format of Intergovernmental Panel on Climate Change (IPCC) Tier 1 values for natural forests, sourced from National Aeronautics and Space Administration’s (NASA’s) Global Ecosystem Dynamics Investigation (GEDI) and Ice, Cloud and land Elevation Satellite (ICESat-2), and European Space Agency’s (ESA’s) Climate Change Initiative (CCI). It also provides the underlying classification used by the IPCC as geospatial layers, delineating global forests by ecozones, continents and status (primary, young (≤20 years) and old secondary (>20 years)). The approaches leverage complementary strengths of various EO-derived datasets that are compiled in an open-science framework through the Multi-mission Algorithm and Analysis Platform (MAAP). This transparency and flexibility enables the adoption of any new incoming datasets in the framework in the future. The EO-based AGBD estimates are expected to be an independent contribution to the IPCC Emission Factors Database in support of UNFCCC processes, and the forest classification expected to support the generation of other policy-relevant datasets while reflecting ongoing shifts in global forests with climate change.

Abstract Benefits of neural mobilization (NM) have been described in musculoskeletal patients. The effects of NM on balance appear to be unclear in research, and no studies have tested the possible effects of NM on plantar pressures. Eighteen subjects were evaluated pre and post bilateral gliding of the sciatic nerve and its branches posterior tibial nerve, lateral dorsocutaneous, medial and intermediate dorsocutaneous nerves. Static variables of the plantar footprint and stabilometric variables were measured in a pre-post study. We found no differences in plantar pressure variables, Rearfoot maximum pressure (p = 0.376), Rearfoot medium pressure (p = 0.106), Rearfoot surface (p = 0.896), Midfoot maximum pressure (p = 0.975), Midfoot medium pressure (p = 0.950), Midfoot surface (p = 0.470) Forefoot maximum pressure (p = 0.559), Forefoot medium pressure(p = 0.481), Forefoot surface (p = 0.234), and stabilometric variables either, X-Displacement eyes-open (p = 0.086), Y-Displacement eyes-open (p = 0.544), Surface eyes-open (p = 0.411), Medium speed latero-lateral displacement eyes-open (p = 0.613), Medium speed anteroposterior displacement eyes-open (p = 0.442), X Displacement eyes-closed (p = 0.126), Y-Displacement eyes-closed (p = 0.077), Surface eyes-closed (p = 0.502), Medium speed latero-lateral displacement eyes-closed (p = 0.956), Medium speed anteroposterior displacement eyes-closed (p = 0.349). All variables don´t have significant differences however the measurements had a high reliability with at least an ICC of 0.769. NM doesn´t change plantar pressures or improve balance in healthy non-athletes subjects. NCT05190900.

Abstract Deficiencies in the electron transport chain (ETC) lead to mitochondrial diseases. While mutations are distributed across the organism, cell and tissue sensitivity to ETC disruption varies, and the molecular mechanisms underlying this variability remain poorly understood. Here we show that, upon ETC inhibition, a non-canonical tricarboxylic acid (TCA) cycle upregulates to maintain malate levels and concomitant production of NADPH. Our findings indicate that the adverse effects observed upon CI inhibition primarily stem from reduced NADPH levels, rather than ATP depletion. Furthermore, we find that Pyruvate carboxylase (PC) and ME1, the key mediators orchestrating this metabolic reprogramming, are selectively expressed in astrocytes compared to neurons and underlie their differential sensitivity to ETC inhibition. Augmenting ME1 levels in the brain alleviates neuroinflammation and corrects motor function and coordination in a preclinical mouse model of CI deficiency. These studies may explain why different brain cells vary in their sensitivity to ETC inhibition, which could impact mitochondrial disease management.

Abstract The evolution of the COVID-19 pandemic has been associated with variations in clinical presentation and severity. Similarly, prediction scores may suffer changes in their diagnostic accuracy. The aim of this study was to test the 30-day mortality predictive validity of the 4C and SEIMC scores during the sixth wave of the pandemic and to compare them with those of validation studies. This was a longitudinal retrospective observational study. COVID-19 patients who were admitted to the Emergency Department of a Spanish hospital from December 15, 2021, to January 31, 2022, were selected. A side-by-side comparison with the pivotal validation studies was subsequently performed. The main measures were 30-day mortality and the 4C and SEIMC scores. A total of 27,614 patients were considered in the study, including 22,361 from the 4C, 4,627 from the SEIMC and 626 from our hospital. The 30-day mortality rate was significantly lower than that reported in the validation studies. The AUCs were 0.931 (95% CI: 0.90–0.95) for 4C and 0.903 (95% CI: 086–0.93) for SEIMC, which were significantly greater than those obtained in the first wave. Despite the changes that have occurred during the coronavirus disease 2019 (COVID-19) pandemic, with a reduction in lethality, scorecard systems are currently still useful tools for detecting patients with poor disease risk, with better prognostic capacity.

Abstract The development of nuclear fusion as a safe and virtually limitless power source is receiving growing attention in the context of looming energy crisis and climate change. ITER project stands as the flagship international initiative and is advancing steadily. The construction of the Tokamak Complex is nearly finished, and the assembly of core components has begun on site. Simultaneously, the design is being finalized, and the safety case is becoming more concrete. Current approaches to radiation safety demonstration using 3D nuclear analysis with the Monte Carlo code MCNP require sophisticated artifacts to sew together simulations in separate models for the Tokamak and the rest of the facility. This results in cumbersome studies and, consequently, challengeable conclusions. To address this issue, we have built the an integral MCNP model of the ITER facility: the ITER full model. Along with improvements to the D1SUNED code, we illustrate its computational practicality and pertinence in two meaningful simulations for ITER safety case. This work represents the culmination of a two-decade-long effort of ITER modelling aiming to demonstrate adequate radiation safety. Beyond supporting the remaining design tasks, this model simplifies the corresponding 3D nuclear analysis and improves the robustness of the ITER safety case.

Abstract Force-driven cellular interactions are crucial for cancer cell invasion but remain underexplored in vascular abnormalities. Cerebral cavernous malformations (CCM), a vascular abnormality characterized by leaky vessels, involves CCM mutant cells recruiting wild-type endothelial cells to form and expand mosaic lesions. The mechanisms behind this recruitment remain poorly understood. Here, we use an in-vitro model of angiogenic invasion with traction force microscopy to reveal that hyper-angiogenic Ccm2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We demonstrate that mechanically hyperactive CCM2-silenced tips guide wild-type cells by transmitting pulling forces and by creating paths in the matrix, in a ROCKs-dependent manner. This is associated with reinforcement of β1 integrin and actin cytoskeleton in wild-type cells. Further, wild-type cells are reprogrammed into stalk cells and activate matrisome and DNA replication programs, thereby initiating proliferation. Our findings reveal how CCM2 mutants hijack wild-type cell functions to fuel lesion growth, providing insight into the etiology of vascular malformations. By integrating biophysical and molecular techniques, we offer tools for studying cell mechanics in tissue heterogeneity and disease progression.

Abstract The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia. This industry, termed here Arlanzian, not only represents the earliest and southernmost evidence of such industries in Iberia but also lacks a direct counterpart. However, it exhibits chronological and technological parallels with the lithic industries associated with the earliest expansion of Homo sapiens throughout Eurasia. We interpret this as potential evidence of its intrusive nature, but not necessarily associated with a migration event, as more complex scenarios derived from inter-population connectivity must be also considered. The biological identity of the Arlanzian makers remains unknown, but they coexisted with declining Neanderthal groups from neighbouring territories.

Abstract The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02–0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56–0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5–0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07–1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97–1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95–1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.

Abstract Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD’s beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

Abstract More than half of the world’s rivers dry up periodically, but our understanding of the biological communities in dry riverbeds remains limited. Specifically, the roles of dispersal, environmental filtering and biotic interactions in driving biodiversity in dry rivers are poorly understood. Here, we conduct a large-scale coordinated survey of patterns and drivers of biodiversity in dry riverbeds. We focus on eight major taxa, including microorganisms, invertebrates and plants: Algae, Archaea, Bacteria, Fungi, Protozoa, Arthropods, Nematodes and Streptophyta. We use environmental DNA metabarcoding to assess biodiversity in dry sediments collected over a 1-year period from 84 non-perennial rivers across 19 countries on four continents. Both direct factors, such as nutrient and carbon availability, and indirect factors such as climate influence the local biodiversity of most taxa. Limited resource availability and prolonged dry phases favor oligotrophic microbial taxa. Co-variation among taxa, particularly Bacteria, Fungi, Algae and Protozoa, explain more spatial variation in community composition than dispersal or environmental gradients. This finding suggests that biotic interactions or unmeasured ecological and evolutionary factors may strongly influence communities during dry phases, altering biodiversity responses to global changes.

Abstract In the digitization era, the battery consumption factor plays a vital role for the devices that operate Android software, expecting them to deliver high performance and good maintainability.The study aims to analyze the Android-specific code smells, their impact on battery consumption, and the formulation of a mathematical model concerning static code metrics hampered by the code smells. We studied the impact on battery consumption by three Android-specific code smells, namely: No Low Memory Resolver (NLMR), Slow Loop (SL) and Unclosed Closable, considering 4,165 classes of 16 Android applications. We used a rule-based classification method that aids the refactoring ideology. Subsequently, multi-linear regression (MLR) modeling is used to evaluate battery usage against the software metrics of smelly code instances. Moreover, it was possible to devise a correlation for the software metric influenced by battery consumption and rule-based classifiers. The outcome confirms that the refactoring of the considered code smells minimizes the battery consumption levels. The refactoring method accounts for an accuracy of 87.47% cumulatively. The applied MLR model has an R-square value of 0.76 for NLMR and 0.668 for SL, respectively. This study can guide the developers towards a complete package for the focused development life cycle of Android code, helping them minimize smartphone battery consumption and use the saved battery lives for other operations, contributing to the green energy revolution in mobile devices.

Abstract Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV. Modeling can shed additional insight on the natural history of HPV, especially across geographical settings with varying prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were exactly identical for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV.

Abstract Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells.

We analyzed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates microtubule-organizing center (MTOC) and multivesicular bodies (MVB) polarization and exosome secretion at an immune synapse (IS) model in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which was independent of protein kinase C δ (PKCδ). Simultaneous RNA interference of all FMNL1 isoforms prevented MTOC/MVB polarization and exosome secretion, which were restored by FMNL1βWT expression. However, expression of the non-phosphorylatable mutant FMNL1βS1086A did not restore neither MTOC/MVB polarization nor exosome secretion to control levels, supporting the crucial role of S1086 phosphorylation in MTOC/MVB polarization and exosome secretion. In contrast, the phosphomimetic mutant, FMNL1βS1086D, restored MTOC/MVB polarization and exosome secretion. Conversely, FMNL1βS1086D mutant did not recover the deficient MTOC/MVB polarization occurring in PKCδ-interfered clones, indicating that S1086 FMNL1β phosphorylation alone is not sufficient for MTOC/MVB polarization and exosome secretion. FMNL1 interference inhibited the depletion of F-actin at the central region of the immune synapse (cIS), which is necessary for MTOC/MVB polarization. FMNL1βWT and FMNL1βS1086D, but not FMNL1βS1086A expression, restored F-actin depletion at the cIS. Thus, actin cytoskeleton reorganization at the IS underlies the effects of all these FMNL1β variants on polarized secretory traffic. FMNL1 was found in the IS made by primary T lymphocytes, both in T cell receptor (TCR) and chimeric antigen receptor (CAR)-evoked synapses. Taken together, these results point out a crucial role of S1086 phosphorylation in FMNL1β activation, leading to cortical actin reorganization and subsequent control of MTOC/MVB polarization and exosome secretion.

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Abstract The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.

Abstract Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.

Abstract The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/β-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program.

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19−CD138+ ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC.

In this study, a series of Acrylate-Styrene-Acrylonitrile (ASA) composites loaded with high amounts of cork agro-waste (10–30 wt.%) are developed to address the increasing demand from industry and society for more sustainable materials, with the aim of reducing the carbon footprint associated with fossil fuel-derived plastics. These materials are suitable for Material Extrusion (ME) technologies, including Large Format Additive Manufacturing (LFAM). We demonstrate that the printing conditions can be optimised to manufacture cork composites with good mechanical properties, even for large particle sizes, around 1 mm. Sustainability analysis of these composites revealed that the carbon footprint can be reduced by up to 25% for composites with 30 wt.% cork, primarily due to the reduction in ASA usage. These composites were used to print a luminaire utilising a biomimetic approach and parametric design, showcasing how new materials and innovative product design can be integrated to produce functional and sustainable prototypes.

Abstract Following infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be “blasting” or proliferative. In this study, we find > 95% nascent blood ASC in culture express Ki-67 but only 6–12% incorporate BrdU after 4 h or 24 h labeling. In contrast,

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.

Abstract Remote sensing technologies are experiencing a surge in adoption for monitoring Earth’s environment, demanding more efficient and scalable methods for image analysis. This paper presents a new approach for the Emirates Mars Mission (Hope probe); A serverless computing architecture designed to analyze images of Martian auroras, a key aspect in understanding the Martian atmosphere. Harnessing the power of OpenCV and machine learning algorithms, our architecture offers image classification, object detection, and segmentation in a swift and cost-effective manner. Leveraging the scalability and elasticity of cloud computing, this innovative system is capable of managing high volumes of image data, adapting to fluctuating workloads. This technology, applied to the study of Martian auroras within the HOPE Mission, not only solves a complex problem but also paves the way for future applications in the broad field of remote sensing.

Abstract The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients' comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment. Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05). Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB− (OR 0.48, p = 0.003) and O− (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor. We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

Abstract Different sport modalities were associate with tendon adaptation or even tendon disturbances, such as volleyball, soccer or basketball. Purpose: the aim of the present study was to determine de difference between indoor and outdoor football players on patellar tendon (PT), Achilles tendon (AT), plantar fascia (FP) and Hoffa’s fat pad thickness assessed with ultrasound imaging (USI). A cross-sectional study was developed with a total sample of 30 soccer players divided in two groups: outdoor group (n = 15) and indoor group (n = 15). The thickness of PT, AT, PF and Hoffa’s fat pad has been assessed with USI. Hoffa’s fat pad reported significant differences for the left side between groups (P = 0.026). The rest of variables did not show any significant difference (P

Abstract Divalent ions (Mg, Ca, and Zn) are being considered as competitive, safe, and earth-abundant alternatives to Li-ion electrochemistry, but present challenges for stable cycling due to undesirable interfacial phenomena. We explore the formation of electroactive species in the electrolyte Ca(BH4)2∣THF using molecular dynamics coupled with a continuum model of bulk and interfacial speciation. Free-energy analysis and unsupervised learning indicate a majority population of neutral Ca dimers and monomers with diverse molecular conformations and an order of magnitude lower concentration of the primary electroactive charged species – the monocation, $${\rm{CaBH}}_{4}^{+}$$ CaBH 4 + – produced via disproportionation of neutral complexes. Dense layering of THF molecules within ~1 nm of the electrode surface strongly modulates local electrolyte species populations. A dramatic increase in monocation population in this interfacial zone is induced at negative bias. We see no evidence for electrochemical activity of fully-solvated Ca2+. The consequences for performance are discussed in light of this molecular-scale insight.

Abstract SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan–Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p

Abstract The presence of Andean plant genera in moist forests of the Brazilian Atlantic Coast has been historically hypothesized as the result of cross-continental migrations starting at the eastern Andean flanks. Here we test hypotheses of former connections between the Atlantic and Andean forests by examining distribution patterns of selected cool and moist-adapted plant arboreal taxa present in 54 South American pollen records of the Last Glacial Maximum (LGM), ca. 19–23 cal ka, known to occur in both plant domains. Pollen taxa studied include Araucaria, Drimys, Hedyosmum, Ilex, Myrsine, Podocarpus, Symplocos, Weinmannia, Myrtaceae, Ericaceae and Arecaceae. Past connectivity patterns between these two neotropical regions as well as individual ecological niches during the LGM were explored by cluster analysis of fossil assemblages and modern plant distributions. Additionally, we examined the ecological niche of 137 plant species with shared distributions between the Andes and coastal Brazil. Our results revealed five complex connectivity patterns for South American vegetation linking Andean, Amazonian and Atlantic Forests and one disjunction distribution in southern Chile. This study also provides a better understanding of vegetation cover on the large and shallow South American continental shelf that was exposed due to a global sea level drop.

Abstract Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.

Abstract Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and essential to maintain cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a critical role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown. In this study, we analyze phosphorylation of FAM134 as a trigger of FAM134-driven ER-phagy upon mTOR (mechanistic target of rapamycin) inhibition. An unbiased screen of kinase inhibitors reveals CK2 to be essential for FAM134B- and FAM134C-driven ER-phagy after mTOR inhibition. Furthermore, we provide evidence that ER-phagy receptors are regulated by ubiquitination events and that treatment with E1 inhibitor suppresses Torin1-induced ER-phagy flux. Using super-resolution microscopy, we show that CK2 activity is essential for the formation of high-density FAM134B and FAM134C clusters. In addition, dense clustering of FAM134B and FAM134C requires phosphorylation-dependent ubiquitination of FAM134B and FAM134C. Treatment with the CK2 inhibitor SGC-CK2-1 or mutation of FAM134B and FAM134C phosphosites prevents ubiquitination of FAM134 proteins, formation of high-density clusters, as well as Torin1-induced ER-phagy flux. Therefore, we propose that CK2-dependent phosphorylation of ER-phagy receptors precedes ubiquitin-dependent activation of ER-phagy flux.

This study evaluates the effectiveness of multispectral imaging via Unmanned Aerial Systems (UAS), in combination with advanced digital image processing techniques, for the detection and mapping of archaeological sites within diverse landscapes. The research focuses on six case studies located in the northwest of the Iberian Peninsula, a region marked by complex vegetation patterns and varying topography. The primary objective is to assess the potential of these non-invasive remote sensing techniques in identifying crop marks associated with buried structures from ancient, fortified settlements. By means of Principal Component Analysis (PCA) and vegetation indices, the study aims to pinpoint areas of interest that may indicate the presence of archaeological features, while effectively distinguishing them from modern disturbances or natural terrain variations. The research encountered several challenges, including seasonal variations in crop conditions and recent land-use changes. The methodology successfully identified distinct archaeological features. In some instances, natural vegetation variability, typically seen as an obstacle, enhanced the visibility of crop marks, aiding in the detection of underlying structures. These results offer a cost-effective and scalable option for preliminary archaeological surveys, particularly in refining survey methodologies and guiding future excavation efforts aimed at uncovering and preserving ancient, fortified settlements in the region.

The dynamic of rangelands results from complex interactions between vegetation, soil, climate, and human activity. This scenario makes rangeland’s condition challenging to monitor, and degradation assessment should be carefully considered when studying grazing pressures. In the present work, we study the interaction of vegetation and soil moisture in semiarid rangelands using vegetation and soil moisture indices. We aim to study the feasibility of using soil moisture negative anomalies as a warning index for vegetation or agricultural drought. Two semiarid agricultural regions were selected in Spain for this study: Los Vélez (Almería) and Bajo Aragón (Teruel). MODIS images, with 250 m and 500 m spatial resolution, from 2002 to 2019, were acquired to calculate the Vegetation Condition Index (VCI) and the Water Condition Index (WCI) based on the Normalised Difference Vegetation Index (NDVI) and soil moisture component (W), respectively. The Optical Trapezoid Model (OPTRAM) estimated this latter W index. From them, the anomaly (Z-score) for each index was calculated, being ZVCI and ZWCI, respectively. The probability of coincidence of their negative anomalies was calculated every 10 days (10-day periods). The results show that for specific months, the ZWCI had a strong probability of informing in advance, where the negative ZVCI will decrease. Soil moisture content and vegetation indices show more similar dynamics in the months with lower temperatures (from autumn to spring). In these months, given the low temperatures, precipitation leads to vegetation growth. In the following months, water availability depends on evapotranspiration and vegetation type as the temperature rises and the precipitation falls. The stronger relationship between vegetation and precipitation from autumn to the beginning of spring is reflected in the feasibility of ZWCI to aid the prediction of ZVCI. During these months, using ZWCI as a warning index is possible for both areas studied. Notably, November to the beginning of February showed an average increase of 20–30% in the predictability of vegetation anomalies, knowing moisture soil anomalies four lags in advance. We found other periods of relevant increment in the predictability, such as March and April for Los Vélez, and from July to September for Bajo Aragón.

SfM (structure from motion) photogrammetry is a technique developed in the field of computer vision that enables the generation of three-dimensional (3D) models from a set of overlapping images captured from disparate angles. The application of this technique in the field of cultural heritage, particularly in the context of megalithic monuments, is inherently challenging due to the spatial constraints of these environments and the usual limitations posed by their architectural design, which often results in poor lighting conditions. This article presents an accurate and cost-efficient methodology for the study and documentation of rock art, which has been applied to three megalithic monuments in the Iberian Peninsula: one in Spain and two in Portugal. The three working environments are complex, but the combination of techniques used and improvements such as rendering for the enhancement of engravings and the creation of 3D stop-motion models made it possible to integrate all the information in 3D formats that allow its universal dissemination. This not only preserves the heritage in graphic form but also makes it accessible to the public, both for study and for virtual visits.

Peripheral neurons are heterogeneous and functionally diverse, but all share the capability to switch to a pro-regenerative state after nerve injury. Despite the assumption that the injury response is similar among neuronal subtypes, functional recovery may differ. Understanding the distinct intrinsic regenerative properties between neurons may help to improve the quality of regeneration, prioritizing the growth of axon subpopulations to their targets. Here, we present a comparative analysis of regeneration across four key peripheral neuron populations: motoneurons, proprioceptors, cutaneous mechanoreceptors, and nociceptors. Using Cre/Ai9 mice that allow fluorescent labeling of neuronal subtypes, we found that nociceptors showed the greater regeneration after a sciatic crush, followed by motoneurons, mechanoreceptors, and, finally, proprioceptors. By breeding these Cre mice with Ribotag mice, we isolated specific translatomes and defined the regenerative response of these neuronal subtypes after axotomy. Only 20% of the regulated genes were common, revealing a diverse response to injury among neurons, which was also supported by the differential influence of neurotrophins among neuron subtypes. Among differentially regulated genes, we proposed MED12 as a specific regulator of the regeneration of proprioceptors. Altogether, we demonstrate that the intrinsic regenerative capacity differs between peripheral neuron subtypes, opening the door to selectively modulate these responses.

Summary: Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals revealed a mitochondria stress signature and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.

Petalocladius dominiensis Andersen & Baranov sp. n. is described and figured based on an adult male collected in the Ebano Verde Scientific Reserve in the Dominican Republic. The new species can be separated from its only congener, P. setosus Sublette & Wirth, 1972 from Jamaica, as it is slightly smaller with about 115 dorsocentrals compared to 56 in P. setosus. The inferior volsella is broadly subtriangular, while more lingulate in P. setosus, and the gonostylus has a small, but distinct megaseta and a subapical brush of spine-like seta, which apparently lack in P. setosus. The generic diagnosis is emended including the new species, and the systematic position is briefly discussed.

Aims Turbulent aortic flow makes the cardiovascular system less effective. It remains unknown if patients with heart failure with preserved ejection fraction (HFpEF) have disturbed aortic flow. This study sought to investigate advanced markers of aortic flow disturbances in HFpEF. Methods This case-controlled observational study used four-dimensional flow cardiovascular magnetic resonance derived, two-dimensional phase-contrast reformatted plane data at an orthogonal plane just above the sino-tubular junction. We recruited 10 young healthy controls (HCs), 10 old HCs and 23 patients with HFpEF. We analysed average systolic aortic flow displacement (FDsavg), systolic flow reversal ratio (sFRR) and pulse wave velocity (PWV). In a sub-group analysis, we compared old HCs versus age-gender-matched HFpEF (N=10). Results Differences were significant in mean age (P 17.7% achieved 74% sensitivity, 70% specificity for differentiating them. sFRR was notably higher in HFpEF (11±10% vs 7±6%, P 7.3% yielded 78% sensitivity, 70% specificity in differentiating these groups. In sub-group analysis, FDsavg remained distinctly elevated in HFpEF (22.4±9.7% vs 16±4.9%, P=0.029). FDsavg of >16% showed 100% sensitivity and 70% specificity (P=0.01). Similarly, sFRR remained significantly higher in HFpEF (11.3±9.5% vs 6.6±6.4%, P=0.007). A sFRR of >7.2% showed 100% sensitivity and 60% specificity (P

Abstract Nonlinear damping, the change in damping rate with the amplitude of oscillations plays an important role in many electrical, mechanical and even biological oscillators. In novel technologies such as carbon nanotubes, graphene membranes or superconducting resonators, the origin of nonlinear damping is sometimes unclear. This presents a problem, as the damping rate is a key figure of merit in the application of these systems to extremely precise sensors or quantum computers. Through measurements of a superconducting resonator, we show that from the interplay of quantum fluctuations and the nonlinearity of a Josephson junction emerges a power-dependence in the resonator response which closely resembles nonlinear damping. The phenomenon can be understood and visualized through the flow of quasi-probability in phase space where it reveals itself as dephasing. Crucially, the effect is not restricted to superconducting circuits: we expect that quantum fluctuations or other sources of noise give rise to apparent nonlinear damping in systems with a similar conservative nonlinearity, such as nano-mechanical oscillators or even macroscopic systems.

Abstract Neurogenesis in the adult mammalian brain relies on the lifelong persistence of quiescent neural stem cell (NSC) reservoirs. Little is known about the mechanisms that lead to the initial establishment of quiescence, the main hallmark of adult stem cells, during development. Here we show that protein aggregates and autophagy machinery components accumulate in developmental radial glia-like NSCs as they enter quiescence and that pharmacological or genetic blockade of autophagy disrupts quiescence acquisition and maintenance. Conversely, increasing autophagy through AMPK/ULK1 activation instructs the acquisition of the quiescent state without affecting BMP signaling, a gatekeeper of NSC quiescence during adulthood. Selective ablation of Atg7, a critical gene for autophagosome formation, in radial glia-like NSCs at early and late postnatal stages compromises the initial acquisition and maintenance of quiescence during the formation of the hippocampal dentate gyrus NSC niche. Therefore, we demonstrate that autophagy is cell-intrinsically required to establish NSC quiescence during hippocampal development. Our results uncover an important role of autophagy in the transition of developmental NSCs into their dormant adult form, paving the way for studies directed at further understanding the mechanisms of stem cell niche formation and maintenance in the mammalian brain.

Abstract Low dimensional carbon-based materials can show intrinsic magnetism associated to p-electrons in open-shell π-conjugated systems. Chemical design provides atomically precise control of the π-electron cloud, which makes them promising for nanoscale magnetic devices. However, direct verification of their spatially resolved spin-moment remains elusive. Here, we report the spin-polarization of chiral graphene nanoribbons (one-dimensional strips of graphene with alternating zig-zag and arm-chair boundaries), obtained by means of spin-polarized scanning tunnelling microscopy. We extract the energy-dependent spin-moment distribution of spatially extended edge states with π-orbital character, thus beyond localized magnetic moments at radical or defective carbon sites. Guided by mean-field Hubbard calculations, we demonstrate that electron correlations are responsible for the spin-splitting of the electronic structure. Our versatile platform utilizes a ferromagnetic substrate that stabilizes the organic magnetic moments against thermal and quantum fluctuations, while being fully compatible with on-surface synthesis of the rapidly growing class of nanographenes.

Abstract The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT–deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.

Abstract One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.

Abstract Large-scale brain networks reveal structural connections as well as functional synchronization between distinct regions of the brain. The latter, referred to as functional connectivity (FC), can be derived from neuroimaging techniques such as functional magnetic resonance imaging (fMRI). FC studies have shown that brain networks are severely disrupted by stroke. However, since FC data are usually large and high-dimensional, extracting clinically useful information from this vast amount of data is still a great challenge, and our understanding of the functional consequences of stroke remains limited. Here, we propose a dimensionality reduction approach to simplify the analysis of this complex neural data. By using autoencoders, we find a low-dimensional representation encoding the fMRI data which preserves the typical FC anomalies known to be present in stroke patients. By employing the latent representations emerging from the autoencoders, we enhanced patients’ diagnostics and severity classification. Furthermore, we showed how low-dimensional representation increased the accuracy of recovery prediction.

Abstract The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. To understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. We collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. We show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. This study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.

Abstract In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.

Tick-borne rickettsioses (TBRs) are distributed worldwide and are recognized as important emerging vector-borne zoonotic diseases in Europe. The aim of this study was to identify tick-associated Rickettsia among ticks removed from humans, and to track how tick populations and their associated pathogens have changed over the years. For this purpose, we conducted a tick surveillance study in northwestern Spain between 2018 and 2022. Ticks were morphologically identified and analyzed for the presence of rickettsial pathogens through the amplification of the citrate synthase (gltA) and the outer membrane protein A (ompA) genes. PCR products were sequenced and subjected to phylogenetic analyses. We collected 7397 ticks, with Ixodes ricinus being the species most frequently isolated. Based on the PCR results, Rickettsia DNA was detected in 1177 (15.91%) ticks, and 10 members of Rickettsia were identified: R. aeschlimannii, R. conorii subsp. conorii, R. conorii subsp. raoultii, R. massiliae, R. monacensis, R. sibirica subsp. mongolitimonae, R. slovaca, R. helvetica, Candidatus R. barbariae, and Candidatus R. rioja. Some of these Rickettsia have gone previously undetected in the study region. There is clear geographic and seasonal expansion not only of tick populations, but also of the associated Rickettsia. The comparison of our data with those obtained years ago provides a clear idea of how the spatiotemporal distributions of ticks and their associated Rickettsiae have changed over the years.

Abstract A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Abstract While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.