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Abstract The mucociliary clearance (MC) system is a vital host defense against infection in the lung. MC system function is dependent on ciliary density, structure, and function and airway surface liquid (ASL) composition and hydration. Animal and human studies indicate that MC rate decreases with age which may contribute to the increased rates of pulmonary infection experienced by older people. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes an anion channel on epithelial surfaces that plays a key role in maintaining ASL hydration. Failure or dysfunction of CFTR could result in the dehydration of airway mucus, depressing MC. Here we use two available databases including bulk (GTEx) and single-cell (CELLxGENE) sequencing data from the lung to determine if CFTR expression decreases with age. Bulk expression data and single-cell expression data from goblet, club, and respiratory basal cells all demonstrated patterns of decreasing CFTR expression with age. Ciliated airway cells did not. Secretory cells (including club and goblet cells) and basal cells are the largest source of CFTR expression in the airway. This indicates that changes in CFTR expression and ASL dehydration may contribute to the decreasing MC associated with aging.

Abstract Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.

Abstract Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8–12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9–11, P

The embryonic extracellular matrix (ECM) undergoes transition to mature ECM as development progresses, yet few mechanisms ensuring ECM proteostasis during this period are known. Fibrillin microfibrils are macromolecular ECM complexes serving structural and regulatory roles. In mice, Fbn1 and Fbn2, encoding the major microfibrillar components, are strongly expressed during embryogenesis, but fibrillin-1 is the major component observed in adult tissue microfibrils. Here, analysis of Adamts6 and Adamts10 mutant mouse embryos, lacking these homologous secreted metalloproteases individually and in combination, along with in vitro analysis of microfibrils, measurement of ADAMTS6-fibrillin affinities and N-terminomics discovery of ADAMTS6-cleaved sites, identifies a proteostatic mechanism contributing to postnatal fibrillin-2 reduction and fibrillin-1 dominance. The lack of ADAMTS6, alone and in combination with ADAMTS10 led to excess fibrillin-2 in perichondrium, with impaired skeletal development defined by a drastic reduction of aggrecan and cartilage link protein, impaired BMP signaling in cartilage, and increased GDF5 sequestration in fibrillin-2-rich tissue. Although ADAMTS6 cleaves fibrillin-1 and fibrillin-2 as well as fibronectin, which provides the initial scaffold for microfibril assembly, primacy of the protease-substrate relationship between ADAMTS6 and fibrillin-2 was unequivocally established by reversal of the defects in Adamts6-/- embryos by genetic reduction of Fbn2, but not Fbn1.

Background/AimsInfectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.MethodsWe investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis.ResultsSingle nucleotide polymorphisms in Mannosidase-1-α-2 (MAN1A2) were significantly associated with BA and with other polymorphisms known to affect MAN1A2 expression but were not differentially enriched in either BA subtype. In zebrafish embryos, man1a2 knockdown caused poor biliary network formation, ciliary dysgenesis in Kupffer’s vesicle, cardiac and liver heterotaxy, and dysregulated egfra and other developmental genes. Suboptimal man1a2 knockdown synergized with suboptimal EGFR signaling or suboptimal knockdown of the EGFR pathway gene, adenosine-ribosylation-factor-6, which had minimal effects individually, to reproduce biliary defects but not heterotaxy. In cultured mouse airway epithelium, Man1a2 knockdown arrested ciliary development and motility. Man1a2–/– mice, which experience respiratory failure, also demonstrated portal and bile ductular inflammation. Human BA liver and Man1a2–/– liver exhibited reduced Man1a2 expression and dysregulated ciliary genes, known to cause multisystem human laterality defects.ConclusionBA requiring transplantation associates with sequence variants in MAN1A2. man1a2 regulates laterality, in addition to hepatobiliary morphogenesis, by regulating ciliogenesis in zebrafish and mice, providing a novel developmental basis for multisystem defects in BA.

Knockout mice deficient in the gap junction gene connexin43 exhibit developmental anomalies associated with abnormal neural crest, primordial germ cell, and proepicardial cell migration. These migration defects are due to a loss of directional cell movement, and are associated with abnormal actin stress fiber organization and a loss of polarized cell morphology. To elucidate the mechanism by which Cx43 regulates cell polarity, we used a wound closure assays with mouse embryonic fibroblasts (MEFs) to examine polarized cell morphology and directional cell movement. Studies using embryonic fibroblasts from Cx43 knockout (Cx43KO) mice showed Cx43 deficiency caused cell polarity defects as characterized by a failure of the Golgi apparatus and the microtubule organizing center to reorient with the direction of wound closure. Actin stress fibers at the wound edge also failed to appropriately align, and stabilized microtubule (Glu-tubulin) levels were markedly reduced. Forced expression of Cx43 with deletion of its tubulin-binding domain (Cx43dT) in both wildtype MEFs and neural crest cell explants recapitulated the cell migration defects seen in Cx43KO cells. However, forced expression of Cx43 with point mutation causing gap junction channel closure had no effect on cell motility. TIRF imaging revealed increased microtubule instability in Cx43KO cells, and microtubule targeting of membrane localized Cx43 was reduced with expression of Cx43dT construct in wildtype cells. Together, these findings suggest the essential role of Cx43 gap junctions in development is mediated by regulation of the tubulin cytoskeleton and cell polarity by Cx43 via a nonchannel function.

Objectives: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. Methods: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. Results: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non–COVID-19 septic patients yielded similar results in cell populations and outcome. Conclusions: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Venezuela’s diverse land ecosystems are grouped into four major regions (coast-islands, low plains, hills and mountains), ranging from sea level up to 4978 m. The Scarabaeinae (Scarabaeidae, Coleoptera) currently encompass 278 genera and 6837 species worldwide, but are poorly inventoried in Venezuela. We reviewed the literature and the material housed at the entomological collection of the Universidade Federal de Mato Grosso (CEMT), Cuiabá, Brazil, and found 32 genera and 149 species of dung beetles as certainly present in Venezuela. Twenty-four of these species are, as far as current knowledge goes, endemic to the country, while another 34 are restricted to Venezuela and the neighbouring countries of Colombia, Brazil, Trinidad and Tobago, and Guyana. Additionally, 36 species are deemed potential inhabitants of the country, whilst 14 others previously recorded in the literature as part of the Venezuelan fauna are here concluded not to be actually present there. Complete literature is listed for each genus and species, and information on type material, material examined, worldwide distribution, and Venezuelan records is also presented.

Abstract Objective To explore Chat Generative Pretrained Transformer's (ChatGPT's) capability to create multiple‐choice questions about otorhinolaryngology (ORL). Study Design Experimental question generation and exam simulation. Setting Tertiary academic center. Methods ChatGPT 3.5 was prompted: “Can you please create a challenging 20‐question multiple‐choice questionnaire about clinical cases in otolaryngology, offering five answer options?.” The generated questionnaire was sent to medical students, residents, and consultants. Questions were investigated regarding quality criteria. Answers were anonymized and the resulting data was analyzed in terms of difficulty and internal consistency. Results ChatGPT 3.5 generated 20 exam questions of which 1 question was considered off‐topic, 3 questions had a false answer, and 3 questions had multiple correct answers. Subspecialty theme repartition was as follows: 5 questions were on otology, 5 about rhinology, and 10 questions addressed head and neck. The qualities of focus and relevance were good while the vignette and distractor qualities were low. The level of difficulty was suitable for undergraduate medical students (n = 24), but too easy for residents (n = 30) or consultants (n = 10) in ORL. Cronbach's α was highest (.69) with 15 selected questions using students' results. Conclusion ChatGPT 3.5 is able to generate grammatically correct simple ORL multiple choice questions for a medical student level. However, the overall quality of the questions was average, needing thorough review and revision by a medical expert to ensure suitability in future exams.

IntroductionIn recent years, prices for veterinary care have received considerable attention in mainstream media, yet scientific literature has not delved into actual figures. This study aims to elucidate veterinary care costs for dogs, cats, and horses across five countries [Sweden (SE), Norway (NO), Denmark (DK), United Kingdom (UK), and Ireland (IR, with limited data)] through web searches.MethodsUtilising online business directories, we located URLs featuring veterinary care prices in autumn 2022, and repeated tri-monthly five times. Vetpris.se (VP), a price comparison site for SE, NO, and DK, emerged from the search. Additionally, we sought to compare price data from veterinary clinics (ranging from animal hospitals to small private clinics) using a similar approach to VP. We targeted elective procedures (e.g., gonadectomy, GDY) and common procedures (e.g., pyometra surgery in dogs).ResultsComparing data from the same clinics’ websites and from VP within extraction from autumn 2022 to winter 2023/2024, median prices for dog and cat GDY were largely consistent. By October 2023, median prices for male cat GDY ranged from €72 (SE) to €230 (DK), and €130 (SE) to €361 (DK) for females; for dog GDY from €390 (SE) to €599 (DK) for males, and €461 (UK) to €1015 (DK) for females. Across sources, median prices for cat and dog GDY increased by 2–24% over a year for procedures with at least 10 clinics per extraction. Equine GDY (per sedation and local analgaesia) in SE saw a 64% increase by year-end, with a median price of €492. Emergency surgeries during regular-hours (e.g., pyometra and caesarean section) in SE were approximately €2,300 at the last extraction, marking a 27% increase for pyometra surgery during regular-hours and 15% after-hours compared to the previous year. Variability existed within and across countries and diagnoses/procedures.DiscussionCross-validation suggested VP generally provided reliable information, though data points for emergencies were limited. Our web searching tool necessitated extensive manual verification, indicating room for further development. We recommend enhancing price transparency for animal owners to become better informed about the cost of veterinary care and be able to make informed choices.

Background Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood.Methods An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected.Results 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity.Conclusions in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Abstract Whereas aging is a whole-organism process, senescence is a cell mechanism that can be triggered by several stimuli. There is increasing evidence that critical conditions activate cell senescence programs irrespective of patient’s age. In this review, we briefly describe the basic senescence pathways and the consequences of their activation in critically ill patients. The available evidence suggests a paradigm in which activation of senescence can be beneficial in the short term by rendering cells resistant to apoptosis, but also detrimental in a late phase by inducing a pro-inflammatory and pro-fibrotic state. Senescence can be a therapeutic target. The use of drugs that eliminate senescent cells (senolytics) or the senescence-associated phenotype (senomorphics) will require monitoring of these cell responses and identification of therapeutic windows to improve the outcome of critically ill patients.

In the Greek regions of Agrafa and Tzoumerka, Tsalafouti, a traditional spreadable cheese made from goat’s and sheep’s milk is produced. This product has emerged in recent years as a result of the campaign to acquire Geographical Indication. This study aimed to assess the biopeptide profile of Tsalafouti cheese in order to highlight its nutritional value. Using HPLC-MS, bioactive peptides in Tsalafouti cheese samples were identified and classified according to their bioactivity. The biopeptides detected are known to present antibacterial, anti-diabetic, anti-hypertensive, anti-thrombotic, antioxidant, and immunomodulatory activities, while ACE enzyme and dipeptidyl-4 (DPP-IV) inhibitors were also identified. Based on these results, Tsalafouti cheese presents an interesting bioactive peptides profile that may act as special motivation for consumers to choose this specific cheese.

Abstract Variations in the Toll‐interacting protein (TOLLIP) gene have been identified in genome‐wide association studies to correlate with risk of disease, mortality, and response to N‐acetylcysteine therapy in idiopathic pulmonary fibrosis. Although TOLLIP is known to modulate innate immune responses, its relevance in organ fibrogenesis remains unknown. Prior work in the literature suggests TOLLIP dampens transforming growth factor beta (TGFβ) signaling in human cell lines. In this study, we examined the role of TOLLIP in mouse lung fibroblast (MLF) responses to TGFβ and in the bleomycin model of experimental lung fibrosis using Tollip−/− mice. We hypothesize that if TOLLIP negatively regulates TGFβ signaling, then Tollip−/− mouse lung fibroblasts (MLFs) would have enhanced response to TGFβ treatment, and Tollip−/− mice would develop increased fibrosis following bleomycin challenge. Primary MLFs were stimulated with TGFβ (1 ng/mL) for 24 h. RNA was obtained to assess global transcriptional responses by RNA‐seq and markers of myofibroblast transition by qPCR. Functional assessment of TGFβ‐stimulated MLFs included cell migration by scratch assay, cell proliferation, and matrix invasion through Matrigel. In the in vivo model of lung fibrosis, Tollip−/− mice and wild‐type (WT) littermates were administered bleomycin intratracheally and assessed for fibrosis. We further examined TGFβ signaling in vivo after bleomycin injury by SMAD2, ERK1/2, and TGFβR1 Western blot. In response to TGFβ treatment, both WT and Tollip−/− MLFs exhibited global transcriptional changes consistent with myofibroblast differentiation. However, Tollip−/− MLFs showed greater number of differentially expressed genes compared to WT MLFs and greater upregulation of Acta2 by qPCR. Functionally, Tollip−/− MLFs also exhibited increased migration and Matrigel invasiveness compared to WT. We found evidence of enhanced TGFβ signaling in Tollip−/− through SMAD2 in vitro and in vivo. Tollip−/− mice experienced lower survival using a standard weight‐adjusted dosing without evidence of differences in fibrosis at Day 21. With adjustment of dosing for sex, no differences were observed in fibrosis at Day 21. However, Tollip−/− mice had greater weight loss and increased bronchoalveolar lavage fluid total protein during early resolution at Day 14 compared to WT without evidence of differences in acute lung injury at Day 7, suggesting impaired resolution of lung injury.

Abstract Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative rare disease characterized by symptoms and signs in the upper and lower motor neurons, leading to progressive neuro-degeneration and muscle atrophy. Our objective was to analyse the quality of life (QoL) in patients with ALS and compare with general population and with patients with cancer. Prospective study from consecutive ALS patients in one center. In order to assess quality of life, during the first visit three questionnaires were administered: Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Short Form-36 (SF-36) and EuroQoL 5D (EQ-5D). We compared SF-36 of ALS patients with a reference population (n = 9151), and we compared the EQ-5D index score of ALS patients versus patients with cancer in the same area and in the same period (2015–2018). Between June 2015 and September 2017, 23 were included. The mean age was 65.1 ± 12.6 years and 56.5% were women. Compared with the general population, patients with ALS showed lowest QoL (p

Esse dossiê apresenta seis textos que analisam, sob diversas óticas, expressões do filossemitismo e do sionismo cristão em três países da América Latina - Brasil, Venezuela e Guatemala -, proporcionando ao/à leitor/a um panorama interessante do debate atual nos campos teológico e das ciências sociais da região.

Com base em entrevistas, observação de evento e informações de sites políticos e religiosos, analisamos diferentes iniciativas de atores coletivos e individuais – evangélicos e israelenses – que contribuem para a construção de uma cultura política pró-Israel na sociedade brasileira. Um dos nossos objetos de análise foi a instalação, em 2023, no Senado Federal do Grupo Parlamentar de Amizade Brasil – Israel, existente no Congresso Nacional. Por ter se tornado lócus importante de ativismo dos cristãos em favor do governo atual de Israel, esse grupo é também espaço de disputas entre os atores religiosos de diferentes igrejas. Além das tensões entre seus membros, nossa análise evidenciou interesses de parlamentares desse grupo por viagens à Terra Santa. Também foram identificadas iniciativas dos últimos governos de Israel visando o apoio dos evangélicos brasileiros ao estado de Israel. Inspiradas pela sociologia weberiana, discutimos os interesses materiais e ideais tanto dos evangélicos quanto do Estado de Israel e das redes transnacionais para fomentar o sionismo cristão no Brasil. Concluímos que, como fenômeno multifatorial, o sionismo cristão no Brasil se reconfigura e responde a interesses materiais e ideais, tanto das lideranças religiosas brasileiras, quanto de setores empresariais e da elite política do moderno Estado de Israel.

Abstract Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor‐dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor‐dependent gene expression suggests new potential genes involved in cell–cell interactions beyond what ligand‐receptor co‐expression can discover.

Abstract Excitability and contraction of cardiac muscle from brain‐dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+‐handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain‐dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole‐cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L‐type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain‐dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.

Resumo: O objetivo deste artigo é analisar o desenvolvimento no meio evangélico brasileiro de discursos sionistas cristãos. A genealogia traçada privilegia os livros escritos em defesa do estado de Israel por lideranças nacionais de diferentes denominações e aponta fatores históricos e políticos que favoreceram essas publicações no século XX. Argumenta-se que, embora ganhe uma maior projeção nas eleições de 2018, o sionismo cristão e a teologia dispensacionalista que deram sustentação à maior parte das publicações sobre o tema, já faziam parte da cosmovisão evangélica brasileira tanto de igrejas históricas quanto das pentecostais. Examina-se ainda o impacto das peregrinações à Terra Santa, da teologia do domínio e do movimento Nova Reforma Apostólica no ativismo sionista cristão a partir da virada d século.

Abstract Characterization of tissue architecture promises to deliver insights into development, cell communication, and disease. In silico spatial domain retrieval methods have been developed for spatial transcriptomics (ST) data assuming transcriptional similarity of neighboring barcodes. However, domain retrieval approaches with this assumption cannot work in complex tissues composed of multiple cell types. This task becomes especially challenging in cellular resolution ST methods. We developed Vesalius to decipher tissue anatomy from ST data by applying image processing technology. Vesalius uniquely detected territories composed of multiple cell types and successfully recovered tissue structures in high‐resolution ST data including in mouse brain, embryo, liver, and colon. Utilizing this tissue architecture, Vesalius identified tissue morphology‐specific gene expression and regional specific gene expression changes for astrocytes, interneuron, oligodendrocytes, and entorhinal cells in the mouse brain.

Background: Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR

Background Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.Methods We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.Results The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum–neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.Conclusion The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.

Abstract This study analyzed the frequency and intensity of acute stress among health professionals caring for COVID-19 patients in four Latin American Spanish-speaking countries during the outbreak. A cross-sectional study involved a non-probability sample of healthcare professionals in four Latin American countries. Participants from each country were invited using a platform and mobile application designed for this study. Hospital and primary care workers from different services caring for COVID-19 patients were included. The EASE Scale (SARS-CoV-2 Emotional Overload Scale, in Spanish named Escala Auto-aplicada de Sobrecarga Emocional) was a previously validated measure of acute stress. EASE scores were described overall by age, sex, work area, and experience of being ill with COVID-19. Using the Mann–Whitney U test, the EASE scores were compared according to the most critical moments of the pandemic. Univariate and multivariate analysis was performed to investigate associations between these factors and the outcome ‘acute stress’. Finally, the Kruskal–Wallis was used to compare EASE scores and the experience of being ill. A total of 1372 professionals responded to all the items in the EASE scale: 375 (27.3%) Argentines, 365 (26.6%) Colombians, 345 (25.1%) Chileans, 209 (15.2%) Ecuadorians, and 78 (5.7%) from other countries. 27% of providers suffered middle-higher acute stress due to the outbreak. Worse results were observed in moments of peak incidence of cases (14.3 ± 5.3 vs. 6.9 ± 1.7, p

Se registran nuevas localidades para la especie Oxysternon ebeninum (Nevison, 1890) al norte del estado Amazonas, Venezuela, donde las condiciones ambientales de estos lugares son significativamente diferentes a las reportadas previamente en la literatura.

Objetivo: proponer un marco de revisión de la literatura sobre los programas de microcrédito para las mujeres y su efecto en la reducción de la pobreza, a partir de un análisis bibliométrico que muestre las relaciones y las tendencias de los conceptos microcrédito y autonomía económica de las mujeres. Metodología: descriptiva con diseño documental en la que se usan las herramientas del software VOSviewer sobre una base de datos de 434 documentos resultante de la búsqueda en la plataforma Scopus. Limitaciones: solo se consideró la base de datos Scopus para el periodo 1992-2021. Resultados: la mayoría de las investigaciones se enfocan en Asia (India y Bangladesh) y se publican principalmente en Estados Unidos. Mediante el análisis de coautorías, se identificaron los principales autores, instituciones y países. Del análisis de coocurrencias de palabras, se desprenden tres clústeres: microcrédito, desarrollo humano y desarrollo económico. Valor: la construcción de una base bibliográfica para estudios sobre microcréditos y autonomía económica. Conclusiones: los estudios más recientes sobre la eficacia del microcrédito para las mujeres muestran la necesidad de incluir, además de las económicas, otras dimensiones al evaluar estas políticas de apoyo, tales como las relaciones de poder, las asimetrías de género y el contexto sociocultural.