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Background Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1‐year outcomes. Methods and Results The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30‐day Holter‐ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1‐year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2‐dimensional and 3‐dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P

Abstract Aims Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. Methods and results We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel

Abstract The major histocompatibility complex (MHC) is a genetic region in jawed vertebrates that contains key genes involved in the immune response. Associations between the MHC and avian malaria infections in wild birds have been observed and mainly explored in the Northern Hemisphere, while a general lack of information remains in the Southern Hemisphere. Here, we investigated the associations between the MHC genes and infections with Plasmodium and Haemoproteus blood parasites along a latitudinal gradient in South America. We sampled 93 rufous‐collared sparrows (Zonotrichia capensis) individuals from four countries, Colombia, Ecuador, Peru, and Chile, and estimated MHC‐I and MHC‐II allele diversity. We detected between 1–4 (MHC‐I) and 1–6 (MHC‐II) amino acidic alleles per individual, with signs of positive selection. We obtained generalized additive mixed models to explore the associations between MHC‐I and MHC‐II diversity and latitude. We also explored the relationship between infection status and latitude/biome. We found a non‐linear association between the MHC‐II amino acidic allele diversity and latitude. Individuals from north Chile presented a lower MHC genetic diversity than those from other locations. We also found an association between deserts and xeric shrublands and a lower prevalence of Haemoproteus parasites. Our results support a lower MHC genetic in arid or semi‐arid habitats in the region with the lower prevalence of Haemoproteus parasites.

Abstract Aim To translate and culturally adapt the FRAIL scale into Spanish and perform a preliminary test of diagnostic accuracy in patients admitted to intensive care units. Design Cross‐sectional diagnostic study. Methods Five intensive care units (ICU) in Spain were participated. Stage 1: Three native Spanish‐speaking bilingual translators familiar with the field of critical care translated the scale from English into Spanish. Stage 2: Three native English‐speaking bilingual translators familiar with critical care medicine. Stage 3: Authors of the original scale compared the English original and back‐translated versions of the scale. Stage 4: Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the comprehension and relevance of each of the items of the Spanish version in 30 patients of 3 different age ranges (65 years). Results The FRAIL scale was translated and adapted cross‐culturally for patients admitted to intensive care units in Spain. The process consisted of four stages: translation, back translation, comparison and pilot test. There was good correspondence between the original scale and the Spanish version in 100% of the items. The participating patients assessed the relevance (content validity) and comprehensibility (face validity) of each of the items of the first Spanish version. The relevance of some of the items scored low when the scale was used in patients younger than 65 years. Conclusions We have cross‐culturally adapted the FRAIL scale, originally in English, to Spanish for its use in the critical care medical setting in Spanish‐speaking countries. Implications for Professionals Physicians and nurses can apply the new scale to all patients admitted to the intensive care units. Nursing care can be adapted according to frailty, trying to reduce the side effects of admission to these units for the most fragile patients. Reporting Method The manuscript's authors have adhered to the EQUATOR guidelines, using the COSMIN reporting guideline for studies on the measurement properties of patient‐reported outcome measures. Patient or Public Contribution In a pilot clinical study, we applied the first version of the FRAIL‐Spain scale to intensive care unit (ICU) patients. Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the relevance (content validity) and comprehensibility (face validity) of the five items of the first Spanish version. Relevance was assessed using a 4‐point Likert scale ranging from 1 (no relevance) to 4 (high relevance), and comprehensibility was assessed as poor, acceptable or good. Each health professional applied the scale to three patients (total number of patients = 30) of three different age ranges (65 years) and recorded the time of application of the scale to each patient. Although the frailty scales were initially created by geriatricians to be applied to the elders, there is little experience with their application in critically ill patients of any age. Therefore, more information is needed to determine the relevance of using this scale in critical care patients. In this pilot study, we considered that nurses and critical care physicians should evaluate frailty using this adapted scale in adult patients admitted to the Intensive Care Units.

Abstract Homogenous enantioselective catalysis is nowadays the cornerstone in the manufacturing of enantiopure substances, but its technological implementation suffers from well‐known impediments like the lack of endurable catalysts exhibiting long‐term stability. The catalytically active intermetallic compound Palladium‐Gallium (PdGa), conserving innate bulk chirality on its surfaces, represent a promising system to study asymmetric chemical reactions by heterogeneous catalysis, with prospective relevance for industrial processes. Here, this work investigates the adsorption of 10,10′‐dibromo‐9,9′‐bianthracene (DBBA) on the PdGa:A(1¯1¯1¯) Pd3‐terminated surface by means of scanning tunneling microscopy (STM) and spectroscopy (STS). A highly enantioselective adsorption of the molecule evolving into a near 100% enantiomeric excess below room temperature is observed. This exceptionally high enantiomeric excess is attributed to temperature activated conversion of the S to the R chiral conformer. Tip‐induced bond cleavage of the R conformer shows a very high regioselectivity of the DBBA debromination. The experimental results are interpreted by density functional theory atomistic simulations. This work extends the knowledge of chirality transfer onto the enantioselective adsorption of non‐planar molecules and manifests the ensemble effect of PdGa surfaces resulting in robust regioselective debromination.

Abstract Background and Aim Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non‐endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain. Methods Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Results Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.

Abstract Studying the vocalisations of wild animals can be a challenge due to the limitations of traditional computational methods, which often are time‐consuming and lack reproducibility. Here, I present pykanto, a new software package that provides a set of tools to build, manage, and explore large sound databases. It can automatically find discrete units in animal vocalisations, perform semi‐supervised labelling of individual repertoires with a new interactive web app and feed data to deep learning models. pykanto can be used to streamline research on, for example, individual vocal signatures and acoustic similarity between individuals and populations. To demonstrate its capabilities, I put the library to the test on the vocalisations of male great tits in Wytham Woods, near Oxford, UK. The results show that the identities of individual birds can be accurately determined from their songs and that the use of pykanto improves the efficiency and reproducibility of the process.

Abstract Aims To evaluate the effectiveness of the ‘reserved therapeutic space’ intervention for improving the nurse–patient therapeutic relationship in acute mental health units in Spain. Design Multicentre intervention study with control group. Methods The study will be carried out in 12 mental health units. The ‘reserved therapeutic space’ intervention to be tested has been co‐designed and validated by both nurses and patients. The quality of the therapeutic relationship, the care received and perceived coercion among patients will be assessed. An estimated 131 patients per group are expected to participate. Funding was granted by the Instituto de Salud Carlos III. Co‐financed by the European Union (European Regional Development Fund (ERDF) (PI21/00605)) and College of Nurses of Barcelona (PR‐487/2021). The proposal was approved by all the Research Ethics Committees of participating centres. Results This project will lead to changes in clinical practice, transforming the current models of organization and care management in mental health hospitalization units. No patient or public contribution.

Abstract Age‐related changes in pharmacokinetics and pharmacodynamics, multimorbidity, frailty, and cognitive impairment represent challenges for drug treatments. Moreover, older adults are commonly exposed to polypharmacy, leading to increased risk of drug interactions and related adverse events, and higher costs for the healthcare systems. Thus, the complex task of prescribing medications to older polymedicated patients encourages the use of Clinical Decision Support Systems (CDSS). This paper evaluates the CDSS miniQ for identifying potentially inappropriate prescribing in poly‐medicated older adults and assesses the usability and acceptability of the system in health care professionals, patients, and caregivers. The results of the study demonstrate that the miniQ system was useful for Primary Care physicians in significantly improving prescription, thereby reducing potentially inappropriate medication prescriptions for elderly patients. Additionally, the system was found to be beneficial for patients and their caregivers in understanding their medications, as well as usable and acceptable among healthcare professionals, patients, and caregivers, highlighting the potential to improve the prescription process and reduce errors, and enhancing the quality of care for elderly patients with polypharmacy, reducing adverse drug events, and improving medication management.

Abstract A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science. The search focused on literature reporting the significance of factors in adherence to treatment between 2011 and 2021, including only experimental studies (e.g., randomized controlled trials [RCT], clinical trials, etc.). We included 47 experimental studies. The results of the systematic review (SR) are grouped according to predetermined categories of the World Health Organization (WHO): socioeconomic, treatment, condition, personal, and healthcare‐related factors. This review gives an actual overview of evidence‐based studies on adherence and analyzed the significance of factors defined by the WHO classification. By showing the strength of certain factors in several independent studies and concomitantly uncovering gaps in research, these insights could serve as a basis for the design of future adherence studies and models.

Abstract Background Anal cancer, although rare, is susceptible to early diagnosis. There is a group of patients who are at high risk for anal cancer, including immunocompromised individuals and particularly people living with human immunodeficiency virus (PLWH). In 2010, an anal cancer screening programme was implemented at the University Hospital La Paz (Hospital Universitario La Paz [HULP]) in Madrid, Spain, to diagnose and treat high‐grade squamous epithelial lesions (HSIL), which are the precursor to anal squamous cell carcinoma (ASCC). Objective To describe the characteristics of patients with ASCC diagnosed during the last 20 years in a Spanish tertiary hospital, and to identify differences between those diagnosed before and after the screening programme was implemented. Methods A retrospective, single‐centre study was conducted in a tertiary care centre. Clinical and demographic characteristics of patients diagnosed with squamous cell carcinoma of the anal or perianal canal between September 2000 and September 2020 at HULP were analysed. Results Forty‐three patients diagnosed with ASCC were included; 55% of them were immunosuppressed and no differences were found in terms of the period distribution of these patients. In the second period, more cases of ASCC were diagnosed in PLWH, but they had a higher CD4(+) T cell nadir count. Although more T1–T2 tumours were observed in the second period studied, the difference in tumour size between periods was not statistically significant (p = 0.103). In 23% of patients, HSIL was present before diagnosis (median time to progression: 67.6 months). At the start of the screening programme, four patients in follow‐up were diagnosed with ASCC. In addition, five patients who were not in follow‐up (despite meeting the criteria of the screening programme) were also diagnosed, but at more advanced stages. Conclusions During the last decade, the cases of ASCC diagnosed in our hospital have not decreased, likely due to the increasing global incidence of this disease, but also to the activity of our screening programme. Nevertheless, four PLWH included in the screening programme were diagnosed at earlier stages of the disease.

Abstract Purple phototrophic bacteria are one of the main actors in chemolithotrophic carbon fixation and, therefore, fundamental in the biogeochemical cycle. These microbes are capable of using insoluble electron donors such as ferrous minerals or even carbon‐based electrodes. Carbon fixation through extracellular electron uptake places purple phototrophic bacteria in the field of microbial electrosynthesis as key carbon capturing microorganisms. In this work we demonstrate biomass production dominated by purple phototrophic bacteria with a cathode (−0.6 V vs. Ag/AgCl) as electron donor. In addition, we compared the growth and microbial population structure with ferrous iron as the electron donor. We detect interaction between the cathode and the consortium showing a midpoint potential of 0.05 V (vs. Ag/AgCl). Microbial community analyses revealed different microbial communities depending on the electron donor, indicating different metabolic interactions. Electrochemical measurements together with population analyses point to Rhodopseudomonas genus as the key genus in the extracellular electron uptake. Furthermore, the genera Azospira and Azospirillum could play a role in the photoelectrotrophic consortium.

Abstract Background Malignant pleural effusions (MPEs) are a common complication of advanced cancers, particularly those adjacent to the pleura, such as lung and breast cancer. The pathophysiology of MPE formation remains poorly understood, and although MPEs are routinely used for the diagnosis of breast cancer patients, their composition and biology are poorly understood. It is difficult to distinguish invading malignant cells from resident mesothelial cells and to identify the directionality of interactions between these populations in the pleura. There is a need to characterize the phenotypic diversity of breast cancer cell populations in the pleural microenvironment, and investigate how this varies across patients. Methods Here, we used single‐cell RNA‐sequencing to study the heterogeneity of 10 MPEs from seven metastatic breast cancer patients, including three Miltenyi‐enriched samples using a negative selection approach. This dataset of almost 65 000 cells was analysed using integrative approaches to compare heterogeneous cell populations and phenotypes. Results We identified substantial inter‐patient heterogeneity in the composition of cell types (including malignant, mesothelial and immune cell populations), in expression of subtype‐specific gene signatures and in copy number aberration patterns, that captured variability across breast cancer cell populations. Within individual MPEs, we distinguished mesothelial cell populations from malignant cells using key markers, the presence of breast cancer subtype expression patterns and copy number aberration patterns. We also identified pleural mesothelial cells expressing a cancer‐associated fibroblast‐like transcriptomic program that may support cancer growth. Conclusions Our dataset presents the first unbiased assessment of breast cancer‐associated MPEs at a single cell resolution, providing the community with a valuable resource for the study of MPEs. Our work highlights the molecular and cellular diversity captured in MPEs and motivates the potential use of these clinically relevant biopsies in the development of targeted therapeutics for patients with advanced breast cancer.

Abstract Objectives Early‐ and late‐onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain‐specific cognitive function in a well characterized cohort of patients with a biomarker‐based diagnosis. Methods In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture. Results We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p

Abstract Background It has not been determined whether ileal appearance differs among dogs with chronic inflammatory enteropathy (CIE) and different serum concentrations of cobalamin. Objective To compare endoscopic and histologic ileal findings in dogs with CIE and different serum cobalamin concentrations and then evaluate the correlation of ileal changes to cobalamin serum concentration using updated scoring systems to assess the ileum. Animals Sixty‐eight dogs with CIE. Methods Retrospective study. Frequency of ileal features and ileal histologic and endoscopic scores (IHS and IES) were obtained and compared among CIE dogs with severe hypocobalaminemia (SHC; 350 ng/L). The correlation of IHS and IES with cobalamin was evaluated. Results Friability, villus atrophy, crypt dilatation, epithelial injury, and intraepithelial lymphocytes were more frequent in SHC than in NC dogs (all P ≤ .01). Median SHC‐IES (2; range, 0‐4) was higher than NC‐IES (1; range, 0‐5; P = .004). Median SHC‐IHS (6; range, 3‐9) was higher than HC‐IHS (4; range, 1‐7; P 350 ng/L in CIE dogs. With updated scales to assess the mucosa, greater ileal damage was associated with lower serum cobalamin concentration.

Background Elevated plasma levels of alpha‐aminoadipic acid (2‐AAA) have been associated with the development of type 2 diabetes and atherosclerosis. However, the nature of the association remains unknown. Methods and Results We identified genetic determinants of plasma 2‐AAA through meta‐analysis of genome‐wide association study data in 5456 individuals of European, African, and Asian ancestry from the Framingham Heart Study, Diabetes Prevention Program, Jackson Heart Study, and Shanghai Women’s and Men’s Health Studies. No single nucleotide polymorphisms reached genome‐wide significance across all samples. However, the top associations from the meta‐analysis included single‐nucleotide polymorphisms in the known 2‐AAA pathway gene DHTKD1, and single‐nucleotide polymorphisms in genes involved in mitochondrial respiration (NDUFS4) and macrophage function (MSR1). We used a Mendelian randomization instrumental variable approach to evaluate relationships between 2‐AAA and cardiometabolic phenotypes in large disease genome‐wide association studies. Mendelian randomization identified a suggestive inverse association between increased 2‐AAA and lower high‐density lipoprotein cholesterol (P=0.005). We further characterized the genetically predicted relationship through measurement of plasma 2‐AAA and high‐density lipoprotein cholesterol in 2 separate samples of individuals with and without cardiometabolic disease (N=98), and confirmed a significant negative correlation between 2‐AAA and high‐density lipoprotein (rs=−0.53, P

Chemotherapy‐induced peripheral neuropathy (CIPN) is a dose‐limiting adverse event associated with treatment with paclitaxel and other chemotherapeutic agents. The prevention and treatment of CIPN are limited by a lack of understanding of the molecular mechanisms underlying this toxicity. In the current study, a human induced pluripotent stem cell–derived sensory neuron (iPSC‐SN) model was developed for the study of chemotherapy‐induced neurotoxicity. The iPSC‐SNs express proteins characteristic of nociceptor, mechanoreceptor, and proprioceptor sensory neurons and show Ca2+ influx in response to capsaicin, α,β‐meATP, and glutamate. The iPSC‐SNs are relatively resistant to the cytotoxic effects of paclitaxel, with half‐maximal inhibitory concentration (IC50) values of 38.1 µM (95% confidence interval (CI) 22.9–70.9 µM) for 48‐hour exposure and 9.3 µM (95% CI 5.7–16.5 µM) for 72‐hour treatment. Paclitaxel causes dose‐dependent and time‐dependent changes in neurite network complexity detected by βIII‐tubulin staining and high content imaging. The IC50 for paclitaxel reduction of neurite area was 1.4 µM (95% CI 0.3–16.9 µM) for 48‐hour exposure and 0.6 µM (95% CI 0.09–9.9 µM) for 72‐hour exposure. Decreased mitochondrial membrane potential, slower movement of mitochondria down the neurites, and changes in glutamate‐induced neuronal excitability were also observed with paclitaxel exposure. The iPSC‐SNs were also sensitive to docetaxel, vincristine, and bortezomib. Collectively, these data support the use of iPSC‐SNs for detailed mechanistic investigations of genes and pathways implicated in chemotherapy‐induced neurotoxicity and the identification of novel therapeutic approaches for its prevention and treatment.

Abstract Accelerated long‐term forgetting (ALF) refers to a rapid loss of information over days or weeks despite normal acquisition/encoding. Notwithstanding its potential relevance as a presymptomatic marker of cognitive dysfunction, no study has addressed the relationship between ALF and Alzheimer’s disease (AD) biomarkers. We examined ALF in APOE ɛ4 carriers versus noncarriers, and its relationships with AD cerebrospinal fluid (CSF) biomarkers. We found ALF over three months in APOE ɛ4 carriers (F(1,19) = 5.60; P