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Abstract Chemical Short-Range Order (CSRO) has attracted recent attention from many researchers, creating intense debates about its impact on material properties. The challenges lie in confirming and quantifying CSRO, as its detection proves exceptionally demanding, contributing to conflicting data in the literature regarding its true effects on mechanical properties. Our work uses high-precision calorimetric data to unambiguously prove the existence and, coupled with atomistic simulations, quantify the type of CSRO. This methodology allows us to propose a mechanism for its formation and destruction based on the heat evolution during thermal analysis and facilitates a precise identification of local ordering in CoCrNi alloys. Samples of CoCrNi (Co33Cr33Ni33) and CrNi2 (Cr33Ni66) alloys are fabricated in varying ordered states, extensively characterized via synchrotron X-ray diffraction, X-ray absorption spectroscopy, and transmission electron microscopy. Samples with considerably different ordered states are submitted to tensile tests with in-situ synchrotron X-ray diffraction. We demonstrate, despite inducing varied CSRO levels in CoCrNi, no significant alterations in overall mechanical behavior emerge. However, the CrNi2 alloy, which undergoes long-range ordering, experiences significant shifts in yield strength, ultimate tensile stress and ductility.

Abstract Batch effects in single-cell RNA-seq data pose a significant challenge for comparative analyses across samples, individuals, and conditions. Although batch effect correction methods are routinely applied, data integration often leads to overcorrection and can result in the loss of biological variability. In this work we present STACAS, a batch correction method for scRNA-seq that leverages prior knowledge on cell types to preserve biological variability upon integration. Through an open-source benchmark, we show that semi-supervised STACAS outperforms state-of-the-art unsupervised methods, as well as supervised methods such as scANVI and scGen. STACAS scales well to large datasets and is robust to incomplete and imprecise input cell type labels, which are commonly encountered in real-life integration tasks. We argue that the incorporation of prior cell type information should be a common practice in single-cell data integration, and we provide a flexible framework for semi-supervised batch effect correction.

A 42-day experiment assessed the effects of phytase and a multicarbohydrase complex containing α-galactosidase (CAG) on broiler performance, processing yield, and nutrient digestibility. Exactly 2250-day-old male broilers were distributed in 90 floor pens and assigned to 1 of 9 treatments (10 replicates). A positive control sufficient in phosphorus (PC-P), a PC sufficient in metabolizable energy (PC-E), and a negative control (NC) with less phosphorus, calcium, and metabolizable energy were formulated. Manufactured using the NC, six additional treatments contained 500 or 1500 FTU/kg of phytase combined with 0, 0.1, or 0.2 g/kg of CAG. Broiler performance was determined on days 14, 28, and 42. Nutrient digestibility and processing yield was determined on days 42 and 43, respectively. Day 1–42 FCR was reduced and fillet yield increased when broilers consumed a 0.2 g/kg CAG diet instead of 0.1 g/kg (P

Abstract Species occurrence data are foundational for research, conservation, and science communication, but the limited availability and accessibility of reliable data represents a major obstacle, particularly for insects, which face mounting pressures. We present BeeBDC, a new R package, and a global bee occurrence dataset to address this issue. We combined >18.3 million bee occurrence records from multiple public repositories (GBIF, SCAN, iDigBio, USGS, ALA) and smaller datasets, then standardised, flagged, deduplicated, and cleaned the data using the reproducible BeeBDC R-workflow. Specifically, we harmonised species names (following established global taxonomy), country names, and collection dates and, we added record-level flags for a series of potential quality issues. These data are provided in two formats, “cleaned” and “flagged-but-uncleaned”. The BeeBDC package with online documentation provides end users the ability to modify filtering parameters to address their research questions. By publishing reproducible R workflows and globally cleaned datasets, we can increase the accessibility and reliability of downstream analyses. This workflow can be implemented for other taxa to support research and conservation.

Abstract Objective Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. Methods This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. Results We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. Conclusions We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Background: This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an anti-synthetase syndrome and treatment with methotrexate and rituximab. Case description: The patient arrived at the Emergency Department with epigastric pain, vomiting and dark urine. Initial examination revealed signs of inflammation and hepatic dysfunction. Subsequent laboratory tests and imaging confirmed acute hepatitis E infection in the context of recent initiation of rituximab therapy. Despite initial suspicion of pancreatitis, subsequent investigations ruled out pancreatic involvement. Treatment with ribavirin, along with supportive measures, led to significant clinical improvement with resolution of jaundice, ascites, and oedema. Conclusions: This case underscores the importance of considering hepatitis E in patients with autoimmune conditions, especially when initiating immunosuppressive therapies, a situation that is not well described in scientific literature and is increasingly common, necessitating proper recognition.

Introducción y objetivos: El Parque Interjurisdiccional Marino Costero Patagonia Austral es un área protegida que alberga una gran biodiversidad. Dentro del Parque se encuentra Isla Valdés, isla de la cual se desconoce su vegetación y en la que se han introducido conejos europeos, una especie herbívora invasora. Los objetivos del presente trabajo son: a) conocer la riqueza florística de Isla Valdés; b) evaluar el estado de conservación de su flora; c) identificar y caracterizar las diferentes unidades de vegetación; d) analizar las diferencias y sus posibles causas entre las unidades de vegetación. M&M: se recorrió la isla estableciendo las diferentes unidades de vegetación. En cada una se realizaron tres transectas, con el Método Holístico Florístico paraáreas áridas, semiáridas y subhúmedas. Con los datos obtenidos se calcularon parámetros de la estructura de la vegetación y ecológicos, se elaboró un listado de la composición florística, se describió cada unidad de vegetación, y se evaluó estado de conservación actual de la vegetación. Resultados: Se identificaron 74 especies, distribuidas en 31 familias botánicas. Se identificaron cinco unidades de vegetación con diferente composición florística y fisonomía vegetal. Doce especies se encuentran en la Lista roja preliminar de las plantas endémicas de la Argentina, y dos presentan categoría de conservación internacional (lista roja de la UICN yCITES). Conclusiones: El trabajo constituye el primer listado florístico de Isla Valdés, y aporta información importante para la toma de decisiones de manejo.

BackgroundArtificial intelligence chatbots such as ChatGPT (OpenAI) have garnered excitement about their potential for delegating writing tasks ordinarily performed by humans. Many of these tasks (eg, writing recommendation letters) have social and professional ramifications, making the potential social biases in ChatGPT’s underlying language model a serious concern. ObjectiveThree preregistered studies used the text analysis program Linguistic Inquiry and Word Count to investigate gender bias in recommendation letters written by ChatGPT in human-use sessions (N=1400 total letters). MethodsWe conducted analyses using 22 existing Linguistic Inquiry and Word Count dictionaries, as well as 6 newly created dictionaries based on systematic reviews of gender bias in recommendation letters, to compare recommendation letters generated for the 200 most historically popular “male” and “female” names in the United States. Study 1 used 3 different letter-writing prompts intended to accentuate professional accomplishments associated with male stereotypes, female stereotypes, or neither. Study 2 examined whether lengthening each of the 3 prompts while holding the between-prompt word count constant modified the extent of bias. Study 3 examined the variability within letters generated for the same name and prompts. We hypothesized that when prompted with gender-stereotyped professional accomplishments, ChatGPT would evidence gender-based language differences replicating those found in systematic reviews of human-written recommendation letters (eg, more affiliative, social, and communal language for female names; more agentic and skill-based language for male names). ResultsSignificant differences in language between letters generated for female versus male names were observed across all prompts, including the prompt hypothesized to be neutral, and across nearly all language categories tested. Historically female names received significantly more social referents (5/6, 83% of prompts), communal or doubt-raising language (4/6, 67% of prompts), personal pronouns (4/6, 67% of prompts), and clout language (5/6, 83% of prompts). Contradicting the study hypotheses, some gender differences (eg, achievement language and agentic language) were significant in both the hypothesized and nonhypothesized directions, depending on the prompt. Heteroscedasticity between male and female names was observed in multiple linguistic categories, with greater variance for historically female names than for historically male names. ConclusionsChatGPT reproduces many gender-based language biases that have been reliably identified in investigations of human-written reference letters, although these differences vary across prompts and language categories. Caution should be taken when using ChatGPT for tasks that have social consequences, such as reference letter writing. The methods developed in this study may be useful for ongoing bias testing among progressive generations of chatbots across a range of real-world scenarios. Trial RegistrationOSF Registries osf.io/ztv96; https://osf.io/ztv96

BackgroundThe physical, paper-based Georgia TB Reference Guide has served as the clinical reference handbook on tuberculosis (TB) diagnostic and treatment guidelines for the state of Georgia in the United States. Supported by the Georgia Department of Public Health, the production of the 112-page palm-sized booklet was previously led by a team of Georgia-based TB experts at Emory University and printed every three-five years with updates to clinical management guidelines and TB consult contact information. However, the costs associated with editorial printing combined with delays in updating a static printed booklet with revised guidance hampered the utility of the tool. Considering the barriers with paper-based production and based on the beneficial use of apps to support the dissemination of clinical management guidance in other settings, the booklet was converted into a mobile application. This paper describes the process of developing a mobile app version of the Georgia TB Reference Guide in an easy-to-update and readily available format.MethodsWe employed a user-centered design approach to develop the app, including a series of qualitative interviews and quantitative surveys. Participants included a mix of state officials and local TB experts. First, initial foundational interviews were conducted to conceptualize current utilization practices of both the paper and PDF versions of the tool. Second, the findings from the initial interviews were organized thematically and informed the design of the app, which was then beta tested by a round of previously unsampled TB experts as well as a re-sample from the initial interviews. Third, the designs were coded into developmental phases and beta tested among users of the current Georgia TB Reference Guide. Fourth, the app was published and downloaded by a pre-selected group of local users who provided answers to a follow-up survey after using the app for one month. Fifth, user growth, self-reported demographics, and app usage between February and July 2022 were recorded through automatic data metrics built into the app.ResultsThe paper copy Georgia TB Reference Guide usage themes included commonly referenced content, navigation paths, and desired features and content. The themes were converted into features and designs such as prioritizing commonly reviewed topics and guide customization with bookmarks and notes. Iterations of the designs were driven by feedback from TB experts and included home page featured content, improving content readability, and improving the search feature. The follow-up survey revealed a 90% preference for the app over the paper version of the guide. In the six months following the app's release, the app was downloaded by 281 individuals in the United States. The majority of downloads were in Georgia and the app also expanded organically to 19 other states.ConclusionThe experience of converting the Georgia TB Reference Guide offers specific and effective steps to converting a medical reference guide into a mobile application tool that is readily available, easy to use, and easy to update. The organic dissemination of the app beyond the state of Georgia's borders within the first six months of app launch underscores desire among TB healthcare professionals for high-quality digital reference content outside the state. This experience offers clear outlines for replication in other contexts and demonstrates the utility of similar mobile medical reference tools.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient’s blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

Abstract Memristors, a cornerstone for neuromorphic electronics, respond to the history of electrical stimuli by varying their electrical resistance across a continuum of states. Much effort has been recently devoted to developing an analogous response to optical excitation. Here we realize a novel tunnelling photo-memristor whose behaviour is bimodal: its resistance is determined by the dual electrical-optical history. This is obtained in a device of ultimate simplicity: an interface between a high-temperature superconductor and a transparent semiconductor. The exploited mechanism is a reversible nanoscale redox reaction between both materials, whose oxygen content determines the electron tunnelling rate across their interface. The redox reaction is optically driven via an interplay between electrochemistry, photovoltaic effects and photo-assisted ion migration. Besides their fundamental interest, the unveiled electro-optic memory effects have considerable technological potential. Especially in combination with high-temperature superconductivity which, in addition to facilitating low-dissipation connectivity, brings photo-memristive effects to the realm of superconducting electronics.

Abstract With today’s pace of rapid technological advancement, many patient issues in modern medicine are increasingly solvable by mobile app solutions, which also have the potential to transform how clinical research is conducted. However, many critical challenges in the app development process impede bringing these translational technologies to patients, caused in large part by the lack of knowledge among clinicians and biomedical researchers of “what it takes” to design, develop, and maintain a successful medical app. Indeed, problems requiring mobile app solutions are often nuanced, requiring more than just clinical expertise, and issues such as the cost and effort required to develop and maintain a well-designed, sustainable, and scalable mobile app are frequently underestimated. To bridge this skill set gap, we established an academic unit of designers, software engineers, and scientists that leverage human-centered design methodologies and multi-disciplinary collaboration to develop clinically viable smartphone apps. In this report, we discuss major misconceptions clinicians and biomedical researchers often hold regarding medical app development, the steps we took to establish this unit to address these issues and the best practices and lessons learned from successfully ideating, developing, and launching medical apps. Overall, this report will serve as a blueprint for clinicians and biomedical researchers looking to better benefit their patients or colleagues via medical mobile apps.

Abstract Background Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia–reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. Methods This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. Results The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. Conclusions MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.

Abstract Cardiac arrest (CA) patients suffer from systemic ischemia–reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P

Heart-Failure (HF) is among the leading hospitalization causes in modern healthcare systems. In this paper, a method for performing continuous patient monitoring with a focus on low power consumption is presented. A prototype wearable device to assist clinical practice and improve patient’s outcomes by collecting biological impedance measurements is being developed at the University of Sevilla. Among the sensing components there are two major blocks formed by a commercial biological impedance analog frontend from Analog Devices (AD5940) and an Inertial Motion Unit (IMU) capable of estimating attitude of the device. This information could provide potential new insight into the patient’s status for the physician and help diagnose and remote monitor patients with HF. A major factor that can be analyzed to provide information on patient status is activity level and body states; time spent walking or standing, laying down or seated. In this work, a body tracking / activity estimation method is proposed for low power continuous monitoring. One key factor that can provide information on a patient’s status is their activity level and body position, such as time spent walking, standing, sitting, or lying down. This paper proposes a body tracking/activity estimation method for low-power continuous monitoring. The study reports a 97.6% prediction accuracy for lying down and standing/walking/seated positions and a 67.2% accuracy for discriminating between sitting and walking/standing positions. These results are highly relevant for clinical practice, as body motion and position can serve as important health markers for patients. Moreover, the motion information obtained can be further processed to better understand variations in the analog impedance measurements.

CHEK2 mutations have been noted in bone, brain, breast, colon, lung, thyroid, and prostate cancer. Although now reported in both clear cell and non-clear cell renal cancer, we have not found CHEK2 2 mutations reported in the papillary type II subtype (PRCC). Here, we report a 63-year-old female with a PRCC type II with a concomitant CHEK2 C1100del mutation, who is currently in complete remission three years post tumor resection.

Abstract BackgroundMaternal mortality in the United States is a public health crisis and national emergency. Missed or delayed recognition of preventable life-threatening symptoms and untimely treatment of preventable high-risk medical conditions have been cited as key contributors to the nation’s worsening mortality rates. Effective strategies are urgently needed to address this maternal health crisis, particularly for Black birthing populations. Morbidity and Mortality Assessment: Lifting Outcomes Via Education (MAMA LOVE) is a web-based platform that focuses on the identification of maternal morbidity and mortality risk factors. ObjectiveThe purpose of this paper is to present the conceptualization, development, heuristics, and utility evaluation of the web-based maternal mortality risk assessment and educational tool MAMA LOVE. MethodsA user-centered design approach was used to gain feedback from clinical experts and potential end users to ensure that the tool would be effective among groups most at risk for maternal morbidity and mortality. A heuristic evaluation was conducted to evaluate usability and need within the current market. Algorithms describing key clinical, mental health, and social conditions were designed using digital canvas software (Miro) and incorporated into the final wireframes of the revised prototype. The completed version of MAMA LOVE was designed in Figma and built with the SurveyJS platform. ResultsThe creation of the MAMA LOVE tool followed three distinct phases: (1) the content development and creation of an initial prototype; (2) the feedback gathering and usability assessment of the prototype; and (3) the design, development, and testing of the final tool. The tool determines the corresponding course of action using the algorithm developed by the authors. A total of 38 issues were found in the heuristic evaluation of the web tool’s initial prototype. ConclusionsMaternal morbidity and mortality is a public health crisis needing immediate effective interventions. In the current market, there are few digital resources available that focus specifically on the identification of dangerous symptoms and risk factors. MAMA LOVE is a tool that can address that need by increasing knowledge and providing resources and information that can be shared with health care professionals.

The Argentine anchovy, Engraulis anchoita, plays a vital role as a key prey species for several marine predators in the north Patagonian marine ecosystem of the Atlantic Ocean. Reconstructing the length and weight of each consumed specimen is essential to provide a detailed description of the trophic ecology of top marine predators. Predictive linear regression equations were calculated for the Patagonian stock of Argentine anchovy to estimate parameters of length-weight relationships using measurements of whole individuals and diagnostic elements such as otoliths, head bones and pectoral fin bones. Among the diagnostic elements analyzed, the cleithrum and dentary exhibited the best fit. This study validates the use of head and pectoral girdle bones as reliable indicators for predicting the weight and length of Argentine anchovy across a wide size range, which corresponds to the target range of various predators. These relationships can contribute to the determination of body condition, estimation of consumed biomass, and calculation of energy density, providing valuable insights into the trophic ecology of predators in the southern Atlantic Ocean.

Abstract Background Single-cell RNA sequencing (scRNA-seq) technologies offer unique opportunities for exploring heterogeneous cell populations. However, in-depth single-cell transcriptomic characterization of complex tissues often requires profiling tens to hundreds of thousands of cells. Such large numbers of cells represent an important hurdle for downstream analyses, interpretation and visualization. Results We develop a framework called SuperCell to merge highly similar cells into metacells and perform standard scRNA-seq data analyses at the metacell level. Our systematic benchmarking demonstrates that metacells not only preserve but often improve the results of downstream analyses including visualization, clustering, differential expression, cell type annotation, gene correlation, imputation, RNA velocity and data integration. By capitalizing on the redundancy inherent to scRNA-seq data, metacells significantly facilitate and accelerate the construction and interpretation of single-cell atlases, as demonstrated by the integration of 1.46 million cells from COVID-19 patients in less than two hours on a standard desktop. Conclusions SuperCell is a framework to build and analyze metacells in a way that efficiently preserves the results of scRNA-seq data analyses while significantly accelerating and facilitating them.

T-cell large granular lymphocyte (T-LGL) leukemia is a rare and indolent clonal disorder of LGLs, associated with rheumatoid arthritis and neutropenia. The authors present a case of a 62-year-old male with rheumatoid arthritis (RA) who was diagnosed with T-LGL leukemia, with predominant neutropenia, and a poor response to conventional treatment. Subsequently, tofacitinib (a Janus Kinase 1 and 3 inhibitor, [JAK1/3 inhibitor]) resulted in improvement of the patient’s RA symptoms and temporary improvement of the neutropenia. Ultimately, upadacitinib (a specific JAK1 inhibitor) resulted in further improvement of the neutropenia and control of his RA. To the best of our knowledge, this is the first case report of coexisting RA and LGL leukemia that was treated with upadacitinib and showed clinical improvement.

En el presente artículo se propone una revisión de la etimología de las palabras de origen propiamente japonés que aparecen en la edición actual del Diccionario de la lengua española (DLE). Se ha rastreado la formación y la evolución primeras de estas palabras dentro de los niveles protojapónico y protojaponés, así como sus cambios desde el idioma antiguo hasta el premoderno o moderno, antes de servir como base para los préstamos a las lenguas europeas y finalmente al castellano. La intención primordial de este trabajo es proporcionar una guía que facilite su labor al lexicógrafo cuando elabore etimologías, tanto para el DLE como para los diccionarios históricos de la lengua castellana.

Abstract Near the threshold of grain motion, sediment transport is “on‐off” intermittent, characterized by large but rare bursts separated by long periods of low transport. Without models that can account for the effects of intermittency, measurements of average sediment flux can be in error by up to an order of magnitude. Despite its known presence and impact, it is not clear whether on‐off intermittency arises from the grain activity (the number of moving grains) or grain velocities, which together determine the sediment flux. We use laboratory flume experiments to show that the on‐off intermittency has its origins in the velocity distributions of grains that move by rolling along the bed, whereas grain activity is not on‐off intermittent. Incorporating the types of intermittency we identify into stochastic models of sediment transport could yield improved predictions of sediment flux, including physically based estimates of the uncertainty in time‐averaged sediment flux.

Neonicotinoids are effective insecticides with specificity for invertebrate nicotinic acetylcholine receptors. Neonicotinoids are chemically stable and tend to remain in the environment for long so concerns about their neurotoxicity in humans do nothing but increase. Herein, we evaluated the chronic toxic effects of acetamiprid- and imidacloprid-based insecticides over the differentiation of human neuroblastoma SH-SY5Y cells, which were exposed to these insecticides at a concentration range similar to that applied to crop fields (0.01–0.5 mM). Both insecticides did not have acute cytotoxic effects in both non-differentiated and in staurosporine-differentiated SH-SY5Y cells cytotoxicity as measured by the MTT and vital-dye exclusion tests. However, after a chronic (7-day) treatment, only imidacloprid dose-dependently decreased the viability of SH-SY5Y cells (F(4,39) = 43.05, P

El aneurisma de la vena retromandibular es una lesión muy poco frecuente, siendo más rara si se complica con trombosis. Debido a la localización cervical cercana al ángulo de la mandíbula, puede simular muchas patologías. Suele presentarse como una tumoración blanda, generalmente asintomática, aunque puede cursar con dolor en caso de trombosis o compresión nerviosa. La ecografía es el método diagnóstico inicial: permite diferenciar la naturaleza sólida o quística de la lesión, la existencia de vascularización y su conexión con estructuras vasculares. La tomografía computarizada con contraste intravenoso es el método de imagen de elección, siendo la ligadura del aneurisma el tratamiento que mejores resultados ofrece. Presentamos el caso de un paciente con múltiples factores de riesgo cardiovascular con el objetivo de describir un aneurisma de la vena retromandibular inicialmente asintomático que en su evolución se complicó con trombosis del aneurisma, seguida de hemorragia cerebral masiva presumiblemente motivada por la anticoagulación, con fallecimiento posterior.

Antecedentes: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. Objetivo: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. Material y métodos: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. Resultados: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. Conclusiones: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.

Recently, there has been renewed interest in lightweight structures; however, a small structure change can strongly affect vehicle dynamic behavior. Therefore, this study provides new insights into non-parametric modeling based on artificial neural networks (ANNs). This work is then motivated by the requirement for a reliable substitute for virtual instrumentation in electric car development to enable the prediction of the current value of the vehicle slip from a given time history of the vehicle (input) and previous values of synthetic data (feedback). The training data are generated from a multi-body simulation using MSC Adams Car; the simulation involves a double lane-change maneuver. This test is commonly used to evaluate vehicle stability. Based on dynamic considerations, this study implements the nonlinear autoregressive exogenous (NARX) identification scheme used in time-series modeling. This work presents an ANN that is able to predict the side slip angle from simulated training data generated employing MSC Adams Car. This work is a specific solution to overtake maneuvers, avoiding the loss of vehicle control and increasing driving safety.

ABSTRACT Introduction and objectives: Coronary artery aneurysms are a complex situation. Our main objective is to describe the frequency of use of covered stents (grafts) for their management, as well as to characterize their long-term results compared to drug-eluting stents. Methods: Ambispective observational study with data from the International Coronary Artery Aneurysm Registry (CAAR) (NCT-02563626). Only patients who received a stent-graft or a drug-eluting stent where the aneurysm occurred were selected. Results: A total of 17 patients received, at least, 1 stent-graft while 196 received 1 drug-eluting in the aneurysmal vessel. Male predominance, a higher rate of dyslipidemia, a past medical history of coronary artery disease, previously revascularized coronary artery disease, and giant aneurysms were reported in the stent-graft cohort. The independent predictive variables of the composite endpoint of all-cause mortality, heart failure, unstable angina, reinfarction, stroke, systemic embolism, bleeding or any aneurysmal complications at the median follow-up of 38 months were suggestive of the existence of connective tissue diseases (HR, 5.94; 95%CI, 1.82-19.37), left ventricular dysfunction ≤ 55% (HR, 1.84; 95%CI, 1.09-3.1), and an acute indication for heart catheterization (HR, 2.98; 95%CI, 1.39-6.3). The use of stent-grafts was not associated with the occurrence of more composite endpoints (23.5% vs 29.6%; P = .598). Conclusions: The use of stent-grafts to treat coronary aneurysms is feasible and safe in the long-term. Randomized clinical trials are needed to decide what the best treatment is for these complex lesions. Keywords: Coronary aneurysm. Registry. Stent. Stent graft. Angioplasty.

RESUMEN Introducción y objetivos: Los aneurismas coronarios son una situación compleja. Planteamos como objetivo principal describir la frecuencia de utilización de stents recubiertos (grafts) para su tratamiento y caracterizar sus resultados a largo plazo en comparación con stents farmacoactivos. Métodos: Estudio observacional ambispectivo, con información procedente del Registro Internacional de Aneurismas Coronarios (CAAR) (NCT-02563626). Se seleccionaron los pacientes que recibieron un stent-graft o un stent farmacoactivo en la zona del aneurisma. Resultados: Un total de 17 pacientes recibieron al menos un stent-graft y 196 un stent farmacoactivo en la zona aneurismática. Se observa un predominio del sexo masculino y una mayor frecuencia de dislipemia, antecedentes de coronariopatía, enfermedad coronaria revascularizada previamente y aneurismas gigantes en la cohorte de stent-graft. Como variables independientes predictoras del desarrollo del evento combinado (muerte por cualquier causa, insuficiencia cardiaca, angina inestable, reinfarto, ictus, embolia sistémica, sangrado o cualquier complicación en el aneurisma), tras una mediana de seguimiento de 38 meses, destacaron la existencia de conectivopatías (hazard ratio [HR] = 5,94; intervalo de confianza del 95% [IC95%], 1,82-19,37), la disfunción del ventrículo izquierdo ≤ 55% (HR = 1,84; IC95%, 1,09-3,1) y la indicación aguda del cateterismo índice (HR = 2,98; IC95%, 1,39-6,3). El uso de stent-grafts comparado con el de stents farmacoactivos no se asoció al desarrollo de más eventos combinados (23,5 frente a 29,6%; p = 0,598). Conclusiones: El uso de stents recubiertos en aneurismas coronarios es factible y seguro a largo plazo. Se necesitan estudios clínicos aleatorizados para decidir el mejor tratamiento de este tipo de lesiones complejas.

Background: Ancestry is often viewed as a more objective and less objectionable population descriptor than race or ethnicity. Perhaps reflecting this, usage of the term “ancestry” is rapidly growing in genetics research, with ancestry groups referenced in many situations. The appropriate usage of population descriptors in genetics research is an ongoing source of debate. Sound normative guidance should rest on an empirical understanding of current usage; in the case of ancestry, questions about how researchers use the concept, and what they mean by it, remain unanswered.Methods: Systematic literature analysis of 205 articles at least tangentially related to human health from diverse disciplines that use the concept of ancestry, and semi-structured interviews with 44 lead authors of some of those articles.Results: Ancestry is relied on to structure research questions and key methodological approaches. Yet researchers struggle to define it, and/or offer diverse definitions. For some ancestry is a genetic concept, but for many—including geneticists—ancestry is only tangentially related to genetics. For some interviewees, ancestry is explicitly equated to ethnicity; for others it is explicitly distanced from it. Ancestry is operationalized using multiple data types (including genetic variation and self-reported identities), though for a large fraction of articles (26%) it is impossible to tell which data types were used. Across the literature and interviews there is no consistent understanding of how ancestry relates to genetic concepts (including genetic ancestry and population structure), nor how these genetic concepts relate to each other. Beyond this conceptual confusion, practices related to summarizing patterns of genetic variation often rest on uninterrogated conventions. Continental labels are by far the most common type of label applied to ancestry groups. We observed many instances of slippage between reference to ancestry groups and racial groups.Conclusion: Ancestry is in practice a highly ambiguous concept, and far from an objective counterpart to race or ethnicity. It is not uniquely a “biological” construct, and it does not represent a “safe haven” for researchers seeking to avoid evoking race or ethnicity in their work. Distinguishing genetic ancestry from ancestry more broadly will be a necessary part of providing conceptual clarity.

Here we document a rare, acute, infection caused by non-toxigenic Corynebacterium diphtheriae and the resulting unique and severe clinical sequelae. Our patient was a young man with no known pre-existing conditions that presented in cardiopulmonary arrest. We contrast this case with prior instances of non-toxigenic C. diphtheriae strain infection in the United States and summarize the literature that suggests systemic infection can result in cardiogenic toxicity. We speculate on a possible missed, pre-existing condition that could have increased this patient’s susceptibility to poor clinical outcome.

Invasive fungal infections as aspergillosis and candidiasis are well-documented complications in critically ill patients with acute respiratory distress syndrome due to COVID-19. However, invasive infections by other molds are rarely reported. We describe a case of invasive fusariosis in a patient with severe COVID-19 with a fatal outcome.

Abstract Background Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. Methods This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. Results Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21–1.62; p

Abstract Background Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. Methods Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. Results The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan–Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in d-glutamine and d-glutamate metabolism. Conclusions H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia–reperfusion injury in critically ill patients who require ECMO support.

BackgroundCardiovascular disease (CVD) is the leading cause of death among women in the United States. A considerable number of young women already have risk factors for CVD. Awareness of CVD and its risk factors is critical to preventing CVD, yet younger women are less aware of CVD prevalence, its risk factors, and preventative behaviors compared to older women. ObjectiveThe purpose of this study is to assess CVD awareness among adolescent and young adult women and develop a lifestyle-based cardiovascular risk assessment tool for the promotion of CVD awareness among this population. MethodsThis study used a 3-phase iterative design process with young women and health care practitioners from primary care and reproductive care clinics in Atlanta, Georgia. In phase 1, we administered a modified version of the American Heart Association Women’s Health Survey to young women, aged 15-24 years (n=67), to assess their general CVD awareness. In phase 2, we interviewed young women, aged 13-21 years (n=10), and their health care practitioners (n=10), to solicit suggestions for adapting the Healthy Heart Score, an existing adult cardiovascular risk assessment tool, for use with this age group. We also aimed to learn more about the barriers and challenges to health behavior change within this population and the clinical practices that serve them. In phase 3, we used the findings from the first 2 phases to create a prototype of a new online cardiovascular risk assessment tool designed specifically for young women. We then used an iterative user-centered design process to collect feedback from approximately 105 young women, aged 13-21 years, as we adapted the tool. ResultsOnly 10.5% (7/67) of the young women surveyed correctly identified CVD as the leading cause of death among women in the United States. Few respondents reported having discussed their personal risk (4/67, 6%) or family history of CVD (8/67, 11.9%) with a health care provider. During the interviews, young women reported better CVD awareness and knowledge after completing the adult risk assessment tool and suggested making the tool more teen-friendly by incorporating relevant foods and activity options. Health care practitioners emphasized shortening the assessment for easier use within practice and discussed other barriers adolescents may face in adopting heart-healthy behaviors. The result of the iterative design process was a youth-friendly prototype of a cardiovascular risk assessment tool. ConclusionsAdolescent and young adult women demonstrate low awareness of CVD. This study illustrates the potential value of a cardiovascular risk assessment tool adapted for use with young women and showcases the importance of user-centered design when creating digital health interventions.

La expansión urbana sobre paisajes agrícolas genera interfases urbano-rurales. La coexistencia de usos del suelo agrícolas y residenciales puede promover conflictos en torno al uso de plaguicidas. En Mendoza, Argentina, la escasez del recurso hídrico limita el traslado de la agricultura más allá de las áreas irrigadas, por lo que es importante mejorar esta convivencia. Para disminuir el uso de plaguicidas se necesitan estrategias asentadas en funciones ecosistémicas como el control biológico de plagas por conservación. Esta estrategia depende de la biodiversidad funcional presente en el paisaje; en especial, de las comunidades vegetales con capacidad de brindar hábitat a especies de artrópodos, parasitoides y depredadores generalistas. El objetivo de este trabajo fue construir un índice para evaluar la capacidad de proveer hábitat potencial para los controladores biológicos (IHPB) en diferentes ambientes de un paisaje, con el fin de aportar conocimientos para el ordenamiento ambiental territorial de áreas de interfase. El IHPB se construyó a partir de 5 indicadores y se puso a prueba en el distrito de Lunlunta (Maipú, Mendoza). Se clasificó el área de estudio en 6 unidades de paisaje (UP): Natural de secano, Natural de ribera, Seminatural, Agrícola convencional, Agrícola biodiverso y Urbana. En ellas se realizaron censos de vegetación para calcular los indicadores. El valor más alto de IHPB ocurrió en la UP Natural de secano por la alta diversidad y la cobertura total y de especies arbóreas y arbustivas nativas presentes en su comunidad vegetal; el IHPB más bajo ocurrió en la UP Agrícola convencional. Su aplicación confirmó la importancia de las áreas naturales en cuanto a su potencialidad para sostener a la entomofauna benéfica base para el control biológico de plagas, y la necesidad de mejorar las condiciones de hábitat en los ambientes agrícolas.

El objetivo de este trabajo fue caracterizar la variabilidad espaciotemporal de clorofila satelital (Clsat), productividad primaria (PP), temperatura de la superficie del mar (TSM) y altura del nivel del mar (ANM) de julio de 2002 a diciembre de 2018 en el banco de Campeche. Se descargaron composiciones mensuales de Clsat y TSM del sensor MODIS-Aqua, y de ANM de la página COPERNICUS. Las composiciones de PP se descargaron de la página de internet de la Universidad Estatal de Oregón. Se estudiaron 4 transectos de 200 km perpendiculares a la costa de Campeche (T1 a T4), y 1 de 300 km paralelo a la misma (T5). Se construyeron series de tiempo y diagramas Hovmöller para estudiar las variaciones espaciales y temporales. La Clsat en T1 a T4 mostró una distinción entre una zona interior (0–60 km) y una exterior (60–200 km). La zona nerítica interior presentó los máximos de Clsat (>2.5 mg·m–3) y PP (>2 g C·m–2·d–1) en época de lluvias y los mínimos en época de secas (0.6 mg·m–3) y PP (>0.7 g C·m–2·d–1) durante los frentes fríos y los mínimos en secas (30 °C) en época de lluvias y mínimos (0.40 m) durante frentes fríos y mínimos (

Goblet cell carcinoma (GCC) is a rare tumor. The diagnosis, management, and classification of GCC are controversial. The North American Neuroendocrine Tumor Society (NANETS) and European Neuroendocrine Tumor Society (ENETS) recommend classifying and treating GCC's as adenocarcinomas. However, recent data shows that GCC has a different driver mutation and prognosis. Therefore, a new classification and strategy of treatment are necessary. We present a case report of advanced GCC and highlight the challenges regarding management recommendations due to the lack of consensus. We believe that this literature review will emphasize the need for multidisciplinary management and highlight the knowledge gap which impacts treatment decisions.

Alexander Vovin. [2005 y 2009] 2020. A Descriptive and Comparative Grammar of Western Old Japanese. Revised, Updated and Enlarged 2nd Edition. 2 vols. History of Oriental Studies. Leiden: Brill. 438 y 1279 pp. ISBN 9789004422117

El presente artículo se propone explorar y analizar tres acepciones del proyecto denominado “enciclopedística”, gestado por el científico y pensador alemán Novalis. Las definiciones examinadas intentan dar con la identidad de este concepto a partir de aquello que lo delimita negativamente, es decir, aquello que no corresponde a la concepción diseñada por su propio autor. Para cumplir con su propósito, este trabajo investiga la fuente textual titulada Das allgemeine Brouillon. Materialien zur Enzyklopädistik, donde Novalis esboza la noción de enciclopedística. Esta obra inconclusa permite descubrir la forma adoptada por dicho proyecto, al tiempo que lo conecta con la Ilustración europea y la tradición de la enciclopedística de los siglos XVI-XVIII.

CD4+ T cells are critical orchestrators of immune responses against a large variety of pathogens, including viruses. While multiple CD4+ T cell subtypes and their key transcriptional regulators have been identified, there is a lack of consistent definition for CD4+ T cell transcriptional states. In addition, the progressive changes affecting CD4+ T cell subtypes during and after immune responses remain poorly defined. Using single-cell transcriptomics, we characterized the diversity of CD4+ T cells responding to self-resolving and chronic viral infections in mice. We built a comprehensive map of virus-specific CD4+ T cells and their evolution over time, and identified six major cell states consistently observed in acute and chronic infections. During the course of acute infections, T cell composition progressively changed from effector to memory states, with subtype-specific gene modules and kinetics. Conversely, in persistent infections T cells acquired distinct, chronicity-associated programs. By single-cell T cell receptor (TCR) analysis, we characterized the clonal structure of virus-specific CD4+ T cells across individuals. Virus-specific CD4+ T cell responses were essentially private across individuals and most T cells differentiated into both Tfh and Th1 subtypes irrespective of their TCR. Finally, we showed that our CD4+ T cell map can be used as a reference to accurately interpret cell states in external single-cell datasets across tissues and disease models. Overall, this study describes a previously unappreciated level of adaptation of the transcriptional states of CD4+ T cells responding to viruses and provides a new computational resource for CD4+ T cell analysis.

Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

Abstract Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

One challenge of single cell RNA sequencing analysis is how to consistently identify cell subtypes and states across different datasets. Here the authors propose the use of a reference single-cell atlas as a stable system of coordinates to characterize T cell states across studies, diseases and species.

Patients with strokes to the Anterior Communicating Artery (ACoA) pose an important challenge to rehabilitation teams due to a particular mix of cognitive and behavioral impairments (anosognosia, anterograde amnesia, prospective memory problems, and executive dysfunction). These deficits often compromise engagement with rehabilitation, learning and generalization. The goal of this article is to describe the long-term presentation of a patient with an ACoA stroke (Mrs. B, a 60-year-old electric engineer) as well as her rehabilitation needs and the many challenges experienced by the rehabilitation team when attempting to facilitate functional, vocational and psychosocial recovery. Based on this case, and the existing literature, a neuropsychological rehabilitation framework to understand and address the specific problems and needs of this population is proposed. This framework demands rehabilitation teams to consider: the slow pattern of recovery of this population, the interaction between cognitive and behavioral impairments, the relevance of physical and social environments, the value of personal projects and the need to include psychological and relational interventions.

Abstract The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p