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Abstract The ALICE experiment was proposed in 1993, to study strongly-interacting matter at extreme energy densities and temperatures. This proposal entailed a comprehensive investigation of nuclear collisions at the LHC. Its physics programme initially focused on the determination of the properties of the quark–gluon plasma (QGP), a deconfined state of quarks and gluons, created in such collisions. The ALICE physics programme has been extended to cover a broader ensemble of observables related to Quantum Chromodynamics (QCD), the theory of strong interactions. The experiment has studied Pb–Pb, Xe–Xe, p–Pb and pp collisions in the multi-TeV centre of mass energy range, during the Run 1–2 data-taking periods at the LHC (2009–2018). The aim of this review is to summarise the key ALICE physics results in this endeavor, and to discuss their implications on the current understanding of the macroscopic and microscopic properties of strongly-interacting matter at the highest temperatures reached in the laboratory. It will review the latest findings on the properties of the QGP created by heavy-ion collisions at LHC energies, and describe the surprising QGP-like effects in pp and p–Pb collisions. Measurements of few-body QCD interactions, and their impact in unraveling the structure of hadrons and hadronic interactions, will be discussed. ALICE results relevant for physics topics outside the realm of QCD will also be touched upon. Finally, prospects for future measurements with the ALICE detector in the context of its planned upgrades will also be briefly described.

Accurately predicting a fetus’s gestational age (GA) is crucial in prenatal care. This study aimed to develop an artificial intelligence (AI) model to predict GA using biometric measurements from fetal brain magnetic resonance imaging (MRI). We assessed the significance of using different reference standards for interpreting GA predictions. Measurements of biparietal diameter (BPD), fronto-occipital diameter (FOD), and head circumference (HC) were obtained from 52 normal fetal MRI cases from Rush University. Both manual and AI-based methods were utilized, and comparisons were made using three reference standards (Garel, Freq, and Bio). The AI model showed a strong correlation with manual measurements, particularly for HC, which exhibited the highest correlation with actual values. Differences between GA predictions and picture archiving and communication system (PACS) records varied by reference, ranging from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Pearson correlation coefficients between PACS records and GA predictions exceeded 0.97 across all references. In conclusion, the AI model demonstrated high accuracy in predicting GA from fetal brain MRI measurements. This approach offers improved accuracy and convenience over manual methods, highlighting the potential of AI in enhancing prenatal care through precise GA estimation.

Abstract Background Telemedicine has expanded rapidly in recent years, and many encounters that were conducted in person now take place remotely. This study aimed to assess primary care physicians’ (PCPs) attitudes towards the different modalities of patient care. Methods This is a cross-sectional nationwide descriptive study conducted in Israel. We asked PCPs to document an entire workday and answer a short questionnaire after each visit. The questions addressed the type of visit (face-to-face, remote synchronous [telephone/video], or remote asynchronous [online requests]), the perceived quality of the visit, and the physicians’ feelings at the end of each visit. Before documenting their working day, we asked the participants to answer a questionnaire about their general attitudes toward different modalities of medical visits and how they affect their well-being and burnout. Results Sixty physicians documented 2,025 visits, of which 39% took place in person, 36% stemmed from online patient requests, 18% were telephone meetings, < 1% were video meetings, and 6% consisted of other types of contact. Mixed effects logistic regressions were used to model the visits’ evaluation. The odds ratios (ORs) for perceived medical quality of visits focused on medical tasks were lower for non-face-to-face visits: OR = 0.39, 95% CI 0.25–0.59 for remote synchronous, and OR = 0.14, 95% CI 0.09–0.23 for remote asynchronous. The perceived medical quality of visits focused on administrative tasks was lower for remote asynchronous than for face-to-face visits (OR = 0.31, 95% CI 0.14–0.65). We found no association between medical quality and patients, physicians, or clinic characteristics. The inappropriateness of the visit modality was also associated with lower medical quality (OR = 0.13, 95% CI 0.09–0.18). We found a correlation between perception of medical quality and physicians’ feelings at the end of the visits, Spearman’s r = 0.82 (p

Accurate and continuous estimates of the thermodynamic structure of the lower atmosphere are highly beneficial to meteorological process understanding and its applications, such as weather forecasting. In this study, the Tropospheric Remotely Observed Profiling via Optimal Estimation (TROPoe) physical retrieval is used to retrieve temperature and humidity profiles from various combinations of input data collected by passive and active remote sensing instruments, in situ surface platforms, and numerical weather prediction models. Among the employed instruments are microwave radiometers (MWRs), infrared spectrometers (IRSs), radio acoustic sounding systems (RASSs), ceilometers, and surface sensors. TROPoe uses brightness temperatures and/or radiances from MWRs and IRSs, as well as other observational inputs (virtual temperature from the RASS, cloud-base height from the ceilometer, pressure, temperature, and humidity from the surface sensors) in a physical iterative retrieval approach. This starts from a climatologically reasonable profile of temperature and water vapor, with the radiative transfer model iteratively adjusting the assumed temperature and humidity profiles until the derived brightness temperatures and radiances match those observed by the MWR and/or IRS instruments within a specified uncertainty, as well as within the uncertainties of the other observations, if used as input. In this study, due to the uniqueness of the dataset that includes all the abovementioned sensors, TROPoe is tested with different observational input combinations, some of which also include information higher than 4 km above ground level (a.g.l.) from the operational Rapid Refresh numerical weather prediction model. These temperature and humidity retrievals are assessed against independent collocated radiosonde profiles under non-cloudy conditions to assess the sensitivity of the TROPoe retrievals to different input combinations.

Abstract According to single-molecule localisation microscopy almost all plasma membrane proteins are clustered. We demonstrate that clusters can arise from variations in membrane topography where the local density of a randomly distributed membrane molecule to a degree matches the variations in the local amount of membrane. Further, we demonstrate that this false clustering can be differentiated from genuine clustering by using a membrane marker to report on local variations in the amount of membrane. In dual colour live cell single molecule localisation microscopy using the membrane probe DiI alongside either the transferrin receptor or the GPI-anchored protein CD59, we found that pair correlation analysis reported both proteins and DiI as being clustered, as did its derivative pair correlation-photoactivation localisation microscopy and nearest neighbour analyses. After converting the localisations into images and using the DiI image to factor out topography variations, no CD59 clusters were visible, suggesting that the clustering reported by the other methods is an artefact. However, the TfR clusters persisted after topography variations were factored out. We demonstrate that membrane topography variations can make membrane molecules appear clustered and present a straightforward remedy suitable as the first step in the cluster analysis pipeline.

In this study, we employed a novel approach of combining Gaussian processes (GPs) with boosting techniques to model the spatial variability inherent in End-Stage Kidney Disease (ESKD) data. Our use of the Gaussian processes boosting, or GPBoost, methodology underscores the efficacy of this hybrid method in capturing intricate spatial dynamics and enhancing predictive accuracy. Specifically, our analysis demonstrates a notable improvement in out-of-sample prediction accuracy regarding the percentage of the population remaining on the wait list within geographic regions. Furthermore, our investigation unveils race and gender-based factors that significantly influence patient wait-listing. By leveraging the GPBoost approach, we identify these pertinent factors, shedding light on the complex interplay between demographic variables and access to kidney transplantation services. Our findings underscore the imperative for a multifaceted strategy aimed at reducing spatial disparities in kidney transplant wait-listing. Key components of such an approach include mitigating gender disparities, bolstering access to healthcare services, fostering greater awareness of transplantation options, and dismantling structural barriers to care. By addressing these multifactorial challenges, we can strive towards a more equitable and inclusive landscape in kidney transplantation.

Abstract Background Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC’s clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC’s role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics. Methods A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios. Analysis: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development. Discussion While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC’s role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants’ involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments’ daily dashboards in Europe, often overlooked in media and public debates.

Abstract Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.

Serious iatrogenic vascular injuries are considered uncommon; however, they are underreported. There are limited studies discussing the proper management of these injuries; therefore, the management is often anecdotal. A 4-month-old female patient presented with elevated liver enzymes and cholecystitis with sludge. Her HIDA scan suggested biliary atresia. During the surgery, there was a bilateral iatrogenic injury to the hepato-duodenal ligament, including the portal vein, hepatic artery, and bile ducts. The patient underwent splenectomy and cholecystectomy, and the hepatic artery transection was successfully managed with a splenic artery jump graft and a portal vein bypass initiated with the SMV using a Gore-TexⓇ vascular graft. The management of iatrogenic vascular injury depends primarily on the assessment of the stage of the injury, which should be conducted by experienced surgeons using proper strategies in an established hepato-biliary surgical center. Additionally, there is little data provided in the literature, mostly case reports. Therefore, no preferred or specific approach can be found.

Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.

Introduction: Internal carotid artery occlusion as a result of a septic embolism is a rare, commonly fatal, complication of mitral valve infectious endocarditis. Prompt recognition of this condition by the emergency physician may improve the chance of functional neurological survival. Case Report: A 50-year-old male presented minimally responsive with a right gaze deviation, left hemiparesis, and a score of 26 on the National Institutes of Health Stroke Scale. A bedside echocardiogram showed a large mitral valve vegetation, and computed tomography angiography demonstrated an internal carotid artery occlusion. Conclusion: The emergency physician should consider this potentially life-threatening condition and know the fundamental management recommendations once identified.

A new, more precise measurement of the Λ hyperon lifetime is performed using a large data sample of Pb-Pb collisions at sNN=5.02 TeV with ALICE. The Λ and Λ¯ hyperons are reconstructed at midrapidity using their two-body weak decay channel Λ→p+π- and Λ¯→p¯+π+. The measured value of the Λ lifetime is τΛ=[261.07±0.37(stat.)±0.72(syst.)] ps. The relative difference between the lifetime of Λ and Λ¯, which represents an important test of CPT invariance in the strangeness sector, is also measured. The obtained value (τΛ-τΛ¯)/τΛ=0.0013±0.0028(stat.)±0.0021(syst.) is consistent with zero within the uncertainties. Both measurements of the Λ hyperon lifetime and of the relative difference between τΛ and τΛ¯ are in agreement with the corresponding world averages of the Particle Data Group and about a factor of three more precise.

This letter reports measurements which characterize the underlying event associated with hard scatterings at mid-pseudorapidity (|η|

Asynchronous skeletal muscle degeneration/regeneration is a hallmark feature of Duchenne muscular dystrophy (DMD); however, traditional -omics technologies that lack spatial context make it difficult to study the biological mechanisms of how asynchronous regeneration contributes to disease progression. Here, using the severely dystrophic D2-mdx mouse model, we generated a high-resolution cellular and molecular spatial atlas of dystrophic muscle by integrating spatial transcriptomics and single-cell RNAseq datasets. Unbiased clustering revealed nonuniform distribution of unique cell populations throughout D2-mdx muscle that were associated with multiple regenerative timepoints, demonstrating that this model faithfully recapitulates the asynchronous regeneration observed in human DMD muscle. By probing spatiotemporal gene expression signatures, we found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and that querying expression signatures within discrete microenvironments can identify targetable pathways for DMD therapy. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.

Hyperphosphorylation of the microtubule-associated protein tau is hypothesized to lead to the development of neurofibrillary tangles in select brain regions during normal aging and in Alzheimer disease (AD). The distribution of neurofibrillary tangles is staged by its involvement starting in the transentorhinal regions of the brain and in final stages progress to neocortices. However, it has also been determined neurofibrillary tangles can extend into the spinal cord and select tau species are found in peripheral tissues and this may be depended on AD disease stage. To further understand the relationships of peripheral tissues to AD, we utilized biochemical methods to evaluate protein levels of total tau and phosphorylated tau (p-tau) as well as other neuronal proteins (i.e., tyrosine hydroxylase (TH), neurofilament heavy chain (NF-H), and microtubule-associated protein 2 (MAP2)) in the submandibular gland and frontal cortex of human cases across different clinicopathological stages of AD (n = 3 criteria not met or low, n = 6 intermediate, and n = 9 high likelihood that dementia is due to AD based on National Institute on Aging-Reagan criteria). We report differential protein levels based on the stage of AD, anatomic specific tau species, as well as differences in TH and NF-H. In addition, exploratory findings were made of the high molecular weight tau species big tau that is unique to peripheral tissues. Although sample sizes were small, these findings are, to our knowledge, the first comparison of these specific protein changes in these tissues.

Health policies and associated research initiatives are constantly evolving and changing. In recent years, there has been a dizzying increase in research on emerging topics such as the implications of changing public and private health payment models, the global impact of pandemics, novel initiatives to tackle the persistence of health inequities, broad efforts to reduce the impact of climate change, the emergence of novel technologies such as whole-genome sequencing and artificial intelligence, and the increase in consumer-directed care. This evolution demands future-thinking research to meet the needs of policymakers in translating science into policy. In this paper, the Health Affairs Scholar editorial team describes ten health policy challenges for the next 10 years. Each of the ten assertions describes the challenges and steps that can be taken to address those challenges. We focus on issues that are traditionally studied by health services researchers such as cost, access, and quality, but then examine emerging and intersectional topics: equity, income, and justice; technology, pharmaceuticals, markets, and innovation; population health; and global health.

BackgroundDonor-derived cell-free DNA (dd-cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd-cfDNA and gene-expression profiling (GEP) testing in heart transplant (HTx) recipients.MethodsThis is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd-cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR.ResultsA total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p

Single-strand RNA (ssRNA) Fiersviridae phages cause host lysis with a product of single gene (sgl for single-gene lysis; product Sgl) that induces autolysis. Many different Sgls have been discovered, but the molecular targets of only a few have been identified. In this study, we used a high-throughput genetic screen to uncover genome-wide host suppressors of diverse Sgls. In addition to validating known molecular mechanisms, we discovered that the Sgl of PP7, an ssRNA phage of Pseudomonas aeruginosa, targets MurJ, the flippase responsible for lipid II export, previously shown to be the target of the Sgl of coliphage M. These two Sgls, which are unrelated and predicted to have opposite membrane topology, thus represent a case of convergent evolution. We extended the genetic screens to other uncharacterized Sgls and uncovered a common set of multicopy suppressors, suggesting that these Sgls act by the same or similar mechanism.

Engaging students in research can take many forms and such research-based learning is widely perceived as beneficial for student engagement and learning outcomes. Here, we report on our experience with organizing a cross-institutional seminar series dedicated to the question of where on Mars to land a coming NASA Mars mission. The seminar series was connected with the professional process for answering the same question and was organized through teleconferences and an internet site together with local discussions at seven participating institutions. We report on our own reflections as well as student reactions collected through group interviews at five participating institutions. We discuss the results against a model for research-based learning. Coordinating the seminar series across seven institutions and several time zones proved inspiring but challenging. Many specific aspects of how the class was organized could have been improved, but students generally reported high levels of engagement derived from the cutting-edge research nature and current relevance of the subject matter.

This study investigates how students experienced a sense of place and a sense of belonging in both in-person and virtual learning environments by analyzing student interview data. As educators and university students grapple with the ongoing COVID-19 pandemic, we consider how students experience the presence and absence of sense of place and belonging, and how this could inform faculty and staff practices. We conclude by offering recommendations for university educators, with a particular focus on the benefits of building communities of practice.

Algebra is a gatekeeper. For the 6% of students with dyscalculia (i.e., mathematical learning disabilities), an inability to pass algebra may significantly limit academic and career opportunities. Unfortunately, prior research on dyscalculia has focused almost exclusively on elementary-aged students' deficits in speed and accuracy in arithmetic calculation. This case study expands our understanding of dyscalculia by documenting how one college student with dyscalculia understood algebra during a one-on-one design experiment. A detailed case study of 19 video recorded sessions revealed that she relied upon unconventional understandings of algebraic quantities and notation, which led to persistent difficulties. The design experiment involved designing alternative tools to enable the student to reason about algebra, but the unconventional understandings persisted. This exploratory case study provides new insights into the character of difficulties that arose and persisted for one student with dyscalculia in the context of algebra and suggests the utility of documenting the persistent understandings that students with dyscalculia rely upon, particularly in understudied mathematical domains, like algebra.

Abstract Li7-xLa3Zr2-xO12-Tax (x =0, 0.1, 0.2, 0.3) nanostructured powders were successfully synthesized using an innovative wet chemical route via spray pyrolysis technique at 800 °C for 10 seconds, followed by post heat treatment at 800 °C for 30 minutes in a muffle furnace. X-ray diffraction (XRD) analysis confirmed that Ta-doping increased the cubic phase up to 99%. Scanning Electron Microscopy (SEM) showed spherical particles with sizes ranging from slightly below 200 nm to 3 µm. The powders were then pressed at 50 MPa and sintered at 850 °C for 7 minutes using Spark Plasma Sintering, followed by post heat-treatment at 900 °C for 2 hours in a muffle furnace. XRD indicated the majority predominance of the garnet cubic phase, and SEM images showed coalescence and longitudinal growth of the particles, forming layers inside the samples. This study reports a fast synthesis and sintering method to obtain cubic garnet crystalline structure in contrast to conventional methods that are widely used and published in the literature, which require longer parameters in the synthesis stages (~24 hours) and sintering stages (over 12 hours).

BackgroundStress related to Alzheimer disease and related dementias (ADRD) is common, particularly among those who care for persons with challenging behaviors and personality or mood changes. Mindfulness and self-compassion programs are efficacious for managing stress. The skills of mindfulness and self-compassion, however, must be integrated with behavioral management skills in order to effectively improve caregiver stress. ObjectiveIn this study, we aimed to describe the development of the Mindful and Self-Compassionate Care (MASC) program, the first program that combines mindfulness and self-compassion with behavioral management skills to decrease caregiver stress, and its evaluation in the Supporting Our Caregivers in ADRD Learning (SOCIAL) study. MethodsUsing the National Institutes of Health (NIH) stage model, we describe 3 phases of work encompassing NIH Stages 1A and 1B. In phase 1, we conducted 5 focus groups (N=28) of stressed individuals caring for persons with ADRD and challenging behaviors. Rapid data analysis informed the development of a 6-week online intervention. Phase 2 (NIH stage 1A) includes an open pilot (N>10) with optional exit interviews. Phase 3 (NIH stage 1B) is a feasibility randomized controlled trial of the intervention versus the Health Education Program control. Primary outcomes focus on feasibility with secondary outcomes encompassing acceptability, credibility, fidelity, and signals of preliminary efficacy. Phase 1 follows traditional recommendations for qualitative analyses (at the point of thematic saturation) which was achieved after 5 focus groups (N=28). For the phase 2 open pilot, up to 12 participants will be recruited. For the phase 3 feasibility study, recruitment of 80 caregivers will allow the assessment of feasibility benchmarks. Data for phase 1 included 5 focus groups. In phases 2 and 3, data collection will occur through REDCap (Research Electronic Data Capture; Vanderbilt University) surveys and an optional qualitative exit interview. Analyses will include hybrid inductive-deductive analyses for qualitative data and assessment of changes in our intervention targets and outcomes using t tests and correlation analyses. ResultsIn phase 1, caregivers reported interest in a brief, online stress management program. Participants held misconceptions about mindfulness and self-compassion, but after detailed explanation thoughts, these skills could be helpful when directly linked to implementation during caregiving routines. Phases 2 and 3 will be completed by the end of 2025. ConclusionsWe describe the protocol for the Supporting Our Caregivers in ADRD Learning study, as well as the development and feasibility testing of the Mindful and Self-Compassionate Care intervention. Future work will include a fully powered efficacy-effectiveness randomized controlled trial. Trial RegistrationClinicalTrials NCT05847153; https://clinicaltrials.gov/study/NCT05847153; and ClinicalTrials.gov NCT06276023; https://clinicaltrials.gov/study/NCT06276023 International Registered Report Identifier (IRRID)DERR1-10.2196/58356

Summary: Background: Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Methods: Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Findings: Integration of data from patients with COVID-19 with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and patients with severe COVID-19, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Interpretation: Consistently, hamsters’ response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species. Funding: This work was supported by German Federal Ministry of Education and Research, (BMBF) grant IDs: 01ZX1304B, 01ZX1604B, 01ZX1906A, 01ZX1906B, 01KI2124, 01IS18026B and German Research Foundation (DFG) grant IDs: 14933180, 431232613.

En esta investigación se discuten aquellos rasgos del clima escolar que atañen a toda la comunidad educativa, tales como: liderazgo directivo, disciplina, orden, motivación, calidad de la comunicación, y nivel de satisfacción con la vida escolar, que deben ser objeto de reflexión por parte de los estudiantes y del personal educativo del centro en que se llevó a cabo el trabajo que ahora se presenta. El objetivo general fue conocer la modalidad de clima escolar presente en un plantel de nivel medio superior en el Estado de Puebla, México, desde la perspectiva de la comunidad escolar. Se utilizó la tipología propuesta por Andrew W. Halpin y Don B. Croft (1963) para la clasificación de dicho fenómeno educativo. Se construyeron instrumentos de diseño propio, basados en un enfoque mixto y una perspectiva crítica de observación de la realidad. Éstos fueron un cuestionario para la comunidad estudiantil (145 informantes) y una entrevista para el personal educativo (11 personas). Este enfoque basado también en la teoría de Pedagogía crítica de Michael Apple (2013) busca promover en los involucrados un acercamiento reflexivo con su realidad.

IntroductionInfections with Fasciola hepatica and Ostertagia ostertagi impinge upon dairy cow health and welfare and represent a major economic factor in livestock industry. Control measures largely rely on the use of anthelminthic drugs. However, reports of anthelmintic resistance necessitate sustainable approaches. Farmer characteristics such as attitude and personality are crucial for the implementation of control strategies and on-farm practices.MethodsIn the present study, the HEXACO (Honesty-Humility, Emotionality, eXtraversion, Agreeableness, Conscientiousness, Openness to experience) model of personality structure, which conceptualizes human personality, was used to evaluate the relationship of farmer aspects with on-farm bulk tank milk seropositivity for F. hepatica and O. ostertagi. Moreover, information on farm structure, housing, management, and farmers’ attitude was collected in a face-to-face interview. Farm-level seropositivity for F. hepatica and O. ostertagi was predicted via elastic net regression.ResultsOut of 193 farms housing 8,774 cows in the German Federal State of Bavaria, 47 farms (24.4%) were seropositive for F. hepatica, 77 farms (39.9%) for O. ostertagi, and 42 farms (21.8%) for both endoparasites. The model for F. hepatica seropositivity selected the covariates pasture access, O. ostertagi seropositivity, higher farmer conscientiousness, and organic farming as relevant predictors. Seropositivity for O. ostertagi was predicted by F. hepatica seropositivity, pasture access, organic farming, and farmers being neutral regarding their satisfaction with animal health on their farm. Higher values for the HEXACO factors extraversion and emotionality were inversely associated with O. ostertagi seropositivity.DiscussionThe present work emphasizes the importance of farmer traits in regard to animal health and parasite occurrence. For the effective acceptance and implementation of sustainable control strategies for livestock helminth infections, it is crucial to consider these aspects to holistically address the challenges of managing parasitic diseases. Moreover, tailored communication strategies can be developed incorporating the understanding of individual stockman characteristics and subsequently ensuring encouragement of stakeholders.

The severe eutrophication of the Baltic Sea requires mussel (Mytilus spp.) farming to remove nutrients, but farming in a low salinity environment results in smaller mussels that require value enhancement to be economically viable. This study evaluates the biomass valorisation of smaller Baltic mussels, focusing on the extraction of oil, protein and glycogen. It analyses the amino acid profiles, oil and fatty acid contents and glycogen levels of the mussels, as well as their prebiotic properties on beneficial gut bacteria. In addition, the study improves the extraction of bioactive compounds through enzymatic hydrolysis. Results indicate significant seasonal differences, with summer mussels having higher meat and lower ash content, and a rich content of essential fatty acids, particularly omega-3, and amino acids, underscoring the mussels' sustainability as a food source. The enzymatically treated biomass exhibited notable prebiotic activity, proposing health-promoting benefits. The study underscores the valorization of Baltic mussel biomass, highlighting its role in health, nutrition, and environmental sustainability.

Introduction: Despite over 15 years of real-world data that supports the safety and efficacy of the human papillomavirus (HPV) vaccine, in the United States vaccine hesitancy persists. Many studies have focused on vaccine-hesitant parents, but fewer have examined provider perspectives on how to address HPV vaccine hesitancy. Methods: Between July 2021-April 2022, we recruited providers in Maryland and the broader Mid-Atlantic region who practiced pediatrics, primary care, family medicine, or adolescent medicine and who provided outpatient care for children ages 10–17. Semi-structured virtual interviews focused on provider-reported strategies to address HPV vaccine-hesitant parents, as well as perceived barriers to successful vaccination and provider perspectives on specific interventions to address parental hesitancy. Audio recordings were transcribed and analyzed via a combination of deductive and inductive coding. Higher-level themes within the domains of strategies, barriers, and perspectives on specific proposed interventions were identified. Results and discussion: A total of sixteen providers completed an interview. Within the domain of provider-reported strategies, the following themes emerged: 1) leveraging continuity of care and established parental trust, 2) supporting parental autonomy, 3) tailoring the approach to specific concerns of vaccine-hesitant parents, 4) normalizing the HPV vaccine, and 5) focusing on health prevention and cancer prevention. Barriers providers identified were: 1) limited time, 2) lack of common ground with parents, 3) parent–child decision discordance, 4) availability of misinformation, and 5) parental concerns such as safety and necessity. In the domain for proposed interventions, providers favored interventions that saved time or were not resource-intense, that did not single out the HPV vaccine as different, were patient friendly, and leveraged efficiency through the electronic medical record. The insights from this study can help inform the development of provider-acceptable and feasible tools and interventions to address parental HPV vaccine hesitancy.

While thousands of health systems have begun to implement the Age-Friendly Health System’s 4Ms Framework to improve care for older patients, an important phase of work is achieving consistent adherence to 4Ms care processes. Identifying mechanisms that may lead to higher versus lower adherence serves to guide efforts to achieve consistent, equitable adherence. Drawing from prior literature, we identified three mechanisms that may influence 4Ms adherence. We then conducted a 3-year retrospective, observational study of inpatient encounters (n = 28 833) at UCSF Health System with patients aged 65+. We used least squares regression models to assess associations between hospital encounter-level measures of 4Ms adherence and proxy measures of patient and encounter characteristics for each hypothesized mechanism along with control variables. Encounter-level adherence to the 4Ms was 65.5% (SD = 14.3%). We found support for all three mechanisms. Negative implicit biases were associated with lower adherence for patients who were obese [0.79 percentage points (PP) lower; P

Human activity recognition (HAR) and brain-machine interface (BMI) are two emerging technologies that can enhance human-robot collaboration (HRC) in domains such as industry or healthcare. HAR uses sensors or cameras to capture and analyze the movements and actions of humans, while BMI uses human brain signals to decode action intentions. Both technologies face challenges impacting accuracy, reliability, and usability. In this article, we review the state-of-the-art techniques and methods for HAR and BMI and highlight their strengths and limitations. We then propose a hybrid framework that fuses HAR and BMI data, which can integrate the complementary information from the brain and body motion signals and improve the performance of human state decoding. We also discuss our hybrid method’s potential benefits and implications for HRC.

IntroductionTo establish clinical trial readiness for dystonia, a crucial step is to develop a Patient-Centered Outcome (PCO) measure to capture therapeutic response in focal dystonia such as in cervical dystonia (CD). Botulinum neurotoxin (BoNT) is the gold standard treatment for focal dystonia and yields improvement; yet the therapy may not meet all patient expectations as there is a high rate of discontinuation. A PCO that can measure therapeutic response, including the waxing and waning benefit of BoNT, across multiple domains and is easy to use on a frequent basis in the home environment is critical.MethodsA modified iterative Delphi process based on FDA (Food and Drug Administration) guidelines was used to develop and select items to document patient symptoms and response to treatment. Potential items then were improved using patient focus groups, validated for content with specialist panels, and confirmed items based on a patient survey. Using data from 200 CD patients in the Dystonia Coalition Natural History Database, initial PCO items were identified. Utilizing Random Forests, prospective items were analyzed for their contribution to the overall severity scores on the clinical and patient-centered outcome scales. Items that were repetitive were merged. Iterative meetings with a specialist panel consisting of neurologists, physical therapists, and Patient Advocacy Group (PAG) representatives as well as virtual focus groups of CD patients were held. An online survey was conducted with over 600 CD patients participating. Finally, specialist panel members provided input for a content validity ratio (CVR) with iterations until there was good agreement as to the relevance and clarity of the items.ResultsPCO measures tailored for CD were successfully developed. The PCO consists of 16 items covering three domains (motor, disability, and psychosocial) and reflects the input of international specialist panels, more than 800 CD patients, and PAGs (patient advocacy groups) following FDA guidance. The PCO is simple enough to be used in an app-based format compatible with smartphones and tablets.ConclusionThis comprehensive CD PCO measure was developed through the combination of using robust existing patient centered data (from previous Dystonia Coalition Projects); active engagement with PAGs to provide the patient voice; and use of virtual focus groups and online surveys. This PCO will be used in a prospective study to characterize the therapeutic response to BoNT over time. This will provide peak effect size as well as capturing the “yo-yo” effect during BoNT treatment; and will prepare for a future trials.

We examined the association among basal metabolic rate (BMR) as well as dietary intakes of vitamin D (Vit D) and calcium on body composition and bone mineral density (BMD) after spinal cord injury (SCI). Cross-sectional design. Veterans Affairs Medical Center, Richmond, VA. About 33 individuals with chronic SCI who recorded their food consumption 3 days per week for 2 weeks. BMR was measured after 10 to 12 h of overnight fast. Average daily vit D and calcium intakes, and total caloric intake were recorded and analyzed using the Nutrition Data System for Research (NDSR) software. Fasting blood analysis for 25-hydroxyvitamin D (25[OH]D) status and Triiodothyronine (T3) status was performed (n = 10). Total and regional BMD, % fat mass (FM), and % lean mass (LM) were measured by dual X-ray absorptiometry scans. Participants consumed less than the Institute of Medicine (IOM) recommended daily allowances (RDA) for vit D (600-800 IU) and calcium (1000-1200 mg) for adults. BMR was positively related to total-lean mass ( r = .62, P = .0001; n = 32) and leg-lean mass ( r = .51, P = .003; n = 32). Adjusted BMR was negatively related to BMD of the left (r = −.38, P = .047; n = 28) and the right (r = −.41, P = .032; n = 28) proximal tibia. Vit D intake was negatively related to percentage total-FM ( r = −.33, P = .07; n = 29) and legs-%FM ( r = −.37, P = .047; n = 29). Multivariate regression models indicated that adjusted BMR explained the variance in leg fat mass (34%; P = .002) and percentage fat mass (44%; P

Healthcare commissioners and those making reimbursement decisions require data on the “natural history” of diseases to estimate quantities such as life expectancy and quality of life. However, such data are commonly acquired from unrepresentative sources like trial placebo arms or case series. We used Scottish Diabetes Research Network-National Diabetes Dataset to characterise life expectancy for people with type 2 diabetes mellitus (T2DM). Data from >99% of people with diabetes in Scotland are available from primary and secondary care (including from clinical investigations) and can be linked to hospital admission and death records for research purposes. As part of an MRC-funded (MR/T017112/1) systematic review and modelling study (PROSPERO registration CRD42020184174) building on work funded by the Chief Scientific Office for Scotland (CSO HIPS_17_26), we used these linked data to define a treatment-eligible population for three drug classes — SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors. Fitting a Gompertz model, we estimated life expectancy for this ‘treatment-eligible’ group. The treatment-eligible population, compared to the entire Scottish T2DM population, was younger (63.8 (12.1) vs. 66.7 (12.7) year-old), with larger proportions of men (60.6% vs. 56.2%), higher HbA1c levels (67.4 (13.1) vs. 60.2 (15.1) mmol/L), larger proportions prescribed metformin (69.2% vs 55.2%) and higher life expectancy at age 65 (in women 21 vs 19 years and in men 20 vs 18 years). Using linked data to define and characterise treatment-eligible populations is feasible and may impact decision models. These findings will be useful to those making resourcing decisions and future economic analyses.

Abstract: Eicosanoids are a class of molecules derived from C20 polyunsaturated fatty acids (PUFAs) that play a vital role in mammalian and insect biological systems, including development, reproduction, and immunity. Recent research has shown that insects have significant but lower levels of C20 PUFAs in circulation in comparison to C18 PUFAs. It has been previously hypothesized in insects that eicosanoids are synthesized from C18 precursors, such as linoleic acid (LA), to produce downstream eicosanoids. In this study, we show that introduction of arachidonic acid (AA) stimulates production of cyclooxygenase, lipoxygenase, and cytochrome P450–derived eicosanoids. Downstream immune readouts showed that LA stimulates phagocytosis by hemocytes, while both LA and AA stimulate increased antimicrobial peptide production when D. melanogaster is exposed to a heat-killed bacterial pathogen. In totality, this work identifies PUFAs that are involved in insect immunity and adds evidence to the notion that Drosophila utilizes immunostimulatory lipid signaling to mitigate bacterial infections. Our understanding of immune signaling in the fly and its analogies to mammalian systems will increase the power and value of Drosophila as a model organism in immune studies.

Background: Physical activity prevents cardiovascular disease, but it may also trigger acute cardiac events like sudden cardiac death in patients with underlying heart disease. The chance of surviving an out-of-hospital cardiac arrest remains low, despite improving medical treatment and rescue chain. Prior studies signaled increased survival in exercise related out-of-hospital cardiac arrest. Objective: The aim of this study was to evaluate the differences between exercise related out-of-hospital cardiac arrest and out-of-hospital cardiac arrest during daily activity in an urban setting. Methods: Retrospective analysis of all out-of-hospital cardiac arrests from 2014 to 2021 treated at a cardiac arrest center of a tertiary hospital. The primary outcome was survival to discharge. Secondary outcomes included differences in pre-hospital care, in-hospital treatment, hypoxic ischemic encephalopathy, and laboratory parameters. Results: 478 OHCA patients were reviewed of which 432 patients (exercise related 36 (8.4%) vs. daily activity 396 (91.6%)) were included in the analysis. Patients suffering an exercise related arrest were younger (57 vs 65 years, p = 0.002) and mostly male (88.9 vs 74.5%, p = 0.054).The exercise related cohort received bystander cardiopulmonary resuscitation (77.8 vs 53.4%, p = 0.005) to a higher extent and had a shorter no-flow time (1.5 vs 2 min, p = 0.049). Exercise related arrest patients more often presented with a shockable rhythm (80.6 vs 64.1%, p = 0.032).At hospital admission exercise related arrest patients had a higher initial pH (7.24 vs 7.19, p = 0.015). In the exercise related group, a cardiac cause was numerically more frequent compared to the daily activity group (80.6 vs 68.7%, p = 0.09). In both groups myocardial infarction (47.2 vs 43.2%) was the most common cause, but a primary arrhythmic event (33.3 vs 25.5%) was more often documented in exercise related arrest patients. Exercise related arrest was mostly related to endurance training (52.8%) followed by ball sports (19.4%) and occurred directly during exercise in 77.8% of cases. Patients suffering exercise related arrest had higher survival till discharge (66.7 vs 47.7%, p = 0.036). Conclusion: Based on this observational data from a highly selected group of out-of-hospital cardiac arrest patients treated at a cardiac arrest center, patients suffering an exercise related out-of-hospital cardiac arrest, differed in substantial characteristics and in the first line response compared to daily activity out-of-hospital cardiac arrest patients. The better survival to discharge of the exercise related out-of-hospital cardiac arrest group might be driven by these beneficial differences. This study underlines the need for public awareness for the importance of a fast first response and a broad distribution of automated external defibrillators in public sport areas since most of the exercise related out-of-hospital cardiac arrest patients presented with a cardiac cause and an initial shockable rhythm.

The importance of single trees and the determination of related parameters has been recognized in recent years, e.g. for forest inventories or management. For urban areas an increasing interest in the data acquisition of trees can be observed concerning aspects like urban climate, CO2 balance, and environmental protection. Urban trees differ significantly from natural systems with regard to the site conditions (e.g. technogenic soils, contaminants, lower groundwater level, regular disturbance), climate (increased temperature, reduced humidity) and species composition and arrangement (habitus and health status) and therefore allometric relations cannot be transferred from natural sites to urban areas. To overcome this problem an extended approach was developed for a fast and non-destructive extraction of branch volume, DBH (diameter at breast height) and height of single trees from point clouds of terrestrial laser scanning (TLS). For data acquisition, the trees were scanned with highest scan resolution from several (up to five) positions located around the tree. The resulting point clouds (20 to 60 million points) are analysed with an algorithm based on voxel (volume elements) structure, leading to an appropriate data reduction. In a first step, two kinds of noise reduction are carried out: the elimination of isolated voxels as well as voxels with marginal point density. To obtain correct volume estimates, the voxels inside the stem and branches (interior voxels) where voxels contain no laser points must be regarded. For this filling process, an easy and robust approach was developed based on a layer-wise (horizontal layers of the voxel structure) intersection of four orthogonal viewing directions. However, this procedure also generates several erroneous "phantom" voxels, which have to be eliminated. For this purpose the previous approach was extended by a special region growing algorithm. In a final step the volume is determined layer-wise based on the extracted branch areas Ai of this horizontal cross-section multiplied by the thickness of the voxel layer. A significant improvement of this method could be obtained by a reasonable determination of the threshold for excluding sparsely filled voxels for noise reduction which can be defined based on the function change of filled voxels. Field measurements were used to validate this method. For a quality assessment nine deciduous trees were selected for control and were scanned before felling and weighing. The results are in good accordance to the control trees within a range of only -5.1% to +14.3%. The determined DBH values show only minor deviations, while the heights of trees are systematically underestimated, mainly due to field measurements. Possible error sources including gaps in surface voxels, influence of thin twigs and others are discussed in detail and several improvements of this approach are suggested. The advantages of the algorithm are the robustness and simple structure as well as the quality of the results obtained. The drawbacks are the high effort both in data acquisition and analysis, even if a remarkable data reduction can be obtained by the voxel structure.