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Abstract Planktonic mixotrophs, including ciliates, are abundant, yet understudied, mediators of primary and secondary production in aquatic food webs. Here, we report high-resolution in situ observations of a thin layer—a vertically limited patch of high organism abundance—of the ciliate, Laboea strobila. Within the thin layer, peak L. strobila abundances were as high as 62,000 cells/L, six times higher than previously reported, and were strongly positively correlated with co-measured chlorophyll a concentrations, indicating that the organism indulged in kleptoplasty, retaining plastids from ingested algae. Estimates indicated L. strobila contributed to ~63–78% of chlorophyll a within the layer, in sharp contrast to conventional expectations that phytoplankton dominate this signature, suggesting that mixotroph biomass, and consequently, their contribution to marine ecosystems is widely underestimated. These observations also highlight the importance of pairing traditional approaches such as chlorophyll a measurements with high-resolution imaging for proper attribution of biomass proxies.

Abstract Background Stigma is increasingly recognised as contributing to disability in MS. This systematic review aimed to answer the following question: To what extent is stigma associated with psychological and physical health outcomes in MS? Methods The inclusion criteria were: scientific publication of original quantitative research in adults with MS and/or Clinically Isolated Syndrome; outcome measures including a measurement of stigma and psychological and/or physical health; peer reviewed articles in the English language. Pubmed, PsycINFO and Science Direct were searched in November 2023. The Joanna Briggs Institute Critical Appraisal Tool was used to assess the methodological quality and risk of bias in all of the identified studies. The following data was extracted: (1) author and publication year, (2) country, (3) design, (4) sample size and demographics, (5) stigma measure, (6) psychological and/or physical health outcomes, 8) key findings. Results 18 Studies were identified, reporting in total 22,021 adult participants with multiple sclerosis, with individual sample sizes ranging from 33 to 6,670. The review consistently identified stigma to be significantly associated with adverse psychological and physical health outcomes in all 18 identified studies. Over half of all identified studies investigated depression and stigma and over half investigated quality of life and stigma, and a significant association was demonstrated for both of these variables with stigma in all of these studies. Discussion Limitations are that most studies were Western with primarily white participants. Only variables studied could be reported and therefore only a selective perspective of stigma in MS could be explored. A meta-analysis was not feasible, due to the variety of stigma definitions and measures employed. A model of stigma in MS is presented and possible interventions to manage stigma in MS are discussed. A need for international action to develop a consensus measure of MS stigma and determine the trajectory and causal dynamics of MS stigma is highlighted.

Historically, low-moisture foods were considered to have minimal microbial risks. However, they have been linked to many high-profile multistate outbreaks and recalls in recent years, drawing research and extension attention to low-moisture food safety. Limited studies have assessed the food safety research and extension needs for the low-moisture food industry. The objectives of this needs assessment were to explore the food safety culture and education needs, identify the food safety challenges and data gaps, and understand the barriers to adopting food-safety-enhancing technologies in the U.S. low-moisture food industry. This needs assessment was composed of two studies. In Study 1, food safety experts from the low-moisture food industry upper management participated in online interviews and a debriefing discussion session. In Study 2, an online anonymous survey was disseminated to a different group of experts with experience in the low-moisture food industry. The qualitative data were analyzed using deductive and inductive coding approaches, while the quantitative data were analyzed via descriptive analysis. Twenty-five experts participated in the studies (Study 1: n = 12; Study 2: n = 13). Common commodities that participants had worked with included nuts and seeds, spices, flour, and dried fruits and vegetables. A food safety culture conceptual framework was adapted, which included three main components: infrastructure conditions (foundation), individual’s food safety knowledge, attitudes, and risk perceptions; and organizational conditions (supporting pillars). Major barriers to establishing a positive food safety culture were identified to be limited resources, difficulties in risk communication, and difficulties in behavioral change. For continual improvement in food safety performance, two major themes of food safety challenges and data gaps were identified: cleaning, sanitation, and hygienic design; and pathogen reduction. Participants perceived the main barriers discouraging the low-moisture food industry from adopting food-safety-enhancing technologies were: (1) budgetary priorities, (2) operation constraints, (3) technology validation, (4) consumer acceptance, and (5) maintaining desired product characteristics such as quality and sensory functionality. The findings of this needs assessment provide guidance for the food industry, academia, and government agencies about the direction of future research and the development of targeted extension programs that might help improve food safety in the low-moisture food industry.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18–87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like temporal inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT) precedes an acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.

In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5′ end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5′ end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.

Epilepsy is a prevalent and serious neurological condition which impacts millions of people worldwide. Stereoelectroencephalography (sEEG) is used in cases of drug resistant epilepsy to aid in surgical resection planning due to its high spatial resolution and ability to visualize seizure onset zones. For accurate localization of the seizure focus, sEEG studies combine pre-implantation magnetic resonance imaging, post-implant computed tomography to visualize electrodes, and temporally recorded sEEG electrophysiological data. Many tools exist to assist in merging multimodal spatial information; however, few allow for an integrated spatiotemporal view of the electrical activity. In the current work, we present SEEG4D, an automated tool to merge spatial and temporal data into a complete, four-dimensional virtual reality (VR) object with temporal electrophysiology that enables the simultaneous viewing of anatomy and seizure activity for seizure localization and presurgical planning. We developed an automated, containerized pipeline to segment tissues and electrode contacts. Contacts are aligned with electrical activity and then animated based on relative power. SEEG4D generates models which can be loaded into VR platforms for viewing and planning with the surgical team. Automated contact segmentation locations are within 1 mm of trained raters and models generated show signal propagation along electrodes. Critically, spatial–temporal information communicated through our models in a VR space have potential to enhance sEEG pre-surgical planning.

Introduction: Ophthalmological adverse events (OAEs) are known to frequently occur following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS). The exact nature of these OAEs and the burden they put on survivors is less well described. Moreover, it is suspected there might be differences in the prevalence and nature of OAEs depending on local treatment strategy applied: external beam radiation therapy with photons, external beam radiation therapy with protons, macroscopically radical surgery combined with brachytherapy, or microscopically radical surgery combined with external beam radiation therapy. Methods: We cross-sectionally assessed 98 HNRMS survivors with long (median 9 years) follow-up time, according to a predefined list of OAEs based on the Common Terminology Criteria for Adverse Events system. We added information from chart reviews on the nature and management of all OAEs scored grade ≥1. We describe the prevalence of OAEs for the different tumor sites and treatment strategies separately. Results: OAEs occurred following treatment of all HNRMS sites. The most frequently observed OAEs are eyelid abnormalities, dry eyes, and cataracts. Sixty-two percent of survivors had several different OAEs simultaneously. In 27 % of survivors additional (surgical) treatment of OAEs was required during follow-up. The patterns observed suggest a possible relationship between OAE type and treatment strategy. Conclusion: OAEs in HNRMS survivors confer a high burden of chronic toxicity. The simultaneous occurrence of multiple OAEs in individual survivors present a particularly challenging clinical scenario and demand specific expertise. We propose a standardized screening scheme to detect possible OAEs in asymptomatic survivors based on primary tumor localization.

Abstract Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Recent outbreaks and recalls linked to flour-based products have highlighted the need for improved cleaning methods in low-moisture environments. The factors affecting adhesion forces of flour particles, and the vacuum cleaning methodologies to overcome these forces, need to be better understood. The objectives of this study were to: (1) Measure electrostatic charge build-up in flour under different environmental conditions (20, 40, 60% relative humidity at room temperature), (2) quantify how powder size (US standard No. 60–80 or 80–100 mesh), electrostatic charge (charged and uncharged), and relative humidity impact the force required to remove the powder from an electropolished 304 stainless steel coupon (8 × 8 × 0.2 cm), and (3) determine the most effective vacuum nozzle angle (0, 45, 90° relative to the surface) for cleaning. Chargeability (nC) of flour samples was assessed using Faraday cup electrometry, while the surface adhesion force of the flour particles was measured using a custom-built impact tester. The surface cleanliness after vacuum treatments was assessed using ATP (adenosine triphosphate) swabs and a luminometer. Charged flour samples at 20% relative humidity (RH) exhibited a significantly higher charge compared to those at 40 and 60% RH. Within the 60–80 mesh range, charged flour showed higher adhesion rates than uncharged samples at both 20 and 40% RH. However, in the 80–100 mesh range, charged flour did not show a significant difference in adhesion when compared to uncharged samples at any RH level. Additionally, at 60% RH, surface residues measured by ATP were significantly lower for a vacuum angle of 90° than for 0° across both 60–80 mesh and 80–100 mesh size ranges of wheat flour. The vacuum cleaning treatment proved capable of overcoming the increase in adhesion from triboelectric forces; however, trace flour residues were still detected on stainless steel surfaces postvacuuming, indicating that vacuuming alone may be insufficient.

This study aims to explore the intersection between immigrants' length of residence and visible minority status, examining how these factors influence the likelihood of obstructive sleep apnea (OSA) reported by a health professional. Utilizing data from the 2015–16 Canadian Community Health Survey and employing logistic regression analyses, we compare the prevalence of OSA reported by a health professional among distinct groups: white native-born, visible minority native-born, white recent immigrants, visible minority recent immigrants, white established immigrants, and visible minority established immigrants. At the unadjusted level, our findings indicate that visible minority native-born (cOR=0.57, p < 0.001) and recent immigrants (cOR=0.34, p < 0.001) are less likely to receive a sleep apnea diagnosis compared to white native-born individuals. However, when adjusting for demographic variables, particularly the age of respondents, the robustness of the significance diminishes for visible minority native-born (aOR=1.07, p > 0.05), while becoming significant for white established immigrants (aOR=0.79, p < 0.01). Despite remaining largely consistent after accounting for socioeconomic, behavioural, and health characteristics, the significance for visible minority recent immigrants (aOR=0.69, p > 0.05) and white established immigrants (aOR=0.82, p < 0.05) is substantially explained when considering BMI. Based on these findings, we discuss implications for policymakers and suggest avenues for future research.

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy – Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS. Plain-Language Summary: This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.

One Health is an integrated approach that aims to balance and optimize the interconnectedness of the health of humans, animals, and ecosystems. Using this transdisciplinary approach, experts from across Canada led the formation of the Wildlife Emerging Pathogens Initiative (Wild EPI) to undertake research and surveillance programs evaluating the potential risks of emerging pathogens at the human-animal interface. Wild EPI is dedicated to implementing the One Health approach to enhance our understanding of the epidemiology and burden of zoonotic infections among humans and other animal hosts.

Validation of baking processes for the inactivation of Salmonella is complicated by the combined effects of product heating and drying. The goal of this study was to quantitatively evaluate a previously disseminated approach to validating baking processes utilizing a predictive model developed using only isothermal and single-moisture inactivation data for the initially formulated dough. A simple cracker dough was formulated using flour inoculated with a five-strain cocktail of Salmonella. Side-by-side isothermal and baking experiments were performed to estimate Salmonella inactivation kinetics and to quantify survivors in a dynamic environment, respectively. Isothermal, single-moisture inactivation experiments were performed with cracker dough (water activity, aw = 0.956 ± 0.002; moisture content = 0.50 ± 0.01 dry basis) at three temperatures (56, 60, or 63°C) with ≥6 time intervals. Baking experiments were performed in a convection oven at 177°C with samples pulled every 30 s up to 360 s, with an endpoint product aw (25°C) of 0.45. The Salmonella isothermal, single-moisture inactivation kinetics in cracker dough resulted in D60°C and z−values of 4.6 min and 4.9°C, respectively; this model was then integrated over the dynamic product temperature profiles from the baking experiments. In the baking experiments, an average of 5-log reductions of Salmonella was achieved by 150 s of treatment; however, >100-log reductions were predicted by the dough-based models at that time point. This fail-dangerous overestimation of Salmonella lethality in crackers explicitly demonstrated that single-level moisture-based prediction models are inappropriate for describing inactivation in a process with both dynamic temperature and moisture, and that model-based validations must incorporate moisture/aw. Furthermore, end-users should exercise caution when utilizing unvalidated models to validate preventive control processes.

Background Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain.Methods The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio.Results We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p

Abstract Blood clots, which are composed of blood cells and a stabilizing mesh of fibrin fibers, are critical in cessation of bleeding following injury. However, their action is transient and after performing their physiological function they must be resolved through a process known as fibrinolysis. Internal fibrinolysis is the degradation of fibrin by the endogenous or innate presence of lytic enzymes in the bloodstream; under healthy conditions, this process regulates hemostasis and prevents bleeding or clotting. Fibrin-bound tissue plasminogen activator (tPA) converts nearby plasminogen into active plasmin, which is bound to the fibrin network, breaking it down into fibrin degradation products and releasing the entrapped blood cells. It is poorly understood how changes in the fibrin structure and lytic protein ratios influence the biochemical regulation and behavior of internal fibrinolysis. We used turbidity kinetic tracking and microscopy paired with mathematical modeling to study fibrin structure and lytic protein ratios that restrict internal fibrinolysis. Analysis of simulations and experiments indicate that fibrinolysis is driven by pore expansion of the fibrin network. We show that this effect is strongly influenced by the ratio of fibrin:tPAwhen compared to absolute tPA concentration. Thus, it is essential to consider relative protein concentrations when studying internal fibrinolysis both experimentally and in the clinic. An improved understanding of effective internal lysis can aid in development of better therapeutics for the treatment of bleeding and thrombosis.

Although the field of low-voltage power-line communications (PLC) has been maturing over the past few decades, the effective, economic and safe coupling of a modem to the live power grid remains a challenging topic. In literature, PLC coupling is covered sparsely, compared to other relevant PLC topics, and limited information is available to PLC researchers and designers. Therefore, this paper aims to achieve the following goals: (i) to guide the reader to a practical understanding of PLC coupling concepts; (ii) to expose the reader to a wide range of low-voltage PLC couplers and their operating principles; (iii) to brief the reader on typical PLC coupler design steps for the various classes of couplers; (iv) to establish good safety principles for these couplers; and (v) to assist researchers and designers with PLC coupler selection, through a qualitative comparison of various coupler pros and cons. This comparison illustrates why the transformer-capacitor coupler remains a coupler of choice, and that the potential of inductor-capacitor (L-C) couplers is perhaps overlooked.

Abstract Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.

Summary: Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generated self-organizing craniofacial cartilage organoids from human embryonic stem cell-derived neural crest stem cells. Histological staining of cartilage organoids revealed tissue architecture and staining typical of elastic cartilage. Protein and post-translational modification (PTM) mass spectrometry and snRNA-seq data showed that chondrocyte organoids expressed robust levels of cartilage extracellular matrix (ECM) components: many collagens, aggrecan, perlecan, proteoglycans, and elastic fibers. We identified two populations of chondroprogenitor cells, mesenchyme cells and nascent chondrocytes, and the growth factors involved in paracrine signaling between them. We show that ECM components secreted by chondrocytes not only create a structurally resilient matrix that defines cartilage, but also play a pivotal autocrine cell signaling role in determining chondrocyte fate.

A wide range of drying parameters and methods are used by industry to produce dried apples. To ensure end-product safety and regulatory compliance, it is essential to evaluate the effectiveness of such industrial practices on microbial inactivation. Therefore, the objective of this study was to evaluate the effects of drying air temperature and velocity on Listeria monocytogenes inactivation during drying of apple slices. Apples (cv. Gala) were cored, sliced as rings (∼6 mm thick), and surface-inoculated with broth-grown culture of an 8-strain cocktail of L. monocytogenes to achieve an inoculation level of 8.6 ± 0.3 log CFU/g. Apple rings were dried in batches using dry air in a pilot-scale impingement oven at 60 or 80 °C air temperature and 0.7 or 2.1 m/s air velocity, and sampled every 30 min for bacterial enumeration, water activity (aw), and moisture content analysis. L. monocytogenes reduction increased (P

Background While World Rugby guidelines do not mandate the inclusion of an electrocardiogram (ECG) for all players, this is required for entry into international rugby competitions. We, therefore, sought to describe sport-specific normative ECG values and evaluate the performance of contemporary athlete ECG guidelines in male and female professional rugby players.Methods We retrospectively analysed professional rugby players’ ECGs (n=356, male 79%) obtained during preparticipation screening (2010–2022), comparing by sex and playing position (forwards vs backs). ECGs were categorised as normal ‘training-related’, borderline and abnormal findings, as defined by the 2017 International Recommendations.Results 84% of players had one or more normal, ‘training-related’ findings, with males having a higher prevalence than females (91% vs 60%, p

Numerical simulation of fluid flow plays an essential role in modeling many physical phenomena, which enables technological advancements, contributes to sustainable practices, and expands our understanding of various natural and engineered systems. The calculation of heat transfer in fluid flow in simple flat channels is a relatively easy task for various simulation methods. However, once the channel geometry becomes more complex, numerical simulations become a bottleneck in optimizing wall geometries. We present a combination of accurate numerical simulations of arbitrary, flat, and non-flat channels as well as machine learning models trained on simulated data to predict the drag coefficient and Stanton number. We show that convolutional neural networks (CNNs) can accurately predict target properties at a fraction of the computational cost of numerical simulations. We use CNN models in a virtual high-throughput screening approach to explore a large number of possible, randomly generated wall architectures. Data augmentation techniques are incorporated to enforce physical invariances toward shifting and flipping, contributing to precise prediction for fluid flow and heat transfer characteristics. Moreover, we approach the interpretation of the trained model to better understand relevant channel structures and their influence on heat transfer. The general approach is not only applicable to simple flow setups as presented here but can be extended to more complex tasks, such as multiphase or even reactive unit operations in chemical engineering.

Background The temporal progression states of the molecular and structural substrate in atrial fibrillation (AF) are not well understood. We hypothesized that these can be detected by AF electrograms and magnetic resonance imaging parametric mapping. Methods and Results AF was induced in 43 dogs (25–35 kg, ≥1 year) by rapid atrial pacing (RAP) (3–33 weeks, 600 beats/min), and 4 controls were used. We performed high‐resolution epicardial mapping (UnEmap, 6 atrial regions, both atria, 130 electrodes, distance 2.5 mm) and analyzed electrogram cycle length, dominant frequency, organization index, and peak‐to‐peak bipolar voltage. Implantable telemetry recordings were used to quantify parasympathetic nerve activity over RAP time. Magnetic resonance imaging native T1, postcontrast T1, T2 mapping, and extracellular volume fraction were assessed (1.5T, Siemens) at baseline and AF. In explanted atrial tissue, DNA oxidative damage (8‐hydroxy‐2′‐deoxyguanosine staining) and percentage of fibrofatty tissue were quantified. Cycle length and organization index decreased (R=0.5, P

This pilot study investigated the feasibility of using magnetic resonance elastography (MRE) for the non-invasive detection and quantification of liver fibrosis in the Oncopig cancer model. Seven 8-week-old Oncopigs underwent alcoholic liver fibrosis induction and serial MRE imaging and liver biopsy at 1, 2, and 3 months post procedure. MRE was utilized to quantify liver stiffness, and liver fibrosis was histologically graded using the METAVIR system. The primary outcome measure was the capability to detect and quantify liver fibrosis using MRE with radiologic–pathologic correlation. Liver fibrosis induction, MRE imaging, and liver biopsy were successfully performed. MRE liver fibrosis was evident in 57% (4/7), 50% (3/6), and 40% (2/5) animal subjects 1, 2, and 3 months after fibrosis induction, with mean liver stiffness of 2.94, 3.25, and 2.91 kPa, respectively. Histological liver fibrosis was noted in 71% (5/7), 100% (5/5), and 100% (5/5) of animal subjects with available tissue samples. There was no significant statistical correlation between the MRE-measured liver stiffness and the METAVIR fibrosis scores. In conclusion, quantifiable liver fibrosis may be induced in the Oncopig. MRE has potential utility in non-invasively detecting liver stiffness in this large-animal preclinical model, though tissue biopsy was more sensitive in demonstrating disease.

Abstract The Antarctic ice sheet is buttressed by floating ice shelves that calve icebergs along large fractures called rifts. Despite the significant influence exerted by rifting on ice shelf geometry and buttressing, the scarcity of in situ observations of rift propagation contributes considerable uncertainty to understanding rift dynamics. Here, we report the first‐ever seismic recording of a multiple‐kilometer rift propagation event. Remote sensing and seismic recordings reveal that a rift in the Pine Island Glacier Ice Shelf extended 10.53 km at a speed of 35.1 m/s, the fastest known ice fracture at this scale. We simulate ocean‐coupled rift propagation and find that the dynamics of water flow within the rift limit the propagation rate, resulting in rupture two orders of magnitude slower than typically predicted for brittle fracture. Using seismic recordings of the elastic waves generated during rift propagation, we estimate that ocean water flows into the rift at a rate of at least 2,300 m3/s during rift propagation and causes mixing in the subshelf cavity. Our observations support the hypotheses that large ice shelf rift propagation events are brittle, hydrodynamically limited, and exhibit sensitive coupling with the surrounding ocean.

Literature of fourth-generation minimally invasive surgery (MIS) on hallux valgus is scarce. In this study, extra-capsular transverse osteotomies were performed on ten cadaveric specimens. The capital fragment was shifted lateral to nearly 100% of the first metatarsal width and then fixated in contemporary fashion following MIS principles. A mixture of radio-opaque solution and methylene blue dye was injected through the second screw hole into the pyramid-shaped space created after the osteotomy shift. The injection was visualized under fluoroscopy and specimen were dissected in layered fashion to assess for containment versus extravasation. The purpose of this study is to observe and describe the preservation of the joint capsule, periosteum, and soft tissue structures adjacent to the osteotomy.

The Internet of Things (IoT) and wearable computing are crucial elements of modern information systems and applications in which advanced features for user interactivity and monitoring are required. However, in the fields of pervasive gaming, IoT has had limited real-world applications. In this work, we present a prototype of a wearable platform for pervasive games that combines IoT with wearable computing to enable the real-time monitoring of physical activity. The main objective of the solution is to promote the utilization of gamification techniques to enhance the physical activity of users through challenges and quests. This aims to create a symbolic link between the virtual gameplay and the real-world environment without the requirement of a smartphone. With the integration of sensors and wearable devices by design, the platform has the capability of real-time monitoring the users’ physical activity during the game. The system performance results highlight the efficiency and attractiveness of the wearable platform for gamifying physical activity.

Objective Over the past decade, geopolitical turmoil in Venezuela has resulted in the displacement of 7.1 million people, resulting in a migration and refugee crisis.Methods and analysis This current cross-sectional, mixed-method research, which is focused on women and girls, examines differences in Venezuelan refugee/migrant demographics, migration characteristics, experiences and perceptions across nine locations in Ecuador, Peru and Brazil.Results A total of 9116 Venezuelan refugees/migrants shared 9339 migration experiences. Respondents in Brazil had been displaced for less time, reported more extreme poverty, perceived that they had received more support from the host community, and had more positive migration experiences. In contrast, respondents in Peru had been displaced for longer, were more likely to share experiences of insecurity/violence, perceived that they had not received adequate support and were more likely to report that the migration experience was negative. Respondents in Ecuador tended to provide more moderate responses somewhere between those from Brazil and Peru with one exception being around the impact of COVID-19, which they perceived more negatively.Conclusion It is critical to recognise that Venezuelan refugee/migrant populations are not homogenous and that their experiences, needs and priorities vary by location of settlement and migration route. From these findings, we recommend more open regularisation policies for Venezuelan nationals in Ecuador and Peru in addition to improved socioeconomic integration in accordance with the Quito Process. Sharing of successful models from other contexts may prove helpful.

Within recent years, there has been an increased interest towards organic photovoltaics (OPVs), especially with their significant device performance reaching beyond 19% since 2022. With these advances in the device performance of laboratory-scaled OPVs, there has also been more attention directed towards using printing and coating methods that are compatible with large-scale fabrication. Though large-area (>100 cm2) OPVs have reached an efficiency of 15%, this is still behind that of laboratory-scale OPVs. There also needs to be more focus on determining strategies for improving the lifetime of OPVs that are suitable for scalable manufacturing, as well as methods for reducing material and manufacturing costs. In this paper, we compare several printing and coating methods that are employed to fabricate OPVs, with the main focus towards the deposition of the active layer. This includes a comparison of performances at laboratory (2), small (1–10 cm2), medium (10–100 cm2), and large (>100 cm2) active area fabrications, encompassing devices that use scalable printing and coating methods for only the active layer, as well as “fully printed/coated” devices. The article also compares the research focus of each of the printing and coating techniques and predicts the general direction that scalable and large-scale OPVs will head towards.

With the steady increase in allergy prevalence worldwide, there is a strong need for novel diagnostic tools for precise, fast, and less invasive testing methods. Herein, a miniatured fluorescence-based biosensing system is developed for the rapid and quantitative detection of allergen-specific immunoglobulin-E. An antibody-based fluorescence assay in a microfluidic-patterned slide, combined with a custom-made portable fluorescence reader for image acquisition and user-friendly software for the data analysis, enables obtaining results for multiple allergens in just ~1 h with only 80 μL of blood serum. The multiplexed detection of common birch, timothy grass, cat epithelia, house dust mite, and dog epithelia shows quantitative IgE-mediated allergic responses to specific allergens in control serum samples with known total IgE concentration. The responses are verified with different control tests and measurements with a commercial fluorescence reader. These results open the door to point-of-care allergy screening for early diagnosis and broader access and for large-scale research in allergies.

The Nipah virus (NiV) and the Hendra virus (HeV) are highly pathogenic zoonotic diseases that can cause fatal infections in humans and animals. Early detection is critical for the control of NiV and HeV infections. We present the development of two antigen-detection ELISAs (AgELISAs) using the henipavirus-receptor EphrinB2 and monoclonal antibodies (mAbs) to detect NiV and HeV. The NiV AgELISA detected only NiV, whereas the NiV/HeV AgELISA detected both NiV and HeV. The diagnostic specificities of the NiV AgELISA and the NiV/HeV AgELISA were 100% and 97.8%, respectively. Both assays were specific for henipaviruses and showed no cross-reactivity with other viruses. The AgELISAs detected NiV antigen in experimental pig nasal wash samples taken at 4 days post-infection. With the combination of both AgELISAs, NiV can be differentiated from HeV. Complementing other henipavirus detection methods, these two newly developed AgELISAs can rapidly detect NiV and HeV in a large number of samples and are suitable for use in remote areas where other tests are not available.

Key Clinical Message We present a case of a quadriplegic male who developed ventricular fibrillation associated with an anomalous aortic origin of the right coronary artery. Successful revascularization was achieved with percutaneous coronary intervention. This case highlights the application of an unconventional approach to resolve ischemia in a patient with prohibitive surgical risk.

Background: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. Methods: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. Results: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41–0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67–1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. Conclusion: In patients with postinfarct VT, catheter ablation reduces mortality.

IntroductionSubcutaneous macroencapsulation devices circumvent disadvantages of intraportal islet therapy. However, a curative dose of islets within reasonably sized devices requires dense cell packing. We measured internal PO2 of implanted devices, mathematically modeled oxygen availability within devices and tested the predictions with implanted devices containing densely packed human islets.MethodsPartial pressure of oxygen (PO2) within implanted empty devices was measured by noninvasive 19F-MRS. A mathematical model was constructed, predicting internal PO2, viability and functionality of densely packed islets as a function of external PO2. Finally, viability was measured by oxygen consumption rate (OCR) in day 7 explants loaded at various islet densities.ResultsIn empty devices, PO2 was 12 mmHg or lower, despite successful external vascularization. Devices loaded with human islets implanted for 7 days, then explanted and assessed by OCR confirmed trends proffered by the model but viability was substantially lower than predicted. Co-localization of insulin and caspase-3 immunostaining suggested that apoptosis contributed to loss of beta cells.DiscussionMeasured PO2 within empty devices declined during the first few days post-transplant then modestly increased with neovascularization around the device. Viability of islets is inversely related to islet density within devices.

Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to 19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.

Abstract Bird flight muscle can lose as much as 20% of its mass during a migratory flight due to protein catabolism, and catabolism can be further exacerbated under dehydrating conditions. However, the functional consequences of exercise and environment induced protein catabolism on muscle has not been examined. We hypothesized that prolonged flight would cause a decline in muscle mass, aerobic capacity, and contractile performance. This decline would be heightened for birds placed under dehydrating environmental conditions, which typically increases lean mass losses. Yellow‐rumped warblers (Setophaga coronata) were exposed to dry or humid (12 or 80% relative humidity at 18°C) conditions for up to 6 h while at rest or undergoing flight. The pectoralis muscle was sampled after flight/rest or after 24 h of recovery, and contractile properties and enzymatic capacity for aerobic metabolism was measured. There was no change in lipid catabolism or force generation of the muscle due to flight or humidity, despite reductions in pectoralis dry mass immediately post‐flight. However, there was a slowing of myosin–actin crossbridge kinetics under dry compared to humid conditions. Aerobic and contractile function is largely preserved after 6 h of exercise, suggesting that migratory birds preserve energy pathways and function in the muscle.

Stereotactic ablative body radiation (SABR) delivers high rates of local control in early-stage non-small cell lung cancer (NSCLC); however, systemic immune effects are poorly understood. Here, we evaluate the early pathologic and immunologic effects of SABR. Blood/core-needle tumor biopsies were collected from six patients with stage I NSCLC before and 5–7 days after SABR (48 Gy/4 or 50 Gy/5 fractions). Serial blood was collected up to 1-year post-SABR. We used immunohistochemistry to evaluate pathological changes, immune-cell populations (CD8, FoxP3), and PD-L1/PD-1 expression within the tumor. We evaluated T-cell receptor (TCR) profile changes in the tumor using TCR sequencing. We used the MANAFEST (Mutation-Associated Neoantigen Functional Expansion of Specific T-cells) assay to detect peripheral neoantigen-specific T-cell responses and dynamics. At a median follow-up of 40 months, 83% of patients (n=5) were alive without tumor progression. Early post-SABR biopsies showed viable tumor and similar distribution of immune-cell populations as compared with baseline samples. Core-needle samples proved insufficient to detect population-level TCR-repertoire changes. Functionally, neoantigen-specific T-cells were detected in the blood prior to SABR. A subset of these patients had a transient increase in the frequency of neoantigen-specific T-cells between 1 week and 3–6 months after SABR. SABR alone could induce a delayed, transient neoantigen-specific T-cell immunologic response in patients with stage I NSCLC.

Abstract Background After ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post-IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy. Methods The transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNA-seq as a function of time and etiology after stroke. Differential expression analyses were performed at 0–24 h, 24–48 h, and >48 h following stroke. Results Unique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils, and whole blood with enrichment of interleukin signaling pathways for different time points and stroke etiologies. Compared to control subjects, gene expression was generally upregulated in neutrophils and generally downregulated in monocytes over all times for cardioembolic, large vessel, and small vessel strokes. Self-organizing maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co-expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood. Conclusions Altogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.

Abstract Background This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes. Methods Peripheral blood samples from the CLEAR trial IS patients at ≤ 3 h, 5 h, and 24 h after stroke were compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome assessed using the modified Rankin Scale (mRS) and the NIH Stroke Scale (NIHSS). Results The expression of 467, 526, and 571 genes measured at ≤ 3, 5 and 24 h after IS, respectively, were associated with poor 90-day mRS outcome (mRS ≥ 3), while 49, 100 and 35 genes at ≤ 3, 5 and 24 h after IS were associated with good mRS 90-day outcome (mRS ≤ 2). Poor outcomes were associated with up-regulated genes or pathways such as IL-6, IL-7, IL-1, STAT3, S100A12, acute phase response, P38/MAPK, FGF, TGFA, MMP9, NF-kB, Toll-like receptor, iNOS, and PI3K/AKT. There were 94 probe sets shared for poor outcomes vs. controls at all three time-points that correlated with 90-day mRS; 13 probe sets were shared for good outcomes vs. controls at all three time-points; and 46 probe sets were shared for poor vs. good outcomes at all three time-points that correlated with 90-day mRS. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome for mRS and NIHSS. Poor outcome modules were enriched with up-regulated neutrophil genes and with down-regulated T cell, B cell and monocyte-specific genes; and good outcome modules were associated with erythroblasts and megakaryocytes. Finally, genes identified by genome-wide association studies (GWAS) to contain significant stroke risk loci or loci associated with stroke outcome including ATP2B, GRK5, SH3PXD2A, CENPQ, HOXC4, HDAC9, BNC2, PTPN11, PIK3CG, CDK6, and PDE4DIP were significantly differentially expressed as a function of stroke outcome in the current study. Conclusions This study suggests the immune response after stroke may impact functional outcomes and that some of the early post-stroke gene expression markers associated with outcome could be useful for predicting outcomes and could be targets for improving outcomes.

Abstract Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.

The peripheral immune system response to Intracerebral Hemorrhage (ICH) may differ with ICH in different brain locations. Thus, we investigated peripheral blood mRNA expression of Deep ICH, Lobar ICH, and vascular risk factor-matched control subjects (n = 59). Deep ICH subjects usually had hypertension. Some Lobar ICH subjects had cerebral amyloid angiopathy (CAA). Genes and gene networks in Deep ICH and Lobar ICH were compared to controls. We found 774 differentially expressed genes (DEGs) and 2 co-expressed gene modules associated with Deep ICH, and 441 DEGs and 5 modules associated with Lobar ICH. Pathway enrichment showed some common immune/inflammatory responses between locations including Autophagy, T Cell Receptor, Inflammasome, and Neuroinflammation Signaling. Th2, Interferon, GP6, and BEX2 Signaling were unique to Deep ICH. Necroptosis Signaling, Protein Ubiquitination, Amyloid Processing, and various RNA Processing terms were unique to Lobar ICH. Finding amyloid processing pathways in blood of Lobar ICH patients suggests peripheral immune cells may participate in processes leading to perivascular/vascular amyloid in CAA vessels and/or are involved in its removal. This study identifies distinct peripheral blood transcriptome architectures in Deep and Lobar ICH, emphasizes the need for considering location in ICH studies/clinical trials, and presents potential location-specific treatment targets.

Distributed Acoustic Sensing (DAS) is increasingly recognised as a valuable tool for glaciological seismic applications, although analysing the large data volumes generated in acquisitions poses computational challenges. We show the potential of active-source DAS to image and characterise subglacial sediment beneath a fast-flowing Greenlandic outlet glacier, estimating the thickness of sediment layers to be 20–30 m. However, the lack of subglacial velocity constraint limits the accuracy of this estimate. Constraint could be provided by analysing cryoseismic events in a counterpart 3-day record of passive seismicity through, for example, seismic tomography, but locating them within the 9 TB data volume is computationally inefficient. We describe experiments with data compression using the frequency-wavenumber (f-k) transform ahead of training a convolutional neural network, that provides a ~300-fold improvement in efficiency. In combining active and passive-source and our machine learning framework, the potential of large DAS datasets could be unlocked for a range of future applications.

Data and insights from fishers are essential sources of information to advance understanding of fishery and ecosystem dynamics. Incorporating fisher and industry knowledge holds prospects for improving marine science and fisheries management. We address cooperative research in the context of collaboration between fishers, scientists, industries, universities, and agencies to develop applied research to understand marine ecosystems, inform fishery management, enhance sustainability, govern resource use, and investigate social-economic dynamics. We leverage the insights of more than 100 research scientists, fisheries managers, industry representatives, and fishers to outline actionable recommendations for effective approaches and mechanisms to integrate industry data, perspectives, and insights in fisheries science. We also highlight opportunities and address challenges and limitations to such collaboration.

Summary: mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.

The initial presentation of pediatric diabetes is variable, making prompt diagnosis and treatment challenging. The overlap between type 1 and type 2 diabetes and presence of developmental delays can complicate diagnosis, resulting in delays and severe illness at presentation. Here we describe a case of a 13-year-old male with autism and attention deficit hyperactivity disorder who presented with severe diabetic ketoacidosis, multiple organ failure, and shock. Within 2 weeks of this initial presentation, he had further clinical decompensation due to an intestinal perforation. Cultures from resected gastrointestinal tissue grew mucormycosis, protracting his hospital stay and recovery. He was able to go home several months later with remarkable improvement. This case highlights the necessity of careful history taking and early testing, and how investigation for rare complications of diabetes is vital when patients do not improve as expected.

Aim: Ravulizumab and eculizumab are complement C5 inhibitors approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Ravulizumab requires less frequent infusions than eculizumab, which may reduce treatment burden. This study investigated patients’ treatment preferences and the impact of both treatments on patient and caregiver quality of life. Materials & methods: Two surveys were conducted (one for adult patients with aHUS and one for caregivers of pediatric patients with aHUS) to quantitatively assess treatment preference and the patient- and caregiver-reported impact of ravulizumab and eculizumab on quality of life. Patients were required to have a diagnosis of aHUS, to be currently receiving treatment with ravulizumab and to have received prior treatment with eculizumab. Participants were recruited via various sources: the Alexion OneSource™ patient support program, the Rare Patient Voice recruitment agency, the aHUS Foundation and directly via a clinician involved in the study. Results: In total, 50 adult patients (mean age: 46.5 years) and 16 caregivers of pediatric patients (mean age: 10.1 years) completed the surveys. Most adult patients (94.0%) and all caregivers reported an overall preference for ravulizumab over eculizumab; infusion frequency was one of the main factors for patients when selecting their preferred treatment. Fewer patients reported disruption to daily life and the ability to go to work/school due to ravulizumab infusion frequency (4.0% and 5.7%, respectively) than eculizumab infusion frequency (72.0% and 60.0%), with similar results for caregivers. Conclusion: Adult patients and caregivers of pediatric patients indicated an overall preference for ravulizumab than eculizumab for the treatment of aHUS, driven primarily by infusion frequency. This study contributes to the emerging realworld evidence on the treatment impact and preference in patients with aHUS.

The foodborne pathogen Listeria monocytogenes generally infects immunocompromised individuals, such as cancer patients, more frequently and with higher morbidity and mortality than the general population. Because of the anticipated risk associated with L. monocytogenes and other pathogens in produce, immunocompromised individuals are often placed on neutropenic diets that exclude fresh produce, though these risks have not been quantified. Therefore, this study developed a data-driven risk model for listeriosis in cancer patients who consume ready-to-eat (RTE) salads, consisting of leafy greens, cucumbers, and tomatoes, as influenced by kitchen-scale treatments and storage practices. Monte Carlo simulations were used to model the risk of invasive listeriosis during one chemotherapy cycle. Refrigerating all salad components decreased the median risk by approximately one-half log. For refrigerated salads with no treatment, the predicted median risk was ≤ 4.3 × 10−08. When salad ingredients were surface blanched with greens rinsed, the predicted risk decreased to 5.4 × 10−10. Predicted risk was lowest (1.4 × 10−13) for a blanched “salad” consisting of solely cucumbers and tomatoes. Interestingly, rinsing, as recommended by FDA, only decreased the median risk by 1 log. A sensitivity analysis revealed that the highly variable dose-response parameter k strongly influenced risk, indicating that reducing uncertainty in this variable may improve model accuracy. Overall, this study demonstrates that kitchen-scale pathogen reduction approaches have high risk reduction efficacy and could be considered as an alternative to diets that exclude produce when making risk management decisions.