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This study examines the correlation between job descriptions and salaries at Immaculate Conception College of Balayan Inc. (ICCBI), a private Catholic institution devoted to faith-based education. Using qualitative research, a single-case study was conducted with ten (10) participants selected through purposive sampling based on specific criteria. Through face-to-face interviews, data was collected and analyzed using a narrative approach. Thus, it was found out that job descriptions at ICCBI are established through methods like job analysis, role and responsibility approaches, qualifications, and the school manual-based method. Salary determination involves factors such as tenure, educational attainment, performance, teaching loads, experience, and collegial care. Key factors influencing job descriptions include salary differentiation, aligned job descriptions, career development opportunities, and increased duties and responsibilities. Variations in the salary structure are affected by teaching loads, department designations, and educational qualifications. The findings indicate that job descriptions impact employee salaries at the institution, and future research is encouraged to explore identified factors for insights into developing more efficient roles and contributing to organizational effectiveness. With this, the study proposed a strategic plan for future use and implementation.

Systemic racism is pervasive in US society and disproportionately limits opportunities for education, work, and health for historically marginalized and minoritized racial and ethnic groups, making it an urgent issue of social justice. Because systemic racism is a social determinant of health prevalent across multiple social and institutional structures, it requires multilevel intervention approaches using effective designs and analytic methods to measure and evaluate outcomes. Racism is a fundamental cause of poor health outcomes, including mental health outcomes; thus, mental health services and programs that address racism and discrimination are key to promoting positive mental health of racial and ethnic minority youth. While multilevel interventions are well-suited for improving outcomes like youth mental health disparities, their evaluation poses unique methodological challenges, requiring specialized design and analytic approaches. There has been limited methodological guidance provided to researchers on how to test multilevel interventions using approaches that balance methodological rigor, practicality, and acceptability across stakeholder groups, especially within communities most affected by systemic racism. This paper addresses this gap by providing an example of how to rigorously evaluate a hypothetical, theoretically based, multilevel intervention promoting mental health equity in three US school systems using an anti-racist approach intervening at the macro- (i.e., school system), meso- (i.e., school), and micro- (i.e., family and student) levels to improve mental health in adolescents. We describe the design, sample size considerations, and analytic methods to comprehensively evaluate its effectiveness while exploring the extent to which the components interact synergistically to improve outcomes. The methodological approach proposed can be adapted to other multilevel interventions that include strategies addressing macro-, meso-, and micro-levels of influence.

This paper presents the design of intelligent models and architectures for global learning-oriented cooperation. The research work brings our current investigations towards the definition of a general development methodology for global intelligent systems. We use a basic top-down approach to analyze global cooperation, adding more natural intelligence into our models. Then we design, integrate and adapt software architectures to be able to extract the computational requirements of our systems at an appropriate level of abstraction. Our architectural designs serve to dynamically generate cooperative knowledge and behaviour using hybrid registries and intelligent engines. The registries store knowledge and behaviour descriptions. The functional engines control knowledge delivery processes and behaviour executions involving single and composite actions. All these elements are evaluated using a designing case study in current Sustainable Development Goals for education. This last part of the paper also discusses how our intelligent models and architectures can be further developed adding implementation details based on recent technologies.

Abstract Microgrids integrating inverter based resources face challenges like stability issues during voltage fluctuations and reliance on diesel generators in islanded mode. This paper presents a novel control strategy for photovoltaic and wind‐integrated microgrids to enhance reliability and efficiency. The strategy utilizes a modified phase‐locked loop with droop control for seamless synchronization in grid‐connected and islanded modes. Central to this approach is the localized autonomous controller with a socket protocol interfaced communication layer, dynamically managing operations based on real‐time conditions such as generation, load, and battery state of charge. By integrating battery storage systems, the strategy reduces diesel generator dependency during grid outages. Comprehensive simulations and controller hardware‐in‐the‐loop testing validate its effectiveness, demonstrating improved stability and decreased reliance on diesel generators. The socket protocol enhances real‐time communication, monitoring, and optimization of microgrid operations, ensuring optimal battery storage system utilization and minimal diesel usage. The proposed strategy addresses critical microgrid challenges, offering significant advancements in enhancing system resilience.

Abstract Objective This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. Method This was a multicenter, retrospective, observational, non‐interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first‐line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure‐free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow‐up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. Results A total of 276 patients were included (48 with BRV as first‐line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first‐line monotherapy group; 90.4% for conversion‐to‐monotherapy group). Seizure‐freedom rates at 12 months were 77.8% (75% for first‐line monotherapy group; 78.4% for conversion‐to‐monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first‐line monotherapy group; 40.4% for conversion‐to‐monotherapy group). Most AEs were mild‐to‐moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. Significance BRV was effective and well tolerated both as first‐line monotherapy and following conversion to monotherapy in a real‐world setting of patients with epilepsy. Plain Language Summary The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new‐generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury).

Introducción: La baja fuerza muscular es un factor de riesgo para diversas condiciones de salud como enfermedades cardiometabólicas, síndromes neurodegenerativos y mortalidad. Objetivo: Evaluar el conocimiento sobre fuerza muscular en profesionales de salud en Colombia. Materiales y Métodos: Se realizó un estudio analítico de tipo corte transversal en profesionales de salud asistentes a dos eventos de educación médica continuada. A través de un cuestionario se evaluaron tres componentes: identificación de la fuerza muscular como factor de riesgo para condiciones de salud, medición de la fuerza muscular y formación en fuerza muscular. Resultados: Se evaluaron 501 participantes (52,49% mujeres). 53,89% (n=270) eran médicos generales, 18,16% (n=91) especialistas y 6,18% (n=31). enfermeros . La asociación entre baja fuerza muscular con enfermedades cardiometabólicas fue identificada por el 56,67% (n=153) de médicos generales y 41,94% (n=13) de enfermeros. El 86,81% (n=79) de médicos especialistas y el 41,93% (n=13) de enfermeros reconocía la indicación de medir la fuerza muscular en adultos mayores. El 32,93% (n=165) de los participantes conocía de algún método de medición. Los fisioterapeutas fueron el grupo que más reportó realizar mediciones 83,33% (n=20). Sólo el 29,03% (n=9) de los enfermeros había recibido información académica sobre fuerza muscular. Discusión y Conclusión: Este estudio muestra el bajo conocimiento sobre la importancia de la fuerza muscular, su asociación a condiciones de salud, los métodos de medición y la falta de información sobre la literatura publicada al respecto. Son necesarias intervenciones educativas sobre fuerza muscular con el fin de incorporarla en la práctica clínica.

Conservation practices are encouraged to improve soil health and sustain agronomic crop production. Mehlich-3 is often used as a multi-nutrient extractant to determine soil fertility status. A study investigated the impacts of the conservation practices of gypsum, cover crops, and crop rotation on 28 Mehlich-3 extractable elements, of which 11 were considered plant nutrients, from soil at three midwestern US locations. Soil was collected from 0 to 15 and 15–30 cm depths 5 years after implementing the conservation practices. Treatments consisted of (1) with and without cereal rye (Secale cereale L.) winter cover, (2) continuous soybean [Glycine max (L.) Merr.] vs. soybean-corn (Zea mays L.) rotation, and (3) annual gypsum application (0, 1.1, and 2.2 Mg ha−1). Differences were observed by site, depth, and conservation practice depending on the element evaluated. Minimal interactive effects were observed among treatments. The most consistent effect was observed for crop rotation across sites. Gypsum only affected the site with the greatest clay content, where more Ca and S were retained, and Mg and Mn displaced. Cover crop only affected elements at this high clay site, where different elements were positively or negatively affected. Results suggest that not one practice fits all, and optimum conservation practices must be tailored for the site.

Research on experiences of gender and racial discrimination among young, racialized college women in Europe is scarce, particularly in Spain where Black women have traditionally had a minority presence in universities. As a result of processes of social mobility, these women are now occupying higher education spaces to an unprecedented extent, where they are becoming increasingly visible. These women's experiences of gender and racial discrimination throughout the education cycle are invisible. The aim of this article is to explore the personal experiences of racialization and discrimination among Black female college students in southern Spain. Twelve in-depth interviews were conducted and analysed to shed light on the experiences of young Black female students in predominantly white educational institutions. The stories of these women show that gender and race intersect and are constructed simultaneously through interactions with their mostly white peers. These women display responses of significant resilience.

Students, even as young as kindergarten, are natural problem solvers (Carpenter et al., 2017). Even before they learn to count, they can make sense of mathematical problems and real- world situations (National Council of Teachers of Mathematics, 2022). Kindergartners can make sense of complex story problems, including Separate Start Unknown problems, which involve an unknown quantity that decreases after an action occurs, resulting in a smaller quantity. This problem type is historically the most challenging of the additive problem types for young learners. This article highlights four students using tools to solve this problem type with included teacher takeaways.

Objective: Suicide is the second leading cause of death among college-age students in the U.S., with disparities in suicide ideation and attempts among Latinas. The current study aims to examine if depression severity predicts suicide ideation and attempts and to examine if caregiver intergeneration acculturation conflict (IAC) moderates this link. Participants: A sample of 246 Mexican-descent female college students. Methods: Self-reported measures for depression severity, male and female caregiver IAC, and suicide ideation and attempts in the previous 12-months were ascertained. Results: In our sample, 31.1% endorsed suicide ideation and 15.9% suicide attempts. Controlling for age, both male and female caregiver IAC moderated the relationship between depression severity and suicide ideation. A similar moderation pattern emerged for the suicide attempts outcome. Conclusions: Understanding this exacerbating contextual factor can help inform prevention/intervention efforts targeting Mexican-descent college students who are experiencing depressive symptoms by focusing on decreasing IAC with both caregivers.

Immigrant young adults without permanent legal status face a complicated set of issues as they try to integrate into adult society in the U.S. In this participatory research study, Latino/a emerging adult participants (n = 7) shared their perspectives about what it was like to live with Deferred Action for Childhood Arrivals (DACA), with temporary or unauthorized legal status, or in a mixed immigrant-status family within communities in central North Carolina. Specifically, participants were asked how those experiences impacted their educational pathways as a key marker of the ease or difficulty of community integration and adult role taking. The study was a qualitative participatory action research study, and the interview data were analyzed using interpretive phenomenological analysis (IPA). Relational cultural theory (RCT) was utilized to illuminate participants’ contexts and experiences, and how they encountered connection/warm welcome or disconnection/chilly welcome. Three key themes emerged from participants’ narratives: The first, self/identity, encompasses both experiences of belonging and backlash from the local community. The second, descriptions of context, details the supports and barriers to integration that were present. The third theme, responses to context, highlights how the participants engaged in self-advocacy at times, but also noted how the lack of basic rights was an obstacle for themselves and their peers. Together, these insights present critical considerations for understanding and supporting young adult immigrants and their integration/participation in U.S. communities.

Abstract Charcoal rot of sorghum (CRS) is a significant disease affecting sorghum crops, with limited genetic resistance available. The causative agent, Macrophomina phaseolina (Tassi) Goid, is a highly destructive fungal pathogen that targets over 500 plant species globally, including essential staple crops. Utilizing field image data for precise detection and quantification of CRS could greatly assist in the prompt identification and management of affected fields and thereby reduce yield losses. The objective of this work was to implement various machine learning algorithms to evaluate their ability to accurately detect and quantify CRS in red‐green‐blue images of sorghum plants exhibiting symptoms of infection. EfficientNet‐B3 and a fully convolutional network emerged as the top‐performing models for image classification and segmentation tasks, respectively. Among the classification models evaluated, EfficientNet‐B3 demonstrated superior performance, achieving an accuracy of 86.97%, a recall rate of 0.71, and an F1 score of 0.73. Of the segmentation models tested, FCN proved to be the most effective, exhibiting a validation accuracy of 97.76%, a recall rate of 0.68, and an F1 score of 0.66. As the size of the image patches increased, both models’ validation scores increased linearly, and their inference time decreased exponentially. This trend could be attributed to larger patches containing more information, improving model performance, and fewer patches reducing the computational load, thus decreasing inference time. The models, in addition to being immediately useful for breeders and growers of sorghum, advance the domain of automated plant phenotyping and may serve as a foundation for drone‐based or other automated field phenotyping efforts. Additionally, the models presented herein can be accessed through a web‐based application where users can easily analyze their own images.

Abstract Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non‐ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCreERT2+Ift88 tm1BkymTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post‐tamoxifen induction; Ift88 loss did not impact T cell development at the DN2‐DN4 stage or the CD4+/CD8+ double‐positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single‐positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88‐proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.

Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can ‘walk’ across the mouse brain slice, termed ‘patch-walking.’ We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e. 58 bidirectional probed connections) averaging 91 μm intersomatic distance, finding three connections. Patch-walking yields 80–92% more probed connections, for experiments with 10–100 cells than the traditional synaptic connection searching method.

Summary: The formation, stabilization, and elimination of synapses are tightly regulated during neural development and into adulthood. Pumilio RNA-binding proteins regulate the translation and localization of many synaptic mRNAs and are developmentally downregulated in the brain. We found that simultaneous downregulation of Pumilio 1 and 2 increases both excitatory and inhibitory synapse density in primary hippocampal neurons and promotes synapse maturation. Loss of Pum1 and Pum2 in the mouse brain was associated with an increase in mRNAs involved in mitochondrial function and synaptic translation. These findings reveal a role for developmental Pumilio downregulation as a permissive step in the maturation of synapses and suggest that modulation of Pumilio levels is a cell-intrinsic mechanism by which neurons tune their capacity for synapse stabilization.

Gastrointestinal disease is a leading cause of death in mature horses. A lack of in vitro modeling has impeded the development of novel therapeutics. The objectives of this study were to develop and further characterize a small intestinal monolayer cell culture derived from equine jejunum including establishing normal measurements of intestinal permeability and restitution. Three-dimensional enteroids, derived from postmortem sampling of equine jejunum, were utilized to develop confluent epithelial monolayers. The presence of differentiated intestinal epithelial cell types and tight junctions were confirmed using histology, reverse transcription PCR (RT-PCR), RNAscope, protein immunofluorescence and transmission electron microscopy. Transepithelial resistance (TER) and macromolecule flux were assessed as measurements of paracellular and transcellular permeability. Scratch assays were utilized to model and assess intestinal restitution. Monolayer cell cultures reached 100% confluency by ~5–7 days. Equine jejunum monolayers were confirmed as epithelial in origin, with identification of differentiated intestinal epithelial cell types and evidence of tight junction proteins. Function of the intestinal barrier was supported by acquisition of physiologically normal TER values (179.9 ± 33.7 ohms*cm2) and limited macromolecule flux (22 ± 8.8% at 60 min). Additionally, following a scratch wound, epithelial cell monolayers migrated to close gap defects within 24 h. In conclusion, this study describes the development of a novel intestinal epithelial monolayer cell culture for equine jejunum, and provides evidence of intestinal epithelial cell differentiation, formation of physiologically relevant barrier function and use as a model of intestinal restitution to test potential therapeutics for equine colic.

Aging is an inevitable and gradual decline in several biological functions. Mitochondrial dysfunction is one of the most important hallmarks of aging. In this context, alterations in metabolites associated with mitochondrial dysfunction may serve as a significant biomarker. This study aimed to investigate the existence of a relationship between the key metabolites involved in bioenergetics metabolism and aging. 53 volunteers ranged 20–85 years participated in the study. We tested the association between different tricarboxylic acid (TCA) cycle metabolites, fatty acid metabolism, and amino acid metabolism with age, sex, body composition, and proxy markers of aging such as walking speed, grip strength and chair test. We found that lactic acid negatively correlated with age while several fatty acid metabolites, such as azelaic, sebacic, and linoleic acids, showed positive correlations with age (p

Background/Objectives: Early postmortem mitochondrial function and apoptotic activation affect meat quality development. Nicotinamide riboside (NR) supplementation to pigs prior to harvest can improve pork color stability, but its mechanism remains unclear. This study aimed to evaluate the impact of NR supplementation on early postmortem mitochondrial functionality and apoptosis. Methods: Sixteen pigs (N = 16) were individually fed a control or NR-supplemented diet (30 mg·kg body weight−1·d−1) for 10 days prior to harvest. Longissimus dorsi muscle samples were collected at 45 min and 24 h postmortem and analyzed for mitochondrial functionality using high-resolution respirometry and apoptotic protein abundance (apoptosis regulator Bcl-2-associated X (BAX), apoptotic inducing factor (AIF), and caspase 3 (CASP3)) via immunoblotting. Results: NR-supplemented muscle exhibited lower proton leak-associated respiration at 45 min postmortem (p < 0.05), followed by a slower accumulation of mitochondrial outer membrane permeabilization (MOMP; p < 0.05) and a slower loss of mitochondrial integral function (p < 0.05) from 45 min to 24 h postmortem. NR supplementation decreased BAX abundance at 45 min postmortem but increased mature AIF abundance (62 kDa) at 24 h postmortem (p < 0.05). The abundance of CASP3 fragments (~29 kDa) decreased from 45 min to 24 h postmortem, independent of treatment (p < 0.05). Conclusions: NR supplementation demonstrated the potential to protect mitochondrial integral function and alleviate apoptotic activation in early postmortem porcine skeletal muscle, which might contribute to a higher meat color stability in NR-supplemented pork during retail display.

When measuring real-time in vivo muscle fatigue with electromyography (EMG), data collection can be compromised by premature sensor removal or environmental noise; therefore, the objective of this study was to develop a postmortem in vivo methodology to induce muscle fatigue and measure it using EMG. Barrows (N = 20) were stratified by weight and randomly allocated into one of two treatments. The treatments consisted of barrows being subjected to a hog electric stunner super-contraction cycle (ES) or not (CON) postmortem. The right hind limb bicep femoris (BF) and semitendinosus (ST) were selected for ambulatory movement simulation using electronic muscle stimulation (EMS). Muscle workload during EMS was measured with EMG using median power frequency (MdPF) and root mean square (RMS) as indicators of action potential velocity and muscle fiber recruitment. Ambulatory movement was induced and recorded for 20 min with a 4:4 duty cycle at 70 Hz. Muscle biopsies were collected pre- and post-EMS for metabolite analyses to corroborate muscle fatigue onset. There was a TRT × Muscle interaction for normalized RMS percentage (p < 0.01), where BF from CON barrows had greater values (p < 0.01). There were no interactions or TRT main effects for the MdPF normalized value (p ≥ 0.25), but there were Period and muscle effects on MdPF (p < 0.01). Bicep femoris had smaller (p < 0.01) MdPF than ST. The percentage of MdPF decreased (p < 0.01) by Period 5 compared to the other Periods, which did not differ from each other (p ≥ 0.38). There were TRT × Muscle and Muscle × Period interactions for ATP muscle concentration (p ≤ 0.03). The concentration of CON BF ATP was greater (p < 0.01) than that of ES BF and CON and ES ST, which did not differ from each other (p ≥ 0.11), but the APT concentration tended to differ between ES BF and ES ST (p = 0.06). Semitendinosus ATP concentration decreased (p < 0.01) post-EMS compared to ST pre- and BF pre- and post-EMS (p ≥ 0.29), but BF and ST concentration tended to differ pre-EMS (p = 0.07). The data indicated that EMS is a valuable tool for replicating ambulatory movement or physical activity, but super-contraction is not a means to accelerate postmortem muscle fatigue onset. Therefore, further refinement, such as longer EMS stimulation time, should be considered.

Hemorrhage is a leading cause of preventable death in military and civilian trauma medicine. Fluid resuscitation is the primary treatment option, which can be difficult to manage when multiple patients are involved. Traditional vital signs needed to drive resuscitation therapy being unavailable without invasive catheter placement is a challenge. To overcome these obstacles, we propose using closed-loop fluid resuscitation controllers managed by non-invasive, intermittent signal sensor inputs to simplify their use in far-forward environments. Using non-invasive, intermittent sensor controllers will allow quicker medical intervention due to negating the need for an arterial catheter to be placed for pressure-guided fluid resuscitation. Two controller designs were evaluated in a swine hemorrhagic shock injury model, with each controller only receiving non-invasive blood pressure (NIBP) measurements simulated from invasive input signals every 60 s. We found that both physiological closed-loop controllers were able to effectively resuscitate subjects out of life-threatening hemorrhagic shock using only intermittent data inputs with a resuscitation effectiveness of at least 95% for each respective controller. We also compared this intermittent signal input to a NIBP cuff and to a deep learning model that predicts blood pressure from a photoplethysmography waveform. Each approach showed evidence of tracking blood pressure, but more effort is needed to refine these non-invasive input approaches. We conclude that resuscitation controllers hold promise to one day be capable of non-invasive sensor input while retaining their effectiveness, expanding their utility for managing patients during mass casualty or battlefield conditions.

Prehospital medical care is a major challenge for both civilian and military situations as resources are limited, yet critical triage and treatment decisions must be rapidly made. Prehospital medicine is further complicated during mass casualty situations or remote applications that require more extensive medical treatments to be monitored. It is anticipated on the future battlefield where air superiority will be contested that prolonged field care will extend to as much 72 h in a prehospital environment. Traditional medical monitoring is not practical in these situations and, as such, wearable sensor technology may help support prehospital medicine. However, sensors alone are not sufficient in the prehospital setting where limited personnel without specialized medical training must make critical decisions based on physiological signals. Machine learning-based clinical decision support systems can instead be utilized to interpret these signals for diagnosing injuries, making triage decisions, or driving treatments. Here, we summarize the challenges of the prehospital medical setting and review wearable sensor technology suitability for this environment, including their use with medical decision support triage or treatment guidance options. Further, we discuss recommendations for wearable healthcare device development and medical decision support technology to better support the prehospital medical setting. With further design improvement and integration with decision support tools, wearable healthcare devices have the potential to simplify and improve medical care in the challenging prehospital environment.

IntroductionHemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage. Here, we evaluate if features extracted from the arterial waveform can allow for early hemorrhage prediction and improved intervention in canines.MethodsIn this effort, we extracted more than 1,900 features from an arterial waveform in canine hemorrhage datasets prior to hemorrhage, during hemorrhage, and during a shock hold period. Different features were used as input to decision tree machine learning (ML) model architectures to track three model predictors—total blood loss volume, estimated percent blood loss, and area under the time versus hemorrhaged blood volume curve.ResultsML models were successfully developed for total and estimated percent blood loss, with the total blood loss having a higher correlation coefficient. The area predictors were unsuccessful at being directly predicted by decision tree ML models but could be calculated indirectly from the ML prediction models for blood loss. Overall, the area under the hemorrhage curve had the highest sensitivity for detecting hemorrhage at approximately 4 min after hemorrhage onset, compared to more than 45 min before detection based on mean arterial pressure.ConclusionML methods successfully tracked hemorrhage and provided earlier prediction in canines, potentially improving hemorrhage detection and objectifying triage for veterinary medicine. Further, its use can potentially be extended to human use with proper training datasets.

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, particularly for older adults, who constitute a majority of the global cancer patient population. This study aimed to assess the inclusion, characteristics, and reporting of older adults enrolled in Food and Drug Administration (FDA) registration clinical trials of ICI between 2018 and 2022. Clinical trials of ICI leading to an FDA approval in solid tumor oncology between 2018 and 2022 were included. Primary study reports and all available secondary publications were assessed. The availability and completeness of older subgroup data for protocol-defined clinical efficacy endpoints, health-related quality of life (HRQOL) and toxicity outcomes, and baseline characteristics were assessed according to predefined criteria which categorized reporting completeness hierarchically in relation to the availability of published data, including effect size, sample size, and measures of precision. 53 registration trials were included, involving a total of 37,094 participants. Most trials (64.2%) were of ICI combination therapy. 42.3% of patients were aged≥65 years; 11.1% were aged≥75. No trials specified an upper age limit for eligibility. 98.1% of trials excluded patients with European Cooperative Oncology Group performance status>1. 87.2% of primary efficacy endpoints and 17.9% of secondary efficacy endpoints were reported completely for older adults. Five studies (9.4%) reported baseline characteristics, three (6.1%) reported HRQOL assessments, and four (7.5%) reported toxicity outcomes completely among older subgroups. No trials conducted baseline geriatric assessments or reported geriatric-specific symptoms or quality of life scales. This analysis highlights significant deficits in the enrollment and reporting of older subgroups in pivotal trials of ICI therapy. The findings highlight an urgent need for improved reporting and inclusion standards in clinical trials of ICI to better inform treatment decisions for older adults.

Summary: Finding an effective therapy against diseases caused by flaviviruses remains a challenge. Here, we present a protocol to test Food and Drug Administration-approved drugs that inhibit host nuclear protein import, promoting a reduction of dengue infection. We describe steps for analyzing the drug effect on nuclear import inhibition of cellular and viral proteins by confocal microscopy or western blotting. We then describe procedures for measuring the antiviral drug effects on virus-infected cells by flow cytometry and testing drug efficacy in dengue-infected AG129 mice by survival assays.For complete details on the use and execution of this protocol, please refer to Palacios-Rápalo et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Central Venous Catheterization (CVC) is conducted in more than 5 million patients annually in the United States. Currently, CVC theoretical knowledge is typically taught with didactic lectures with minimal assessment of knowledge before simulation training and clinical environment. To assess CVC theoretical knowledge, virtual reality (VR) can develop residents’ surgical skills and can provide feedback on performance. While all types of VR can be used to assess improvements in residents’ knowledge prior to simulation training, few studies have compared the impact of non-immersive VR on improving resident knowledge. The current study was developed to identify the utility of a non-immersive CathSim VR on improvements in resident CVC theoretical knowledge, self-efficacy, and satisfaction when compared to a traditional multiple-choice assessment This was completed through an empirical investigation with 34 medical residents. The results showed that when compared to a traditional multiple-choice assessment, the non-immersive CathSim VR assessment led to improvements in self-efficacy and potentially better learning experience. Meanwhile, results also showed that there were no differences in assessment score, number of attempts, and overall satisfaction. Thus, we can conclude that non-immersive VR has the potential to be more effective than traditional multiple-choice test in improving self-efficacy and is as effective for residents’ assessment score, number of attempts, and overall satisfaction.

The purpose of this study was to examine the frequency and quality of primary care physician (PCP) recommendations to investigate the management of young children with delays and self-injury (SIB; e.g., head banging) from the time of initial SIB concern to specialty referral as recommended by the American Academy of Pediatrics (AAP). Via a structured electronic health record review, PCP referrals and recommendations were examined for a cohort of 250 children (10-59 months old) with delays and SIB. Only a small portion of cohort charts reviewed (8.0%) received AAP recommended intervention via referral to subspecialty providers by their PCP. Further, only 37.5% received SIB-specific care recommendations. Findings suggest that future targeted education is needed to improve primary care access to AAP recommended intervention for young children with delays and early SIB.

Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi. One of the complications of the disease is the infection of the central nervous system (CNS), as it can result from either the acute phase or by reactivation during the chronic phase, exhibiting high mortality in immunocompromised patients. This systematic review aimed to determine clinical and paraclinical characteristics of patients with Chagas disease in the CNS. Articles were searched from PubMed, Scopus and LILACS until January 2023. From 2325 articles, 59 case reports and 13 case series of patients with Chagas in the CNS were retrieved from which 138 patients were identified. In this population, 77% of the patients were male, with a median age of 35 years old, from which most of them came from Argentina and Brazil. Most of the individuals were immunocompromised from which 89% were HIV-positive, and 54 patients had an average of 48 cells per mm3 CD4+ T cells. Motor deficits and seizures were the most common manifestation of CNS compromise. Furthermore, 90 patients had a documented CNS lesion by imaging from which 89% were supratentorial and 86% were in the anterior/middle cranial fossa. The overall mortality was of 74%. Among patients who were empirically treated with anti-toxoplasma drugs, 70% died. This review shows how Chagas disease in the CNS is a devastating complication requiring prompt diagnosis and treatment to improve patients’ outcomes.

Abstract Lightning strikes, snow, and wind are common causes of power system failures. Their frequency of occurrence varies depending on weather patterns and seasons. Here, we analyse the occurrence of thirty pre-defined daily weather patterns along with nearly 70,000 power system failures in the United Kingdom between 2010 and 2019 to investigate the predictability of weather-induced power outages. We identify high-risk weather patterns and pattern transitions for all seasons. Winter weather patterns characterized by high wind speeds and high precipitation volumes are responsible for many instances of power outages caused by wind, gale, and lightning strikes. Weather patterns with moderate to high snowfall are often linked to power outages caused by snow and ice. Because high-risk weather patterns can be forecast reliably with valuable lead time, clear links between specific patterns and transitions can significantly improve the preparedness of the United Kingdom and broader European distribution network operators for adverse weather conditions.

Background: The humoral immune response against human papillomavirus (HPV) has been suggested as a source of biomarkers for the early detection of cervical cancer (CC). Therefore, we aimed to characterize the antibody response against HPV16 E5 in the natural history of cervical cancer and to determine its usefulness as a biomarker of HPV-associated cervical lesions. Methods: This study was conducted at the Cuautla General Hospital, Morelos, Mexico, with women (18 to 64 years) who agreed to participate. Samples were obtained from 335 women with cervical lesions and 150 women with negative Papanicolaou tests. HPV genotyping was performed by PCR and pyrosequencing, and anti-E5 antibodies were detected by slot blot. Results: The overall anti-E5 antibodies prevalence in the study was 17.9%, with the higher prevalence observed in the no lesion (NL, 49.4%) group, and with a downward trend according to the degree of the cervical lesion, from cervical intraepithelial neoplasia-1 (CIN1, 32.2%) to CIN2 (11.5%) and CIN3/CC (6.9%). The logistic regression model showed negative associations of anti-E5 antibodies with CIN1 (OR = 0.38), CIN2 (OR = 0.42), and CIN3/CC (OR = 0.32) groups, being statistically significant. Contrast analysis showed an inverse relationship between anti-E5 antibodies with HPV DNA and the CIN1 (OR = 0.35), CIN2 (OR = 0.39), and CIN3/CC (OR = 0.31) groups. Conclusions: These results suggest that anti-E5 antibodies could be associated with clearance of infection in women without lesions and with CIN1 lesions since an inverse relationship was observed between the presence of HPV DNA and anti-E5 antibodies. In contrast, with progression from CIN2/CIN3 to CC, the relationship was reversed, as the anti-E5 antibodies disappeared, and the frequency of the viral genome increased.

Hemorrhage leading to life-threatening shock is a common and critical problem in both civilian and military medicine. Due to complex physiological compensatory mechanisms, traditional vital signs may fail to detect patients’ impending hemorrhagic shock in a timely manner when life-saving interventions are still viable. To address this shortcoming of traditional vital signs in detecting hemorrhagic shock, we have attempted to identify metrics that can predict blood loss. We have previously combined feature extraction and machine learning methodologies applied to arterial waveform analysis to develop advanced metrics that have enabled the early and accurate detection of impending shock in a canine model of hemorrhage, including metrics that estimate blood loss such as the Blood Loss Volume Metric, the Percent Estimated Blood Loss metric, and the Hemorrhage Area metric. Importantly, these metrics were able to identify impending shock well before traditional vital signs, such as blood pressure, were altered enough to identify shock. Here, we apply these advanced metrics developed using data from a canine model to data collected from a swine model of controlled hemorrhage as an interim step towards showing their relevance to human medicine. Based on the performance of these advanced metrics, we conclude that the framework for developing these metrics in the previous canine model remains applicable when applied to a swine model and results in accurate performance in these advanced metrics. The success of these advanced metrics in swine, which share physiological similarities to humans, shows promise in developing advanced blood loss metrics for humans, which would result in increased positive casualty outcomes due to hemorrhage in civilian and military medicine.

Research examining the changes in muscle oxygen saturation across multiple sets of resistance exercise is limited. The purpose of this study was to describe the physiological response of muscle oxygenation parameters during upper-body resistance exercise and examine the differential effects of relevant participant characteristics on resistance training performance and muscle oxygen saturation dynamics. Sixty-one recreationally trained men (n = 44; 21.8 ± 2.6 years) and women (n = 17; 20.2 ± 1.8 years) completed five-repetition maximum sets of barbell bench presses at a load equal to 75% 1-RM with a 2 min rest interval. Muscle oxygen saturation (SmO2) dynamics within the anterior deltoid were monitored using a portable near-infrared spectroscopy sensor. The percent change in SmO2 (∆%SmO2), the muscle oxygen re-saturation rate (SmO2RecSlope), and the highest measured SmO2 value during recovery periods (SmO2Peak) were measured. Two-way (sex [men, women] x time [sets 1–5]) repeated measures analyses of variance (ANOVA) were performed on muscle saturation variables. To examine the effect of relevant controlling variables, separate analyses of covariance (ANCOVA) with repeated measures were also performed. No differences were seen with ∆%SmO2 across sets. The main effects for sets occurred for SmO2RecSlope, whereby a decline was noted on sets 4 and 5 (p = 0.001) compared to set 1. Additionally, SmO2Peak was the lowest on set 5 (p < 0.001) compared to all other sets. Moreover, body mass (p = 0.013), diastolic blood pressure (p = 0.044), and mean arterial pressure (p = 0.033) for ∆%SmO2 were the only significant covariates noted amongst the muscle oxygenation variables. In conclusion, no sex differences and only a few set differences in muscle oxygen saturation dynamics were seen without employing any covariates. Body mass, diastolic blood pressure, and mean arterial pressure were identified as factors that could influence observed responses.

Background: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition. Methods: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts. Results: The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study. Conclusions: Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity.

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Abstract The intestinal lumen is filled with diverse chemical and physical stimuli. Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function. Yet, the neuro-epithelial connections remain poorly resolved, in part because the tools for orchestrating interactions between these cellular compartments are lacking. We describe the development of a two-compartment microfluidic device for co-culturing enteric neurons with intestinal epithelial cells. The device contains epithelial and neuronal compartments connected by microgrooves. The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids. We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week. In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons (IPANs) from transgenic mice that expressed the fluorescent protein tdTomato. IPANs extended projections into microgrooves, surrounded and frequently made contacts with epithelial cells. The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment. Our microfluidic device represents a platform that may, in the future, be used to dissect structure and function of neuro-epithelial connections in the gut and other organs (skin, lung, bladder, and others) in health and disease.

The ability to maintain functional hepatocytes has important implications for bioartificial liver development, cell-based therapies, drug screening, and tissue engineering. Several approaches can be used to restore hepatocyte function in vitro, including coating a culture substrate with extracellular matrix (ECM), encapsulating cells within biomimetic gels (Collagen- or Matrigel-based), or co-cultivation with other cells. This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids. These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors. We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes. We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor (HGF) into microcapsules and inhibiting transforming growth factor (TGF)-β1 signaling. Overall, bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering, regenerative medicine, and drug testing applications.

Introduction: The objective of this study was to examine the effects of in ovo nicotinamide riboside (NR) feeding on high-yield broiler growth and meat quality.Methods: Fertilized Cobb 700 by-product eggs (N = 3,240) were randomly assigned to one of four in ovo treatments and injected with 0 (0NR), 250 (250NR), 500 (500NR), or 1,000 (1,000NR) mM NR at incubation-day 10. Chicks were hatched, vent sexed, and randomly placed 18 per pen in one of 32 floor pens. On day 48, birds were processed and deboned.Results: There were dose effects for all part weights (p < 0.05). Pectoralis major weight of 250, 500, and 1,000NR carcasses were heavier than 0NR (p < 0.03) but did not differ from remaining NR doses (p > 0.26). Pectoralis minor weight of 250NR carcasses was greater (p < 0.01) than 0NR and did not differ from other NR tenders (p > 0.21). Pectoralis minor weight of 500 and 1,000NR carcasses was greater than 0NR (p < 0.09), but did not differ (P = 0.82) from each other. There were no dose effects for all Pectoralis major and minor myopathy scores and incidence except incidence of tenders scoring “0” and “1” for woody-like tender. Percentage of NR1,000 tenders scoring 0 and 1 for woody-like tender were less than and greater than all other treatments, respectively (p < 0.05). There were no differences among remaining NR doses and NR0 tenders (p > 0.10). There were dose effects for muscle fiber number (P = 0.03). There tended to be more muscle fibers within 250 and 1,000NR muscles compared to 0NR (p < 0.09). Pectoralis major muscle from 500NR did not differ in muscle fiber number compared to 250 and 1,000NR (p > 0.18), but had more (p < 0.01) fibers than 0NR muscle. There tended to be more fibers in 250 and 1,000NR muscles compared to 0NR muscle (p < 0.09).Discussion: Nicotinamide riboside in ovo feeding caused birds to produce heavier parts; however, myopathy scores and incidence were minimally affected which may have been due greater muscle fiber number.

Abstract Introduction Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. Results A simple sum of 5 PRSs (“PRSsum”), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE- $$\epsilon 2$$ ϵ 2 and APOE- $$\epsilon 4$$ ϵ 4 alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE- $$\epsilon 4$$ ϵ 4 and APOE- $$\epsilon 2$$ ϵ 2 alleles were not associated with MCI. Discussion A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE- $$\epsilon 4$$ ϵ 4 and APOE- $$\epsilon 2$$ ϵ 2 alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.

Abstract The Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/c charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1 $$\pm 0.6$$ ± 0.6 % and 84.1 $$\pm 0.6$$ ± 0.6 %, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation.

Abstract Forests play a critical role in stabilizing Earth’s climate. Establishing protected areas (PAs) represents one approach to forest conservation, but PAs were rarely created to mitigate climate change. The global impact of PAs on the carbon cycle has not previously been quantified due to a lack of accurate global-scale carbon stock maps. Here we used ~412 million lidar samples from NASA’s GEDI mission to estimate a total PA aboveground carbon (C) stock of 61.43 Gt (+/− 0.31), 26% of all mapped terrestrial woody C. Of this total, 9.65 + /− 0.88 Gt of additional carbon was attributed to PA status. These higher C stocks are primarily from avoided emissions from deforestation and degradation in PAs compared to unprotected forests. This total is roughly equivalent to one year of annual global fossil fuel emissions. These results underscore the importance of conservation of high biomass forests for avoiding carbon emissions and preserving future sequestration.

Abstract Background Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case–control study within the European Prospective Investigation into Cancer and Nutrition. Methods Concentrations of C‐peptide—a marker for insulin secretion—were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C‐peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI

Abstract Background The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality. Methods A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0–5), medium (score 6–8), and high (score 9–16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality. Results After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01–1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84–1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87–0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72–0.91). Conclusions Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.

The objective of this study was to determine the daily dietary nicotinamide riboside (NR) dose required to maximize the delay of subjective muscle fatigue onset. Barrows (N = 100) were assigned to one of five treatments: a conventional swine finishing diet containing 0 (CON), 15 (15NR), 30 (30NR), 45 (45NR) mg·kg body weight−1·d−1 NR, or CON supplemented with 45 mg·kg body weight−1·d−1 NR by drench or cookie dough (DRE). All treatments were administered for the final 11 days of feeding. On supplementation d 10, barrows individually experienced a performance test at 1.09 m/s until they were subjectively exhausted. Wireless electromyography (EMG) sensors were affixed to the biceps femoris (BF), tensor fascia latae (TFL), and semitendinosus (ST) to measure real-time muscle activity. There were no treatment effects for barrow speed (p = 0.57), a tendency for a treatment effect (p = 0.07) for distance, and a treatment effect (p = 0.04) on time to exhaustion. Barrows of the 15NR and DRE treatments had greater (p = 0.05) distances to exhaustion than CON barrows but did not differ from other NR barrows (p > 0.11). Barrows in the 45NR treatment did not differ (p = 0.11) in distance from 30NR barrows but tended to have a greater (p = 0.07) distance compared to CON barrows. All other treatment comparisons did not differ (p > 0.27). Barrows in the DRE treatment moved for longer (p < 0.01) than CON barrows, but all other treatments did not differ from each other (p > 0.15). There was no treatment × period interaction for all muscles’ root mean square (RMS) values (p > 0.16), but there were Period effects for all muscles (p < 0.01) and a Treatment effect (p = 0.04) in the TFL. For all muscles, period 4 had greater RMS values than all other periods (p < 0.01), who did not differ from each other (p > 0.29). In the TFL, CON barrows had greater RMS values during the performance test compared to all NR treatments (p < 0.02), who did not differ from each other (p > 0.18). Overall, NR demonstrates potential in being a useful tool in fatigue prevention, but efficient administration of the compound needs further investigation.

Abstract Patient‐derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non‐resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold‐standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.

Species differentiation and the appearance of novel diversity on Earth is a major issue to understand the past and future of microbial evolution. Herein, we propose the analysis of a singular evolutive example, the case of microorganisms carrying out the process of anammox (anaerobic ammonium oxidation). Anammox represents a singular physiology active on Earth from ancient times and, at present, this group is still represented by a relatively limited number of species carrying out a specific metabolism within the Phylum Planctomycetota. The key enzyme on the anammox pathway is hydrazine dehydrogenase (HDH) which has been used as a model in this study. HDH and rRNA (16S subunit) phylogenies are in agreement suggesting a monophyletic origin. The diversity of this singular phylogenetic group is represented by a few enriched bacterial consortia awaiting to be cultured as monospecific taxa. The apparent evolution of the HDH genes in these anammox bacteria is highly related to the diversification of the anammox clades and their genomes as pointed by phylogenomics, their GC content and codon usage profile. This study represents a clear case where bacterial evolution presents a paralleled genome, gene and species diversification through time from a common ancestor; a scenario that most times is masked by a web-like phylogeny and the huge complexity within the prokaryotes. Besides, this contribution suggests that microbial evolution of the anammox bacteria has followed an ordered, vertical diversification through Earth history and will present a potentially similar speciation fate in the future.