Nitrogen accountancy in space agriculture.

Food production and pharmaceutical synthesis are posited as essential biotechnologies for facilitating human exploration beyond Earth. These technologies not only offer critical green space and food agency to astronauts but also promise to minimize mass and volume requirements through scalable, modular agriculture within closed-loop systems, offering an advantage over traditional bring-along strategies. Despite these benefits, the prevalent model for evaluating such systems exhibits significant limitations. It lacks comprehensive inventory and mass balance analyses for crop cultivation and life support, and fails to consider the complexities introduced by cultivating multiple crop varieties, which is crucial for enhancing food diversity and nutritional value. Here we expand space agriculture modeling to account for nitrogen dependence across an array of crops and demonstrate our model with experimental fitting of parameters. By adding nitrogen limitations, an extended model can account for potential interruptions in feedstock supply. Furthermore, sensitivity analysis was used to distill key consequential parameters that may be the focus of future experimental efforts.

Understanding the Scope of Acute Care Vascular Surgery at a Tertiary Academic Medical System.

OBJECTIVE: The restructuring of non-elective general surgery and nationwide implementation of the acute care surgery paradigm has improved patient outcomes and healthcare resource utilization. Although vascular surgery maintains one of the highest acuity rates among surgical specialties, the acute care vascular surgery (ACVS) practice model has not been widely accepted. In the present study, we investigate the scope and burden of ACVS at a tertiary academic medical system. METHODS: All vascular surgical procedures performed at three hospitals comprising a large tertiary academic medical system were retrospectively queried through electronic medical records. Data were collected on procedure, acuity, timing of intervention, primary service, admission type, and total costs and charges. Patients were stratified by acuity of surgical intervention, with ACVS being defined as urgent or emergent operation. RESULTS: A total of 12,689 vascular surgeries were performed from 2018 to 2022. ACVS procedures comprised 22.1% this total (n=2,803; 12.5% urgent, 9.6% emergent), with an annual burden ranging from 19.1% to 28.3%. Vascular surgeons served as primary surgeon in 91.3% of ACVS and co-surgeon in 8.7%. Fourteen separate surgical specialties requested acute vascular assistance, with the most frequently consulting specialties including trauma/acute care surgery (n=109, 3.9%) and cardiac surgery (n=74, 2.6%). ACVS cases were more frequently performed after-hours (30.7% vs 11.6%) and on weekends (27.1% vs 2.0%) compared with elective vascular procedures (p<0.0001 each). The majority of ACVS cases originated from inpatient (n=2,353, 85.0%) and emergency department (n=379, 13.5%) consultations. Overall, ACVS generated $37.5 million in charges, accounting for 14% of total procedure-related charges over the study period. CONCLUSIONS: ACVS comprises a substantial portion of modern vascular practice, and is associated with significant human and healthcare resource expenditure. These data support the development of practice models dedicated to acute vascular surgical care.

Association of inadequate sleep with mortality among persons who inject drugs.

BACKGROUND: Inadequate sleep is associated with all-cause mortality in the general population. Substance use has adverse effects on sleep, and insomnia symptoms are common among people with HIV. Therefore, persons who inject drugs may face a heightened risk of adverse outcomes from inadequate sleep. We evaluated the association of inadequate sleep with mortality among persons who inject drugs in a long-standing community cohort. METHODS: Participants were from the AIDS Linked to the IntraVenous Experience (ALIVE) study, a cohort of persons who inject drugs in Baltimore, Maryland, USA. From 2005-2020, perceived sleep adequacy and duration were assessed semiannually using survey. Mortality data were obtained through linkage to the National Death Index-Plus. Cause of death was independently characterized and validated by three physicians. Hazards of all-cause and cause-specific mortality were evaluated using Cox regression accounting for repeated measurements. RESULTS: A total of 2633 participants were included, with a median age at entry of 45.8years; 32.5% were female, and 75% were Black. After adjustment for demographics, mental health, and comorbidities, inadequate sleep was associated with a 32% greater hazard of all-cause mortality (hazard ratio: 1.32, 95% confidence interval: 1.12-1.55) and a 67% greater hazard of HIV/infectious disease-related deaths (hazard ratio: 1.67, 95% confidence interval: 1.15-2.42). Short (<6 hours) and long (≥8 hours) duration of sleep were both associated with higher hazard of all-cause and chronic disease-related mortality (all p < .05). CONCLUSIONS: Sleep plays a critical role in longevity in persons who inject drugs. Research is needed to determine whether interventions targeting sleep improve health and longevity in persons who inject drugs.

Characterizing Acute Low Back Pain in a Community-Based Cohort: Results from a Feasibility Cohort Study.

Introduction: Acute low back pain (LBP) is a common experience; however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, two acute-LBP severity categorization definitions were developed: 1) pain impact frequency (impact-based) and 2) pain intensity (intensity-based) severity categories. The purpose of this manuscript is to describe and then compare these acute-LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological using a feasibility cohort study. Methods: This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios of categorical variables and Hedges' g for continuous variables. Results: Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. Discussion: This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute-LBP. The robust differences observed between these categorization approaches suggest that how we define acute-LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic-LBP.

The human milk oligosaccharide 3'sialyllactose reduces low-grade inflammation and atherosclerosis development in mice.

Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of Toll-Like Receptor (TLR) 4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3'SL attenuates mRNA levels of a selected set of inflammatory genes and promotes the activity of Liver X Receptor (LXR) and Sterol Regulatory Element-binding Protein-1 (SREBP). These acute anti-inflammatory effects of 3'SL were associated with reduced histone H3K27 acetylation at a subset of lipopolysaccharide (LPS)-inducible enhancers distinguished by preferential enrichment for CCCTC-binding factor (CTCF), Interferon Regulatory Factor 2 (IRF2), B-cell lymphoma 6 (BCL6), and other transcription factor recognition motifs. In a murine atherosclerosis model, both subcutaneous and oral administration of 3'SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3'SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.

Freshwater Habitats Promote Rapid Rates of Phenotypic Evolution in Sculpin Fishes (Perciformes: Cottoidea).

AbstractInvasions of freshwater habitats by marine fishes provide exceptional cases of habitat-driven biological diversification. Freshwater habitats make up less than 1% of aquatic habitats but contain ∼50% of fish species. However, while the dominant group of freshwater fishes (Otophysi) is older than that of most marine fishes (Percomorphaceae), it is less morphologically diverse. Classically, scientists have invoked differences in the tempo and/or mode of evolution to explain such cases of unequal morphological diversification. We tested for evidence of these phenomena in the superfamily Cottoidea (sculpins), which contains substantial radiations of marine and freshwater fishes. We find that the morphology of freshwater sculpins evolves faster but under higher constraint than that of marine sculpins, causing widespread convergence in freshwater sculpins and more morphological disparity in marine sculpins. The endemic freshwater sculpins of Lake Baikal, Siberia, are exceptions that demonstrate elevated novelty akin to that of marine sculpins. Several tantalizing factors may explain these findings, such as differences in habitat stability and/or habitat connectivity between marine and freshwater systems.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

INTRODUCTION: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results. METHODS: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative. RESULTS: Within CN participants with hearing loss, there was a significantly greater rate of cognitive decline per modified preclinical Alzheimer's cognitive composite. Within both CN and MCI participants with hearing loss, there was a significantly greater rate of functional decline per the functional activities questionnaire (FAQ). In CN and MCI participants, hearing loss did not significantly contribute to the risk of progression to a more impaired diagnosis. DISCUSSION: These results confirm previous studies demonstrating a significant longitudinal association between self-reported hearing loss and cognition/function but do not demonstrate an increased risk of conversion to a more impaired diagnosis. CLINICAL TRIAL REGISTRATION INFORMATION: NCT00106899 (ADNI: Alzheimer's Disease Neuroimaging Initiative, clinicaltrials.gov), NCT01078636 (ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity, clinicaltrials.gov), NCT01231971 (ADNI2: Alzheimer's Disease Neuroimaging Initiative 2, clinicaltrials.gov), NCT02854033 (ADNI3: Alzheimer's Disease Neuroimaging Initiative 3, clinicaltrials.gov). HIGHLIGHTS: Hearing loss is a potential modifiable risk factor for dementia. We assessed the effect of self-reported hearing loss on cognition and function in the ADNI cohort. Hearing loss contributes to significantly faster cognitive and functional decline. Hearing loss was not associated with conversion to a more impaired diagnosis.

Synergistic blockade of TIGIT and PD-L1 increases type-1 inflammation and improves parasite control during murine blood-stage Plasmodium yoelii non-lethal infection.

Pro-inflammatory immune responses are rapidly suppressed during blood-stage malaria but the molecular mechanisms driving this regulation are still incompletely understood. In this study, we show that the co-inhibitory receptors TIGIT and PD-1 are upregulated and co-expressed by antigen-specific CD4+ T cells (ovalbumin-specific OT-II cells) during non-lethal Plasmodium yoelii expressing ovalbumin (PyNL-OVA) blood-stage infection. Synergistic blockade of TIGIT and PD-L1, but not individual blockade of each receptor, during the early stages of infection significantly improved parasite control during the peak stages (days 10-15) of infection. Mechanistically, this protection was correlated with significantly increased plasma levels of IFN-γ, TNF, and IL-2, and an increase in the frequencies of IFN-γ-producing antigen-specific T-bet+ CD4+ T cells (OT-II cells), but not antigen-specific CD8+ T cells (OT-I cells), along with expansion of the splenic red pulp and monocyte-derived macrophage populations. Collectively, our study identifies a novel role for TIGIT in combination with the PD1-PD-L1 axis in regulating specific components of the pro-inflammatory immune response and restricting parasite control during the acute stages of blood-stage PyNL infection.

Predicting peritumoral glioblastoma infiltration and subsequent recurrence using deep-learning-based analysis of multi-parametric magnetic resonance imaging.

Purpose: Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor. The standard treatment approach is surgical resection to target the enhancing tumor mass, followed by adjuvant chemoradiotherapy. However, malignant cells often extend beyond the enhancing tumor boundaries and infiltrate the peritumoral edema. Traditional supervised machine learning techniques hold potential in predicting tumor infiltration extent but are hindered by the extensive resources needed to generate expertly delineated regions of interest (ROIs) for training models on tissue most and least likely to be infiltrated. Approach: We developed a method combining expert knowledge and training-based data augmentation to automatically generate numerous training examples, enhancing the accuracy of our model for predicting tumor infiltration through predictive maps. Such maps can be used for targeted supra-total surgical resection and other therapies that might benefit from intensive yet well-targeted treatment of infiltrated tissue. We apply our method to preoperative multi-parametric magnetic resonance imaging (mpMRI) scans from a subset of 229 patients of a multi-institutional consortium (Radiomics Signatures for Precision Diagnostics) and test the model on subsequent scans with pathology-proven recurrence. Results: Leave-one-site-out cross-validation was used to train and evaluate the tumor infiltration prediction model using initial pre-surgical scans, comparing the generated prediction maps with follow-up mpMRI scans confirming recurrence through post-resection tissue analysis. Performance was measured by voxel-wised odds ratios (ORs) across six institutions: University of Pennsylvania (OR: 9.97), Ohio State University (OR: 14.03), Case Western Reserve University (OR: 8.13), New York University (OR: 16.43), Thomas Jefferson University (OR: 8.22), and Rio Hortega (OR: 19.48). Conclusions: The proposed model demonstrates that mpMRI analysis using deep learning can predict infiltration in the peri-tumoral brain region for GBM patients without needing to train a model using expert ROI drawings. Results for each institution demonstrate the model's generalizability and reproducibility.

Enumerative Discovery of Noncanonical Polypeptide Secondary Structures.

Energetically favorable local interactions can overcome the entropic cost of chain ordering and cause otherwise flexible polymers to adopt regularly repeating backbone conformations. A prominent example is the α helix present in many protein structures, which is stabilized by i, i + 4 hydrogen bonds between backbone peptide units. With the increased chemical diversity offered by unnatural amino acids and backbones, it has been possible to identify regularly repeating structures not present in proteins, but to date, there has been no systematic approach for identifying new polymers likely to have such structures despite their considerable potential for molecular engineering. Here we describe a systematic approach to search through dipeptide combinations of 130 chemically diverse amino acids to identify those predicted to populate unique low-energy states. We characterize ten newly identified dipeptide repeating structures using circular dichroism spectroscopy and comparison with calculated spectra. NMR and X-ray crystallographic structures of two of these dipeptide-repeat polymers are similar to the computational models. Our approach is readily generalizable to identify low-energy repeating structures for a wide variety of polymers, and our ordered dipeptide repeats provide new building blocks for molecular engineering.

A Review for Clinical Practice in the Treatment and Prevention of Recurrent Urinary Tract Infections in Women over Age 65.

Urinary tract infection (UTI) is a pervasive, costly, and dangerous cause of morbidity and mortality worldwide, which can lead to further complications if they become recurrent or progress to urosepsis. Recurrent UTI is a particular concern among postmenopausal females because of increased risk factors and decreased estrogen levels, leading to changes in the urogenital epithelium and subsequently causing alterations in the urogenital microbiome. Prevention strategies for recurrent UTIs are often incorporated into patient-centered care plans, but finding the right management can be difficult for older women since many of the common treatment options have contraindications and adverse side effects. This review aims to describe the diagnosis, treatment, and special considerations for the treatment and prevention of recurrent UTIs in women over 65. Current prevention strategies include both antibiotic and nonantibiotic options. The antibiotic choice for older women presents a few unique challenges, including frequent allergy or intolerance of side effects, renal or liver dysfunction, and polypharmacy or drug interactions. Nonantibiotic options range from readily accessible drugstore remedies to experimental vaccines, which all are accompanied by certain advantages and disadvantages. Appropriate management plans can help to reduce symptoms and poor outcomes among older females. In addition, we hope future studies continue to investigate the proper dosing and routes for optimal management in this aging female population.

Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [11C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60-90 or 70-90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD.

The Use of Artificial Intelligence for Orthopedic Surgical Backlogs Such as the One Following the COVID-19 Pandemic: A Narrative Review.

➤ The COVID-19 pandemic created a persistent surgical backlog in elective orthopedic surgeries. ➤ Artificial intelligence (AI) uses computer algorithms to solve problems and has potential as a powerful tool in health care. ➤ AI can help improve current and future orthopedic backlogs through enhancing surgical schedules, optimizing preoperative planning, and predicting postsurgical outcomes. ➤ AI may help manage existing waitlists and increase efficiency in orthopedic workflows.

Research Priorities for Atrial Fibrillation in Australia: A Statement From the Australian Cardiovascular Alliance Clinical Arrhythmia Theme.

Atrial fibrillation (AF) is highly prevalent in the Australian community, ranking amongst the highest globally. The consequences of AF are significant. Stroke, dementia and heart failure risk are increased substantially, hospitalisations are amongst the highest for all cardiovascular causes, and Australians living with AF suffer from substantial symptoms that impact quality of life. Australian research has made a significant impact at the global level in advancing the care of patients living with AF. However, new strategies are required to reduce the growing incidence of AF and its associated healthcare demand. The Australian Cardiovascular Alliance (ACvA) has led the development of an arrhythmia clinical theme with the objective of tackling major research priorities to achieve a reduction in AF burden across Australia. In this summary, we highlight these research priorities with particular focus on the strengths of Australian research and the strategies needed to move forward in reducing incident AF and improving outcomes for those who live with this chronic condition.

Impact of Disease Burden of Patients with Psoriasis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Due to variable psoriasis symptoms, disease progression, and individual responses to therapy, patients may start, stop, or switch biologic therapies. Real-world data on the associated disease burden of patients with psoriasis who do and do not switch biologics are incomplete. METHODS: This study compared disease burden among patients from the CorEvitas Psoriasis Registry (July 2017-December 2021) who switched biologics and those who did not within 4-12 months following initiation. Disease-related patient-reported outcomes (PROs) were recorded, including skin pain, itching, activity impairment, and effects on health-related quality of life (HRQoL). Disease severity was measured by body surface area (BSA) and Psoriasis Area and Severity Index (PASI). Unadjusted and adjusted regression models were used to compare study outcome measures between the two groups. RESULTS: This study included 2145 patients, with 159 classified as switchers and 1986 as non-switchers. The most common reason for switching therapy was failure to maintain initial response (51.7%; n = 78). Moderate-to-severe disease (BSA ≥ 3) was found among 83.0% (n = 132) of switchers versus 26.1% (n = 516) of non-switchers. PASI > 5 was reported among 49.7% (n = 79) of switchers versus 8.6% (n = 171) of non-switchers. Differences in skin pain, itching, and effects on HRQoL between switchers and non-switchers were larger in magnitude for bio-experienced patients. CONCLUSIONS: Patients who switched biologic therapy experienced a greater disease burden of psoriasis across PROs than non-switchers. Patient-centered factors may be important drivers of biologic switching. Our findings suggest the association between switching and disease burden may be stronger among patients with prior biologic therapy experience.

Patients with psoriasis often need treatment over a long period of time. Common treatments include biologic medications, which help to reduce inflammation. Different patients may experience different psoriasis symptoms, and these symptoms can lead to changes in biologic over time. It is important that we understand how psoriasis severity and patients' day-to-day well-being affect switching of psoriasis biologic medications.In this study, we used information from a database of patients with psoriasis. The database includes information on patients' psoriasis-related medication history, including whether they change their medication. We looked at data from patients who switched and patients who did not switch their biologic medication, and examined differences in their skin pain, itching, tiredness, difficulty participating in normal activities, and effects on day-to-day well-being. Patterns between these two groups were also studied on the basis of whether patients had used biologic medications before or whether they had a related condition, called psoriatic arthritis, in addition to psoriasis.Overall, we found that patients who changed their biologic medication had experienced more difficult psoriasis symptoms than those who had not changed their medication, such as itching and skin pain. These symptoms had a greater impact on switching biologic medication in patients who had used a biologic medication before than for those who were using their first biologic medication.

Impact of Disease Factors of Patients with Psoriasis and Psoriatic Arthritis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited. METHODS: This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015-August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling. RESULTS: Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5). CONCLUSIONS: Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5.

Many patients with psoriasis may also have a related condition called psoriatic arthritis. Biologic medications work by helping to reduce inflammation and are commonly used to treat the symptoms of psoriasis and psoriatic arthritis. Patients might not all respond the same way to treatment and may need to change their medications over time. It is important we understand the reasons for switching medications to help patients better manage their symptoms.This study used information from a database on patients with both psoriasis and psoriatic arthritis. The database includes information on patients' medical history, including when they start and change their medication. We looked at data from patients who switched medications and patients who did not switch medications and examined differences in both how serious a doctor found their disease and the patients' own opinions of their overall health.We found that patients were more likely to change their biologic medication if they had more difficult psoriasis and psoriatic arthritis symptoms that caused worse skin problems, joint pain, and effects on their overall health compared with patients who had not changed their medication. These results suggest that it is important to consider both how serious a doctor finds their disease and patients' opinions of how much their symptoms affect their overall health. Understanding the reasons why patients switch medications will help to develop better ways of managing psoriasis and psoriatic arthritis.