Northwestern University resource and education development initiatives to advance collaborative artificial intelligence across the learning health system.

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare. Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare. We built bulk-natural language processing pipelines to extract structured information from clinical notes and stored them in common data models. We developed multimodal AI/machine learning (ML) tools and tutorials to enrich the toolbox of the multidisciplinary workforce to analyze multimodal healthcare data. We have created a fertile ground to cross-pollinate clinicians and AI scientists and train the next generation of AI health workforce to collaborate effectively. Results: Our work has democratized access to unstructured health information, AI/ML tools and resources for healthcare, and collaborative education resources. From 2017 to 2022, this has enabled studies in multiple clinical specialties resulting in 68 peer-reviewed publications. In 2022, our cross-discipline efforts converged and institutionalized into the Center for Collaborative AI in Healthcare. Conclusions: Our Collaborative AI in Healthcare initiatives has created valuable educational and practical resources. They have enabled more clinicians, scientists, and hospital administrators to successfully apply AI methods in their daily research and practice, develop closer collaborations, and advanced the institution-level learning health system.

Prediction of Time to Hemodynamic Stabilization of Unstable Injured Patient Encounters Using Electronic Medical Record Data.

BACKGROUND: This study sought to predict time to patient hemodynamic stabilization during trauma resuscitations of hypotensive patient encounters using electronic medical records (EMR) data. METHODS: This observational cohort study leveraged EMR data from a nine-hospital academic system composed of Level I, Level II and non-trauma centers. Injured, hemodynamically unstable (initial systolic blood pressure < 90 mmHg) emergency encounters from 2015-2020 were identified. Stabilization was defined as documented subsequent systolic blood pressure > 90 mmHg. We predicted time to stabilization testing random forests, gradient boosting and ensembles using patient, injury, treatment, EPIC Trauma Narrator and hospital features from the first four hours of care. RESULTS: Of 177,127 encounters, 1347 (0.8%) arrived hemodynamically unstable; 168 (12.5%) presented to Level I trauma centers, 853 (63.3%) to Level II, and 326 (24.2%) to non-trauma centers. Of those, 747 (55.5%) were stabilized with a median of 50 minutes (IQR 21-101 min). Stabilization was documented in 94.6% of unstable patient encounters at Level I, 57.6% at Level II and 29.8% at non-trauma centers (p < 0.001). Time to stabilization was predicted with a C-index of 0.80. The most predictive features were EPIC Trauma Narrator measures; documented patient arrival, provider exam, and disposition decision. In-hospital mortality was highest at Level I, 3.0% vs. 1.2% at Level II, and 0.3% at non-trauma centers (p < 0.001). Importantly, non-trauma centers had the highest re-triage rate to another acute care hospital (12.0%) compared to Level II centers (4.0%, p < 0.001). CONCLUSION: Time to stabilization of unstable injured patients can be predicted with EMR data.

How warm are political interactions? A new measure of affective fractionalization.

Affective polarization measures account for partisans' feelings towards their own party versus its opponent(s), but not for how likely partisans are to encounter co-partisans versus out-partisans. However, the intensity of out-party dislike and the probability with which this comes into play both determine the social impact of cross-party hostility. We develop an affective fractionalization measure that accounts for both factors, and apply it to longitudinal survey data from 20 Western publics. From this perspective, countries with fewer dominant parties may be more harmonious because partisans have lower probabilities of interacting with political opponents. At the party level, partisans of smaller, more radical parties are particularly troubled because they strongly dislike out-partisans and have few co-partisans. Affective fractionalization has increased in most Western publics over time, primarily because of growing party-system fragmentation.

Precision synbiotics increase gut microbiome diversity and improve gastrointestinal symptoms in a pilot open-label study for autism spectrum disorder.

The efficacy of prebiotics and probiotics (synbiotics when combined) to improve symptoms associated with autism spectrum disorder (ASD) has shown considerable inter-study variation, likely due to the complex, heterogeneous nature of the disorder and its associated behavioral, developmental, and gastrointestinal symptoms. Here, we present a precision synbiotic supplementation study in 296 children and adults diagnosed with ASD versus 123 age-matched neurotypical controls. One hundred seventy ASD participants completed the study. Baseline and post-synbiotic assessment of ASD and gastrointestinal (GI) symptoms and deep metagenomic sequencing were performed. Within the ASD cohort, there were significant differences in microbes between subpopulations based on the social responsiveness scale (SRS2) survey (Prevotella spp., Bacteroides, Fusicatenibacter, and others) and gluten and dairy-free diets (Bifidobacterium spp., Lactococcus, Streptococcus spp., and others). At the baseline, the ASD cohort maintained a lower taxonomic alpha diversity and significant differences in taxonomic composition, metabolic pathways, and gene families, with a greater proportion of potential pathogens, including Shigella, Klebsiella, and Clostridium, and lower proportions of beneficial microbes, including Faecalibacterium compared to controls. Following the 3-month synbiotic supplementation, the ASD cohort showed increased taxonomic alpha diversity, shifts in taxonomy and metabolic pathway potential, and improvements in some ASD-related symptoms, including a significant reduction in GI discomfort and overall improved language, comprehension, cognition, thinking, and speech. However, the open-label study design may include some placebo effects. In summary, we found that precision synbiotics modulated the gut microbiome and could be used as supplementation to improve gastrointestinal and ASD-related symptoms. IMPORTANCE: Autism spectrum disorder (ASD) is prevalent in 1 out of 36 children in the United States and contributes to health, financial, and psychological burdens. Attempts to identify a gut microbiome signature of ASD have produced varied results. The limited pre-clinical and clinical population sizes have hampered the success of these trials. To understand the microbiome associated with ASD, we employed whole metagenomic shotgun sequencing to classify microbial composition and genetic functional potential. Despite being one of the most extensive ASD post-synbiotic assessment studies, the results highlight the complexity of performing such a case-control supplementation study in this population and the potential for a future therapeutic approach in ASD.

Chemical constituents, viable micro-organism and malignant cell content in ultrasonic scalpel plume: A literature review.

PURPOSE: To identify all published data on the chemical, micro-organism and malignant cell contents of ultrasonic scalpel plume, if any, and on any clinical implications of the contents on patients and operating staff. METHODS: Searches were conducted aiming to identify all published evidence on the chemical constituents, presence/absence of viable micro-organisms and malignant cells in ultrasonic scalpel plume. Attempts were made to source unpublished industry data. RESULTS: There is evidence from human and in vitro studies of the presence of a range of harmful, and some human carcinogenic, chemicals within ultrasonic plume, mostly at very low concentrations. Any clinical relevance of this has not been studied. There is evidence from experimental studies of the presence of hepatitis virus, human coronavirus and human papillomavirus material within ultrasonic plume. Any clinical effect of this has not been studied. There is conflicting evidence from combined in vitro and mouse model studies of the presence of viable malignant cells within ultrasonic plume. Any clinical relevance of this has also not been studied. CONCLUSION: Overall, relatively little research into the plume has been published, and further study is required to more clearly delineate any potential risk to patients, surgeons and other theatre staff. Current safety recommendations are discussed.

When the economy falters, hearts suffer: Economic recessions as a social determinant of health in cardiovascular emergencies.

INTRODUCTION: While the relationships between cardiovascular disease (CVD), stress, and financial strain are well studied, the association between recessionary periods and macroeconomic conditions on incidence of disease-specific CVD emergency department (ED) visits is not well established. OBJECTIVES: This retrospective observational study aimed to assess the relationship between macroeconomic trends and CVD ED visits. METHODS: This study uses data from the National Hospital Ambulatory Care Survey (NHAMCS), Federal Reserve Economic Database (FRED), National Bureau of Economic Research (NBER), and CVD groupings from National Vital Statistics (NVS) and Center for Medicare and Medicaid Services (CMS) from 1999 to 2020 to analyze ED visits in relation to macroeconomic indicators and NBER defined recessions and expansions. RESULTS: CVD ED visits grew by 79.7% from 1999 to 2020, significantly more than total ED visits (27.8%, p < 0.001). A national estimate of 213.2 million CVD ED visits, with 22.9 million visits in economic recessions were analyzed. A secondary group including a 6-month period before and after each recession (defined as a "broadened recession") was also analyzed to account for potential leading and lagging effects of the recession, with a total of 50.0 million visits. A significantly higher proportion of CVD ED visits related to heart failure (HF) and other acute ischemic heart diseases (IHD) was observed during recessionary time periods both directly and with a 6-month lead and lag (p < 0.05). The proportion of aortic aneurysm and dissection (AAA) and atherosclerosis (ASVD) ED visits was significantly higher (p = 0.024) in the recession period with a 6-month lead and lag. When controlled for common demographic factors, economic approximations of recession such as the CPI, federal funds rate, and real disposable income were significantly associated with increased CVD ED visits. CONCLUSION: Macroeconomic trends have a significant relationship with the overall mix of CVD ED visits and represent an understudied social determinant of health.

Novel method to plan and design services. Using software to optimise the head and neck cancer patient's commute to hospital.

Travelling for hospital appointments represents a significant burden to patients. We have developed a computer programme that accurately evaluates patient commutes between their home and treatment hospital in public and private transport. This has been applied to a cohort of Head and Neck Cancer (HNC) patients to plan the locations of satellite hospitals and assess their impact on patients' commutes. Patients diagnosed with HNC were identified from our hospital's database between December 2019 and January 2022. Using Python, commuting distances from patients' postcodes to our tertiary referral hospital were calculated. These commutes incorporated routes along defined roads, traffic data, and were calculated using public and private transport. Patient commutes from their postcodes to four satellite hospitals were also calculated. We identified their closest hospital and compared that journey to the patients' journey to our tertiary centre. We included 709 patients in our analysis. Patients would have a significantly shorter journey distance and time in both public and private transport if satellite hospitals were used for appointments alongside our tertiary centre. Average travel times would reduce by 10 minutes in private and 25 minutes in public transport. Furthermore, 70% of patients required ≥2 forms of public transport to get to our hospital. This would drop to 44.1% of patients if satellite hospitals were included in our service. Our programme would allow the most accessible sites to be identified for establishing outreach clinics at appropriate satellite hospitals, therefore improving patient access to healthcare.

Ratings of the Effectiveness of 13 Therapeutic Diets for Autism Spectrum Disorder: Results of a National Survey.

This study presents the results of the effectiveness of 13 therapeutic diets for autism spectrum disorder from 818 participants of a national survey, including benefits, adverse effects, and symptom improvements. The average Overall Benefit of diets was 2.36 (0 = no benefit, 4 = great benefit), which was substantially higher than for nutraceuticals (1.59/4.0) and psychiatric/seizure medications (1.39/4.0), p < 0.001. The average Overall Adverse Effects of diets was significantly lower than psychiatric/seizure medications (0.10 vs. 0.93, p < 0.001) and similar to nutraceuticals (0.16). Autism severity decreased slightly over time in participants who used diet vs. increasing slightly in those that did not (p < 0.001). Healthy and Feingold diets were the two top-rated diets by Overall Benefit; the ketogenic diet was the highest for nine symptoms (though had fewer respondents); and the gluten-free/casein-free diet was among the top for overall symptom improvements. Different diets were reported to affect different symptoms, suggesting that an individual's symptoms could be used to guide which diet(s) may be the most effective. The results suggest that therapeutic diets can be safe and effective interventions for improving some ASD-related symptoms with few adverse effects. We recommend therapeutic diets that include healthy foods and exclude problematic foods. Therapeutic diets are inexpensive treatments that we recommend for consideration by most people with ASD.

Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use.

The widespread use of antibiotics in the poultry industry has led to the emergence of antibiotic-resistant bacteria, which pose a significant health risk to humans and animals. These public health concerns, which have led to legislation limiting antibiotic use in animals, drive the need to find alternative strategies for controlling and treating bacterial infections. Modulation of the avian innate immune system using immunostimulatory compounds provides a promising solution to enhance poultry immune responses to a broad range of bacterial infections without the risk of generating antibiotic resistance. An array of immunomodulatory compounds have been investigated for their impact on poultry performance and immune responses. However, further research is required to identify compounds capable of controlling bacterial infections without detrimentally affecting bird performance. It is also crucial to determine the safety and effectiveness of these compounds in conjunction with poultry vaccines. This review provides an overview of the various immune modulators known to enhance innate immunity against avian bacterial pathogens in chickens, and describes the mechanisms involved.

Age-Related Changes in Epilepsy Characteristics and Response to Antiepileptic Treatment in Autism Spectrum Disorders.

Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an online survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities, potential etiologies, and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic-clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood, while surgery and the Atkins/modified Atkins Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau-Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but nonetheless, these data provide insights into novel relationships that may assist in a better understanding of epilepsy in ASD and provide insight into personalizing epilepsy care in ASD.

Efficient Genomic Prediction of Yield and Dry Matter in Hybrid Potato.

There is an ongoing endeavor within the potato breeding sector to rapidly adapt potato from a clonal polyploid crop to a diploid hybrid potato crop. While hybrid breeding allows for the efficient generation and selection of parental lines, it also increases breeding program complexity and results in longer breeding cycles. Over the past two decades, genomic prediction has revolutionized hybrid crop breeding through shorter breeding cycles, lower phenotyping costs, and better population improvement, resulting in increased genetic gains for genetically complex traits. In order to accelerate the genetic gains in hybrid potato, the proper implementation of genomic prediction is a crucial milestone in the rapid improvement of this crop. The authors of this paper set out to test genomic prediction in hybrid potato using current genotyped material with two alternative models: one model that predicts the general combining ability effects (GCA) and another which predicts both the general and specific combining ability effects (GCA+SCA). Using a training set comprising 769 hybrids and 456 genotyped parental lines, we found that reasonable a prediction accuracy could be achieved for most phenotypes with both zero common parents (ρ=0.36-0.61) and one (ρ=0.50-0.68) common parent between the training and test sets. There was no benefit with the inclusion of non-additive genetic effects in the GCA+SCA model despite SCA variance contributing between 9% and 19% of the total genetic variance. Genotype-by-environment interactions, while present, did not appear to affect the prediction accuracy, though prediction errors did vary across the trial's targets. These results suggest that genomically estimated breeding values on parental lines are sufficient for hybrid yield prediction.

Using neurotechnology in the emergency and safety management for creating a safer work environment.

Brain-computer interfaces are emerging neurotechnology conducting specific commands or outputs based on acquiring brain signals or inputs. This study examines the common hazards present in industries, which can be managed by neurotechnology, as well as compares two types of brain-computer interfaces in the neurotechnology area. The findings from this work suggest acknowledging current safety management practices and technology that can promote a safer work environment, in addition to increasing probable applications of use of the current research findings related to neurotechnology. This study advises understanding the risks associated between noninvasive and invasive neurotechnologies, whereas noninvasive technologies are safer that exhibit lesser degrees of accuracy or applications of use compared to its counterpart, which is invasive technology. This study proposes future development of this technology, which can integrate components based on common practices by industry.

Non-Antibiotic Compounds Synergistically Kill Chronic Wound-Associated Bacteria and Disrupt Their Biofilms.

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

Real-time analysis of dynamic compartmentalized GSH redox shifts and H2O2 availability in undifferentiated and differentiated cells.

BACKGROUND: Glutathione (GSH) is the most abundant, small biothiol antioxidant. GSH redox state (Eh) supports developmental processes, yet with disrupted GSH Eh, poor developmental outcomes may occur. The role of subcellular, compartmentalized redox environments in the context of redox regulation of differentiation is not well understood. Here, using the P19 neurogenesis model of cellular differentiation, kinetics of subcellular H2O2 availability and GSH Eh were evaluated following oxidant exposure. METHODS: Stably transfected P19 cell lines expressing H2O2 availability or GSH Eh sensors, Orp1-roGFP or Grx1-roGFP, respectively, targeted to the cytosol, mitochondria, or nucleus were used. Dynamic, compartmentalized changes in H2O2 availability and GSH Eh were measured via spectrophotometric and confocal microscopy over 120 min following treatment with H2O2 (100 µM) in both differentiated and undifferentiated cells. RESULTS: Generally, treated undifferentiated cells showed a greater degree and duration of both H2O2 availability and GSH Eh disruption than differentiated neurons. In treated undifferentiated cells, H2O2 availability was similar in all compartments. Interestingly, in treated undifferentiated cells, mitochondrial GSH Eh was most affected in both the initial oxidation and the rebound kinetics compared to other compartments. Pretreatment with an Nrf2 inducer prevented H2O2-induced effects in all compartments of undifferentiated cells. CONCLUSIONS: Disruption of redox-sensitive developmental pathways is likely stage specific, where cells that are less differentiated and/or are actively differentiating are most affected. GENERAL SIGNIFICANCE: Undifferentiated cells are more susceptible to oxidant-induced redox dysregulation but are protected by chemicals that induce Nrf2. This may preserve developmental programs and diminish the potential for poor developmental outcomes.

Synchrony 2022: Epilepsy and Seizures in Autism Spectrum Disorder Roundtable.

The BRAIN Foundation (Pleasanton, CA, USA) hosted Synchrony 2022, a translational medicine conference focused on research into treatments for individuals with neurodevelopmental disorders (NDD), including those with autism spectrum disorders (ASD) [...].

Converting Hybrid Potato Breeding Science into Practice.

Research on diploid hybrid potato has made fast advances in recent years. In this review we give an overview of the most recent and relevant research outcomes. We define different components needed for a complete hybrid program: inbred line development, hybrid evaluation, cropping systems and variety registration. For each of these components the important research results are discussed and the outcomes and issues that merit further study are identified. We connect fundamental and applied research to application in a breeding program, based on the experiences at the breeding company Solynta. In the concluding remarks, we set hybrid breeding in a societal perspective, and we identify bottlenecks that need to be overcome to allow successful adoption of hybrid potato.

Functional outcomes following mandibulectomy and fibular free-flap reconstruction.

There remains a paucity of evidence with regards to functional outcomes following the reconstruction of segmental defects in the mandible. It is, however, well recognised that oral rehabilitation following head and neck surgery is a driver of improved quality of life outcomes. We present a prospective service review of functional outcomes of a consecutive cohort of patients following segmental mandibulectomy and virtual surgical planning (VSP) composite fibular free-flap reconstruction. Twenty-five patients, who were identified as having a complete dataset with a minimum of 12 months' follow up, ultimately met the inclusion criteria. Validated functional outcome measures were used primarily to assess speech, diet, and swallowing outcomes. The results demonstrate a decline in both speech and swallowing outcomes at three months postoperatively, with a decline of 37% in the Speech Handicap Index from the preoperative baseline, and a decline of 35% in the MD Anderson Dysphagia Inventory score over the same period. The MD Anderson Dysphagia Inventory score improved at 12 months, whereas the Speech Handicap Index did not. Fundamentally a collaborative approach is required between members of the multidisciplinary team (MDT) to enable optimal patient outcomes.

Profiling plasma levels of thiamine and histamine in Jordanian children with autism spectrum disorder (ASD): potential biomarkers for evaluation of ASD therapies and diet.

Background: The current work involved monitoring two biomarkers in the plasma of children with ASD: the cofactor thiamine that is involved in neurotransmitters modulation for acetylcholine, and the compound histamine, which acts as a neuromodulator by regulating the release of other neurotransmitters. This is the first report to highlight the potential utilization of plasma levels of the selected two brain-related biomarkers in children with ASD.Methods: A total of 43 children with ASD of both genders (age 4-12 years) were involved in this study and compared to age and gender-matched control children (n = 42). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), followed by an additional assessment using the Childhood Autism Rating Scale (CARS). All participants were Jordanian children on Mediterranean diet, and had no history of chronic illness or medications. Measurement of thiamine and histamine in plasma was performed using enzyme-linked immunosorbent assay (ELISA).Results: The outcomes revealed that average histamine levels (31.7 ± 18.5 ng/ml) of ASD group were 5.3× higher (p < .001) compared to their control (0.013 ± 0.011 ng/ml; 6.03 ± 4.25 ng/ml), while thiamine (10.78 ± 7.49 ng/ml) levels of ASD group were significantly lower (p < .001) than the control (37.92 ± 26.87 ng/ml; 0.209 ± 0.054 ng/ml).Conclusions: The study is proposing that monitoring of the plasma levels of thiamine and histamine as biomarkers for future evaluation and development of ASD therapies and nutritious diets.