Models of Photoreceptor Degeneration in Adult Zebrafish.

Zebrafish maintain a remarkable ability to regenerate their neural retina following rapid and extensive loss of retinal neurons. This is mediated by Müller glial cells (MG), which re-enter the cell cycle to produce amplifying progenitor cells that eventually differentiate into the lost retinal neurons. For example, exposing adult albino zebrafish to intense light destroys large numbers of rod and cone photoreceptors, which are then restored by MG-mediated regeneration. Here, we describe an updated method for performing these acute phototoxic lesions to adult zebrafish retinas. Next, we contrast this method to a chronic, low light lesion model that results in a more muted and sustained damage to photoreceptors and does not trigger a MG-mediated regeneration response. Thus, these two methods can be used to compare and contrast the genetic and morphological changes associated with acute and chronic methods of photoreceptor degeneration.

The devastating dance between opioid and housing crises: Evidence from OxyContin reformulation.

Housing instability and drug misuse are two of the United States' most pressing challenges, each bearing profound health and societal consequences. A crucial yet largely underexplored question is the extent to which the opioid crisis has intensified housing instability. Our study ventures into this relatively uncharted nexus, investigating how the OxyContin reformulation, a pivotal moment in the U.S. opioid epidemic, impacted eviction rates. Employing a dose-response Difference-in-Differences model and analyzing eviction data from 2004 to 2016, we demonstrate that the OxyContin reformulation precipitated a significant increase in evictions, especially in areas with weak eviction protections or limited access to psychiatric treatment resources. Channel analyses reveal increased marijuana initiation and heightened mental and physical health issues following the reformulation. Moreover, the OxyContin reformulation leads to greater reliance on the Supplemental Nutrition Assistance Program, signaling an escalated financial strain on governmental resources. Finally, we find evidence of increased marital disruption post-reformulation. Our findings underscore the urgent need for collaborative efforts between public health and housing authorities to address both the opioid and housing crises.

Clinical Interventions Following Escalations from a Continuous Respiratory Monitoring Service in Patients With Chronic Obstructive Pulmonary Disease.

Background: Continuous respiratory monitoring can support integrated care for chronic obstructive pulmonary disease (COPD) patients, by coupling them with remote clinical personnel who triage patients in coordination with their health care providers. When deploying such services, there remains uncertainty surrounding outcomes when at-risk patients are proactively identified and escalated for provider evaluation. This study presents findings from a service deployed in a real-world COPD cohort by analyzing the clinical interventions made during in-person and telehealth pulmonary outpatient visits following remote escalations. Methods: A single-center, retrospective, observational study of real-world COPD patients at a multi-site pulmonary practice was conducted. Patients who were enrolled in a continuous respiratory monitoring service for at least one year and were seen by a provider within seven days of an escalation by the service (N=168) were included. To evaluate the potential impact of these escalations on provider and patient burden, medical charts from outpatient visits were manually reviewed and grouped into six categories based on the clinical action(s) taken by the provider. Results: A total of 245 outpatient visits occurred from 168 patients within seven days of escalation. Of the 245 visits, 206 (84.1%) resulted in clinical intervention and 163 (66.5%) resulted in treatment consistent with acute exacerbations of COPD (AECOPDs). 1.6% of the outpatient visits resulted in referral to the emergency room. Conclusion: Provider encounters occurring following the escalation of a patient from a continuous respiratory monitoring service consistently resulted in that provider administering a treatment to the escalated patient.

Point-of-Care Cardiac Troponin I Assay Evaluation in New Zealand White Rabbits (Oryctolagus cuniculus).

Cardiac troponin I (cTnI) is a cardiac-specific biomarker, used for the detection of myocardial injury. While rabbits develop naturally occurring cardiovascular disease, they are also an animal model for human disease; thus, rapid detection of cTnI has implications for both veterinary and human medicine. The objective of this study was to validate and establish a reference interval for a point-of-care (POC) cTnI assay in New Zealand White rabbits. In the first portion of the study, rabbit cardiac and skeletal muscle tissues were used to create homogenates, serially diluted with saline or rabbit whole blood, and run by repeated analysis on the POC assay. In the second portion of the study, a reference interval of peripheral whole blood cTnI was determined by robust methods from 49 New Zealand White rabbits. The least diluted cardiac muscle homogenates produced detectable cTnI (mean 23.12 ± 3.557 ng/mL), while skeletal muscle homogenates produced low to undetectable cTnI. The CV ranged from 0.00% to 32.51% for cTnI of diluted cardiac muscle homogenates. Rabbit cardiac homogenate diluted in blood had a linear relationship to cTnI concentration (Y = 0.2254 × X + 0.5396, R² = 0.975). The reference interval for cTnI in this population was less than 0.04 ng/mL. This POC assay may be useful when rapid detection of cTnI is needed and differentiation between normal and elevated values is required. Given the high CV, this assay may not be appropriate for cases that require high sensitivity or detection of low concentrations of cTnI.

Leveraging ultra-high field (7T) MRI in psychiatric research.

Non-invasive brain imaging has played a critical role in establishing our understanding of the neural properties that contribute to the emergence of psychiatric disorders. However, characterizing core neurobiological mechanisms of psychiatric symptomatology requires greater structural, functional, and neurochemical specificity than is typically obtainable with standard field strength MRI acquisitions (e.g., 3T). Ultra-high field (UHF) imaging at 7 Tesla (7T) provides the opportunity to identify neurobiological systems that confer risk, determine etiology, and characterize disease progression and treatment outcomes of major mental illnesses. Increases in scanner availability, regulatory approval, and sequence availability have made the application of UHF to clinical cohorts more feasible than ever before, yet the application of UHF approaches to the study of mental health remains nascent. In this technical review, we describe core neuroimaging methodologies which benefit from UHF acquisition, including high resolution structural and functional imaging, single (1H) and multi-nuclear (e.g., 31P) MR spectroscopy, and quantitative MR techniques for assessing brain tissue iron and myelin. We discuss advantages provided by 7T MRI, including higher signal- and contrast-to-noise ratio, enhanced spatial resolution, increased test-retest reliability, and molecular and neurochemical specificity, and how these have begun to uncover mechanisms of psychiatric disorders. Finally, we consider current limitations of UHF in its application to clinical cohorts, and point to ongoing work that aims to overcome technical hurdles through the continued development of UHF hardware, software, and protocols.

The role of cardiac acoustic biomarkers in monitoring patients with heart failure: A systematic literature review.

Heart failure (HF) creates a considerable clinical, humanistic and economic burden on patients and caregivers as well as on healthcare systems. To attenuate the significant burden of HF, there is a need for enhanced management of patients with HF. The use of digital tools for remote non-invasive monitoring of heart parameters is gaining traction, and cardiac acoustic biomarkers (CABs) have been proposed as a complementary set of measures to assess heart function alongside traditional methods such as electrocardiogram and echocardiography. We conducted a systematic literature review to evaluate associations between CABs and HF outcomes. Embase and MEDLINE databases were searched for recent studies published between 2013 and 2023 that evaluated CABs in patients with HF. Additional grey literature (i.e., conference, congress and pre-print publications from January 2021 to May 2023) searches were included. Two reviewers independently examined all articles; a third resolved conflicts. Data were extracted from articles meeting inclusion criteria. Extracted studies underwent quality and bias assessments using the Joanna Briggs Institute (JBI) critical appraisal tools. In total, 3074 records were screened, 73 full-text articles were assessed for eligibility and 27 publications were included. Third heart sound (S3) and electromechanical activation time (EMAT) were the CABs most often reported in the literature for monitoring HF. Fifteen publications discussed changes in S3 characteristics and its role in HF detection or outcomes: six studies highlighted S3 assessment among various groups of patients with HF; four studies evaluated the strength or amplitude of S3 with clinical outcomes; five studies assessed the relationship between S3 presence and clinical outcomes; and one study assessed both S3 presence and amplitude in relation to HF clinical outcomes. Eleven publications reported on EMAT and its derivatives: five studies on the relationship between EMAT and HF and six studies on the association of EMAT and HF clinical outcomes. Studies reporting the first and fourth heart sound, left ventricular ejection time and systolic dysfunction index were limited. Published literature supported S3 and EMAT as robust CAB measures in HF that may have value in remote clinical monitoring and management of patients with HF. Additional studies designed to test the predictive power of these CABs, and others less well-characterized, are needed. This work was funded by Astellas Pharma Inc.

Assembly and evaluation of a confocal microscopy image analysis pipeline useful in revealing the secrets of plant-fungal interactions.

The ability of laser scanning confocal microscopy to generate high-contrast 2D and 3D images has become essential in studying plant-fungal interactions. Techniques such as visualization of native fluorescence, fluorescent protein tagging of microbes, GFP/RFP-fusion proteins, and fluorescent labelling of plant and fungal proteins have been widely used to aid in these investigations. Use of fluorescent proteins has several pitfalls including variability of expression in planta and the requirement of gene transformation. Here we used the unlabeled pathogens Parastagonospora nodorum, Pyrenophora teres f. teres, and Cercospora beticola infecting wheat, barley, and sugar beet respectively, to show the utility of a staining and imaging pipeline that uses propidium iodide (PI), which stains RNA and DNA, and wheat germ agglutinin labeled with fluorescein isothiocyanate (WGA-FITC), which stains chitin, to visualize fungal colonization of plants. This pipeline relies on the use of KOH to remove the cutin layer of the leaf, increasing its permeability, allowing the different stains to penetrate and effectively bind to their targets, resulting in a consistent visualization of cellular structures. To expand the utility of this pipeline, we used the staining techniques in conjunction with machine learning to analyze fungal biomass through volume analysis, as well as quantifying nuclear breakdown, an early indicator of programmed cell death (PCD). This pipeline is simple to use, robust, consistent across host and fungal species and can be applied to most plant-fungal interactions. Therefore, this pipeline can be used to characterize model systems as well as non-model interactions where transformation is not routine.

Erratum to 'Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress' [Research and Practice in Thrombosis and Haemostasis Volume 8, Issue 4, May 2024, 102432].

[This corrects the article DOI: 10.1016/j.rpth.2024.102432.].

Detection and spread of high pathogenicity avian influenza virus H5N1 in the Antarctic Region.

Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8th October 2023. Since this detection, mortalities were observed in several avian and mammalian species at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations above that observed in other instances of mammalian infections globally. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.

Cannabis Laws and Utilization of Medications for the Treatment of Mental Health Disorders.

Importance: Mental health disorders are prevalent yet undertreated health conditions in the US. Given perceptions about the potential effect of cannabis on individuals with mental health disorders, there is a need to understand the association of cannabis laws with psychotropic use. Objective: To investigate the association of medical and recreational cannabis laws and dispensary openings with the dispensing of psychotropic medications used to treat mental health disorders in the US. Design, Setting, and Participants: This cross-sectional study of 10 013 948 commercially insured patients used a synthetic control method to examine the association of cannabis policies with prescribing. Data on all patients dispensed prescriptions for each of the 5 classes of psychotropic medications from January 1, 2007, to December 31, 2020, were extracted from Optum's deidentified Clinformatics Data Mart Database. Statistical analysis was performed from September 2022 to November 2023. Exposures: The 4 exposure variables measured were whether medical or recreational cannabis laws were in effect and whether medical or recreational cannabis dispensaries were open in each state and calendar quarter. Main Outcome and Measures: One measure of the extensive margins of dispensing and 2 measures of the intensive margins of dispensing were constructed for 5 medication classes (benzodiazepines, antidepressants, antipsychotics, barbiturates, and sleep medications). Results: The primary sample (the benzodiazepine sample) included 3 848 721 patients (mean [SD] age, 46.1 [11.4] years; 65.4% women; 53.7% aged 35-54 years). Medical cannabis laws were associated with a 12.4% reduction in the benzodiazepine fill rate (average treatment effect on the treated [ATT], -27.4; 95% CI, -14.7 to 12.0; P = .001), recreational cannabis laws were associated with a 15.2% reduction in the fill rate (ATT, -32.5; 95% CI, -24.4 to 20.1; P = .02), and medical cannabis laws were associated with a 1.3% reduction in the mean number of benzodiazepine fills per patient (ATT, -0.02; 95% CI, -0.02 to 0.02; P = .04). Medical dispensaries were associated with a 3.9% reduction in mean days' supply per benzodiazepine fill (ATT, -1.7; 95% CI, -0.8 to 0.6; P = .001), while recreational dispensaries were associated with a 6.2% reduction (ATT, -2.4; 95% CI, -1.0 to 0.9; P < .001). Medical cannabis laws were associated with a 3.8% increase in antidepressant fills (ATT, 27.2; 95% CI, -33.5 to 26.9; P = .048), and medical dispensaries were associated with an 8.8% increase (ATT, 50.7; 95% CI, -32.3 to 28.4; P = .004). The mean number of antipsychotic medication fills per patient increased by 2.5% (ATT, 0.06; 95% CI, -0.04 to 0.05; P = .02) after medical cannabis laws and by 2.5% (ATT, 0.06; 95% CI, -0.04 to 0.04; P = .02) after medical dispensary openings. Findings for the other drug classes showed substantial heterogeneity by state and direction of association. Conclusions and Relevance: This cross-sectional study of commercially insured patients suggests that there may have been meaningful heterogeneous associations between cannabis policy and state and between cannabis policy and drug class (eg, decreases in dispensing of benzodiazepines but increases in dispensing of antidepressants and antipsychotics). This finding suggests additional clinical research is needed to understand the association between cannabis use and mental health. The results have implications for patient substance use and mental health-related outcomes.

Utilizing citizen science data to rapidly assess changing associations between wild birds and avian influenza outbreaks in poultry.

High pathogenicity avian influenza virus (HPAIV) is a rapidly evolving virus causing significant economic and environmental harm. Wild birds are a key viral reservoir and an important source of viral incursions into animal populations, including poultry. However, we lack a thorough understanding of which species drive incursions and whether this changes over time. We explored associations between the abundances of 152 avian species and outbreaks of highly pathogenic avian influenza (HPAI) in poultry premises across Great Britain between October 2021 and January 2023. Spatial generalized additive models were used, with species abundance distributions sourced from eBird. Associations were investigated at the species-specific level and across species aggregations. During autumn/winter, associations were generally strongest with waterbirds such as ducks and geese; however, we also found significant associations in groups such as non-native gamebirds and rapid change in species-specific associations over time. Our results demonstrate the value of citizen science to rapidly explore wild species as potential facilitators of disease incursions into well-monitored populations, especially in regions where viral surveillance in wild species is limited. This can be a critical step towards prioritizing targeted surveillance that could inform species-specific biosecurity measures; particularly for HPAIV, which has undergone sudden shifts in host range and continues to rapidly evolve.

mHealth Physical Activity and Patient-Reported Outcomes in Patients With Inflammatory Bowel Diseases: Cluster Analysis.

BACKGROUND: Regular physical activity is associated with improved quality of life in patients with inflammatory bowel diseases (IBDs), although much of the existing research is based on self-reported data. Wearable devices provide objective data on many rich physical activity dimensions including steps, duration, distance, and intensity. Little is known about how patients with IBDs engage in these varying dimensions of exercise and how it may influence their symptom and disease-specific patient-reported outcomes (PROs). OBJECTIVE: This study aims to (1) cluster physical activity patterns from consumer-grade wearable devices and (2) assess the relationship between the clusters and PROs in patients with IBDs. METHODS: We conducted a cross-sectional and longitudinal cohort study among adults with IBDs in the Crohn's and Colitis Foundation IBD Partners cohort. Participants contribute physical activity data through smartphone apps or wearable devices in a bring-your-own-device model. Participants also complete biannual PRO questionnaires from the Patient-Reported Outcomes Measurement Information System short forms and IBD-specific questionnaires. K-means cluster analysis was used to generate physical activity clusters based on 3 key features: number of steps, duration of moderate to vigorous activity (minutes), and distance of activity (miles). Based on the clusters, we conducted a cross-sectional analysis to examine differences in mean questionnaire scores and participant characteristics using one-way ANOVA and chi-square tests. We also conducted a longitudinal analysis to examine individual cluster transitions among participants who completed multiple questionnaires, and mean differences in questionnaire scores were compared using 2-tailed paired sample t tests across 6-month periods. RESULTS: Among 430 participants comprising 1255 six-week physical activity periods, we identified clusters of low (33.7%, n=423), moderate (46%, n=577), and high (20.3%, n=255) physical activity. Scores varied across clusters for depression (P=.004), pain interference (P<.001), fatigue (P<.001), sleep disturbance (P<.001), social satisfaction (P<.001), and short Crohn Disease Activity Index (P<.001), with those in the low activity cluster having the worst scores. Sociodemographic characteristics also differed, and those with low physical activity were older (P=.002), had higher BMIs (P<.001), and had longer disease durations (P=.02) compared to other clusters. Among 246 participants who completed at least 2 consecutive questionnaires consisting of 726 questionnaire periods, 67.8% (n=492) remained in the same cluster, and only 1.2% (n=9) moved to or from the furthest clusters of low and high activity across 6-month periods. CONCLUSIONS: For patients with IBDs, there were positive associations between physical activity and PROs related to disease activity and psychosocial domains. Physical activity patterns mostly did not fluctuate over time, suggesting little variation in exercise levels in the absence of an intervention. The use of real-world data to identify subgroups with similar lifestyle behaviors could be leveraged to develop targeted interventions that provide support for psychosocial symptoms and physical activity for personalized IBD care.

Genomic Diversity and Evolutionary Insights of Avian Paramyxovirus-1 in Avian Populations in Pakistan.

The virulent form of Avian paramyxovirus-1 (APMV-1), commonly known as Newcastle Disease Virus (NDV), is a pathogen with global implications for avian health, affecting both wild and domestic bird populations. In Pakistan, recurrent Newcastle Disease (caused by NDV) outbreaks have posed significant challenges to the poultry industry. Extensive surveillance in Pakistan over 20 years has demonstrated a dynamic genetic diversity among circulating APMV-1 strains, emphasizing the potential necessity for customized vaccination strategies and continuous surveillance. In this study, 13 APMV-1-positive isolates harboring four different APMV-1 genotypes circulating throughout Pakistan were identified. These included the highly virulent genotypes VII and XIII, genotype XXI, commonly associated with Columbiformes, and genotype II, hypothesized to have been detected following vaccination. These findings underscore the intricate interplay of mutational events and host-immune interactions shaping the evolving NDV landscape. This study advances our understanding of the evolutionary dynamics of APMV-1 in Pakistan, highlighting the need for tailored vaccination strategies and continuous surveillance to enable effective APMV-1 management in avian populations, further emphasizing the importance of globally coordinated strategies to tackle APMV-1, given its profound impact on wild and domestic birds.

Effect of In Vivo Administration of Fibrinogen Concentrate Versus Cryoprecipitate on Ex Vivo Clot Degradation in Neonates Undergoing Cardiac Surgery.

BACKGROUND: Neonates undergoing cardiac surgery require fibrinogen replacement to restore hemostasis after cardiopulmonary bypass (CPB). Cryoprecipitate is often the first-line treatment, but recent studies demonstrate that fibrinogen concentrate (RiaSTAP; CSL Behring) may be acceptable in this population. This investigator-initiated, randomized trial compares cryoprecipitate to fibrinogen concentrate in neonates undergoing cardiac surgery (ClinicalTrials.gov NCT03932240). The primary end point was the percent change in ex vivo clot degradation from baseline at 24 hours after surgery between groups. Secondary outcomes included intraoperative blood transfusions, coagulation factor levels, and adverse events. METHODS: Neonates were randomized to receive cryoprecipitate (control group) or fibrinogen concentrate (study group) as part of a post-CPB transfusion algorithm. Blood samples were drawn at 4 time points: presurgery (T1), after treatment (T2), arrival to the intensive care unit (ICU) (T3), and 24 hours postsurgery (T4). Using the mixed-effect models, we analyzed the percent change in ex vivo clot degradation from a patient's presurgery baseline at each time point. Intraoperative blood product transfusions, coagulation factor levels, perioperative laboratory values, and adverse events were collected. RESULTS: Thirty-six neonates were enrolled (intent to treat [ITT]). Thirteen patients in the control group and seventeen patients in the study group completed the study per protocol (PP). After normalizing to the patient's own baseline (T1), no significant differences were observed in clot degradation at T2 or T3. At T4, patients in the study group had greater degradation when compared to those in the control group (826.5%, 95% confidence interval [CI], 291.1-1361.9 vs -545.9%, 95% CI, -1081.3 to -10.4; P < .001). Study group patients received significantly less median post-CPB transfusions than control group patients (ITT, 27.2 mL/kg [19.0-36.9] vs 41.6 [29.2-52.4]; P = .043; PP 26.7 mL/kg [18.8-32.2] vs 41.2 mL/kg [29.0-51.4]; P < .001). No differences were observed in bleeding or thrombotic events. CONCLUSIONS: Neonates who received fibrinogen concentrate, as compared to cryoprecipitate, have similar perioperative ex vivo clot degradation with faster degradation at 24 hours postsurgery, less post-CPB blood transfusions, and no increased bleeding or thrombotic complications. Our findings suggest that fibrinogen concentrate adequately restores hemostasis and reduces transfusions in neonates after CPB without increased bleeding or thrombosis risk.

Silicosis: No longer exclusively a chronic disease.

ABSTRACT: Silicosis typically has been classified as a chronic disease that develops after at least 10 years of exposure to silica dust, and often is associated with miners and stone workers. As industries have changed over time, other types of workers (including those in artificial stonework, jewelry polishing, and denim production) have become exposed to high levels of silica, leading to the development of acute and accelerated silicosis. Acute silicosis can develop in as little as a few months, and accelerated silicosis can develop in as little as 2 years. No cure exists for any form of silicosis, and lung transplantation is the only lifesaving treatment. Primary care clinicians must understand when patients are at risk for developing silicosis and not assume that a short time of exposure precludes the development of silicosis.

Evaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys.

Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing 'turkey-adapted' (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.

Preparation and Characterization of Hydrogels Fabricated From Chitosan and Poly(vinyl alcohol) for Tissue Engineering Applications.

In this study, we report on the preparation, characterization, and cytocompatibility of hydrogels for biomedical applications made from two different molecular weights of chitosan (CS) blended with poly(vinyl alcohol) (PVA) and chemically cross-linked with tetraethyl orthosilicate (TEOS) followed by freeze-drying. A series of CS-PVA hydrogels were synthesized with different amounts of chitosan (1%, 2%, and 3% by weight). The structure of these CS-PVA hydrogels was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The hydrogel samples were also characterized for tensile strength, contact angle, swelling behavior, and degradation at physiological body temperature. Their physicochemical properties, biocompatibility, and cell viability when cultured with human dermal fibroblasts were assessed using alamarBlue and live/dead assays and compared to optimize their functionality. SEM analysis showed that the concentration and molecular weight of the chitosan component affected the pore size. Furthermore, the contact angle decreased with increasing chitosan content, indicating that chitosan increased its hydrophilic properties. The in vitro degradation study revealed a nonlinear time-dependent relationship between chitosan concentration or molecular weight, and the rate of degradation was affected by the pore size of the hydrogel. All of the CS-PVA hydrogels exhibited good cell proliferation, particularly with the high molecular weight chitosan samples.

Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.

Proline is widely known as the only proteogenic amino acid with a secondary amine. In addition to its crucial role in protein structure, the secondary amino acid modulates neurotransmission and regulates the kinetics of signaling proteins. To understand the structural basis of proline import, we solved the structure of the proline transporter SIT1 in complex with the COVID-19 viral receptor ACE2 by cryo-electron microscopy. The structure of pipecolate-bound SIT1 reveals the specific sequence requirements for proline transport in the SLC6 family and how this protein excludes amino acids with extended side chains. By comparing apo and substrate-bound SIT1 states, we also identify the structural changes that link substrate release and opening of the cytoplasmic gate and provide an explanation for how a missense mutation in the transporter causes iminoglycinuria.

Recommendations to promote fairness and inclusion in biomedical AI research and clinical use.

OBJECTIVE: Understanding and quantifying biases when designing and implementing actionable approaches to increase fairness and inclusion is critical for artificial intelligence (AI) in biomedical applications. METHODS: In this Special Communication, we discuss how bias is introduced at different stages of the development and use of AI applications in biomedical sciences and health care. We describe various AI applications and their implications for fairness and inclusion in sections on 1) Bias in Data Source Landscapes, 2) Algorithmic Fairness, 3) Uncertainty in AI Predictions, 4) Explainable AI for Fairness and Equity, and 5) Sociological/Ethnographic Issues in Data and Results Representation. RESULTS: We provide recommendations to address biases when developing and using AI in clinical applications. CONCLUSION: These recommendations can be applied to informatics research and practice to foster more equitable and inclusive health care systems and research discoveries.