A New Era of Ophthalmology Leadership? A Descriptive and Comparative Analysis of Ophthalmology Department Chairs in 2024.

PURPOSE: To (1) characterize and analyze the demographics and scholarly achievements of United States (US) academic ophthalmology department chairs, and (2) to elucidate trends in the academic and demographic profiles of newly hired department chairs. DESIGN: Cross-sectional study. METHODS: none SETTING: Online search of publicly available resources conducted January 1, 2024. PATIENT OR STUDY POPULATION: 107 ophthalmology chairs of accredited US departments. MAIN OUTCOME MEASURES: Department chair demographic and academic data. RESULTS: Of the 107 chairs analyzed, 83% (89/107) are male. The mean age of chairs is 60.9 ± 7.9 years and the mean age at appointment is 51.9 ± 7.6 years. There has been significant turnover in department chairs recently, with 47 (44%, 47/107) chairs newly appointed in the past seven years. Approximately 40% (41/107) of current chairs completed at least one component of their medical training at the program where they are currently chair. Approximately 1/3 (31%, 33/107) of current chairs earned an additional graduate degree, most frequently a PhD (16%, 17/107), MBA (8%, 10/107), and MS (4%, 8/107). More than 96% (103/107) of chairs completed a clinical fellowship, often in vitreoretinal surgery (28%, 30/107), cornea (25%, 27/107), or glaucoma (22%, 24/107). The average number of peer-reviewed publications amongst chairs is 214.9 ± 294.7 (range 0-1901), and the mean h-index is 35.0 ± 25.4 (range 0-147). When comparing profiles of newly appointed chairs in the past 7 years to chairs appointed prior to 2017, there was not a statistically significant difference in gender distribution (21% female vs. 13% female, respectively, p = 0.276). Newly hired chairs were significantly older at the time of their appointment to chair (54 years vs. 50 years, respectively, p = 0.008) and averaged significantly more years from residency completion to appointment as chair (23 years vs. 19 years, respectively, p = 0.005). CONCLUSIONS: Ophthalmology department chairs remain predominantly fellowship-trained males who have frequently trained at the institution they currently chair. Newly hired chairs have accumulated more experience prior to their appointment, starting the role later in their careers, with implications for the frequency of future chair turnover. While females compose a higher proportion of newly hired chairs in the past 7 years compared to prior, females remain underrepresented in ophthalmology chair positions.

Comparing the Ability of Google and ChatGPT to Accurately Respond to Oculoplastics-Related Patient Questions and Generate Customized Oculoplastics Patient Education Materials.

Purpose: To compare the accuracy and readability of responses to oculoplastics patient questions provided by Google and ChatGPT. Additionally, to assess the ability of ChatGPT to create customized patient education materials. Methods: We executed a Google search to identify the 3 most frequently asked patient questions (FAQs) related to 10 oculoplastics conditions. FAQs were entered into both the Google search engine and the ChatGPT tool and responses were recorded. Responses were graded for readability using five validated readability indices and for accuracy by six oculoplastics surgeons. ChatGPT was instructed to create patient education materials at various reading levels for 8 oculoplastics procedures. The accuracy and readability of ChatGPT-generated procedural explanations were assessed. Results: ChatGPT responses to patient FAQs were written at a significantly higher average grade level than Google responses (grade 15.6 vs 10.0, p < 0.001). ChatGPT responses (93% accuracy) were significantly more accurate (p < 0.001) than Google responses (78% accuracy) and were preferred by expert panelists (79%). ChatGPT accurately explained oculoplastics procedures at an above average reading level. When instructed to rewrite patient education materials at a lower reading level, grade level was reduced by approximately 4 (15.7 vs 11.7, respectively, p < 0.001) without sacrificing accuracy. Conclusion: ChatGPT has the potential to provide patients with accurate information regarding their oculoplastics conditions. ChatGPT may also be utilized by oculoplastic surgeons as an accurate tool to provide customizable patient education for patients with varying health literacy. A better understanding of oculoplastics conditions and procedures amongst patients can lead to informed eye care decisions.

Direct computations of viscoelastic moduli of biomolecular condensates.

Biomolecular condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model that leverages information regarding intra- and inter-chain contacts, which we extract from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations of phase separation. The key ingredient of the generalized Rouse model is a graph Laplacian that we compute from equilibrium MMC simulations. We compute two flavors of graph Laplacians, one based on a single-chain graph that accounts only for intra-chain contacts, and the other referred to as a collective graph that accounts for inter-chain interactions. Calculations based on the single-chain graph systematically overestimate the storage and loss moduli, whereas calculations based on the collective graph reproduce the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two graphs proves to be most accurate. In line with the theory of Rouse and contrary to recent assertions, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic vs dominantly viscous behaviors does not imply a single relaxation time. Instead, it is influenced by the totality of the relaxation modes. Hence, our analysis affirms that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain the relaxation time spectra that underlie the dynamics within condensates. This is of practical importance given advancements in passive and active microrheology measurements of condensate viscoelasticity.

Benchtop Flow Stasis Quantification: In Vitro Methods and In Vivo Possibilities.

PURPOSE: Neo-sinus flow stasis has ben correlated with transcatheter heart valve (THV) thrombosis severity and occurrence. Standard benchtop flow field quantification techniques require optical access or modified prosthesis models that may not reflect the true nature of the original valve. En face and fluoroscopic videodensitometry enable visualization of washout in regions otherwise unviewable. METHODS: This study compares two in vitro methods of assessing flow stasis in scenarios with insufficient optical access for traditional techniques such as particle image velocimetry (PIV). A series of seven paired experiments were conducted using a previously described laser-enhanced video densitometry (LEVD) and fluoroscopic video densitometry (FVD). Both sets of experiments were analyzed to calculate washout time as a measure of flow stasis. A novel flow stasis measure termed contrast attenuation ratio (CAR) is proposed as a viable single measure of flow stasis obtainable from only a small number of cardiac cycles of in vitro or in vivo fluoroscopic data. Retrospective fluoroscopic datasets (n = 72) were analyzed to assess the feasibility of obtaining this metric from routine clinical practice and its ability to stratify results. RESULTS: Neo-sinus flow stasis calculated from in vitro fluoroscopy was well correlated with LEVD (r2 = 0.77, p = 0.009). The newly proposed CAR metric showed good agreement with the commonly used "washout time" measure of flow stasis (r2 = 0.91, p < 0.001) while allowing for assessment with incomplete or truncated data. As a proof of concept, CAR was measured in 72 consecutive retrospective fluoroscopic datasets. CAR averaged 10.6 ± 4.6% with a range of 1.5-20.3% in these patients. CONCLUSIONS: This study demonstrates two in vitro methods that can be used to assess relative flow stasis in otherwise optically inaccessible regions surrounding cardiac or vascular implants. In addition, the fluoroscopic benchtop technique was used to validate a metric that allows for extension to routine clinical fluoroscopy. This contrast attenuation ratio (CAR) metric was found to be both accurate and clinically obtainable, and potentially offers a new method for valve thrombosis risk stratification.

A transcriptomic biomarker predictive of cell proliferation for use in adverse outcome pathway-informed testing and assessment.

High-throughput transcriptomics (HTTr) is increasingly being used to identify molecular targets of chemicals that can be linked to adverse outcomes. Cell proliferation (CP) is an important key event in chemical carcinogenesis. Here, we describe the construction and characterization of a gene expression biomarker that is predictive of the CP status in human and rodent tissues. The biomarker was constructed from 30 genes known to be increased in expression in prostate cancers relative to surrounding tissues and in cycling human MCF-7 cells after estrogen receptor (ER) agonist exposure. Using a large compendium of gene expression profiles to test utility, the biomarker could identify increases in CP in (i) 308 out of 367 tumor vs. normal surrounding tissue comparisons from 6 human organs, (ii) MCF-7 cells after activation of ER, (iii) after partial hepatectomy in mice and rats, and (iv) the livers of mice and rats after exposure to nongenotoxic hepatocarcinogens. The biomarker identified suppression of CP (i) under conditions of p53 activation by DNA damaging agents in human cells, (ii) in human A549 lung cells exposed to therapeutic anticancer kinase inhibitors (dasatinib, nilotnib), and (iii) in the mouse liver when comparing high levels of CP at birth to the low background levels in the adult. The responses using the biomarker were similar to those observed using conventional markers of CP including PCNA, Ki67, and BrdU labeling. The CP biomarker will be a useful tool for interpretation of HTTr data streams to identify CP status after exposure to chemicals in human cells or in rodent tissues.

Differential immunometabolic responses to Delta and Omicron SARS-CoV-2 variants in golden syrian hamsters.

Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2 represents unique clinical characteristics. However, their role in altering immunometabolic regulations during acute infection remains convoluted. Here, we evaluated the differential immunopathogenesis of Delta vs. Omicron variants in Golden Syrian hamsters (GSH). The Delta variant resulted in higher virus titers in throat swabs and the lungs and exhibited higher lung damage with immune cell infiltration than the Omicron variant. The gene expression levels of immune mediators and metabolic enzymes, Arg-1 and IDO1 in the Delta-infected lungs were significantly higher compared to Omicron. Further, Delta/Omicron infection perturbed carbohydrates, amino acids, nucleotides, and TCA cycle metabolites and was differentially regulated compared to uninfected lungs. Collectively, our data provide a novel insight into immunometabolic/pathogenic outcomes for Delta vs. Omicron infection in the GSH displaying concordance with COVID-19 patients associated with inflammation and tissue injury during acute infection that offered possible new targets to develop potential therapeutics.

Google Trends-Assisted Analysis of the Readability, Accountability, and Accessibility of Online Patient Education Materials for the Treatment of AMD After US FDA Approval of Pegcetacoplan.

Purpose: To evaluate the readability, accountability, accessibility, and source of online patient education materials for treatment of age-related macular degeneration (AMD) and to quantify public interest in Syfovre and geographic atrophy after US Food and Drug Administration (FDA) approval. Methods: Websites were classified into 4 categories by information source. Readability was assessed using 5 validated readability indices. Accountability was assessed using 4 benchmarks of the Journal of the American Medical Association (JAMA). Accessibility was evaluated using 3 established criteria. The Google Trends tool was used to evaluate temporal trends in public interest in "Syfovre" and "geographic atrophy" in the months after FDA approval. Results: Of 100 websites analyzed, 22% were written below the recommended sixth-grade reading level. The mean (±SD) grade level of analyzed articles was 9.76 ± 3.35. Websites averaged 1.40 ± 1.39 (of 4) JAMA accountability metrics. The majority of articles (67%) were from private practice/independent organizations. A significant increase in the public interest in the terms "Syfovre" and "geographic atrophy" after FDA approval was found with the Google Trends tool (P < .001). Conclusions: Patient education materials related to AMD treatment are often written at inappropriate reading levels and lack established accountability and accessibility metrics. Articles from national organizations ranked highest on accessibility metrics but were less visible on a Google search, suggesting the need for visibility-enhancing measures. Patient education materials related to the term "Syfovre" had the highest average reading level and low accountability, suggesting the need to modify resources to best address the needs of an increasingly curious public.

Mode of action of dieldrin-induced liver tumors: application to human risk assessment.

Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.

Geographic Trends in Ophthalmology Resident Physician Compensation and Cost-of-Living Expenses.

Importance: Given that resident physician financial strain has been associated with poor outcomes, objective metrics to forecast financial well-being may be useful to (1) applicants when evaluating ophthalmology residency programs and (2) programs when determining resident benefits. Objectives: To determine and compare the relative value of ophthalmology resident stipends plus benefits when adjusted for cost-of-living expenses and to analyze program characteristics associated with greater resident net incomes. Design, Setting, and Participants: In this cross-sectional study, the American Medical Association's Fellowship and Residency Electronic Interactive Database was used to identify US Accreditation Council for Graduate Medical Education-accredited ophthalmology residency programs. Resident physician stipends and stipends plus benefits as well as residency program characteristics from the 2023-2024 academic year were noted for all eligible programs. The Massachusetts Institute of Technology's Living Wage Calculator's required annual income (RAI) was selected as a surrogate to approximate cost-of-living expenses. Exposure: Residency program characteristics, including affiliation, size, ranking, presence of housing benefit, and training year. Main Outcomes and Measures: The primary outcome was the annual stipend plus benefits income surplus (SPBIS) for each residency program, defined as the resident's stipend plus benefits (SPB) minus the RAI for the county in which the residency program is located. Secondary outcomes included income surplus variation by program characteristics. Results: Of 116 ophthalmology residency programs analyzed, 37 (31.9%) were located in the Northeast, 36 (31.0%) in the South, 29 (25.0%) in the Midwest, and 14 (12.1%) in the West. The mean (SD) postgraduate year 1 resident annual SPB was $65 397 ($8205), and the median (IQR) was $63 986 ($59 992-$69 698). After adjusting for the cost of living, the mean (SD) SPBIS was $27 459 ($5734) and the median (IQR) was $27 380 ($23 625-$31 796). Annual cost-of-living expenses varied by as much as $8628 (95% CI, $6310-$10 947) and SPBIS varied by as much as $6283 (95% CI, $3367-$9198) between regions. Resident SPB increased by a mean (SD) of 3.97% (0.98%) for each subsequent training year (range, 0.93%-7.26%). Annual SPBIS increased by a mean (SD) of 9.48% (3.60%) for each subsequent training year. Conclusions and Relevance: After adjusting for living costs, intraregional and interregional differences in SPBIS among ophthalmology residents can vary by thousands of dollars, impacting residents' financial security. Further discussion regarding compensation may lead to innovative strategies that aim to improve resident well-being and performance.

Direct computations of viscoelastic moduli of biomolecular condensates.

In vitro facsimiles of biomolecular condensates are formed by different types of intrinsically disordered proteins including prion-like low complexity domains (PLCDs). PLCD condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model and information regarding intra- and inter-chain contacts that is extracted from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations. The key ingredient of the generalized Rouse model is the Zimm matrix that we compute from equilibrium MMC simulations. We compute two flavors of Zimm matrices, one referred to as the single-chain model that accounts only for intra-chain contacts, and the other referred to as a collective model, that accounts for inter-chain interactions. The single-chain model systematically overestimates the storage and loss moduli, whereas the collective model reproduces the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two models proves to be most accurate. In line with the theory of Rouse, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic versus dominantly viscous behaviors is influenced by the totality of the relaxation modes. Hence, our analysis suggests that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain distributions of relaxation times that underlie the dynamics within condensates.

CCR5 Decorated Rilpivirine Lipid Nanoparticles Build Myeloid Drug Depots Which Sustains Antiretroviral Activities.

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. A novel drug formulation is made whereby a lipid nanoparticle (LNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5). This facilitates myeloid drug depot deposition. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated RPV LNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice. Focused ultrasound allows the decorated LNP to penetrate the blood-brain barrier and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression.

Cell proliferation and carcinogenesis: an approach to screening for potential human carcinogens.

Cancer arises from multiple genetic errors occurring in a single stem cell (clonality). Every time DNA replicates, mistakes occur. Thus, agents can increase the risk of cancer either by directly damaging DNA (DNA-reactive carcinogens) or increasing the number of DNA replications (increased cell proliferation). Increased cell proliferation can be achieved either by direct mitogenesis or cytotoxicity with regenerative proliferation. Human carcinogens have a mode of action of DNA reactivity, immunomodulation (mostly immunosuppression), increased estrogenic activity (mitogenesis), or cytotoxicity and regeneration. By focusing on screening for these four effects utilizing in silico, in vitro, and short-term in vivo assays, a biologically based screening for human chemical carcinogens can be accomplished with greater predictivity than the traditional 2-year bioassay with considerably less cost, less time, and the use of fewer animals.

Biomolecular condensates form spatially inhomogeneous network fluids.

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.

Biomarker Assessment of Nicotine Exposure Among Adolescent E-Cigarette Users: 2018-2019.

BACKGROUND: Despite the increasing prevalence of vaping e-cigarettes among adolescents, there remains a lack of population-level assessments regarding the objective measurement of nicotine exposure. METHODS: This study analyzed a nationally representative sample of adolescents aged 13 to 17 years from Wave 5 of the Population Assessment of Tobacco and Health Study conducted between 2018 and 2019. Urinary nicotine metabolites, including cotinine and trans-3'-hydroxycotinine (3-HC), were assessed among exclusive nonnicotine e-cigarette users (n = 56), exclusive nicotine e-cigarette users (n = 200), and nonusers (n = 1059). We further examined nicotine exposure by past 30-day vaping frequency (ie, occasional [1-5 days], intermittent [6-19 days], and frequent [20+ days]) and flavor types among nicotine e-cigarette users. Multivariable linear regressions tested pairwise group effects, and biomarkers were normalized by the log transformation. RESULTS: Compared with nonusers, both nonnicotine and nicotine e-cigarette users exhibited higher levels of cotinine and 3-HC. Nicotine e-cigarette users had mean cotinine concentrations (61.3; 95% confidence interval, 23.8-158.0, ng/mg creatinine) approximately 146 times higher (P < .0001) than nonusers (0.4; 0.3-0.5), whereas nonnicotine users (4.9; 1.0-23.2) exhibited cotinine concentrations ∼12 times higher (P = .02). Among nicotine e-cigarette users, the levels of cotinine and 3-HC increased by vaping frequency, with cotinine increasing from 10.1 (2.5-40.1) among occasional users to 73.6 (31.8-170.6) among intermittent users and 949.1 (482.5-1866.9) among frequent users. Nicotine exposure was not significantly different by flavor type. CONCLUSIONS: E-cigarette use poses health-related risks resulting from nicotine exposure among adolescents. Comprehensive regulations of e-cigarette products and marketing, vaping prevention, cessation, and public policies are needed to prevent youth from developing nicotine addiction.

Dr. Google vs. Dr. ChatGPT: Exploring the Use of Artificial Intelligence in Ophthalmology by Comparing the Accuracy, Safety, and Readability of Responses to Frequently Asked Patient Questions Regarding Cataracts and Cataract Surgery.

PURPOSE: Patients are using online search modalities to learn about their eye health. While Google remains the most popular search engine, the use of large language models (LLMs) like ChatGPT has increased. Cataract surgery is the most common surgical procedure in the US, and there is limited data on the quality of online information that populates after searches related to cataract surgery on search engines such as Google and LLM platforms such as ChatGPT. We identified the most common patient frequently asked questions (FAQs) about cataracts and cataract surgery and evaluated the accuracy, safety, and readability of the answers to these questions provided by both Google and ChatGPT. We demonstrated the utility of ChatGPT in writing notes and creating patient education materials. METHODS: The top 20 FAQs related to cataracts and cataract surgery were recorded from Google. Responses to the questions provided by Google and ChatGPT were evaluated by a panel of ophthalmologists for accuracy and safety. Evaluators were also asked to distinguish between Google and LLM chatbot answers. Five validated readability indices were used to assess the readability of responses. ChatGPT was instructed to generate operative notes, post-operative instructions, and customizable patient education materials according to specific readability criteria. RESULTS: Responses to 20 patient FAQs generated by ChatGPT were significantly longer and written at a higher reading level than responses provided by Google (p < .001), with an average grade level of 14.8 (college level). Expert reviewers were correctly able to distinguish between a human-reviewed and chatbot generated response an average of 31% of the time. Google answers contained incorrect or inappropriate material 27% of the time, compared with 6% of LLM generated answers (p < .001). When expert reviewers were asked to compare the responses directly, chatbot responses were favored (66%). CONCLUSIONS: When comparing the responses to patients' cataract FAQs provided by ChatGPT and Google, practicing ophthalmologists overwhelming preferred ChatGPT responses. LLM chatbot responses were less likely to contain inaccurate information. ChatGPT represents a viable information source for eye health for patients with higher health literacy. ChatGPT may also be used by ophthalmologists to create customizable patient education materials for patients with varying health literacy.

Subtle variation in sepsis-III definitions markedly influences predictive performance within and across methods.

Early detection of sepsis is key to ensure timely clinical intervention. Since very few end-to-end pipelines are publicly available, fair comparisons between methodologies are difficult if not impossible. Progress is further limited by discrepancies in the reconstruction of sepsis onset time. This retrospective cohort study highlights the variation in performance of predictive models under three subtly different interpretations of sepsis onset from the sepsis-III definition and compares this against inter-model differences. The models are chosen to cover tree-based, deep learning, and survival analysis methods. Using the MIMIC-III database, between 867 and 2178 intensive care unit admissions with sepsis were identified, depending on the onset definition. We show that model performance can be more sensitive to differences in the definition of sepsis onset than to the model itself. Given a fixed sepsis definition, the best performing method had a gain of 1-5% in the area under the receiver operating characteristic (AUROC). However, the choice of onset time can cause a greater effect, with variation of 0-6% in AUROC. We illustrate that misleading conclusions can be drawn if models are compared without consideration of the sepsis definition used which emphasizes the need for a standardized definition for sepsis onset.

Biomolecular condensates form spatially inhomogeneous network fluids.

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.

Placement of Temporary Left Ventricular Assist Device Using Monitored Anesthesia Care and Regional Anesthesia.

Patients with advanced cardiogenic shock requiring mechanical circulatory support are uniquely susceptible to clinical deterioration. Limiting physiologic perturbations via avoidance of general anesthesia and endotracheal intubation by awake Impella 5.5 placement is safe and may represent a novel strategy in mechanical circulatory support initiation among patients in cardiogenic shock. (Level of Difficulty: Intermediate.).

Pleural Uptake Patterns in F18Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scans Improve the Identification of Malignant Pleural Effusions.

BACKGROUND: The confirmation of malignant pleural effusions (MPE) requires an invasive procedure. Diagnosis can be difficult and may require repeated thoracentesis or biopsies. F18Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) can characterize the extent of malignant involvement in areas of increased uptake. Patterns of uptake in the pleura may be sufficient to obviate the need for further invasive procedures. METHODS: This is a retrospective review of patients with confirmed malignancy and suspected MPE. Patients who underwent diagnostic thoracentesis with cytology and contemporaneous FDG-PET were identified for analysis. Some underwent confirmatory pleural biopsy. The uptake pattern on FDG-PET underwent blinded review and was categorized based on the pattern of uptake. RESULTS: One hundred consecutive patients with confirmed malignancy, suspected MPE and corresponding FDG-PET scans were reviewed. MPE was confirmed in 70 patients with positive pleural fluid cytology or tissue pathology. Of the remaining patients, 15 had negative cytopathology, 14 had atypical cells and 1 had reactive cells. Positive uptake on FDG-PET was noted in 76 patients. The concordance of malignant histology and positive FDG-PET occurred in 58 of 76 patients (76%). Combining histologically confirmed MPE with atypical cytology, positive pleural FDG-PET uptake had a positive predictive value of 91% for MPE. An encasement pattern had a 100% PPV for malignancy. CONCLUSION: Positive FDG-PET pleural uptake represents an excellent method to identify MPE, especially in patients with an encasement pattern. This may eliminate the need for additional invasive procedures in some patients, even when initial pleural cytology is negative.

Biomolecular condensates form spatially inhomogeneous network fluids.

The functions of biomolecular condensates are thought to be influenced by their material properties, and these are in turn determined by the multiscale structural features within condensates. However, structural characterizations of condensates are challenging, and hence rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and bespoke coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that mimic nucleolar granular components (GCs). We show that facsimiles of GCs are network fluids featuring spatial inhomogeneities across hierarchies of length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights, extracted from a combination of approaches, suggest that condensates formed by multivalent proteins share features with network fluids formed by associative systems such as patchy or hairy colloids.