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INTRODUCTION: The ARCOS-V study, an epidemiological study on stroke and transient ischemic attack (TIA), faced the challenge of continuing data collection amidst the COVID-19 pandemic. This study aims to describe the methodological changes and challenges encountered during the transition from paper-based methods to digital data collection for the ARCOS-V study, and to provide insights into the potential of using digital tools to transform epidemiological research. METHODS: The study adapted to remote data collection using REDCap and Zoom, involving daily health record reviews, direct data entry by trained researchers, and remote follow-up assessments. The process was secured with encryption and role-based access controls. The transition period was analyzed to evaluate the effectiveness and challenges of the new approach. RESULTS: The digital transition allowed for uninterrupted monitoring of stroke and TIA cases during lockdowns. Using REDCap and Zoom improved data reach, accuracy, and security. However, it also revealed issues such as the potential for systematic data entry errors and the need for robust security measures to protect sensitive health information. CONCLUSION: The ARCOS-V study's digital transformation exemplifies the resilience of epidemiological research in the face of a global crisis. The successful adaptation to digital data collection methods highlights the potential benefits of such tools, particularly as we enter a new age of Artificial Intelligence (AI).

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Benzodiazepines are effective in managing anxiety and related disorders when used properly (short-term). Their inappropriate use, however, carries significant risks, involving amnesia, rebound insomnia, rebound anxiety, depression, dependence, abuse, addiction, and an intense and exceedingly prolonged withdrawal, among other complications. Benzodiazepines also amplify the effects of opioids and, consequently, have been implicated in approximately 30 % of opioid overdose deaths. Despite their unfavorable profile, sharp increases in medical and non-medical use of benzodiazepines have been steadily reported worldwide. Alprazolam (Xanax®), a potent, short-acting benzodiazepine, is among the most prescribed and abused anxiolytics in the United States. This medication is commonly co-abused with opioids, increasing the likelihood for oversedation, overdose, and death. Notwithstanding these risks, it is surprising that research investigating how benzodiazepines, such as alprazolam, interact with opioids is severely lacking in clinical and preclinical settings. This review therefore aims to present our current knowledge of benzodiazepine use and misuse, with an emphasis on alprazolam when data is available, and particularly in populations at higher risk for developing substance use disorders. Additionally, the potential mechanism(s) surrounding tolerance, dependence and abuse liability are discussed. Despite their popularity, our understanding of how benzodiazepines and opioids interact is less than adequate. Therefore, it is now more important than ever to understand the short- and long-term consequences of benzodiazepine/alprazolam use.

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Shortwave infrared (SWIR, 1000-1700 nm) and extended SWIR (ESWIR, 1700-2700 nm) absorbing materials are valuable for applications including fluorescence based biological imaging, photodetectors, and light emitting diodes. Currently, ESWIR absorbing materials are largely dominated by inorganic semiconductors which are often costly both in raw materials and manufacturing processes used to produce them. The development of ESWIR absorbing organic molecules is thus of interest due to the tunability, solution processability, and low cost of organic materials compared to their inorganic counterparts. Herein, through the combination of heterocyclic indolizine donors and an antiaromatic fluorene core, a series of organic chromophores with absorption maxima ranging from 1470-2088 nm (0.84-0.59 eV) and absorption onsets ranging from 1693-2596 nm (0.73-0.48 eV) are designed and synthesized. The photophysical and electrochemical properties of these chromophores, referred to as FluIndz herein, are described via absorption spectroscopy in 17 solvents, cyclic voltammetry, solution photostability, and transient absorption spectroscopy. Molecular orbital energies, predicted electronic transitions, and antiaromaticity are compared to higher energy absorbing chromophores using density functional theory. The presence of thermally accessible diradical states is demonstrated using density functional theory and EPR spectroscopy, while XRD crystallography confirms structural connectivity and existence as a single molecule. Overall, the FluIndz chromophore scaffold exhibits a rational means to access organic chromophores with extremely narrow optical gaps.

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BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

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SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper-proinflammatory state involves activation of signaling by NFκB, and unexpectedly, ENaC, the epithelial sodium channel. Post-infection inflammation may also contribute to "Long COVID"/PASC. Enhanced signaling by NFκB and ENaC also marks the airway of patients suffering from cystic fibrosis, a life-limiting proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 spike protein, and therefore activation of both NFκB and ENaC signaling. We used western blot and electrophysiological techniques, and an organoid model of normal airway epithelia, differentiated on an air-liquid-interface (ALI). We found that CFTR protein expression and CFTR cAMP-activated chloride channel activity were lost when the model epithelium was exposed to SARS-CoV-2 spike proteins. As hypothesized, the absence of CFTR led to activation of both TNFα/NFκB signaling and α and γ ENaC. We had previously shown that the cardiac glycoside drugs digoxin, digitoxin and ouabain blocked interaction of spike protein and ACE2. Consistently, addition of 30 nM concentrations of the cardiac glycoside drugs, prevented loss of both CFTR protein and CFTR channel activity. ACE2 and CFTR were found to co-immunoprecipitate in both basal cells and differentiated epithelia. Thus spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane. Thus, failure of CFTR recovery from endosomal recycling might be a mechanism for spike-dependent loss of CFTR. Finally, we found that authentic SARS-CoV-2 virus infection induced loss of CFTR protein, which was rescued by the cardiac glycoside drugs digitoxin and ouabain. Based on experiments with this organoid model of small airway epithelia, and comparisons with 16HBE14o- and other cell types expressing normal CFTR, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by the SARS-CoV-2 spike protein, thus inducing a cystic fibrosis-like clinical phenotype. To our knowledge this is the first time COVID-19 airway inflammation has been experimentally traced in normal subjects to a contribution from SARS-CoV-2 spike-dependent inhibition of CFTR signaling.

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BACKGROUND: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD. METHODS: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90. RESULTS: Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29-0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0-7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9-8.1). CONCLUSIONS: In patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy. TRIAL REGISTRATION: NCT03434028 (2018-02-09), BioLINCC 14149.

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Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

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BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

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In absence of a "gold standard", a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician. Agreement among 955 cases was 74.1% (708/955) for bacterial, 75.6% (722/955) for viral infections, and 71.2% (680/955) overall. Most discordances were minor (85.2%; 409/480) versus moderate (11.7%; 56/480) or complete (3.3%; 16/480). Concordance levels were lowest for bacterial skin and soft tissue infections (8.2%) and for viral respiratory tract infections (4.5%). This robust adjudication process can be used to evaluate HR tests and other diagnostics by regulatory agencies and for educating clinicians, laboratorians, and clinical researchers. Clinicaltrials.gov NCT04094818. SUMMARY: Without a gold standard for evaluating host response tests, clinical adjudication is a robust reference standard that is essential to determine the true infection status in diagnostic registrational clinical studies.

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Shortwave infrared (SWIR, 1000-1700 nm) absorbing and emitting dyes are needed for infrared diodes and sensors used in a wide variety of industrial and medical applications. Herein, an electron-withdrawing phosphine oxide (P═O) substituted xanthene is coupled with strong indolizine donors to produce a SWIR absorbing (λabs = 1294 nm in DCM) and emitting (λemis = 1450 nm in DCM) dye called PRos1450. The unique properties of this dye are characterized via photophysical, electrochemical, and computational analyses.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

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Importance: Emergency department (ED) visits by older adults with life-limiting illnesses are a critical opportunity to establish patient care end-of-life preferences, but little is known about the optimal screening criteria for resource-constrained EDs. Objectives: To externally validate the Geriatric End-of-Life Screening Tool (GEST) in an independent population and compare it with commonly used serious illness diagnostic criteria. Design, Setting, and Participants: This prognostic study assessed a cohort of patients aged 65 years and older who were treated in a tertiary care ED in Boston, Massachusetts, from 2017 to 2021. Patients arriving in cardiac arrest or who died within 1 day of ED arrival were excluded. Data analysis was performed from August 1, 2023, to March 27, 2024. Exposure: GEST, a logistic regression algorithm that uses commonly available electronic health record (EHR) datapoints and was developed and validated across 9 EDs, was compared with serious illness diagnoses as documented in the EHR. Serious illnesses included stroke/transient ischemic attack, liver disease, cancer, lung disease, and age greater than 80 years, among others. Main Outcomes and Measures: The primary outcome was 6-month mortality following an ED encounter. Statistical analyses included area under the receiver operating characteristic curve, calibration analyses, Kaplan-Meier survival curves, and decision curves. Results: This external validation included 82 371 ED encounters by 40 505 unique individuals (mean [SD] age, 76.8 [8.4] years; 54.3% women, 13.8% 6-month mortality rate). GEST had an external validation area under the receiver operating characteristic curve of 0.79 (95% CI, 0.78-0.79) that was stable across years and demographic subgroups. Of included encounters, 53.4% had a serious illness, with a sensitivity of 77.4% (95% CI, 76.6%-78.2%) and specificity of 50.5% (95% CI, 50.1%-50.8%). Varying GEST cutoffs from 5% to 30% increased specificity (5%: 49.1% [95% CI, 48.7%-49.5%]; 30%: 92.2% [95% CI, 92.0%-92.4%]) at the cost of sensitivity (5%: 89.3% [95% CI, 88.8-89.9]; 30%: 36.2% [95% CI, 35.3-37.1]). In a decision curve analysis, GEST outperformed serious illness criteria across all tested thresholds. When comparing patients referred to intervention by GEST with serious illness criteria, GEST reclassified 45.1% of patients with serious illness as having low risk of mortality with an observed mortality rate 8.1% and 2.6% of patients without serious illness as having high mortality risk with an observed mortality rate of 34.3% for a total reclassification rate of 25.3%. Conclusions and Relevance: The findings of this study suggest that both serious illness criteria and GEST identified older ED patients at risk for 6-month mortality, but GEST offered more useful screening characteristics. Future trials of serious illness interventions for high mortality risk in older adults may consider transitioning from diagnosis code criteria to GEST, an automatable EHR-based algorithm.

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Objectives: This study aimed to compare the different respiratory rate (RR) monitoring methods used in the emergency department (ED): manual documentation, telemetry, and capnography. Methods: This is a retrospective study using recorded patient monitoring data. The study population includes patients who presented to a tertiary care ED between January 2020 and December 2022. Inclusion and exclusion criteria were patients with simultaneous recorded RR data from all three methods and less than 10 min of recording, respectively. Linear regression and Bland-Altman analysis were performed between different methods. Results: A total of 351 patient encounters met study criteria. Linear regression yielded an R-value of 0.06 (95% confidence interval [CI] 0.00-0.12) between manual documentation and telemetry, 0.07 (95% CI 0.01-0.13) between manual documentation and capnography, and 0.82 (95% CI 0.79-0.85) between telemetry and capnography. The Bland-Altman analysis yielded a bias of -0.8 (95% limits of agreement [LOA] -12.2 to 10.6) between manual documentation and telemetry, bias of -0.6 (95% LOA -13.5 to 12.3) between manual documentation and capnography, and bias of 0.2 (95% LOA -6.2 to 6.6) between telemetry and capnography. Conclusion: There is a poor correlation between manual documentation and both automated methods, while there is relatively good agreement between the automated methods. This finding highlights the need to further investigate the methodology used by the ED staff in monitoring and documenting RR and ways to improve its reliability given that many important clinical decisions are made based on these assessments.

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Animals live in visually complex environments. As a result, visual systems have evolved mechanisms that simplify visual processing and allow animals to focus on the information that is most relevant to adaptive decision making. This review explores two key mechanisms that animals use to efficiently process visual information: categorization and specialization. Categorization occurs when an animal's perceptual system sorts continuously varying stimuli into a set of discrete categories. Specialization occurs when particular classes of stimuli are processed using distinct cognitive operations that are not used for other classes of stimuli. We also describe a nonadaptive consequence of simplifying heuristics: visual illusions, where visual perception consistently misleads the viewer about the state of the external world or objects within it. We take an explicitly comparative approach by exploring similarities and differences in visual cognition across human and nonhuman taxa. Considering areas of convergence and divergence across taxa provides insight into the evolution and function of visual systems and associated perceptual strategies.

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In the past decade, medical education has increasingly incorporated evidence-based lifestyle interventions as primary strategies for preventing and managing noncommunicable diseases. This shift embraces the growing recognition of the significant impact of lifestyle on health outcomes, driving diseases including obesity, diabetes, heart disease, and cancer. Now deemed "food is medicine" (FIM), diet-related interventions witnessed integration into healthcare systems and recognition in the United States' White House Conference on Hunger, Nutrition, and Health in 2023. As FIM gains traction, investigating optimal strategies for team-based education becomes essential. Healthcare teams need the necessary knowledge and tools to effectively administer FIM services and collaborate across disciplines, ultimately enhancing disease prevention, chronic disease management, health quality, value, and overall wellness. Culinary medicine (CM), a vital component of FIM, bridges nutrition education, pragmatic culinary skills, and conventional strategies to improve chronic disease management. CM involves experiential learning, imparts practical skills, and encourages behavior change by addressing food-related determinants of health and promoting equitable access. Teaching kitchens serve as physical or virtual learning spaces and as a didactic and experiential method (skills lab), playing a crucial role by integrating culinary, lifestyle, integrative, and conventional medicine. A growing number of medical schools in the United States and globally offer CM education via diverse methods including interest groups, electives, and specialty tracks, encompassing didactic sessions, hands-on kitchen education, and virtual teaching methods. Given the rising demand for CM programs, this article aims to describe, map, and compare existing CM education types in medical education. It provides actionable recommendations for medical schools to establish and expand CM programs by fostering service-learning partnerships, clinical innovation, and interdisciplinary research. As FIM gains prominence, cultivating a robust foundation of educational strategies is vital to ensure seamless integration into both medical education and collaborative medical practice.

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Since the end of the Cold War, millions of migrants from Eastern Europe have sought better opportunities in Western European countries, yet few studies have assessed the impact of such moves on these migrants' children. In the aim of isolating a "treatment effect" of migration on educational outcomes, this study analyzes Programme for International Student Assessment (PISA) scores from 2012, 2015, and 2018 for adolescents born in twelve Eastern European countries and living in eight Western European countries. It employs propensity-score matching within a homeland dissimilation framework, comparing immigrants' outcomes on reading, math, and science assessments to similar stay-at-homes in their countries of origin. In unadjusted comparisons to their counterparts who remained behind, migrant children attain lower scores across all three subjects. Once immigrant children are matched to non-immigrants with similar propensities to migrate, the disparity for math scores disappears, while those for reading and science remain. Disparities are wider for adolescents who come from within the EU, migrate at older ages, or speak a foreign language at home. This paper indicates the need for policymakers and educational administrators to better handle the negative academic effects that migration can have on children from within Europe.

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Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

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Subsurface microorganisms make up the majority of Earth's microbial biomass, but ecological processes governing surface communities may not explain community patterns at depth because of burial. Depth constrains dispersal and energy availability, and when combined with geographic isolation across landscapes, may influence community assembly. We sequenced the 16S rRNA gene of bacteria and archaea from 48 sediment cores across 36 lakes in four disconnected mountain ranges in Wyoming, USA and used null models to infer assembly processes across depth, spatial isolation, and varying environments. Although we expected strong dispersal limitations across these isolated settings, community composition was primarily shaped by environmental selection. Communities consistently shifted from domination by organisms that degrade organic matter at the surface to methanogenic, low-energy adapted taxa in deeper zones. Stochastic processes-like dispersal limitation-contributed to differences among lakes, but because these effects weakened with depth, selection processes ultimately governed subsurface microbial biogeography.

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Latent bloodstain detection remains imperative for crime scene investigators. Widely used luminol offers high sensitivity to human blood, but can produce untrustworthy results from a bleach-cleaned crime scene or in a room not dark enough. Furthermore, dark pigments impede imaging bloodstains covered by dark materials with previously reported bloodstain detection agents. A novel on/off human albumin-sensing dye (SO3C7) is reported herein with a longer emission wavelength (942 nm) than previous materials that allows imaging behind ∼5 mm of black fabric. The switch-on emission of SO3C7 is selective and sensitive to human albumin and lasts longer than luminol (24-48 hours). Emission studies, transient absorption spectra (TAS), and near-infrared (NIR) photographs herein describe the albumin sensing properties of the dye.

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In vivo fluorescence imaging in the shortwave infrared (SWIR, 1,000-1,700 nm) and extended SWIR (ESWIR, 1,700-2,700 nm) regions has tremendous potential for diagnostic imaging. Although image contrast has been shown to improve as longer wavelengths are accessed, the design and synthesis of organic fluorophores that emit in these regions is challenging. Here we synthesize a series of silicon-RosIndolizine (SiRos) fluorophores that exhibit peak emission wavelengths from 1,300-1,700 nm and emission onsets of 1,800-2,200 nm. We characterize the fluorophores photophysically (both steady-state and time-resolved), electrochemically and computationally using time-dependent density functional theory. Using two of the fluorophores (SiRos1300 and SiRos1550), we formulate nanoemulsions and use them for general systemic circulatory SWIR fluorescence imaging of the cardiovascular system in mice. These studies resulted in high-resolution SWIR images with well-defined vasculature visible throughout the entire circulatory system. This SiRos scaffold establishes design principles for generating long-wavelength emitting SWIR and ESWIR fluorophores.

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