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Item type: Item , Access status: Open Access , Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.(PLoS pathogens, 2024-10) SoRelle, Elliott D; Haynes, Lauren E; Willard, Katherine A; Chang, Beth; Ch'ng, James; Christofk, Heather; Luftig, Micah AViral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.Item type: Item , Access status: Open Access , Implementation of contextualized, emergency management cognitive aids in a periodontics clinic.(Journal of dental anesthesia and pain medicine, 2021-06) Siemens, Mikaela J; Rice, Andi N; Jensen, Trenton F; Muckler, Virginia C SimmonsBackground
Emergencies in outpatient clinics are rare. However, potentially catastrophic events can be challenging to manage due to a variety of factors, including limited equipment and staff. The purpose of this quality improvement project was to improve the staff knowledge and familiarity with critical performance elements for emergencies encountered in the setting of a periodontics clinic.Methods
Emergency cognitive aids tailored to the clinic's resources were created for anaphylaxis, airway obstruction, and sublingual hemorrhage. The project pre-post-test repeated measures design evaluated the effectiveness of cognitive aids using a combination of hands-on simulation, written knowledge assessments, and self-efficacy surveys. Training sessions and simulations were provided to the clinic's existing care teams made up of a periodontist and two dental assistants with an anesthetist who was present for simulations involving sedation. Due to the small sample size (N = 14) and non-normal distribution, all metrics were evaluated using non-parametric statistics.Results
Significant improvements were found in knowledge assessment (-2.310, P = 0.021) and self-efficacy (-2.486, P = 0.013) scores when retention after a training session before and after the introduction of cognitive aid was compared. The mean simulation scores and times improved steadily or reached maximum scores during the project progression.Conclusion
Training sessions before and after cognitive aid introduction were effective in improving knowledge, self-efficacy, and simulation performance. Future projects should focus on validating the process for creating contextualized cognitive aids and evaluating the effectiveness of these cognitive aids in larger samples.Item type: Item , Access status: Open Access , Inositol phosphate kinase 2 is required for imaginal disc development in Drosophila.(Proceedings of the National Academy of Sciences of the United States of America, 2015-12) Seeds, Andrew M; Tsui, Marco M; Sunu, Christine; Spana, Eric P; York, John DInositol phosphate kinase 2 (Ipk2), also known as IP multikinase IPMK, is an evolutionarily conserved protein that initiates production of inositol phosphate intracellular messengers (IPs), which are critical for regulating nuclear and cytoplasmic processes. Here we report that Ipk2 kinase activity is required for the development of the adult fruit fly epidermis. Ipk2 mutants show impaired development of their imaginal discs, the primordial tissues that form the adult epidermis. Although disk tissue seems to specify normally during early embryogenesis, loss of Ipk2 activity results in increased apoptosis and impairment of proliferation during larval and pupal development. The proliferation defect is in part attributed to a reduction in JAK/STAT signaling, possibly by controlling production or secretion of the pathway's activating ligand, Unpaired. Constitutive activation of the JAK/STAT pathway downstream of Unpaired partially rescues the disk growth defects in Ipk2 mutants. Thus, IP production is essential for proliferation of the imaginal discs, in part, by regulating JAK/STAT signaling. Our work demonstrates an essential role for Ipk2 in producing inositide messengers required for imaginal disk tissue maturation and subsequent formation of adult body structures and provides molecular insights to signaling pathways involved in tissue growth and stability during development.Item type: Item , Access status: Open Access , The <i>tilt</i> ( <i>tt</i> ) mutation of <i>Drosophila melanogaster</i> maps to the cis-regulatory region of the Iroquois Complex (Iro-C) located in the <i>sosondowah</i> ( <i>sowah)</i> gene.(microPublication biology, 2025-01) Gruber, Samuel; Houtman, Arno; Reisert, Hailey; Amini, Mina; Fiore, Caroline; Gonzalez, Paula; Han, Veronica; Jazic, Aeva; Kusupholnand, Mie; Miller, Max; Nam, Jiung; Wang, Ziqin; Yu, Yang; Dong, Peter; Oak, Allen SW; Sharma, Arun; Spana, Eric PThe tilt ( tt ) mutation first described by Morgan and Bridges in 1915 has adult visible phenotypes in wing posture and vein formation. We have mapped tt to a genomic region within the sosondowah ( sowah ) gene that houses the cis-regulatory elements that control expression of the Iroquois Complex genes araucan ( ara ) and caup olican ( caup ) in the wing hinge and wing veins. Sequence analysis of the tt1 allele has identified a gtwin retrotransposon containing su(Hw) insulator binding sites within this region of sowah . We find that mutations in su(Hw) suppress the tilt phenotype, providing a potential mechanism for the insertion to affect the function of the Iroquois Complex.Item type: Item , Access status: Open Access , Clean hands are caring hands: Improving anesthesia provider hand hygiene and double-glove compliance during induction of general anesthesia.(American journal of infection control, 2025-01) Regier, Allie-Lane F; Simmons, Virginia C; Kempel, Sarah; Reynolds, Staci SBackground
Hand hygiene and double-gloving practices during induction of general anesthesia can decrease transmission of bacteria to patients and subsequent health care-associated infections; however, compliance to these practices is low.Methods
A pre- and postimplementation quality improvement design was used with Plan-Do-Study-Act cycles. Several implementation strategies were used to improve hand hygiene and double-glove compliance among anesthesia providers, including printed educational materials, video, in-person, and virtual meetings, visual reminders, audit, and feedback, and improved access to hand sanitizer dispensers in the anesthesia workstation.Results
Average hand hygiene compliance increased from 0% to 11.8% and double-gloving compliance increased from 18.5% to 34.5%. A decrease in surgical site infections was shown in the postimplementation period.Discussion
Although hand hygiene and double-gloving practices increased after the initial implementation, the improvements were not sustained long-term. Practices to support sustainability, such as routine booster sessions, may be considered.Conclusions
Incorporating these quality improvement measures into practice may improve anesthesia provider hand hygiene compliance during induction of general anesthesia and impact subsequent infection rates.Item type: Item , Access status: Open Access , Timely intervention in HMG-CoA Lyase deficiency: The role of newborn screening, metabolic management, and genomic sequencing(Molecular Genetics and Metabolism Reports, 2025-12-01) Menkovic, I; Makhijani, N; Francescatto, L; Pendyal, S; Stanley, C; Young, SP; Koeberl, DD; Niyazov, D; Stiles, AR3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency is a rare autosomal recessive metabolic disease caused by variants in the HMGCL gene leading to an impairment in leucine catabolism and ketone synthesis. In the United States, HMG-CoA lyase deficiency is listed on the recommended uniform screening panel as a core condition for newborn screening. A positive newborn screen will typically show an elevation of C5-hydroxylated species on the acylcarnitine profile using a dried-blood spot collected between 24 and 48 h of life. Initial follow-up testing generally includes a plasma acylcarnitine profile and a urine organic acid profile. Clinically, this metabolic alteration can lead to severe metabolic decompensation, presenting as hypoketotic hypoglycemia and, when left untreated, potential long-term neurological impairments. This report highlights the case of a 38-day-old male with an initial abnormal newborn screen. Follow-up testing showed moderate elevations of C5-hydroxylated and C6-dicarboxylated species on the plasma acylcarnitine profile and marked elevations of 3-hydroxy-3-methylglutaric acid, 3-methylglutaconic acid, 3-methylglutaric and 3-hydroxyisovaleric acid detected by urine organic acid analysis. These findings were consistent with a biochemical diagnosis of HMG-CoA lyase deficiency. Confirmatory molecular testing included targeted HMGCL sequencing including deletion/duplication analysis; the results of which were negative. Genome sequencing was then requested which identified a deep intronic complex variant of unknown significance within intron 1 of HGMCL. RNA sequencing studies were sent as follow-up which revealed that the level of expression of the HMGCL gene was negligible in comparison with tissue-matched controls, thus confirming the biochemical diagnosis of HMG-CoA lyase deficiency.Item type: Item , Access status: Open Access , Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies.(Nature communications, 2025-11) Küry, Sébastien; Stanton, Janelle E; van Woerden, Geeske M; Bosc-Rosati, Amélie; Hsieh, Tzung-Chien; Bray, Lise; Oloudé, Marielle; Rosenfelt, Cory; Scott-Boyer, Marie Pier; Most, Victoria; Wang, Tianyun; Papendorf, Jonas J; de Konink, Charlotte; Deb, Wallid; Vignard, Virginie; Studencka-Turski, Maja; Besnard, Thomas; Hajdukowicz, Anna M; Thiel, Franziska G; Wolfgramm, Sophie; Florenceau, Laëtitia; Cuinat, Silvestre; Marsac, Sylvain; Verrès, Yann; Dangoumau, Audrey; Poirier, Léa; Wentzensen, Ingrid M; Tuttle, Annabelle; Forster, Cara; Striesow, Johanna; Golnik, Richard; Ortiz, Damara; Jenkins, Laura; Rosenfeld, Jill A; Ziegler, Alban; Houdayer, Clara; Bonneau, Dominique; Torti, Erin; Begtrup, Amber; Monaghan, Kristin G; Mullegama, Sureni V; Volker-Touw, Catharina ML Nienke; van Gassen, Koen LI; Oegema, Renske; de Pagter, Mirjam S; Steindl, Katharina; Rauch, Anita; Ivanovski, Ivan; McDonald, Kimberly; Boothe, Emily; Dauber, Andrew; Baker, Janice; Fabie, Noelle Andrea V; Bernier, Raphael A; Turner, Tychele N; Srivastava, Siddharth; Dies, Kira A; Swanson, Lindsay C; Costin, Carrie; Abdulrazak, Alali; Jobling, Rebekah K; Pappas, John; Rabin, Rachel; Niyazov, Dmitriy; Chun-Hui Tsai, Anne; Kovak, Karen; Beck, David B; Malicdan, May Christine V; Adams, David R; Wolfe, Lynne; Ganetzky, Rebecca D; Muraresku, Colleen C; Babikyan, Davit; Sedláček, Zdeněk; Hančárová, Miroslava; Timberlake, Andrew T; Saif, Hind Al; Nestler, Berkley; King, Kayla; Hajianpour, MJ; Costain, Gregory; Prendergast, D'Arcy; Li, Chumei; Geneviève, David; Vitobello, Antonio; Sorlin, Arthur; Philippe, Christophe; Harel, Tamar; Toker, Ori; Sabir, Ataf; Lim, Derek; Hamilton, Mark J; Bryson, Lisa J; Cleary, Elaine; Weber, Sacha; Hoffman, Trevor L; Cueto-González, Anna M; Tizzano, Eduardo F; Gómez-Andrés, David; Codina-Solà, Marta; Ververi, Athina; Pavlidou, Efterpi; Lambropoulos, Alexandros; Garganis, Kyriakos; Rio, Marlène; Levy, Jonathan; Langas, Sarah J; McRae, Anne M; Lessard, Mathieu K; D'Agostino, Maria Daniela; De Bie, Isabelle; Wegler, Meret; Abou Jamra, Rami; Kamphausen, Susanne B; Bothe, Viktoria; Potocki, Lorraine; Olinger, Eric; Sznajer, Yves; Wiame, Elsa; Thompson, Michelle L; Schroeder, Molly C; Gooch, Catherine; Smith, Raphael A; Pandya, Arti; Busch, Larissa M; Völker, Uwe; Hammer, Elke; Wende, Kristian; Cogné, Benjamin; Isidor, Bertrand; Meiler, Jens; Ripoll, Clémentine; Bigou, Stéphanie; Laumonnier, Frédéric; Hildebrand, Peter W; Eichler, Evan E; McWalter, Kirsty; Krawitz, Peter M; Roux-Dalvai, Florence; Elgersma, Ype; Marcoux, Julien; Bousquet, Marie-Pierre; Droit, Arnaud; Poschmann, Jeremie; Grabrucker, Andreas M; Bolduc, Francois V; Bézieau, Stéphane; Ebstein, Frédéric; Krüger, ElkeNeurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor cell stemness, causing deficits in higher-order functions, including learning and locomotion. Pharmacological targeting of integrated stress response kinases reveals a mechanistic link between proteotoxic stress and spontaneous type I interferon activation. These findings expand our understanding of proteasome-dependent quality control in neurodevelopment and suggest potential therapeutic strategies for neurodevelopmental proteasomopathies.Item type: Item , Access status: Open Access , Normative values of ankle strength and its importance for rehabilitation and return to activity: A cross-sectional study.(World journal of orthopedics, 2025-10) da Fonseca, Lucas Furtado; Jeyaraman, Madhan; Jeyaraman, Naveen; Inojossa, Thiago Resende; Maciel, Eduardo Souza; de Cesar Netto, Cesar; Mansur, Nacime Salomão; Astur, Diego CostaBackground
Ankle normative values are limited compared to isokinetic knee assessments. Chronic ankle instability correlates with agonist-antagonist imbalances, decreased evertor/invertor ratio, and plantar flexion deficits. Strengthening programs targeting evertor/invertor and dorsiflexor/plantar flexor balance help reduce injury recurrence. Bilateral neuromuscular deficits compromise the contralateral side, rendering healthy limbs unsuitable as recovery references. Defining normative healthy ankle parameters is crucial for establishing precise limits in non-surgical treatments and sports return criteria. While the limb symmetry index (LSI) is used for knees with a cutoff of > 90%, no such standardization exists for the ankle.Aim
To comprehensively evaluate isokinetic ankle strength profiles in non-athletic individuals.Methods
This is a cross-sectional study. Two hundred ankles were evaluated using the Biodex 3 System to assess eversion, inversion, dorsiflexion, and plantar flexion. Healthy individuals with an active lifestyle and no previous injuries were evaluated. The Maximum Torque, Agonist/Antagonist Ratio, LSI, and Muscular Deficiency Index (MDI) and the correlation with demographic variables were evaluated.Results
The mean age (mean ± SD) was 38.5 ± 13.5 years, and the body mass index (BMI) was 25.8 ± 4.2 in 69 men and 31 women. The mean maximum torque values by gender were (mean ± SD): 22.3 ± 6.6 female (F) and 33.4 ± 9.9 male (M) N/m for eversion; 30.10 ± 10.0 (F) and 37.0 ± 11.6 N/m (M) for inversion, 37.4 ± 10.0 (F) and 53.6 ± 13.0 N/m (M) for dorsiflexion, and 100.4 ± 37.2 (F) and 158.1 ± 33.4 (M) N/m for flexion. There was no correlation between age or BMI and maximum torque. The evertors/invertors ratio was 88.8%, and the dorsiflexors/plantar flexors ratio was 36.1%. The MDI and LSI were balanced between sides for every movement, having an average global difference of less than 10%.Conclusion
These findings provide gender-specific normative isokinetic values for the ankle in healthy, physically active adults. These reference parameters-especially LSI and MDI above 90%-can support clinical decision-making in rehabilitation planning and return-to-sport assessment, offering objective benchmarks for functional recovery.Item type: Item , Access status: Open Access , Discrete Superconvergence Analysis for Quantum Magnus Algorithms of Unbounded Hamiltonian SimulationFang, Di; Borns-Weil, Yonah; Zhang, JiaqiItem type: Item , Access status: Open Access , A molecular cell atlas of mouse lemur, an emerging model primate.(Nature, 2025-08) Tabula Microcebus Consortium; Ezran, Camille; Liu, Shixuan; Chang, Stephen; Ming, Jingsi; Botvinnik, Olga; Penland, Lolita; Tarashansky, Alexander; de Morree, Antoine; Travaglini, Kyle J; Zhao, Jia; Wang, Gefei; Hasegawa, Kazuteru; Sin, Hosu; Sit, Rene; Okamoto, Jennifer; Sinha, Rahul; Zhang, Yue; Karanewsky, Caitlin J; Pendleton, Jozeph L; Morri, Maurizio; Perret, Martine; Aujard, Fabienne; Stryer, Lubert; Artandi, Steven; Fuller, Margaret T; Weissman, Irving L; Rando, Thomas A; Ferrell, James E; Wang, Bo; De Vlaminck, Iwijn; Yang, Can; Casey, Kerriann M; Albertelli, Megan A; Pisco, Angela Oliveira; Karkanias, Jim; Neff, Norma; Wu, Angela Ruohao; Quake, Stephen R; Krasnow, Mark AMouse lemurs are the smallest and fastest reproducing primates, as well as one of the most abundant, and they are emerging as a model organism for primate biology, behaviour, health and conservation. Although much has been learnt about their ecology and phylogeny in Madagascar and their physiology, little is known about their cellular and molecular biology. Here we used droplet-based and plate-based single-cell RNA sequencing to create Tabula Microcebus, a transcriptomic atlas of 226,000 cells from 27 mouse lemur organs opportunistically obtained from four donors clinically and histologically characterized. Using computational cell clustering, integration and expert cell annotation, we define and biologically organize more than 750 lemur molecular cell types and their full gene expression profiles. This includes cognates of most classical human cell types, including stem and progenitor cells, and differentiating cells along the developmental trajectories of spermatogenesis, haematopoiesis and other adult tissues. We also describe dozens of previously unidentified or sparsely characterized cell types. We globally compare expression profiles to define the molecular relationships of cell types across the body, and explore primate cell and gene expression evolution by comparing lemur transcriptomes to those of human, mouse and macaque. This reveals cell-type-specific patterns of primate specialization and many cell types and genes for which the mouse lemur provides a better human model than mouse1. The atlas provides a cellular and molecular foundation for studying this model primate and establishes a general approach for characterizing other emerging model organisms.Item type: Item , Access status: Open Access , Mouse lemur cell atlas informs primate genes, physiology and disease.(Nature, 2025-08) Ezran, Camille; Liu, Shixuan; Chang, Stephen; Ming, Jingsi; Guethlein, Lisbeth A; Wang, Michael FZ; Dehghannasiri, Roozbeh; Olivieri, Julia; Frank, Hannah K; Tarashansky, Alexander; Koh, Winston; Jing, Qiuyu; Botvinnik, Olga; Antony, Jane; Tabula Microcebus Consortium; Pisco, Angela Oliveira; Karkanias, Jim; Yang, Can; Ferrell, James E; Boyd, Scott D; Parham, Peter; Long, Jonathan Z; Wang, Bo; Salzman, Julia; De Vlaminck, Iwijn; Wu, Angela Ruohao; Quake, Stephen R; Krasnow, Mark AMouse lemurs (Microcebus spp.) are an emerging primate model organism, but their genetics, cellular and molecular biology remain largely unexplored. In an accompanying paper1, we performed large-scale single-cell RNA sequencing of 27 organs from mouse lemurs. We identified more than 750 molecular cell types, characterized their transcriptomic profiles and provided insight into primate evolution of cell types. Here we use the generated atlas to characterize mouse lemur genes, physiology, disease and mutations. We uncover thousands of previously unidentified lemur genes and hundreds of thousands of new splice junctions including over 85,000 primate splice junctions missing in mice. We systematically explore the lemur immune system by comparing global expression profiles of key immune genes in health and disease, and by mapping immune cell development, trafficking and activation. We characterize primate-specific and lemur-specific physiology and disease, including molecular features of the immune program, lemur adipocytes and metastatic endometrial cancer that resembles the human malignancy. We present expression patterns of more than 400 primate genes missing in mice, many with similar expression patterns to humans and some implicated in human disease. Finally, we provide an experimental framework for reverse genetic analysis by identifying naturally occurring nonsense mutations in three primate immune genes missing in mice and by analysing their transcriptional phenotypes. This work establishes a foundation for molecular and genetic analyses of mouse lemurs and prioritizes primate genes, isoforms, physiology and disease for future study.Item type: Item , Access status: Open Access , Model Uncertainty and Missing Data: An Objective Bayesian Perspective (with Discussion)(Bayesian Analysis, 2025-12-01) García-Donato, Gonzalo; Castellanos, María Eugenia; Cabras, Stefano; Quirós, Alicia; Forte, AnabelItem type: Item , Access status: Open Access , Generalized Beta Mixtures of Gaussians(Advances in Neural Information Processing Systems, 2011) Armagan, A; Dunson, DB; Clyde, MAIn recent years, a rich variety of shrinkage priors have been proposed that have great promise in addressing massive regression problems. In general, these new priors can be expressed as scale mixtures of normals, but have more complex forms and better properties than traditional Cauchy and double exponential priors. We first propose a new class of normal scale mixtures through a novel generalized beta distribution that encompasses many interesting priors as special cases. This encompassing framework should prove useful in comparing competing priors, considering properties and revealing close connections. We then develop a class of variational Bayes approximations through the new hierarchy presented that will scale more efficiently to the types of truly massive data sets that are now encountered routinely.Item type: Item , Access status: Open Access , Multimodality word-finding distinctions in cortical stimulation mapping.(Neurosurgery, 2013) Serafini, S; Clyde, MA; Tolson, M; Haglund, MMBACKGROUND: Cortical stimulation mapping (CSM) commonly uses visual naming to determine resection margins in the dominant hemisphere of patients with epilepsy. Visual naming alone may not identify all language sites in resection-prone areas, prompting additional tasks for comprehensive language mapping. OBJECTIVE: To demonstrate word-finding distinctions between visual, auditory, and reading modalities during CSM and the percentage of modality-specific language sites within dominant hemisphere subregions. METHODS: Twenty-eight patients with epilepsy underwent CSM by the use of visual, auditory, and sentence-completion tasks. Hierarchical logistic regression analyzed errors to identify language sites and provide modality-specific percentages within subregions. RESULTS: The percentage of sites classified as language sites based on auditory naming was twice as high in anterior temporal regions compared with visual naming, marginally higher in posterior temporal areas, and comparable in parietal regions. Sentence completion was comparable to visual and auditory naming in parietal regions and lower in most temporal areas. Of 470 sites tested with both visual and auditory naming, 95 sites were distinctly auditory, whereas 48 sites were distinctly visual. The remaining sites overlapped. CONCLUSION: Distinct cortical areas were found for distinct input modalities, with language sites in anterior tip regions found most often by using auditory naming. The vulnerability of anterior temporal tip regions to resection in this population and distinct sites for each modality suggest that a multimodality approach may be needed to spare crucial language sites, if sparing those sites can be shown to significantly reduce the rate of postoperative language deficits without sacrificing seizure control.Item type: Item , Access status: Open Access , Combined use of an electrostatic precipitator and a high-efficiency particulate air filter in building ventilation systems: Effects on cardiorespiratory health indicators in healthy adults.(Indoor air, 2018-05) Day, DB; Xiang, J; Mo, J; Clyde, MA; Weschler, CJ; Li, F; Gong, J; Gong, J; Chung, M; Zhang, Y; Zhang, JHigh-efficiency particulate air (HEPA) filtration in combination with an electrostatic precipitator (ESP) can be a cost-effective approach to reducing indoor particulate exposure, but ESPs produce ozone. The health effect of combined ESP-HEPA filtration has not been examined. We conducted an intervention study in 89 volunteers. At baseline, the air-handling units of offices and residences for all subjects were comprised of coarse, ESP, and HEPA filtration. During the 5-week long intervention, the subjects were split into 2 groups, 1 with just the ESP removed and the other with both the ESP and HEPA removed. Each subject was measured for cardiopulmonary risk indicators once at baseline, twice during the intervention, and once 2 weeks after baseline conditions were restored. Measured indoor and outdoor PM2.5 and ozone concentrations, coupled with time-activity data, were used to calculate exposures. Removal of HEPA filters increased 24-hour mean PM2.5 exposure by 38 (95% CI: 31, 45) μg/m3 . Removal of ESPs decreased 24-hour mean ozone exposure by 2.2 (2.0, 2.5) ppb. No biomarkers were significantly associated with HEPA filter removal. In contrast, ESP removal was associated with a -16.1% (-21.5%, -10.4%) change in plasma-soluble P-selectin and a -3.0% (-5.1%, -0.8%) change in systolic blood pressure, suggesting reduced cardiovascular risks.Item type: Item , Access status: Open Access , Age modification of ozone associations with cardiovascular disease risk in adults: a potential role for soluble P-selectin and blood pressure.(Journal of thoracic disease, 2018-07) Day, Drew B; Clyde, Merlise A; Xiang, Jianbang; Li, Feng; Cui, Xiaoxing; Mo, Jinhan; Gong, Jicheng; Weschler, Charles J; Zhang, Yinping; Zhang, Junfeng JimBackground
Studies have suggested that age increases susceptibility to ozone-associated mortality, but the underlying mechanisms are unclear. In a previous study, personal exposure to ozone was significantly associated with a platelet activation biomarker, plasma soluble P-selectin (sCD62P), and blood pressure in 89 healthy adults, aged 22-52 years. The present study examines whether age modifies these associations in the same adults and in additional adults.Methods
Interaction terms of age and exposure were analyzed using hierarchical Bayesian mixed effects ridge regressions. Data from a similar additional study involving 71 healthy participants, aged 19-26 years, were pooled with the data from the first study to evaluate age effect modification when more young adults were added to the analysis.Results
In the 89 adults, significant age interactions were observed for past 24-hour and 2-week ozone exposures and sCD62P. Based on the pooled data (89 plus 71 adults), a 10 ppb increase in 24-hour ozone exposure was associated with increases in sCD62P and systolic blood pressure (SBP) by 22.3% (95% CI: 14.3%, 31.2%) and 1.35 (-0.18, 2.84) mmHg, respectively, at age 25; these values increased to 48.6% (32.7%, 65.1%) and 4.98 (2.56, 7.35) mmHg, respectively, at age 40.Conclusions
These results mechanistically suggest that increasing age enhances cardiovascular effects of ozone.Item type: Item , Access status: Open Access , AAPM Truth-based CT (TrueCT) reconstruction grand challenge.(Medical physics, 2025-04) Abadi, Ehsan; Segars, W Paul; Felice, Nicholas; Sotoudeh-Paima, Saman; Hoffman, Eric A; Wang, Xiao; Wang, Wei; Clark, Darin; Ye, Siqi; Jadick, Giavanna; Fryling, Milo; Frush, Donald P; Samei, EhsanBackground
This Special Report summarizes the 2022, AAPM grand challenge on Truth-based CT image reconstruction.Purpose
To provide an objective framework for evaluating CT reconstruction methods using virtual imaging resources consisting of a library of simulated CT projection images of a population of human models with various diseases.Methods
Two hundred unique anthropomorphic, computational models were created with varied diseases consisting of 67 emphysema, 67 lung lesions, and 66 liver lesions. The organs were modeled based on clinical CT images of real patients. The emphysematous regions were modeled using segmentations from patient CT cases in the COPDGene Phase I dataset. For the lung and liver lesion cases, 1-6 malignant lesions were created and inserted into the human models, with lesion diameters ranging from 5.6 to 21.9 mm for lung lesions and 3.9 to 14.9 mm for liver lesions. The contrast defined between the liver lesions and liver parenchyma was 82 ± 12 HU, ranging from 50 to 110 HU. Similarly, the contrast between the lung lesions and the lung parenchyma was defined as 781 ± 11 HU, ranging from 725 to 805 HU. For the emphysematous regions, the defined HU values were -950 ± 17 HU ranging from -918 to -979 HU. The developed human models were imaged with a validated CT simulator. The resulting CT sinograms were shared with the participants. The participants reconstructed CT images from the sinograms and sent back their reconstructed images. The reconstructed images were then scored by comparing the results against the corresponding ground truth values. The scores included both task-generic (root mean square error [RMSE] and structural similarity matrix [SSIM]), and task-specific (detectability index [d'] and lesion volume accuracy) metrics. For the cases with multiple lesions, the measured metric was averaged across all the lesions. To combine the metrics with each other, each metric was normalized to a range of 0 to 1 per disease type, with "0" and "1" being the worst and best measured values across all cases of the disease type for all received reconstructions.Results
The True-CT challenge attracted 52 participants, out of which 5 successfully completed the challenge and submitted the requested 200 reconstructions. Across all participants and disease types, SSIM absolute values ranged from 0.22 to 0.90, RMSE from 77.6 to 490.5 HU, d' from 0.1 to 64.6, and volume accuracy ranged from 1.2 to 753.1 mm3. The overall scores demonstrated that participant "A" had the best performance in all categories, except for the metrics of d' for lung lesions and RMSE for liver lesions. Participant "A" had an average normalized score of 0.41 ± 0.22, 0.48 ± 0.32, and 0.42 ± 0.33 for the emphysema, lung lesion, and liver lesion cases, respectively.Conclusions
The True-CT challenge successfully enabled objective assessment of CT reconstructions with the unique advantage of access to a diverse population of diseased human models with known ground truth. This study highlights the significant potential of virtual imaging trials in objective assessment of medical imaging technologies.Item type: Item , Access status: Open Access , Association of Vasopressor Choice with Clinical and Functional Outcomes Following Moderate to Severe Traumatic Brain Injury: A TRACK-TBI Study.(Neurocritical care, 2022-02) Toro, Camilo; Temkin, Nancy; Barber, Jason; Manley, Geoffrey; Jain, Sonia; Ohnuma, Tetsu; Komisarow, Jordan; Foreman, Brandon; Korley, Frederick K; Vavilala, Monica S; Laskowitz, Daniel T; Mathew, Joseph P; Hernandez, Adrian; Sampson, John; James, Michael L; Goldstein, Benjamin A; Markowitz, Amy J; Krishnamoorthy, Vijay; TRACK-TBI InvestigatorsBackground
Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury.Methods
We conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score < 13) who were admitted to the intensive care unit and received an intravenous vasopressor within 48 h of admission. The primary exposure was initial vasopressor choice (phenylephrine versus norepinephrine), and the primary outcome was 6-month Glasgow Outcomes Scale Extended (GOSE), with the following secondary outcomes: length of hospital stay, length of intensive care unit stay, in-hospital mortality, new requirement for dialysis, and 6-month Disability Rating Scale. Regression analysis was used to assess differences in outcomes between patients exposed to norepinephrine versus phenylephrine, with propensity weighting to address selection bias due to the nonrandom allocation of the treatment groups and patient dropout.Results
The final study sample included 156 patients, of whom 79 (51%) received norepinephrine, 69 (44%) received phenylephrine, and 8 (5%) received an alternate drug as their initial vasopressor. 121 (77%) of patients were men, with a mean age of 43.1 years. Of patients receiving norepinephrine as their initial vasopressor, 32% had a favorable outcome (GOSE 5-8), whereas 40% of patients receiving phenylephrine as their initial vasopressor had a favorable outcome. Compared with phenylephrine, exposure to norepinephrine was not significantly associated with improved 6-month GOSE (weighted odds ratio 1.40, 95% confidence interval 0.66-2.96, p = 0.37) or any secondary outcome.Conclusions
The majority of patients with moderate to severe TBI received either phenylephrine or norepinephrine as first-line agents for blood pressure support following brain injury. Initial choice of norepinephrine, compared with phenylephrine, was not associated with improved clinical or functional outcomes.Item type: Item , Access status: Open Access , Current Concepts in Cranial Reconstruction: Review of Alloplastic Materials.(Plastic and reconstructive surgery. Global open, 2022-08) Johnston, Darin T; Lohmeier, Steven J; Langdell, Hannah C; Pyfer, Bryan J; Komisarow, Jordan; Powers, David B; Erdmann, DetlevCranioplasty for acquired cranial defects can be complex and challenging. Benefits include improved cosmesis, protection of intracranial structures, and restoration of neurocognitive function. These defects can be reconstructed with preserved craniectomy bone flaps, split autografts, or alloplastic materials. When alloplastic cranioplasty is planned, the material should be carefully selected. There is confusion on which material should be used in certain scenarios, particularly in composite defects.Methods
The PubMed database was used to conduct a nonsystematic review of literature related to these materials and the following factors: time required in preoperative planning and fabrication, intraoperative time, feasibility of intraoperative modification, fixation method (direct or indirect), implant cost, overall complication rate, and surgical revision rates.Results
Surgical revision rates for alloplastic materials range from 10% to 23%. Retention of titanium mesh at 4 years is 85% in composite reconstruction with free fasciocutaneous and free myocutaneous flaps. In composite reconstruction with locoregional and free muscle flaps, the retention of titanium mesh at 4 years is 47%. The retention of nontitanium and nonpreserved autogenous reconstruction is 72% and 82%, respectively.Conclusions
Alloplastic materials should be considered for reconstruction of large (>100 cm2) cranial defects, especially for adult patients younger than 30 years, and all patients with bone flaps that are fragmented or have been cryopreserved for an extended period. Preformed titanium mesh provides a favorable primary reconstructive option when a staged reconstruction is not possible or indicated but should be avoided in composite defects reconstructed with locoregional scalp and free muscle flaps.Item type: Item , Access status: Open Access , Incidence and Clinical Impact of Myocardial Injury Following Traumatic Brain Injury: A Pilot TRACK-TBI Study.(Journal of neurosurgical anesthesiology, 2022-04) Krishnamoorthy, Vijay; Manley, Geoffrey T; Jain, Sonia; Sun, Shelly; Foreman, Brandon; Komisarow, Jordan; Laskowitz, Daniel T; Mathew, Joseph P; Hernandez, Adrian; James, Michael L; Vavilala, Monica S; Markowitz, Amy J; Korley, Frederick K; TRACK-TBI InvestigatorsBackground
Traumatic brain injury (TBI) is a major global health problem. Little research has addressed extracranial organ dysfunction following TBI, particularly myocardial injury. Using a sensitive marker of myocardial injury-high sensitivity troponin (hsTn)-we examined the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI.Methods
We conducted a pilot cohort study of 133 adult (age above 17 y) subjects enrolled in the TRACK-TBI 18-center prospective cohort study. Descriptive statistics were used to examine the incidence of myocardial injury (defined as hsTn >99th percentile for a standardized reference population) across TBI severities, and to explore the association of myocardial injury with a 6-month extended Glasgow Outcome Score among patients with moderate-severe TBI.Results
The mean (SD) age of the participants was 44 (17) years, and 87 (65%) were male. Twenty-six patients (20%) developed myocardial injury following TBI; myocardial injury was present in 15% of mild TBI patients and 29% of moderate-severe TBI patients (P=0.13). Median (interquartile range) hsTn values were 3.8 ng/L (2.1, 9.0), 5.8 ng/L (4.5, 34.6), and 10.2 ng/L (3.0, 34.0) in mild, moderate, and severe TBI participants, respectively (P=0.04). Overall, 11% of participants with moderate-severe TBI and myocardial injury experienced a good outcome (6-mo extended Glasgow Outcome Score≥5) at 6 months, compared with 65% in the group that did not experience myocardial injury (P=0.01).Conclusions
Myocardial injury is common following TBI, with a likely dose-response relationship with TBI severity. Early myocardial injury was associated with poor 6-month clinical outcomes following moderate-severe TBI.