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2. Current Status and Principles for the Treatment and Prevention of Diabetic Foot Ulcers in the Cardiovascular Patient Population: A Scientific Statement From the American Heart Association.

Author

Gallagher, Katherine, Mills, Joseph, Armstrong, David, Conte, Michael, Kirsner, Robert, Minc, Samantha, Plutzky, Jorge, Southerland, Kevin, and Tomic-Canic, Marjana

Subjects
AHA Scientific Statements, amputation, surgical, cardiovascular diseases, diabetes, type 2, diabetic foot, health care disparities, health inequities, peripheral arterial disease, Humans, United States, Diabetic Foot, Diabetes Mellitus, Type 2, Cardiovascular Diseases, American Heart Association
Abstract

Despite the known higher risk of cardiovascular disease in individuals with type 2 diabetes, the pathophysiology and optimal management of diabetic foot ulcers (DFUs), a leading complication associated with diabetes, is complex and continues to evolve. Complications of type 2 diabetes, such as DFUs, are a major cause of morbidity and mortality and the leading cause of major lower extremity amputation in the United States. There has recently been a strong focus on the prevention and early treatment of DFUs, leading to the development of multidisciplinary diabetic wound and amputation prevention clinics across the country. Mounting evidence has shown that, despite these efforts, amputations associated with DFUs continue to increase. Furthermore, due to increasing patient complexity of management secondary to comorbid conditions, such as cardiovascular disease, the management of peripheral artery disease associated with DFUs has become increasingly difficult, and care delivery is often episodic and fragmented. Although structured, process-specific approaches exist at individual institutions for the management of DFUs in the cardiovascular patient population, there is insufficient awareness of these principles in the general medicine communities. Furthermore, there is growing interest in better understanding the mechanistic underpinnings of DFUs to better define personalized medicine to improve outcomes. The goals of this scientific statement are to provide salient background information on the complex pathogenesis and current management of DFUs in cardiovascular patients, to guide therapeutic and preventive strategies and future research directions, and to inform public policy makers on health disparities and other barriers to improving and advancing care in this expanding patient population.

Published
2024

3. Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target

Author

Roychowdhury, Tanmoy, Klarin, Derek, Levin, Michael G., Spin, Joshua M., Rhee, Yae Hyun, Deng, Alicia, Headley, Colwyn A., Tsao, Noah L., Gellatly, Corry, Zuber, Verena, Shen, Fred, Hornsby, Whitney E., Laursen, Ina Holst, Verma, Shefali S., Locke, Adam E., Einarsson, Gudmundur, Thorleifsson, Gudmar, Graham, Sarah E., Dikilitas, Ozan, Pattee, Jack W., Judy, Renae L., Pauls-Verges, Ferran, Nielsen, Jonas B., Wolford, Brooke N., Brumpton, Ben M., Dilmé, Jaume, Peypoch, Olga, Juscafresa, Laura Calsina, Edwards, Todd L., Li, Dadong, Banasik, Karina, Brunak, Søren, Jacobsen, Rikke L., Garcia-Barrio, Minerva T., Zhang, Jifeng, Rasmussen, Lars M., Lee, Regent, Handa, Ashok, Wanhainen, Anders, Mani, Kevin, Lindholt, Jes S., Obel, Lasse M., Strauss, Ewa, Oszkinis, Grzegorz, Nelson, Christopher P., Saxby, Katie L., van Herwaarden, Joost A., van der Laan, Sander W., van Setten, Jessica, Camacho, Mercedes, Davis, Frank M., Wasikowski, Rachael, Tsoi, Lam C., Gudjonsson, Johann E., Eliason, Jonathan L., Coleman, Dawn M., Henke, Peter K., Ganesh, Santhi K., Chen, Y. Eugene, Guan, Weihua, Pankow, James S., Pankratz, Nathan, Pedersen, Ole B., Erikstrup, Christian, Tang, Weihong, Hveem, Kristian, Gudbjartsson, Daniel, Gretarsdottir, Solveig, Thorsteinsdottir, Unnur, Holm, Hilma, Stefansson, Kari, Ferreira, Manuel A., Baras, Aris, Kullo, Iftikhar J., Ritchie, Marylyn D., Christensen, Alex H., Iversen, Kasper K., Eldrup, Nikolaj, Sillesen, Henrik, Ostrowski, Sisse R., Bundgaard, Henning, Ullum, Henrik, Burgess, Stephen, Gill, Dipender, Gallagher, Katherine, Sabater-Lleal, Maria, Surakka, Ida, Jones, Gregory T., Bown, Matthew J., Tsao, Philip S., Willer, Cristen J., and Damrauer, Scott M.

Published
2023
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4. Breast MRI Background Parenchymal Enhancement Categorization Using Deep Learning: Outperforming the Radiologist.

Author

Eskreis-Winkler, Sarah, Sutton, Elizabeth, DAlessio, Donna, Gallagher, Katherine, Saphier, Nicole, Stember, Joseph, Martinez, Danny, Pinker, Katja, and Morris, Elizabeth

Subjects
artificial intelligence, background parenchymal enhancement, breast MRI, cancer risk assessment, deep learning, Artificial Intelligence, Breast Neoplasms, Deep Learning, Female, Humans, Magnetic Resonance Imaging, Radiologists, Retrospective Studies
Abstract

BACKGROUND: Background parenchymal enhancement (BPE) is assessed on breast MRI reports as mandated by the Breast Imaging Reporting and Data System (BI-RADS) but is prone to inter and intrareader variation. Semiautomated and fully automated BPE assessment tools have been developed but none has surpassed radiologist BPE designations. PURPOSE: To develop a deep learning model for automated BPE classification and to compare its performance with current standard-of-care radiology report BPE designations. STUDY TYPE: Retrospective. POPULATION: Consecutive high-risk patients (i.e. >20% lifetime risk of breast cancer) who underwent contrast-enhanced screening breast MRI from October 2013 to January 2019. The study included 5224 breast MRIs, divided into 3998 training, 444 validation, and 782 testing exams. On radiology reports, 1286 exams were categorized as high BPE (i.e., marked or moderate) and 3938 as low BPE (i.e., mild or minimal). FIELD STRENGTH/SEQUENCE: A 1.5 T or 3 T system; one precontrast and three postcontrast phases of fat-saturated T1-weighted dynamic contrast-enhanced imaging. ASSESSMENT: Breast MRIs were used to develop two deep learning models (Slab artificial intelligence (AI); maximum intensity projection [MIP] AI) for BPE categorization using radiology report BPE labels. Models were tested on a heldout test sets using radiology report BPE and three-reader averaged consensus as the reference standards. STATISTICAL TESTS: Model performance was assessed using receiver operating characteristic curve analysis. Associations between high BPE and BI-RADS assessments were evaluated using McNemars chi-square test (α* = 0.025). RESULTS: The Slab AI model significantly outperformed the MIP AI model across the full test set (area under the curve of 0.84 vs. 0.79) using the radiology report reference standard. Using three-reader consensus BPE labels reference standard, our AI model significantly outperformed radiology report BPE labels. Finally, the AI model was significantly more likely than the radiologist to assign high BPE to suspicious breast MRIs and significantly less likely than the radiologist to assign high BPE to negative breast MRIs. DATA CONCLUSION: Fully automated BPE assessments for breast MRIs could be more accurate than BPE assessments from radiology reports. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Published
2022

7. Biofilm-derived oxylipin 10-HOME mediated immune response in women with breast implants

Author

Bauer, Tyler M. and Gallagher, Katherine A.

Subjects
Women, T cells, Prosthesis, Implants, Artificial, Immune response, Health care industry
Abstract

Breast implant illness (BII) is a poorly understood disease in which patients develop symptoms typical of autoimmune conditions following breast implantation. There is no known underlying cause, and patients often resort to breast implant removal and capsulectomy to alleviate symptoms. In this issue of the JCI, Khan and colleagues examined 86 breast explants from patients that reported BII symptoms and 55 control explants. The BII group showed a disproportionally high degree of biofilm, which was associated with oxylipin (10-HOME) on the implant surfaces. Injections of 10-HOME in the mammary fat pad of a murine model recapitulated BII symptoms and increased Th1 cell populations. Notably, macrophages in the periprosthetic tissue from BII patients were more likely to exhibit a proinflammatory phenotype, and naive T cells exposed to 10-HOME caused naive macrophages to differentiate to a proinflammatory phenotype. This work provides a pathophysiologic mechanism for a currently understudied and poorly characterized disease., Breast implant illness is rare and poorly understood While silicone was long thought to be biologically inert, there has been a growing interest in potential associations between various diseases and [...]

Published
2024
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9. Transforming the Future of Surgeon-Scientists

Author

Ladner, Daniela P., Goldstein, Allan M., Billiar, Timothy R., Cameron, Andrew M., Carpizo, Darren R., Chu, Daniel I., Coopersmith, Craig M., DeMatteo, Ronald P., Feng, Sandy, Gallagher, Katherine A., Gillanders, William E., Lal, Brajesh K., Lipshutz, Gerald S., Liu, Annie, Maier, Ronald V., Mittendorf, Elizabeth A., Morris, Arden M., Sicklick, Jason K., Velazquez, Omaida C., Whitson, Bryan A., Wilke, Lee G., Yoon, Sam S., Zeiger, Martha A., Farmer, Diana L., and Hwang, E. Shelley

Published
2024
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12. Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

Author

Audu, Christopher O., Melvin, William J., Joshi, Amrita D., Wolf, Sonya J., Moon, Jadie Y., Davis, Frank M., Barrett, Emily C., Mangum, Kevin D., Deng, Hongping, Xing, Xianying, Wasikowski, Rachel, Tsoi, Lam C., Sharma, Sriganesh B., Bauer, Tyler M., Shadiow, James, Corriere, Matthew A., Obi, Andrea T., Kunkel, Steven L., Levi, Benjamin, Moore, Bethany B., Gudjonsson, Johann E., Smith, Andrew M., and Gallagher, Katherine A.

Published
2022
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13. Prevalence of immunoglobulin G and M to SARS-CoV-2 and other human coronaviruses in The Democratic Republic of Congo, Sierra Leone, and Uganda: A longitudinal study

Author

Lawal, Bolarinde J., Gallagher, Katherine E., Kitonsa, Jonathan, Tindanbil, Daniel, Kasonia, Kambale, Drammeh, Abdoulie, Lowe, Brett, Mukadi-Bamuleka, Daniel, Patterson, Catriona, Greenwood, Brian, Samai, Mohamed, Leigh, Bailah, Tetteh, Kevin K.A., Ruzagira, Eugene, Watson-Jones, Deborah, and Kavunga-Membo, Hugo

Published
2023
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14. Ultrafast dynamic contrast-enhanced breast MRI may generate prognostic imaging markers of breast cancer.

Author

Onishi, Natsuko, Sadinski, Meredith, Hughes, Mary, Ko, Eun, Gibbs, Peter, Gallagher, Katherine, Fung, Maggie, Hunt, Theodore, Martinez, Danny, Shukla-Dave, Amita, Sutton, Elizabeth, and Morris, Elizabeth

Subjects
Bolus arrival time, Breast carcinoma, Ductal carcinoma in situ, Invasive lobular carcinoma, Maximum slope, Molecular subtype, Ultrafast dynamic contrast-enhanced magnetic resonance imaging, Adult, Aged, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Contrast Media, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Middle Aged, Prognosis, Retrospective Studies, Young Adult
Abstract

BACKGROUND: Ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics. METHODS: Consecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4-6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7-4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values

Published
2020

15. Differentiation between subcentimeter carcinomas and benign lesions using kinetic parameters derived from ultrafast dynamic contrast-enhanced breast MRI.

Author

Onishi, Natsuko, Sadinski, Meredith, Gibbs, Peter, Gallagher, Katherine, Hughes, Mary, Ko, Eun, Dashevsky, Brittany, Shanbhag, Dattesh, Fung, Maggie, Hunt, Theodore, Martinez, Danny, Shukla-Dave, Amita, Sutton, Elizabeth, and Morris, Elizabeth

Subjects
Breast, Cancer, Differential diagnosis, Kinetics, Magnetic resonance imaging, Adult, Breast, Breast Neoplasms, Contrast Media, Diagnosis, Differential, Female, Humans, Image Enhancement, Kinetics, Magnetic Resonance Imaging, Middle Aged, Retrospective Studies
Abstract

OBJECTIVES: This study aims to evaluate ultrafast DCE-MRI-derived kinetic parameters that reflect contrast agent inflow effects in differentiating between subcentimeter BI-RADS 4-5 breast carcinomas and benign lesions. METHODS: We retrospectively reviewed consecutive 3-T MRI performed from February to October 2017, during which ultrafast DCE-MRI was performed as part of a hybrid clinical protocol with conventional DCE-MRI. In total, 301 female patients with 369 biopsy-proven breast lesions were included. Ultrafast DCE-MRI was acquired continuously over approximately 60 s (temporal resolution, 2.7-7.1 s/phase) starting simultaneously with the start of contrast injection. Four ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS], contrast enhancement ratio [CER], bolus arrival time [BAT], and initial area under gadolinium contrast agent concentration [IAUGC]) and one conventional DCE-MRI-derived kinetic parameter (signal enhancement ratio [SER]) were calculated for each lesion. Wilcoxon rank sum test or Fishers exact test was performed to compare kinetic parameters, volume, diameter, age, and BI-RADS morphological descriptors between subcentimeter carcinomas and benign lesions. Univariate/multivariate logistic regression analyses were performed to determine predictive parameters for subcentimeter carcinomas. RESULTS: In total, 125 lesions (26 carcinomas and 99 benign lesions) were identified as BI-RADS 4-5 subcentimeter lesions. Subcentimeter carcinomas demonstrated significantly larger MS and SER and shorter BAT than benign lesions (p = 0.0117, 0.0046, and 0.0102, respectively). MS, BAT, and age were determined as significantly predictive for subcentimeter carcinoma (p = 0.0208, 0.0023, and

Published
2020

16. Validation of the UCLA PTSD Reaction Index for DSM-5: A Developmentally Informed Assessment Tool for Youth

Author

Kaplow, Julie B, Rolon-Arroyo, Benjamin, Layne, Christopher M, Rooney, Evan, Oosterhoff, Benjamin, Hill, Ryan, Steinberg, Alan M, Lotterman, Jennifer, Gallagher, Katherine AS, and Pynoos, Robert S

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Violence Research, Mental Health, Clinical Research, Post-Traumatic Stress Disorder (PTSD), Depression, Behavioral and Social Science, Pediatric, Mental health, Good Health and Well Being, Adolescent, Child, Diagnostic and Statistical Manual of Mental Disorders, Female, Humans, Male, Psychometrics, Reproducibility of Results, Stress Disorders, Post-Traumatic, United States, posttraumatic stress disorder, assessment, psychometrics, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Paediatrics, Applied and developmental psychology
Abstract

ObjectiveTo describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD Reaction Index for DSM-5 (RI-5) across 2 independent samples.MethodStudy 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a "gold standard" structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version.ResultsRI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94).ConclusionThe developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health.

Published
2020

20. Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2

Author

Melvin, William J., Audu, Christopher O., Davis, Frank M., Sharma, Sriganesh B., Joshi, Amrita, DenDekker, Aaron, Wolf, Sonya, Barrett, Emily, Mangum, Kevin, Zhou, Xiaofeng, Bame, Monica, Ruan, Alex, Obi, Andrea, Kunkel, Steven L., Moore, Bethany B., and Gallagher, Katherine A.

Published
2021

22. Lacunarity of Han-Nekrasov-Okounkov $q$-series

Author

Gallagher, Katherine, Li, Lucia, and Vassilev, Katja

Subjects
Mathematics - Number Theory
Abstract

A power series is called lacunary if `almost all' of its coefficients are zero. Integer partitions have motivated the classification of lacunary specializations of Han's extension of the Nekrasov-Okounkov formula. More precisely, we consider the modular forms \[F_{a,b,c}(z) := \frac{\eta(24az)^a \eta(24acz)^{b-a}}{\eta(24z)},\] defined in terms of the Dedekind $\eta$-function, for integers $a,c \geq 1$ where $b \geq 1$ is odd throughout. Serre determined the lacunarity of the series when $a = c = 1$. Later, Clader, Kemper, and Wage extended this result by allowing $a$ to be general, and completely classified the $F_{a,b,1}(z)$ which are lacunary. Here, we consider all $c$ and show that for ${a \in \{1,2,3\}}$, there are infinite families of lacunary series. However, for $a \geq 4$, we show that there are finitely many triples $(a,b,c)$ such that $F_{a,b,c}(z)$ is lacunary. In particular, if $a \geq 4$, $b \geq 7$, and $c \geq 2$, then $F_{a,b,c}(z)$ is not lacunary. Underlying this result is the proof the $t$-core partition conjecture proved by Granville and Ono., Comment: 11 pages

Published
2018

23. Generating functions for power moments of elliptic curves over $\mathbb{F}_p$

Author

Gallagher, Katherine, Li, Lucia, Sweeting, Naomi, Vassilev, Katja, and Woo, Katharine

Subjects
Mathematics - Number Theory
Abstract

Seminal works by Birch and Ihara gave formulas for the $m$th power moments of the traces of Frobenius endomorphisms of elliptic curves over $\mathbb{F}_{p}$ for primes $p \geq 5$. Recent works by Kaplan and Petrow generalized these results to the setting of elliptic curves that contain a subgroup isomorphic to a fixed finite abelian group $A$. We revisit these formulas and determine a simple expression for the zeta function $Z_p(A; t)$, the generating function for these $m$th power moments. In particular, we find that \[ Z_p(A;t) = \frac{\widehat{Z}_p(A; t)}{\displaystyle \prod_{a \in \textrm{Frob}_p(A)}(1 - at)},\] where $\textrm{Frob}_p(A) := \{ a \, \colon -2\sqrt{p} \leq a \leq 2\sqrt{p}\, \text{ and } a \equiv p+1 \pmod{|A|}\}$, and $\widehat{Z}_p(A;t)$ is an easily computed polynomial that is determined by the first $\Big\lceil\frac{2\lfloor 2\sqrt{p}\rfloor}{|A|}\Big\rceil$ power moments. These rational zeta functions have two natural applications. We find rational generating functions in weight aspect for traces of Hecke operators on $S_k(\Gamma)$ for various congruence subgroups $\Gamma$. We also prove congruence relations for power moments by making use of known congruences for traces of Hecke operators., Comment: 11 pages

Published
2018

26. Ebola Virus Glycoprotein IgG Seroprevalence in Community Previously Affected by Ebola, Sierra Leone

Author

Manno, Daniela, Ayieko, Philip, Ishola, David, Afolabi, Muhammed O., Rogers, Baimba, Baiden, Frank, Serry-Bangura, Alimamy, Bah, Osman M., Kohn, Brian, Swaray, Ibrahim, Owusu-Kyei, Kwabena, Otieno, Godfrey T., Kowuor, Dickens, Tindanbil, Daniel, Smout, Elizabeth, Robinson, Cynthia, Keshinro, Babajide, Foster, Julie, Gallagher, Katherine, Lowe, Brett, Douoguih, Macaya, Leigh, Bailah, Greenwood, Brian, and Watson-Jones, Deborah

Subjects
Ebola virus infections -- Statistics, Immunoglobulin G -- Health aspects -- Measurement, Ebola virus -- Physiological aspects, Health
Abstract

Ebola virus (EBOV) antibodies have been found in populations that have never experienced documented Ebola outbreaks and in persons who reported no history of Ebola virus disease (EVD) (1). The [...]

Published
2022
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29. Diabetic Wound Keratinocytes Induce Macrophage JMJD3-Mediated Nlrp3 Expression via IL-1R Signaling.

Author

Wolf, Sonya J., Audu, Christopher O., Moon, Jadie Y., Joshi, Amrita D., Melvin, William J., Barrett, Emily C., Mangum, Kevin, de Jimenez, Gabriela Saldana, Rocco, Sabrina, Buckley, Sam, Ahmed, Zara, Wasikowski, Rachael, Kahlenberg, J. Michelle, Tsoi, Lam C., Gudjonsson, Johann E., and Gallagher, Katherine A.

Subjects
MYELOID cells, GENE expression, WOUND healing, NLRP3 protein, TISSUE wounds
Abstract

Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist in a low-grade inflammatory state that prevents the resolution of wound inflammation. Increased NLRP3 inflammasome activity has been shown in diabetic wound Mφs; however, the molecular mechanisms regulating NLRP3 expression and activity are unclear. Here, we identified that diabetic wound keratinocytes induce Nlrp3 gene expression in wound Mφs through IL-1 receptor–mediated signaling, resulting in enhanced inflammasome activation in the presence of pathogen-associated molecular patterns and damage-associated molecular patterns. We found that IL-1α is increased in human and murine wound diabetic keratinocytes compared with nondiabetic controls and directly induces Mφ Nlrp3 expression through IL-1 receptor signaling. Mechanistically, we report that the histone demethylase, JMJD3, is increased in wound Mφs late post-injury and is induced by IL-1α from diabetic wound keratinocytes, resulting in Nlrp3 transcriptional activation through an H3K27me3-mediated mechanism. Using genetically engineered mice deficient in JMJD3 in myeloid cells (Jmjd3 f/f lyz2 Cre+), we demonstrate that JMJD3 controls Mφ-mediated Nlrp3 expression during diabetic wound healing. Thus, our data suggest a role for keratinocyte-mediated IL-1α/IL-1R signaling in driving enhanced NLRP3 inflammasome activity in wound Mφs. These data also highlight the importance of cell cross-talk in wound tissues and identify JMJD3 and the IL-1R signaling cascade as important upstream therapeutic targets for Mφ NLRP3 inflammasome hyperactivity in nonhealing diabetic wounds. Article Highlights: The molecular mechanism regulating macrophage (Mφ) NLRP3 inflammasome activity in diabetic wounds remains unclear. Diabetic wound keratinocytes induce Nlrp3 gene expression and enhance inflammasome activation in wound Mφs through IL-1 receptor–mediated signaling. IL-1α is increased in human and murine wound diabetic keratinocytes compared with nondiabetic controls and directly induces Mφ Nlrp3 expression via histone demethylase, JMJD3. JMJD3 controls Mφ-mediated Nlrp3 expression during wound healing. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Keratinocytes sense and eliminate CRISPR DNA through STING/IFN-[kappa] activation and APOBEC3G induction

Author

Sarkar, Mrinal K., Uppala, Ranjitha, Zeng, Chang, Billi, Allison C., Tsoi, Lam C., Kidder, Austin, Xing, Xianying, White, Bethany E. Perez, Shao, Shuai, Plazyo, Olesya, Sirobhushanam, Sirisha, Xing, Enze, Jiang, Yanyun, Gallagher, Katherine A., Voorhees, John J., Kahlenberg, J. Michelle, and Gudjonsson, Johann E.

Subjects
Gene expression -- Health aspects, Skin diseases -- Genetic aspects -- Development and progression -- Care and treatment, Immune response -- Genetic aspects, Health care industry
Abstract

CRISPR/Cas9 has been proposed as a treatment for genetically inherited skin disorders. Here we report that CRISPR transfection activates STING-dependent antiviral responses in keratinocytes, resulting in heightened endogenous interferon (IFN) responses through induction of IFN-[kappa], leading to decreased plasmid stability secondary to induction of the cytidine deaminase gene APOBEC3G. Notably, CRISPR-generated KO keratinocytes had permanent suppression of IFN-[kappa] and IFN- stimulated gene (ISG) expression, secondary to hypermethylation of the IFNK promoter region by the DNA methyltransferase DNMT3B. JAK inhibition via baricitinib prior to CRISPR transfection increased transfection efficiency, prevented IFNK promoter hypermethylation, and restored normal IFN-[kappa] activity and ISG responses. This work shows that CRISPR- mediated gene correction alters antiviral responses in keratinocytes, has implications for future gene therapies for inherited skin diseases using CRISPR technology, and suggests pharmacologic JAK inhibition as a tool for facilitating and attenuating inadvertent selection effects in CRISPR/Cas9 therapeutic approaches., Introduction Keratinocytes (KCs) have long been recognized as one of the most difficult cell types to transfect (1, 2), but the mechanisms behind this resistance have remained unknown. KCs are [...]

Published
2023
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31. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Author

Kargbo, M, Bockarie, E, James, N L, Kabbah, A, Kamara, A, Koroma, K H, Langley, S O, William, N, Kessebeh, R, Mooney, T, Conteh, L, Smout, E, Allieu, K, Bangura, K, Bangura, M S, Bangura, M A, Jalloh, H, Jalloh, A B, Kamara, I, Kamara, M, Konteh, A, Koroma, S, Marrah, C, Sesay, M, Sesay, M T, Deen, A T, Jalloh, A, Kaimbay, R M, Kain, D, Kamara, E L, Kamara, M P, Kamara, O J, Kamara, S L M, Kanneh, M, Koroma, A H, Lahai, D, Mansaray, I S, Marah, W S, Massaquoi, M J, Nabie, A, Saidu, N S, Samai, I, Tengheh, J N, Turay, A S, Fornah, A, Sesay, F, Sow, A, Swaray, E, Mansaray, F, Ade-Cole, T, Bangura, L M, Conteh, M L, Koroma, A M, Koroma, M, Sam, A, Scott, T, Sessie, T, Sunders, J-H C, Turay, S I-S, Weekes, J, Sheku, M, Gibson, L, Kowuor, D, Ahamed, I, Allieu, W, Kabba, D U, Kamara, F J, Kebbie, M S, Pessima, M, Wurie, A, Bah, F, Bangura, A I, Bangura, R A S, Blango, L, Boima, S, Conteh, M, Conteh, Y, Daramy, M L, Fofanah, O, George, E, Hanson, T F, Jalloh, M I, Kalawa, M, Kamara, A M, Kamara, F E, Kamara, G M, Kamara, H M, Kamara, P B D, Kamara, R T, Kamara, R, Kanneh, D P, Komeh, I, Kuyateh, M, Mansaray, F F, Mansaray, M M, Sillah, A B, Tarawally, M A, Turya, O S, Yawmah, J B, Leigh, B, Watson-Jones, D, Greenwood, B, Samai, M H, Deen, G F, Marke, D, Sesay, T, Piot, P, Smith, P, Edmunds, J, Lees, S, Larson, H, Weiss, H, Wilson, P, Phillips, R, Maxwell, C, Ishola, D, Afolabi, M, Baiden, F, Akoo, P, Owusu-Kyei, K, Tindanbil, D, Bower, H, Stuart, J, Bah, O M, Rogers, B T, Serry-Bangura, A, Swaray, I B, Bangura, A, David, I J, Davies, D G M, Kallon, J A, Kamara, A B, Kamara, I F, Kamara, M M, Morovia, F E, Suma, F B, Thompson, F, Murray, M, Kakay, O, Suma, F, Sesay, I, Foster, J, Manno, D, Gallagher, K, Cox, S, Howard, N, Cesay, M, Torrani, P, Sharma, S, Snowden, E, Banks, T, Harber, T, Brown, J, Howard, K, Melton, N, Malcolm, S, Welsh, S, Eggo, R, Jendrossek, M, Pearson, C, Offergeld, K, Ferrault, C, Van Alst, M, Mahajan, N, Van Looveren, M, Van Ballaert, S, De Cnodder, T, Grobler, N, Roza, L, Liberi, T, Armishaw, L, Verkleij, C, Henrick, T, Banaszkiewicz, A, Lowe, B, Awuondo, K, Hafezi, H, Hancox, E, Kohn, B, Tuda, G O, Bangura, G, Kroma, M T, Fofanah, L, Pessima, A, Rogers, M, Sheriff, O, Ajala, T W, Fangawa, J, Foday Jr, S, Koroma, I S F, Mansaray, B, Mansaray, H A, Sesay, K, Charles, M K, Heroe, P C, Lamin Karbo, M, Yansaneh, I S, Gogo Egoeh, S, Trye, A, Amponsah, M, Donelson, L, Sylvester, T, Owira, V, Onyuka, G, Nambuchi, L, Oburu, A, Apollo, D, Vandi, L, Alghali, N D, Bah, A, Bangura, I J, Cole, A C, Fofanah, S, Jalloh, H U, Jalloh, K F N, Jalloh, N, Kabba, H U, Kabba, J N, Kabba, M, Kamara, J S, Kanjie, F, Kanu, A P, Kargbo, I, Kassa-Koroma, G, Koroma, S B, Sankoh, A, Sankoh, T, Sesay, O D, Wilhem, H, Williams, C T, Bangura, I, Ben-Rogers, Y, Jamboria, F J, Kamara, N, Kanawah, I, Kargbo, A T, Swaray, I, Amara, L, Bundu, I, Jakema, H B, Kamara, K, Sheku, M F, Adeleye, Q, Akhigbe, I, Bakalemwa, R, Chami, N P, Altmann, L, Kamara, B, van Roey, K, Conteh, P, Samura, M, Gandie, V, Marrah, M, Moinina, E, Kalokoh, J, Bosompem, S, Hilton, T, Jusu, M O, Borboh, P, Brima, A S, Caulker, A F Y, Kallon, A, Koroma, B, Macauley, R C, Saquee, T M D, Williams, H I, Bangura, A R, Fornah, J, Idriss, B, Sillah, M, Mackay, W, Aleghen, B, Murray, T, Edem-Hotah, J, Fatorma, T, Amara, F, Bangura, S, Bonnie, E, Sannoh, M, Donaldson, A, Ndingi, S, Nyaberi, D, Pereira, M, Rothwell, A, Vy, V, Nyallay, L, Fombah, A, Saidu, S, Dambo, T P, Fakaba, P J, Fatorma, M M E, Freeman, R H, Johnson, C L, Kogba, D B, Lahai, A, Vincent, W, Yambasu, N, Bangura, M, Tengbeh, A, Kabia, R, Nyakoi, A M, Callaghan, M, Enria, L, Lee, S, Afolabi, Muhammed O, Ishola, David, Manno, Daniela, Keshinro, Babajide, Bockstal, Viki, Rogers, Baimba, Owusu-Kyei, Kwabena, Serry-Bangura, Alimamy, Swaray, Ibrahim, Lowe, Brett, Kowuor, Dickens, Baiden, Frank, Mooney, Thomas, Smout, Elizabeth, Köhn, Brian, Otieno, Godfrey T, Jusu, Morrison, Foster, Julie, Samai, Mohamed, Deen, Gibrilla Fadlu, Larson, Heidi, Lees, Shelley, Goldstein, Neil, Gallagher, Katherine E, Gaddah, Auguste, Heerwegh, Dirk, Callendret, Benoit, Luhn, Kerstin, Robinson, Cynthia, Greenwood, Brian, Leyssen, Maarten, Douoguih, Macaya, Leigh, Bailah, and Watson-Jones, Deborah

Published
2022
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32. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial

Author

Kargbo, M, Bockarie, E, James, N L, Kabbah, A, Kamara, A, Koroma, K H, Langley, S O, William, N, Kessebeh, R, Mooney, T, Conteh, L, Smout, E, Allieu, K, Bangura, K, Bangura, M S, Bangura, M A, Jalloh, H, Jalloh, A B, Kamara, I, Kamara, M, Konteh, A, Koroma, S, Marrah, C, Sesay, M, Sesay, M T, Deen, A T, Jalloh, A, Kaimbay, R M, Kain, D, Kamara, E L, Kamara, M P, Kamara, O J, Kamara, S L M, Kanneh, M, Koroma, A H, Lahai, D, Mansaray, I S, Marah, W S, Massaquoi, M J, Nabie, A, Saidu, N S, Samai, I, Tengheh, J N, Turay, A S, Fornah, A, Sesay, F, Sow, A, Swaray, E, Mansaray, F, Ade-Cole, T, Bangura, L M, Conteh, M L, Koroma, A M, Koroma, M, Sam, A, Scott, T, Sessie, T, Sunders, J-H C, Turay, S I-S, Weekes, J, Sheku, M, Gibson, L, Kowuor, D, Ahamed, I, Allieu, W, Kabba, D U, Kamara, F J, Kebbie, M S, Pessima, M, Wurie, A, Bah, F, Bangura, A I, Bangura, R A S, Blango, L, Boima, S, Conteh, M, Conteh, Y, Daramy, M L, Fofanah, O, George, E, Hanson, T F, Jalloh, M I, Kalawa, M, Kamara, A M, Kamara, F E, Kamara, G M, Kamara, H M, Kamara, P B D, Kamara, R T, Kamara, R, Kanneh, D P, Komeh, I, Kuyateh, M, Mansaray, F F, Mansaray, M M, Sillah, A B, Tarawally, M A, Turya, O S, Yawmah, J B, Leigh, B, Watson-Jones, D, Greenwood, B, Samai, M H, Deen, G F, Marke, D, Piot, P, Smith, P, Edmunds, J, Lees, S, Larson, H, Weiss, H, Wilson, P, Maxwell, C, Ishola, D, Afolabi, M, Baiden, F, Akoo, P, Owusu-Kyei, K, Tindanbil, D, Bower, H, Stuart, J, Bah, O M, Rogers, B T, Serry-Bangura, A, Swaray, I B, Bangura, A, David, I J, Davies, D G M, Kallon, J A, Kamara, A B, Kamara, I F, Kamara, M M, Morovia, F E, Suma, F B, Thompson, F, Murray, M, Sesay, I, Kakay, O, Suma, F, Foster, J, Philips, R, Manno, D, Gallager, K, Cox, S, Howard, N, Cesay, M, Torrani, P, Sharma, S, Snowden, E, Banks, T, Harber, T, Brown, J, Howard, K, Melton, N, Malcolm, S, Welsh, S, Eggo, R, Jendrossek, M, Pearson, C, Van Hoof, J, Douoguih, M, Offergelt, K, Robinson, C, Keshinro, B, Van Alst, M, Mahajan, N, Bockstal, V, Goldstein, N, Gaddah, A, Heerwegh, D, Luhn, K, Leyssen, M, Lowe, B, Awuondo, K, Hafezi, H, Hancox, E, Kohn, B, Tuda, G O, Koroma, F, Bangura, G, Kroma, M T, Fofanah, L, Pessima, A, Rogers, M, Sheriff, O, Ajala, T W, Fangawa, J, Foday Jr, S, Jabbie, I, Mansaray, B, Mansaray, H A, Sesay, K, Charles, M K, Heroe, P C, Karbo, M L, Yansaneh, IS, Egoeh, S G, Trye, A, Amponsah, M, Alghali, N D, Bah, A, Bangura, IJ, Cole, A C, Fofanah, K, Fofanah, S, Jalloh, H U, Jalloh, K F N, Jalloh, N, Kabba, H U, Kabba, J N, Kabba, M, Kamara, J S, Kanjie, F, Kanu, A P, Kargbo, I, Kassa-Koroma, G, Koroma, S B, Sankoh, A, Sankoh, T, Sesay, O D, Wilhem, H, Williams, C T, Bangura, I, Ben-Rogers, Y, Jamboria, F J, Kamara, N, Kanawah, I, Kargbo, A T, Swaray, I, Amara, L, Bundu, I, Jakema, H B, Kamara, K, Sheku, M F, Adeleye, Q, Akhigbe, I, Bakalemwa, R, Chami, N P, Sylvester, T, Altmann, L, Kamara, B, van Roey, K, Conteh, P, Samura, M, Gandie, V, Marrah, M, Moinina, E, Kalokoh, J, Bangura, M I, Bosompem, S, Hilton, T, Jusu, M O, Borboh, P, Brima, A S, Caulker, A F Y, Kallon, A, Koroma, B, Macauley, RC, Saquee, T M D, Williams, H I, Bangura, A R, Fornah, J, Idriss, B, Sillah, M, Mackay, W, Aleghen, B, Murray, T, Edem-Hotah, J, Fatorma, T, Amara, F, Bangura, S, Bonnie, E, Sannoh, M, Donaldson, A, Ndingi, S, Nyaberi, D, Pereira, M, Rothwell, A, Vy, V, Nyallay, L, Fombah, A, Saidu, S, Connor, N, Dambo, T P, Fakaba, P J, Fatorma, M M E, Johnson, C L, Kogba, D B, Lahai, A, Vincent, W, Yambasu, N, Bangura, M, Tengbeh, A, Kabia, R, Nyakoi, AM, Callaghan, M, Enria, L, Lee, S, Ishola, David, Manno, Daniela, Afolabi, Muhammed O, Keshinro, Babajide, Bockstal, Viki, Rogers, Baimba, Owusu-Kyei, Kwabena, Serry-Bangura, Alimamy, Swaray, Ibrahim, Lowe, Brett, Kowuor, Dickens, Baiden, Frank, Mooney, Thomas, Smout, Elizabeth, Köhn, Brian, Otieno, Godfrey T, Jusu, Morrison, Foster, Julie, Samai, Mohamed, Deen, Gibrilla Fadlu, Larson, Heidi, Lees, Shelley, Goldstein, Neil, Gallagher, Katherine E, Gaddah, Auguste, Heerwegh, Dirk, Callendret, Benoit, Luhn, Kerstin, Robinson, Cynthia, Leyssen, Maarten, Greenwood, Brian, Douoguih, Macaya, Leigh, Bailah, and Watson-Jones, Deborah

Published
2022
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33. Evaluation of statistical models of carriage to predict the impact of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in Nigeria

Author

Adamu, Aishatu L, primary, Ojal, John, additional, Mburu, Caroline, additional, Gallagher, Katherine E, additional, Flasche, Stefan, additional, Odeyemi, Kofo, additional, Okoromah, Christy A.N, additional, Abubakar, Isa S, additional, Bello, Musa M, additional, Inem, Victor, additional, Karani, Angela, additional, Karia, Boniface, additional, Adetifa, Ifedayo M. O, additional, and Scott, J. Anthony G, additional

Published
2024
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35. Lower Extremity Ischemia

Author

Gallagher, Katherine A., Rectenwald, John E., Froehlich, James B., Henke, Peter K., Baliga, Ragavendra R., editor, and Eagle, Kim A., editor

Published
2020
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37. Scavengers in islets fuel diabetic autoimmunity.

Author

Moon, Jadie Y. and Gallagher, Katherine A.

Subjects
*AUTOIMMUNITY, *TYPE 1 diabetes, *LOW density lipoproteins, *T cells, *ISLANDS of Langerhans
Abstract

Autoreactive lymphocytes that infiltrate the pancreatic islet environment and target β cells are primary drivers of type 1 diabetes. In this issue of Immunity , Srivastava et al. 1 examine the role of the islet microenvironment in autoimmunity and find that the scavenging receptor CXCL16 on islet-resident macrophages uptakes oxidized low-density lipoproteins and promotes the differentiation and survival of infiltrating pathogenic CD8+ T cells. Autoreactive lymphocytes that infiltrate the pancreatic islet environment and target β cells are primary drivers of type 1 diabetes. In this issue of Immunity , Srivastava et al. examine the role of the islet microenvironment in autoimmunity and find that the scavenging receptor CXCL16 on islet-resident macrophages uptakes oxidized low-density lipoproteins and promotes the differentiation and survival of infiltrating pathogenic CD8+ T cells. [ABSTRACT FROM AUTHOR]

Published
2024
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40. OA-240 Determining whether mass vaccination campaigns with fractional-dose PCV10 (PNEUMOSIL) could accelerate group protection against pneumococcal transmission in sub-Saharan Africa

Author

Coldiron, Matthew, primary, Soumana, Issaka, additional, Langendorf, Céline, additional, Kagucia, Eunice, additional, Karani, Angela, additional, Baudin, Elisabeth, additional, Brah, Souleymane, additional, Guindo, Ousmane, additional, Gallagher, Katherine, additional, Scott, Anthony, additional, and Grais, Rebecca, additional

Published
2023
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43. Temporal trends of SARS-CoV-2 seroprevalence during the first wave of the COVID-19 epidemic in Kenya

Author

Adetifa, Ifedayo M. O., Uyoga, Sophie, Gitonga, John N., Mugo, Daisy, Otiende, Mark, Nyagwange, James, Karanja, Henry K., Tuju, James, Wanjiku, Perpetual, Aman, Rashid, Mwangangi, Mercy, Amoth, Patrick, Kasera, Kadondi, Ng’ang’a, Wangari, Rombo, Charles, Yegon, Christine, Kithi, Khamisi, Odhiambo, Elizabeth, Rotich, Thomas, Orgut, Irene, Kihara, Sammy, Bottomley, Christian, Kagucia, Eunice W., Gallagher, Katherine E., Etyang, Anthony, Voller, Shirine, Lambe, Teresa, Wright, Daniel, Barasa, Edwine, Tsofa, Benjamin, Bejon, Philip, Ochola-Oyier, Lynette I., Agweyu, Ambrose, Scott, J. Anthony G., and Warimwe, George M.

Published
2021
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45. Request Confirmation Networks in MicroPsi 2

Author

Bach, Joscha, Gallagher, Katherine, Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Iklé, Matthew, editor, Franz, Arthur, editor, Rzepka, Rafal, editor, and Goertzel, Ben, editor

Published
2018
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49. Factors predicting mortality in hospitalised HIV-negative children with lower-chest-wall indrawing pneumonia and implications for management.

Author

Gallagher, Katherine E., Awori, Juliet O., Knoll, Maria D., Rhodes, Julia, Higdon, Melissa M., Hammitt, Laura L., Prosperi, Christine, Baggett, Henry C., Brooks, W. Abdullah, Fancourt, Nicholas, Feikin, Daniel R., Howie, Stephen R. C., Kotloff, Karen L., Tapia, Milagritos D., Levine, Orin S., Madhi, Shabir A., Murdoch, David R., O'Brien, Katherine L., Thea, Donald M., and Baillie, Vicky L.

Subjects
*ETIOLOGY of pneumonia, *PNEUMONIA, *HOSPITAL care of children, *HOSPITAL administration, MORTALITY risk factors
Abstract

Introduction: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. Methods: PERCH enrolled a cohort of 2189 HIV-negative children aged 2–59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011–2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. Results: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99–5·99), HIV negative but exposed status (4·59, 1·81–11·7), moderate or severe malnutrition (6·85, 3·22–14·6) and younger age (infants compared to children 12–59 months old, OR 2·03, 95%CI 1·05–3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). Conclusions: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Symptom prevalence and secondary attack rate of SARS‐CoV‐2 in rural Kenyan households: A prospective cohort study

Author

Gallagher, Katherine E., primary, Nyiro, Joyce, additional, Agoti, Charles N., additional, Maitha, Eric, additional, Nyagwange, James, additional, Karani, Angela, additional, Bottomley, Christian, additional, Murunga, Nickson, additional, Githinji, George, additional, Mutunga, Martin, additional, Ochola‐Oyier, Lynette Isabella, additional, Kombe, Ivy, additional, Nyaguara, Amek, additional, Kagucia, E. Wangeci, additional, Warimwe, George, additional, Agweyu, Ambrose, additional, Tsofa, Benjamin, additional, Bejon, Philip, additional, Scott, J. Anthony G., additional, and Nokes, David James, additional

Published
2023
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