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Article: Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity.

Pilewski, Kelsey A / Kramer, Kevin J / Georgiev, Ivelin S

2021 Volume 9, Issue 9

Abstract: Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have ... ...

Abstract	Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic
Language	English
Publishing date	2021-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9090964
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Article ; Online: Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy.

Zhang, Qinrong / Yang, Yuhan / Cao, Kevin J / Chen, Wei / Paidi, Santosh / Xia, Chun-Hong / Kramer, Richard H / Gong, Xiaohua / Ji, Na

eLife

2023 Volume 12

Abstract: The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation ... ...

Abstract	The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.
MeSH term(s)	Mice ; Animals ; Retina/pathology ; Retinal Ganglion Cells ; Retinal Degeneration/pathology ; Microscopy, Fluorescence ; Optics and Photonics
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.84853
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Article ; Online: Simple versus radical cholecystectomy and survival for pathologic stage T1B gallbladder cancer.

Rhodin, Kristen E / Goins, Stacy / Kramer, Ryan / Eckhoff, Austin M / Herbert, Garth / Shah, Kevin N / Allen, Peter J / Nussbaum, Daniel P / Blazer, Dan G / Zani, Sabino / Lidsky, Michael E

HPB : the official journal of the International Hepato Pancreato Biliary Association

2024 Volume 26, Issue 4, Page(s) 594–602

Abstract: Background: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical ... ...

Abstract	Background: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer. Methods: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018. Patients were stratified by surgical management. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. Results: Altogether, 950 patients were identified with pathologic T1B gallbladder cancer: 187 (19.7 %) receiving simple and 763 (80.3 %) radical cholecystectomy. Median OS was 89.5 (95 % CI 62.5-137) and 91.4 (95 % CI 75.9-112) months for simple and radical cholecystectomy, respectively (log-rank p = 0.55). Receipt of simple cholecystectomy was not associated with greater hazard of mortality compared to radical cholecystectomy (HR 1.23, 95 % CI 0.95-1.59, p = 0.12). Discussion: In this analysis, we report comparable outcomes with simple cholecystectomy among patients with pathologic T1B gallbladder cancer. These findings suggest that highly selected patients, such as those with R0 resection and imaging at low risk for residual disease and/or nodal metastasis, may not benefit from extended resection; however, radical cholecystectomy remains standard of care until prospective validation can be achieved.
MeSH term(s)	Humans ; Gallbladder Neoplasms/pathology ; Neoplasm Staging ; Retrospective Studies ; Cholecystectomy ; Lymph Node Excision ; Carcinoma in Situ/pathology
Language	English
Publishing date	2024-01-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2024.01.012
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Article ; Online: Prevalence and clinical significance of increasing head height asymmetry as a measure of forelimb lameness in horses when trotting in a straight line after palmar digital nerve block.

Kolding, Susanne A / Sørensen, Johnny N / Kramer, Joanne / McCracken, Megan J / Reed, Shannon K / Keegan, Kevin G

Equine veterinary journal

2023 Volume 55, Issue 6, Page(s) 988–994

Abstract: Background: Some horses increase in forelimb lameness, measured as vertical head height asymmetry, or differences in maximums and minimums of head heights (HDmax, HDmin), after a palmar digital nerve (PDN) block. The prevalence of this finding, or what ... ...

Abstract	Background: Some horses increase in forelimb lameness, measured as vertical head height asymmetry, or differences in maximums and minimums of head heights (HDmax, HDmin), after a palmar digital nerve (PDN) block. The prevalence of this finding, or what it means clinically, has not been reported in peer-reviewed literature. Objectives: To estimate the prevalence of increasing head height asymmetry after a PDN block and determine if this is associated with cause of forelimb lameness. Study design: Retrospective case series. Methods: Head height asymmetry, normalised to expected vertical head displacement, from inertial-sensor data collections of all horses evaluated for forelimb lameness while trotting in a straight line at two different clinics were screened for cases that had an initial PDN block and then another more proximal block in the same limb during the same lameness evaluation. Medical records of the screened cases (n = 213) were evaluated to determine the cause of lameness. Prevalence of increasing head height asymmetry was calculated. Differences in lameness amplitude between groups of cases that remained unchanged (Group 1), that increased (Group 2), and that decreased (Group 3) in head height asymmetry before and after the initial PDN block were compared (Kruskal-Wallis). Determination of the location of the cause of lameness and final diagnoses of cases were compared between Group 1 and Group 2 (chi-squared tests of independence). Results: The PDN block increased head height asymmetry at a prevalence of 32.5% (95% CI = 24.5%-41.5%) and 13.8% (95% CI = 7.3%-22.9%), in clinic 1 and 2, respectively. Increasing head height asymmetry after an initial PDN block did not predict localization of the cause of forelimb lameness or specific diagnosis (p = 0.1), other than indicating that it is unlikely to be in the foot (p = 0.02). Main limitations: Study samples consisted primarily of Warmbloods (clinic 1) and Quarter Horses (clinic 2). Analysis of blocking induced changes was limited to straight line trot only. Conclusions: Increasing head height asymmetry after PDN block is common during forelimb lameness evaluations. Other than indicating that the cause of lameness is more proximal in the blocked forelimb, this does not help determine the final diagnosis.
MeSH term(s)	Horses ; Animals ; Lameness, Animal/diagnosis ; Lameness, Animal/epidemiology ; Clinical Relevance ; Prevalence ; Retrospective Studies ; Horse Diseases/diagnosis ; Horse Diseases/epidemiology ; Biomechanical Phenomena ; Nerve Block/veterinary ; Forelimb ; Gait/physiology ; Hindlimb
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	41606-x
ISSN	2042-3306 ; 0425-1644
ISSN (online)	2042-3306
ISSN	0425-1644
DOI	10.1111/evj.13921
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Article ; Online: Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity

Kelsey A. Pilewski / Kevin J. Kramer / Ivelin S. Georgiev

Vaccines, Vol 9, Iss 964, p

2021 Volume 964

Abstract	Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli , Mycobacterium tuberculosis , and Neisseria meningitides , and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.
Keywords	immunization ; antibodies ; subunit vaccines ; humoral immunity ; bacterial pathogens ; Medicine ; R
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Underrepresented and Underserved Populations in Neurological Research.

Windon, Charles C / Jackson, Ashley J / Aguirre, Gloria A / Tucker, Miwa / Amuiri, Alinda / Hill-Jarrett, Tanisha / Chen, Miranda / Pina Escuedro, Stefanie D / Lieu, Kevin / Lopez, Lucia / Mei, Diana / Tee, Boon Lead / Watson, Caitlin W / Agwu, Chidera / Kramer, Joel / Lanata, Serggio

Seminars in neurology

2024 Volume 44, Issue 2, Page(s) 168–177

Abstract: Underserved and underrepresented populations have historically been excluded from neurological research. This lack of representation has implications for translation of research findings into clinical practice given the impact of social determinants of ... ...

Abstract	Underserved and underrepresented populations have historically been excluded from neurological research. This lack of representation has implications for translation of research findings into clinical practice given the impact of social determinants of health on neurological disease risk, progression, and outcomes. Lack of inclusion in research is driven by individual-, investigator-, and study-level barriers as well as larger systemic injustices (e.g., structural racism, discriminatory practices). Although strategies to increase inclusion of underserved and underrepresented populations have been put forth, numerous questions remain about the most effective methodology. In this article, we highlight inclusivity patterns and gaps among the most common neurological conditions and propose best practices informed by our own experiences in engagement of local community organizations and collaboration efforts to increase underserved and underrepresented population participation in neurological research.
MeSH term(s)	Humans ; Vulnerable Populations ; Medically Underserved Area
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0044-1782516
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Zs.A 1737: Show issues

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Article ; Online: Using bioacoustics to enhance the efficiency of spotted owl surveys and facilitate forest restoration

Kramer, H. Anu / Kelly, Kevin G. / Whitmore, Sheila A. / Berigan, William J. / Reid, Dana S. / Wood, Connor M. / Klinck, Holger / Kahl, Stefan / Manley, Patricia N. / Sawyer, Sarah C. / Peery, M. Zachariah

The Journal of Wildlife Management. 2024 Feb., v. 88, no. 2 p.e22533-

2024

Abstract: The California spotted owl (Strix occidentalis occidentalis) is an older‐forest associated species that resides at the center of forest management planning in the Sierra Nevada and Southern California, USA, which are experiencing increasingly large and ... ...

Abstract	The California spotted owl (Strix occidentalis occidentalis) is an older‐forest associated species that resides at the center of forest management planning in the Sierra Nevada and Southern California, USA, which are experiencing increasingly large and severe wildfires and drought‐related tree mortality. We leveraged advances in passive acoustic survey technologies to develop an acoustically assisted survey design that could increase the efficiency and effectiveness of project‐level surveys for spotted owls, allowing surveys to be completed in a single year instead of in multiple years. We deployed an array of autonomous recording units (ARUs) across a landscape and identified spotted owl vocalizations in the resulting audio using BirdNET. We then evaluated spatio‐temporal patterns in spotted owl vocalizations near occupied territories and the ability of a crew naïve to the location of occupied territories to locate spotted owls based on patterns of acoustic detections. After only 3 weeks of acoustic surveys, ≥1 ARU within 750 m of all 17 occupied territories obtained spotted owl detections across ≥2 nights. When active surveys using broadcast calling were conducted near ARUs with spotted owl detections by surveyors naïve to territory occupancy status and locations, surveyors located owls in 93% to 100% of occupied territories with ≤3 surveys. To further improve the efficiency of spotted owl surveys, we developed a statistical model to identify and prioritize areas across the Sierra Nevada for different survey methods (active only, acoustically assisted, no surveys) based on the expected probability of occupancy predicted from remotely sensed measurements of tree height and historical occupancy. Depending on managers' tolerance for false negatives, this model could help identify large areas that might not benefit from surveys based on low expected occupancy probabilities and areas where acoustically assisted surveys might enhance survey effectiveness and efficiency. Collectively, these findings can help managers streamline the survey process and thus increase the pace of forest restoration while minimizing potential near‐term adverse effects on California spotted owls.
Keywords	Strix occidentalis ; bioacoustics ; forest management ; forest restoration ; landscapes ; mountains ; probability ; remote sensing ; statistical models ; surveys ; territoriality ; tree height ; tree mortality ; California
Language	English
Dates of publication	2024-02
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	410712-3
ISSN	0022-541X
ISSN	0022-541X
DOI	10.1002/jwmg.22533
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Correction: Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy.

Mączyńska, Justyna / Raes, Florian / Da Pieve, Chiara / Turnock, Stephen / Boult, Jessica K R / Hoebart, Julia / Niedbala, Marcin / Robinson, Simon P / Harrington, Kevin J / Kaspera, Wojciech / Kramer-Marek, Gabriela

BMC medicine

2022 Volume 20, Issue 1, Page(s) 179

Language	English
Publishing date	2022-05-03
Publishing country	England
Document type	Published Erratum
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02388-z
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Article ; Online: Prevalence and clinical significance of increasing head height asymmetry as a measure of forelimb lameness in horses when trotting in a straight line after palmar digital nerve block

Kolding, Susanne A. / Sørensen, Johnny N. / Kramer, Joanne / McCracken, Megan J. / Reed, Shannon K. / Keegan, Kevin G.

Equine Veterinary Journal. 2023 Nov., v. 55, no. 6 p.988-994

2023

Abstract: BACKGROUND: Some horses increase in forelimb lameness, measured as vertical head height asymmetry, or differences in maximums and minimums of head heights (HDmax, HDmin), after a palmar digital nerve (PDN) block. The prevalence of this finding, or what ... ...

Abstract	BACKGROUND: Some horses increase in forelimb lameness, measured as vertical head height asymmetry, or differences in maximums and minimums of head heights (HDmax, HDmin), after a palmar digital nerve (PDN) block. The prevalence of this finding, or what it means clinically, has not been reported in peer‐reviewed literature. OBJECTIVES: To estimate the prevalence of increasing head height asymmetry after a PDN block and determine if this is associated with cause of forelimb lameness. STUDY DESIGN: Retrospective case series. METHODS: Head height asymmetry, normalised to expected vertical head displacement, from inertial‐sensor data collections of all horses evaluated for forelimb lameness while trotting in a straight line at two different clinics were screened for cases that had an initial PDN block and then another more proximal block in the same limb during the same lameness evaluation. Medical records of the screened cases (n = 213) were evaluated to determine the cause of lameness. Prevalence of increasing head height asymmetry was calculated. Differences in lameness amplitude between groups of cases that remained unchanged (Group 1), that increased (Group 2), and that decreased (Group 3) in head height asymmetry before and after the initial PDN block were compared (Kruskal‐Wallis). Determination of the location of the cause of lameness and final diagnoses of cases were compared between Group 1 and Group 2 (chi‐squared tests of independence). RESULTS: The PDN block increased head height asymmetry at a prevalence of 32.5% (95% CI = 24.5%–41.5%) and 13.8% (95% CI = 7.3%–22.9%), in clinic 1 and 2, respectively. Increasing head height asymmetry after an initial PDN block did not predict localization of the cause of forelimb lameness or specific diagnosis (p = 0.1), other than indicating that it is unlikely to be in the foot (p = 0.02). MAIN LIMITATIONS: Study samples consisted primarily of Warmbloods (clinic 1) and Quarter Horses (clinic 2). Analysis of blocking induced changes was limited to straight line trot only. CONCLUSIONS: Increasing head height asymmetry after PDN block is common during forelimb lameness evaluations. Other than indicating that the cause of lameness is more proximal in the blocked forelimb, this does not help determine the final diagnosis.
Keywords	asymmetry ; head ; horses ; lameness ; nerve tissue
Language	English
Dates of publication	2023-11
Size	p. 988-994.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	41606-x
ISSN	0425-1644
ISSN	0425-1644
DOI	10.1111/evj.13921
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis.

Howlett-Prieto, Quentin / Feng, Xuan / Kramer, John F / Kramer, Kevin J / Houston, Timothy W / Reder, Anthony T

Multiple sclerosis (Houndmills, Basingstoke, England)

2021 Volume 27, Issue 14, Page(s) 2170–2179

Abstract: Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients.: Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab ...

Abstract	Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8 Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8
MeSH term(s)	CD8-Positive T-Lymphocytes ; Humans ; Leukocytes, Mononuclear ; Multiple Sclerosis/drug therapy ; T-Lymphocyte Subsets ; T-Lymphocytes, Regulatory
Language	English
Publishing date	2021-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/13524585211003301
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