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Article ; Online: The CARB-X Portfolio of Nontraditional Antibacterial Products.

Duffy, Erin M / Buurman, Ed T / Chiang, Su L / Cohen, Nadia R / Uria-Nickelsen, Maria / Alm, Richard A

ACS infectious diseases

2021 Volume 7, Issue 8, Page(s) 2043–2049

Abstract: The growing prevalence of antibiotic-resistant bacterial pathogens and the lack of new medicines to treat the infections they cause remain a significant global threat. In recent years, this ongoing unmet need has encouraged more research groups to focus ... ...

Abstract	The growing prevalence of antibiotic-resistant bacterial pathogens and the lack of new medicines to treat the infections they cause remain a significant global threat. In recent years, this ongoing unmet need has encouraged more research groups to focus on the discovery and development of nontraditional antibacterial agents, ranging from anti-virulence strategies to bacteriophage and ways to modulate the microbiome. The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global nonprofit public-private partnership dedicated to accelerating antibacterial-related research. Importantly, the CARB-X portfolio supports a wide variety of novel and innovative nontraditional programs to help the global antibacterial research ecosystem understand the potential that these modalities can play in the management or prevention of serious infections. We describe here the breadth of the CARB-X pipeline of novel nontraditional products.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteria ; Drug Discovery ; Drug Resistance, Bacterial ; Microbiota
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.1c00331
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Article ; Online: Procedural outcomes on Twitter: too good to be true?

Gualano, Sarah K / Trumpower, Brad / Wanamaker, Brett L / Cohen, David G / Arain, Mansoor A / Kawamoto, Kris / Atreya, Auras R / Sutton, Nadia R / Nallamothu, Brahmajee K

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

2021 Volume 17, Issue 12, Page(s) e1019–e1021

MeSH term(s)	Humans ; Social Media
Language	English
Publishing date	2021-12-17
Publishing country	France
Document type	Journal Article
ZDB-ID	2457174-X
ISSN	1969-6213 ; 1774-024X
ISSN (online)	1969-6213
ISSN	1774-024X
DOI	10.4244/EIJ-D-21-00498
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Zs.A 6680: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 571: Show issues

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Article ; Online: Common and Divergent Features of T Cells from Blood, Gut, and Genital Tract of Antiretroviral Therapy-Treated HIV

Xie, Guorui / Moron-Lopez, Sara / Siegel, David A / Yin, Kailin / Polos, Anastasia / Cohen, Jennifer / Greenblatt, Ruth M / Tien, Phyllis C / Lee, Sulggi A / Yukl, Steven A / Roan, Nadia R

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 208, Issue 7, Page(s) 1790–1801

Abstract: T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but they differ in the kinds of foreign Ags they need to ... ...

Abstract	T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but they differ in the kinds of foreign Ags they need to tolerate. How these different environments influence the properties of their T cells is poorly understood, but important for understanding women's health. We recruited antiretroviral therapy-suppressed women living with HIV who donated, within one visit, blood and tissue samples from the ileum, colon, rectosigmoid, endometrium, endocervix, and ectocervix. With these samples, we conducted 36-parameter cytometry by time of flight phenotyping of T cells. Although gut and FRT T cells shared features discriminating them from their blood counterparts, they also harbored features distinguishing them from one another. These included increased proportions of CD69
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; CD8-Positive T-Lymphocytes ; Female ; Genitalia ; HIV Infections/drug therapy ; Humans ; Lymphocyte Count
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2022-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2101102
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.

deCamp, Allan C / Corcoran, Martin M / Fulp, William J / Willis, Jordan R / Cottrell, Christopher A / Bader, Daniel L V / Kalyuzhniy, Oleksandr / Leggat, David J / Cohen, Kristen W / Hyrien, Ollivier / Menis, Sergey / Finak, Greg / Ballweber-Fleming, Lamar / Srikanth, Abhinaya / Plyler, Jason R / Rahaman, Farhad / Lombardo, Angela / Philiponis, Vincent / Whaley, Rachael E /

NPJ vaccines

2024 Volume 9, Issue 1, Page(s) 58

Abstract: Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting ... ...

Abstract	Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-024-00811-5
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Article ; Online: A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses.

Cohen, Kristen W / De Rosa, Stephen C / Fulp, William J / deCamp, Allan C / Fiore-Gartland, Andrew / Mahoney, Celia R / Furth, Sarah / Donahue, Josh / Whaley, Rachael E / Ballweber-Fleming, Lamar / Seese, Aaron / Schwedhelm, Katharine / Geraghty, Daniel / Finak, Greg / Menis, Sergey / Leggat, David J / Rahaman, Farhad / Lombardo, Angela / Borate, Bhavesh R /

Philiponis, Vincent / Maenza, Janine / Diemert, David / Kolokythas, Orpheus / Khati, Nadia / Bethony, Jeffrey / Hyrien, Ollivier / Laufer, Dagna S / Koup, Richard A / McDermott, Adrian B / Schief, William R / McElrath, M Juliana

Science translational medicine

2023 Volume 15, Issue 697, Page(s) eadf3309

Abstract: The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to ... ...

Abstract	The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01
MeSH term(s)	Humans ; AIDS Vaccines ; T-Lymphocytes, Helper-Inducer ; Epitopes ; Germ Cells ; HIV Antigens ; Immunodominant Epitopes ; HIV Infections/prevention & control
Chemical Substances	AIDS Vaccines ; Epitopes ; HIV Antigens ; Immunodominant Epitopes
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adf3309
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Zs.A 6941: Show issues

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Article ; Online: Differential impact of antiretroviral therapy initiated before or during pregnancy on placenta pathology in HIV-positive women.

Ikumi, Nadia M / Malaba, Thokozile R / Pillay, Komala / Cohen, Marta C / Madlala, Hlengiwe P / Matjila, Mushi / Anumba, Dilly / Myer, Landon / Newell, Marie-Louise / Gray, Clive M

AIDS (London, England)

2021 Volume 35, Issue 5, Page(s) 717–726

Abstract: Objective: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology.: Design: A nested substudy in a larger cohort of HIV-infected women which examined the association ... ...

Abstract	Objective: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology. Design: A nested substudy in a larger cohort of HIV-infected women which examined the association between ART status and birth outcomes. Methods: Placentas (n = 130) were examined for histopathology from two ART groups: stable (n = 53), who initiated ART before conception and initiating (n = 77), who started ART during pregnancy [median (interquartile range) 15 weeks gestation (11-18)]. Using binomial regression we quantified associations between ART initiation timing with placental histopathology and pregnancy outcomes. Results: One-third of all placentas were less than 10th percentile weight-for-gestation and there was no significant difference between ART groups. Placental diameter, thickness, cord insertion position and foetal-placental weight ratio were also similar by group. However, placentas from the stable group showed increased maternal vascular malperfusion (MVM) (39.6 vs. 19.4%), and decreased weight (392 vs. 422 g, P = 0.09). MVM risk was twice as high [risk ratios 2.03 (95% confidence interval: 1.16-3.57); P = 0.01] in the stable group; the increased risk remaining significant when adjusting for maternal age [risk ratios 2.04 (95% confidence interval: 1.12-3.72); P = 0.02]. Furthermore, MVM was significantly associated with preterm delivery and low birth weight (P = 0.002 and <0.0001, respectively). Conclusion: Preconception initiation of ART was associated with an increased MVM risk, and may contribute to placental dysfunction. The association between MVM with preterm delivery and low birth weight suggests that a placenta-mediated mechanism likely links the putative association between long-term use of ART and adverse birth outcomes.
MeSH term(s)	Female ; Gestational Age ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Infant, Newborn ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy ; Pregnancy Outcome
Language	English
Publishing date	2021-06-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000002824
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Article ; Online: Ultrasound-guided lymph node fine-needle aspiration for evaluating post-vaccination germinal center responses in humans.

Scholte, Larissa L S / Leggat, David J / Cohen, Kristen W / Hoeweler, Lara / Erwin, Guacyara C / Rahaman, Farhard / Lombardo, Angela / Philiponis, Vincent / Laufer, Dagna S / Siefers, Heather / Ruppel, Alexis M / Brand, Joshua / Maenza, Janine / Bronson, Rhi / Prabhakaran, Madhu / Jean-Baptiste, Jalen / Kolokythas, Orpheus / Desrosiers, Aimee A / Thoreson, Caroline K /

Heit, Antje / Khati, Nadia J / Malkin, Elissa / McElrath, M Juliana / McDermott, Adrian B / Schief, William R / Diemert, David / Bethony, Jeffrey M

STAR protocols

2023 Volume 4, Issue 4, Page(s) 102576

Abstract: The lymph node (LN) is a critical biological site for immune maturation after vaccination as it includes several cell populations critical for priming the antibody response. Here, we present a protocol for sampling the LN and isolating cell populations ... ...

Abstract	The lymph node (LN) is a critical biological site for immune maturation after vaccination as it includes several cell populations critical for priming the antibody response. Here, we present a protocol for sampling the LN and isolating cell populations to evaluate immunogens targeting germline cells. We describe steps for media and tube preparation and sample collection using an ultrasound-guided LN fine-needle aspiration procedure. This protocol is safe, quick, low-cost, and less invasive than excisional biopsy. For complete details on the use and execution of this protocol, please refer to Leggat et al. (2022).
MeSH term(s)	Humans ; Biopsy, Fine-Needle ; Lymph Nodes/diagnostic imaging ; Lymph Nodes/pathology ; Germinal Center ; Vaccination ; Ultrasonography, Interventional
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102576
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Article ; Online: Microbial persistence and the road to drug resistance.

Cohen, Nadia R / Lobritz, Michael A / Collins, James J

Cell host & microbe

2013 Volume 13, Issue 6, Page(s) 632–642

Abstract: Microbial drug persistence is a widespread phenomenon in which a subpopulation of microorganisms is able to survive antimicrobial treatment without acquiring resistance-conferring genetic changes. Microbial persisters can cause recurrent or intractable ... ...

Abstract	Microbial drug persistence is a widespread phenomenon in which a subpopulation of microorganisms is able to survive antimicrobial treatment without acquiring resistance-conferring genetic changes. Microbial persisters can cause recurrent or intractable infections, and, like resistant mutants, they carry an increasing clinical burden. In contrast to heritable drug resistance, however, the biology of persistence is only beginning to be unraveled. Persisters have traditionally been thought of as metabolically dormant, nondividing cells. As discussed in this review, increasing evidence suggests that persistence is in fact an actively maintained state, triggered and enabled by a network of intracellular stress responses that can accelerate processes of adaptive evolution. Beyond shedding light on the basis of persistence, these findings raise the possibility that persisters behave as an evolutionary reservoir from which resistant organisms can emerge. As persistence and its consequences come into clearer focus, so too does the need for clinically useful persister-eradication strategies.
MeSH term(s)	Drug Resistance, Microbial ; Eukaryotic Cells/drug effects ; Prokaryotic Cells/drug effects ; Stress, Physiological
Language	English
Publishing date	2013-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2013.05.009
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Article ; Online: High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy.

McLellan, Micheal A / Skelly, Daniel A / Dona, Malathi S I / Squiers, Galen T / Farrugia, Gabriella E / Gaynor, Taylah L / Cohen, Charles D / Pandey, Raghav / Diep, Henry / Vinh, Antony / Rosenthal, Nadia A / Pinto, Alexander R

Circulation

2020 Volume 142, Issue 15, Page(s) 1448–1463

Abstract: Background: Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators ... ...

Abstract	Background: Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative effect of disparate cell populations on cardiac fibrosis, remain unclear. Methods: We developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome, the network of cells that forms the heart. This method was used to profile the cardiac cellular ecosystem in response to 2 weeks of continuous administration of angiotensin II, a profibrotic stimulus that drives pathological cardiac remodeling. Results: Our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations, Fibroblast- Conclusions: These results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes that precede chronic cardiac fibrosis.
MeSH term(s)	Animals ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Fibrosis ; Gene Expression Profiling ; Mice ; Myocardium/metabolism ; Myocardium/pathology ; Pyrophosphatases/metabolism ; Single-Cell Analysis ; Stress, Physiological ; Thrombospondins/metabolism
Chemical Substances	Thrombospondins ; thrombospondin 4 ; CILP protein, mouse (EC 3.6.1.-) ; Pyrophosphatases (EC 3.6.1.-)
Language	English
Publishing date	2020-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.119.045115
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Article ; Online: The use of proxies and proxy-reported measures: a report of the international society for quality of life research (ISOQOL) proxy task force.

Roydhouse, Jessica K / Cohen, Matthew L / Eshoj, Henrik R / Corsini, Nadia / Yucel, Emre / Rutherford, Claudia / Wac, Katarzyna / Berrocal, Allan / Lanzi, Alyssa / Nowinski, Cindy / Roberts, Natasha / Kassianos, Angelos P / Sebille, Veronique / King, Madeleine T / Mercieca-Bebber, Rebecca

Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation

2021 Volume 31, Issue 2, Page(s) 317–327

Abstract: Aims: Proxy reports are often used when patients are unable to self-report. It is unclear how proxy measures are currently in use in adult health care and research settings. We aimed to describe how proxy reports are used in these settings, including ... ...

Abstract	Aims: Proxy reports are often used when patients are unable to self-report. It is unclear how proxy measures are currently in use in adult health care and research settings. We aimed to describe how proxy reports are used in these settings, including the use of measures developed specifically for proxy reporting in adult health populations. Methods: We systematically searched Medline, PsycINFO, PsycTESTS, CINAHL and EMBASE from database inception to February 2018. Search terms included a combination of terms for quality of life and health outcomes, proxy-reporters, and health condition terms. The data extracted included clinical context, the name of the proxy measure(s) used and other descriptive data. We determined whether the measures were developed specifically for proxy use or were existing measures adapted for proxy use. Results: The database search identified 17,677 possible articles, from which 14,098 abstracts were reviewed. Of these, 11,763 were excluded and 2335 articles were reviewed in full, with 880 included for data extraction. The most common clinical settings were dementia (30%), geriatrics (15%) and cancer (13%). A majority of articles (51%) were paired studies with proxy and patient responses for the same person on the same measure. Most paired studies (77%) were concordance studies comparing patient and proxy responses on these measures. Discussion: Most published research using proxies has focused on proxy-patient concordance. Relatively few measures used in research with proxies were specifically developed for proxy use. Future work is needed to examine the performance of measures specifically developed for proxies. Systematic review registration: PROSPERO No. CRD42018103179.
MeSH term(s)	Adult ; Humans ; Proxy ; Quality of Life/psychology
Language	English
Publishing date	2021-07-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1161148-0
ISSN	1573-2649 ; 0962-9343
ISSN (online)	1573-2649
ISSN	0962-9343
DOI	10.1007/s11136-021-02937-8
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