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Article ; Online: Reduction in GABAB on glia induce Alzheimer's disease related changes.

Osse, Amanda M Leisgang / Pandey, Ravi S / Wirt, Ryan A / Ortiz, Andrew A / Salazar, Arnold / Kimmich, Michael / Toledano Strom, Erin N / Oblak, Adrian / Lamb, Bruce / Hyman, James M / Carter, Gregory W / Kinney, Jefferson

Brain, behavior, and immunity

2023 Volume 110, Page(s) 260–275

Abstract: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques (Aβ), neurofibrillary tangles (NFT), and neuroinflammation. Data have demonstrated that neuroinflammation contributes to Aβ and NFT onset and progression, ... ...

Abstract	Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques (Aβ), neurofibrillary tangles (NFT), and neuroinflammation. Data have demonstrated that neuroinflammation contributes to Aβ and NFT onset and progression, indicating inflammation and glial signaling is vital to understanding AD. A previous investigation demonstrated a significant decrease of the GABA
MeSH term(s)	Mice ; Animals ; Alzheimer Disease/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Neuroinflammatory Diseases ; Mice, Transgenic ; Amyloid beta-Peptides/metabolism ; Neuroglia/metabolism ; Plaque, Amyloid ; gamma-Aminobutyric Acid ; Disease Models, Animal
Chemical Substances	Amyloid beta-Protein Precursor ; Amyloid beta-Peptides ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2023-03-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.03.002
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Zs.MO 327: Show issues

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Article ; Online: Incidence and Risk Factors for Retinal Detachment and Retinal Tear after Cataract Surgery: IRIS® Registry (Intelligent Research in Sight) Analysis.

Morano, Michael J / Khan, M Ali / Zhang, Qiang / Halfpenny, Colleen P / Wisner, Douglas M / Sharpe, James / Li, Alexander / Tomaiuolo, Maurizio / Haller, Julia A / Hyman, Leslie / Ho, Allen C

Ophthalmology science

2023 Volume 3, Issue 4, Page(s) 100314

Abstract: Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® ... ...

Abstract	Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017. Methods: Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery. Main outcome measures: Incidence and risk factors for RRD or RT within 1 year of cataract surgery. Results: Of the 3 177 195 eyes of 1 983 712 patients included, 6690 (0.21%) developed RRD and 5489 (0.17%) developed RT without RRD within 1 year after cataract surgery. Multivariable logistic regression odds ratios (ORs) showed increased risk of RRD and RT, respectively, among men (OR 3.15; 95% confidence interval [CI], 2.99-3.32; Conclusion: In the IRIS Registry, RRD occurs in approximately 1 in 500 cataract surgeries in patients aged > 40 years within 1 year of surgery. The presence of LD conferred the highest odds for RRD and RT after surgery. Additional risk factors for RRD included male gender, younger age, hypermature cataract, PVD, and high myopia. These data may be useful during the informed consent process for cataract surgery and help identify patients at a higher risk of retinal complications. Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Language	English
Publishing date	2023-04-18
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-9145
ISSN (online)	2666-9145
DOI	10.1016/j.xops.2023.100314
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Article ; Online: Lewy body dementia: Overcoming barriers and identifying solutions.

Agarwal, Kanishka / Backler, Wendi / Bayram, Ece / Bloom, Leah / Boeve, Bradley F / Cha, Jang-Ho / Denslow, Maria / Ferman, Tanis J / Galasko, Douglas / Galvin, James E / Gomperts, Stephen N / Irizarry, Michael C / Kantarci, Kejal / Kaushik, Harsh / Kietlinski, Matt / Koenig, Aaron / Leverenz, James B / McKeith, Ian / McLean, Pamela J /

Montine, Thomas J / Moose, Sandra O / O'Brien, John T / Panier, Valery / Ramanathan, Sharad / Ringel, Michael S / Scholz, Sonja W / Small, Jonnell / Sperling, Reisa A / Taylor, Angela / Taylor, John-Paul / Ward, Rebecca A / Witten, Lisa / Hyman, Bradley T

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 3, Page(s) 2298–2308

Abstract: Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to ... ...

Abstract	Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.
MeSH term(s)	Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/therapy
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13674
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Article ; Online: A Novel Neural Prediction Error Found in Anterior Cingulate Cortex Ensembles.

Hyman, James Michael / Holroyd, Clay Brian / Seamans, Jeremy Keith

Neuron

2017 Volume 95, Issue 2, Page(s) 447–456.e3

Abstract: The function of the anterior cingulate cortex (ACC) remains controversial, yet many theories suggest a role in behavioral adaptation, partly because a robust event-related potential, the feedback-related negativity (FN), is evoked over the ACC whenever ... ...

Abstract	The function of the anterior cingulate cortex (ACC) remains controversial, yet many theories suggest a role in behavioral adaptation, partly because a robust event-related potential, the feedback-related negativity (FN), is evoked over the ACC whenever expectations are violated. We recorded from the ACC as rats performed a task identical to one that reliably evokes an FN in humans. A subset of neurons was found that encoded expected outcomes as abstract outcome representations. The degree to which a reward/non-reward outcome representation emerged during a trial depended on the history of outcomes that preceded it. A prediction error was generated on incongruent trials as the ensembles shifted from representing the expected to the actual outcome, at the same time point we have previously reported an FN in the local field potential. The results describe a novel mode of prediction error signaling by ACC neurons that is associated with the generation of an FN.
MeSH term(s)	Animals ; Brain Mapping ; Electroencephalography/methods ; Evoked Potentials/physiology ; Feedback, Psychological/physiology ; Gyrus Cinguli/physiology ; Learning/physiology ; Male ; Neurons/physiology ; Rats, Long-Evans ; Reaction Time ; Reward
Language	English
Publishing date	2017-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2017.06.021
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis.

Ly, Cindy V / Ireland, Margaret D / Self, Wade K / Bollinger, James / Jockel-Balsarotti, Jennifer / Herzog, Hillary / Allred, Peggy / Miller, Leah / Doyle, Michael / Anez-Bruzual, Isabel / Trikamji, Bhavesh / Hyman, Ted / Kung, Tyler / Nicholson, Katherine / Bucelli, Robert C / Patterson, Bruce W / Bateman, Randall J / Miller, Timothy M

Annals of clinical and translational neurology

2023 Volume 10, Issue 6, Page(s) 1012–1024

Abstract: Objective: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo ... ...

Abstract	Objective: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. Methods: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. Results: In participants with heterozygous SOD1 Interpretation: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. Trial registration: Clinicaltrials.gov: NCT03449212.
MeSH term(s)	Humans ; Superoxide Dismutase-1/genetics ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Superoxide Dismutase/genetics ; Kinetics
Chemical Substances	Superoxide Dismutase-1 (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2023-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51784
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Article ; Online: Do financial incentives increase mental health treatment engagement? A meta-analysis.

Khazanov, Gabriela K / Morris, Paige E / Beed, Alexander / Jager-Hyman, Shari / Myhre, Karoline / McKay, James R / Feinn, Richard S / Boland, Elaine M / Thase, Michael E

Journal of consulting and clinical psychology

2022 Volume 90, Issue 6, Page(s) 528–544

Abstract: Objective: Engagement in mental health treatment is low, which can lead to poor outcomes. We evaluated the efficacy of offering patients financial incentives to increase their mental health treatment engagement, also referred to as contingency ... ...

Abstract	Objective: Engagement in mental health treatment is low, which can lead to poor outcomes. We evaluated the efficacy of offering patients financial incentives to increase their mental health treatment engagement, also referred to as contingency management. Method: We meta-analyzed studies offering financial incentives for mental health treatment engagement, including increasing treatment attendance, medication adherence, and treatment goal completion. Analyses were run within a multilevel framework. All study designs were included, and sensitivity analyses were run including only randomized and high-quality studies. Results: About 80% of interventions incentivized treatment for substance use disorders. Financial incentives significantly increased treatment attendance (Hedges' g = 0.49, [0.33, 0.64], k = 30, I2 = 83.14), medication adherence (Hedges' g = 0.95, [0.47, 1.44], k = 6, I2 = 87.73), and treatment goal completion (Hedges' g = 0.61, [0.22, 0.99], k = 5, I2 = 60.55), including completing homework, signing treatment plans, and reducing problematic behavior. Conclusions: Financial incentives increase treatment engagement with medium to large effect sizes. We provide strong evidence for their effectiveness in increasing substance use treatment engagement and preliminary evidence for their effectiveness in increasing treatment engagement for other mental health disorders. Future research should prioritize testing the efficacy of incentivizing treatment engagement for mental health disorders aside from substance use. Research must also identify ways to incentivize treatment engagement that improve functioning and long-term outcomes and address ethical and systemic barriers to implementing these interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
MeSH term(s)	Behavior Therapy ; Humans ; Medication Adherence ; Mental Health ; Motivation ; Randomized Controlled Trials as Topic ; Substance-Related Disorders/therapy
Language	English
Publishing date	2022-06-25
Publishing country	United States
Document type	Journal Article ; Meta-Analysis
ZDB-ID	121321-0
ISSN	1939-2117 ; 0022-006X
ISSN (online)	1939-2117
ISSN	0022-006X
DOI	10.1037/ccp0000737
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Article ; Online: Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial.

EBioMedicine

2024 Volume 100, Page(s) 104987

Abstract: Background: Elicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection ... ...

Abstract	Background: Elicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination. Methods: We randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine. Findings: CD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group. Interpretation: This study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans. Funding: National Institute of Allergy and Infectious Diseases, NIH.
MeSH term(s)	Humans ; AIDS Vaccines ; Epitopes ; HIV Infections ; CD4-Positive T-Lymphocytes ; Vaccination ; Immunoglobulin G
Chemical Substances	AIDS Vaccines ; Epitopes ; Immunoglobulin G
Language	English
Publishing date	2024-02-01
Publishing country	Netherlands
Document type	Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2024.104987
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Article ; Online: What is the Functional Relevance of Prefrontal Cortex Entrainment to Hippocampal Theta Rhythms?

Hyman, James Michael / Hasselmo, Michael Erik / Seamans, Jeremy Keith

Frontiers in neuroscience

2011 Volume 5, Page(s) 24

Abstract: ... trials even though the firing rates of these cells did not change (Hyman et al., 2010). This implied ... of the Hyman et al. (2010) data set. This re-analysis revealed that theta-entrained mPFC cells selectively ...

Abstract	There has been considerable interest in the importance of oscillations in the brain and in how these oscillations relate to the firing of single neurons. Recently a number of studies have shown that the spiking of individual neurons in the medial prefrontal cortex (mPFC) become entrained to the hippocampal (HPC) theta rhythm. We recently showed that theta-entrained mPFC cells lost theta-entrainment specifically on error trials even though the firing rates of these cells did not change (Hyman et al., 2010). This implied that the level of HPC theta-entrainment of mPFC units was more predictive of trial outcome than differences in firing rates and that there is more information encoded by the mPFC on working memory tasks than can be accounted for by a simple rate code. Nevertheless, the functional meaning of mPFC entrainment to HPC theta remains a mystery. It is also unclear as to whether there are any differences in the nature of the information encoded by theta-entrained and non-entrained mPFC cells. In this review we discuss mPFC entrainment to HPC theta within the context of previous results as well as provide a more detailed analysis of the Hyman et al. (2010) data set. This re-analysis revealed that theta-entrained mPFC cells selectively encoded a variety of task-relevant behaviors and stimuli while never theta-entrained mPFC cells were most strongly attuned to errors or the lack of expected rewards. In fact, these error responsive neurons were responsible for the error representations exhibited by the entire ensemble of mPFC neurons. A theta reset was also detected in the post-error period. While it is becoming increasingly evident that mPFC neurons exhibit correlates to virtually all cues and behaviors, perhaps phase-locking directs attention to the task-relevant representations required to solve a spatially based working memory task while the loss of theta-entrainment at the start of error trials may represent a shift of attention away from these representations. The subsequent theta reset following error commission, when coupled with the robust responses of never theta-entrained cells, could produce a potent error-evoked signal used to alert the rat to changes in the relationship between task-relevant cues and reward expectations.
Language	English
Publishing date	2011-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-453X
ISSN (online)	1662-453X
ISSN	1662-453X
DOI	10.3389/fnins.2011.00024
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Article ; Online: Author Correction: The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers.

Rosen, Ezra Y / Won, Helen H / Zheng, Youyun / Cocco, Emiliano / Selcuklu, Duygu / Gong, Yixiao / Friedman, Noah D / de Bruijn, Ino / Sumer, Onur / Bielski, Craig M / Savin, Casey / Bourque, Caitlin / Falcon, Christina / Clarke, Nikeysha / Jing, Xiaohong / Meng, Fanli / Zimel, Catherine / Shifman, Sophie / Kittane, Srushti /

Wu, Fan / Ladanyi, Marc / Ebata, Kevin / Kherani, Jennifer / Brandhuber, Barbara J / Fagin, James / Sherman, Eric J / Rekhtman, Natasha / Berger, Michael F / Scaltriti, Maurizio / Hyman, David M / Taylor, Barry S / Drilon, Alexander

Nature communications

2022 Volume 13, Issue 1, Page(s) 1936

Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-29700-y
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Article ; Online: Correction: An Acquired

Hanker, Ariella B / Brewer, Monica Red / Sheehan, Jonathan H / Koch, James P / Sliwoski, Gregory R / Nagy, Rebecca / Lanman, Richard / Berger, Michael F / Hyman, David M / Solit, David B / He, Jie / Miller, Vincent / Cutler, Richard E / Lalani, Alshad S / Cross, Darren / Lovly, Christine M / Meiler, Jens / Arteaga, Carlos L

Cancer discovery

2019 Volume 9, Issue 2, Page(s) 303

Language	English
Publishing date	2019-02-05
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-18-1515
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