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Article ; Online: Imbalance in glucose metabolism regulates the transition of microglia from homeostasis to Disease Associated Microglia stage 1.

Liu, Yuxi / Kwok, Witty / Yoon, Hyojung / Ryu, Jae Cheon / Stevens, Patrick / Hawkinson, Tara R / Shedlock, Cameron J / Ribas, Roberto A / Medina, Terrymar / Keohane, Shannon B / Scharre, Douglas / Bruschweiler-Li, Lei / Bruschweiler, Rafael / Gaultier, Alban / Obrietan, Karl / Sun, Ramon C / Yoon, Sung Ok

The Journal of neuroscience : the official journal of the Society for Neuroscience

2024

Abstract: Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose ... ...

Abstract	Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose dyshomeostasis inhibits DAM1 activation, and PKM2 plays a role. As in tumors, PKM2 was aberrantly elevated in both male and female human AD brains, but unlike in tumors, it is expressed as active tetramers, as well as among TREM2
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1563-23.2024
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Article ; Online: Striatal dopamine neurotransmission is altered in age- and region-specific manner in a Parkinson's disease transgenic mouse.

Medina-Luque, Jose / Piechocinski, Patrick / Feyen, Paul / Sgobio, Carmelo / Herms, Jochen

Scientific reports

2024 Volume 14, Issue 1, Page(s) 164

Abstract: Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson's disease (PD). The progression of the disease and inherent ... ...

Abstract	Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson's disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has been closely related to accumulation of the synaptic protein α-synuclein. However, it is still unclear how α-synuclein affects dopaminergic terminals in different areas of dorsal striatum. Here we demonstrate that the overexpression of human α-synuclein (h-α-syn) interferes with the striatal DA neurotransmission in an age-dependent manner, preferentially in the dorsolateral striatum (DLS) of PDGF-h-α-syn mice. While 3-month-old mice showed an increase at the onset of h-α-syn accumulation in the DLS, 12-month-old mice revealed a decrease in electrically-evoked DA release. The enhanced DA release in 3-month-old mice coincided with better performance in a behavioural task. Notably, DA amplitude alterations were also accompanied by a delay in the DA clearance independently from the animal age. Structurally, dopamine transporter (DAT) was found to be redistributed in larger DAT-positive clumps only in the DLS of 3- and 12-month-old mice. Together, our data provide new insight into the vulnerability of DLS and suggest DAT-related dysfunctionalities from the very early stages of h-α-syn accumulation.
MeSH term(s)	Mice ; Humans ; Animals ; Infant ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Mice, Transgenic ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism ; Dopamine/metabolism ; Corpus Striatum/metabolism ; Synaptic Transmission
Chemical Substances	alpha-Synuclein ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-49600-5
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Article ; Online: Pre-lymphodepletion & infusion endothelial activation and stress index as predictors of clinical outcomes in CAR-T therapy for B-cell lymphoma.

Acosta-Medina, Aldo A / Johnson, Isla McKerrow / Bansal, Radhika / Hathcock, Matthew / Kenderian, Saad J / Durani, Urshila / Khurana, Arushi / Wang, Yucai / Paludo, Jonas / Villasboas, Jose C / Bennani, N Nora / Johnston, Patrick B / Ansell, Stephen M / Lin, Yi / Alkhateeb, Hassan B

Blood cancer journal

2023 Volume 13, Issue 1, Page(s) 7

MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Lymphoma, B-Cell/therapy ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Antigens, CD19
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Letter
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-022-00777-4
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Article ; Online: PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.

Medina, Patrick J / Adams, Val R

Pharmacotherapy

2016 Volume 36, Issue 3, Page(s) 317–334

Abstract: Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab ... ...

Abstract	Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non-small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25-40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard-of-care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD-1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD-1 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune-mediated adverse events (including grade 3-4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD-1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD-1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Checkpoints/immunology ; Humans ; Immunomodulation/drug effects ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/pathology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Programmed Cell Death 1 Receptor ; nivolumab (31YO63LBSN) ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603158-4
ISSN	1875-9114 ; 0277-0008
ISSN (online)	1875-9114
ISSN	0277-0008
DOI	10.1002/phar.1714
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Zs.A 1738: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 585: Show issues

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Article ; Online: Fibroblast activation protein drives tumor metastasis via a protease-independent role in invadopodia stabilization.

Bukhari, Maurish / Patel, Navneeta / Fontana, Rosa / Santiago-Medina, Miguel / Jiang, Yike / Li, Dongmei / Pestonjamasp, Kersi / Christiansen, Victoria J / Jackson, Kenneth W / McKee, Patrick A / Yang, Jing

Cell reports

2023 Volume 42, Issue 10, Page(s) 113302

Abstract: During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels and then extravasate into distant organs to establish metastases. Here, we report a critical role of a transmembrane serine protease fibroblast ... ...

Abstract	During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels and then extravasate into distant organs to establish metastases. Here, we report a critical role of a transmembrane serine protease fibroblast activation protein (FAP) in tumor metastasis. Expression of FAP and TWIST1, a metastasis driver, is significantly correlated in several types of human carcinomas, and FAP is required for TWIST1-induced breast cancer metastasis to the lung. Mechanistically, FAP is localized at invadopodia and required for invadopodia-mediated extracellular matrix degradation independent of its proteolytic activity. Live cell imaging shows that association of invadopodia precursors with FAP at the cell membrane promotes the stabilization and growth of invadopodia precursors into mature invadopodia. Together, our study identified FAP as a functional target of TWIST1 in driving tumor metastasis via promoting invadopodia-mediated matrix degradation and uncovered a proteolytic activity-independent role of FAP in stabilizing invadopodia precursors for maturation.
MeSH term(s)	Humans ; Female ; Podosomes/metabolism ; Cell Line, Tumor ; Peptide Hydrolases/metabolism ; Neoplasm Invasiveness/pathology ; Breast Neoplasms/pathology ; Membrane Proteins/metabolism ; Serine Endopeptidases/metabolism ; Fibroblasts/metabolism ; Extracellular Matrix/metabolism ; Melanoma, Cutaneous Malignant
Chemical Substances	Peptide Hydrolases (EC 3.4.-) ; Membrane Proteins ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113302
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Article ; Online: Does food play a prominent role in visual attention to disgusting stimuli?

Fančovičová, Jana / Prokop, Pavol / Šramelová, Dominika / Thiebaut, Gaëtan / Méot, Alain / Witt, Arnaud / Bonin, Patrick / Medina-Jerez, William

J Ethol. 2022 Jan., v. 40, no. 1 p.23-29

2022

Abstract: Disgust is a basic emotion which protects individuals from potential contamination. It is hypothesized that disgust evolved primarily as a mechanism against oral contamination or as a strategy against disease infections in general. We investigated visual ...

Abstract	Disgust is a basic emotion which protects individuals from potential contamination. It is hypothesized that disgust evolved primarily as a mechanism against oral contamination or as a strategy against disease infections in general. We investigated visual attention to disgusting oral (rotten food) and non-oral (e.g., a tick) and control (e.g., a gull), non-disgusting stimuli using a touch-screen paradigm with a sample of 60 adult participants in Slovakia. We found that disgusting pictures triggered visual attention more than control pictures and that visual attention was not related to an individual’s sensitivity to pathogen disgust. Although participants identified disgusting food items quicker than non-disgusting food pictures, these differences did not reach statistical significance. Findings in this study suggest that the evolution of disgust could have been originally favoured by the repulsion of contaminated food, but the benefits from disease avoidance were soon extended to disgust sensitivity to pathogens that threaten our bodies using non-oral entry points.
Keywords	adults ; evolution ; food contamination ; pathogens ; ticks ; Slovakia
Language	English
Dates of publication	2022-01
Size	p. 23-29.
Publishing place	Springer Japan
Document type	Article ; Online
ZDB-ID	2020048-1
ISSN	1439-5444 ; 0289-0771
ISSN (online)	1439-5444
ISSN	0289-0771
DOI	10.1007/s10164-021-00722-1
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Navigating Athletic Training Position Statements: The Strength of Recommendation Taxonomy System.

Yeargin, Susan / Lopez, Rebecca M / Snyder Valier, Alison R / DiStefano, Lindsay J / McKeon, Patrick O / Medina McKeon, Jennifer M

Journal of athletic training

2020 Volume 55, Issue 8, Page(s) 863–868

Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2070051-9
ISSN	1938-162X ; 1062-6050
ISSN (online)	1938-162X
ISSN	1062-6050
DOI	10.4085/1062-6050-240-19
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Article ; Online: Management of Regional Metastases of Malignant Salivary Gland Neoplasms.

Medina, Jesus / Zbären, Peter / Bradley, Patrick J

Advances in oto-rhino-laryngology

2016 Volume 78, Page(s) 132–140

Abstract: Metastases from salivary gland carcinomas to the cervical lymph nodes are relatively uncommon. However, their impact on prognosis is significant and, thus, it is important to manage them appropriately. Treatment of clinically evident metastases consists ... ...

Abstract	Metastases from salivary gland carcinomas to the cervical lymph nodes are relatively uncommon. However, their impact on prognosis is significant and, thus, it is important to manage them appropriately. Treatment of clinically evident metastases consists primarily of surgery, frequently followed by radiation. Management of the N0 neck, on the other hand, remains controversial. While there seems to be agreement regarding the tumor and patient factors that make it more likely for a patient to harbor subclinical metastases in the lymph nodes, some clinicians prefer to treat those patients with surgery, i.e. a neck dissection, and others prefer to use elective radiation. These different approaches and their rationale will be discussed in detail.
MeSH term(s)	Disease Management ; Humans ; Neoplasm Metastasis ; Salivary Gland Neoplasms/diagnosis ; Salivary Gland Neoplasms/secondary ; Salivary Gland Neoplasms/therapy
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	1662-2847 ; 0065-3071
ISSN (online)	1662-2847
ISSN	0065-3071
DOI	10.1159/000442133
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Article ; Online: Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia.

Leongamornlert, Daniel / Gutiérrez-Abril, Jesús / Lee, SooWah / Barretta, Emilio / Creasey, Thomas / Gundem, Gunes / Levine, Max F / Arango-Ossa, Juan E / Liosis, Konstantinos / Medina-Martinez, Juan S / Zuborne Alapi, Krisztina / Kirkwood, Amy A / Clifton-Hadley, Laura / Patrick, Pip / Jones, David / O'Neill, Laura / Butler, Adam P / Harrison, Christine J / Campbell, Peter /

Patel, Bela / Moorman, Anthony V / Fielding, Adele K / Papaemmanuil, Elli

Blood advances

2023 Volume 7, Issue 15, Page(s) 3862–3873

Abstract: Genomic profiling during the diagnosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification, and treatment decisions. Patients for whom diagnostic screening fails to identify ... ...

Abstract	Genomic profiling during the diagnosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification, and treatment decisions. Patients for whom diagnostic screening fails to identify disease-defining or risk-stratifying lesions are classified as having B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) of paired tumor-normal samples. For 52 patients with B-other, we compared the WGS findings with data from clinical and research cytogenetics. WGS identified a cancer-associated event in 51 of 52 patients, including an established subtype defining genetic alterations that were previously missed with standard-of-care (SoC) genetics in 5 of them. Of the 47 true B-other ALL, we identified a recurrent driver in 87% (41). A complex karyotype via cytogenetics emerges as a heterogeneous group, including distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r and IGK::BCL2). For a subset of 31 cases, we integrated the findings from RNA sequencing (RNA-seq) analysis to include fusion gene detection and classification based on gene expression. Compared with RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes; however, RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrated that WGS can identify clinically relevant genetic abnormalities missed with SoC testing as well as identify leukemia driver events in virtually all cases of B-other ALL.
MeSH term(s)	Humans ; Adult ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Mutation ; Whole Genome Sequencing ; Abnormal Karyotype
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008992
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Zs.A 7153: Show issues

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Article: Distributed Temperature Sensing to Measure Infiltration Rates Across a Groundwater Recharge Basin

Medina, Ricardo / Pham, Christine / Plumlee, Megan H / Hutchinson, Adam / Becker, Matthew W / O'Connell, Patrick J

Ground water. 2020 Nov., v. 58, no. 6

2020

Abstract: Managed aquifer recharge is used to augment groundwater resources and provide resiliency to water supplies threatened by prolonged droughts. It is important that recharge facilities operate at their maximum efficiency to increase the volume of water ... ...

Abstract	Managed aquifer recharge is used to augment groundwater resources and provide resiliency to water supplies threatened by prolonged droughts. It is important that recharge facilities operate at their maximum efficiency to increase the volume of water stored for future use. In this study, we evaluate the use of distributed temperature sensing (DTS) technology as a tool to measure high‐resolution infiltration rates at a large‐scale recharge facility. Fiber optic cable was laid out inside a spreading basin in a spiral pattern, at two different depths. The cables measured the propagation of diurnal surface water temperature oscillations into the basin depth. The rate of heat propagation is proportional to the velocity of the water, making it possible to estimate the infiltration rate from the temperature measurements. Our results showed that the infiltration rate calculated from DTS, averaged over the entire basin, was within 5% of the infiltration rate calculated using a conventional metering method. The high‐resolution data obtained from DTS, both spatially and temporally, revealed heterogeneous infiltration rates throughout the basin; furthermore, tracking the evolution of infiltration rates over time revealed regions with consistently high infiltration rates, regions with consistently low infiltration rates, and regions that evolved from high to low rates, which suggested clogging within that region. Water utilities can take advantage of the high‐resolution information obtained from DTS to better manage recharge basins and make decisions about cleaning schedule, frequency, and extent, leading to improved basin management strategies, reduced O&M costs, and increased groundwater recharge.
Keywords	aquifers ; basins ; evolution ; fiber optics ; groundwater ; groundwater recharge ; heat ; infiltration rate ; surface water temperature
Language	English
Dates of publication	2020-11
Size	p. 913-923.
Publishing place	Blackwell Publishing Ltd
Document type	Article
Note	NAL-AP-2-clean ; JOURNAL ARTICLE
ZDB-ID	246212-6
ISSN	1745-6584 ; 0017-467X
ISSN (online)	1745-6584
ISSN	0017-467X
DOI	10.1111/gwat.13007
Database	NAL-Catalogue (AGRICOLA)

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