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Article ; Online: A phase I, single-center, open-label study to investigate the absorption, distribution, metabolism and excretion of encorafenib following a single oral dose of 100 mg [

Wollenberg, Lance / Hahn, Erik / Williams, Jason / Litwiler, Kevin

2023 Volume 11, Issue 5, Page(s) e01140

Abstract: Encorafenib is a novel kinase inhibitor of BRAF V600E as well as wild-type BRAF and CRAF and has received approval, in combination with binimetinib, to treat BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma or in combination with ...

Abstract	Encorafenib is a novel kinase inhibitor of BRAF V600E as well as wild-type BRAF and CRAF and has received approval, in combination with binimetinib, to treat BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma or in combination with cetuximab to treat BRAF V600E mutation-positive colorectal cancer. The absorption, distribution, metabolism and excretion (ADME) of encorafenib was studied by administering [
MeSH term(s)	Humans ; Male ; Proto-Oncogene Proteins B-raf/therapeutic use ; Sulfonamides ; Antineoplastic Agents ; Melanoma/drug therapy
Chemical Substances	encorafenib (8L7891MRB6) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Sulfonamides ; Antineoplastic Agents
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.1140
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Detection and molecular characterization of

van den Wollenberg, L / van Maanen, C / Buter, R / Janszen, P / Rey, F / van Engelen, E

Frontiers in veterinary science

2023 Volume 10, Page(s) 1225528

Abstract: Introduction: Abscessation of equine head lymph nodes can be caused by various bacteria, but Streptococcus : Methods: Culture followed by identification using MALDI-TOF MS, MIC testing and whole genome sequencing (WGS) was performed to characterize ... ...

Abstract	Introduction: Abscessation of equine head lymph nodes can be caused by various bacteria, but Streptococcus Methods: Culture followed by identification using MALDI-TOF MS, MIC testing and whole genome sequencing (WGS) was performed to characterize the bacteria. Results: Bacterial culture and subsequent identification with MALDI-TOF MS resulted in the reliable identification of Conclusion: We conclude that
Language	English
Publishing date	2023-07-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1225528
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Article ; Online: The role of habitual learning in premotor attention allocation.

Topfstedt, Christof Elias / Wollenberg, Luca / Schenk, Thomas

Journal of vision

2022 Volume 23, Issue 5, Page(s) 19

Abstract: Dual-task studies have demonstrated that goal-directed actions are typically preceded by a premotor shift of visual attention toward the movement goal location. This finding is often taken as evidence for an obligatory coupling between attention and ... ...

Abstract	Dual-task studies have demonstrated that goal-directed actions are typically preceded by a premotor shift of visual attention toward the movement goal location. This finding is often taken as evidence for an obligatory coupling between attention and motor preparation. Here, we examined whether this coupling entails a habitual component relating to an expectation of spatial congruence between visual and motor targets. In two experiments, participants had to identify a visual discrimination target (DT) while preparing variably delayed pointing movements to a motor target (MT). To induce distinct expectations regarding the DT position, different groups of participants performed a training phase in which the DT either always appeared at MT, opposite to MT, or at an unpredictable position. In a subsequent test phase, the DT position was randomized to assess the impact of learned expectancy on premotor attention allocation. Although we applied individually determined DT presentation times in the test phase of Experiment 1, a fixed DT presentation time was used in Experiment 2. Both experiments yielded evidence for attentional enhancement at the expected DT position. Although interpretability of this effect was limited in Experiment 1 because of between-group differences in DT presentation time, results of Experiment 2 were much clearer. Specifically, a marked discrimination benefit was observed at the position opposite to MT in participants anticipating the DT at this position, whereas no statistically significant benefit was found at MT. Crucially, this was observed at short movement delays, demonstrating that expectation of spatial incongruence between visual and motor targets allows for decoupling of attentional resources from ongoing motor preparation. Based on our findings, we suggest that premotor attention shifts entail a considerable habitual component rather than being the sole result of motor programming.
MeSH term(s)	Humans ; Reaction Time ; Visual Perception ; Learning ; Movement ; Discrimination, Psychological ; Psychomotor Performance
Language	English
Publishing date	2022-08-28
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2106064-2
ISSN	1534-7362 ; 1534-7362
ISSN (online)	1534-7362
ISSN	1534-7362
DOI	10.1167/jov.23.5.19
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Article ; Online: Eye and hand movements disrupt attentional control.

Hanning, Nina Maria / Wollenberg, Luca / Jonikaitis, Donatas / Deubel, Heiner

PloS one

2022 Volume 17, Issue 1, Page(s) e0262567

Abstract: Voluntary attentional control is the ability to selectively focus on a subset of visual information in the presence of other competing stimuli-a marker of cognitive control enabling flexible, goal-driven behavior. To test its robustness, we contrasted ... ...

Abstract	Voluntary attentional control is the ability to selectively focus on a subset of visual information in the presence of other competing stimuli-a marker of cognitive control enabling flexible, goal-driven behavior. To test its robustness, we contrasted attentional control with the most common source of attentional orienting in daily life: attention shifts prior to goal-directed eye and hand movements. In a multi-tasking paradigm, human participants attended at a location while planning eye or hand movements elsewhere. Voluntary attentional control suffered with every simultaneous action plan, even under reduced task difficulty and memory load-factors known to interfere with attentional control. Furthermore, the performance cost was limited to voluntary attention: We observed simultaneous attention benefits at two movement targets without attentional competition between them. This demonstrates that the visual system allows for the concurrent representation of multiple attentional foci. Since attentional control is extremely fragile and dominated by premotor attention shifts, we propose that action-driven selection plays the superordinate role for visual selection.
MeSH term(s)	Adult ; Attention/physiology ; Cues ; Eye Movements/physiology ; Female ; Hand/physiology ; Healthy Volunteers ; Humans ; Male ; Movement/physiology ; Photic Stimulation/methods ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Saccades/physiology ; Visual Perception/physiology
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0262567
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Article ; Online: Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations.

Hahn, Erik / Chavira, Renae / Wollenberg, Lance / Tan, Weiwei / Reddy, Micaela B

Clinical and translational science

2023 Volume 16, Issue 12, Page(s) 2675–2686

Abstract: Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600-mutant kinase approved for patients with BRAF-mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be ... ...

Abstract	Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600-mutant kinase approved for patients with BRAF-mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug-drug interactions when co-administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P-gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50-mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUC
MeSH term(s)	Humans ; Antineoplastic Agents/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Diltiazem/therapeutic use ; Drug Interactions ; Headache/chemically induced ; Melanoma/drug therapy ; Melanoma/genetics ; Mutation ; Protein Kinase Inhibitors/pharmacokinetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/therapeutic use
Chemical Substances	Antineoplastic Agents ; BRAF protein, human (EC 2.7.11.1) ; Cytochrome P-450 CYP3A Inhibitors ; Diltiazem (EE92BBP03H) ; encorafenib (8L7891MRB6) ; posaconazole (6TK1G07BHZ) ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13662
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Article ; Online: Clinical Evaluation of the Effect of Encorafenib on Bupropion, Rosuvastatin, and Coproporphyrin I and Considerations for Statin Coadministration.

Piscitelli, Joseph / Reddy, Micaela B / Wollenberg, Lance / Del Frari, Laurence / Gong, Jason / Wood, Linda / Zhang, Yizhong / Matschke, Kyle / Williams, Jason H

Clinical pharmacokinetics

2024 Volume 63, Issue 4, Page(s) 483–496

Abstract: Background and objectives: Encorafenib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma or metastatic colorectal cancer, respectively, with selected BRAF V600 mutations. A clinical drug-drug ... ...

Abstract	Background and objectives: Encorafenib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma or metastatic colorectal cancer, respectively, with selected BRAF V600 mutations. A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of encorafenib on rosuvastatin, a sensitive substrate of OATP1B1/3 and breast cancer resistance protein (BCRP), and bupropion, a sensitive CYP2B6 substrate. Coproporphyrin I (CP-I), an endogenous substrate for OATP1B1, was measured in a separate study to deconvolute the mechanism of transporter DDI. Methods: DDI study participants received a single oral dose of rosuvastatin (10 mg) and bupropion (75 mg) on days - 7, 1, and 14 and continuous doses of encorafenib (450 mg QD) and binimetinib (45 mg BID) starting on day 1. The CP-I data were collected from participants in a phase 3 study who received encorafenib (300 mg QD) and cetuximab (400 mg/m Results: Bupropion exposure was not increased, whereas rosuvastatin C Conclusion: The results from these clinical studies suggest that encorafenib does not cause clinically relevant CYP2B6 induction or inhibition but is an inhibitor of BCRP and may also inhibit OATP1B1/3 to a lesser extent. Based on these results, it may be necessary to consider switching statins or reducing statin dosage accordingly for coadministration with encorafenib. Clinical trial registration: ClinicalTrials.gov NCT03864042, registered 6 March 2019.
MeSH term(s)	Humans ; Rosuvastatin Calcium/pharmacokinetics ; Rosuvastatin Calcium/administration & dosage ; Male ; Drug Interactions ; Female ; Middle Aged ; Adult ; Sulfonamides/administration & dosage ; Sulfonamides/pharmacokinetics ; Sulfonamides/pharmacology ; Carbamates/administration & dosage ; Carbamates/pharmacokinetics ; Bupropion/administration & dosage ; Bupropion/pharmacokinetics ; Coproporphyrins ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Liver-Specific Organic Anion Transporter 1/antagonists & inhibitors ; Liver-Specific Organic Anion Transporter 1/genetics ; Liver-Specific Organic Anion Transporter 1/metabolism ; Aged ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; Young Adult
Chemical Substances	Rosuvastatin Calcium (83MVU38M7Q) ; encorafenib (8L7891MRB6) ; Sulfonamides ; Carbamates ; Bupropion (01ZG3TPX31) ; Coproporphyrins ; coproporphyrin I (531-14-6) ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Liver-Specific Organic Anion Transporter 1 ; SLCO1B1 protein, human ; ATP Binding Cassette Transporter, Subfamily G, Member 2
Language	English
Publishing date	2024-02-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-024-01352-9
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Article ; Online: Visual attention and eye movement control during oculomotor competition.

Wollenberg, Luca / Hanning, Nina M / Deubel, Heiner

Journal of vision

2020 Volume 20, Issue 9, Page(s) 16

Abstract: Saccadic eye movements are typically preceded by selective shifts of visual attention. Recent evidence, however, suggests that oculomotor selection can occur in the absence of attentional selection when saccades erroneously land in between nearby ... ...

Abstract	Saccadic eye movements are typically preceded by selective shifts of visual attention. Recent evidence, however, suggests that oculomotor selection can occur in the absence of attentional selection when saccades erroneously land in between nearby competing objects (saccade averaging). This study combined a saccade task with a visual discrimination task to investigate saccade target selection during episodes of competition between a saccade target and a nearby distractor. We manipulated the spatial predictability of target and distractor locations and asked participants to execute saccades upon variably delayed go-signals. This allowed us to systematically investigate the capacity to exert top-down eye movement control (as reflected in saccade endpoints) based on the spatiotemporal dynamics of visual attention during movement preparation (measured as visual sensitivity). Our data demonstrate that the predictability of target and distractor locations, despite not affecting the deployment of visual attention prior to movement preparation, largely improved the accuracy of short-latency saccades. Under spatial uncertainty, a short go-signal delay likewise enhanced saccade accuracy substantially, which was associated with a more selective deployment of attentional resources to the saccade target. Moreover, we observed a systematic relationship between the deployment of visual attention and saccade accuracy, with visual discrimination performance being significantly enhanced at the saccade target relative to the distractor only before the execution of saccades accurately landing at the saccade target. Our results provide novel insights linking top-down eye movement control to the operation of selective visual attention during movement preparation.
MeSH term(s)	Adult ; Discrimination, Psychological/physiology ; Eye Movements/physiology ; Female ; Humans ; Male ; Saccades ; Visual Perception/physiology ; Young Adult
Language	English
Publishing date	2020-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2106064-2
ISSN	1534-7362 ; 1534-7362
ISSN (online)	1534-7362
ISSN	1534-7362
DOI	10.1167/jov.20.9.16
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Article ; Online: Reference intervals for trace mineral and heavy metal concentrations in horse livers in the Netherlands.

van der Merwe, Deon / van den Wollenberg, Linda / van Hees-Valkenborg, Jolien / de Haan, Tara / van der Drift, Saskia

Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc

2023 Volume 35, Issue 6, Page(s) 737–741

Abstract: We determined reference intervals (RIs) for concentrations of trace minerals and toxic elements based on liver samples from 122 apparently healthy horses at 2 slaughter facilities in the Netherlands. Samples were collected during the spring and fall of ... ...

Abstract	We determined reference intervals (RIs) for concentrations of trace minerals and toxic elements based on liver samples from 122 apparently healthy horses at 2 slaughter facilities in the Netherlands. Samples were collected during the spring and fall of 2021, and the sex and age of the horses were registered upon sampling. Concentrations of arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel, selenium, vanadium, and zinc were measured in liver samples using inductively coupled plasma-mass spectrometry (ICP-MS) after nitric acid digestion. RIs were calculated using Reference Value Advisor software. The concentrations of most elements were not significantly different between sexes or in different seasons. Cadmium concentrations were higher than the European maximum residue limit of 2 mg/kg DW in 89% of livers. Positive significant correlations were observed between some elements (iron, molybdenum, lead, vanadium), and significant negative correlations between others (manganese, iron).
MeSH term(s)	Horses ; Animals ; Trace Elements ; Manganese ; Molybdenum/analysis ; Cadmium/analysis ; Vanadium/analysis ; Netherlands ; Metals, Heavy/analysis ; Copper ; Iron/analysis ; Selenium ; Liver/chemistry
Chemical Substances	Trace Elements ; Manganese (42Z2K6ZL8P) ; Molybdenum (81AH48963U) ; Cadmium (00BH33GNGH) ; Vanadium (00J9J9XKDE) ; Metals, Heavy ; Copper (789U1901C5) ; Iron (E1UOL152H7) ; Selenium (H6241UJ22B)
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	287603-6
ISSN	1943-4936 ; 1040-6387
ISSN (online)	1943-4936
ISSN	1040-6387
DOI	10.1177/10406387231193328
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Zs.A 3645: Show issues

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Article ; Online: Effect of Food and a Proton-Pump Inhibitor on the Absorption of Encorafenib: An

Piscitelli, Joseph / Hens, Bart / Tomaszewska, Irena / Wollenberg, Lance / Litwiler, Kevin / McAllister, Mark / Reddy, Micaela

Molecular pharmaceutics

2023 Volume 20, Issue 5, Page(s) 2589–2599

Abstract: Encorafenib is a kinase inhibitor indicated for the treatment of patients with BRAF mutant melanoma and BRAF mutant metastatic colorectal cancer. To understand the effect of food and coadministration with a proton-pump inhibitor (PPI), ...

Abstract	Encorafenib is a kinase inhibitor indicated for the treatment of patients with BRAF mutant melanoma and BRAF mutant metastatic colorectal cancer. To understand the effect of food and coadministration with a proton-pump inhibitor (PPI),
MeSH term(s)	Humans ; Proton Pump Inhibitors/pharmacokinetics ; Proto-Oncogene Proteins B-raf ; Administration, Oral ; Food-Drug Interactions ; Pharmaceutical Preparations ; Solubility ; Cross-Over Studies ; Biological Availability
Chemical Substances	Proton Pump Inhibitors ; encorafenib (8L7891MRB6) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Pharmaceutical Preparations
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c00016
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Zs.A 6250: Show issues

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Article ; Online: Investigating the Deployment of Visual Attention Before Accurate and Averaging Saccades via Eye Tracking and Assessment of Visual Sensitivity.

Wollenberg, Luca / Deubel, Heiner / Szinte, Martin

Journal of visualized experiments : JoVE

2019 , Issue 145

Abstract: This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we recorded the eye position of human participants engaged in a saccade task via eye tracking and assessed ... ...

Abstract	This experimental protocol was designed to investigate whether visual attention is obligatorily deployed at the endpoint of saccades. To this end, we recorded the eye position of human participants engaged in a saccade task via eye tracking and assessed visual orientation discrimination performance at various locations during saccade preparation. Importantly, instead of using a single saccade target paradigm for which the saccade endpoint typically coincides roughly with the target, this protocol comprised the presentation of two nearby saccade targets, leading to a distinct spatial dissociation between target locations and saccade endpoint on a substantial number of trials. The paradigm allowed us to compare presaccadic visual discrimination performance at the endpoint of accurate saccades (landing at one of the saccade targets) and of averaging saccades (landing at an intermediate location in between the two targets). We observed a selective enhancement of visual sensitivity at the endpoint of accurate saccades but not at the endpoint of averaging saccades. Rather, before the execution of averaging saccades, visual sensitivity was equally enhanced at both targets, suggesting that saccade averaging follows from unresolved attentional selection among the saccade targets. These results argue against a mandatory coupling between visual attention and saccade programming based on a direct measure of presaccadic visual sensitivity rather than saccadic reaction times, which have been used in other protocols to draw similar conclusions. While our protocol provides a useful framework to investigate the relationship between visual attention and saccadic eye movements at the behavioral level, it can also be combined with electrophysiological measures to extend insights at the neuronal level.
MeSH term(s)	Adult ; Attention/physiology ; Female ; Humans ; Male ; Photic Stimulation ; Reaction Time ; Saccades/physiology ; Visual Perception/physiology ; Young Adult
Language	English
Publishing date	2019-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59162
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