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Article ; Online: Een 17-jarig meisje met oedeem van de bovenoogleden.

Verkaik, Romy C J / Hendricx, Melanie F M / Timmer, Ferdinand C A

2023 Volume 167

Abstract: Case of a 17-year-old female with rhinitis, intermittent fever, painful enlarged lymph nodes and painless bilateral upper eyelid swelling. Complicated sinusitis and vascular pathology were ruled out, but Epstein-Barr serology was positive. Bilateral ... ...

Title translation	A 17-year-old girl with bilateral swollen upper eyelids.
Abstract	Case of a 17-year-old female with rhinitis, intermittent fever, painful enlarged lymph nodes and painless bilateral upper eyelid swelling. Complicated sinusitis and vascular pathology were ruled out, but Epstein-Barr serology was positive. Bilateral upper eyelid edema can be an early presentation of mononucleosis infectiosa and is called the Hoagland sign.
MeSH term(s)	Female ; Humans ; Adolescent ; Eyelids/pathology ; Infectious Mononucleosis/complications ; Fever/etiology ; Angioedema ; Lymph Nodes
Language	Dutch
Publishing date	2023-05-10
Publishing country	Netherlands
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Likelihood-ratio test statistic for the finite-sample case in nonlinear ordinary differential equation models.

Tönsing, Christian / Steiert, Bernhard / Timmer, Jens / Kreutz, Clemens

PLoS computational biology

2023 Volume 19, Issue 9, Page(s) e1011417

Abstract: Likelihood ratios are frequently utilized as basis for statistical tests, for model selection criteria and for assessing parameter and prediction uncertainties, e.g. using the profile likelihood. However, translating these likelihood ratios into p-values ...

Abstract	Likelihood ratios are frequently utilized as basis for statistical tests, for model selection criteria and for assessing parameter and prediction uncertainties, e.g. using the profile likelihood. However, translating these likelihood ratios into p-values or confidence intervals requires the exact form of the test statistic's distribution. The lack of knowledge about this distribution for nonlinear ordinary differential equation (ODE) models requires an approximation which assumes the so-called asymptotic setting, i.e. a sufficiently large amount of data. Since the amount of data from quantitative molecular biology is typically limited in applications, this finite-sample case regularly occurs for mechanistic models of dynamical systems, e.g. biochemical reaction networks or infectious disease models. Thus, it is unclear whether the standard approach of using statistical thresholds derived for the asymptotic large-sample setting in realistic applications results in valid conclusions. In this study, empirical likelihood ratios for parameters from 19 published nonlinear ODE benchmark models are investigated using a resampling approach for the original data designs. Their distributions are compared to the asymptotic approximation and statistical thresholds are checked for conservativeness. It turns out, that corrections of the likelihood ratios in such finite-sample applications are required in order to avoid anti-conservative results.
MeSH term(s)	Algorithms ; Likelihood Functions ; Nonlinear Dynamics ; Uncertainty
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1011417
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Article ; Online: Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds.

Dewey, Marley J / Timmer, Kyle B / Blystone, Ashley / Lu, Crislyn / Harley, Brendan A C

Journal of biomedical materials research. Part A

2023 Volume 112, Issue 3, Page(s) 336–347

Abstract: ... the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization ...

Abstract	Current treatments for craniomaxillofacial (CMF) defects motivate the design of instructive biomaterials that can promote osteogenic healing of complex bone defects. We report methods to promote in vitro osteogenesis of human mesenchymal stem cells (hMSCs) within a model mineralized collagen scaffold via the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization. An addition of 5 w/v% ascorbic acid into the base mineralized collagen scaffold significantly changes key morphology characteristics including porosity, macrostructure, and microstructure. This modification promotes hMSC metabolic activity, ALP activity, and hMSC-mediated deposition of calcium and phosphorous. Additionally, the incorporation of ascorbic acid influences osteogenic gene expression (BMP-2, RUNX2, COL1A2) and delays the expression of genes associated with osteoclast activity and bone resorption (OPN, CTSK), though it reduces the secretion of OPG. Together, these findings highlight ascorbic acid as a relevant component for mineralized collagen scaffold design to promote osteogenic differentiation and new bone formation for improved CMF outcomes.
MeSH term(s)	Humans ; Osteogenesis ; Tissue Scaffolds/chemistry ; Ascorbic Acid/pharmacology ; Mesenchymal Stem Cells ; Collagen/chemistry ; Cell Differentiation ; Cells, Cultured
Chemical Substances	Ascorbic Acid (PQ6CK8PD0R) ; Collagen (9007-34-5)
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37628
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Article: Palliative Care and Mental Health among Pancreatic Cancer Patients in the United States: An Examination of Service Utilization and Health Outcomes.

Subramaniam, Divya S / Zhang, Zidong / Timmer, Zachary / DeMarco, Elisabeth C / Poirier, Michael P / Hinyard, Leslie J

Healthcare (Basel, Switzerland)

2024 Volume 12, Issue 8

Abstract: Introduction: Palliative care (PC) utilization remains low among pancreatic cancer patients. This study explores the association of PC with mental health service and pharmacotherapy utilization among pancreatic cancer patients.: Methods: ... ...

Abstract	Introduction: Palliative care (PC) utilization remains low among pancreatic cancer patients. This study explores the association of PC with mental health service and pharmacotherapy utilization among pancreatic cancer patients. Methods: Retrospective analysis was conducted on a sample of patients in the United States with newly diagnosed pancreatic cancer using Electronic Health Record data from Optum's Integrated Claims-Clinical data set. Subsequent diagnoses of anxiety and depression and PC consultation encounters were determined using ICD-9/10 codes. Adjusted associations of mental health treatments with PC and patient characteristics were quantified using multiple logistic regression. Results: Among newly diagnosed pancreatic cancer patients ( Discussion: Our study emphasizes underutilization of PC and MH treatment for pancreatic cancer patients. These findings imply a crucial need for further investigation into palliative care's role in addressing mental health concerns among pancreatic cancer patients.
Language	English
Publishing date	2024-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare12080842
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Article: Optimal Experimental Design Based on Two-Dimensional Likelihood Profiles.

Litwin, Tim / Timmer, Jens / Kreutz, Clemens

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 800856

Abstract: Dynamic behavior of biological systems is commonly represented by non-linear models such as ordinary differential equations. A frequently encountered task in such systems is the estimation of model parameters based on measurement of biochemical compounds. ...

Abstract	Dynamic behavior of biological systems is commonly represented by non-linear models such as ordinary differential equations. A frequently encountered task in such systems is the estimation of model parameters based on measurement of biochemical compounds. Non-linear models require special techniques to estimate the uncertainty of the obtained model parameters and predictions, e.g. by exploiting the concept of the profile likelihood. Model parameters with significant uncertainty associated with their estimates hinder the interpretation of model results. Informing these model parameters by optimal experimental design minimizes the additional amount of data and therefore resources required in experiments. However, existing techniques of experimental design either require prior parameter distributions in Bayesian approaches or do not adequately deal with the non-linearity of the system in frequentist approaches. For identification of optimal experimental designs, we propose a two-dimensional profile likelihood approach, providing a design criterion which meaningfully represents the expected parameter uncertainty after measuring data for a specified experimental condition. The described approach is implemented into the open source toolbox Data2Dynamics in Matlab. The applicability of the method is demonstrated on an established systems biology model. For this demonstration, available data has been censored to simulate a setting in which parameters are not yet well determined. After determining the optimal experimental condition from the censored ones, a realistic evaluation was possible by re-introducing the censored data point corresponding to the optimal experimental condition. This provided a validation that our method is feasible in real-world applications. The approach applies to, but is not limited to, models in systems biology.
Language	English
Publishing date	2022-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.800856
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Article ; Online: Detecting frequency modulation in stochastic time-series data.

Hauber, Adrian L / Sigloch, Christian / Timmer, Jens

Physical review. E

2022 Volume 106, Issue 2-1, Page(s) 24204

Abstract: We propose a statistical test to identify nonstationary frequency-modulated stochastic processes from time-series data. Our method uses the instantaneous phase as a discriminatory statistics with reliable critical values derived from surrogate data. We ... ...

Abstract	We propose a statistical test to identify nonstationary frequency-modulated stochastic processes from time-series data. Our method uses the instantaneous phase as a discriminatory statistics with reliable critical values derived from surrogate data. We simulated an oscillatory second-order autoregressive process to evaluate the size and power of the test. We found that the test we propose is able to correctly identify more than 99% of nonstationary data when the frequency of the simulated data is doubled after the first half of the time series. Our method is easily interpretable, computationally cheap, and does not require choosing hyperparameters that are dependent on the data.
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.106.024204
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Article ; Online: Comparison of Two Versus Three Bilateral Botulinum Toxin Injections Prior to Abdominal Wall Reconstruction.

Timmer, Allard S / Ibrahim, Faduma / Claessen, Jeroen J M / Aehling, Carolin J / Kemper, Tom C P M / Rutten, Martin V H / Boermeester, Marja A

Journal of abdominal wall surgery : JAWS

2023 Volume 2, Page(s) 11382

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article
ISSN	2813-2092
ISSN (online)	2813-2092
DOI	10.3389/jaws.2023.11382
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Article ; Online: Response to: Comment on: The extent of unnecessary tooth loss due to extractions prior to radiotherapy based on radiation field and dose in patients with head and neck cancer.

Buurman, Doke J M / Speksnijder, Caroline M / Granzier, Marlies E / Timmer, Veronique C M L / Hoebers, Frank J P / Kessler, Peter

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 190, Page(s) 110026

MeSH term(s)	Humans ; Tooth Loss ; Head and Neck Neoplasms/radiotherapy ; Radiotherapy Dosage ; Radiation Oncology
Language	English
Publishing date	2023-11-24
Publishing country	Ireland
Document type	Letter
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.110026
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Zs.A 1926: Show issues

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Article ; Online: Functional decline in persons with haemophilia and factors associated with deterioration.

Blokzijl, Johan / Pisters, Martijn F / Veenhof, Cindy / Schutgens, Roger E G / Timmer, Merel A

Haemophilia : the official journal of the World Federation of Hemophilia

2023 Volume 29, Issue 3, Page(s) 790–798

Abstract: Introduction: The World Haemophilia Federation advises regular musculoskeletal assessment covering all International Classification of Functioning and Health (ICF) domains, including limitations in activities and participation in persons with ... ...

Abstract	Introduction: The World Haemophilia Federation advises regular musculoskeletal assessment covering all International Classification of Functioning and Health (ICF) domains, including limitations in activities and participation in persons with haemophilia (PWH). This enables clinicians to detect changes early and enable adjustments in personalized healthcare when needed. However, data on the course of physical functioning and occurrence of decline is lacking. The aim of this study is to describe changes in perceived limitations in activities of PWH and to identify factors associated with a change. Methods: Data were collected from medical health records of regular check-up visits of adults with moderate and severe haemophilia in two time periods. Perceived limitations in activities was measured with the Haemophilia Activities List (HAL). Association between variables (e.g., age, body mass index, bleeding rate and synovitis) and change in perceived limitations was assessed using a generalized linear model. Results: A total of 104 PWH were included. At T0, the median HAL sum score was 79.5 (IQR 62.1-93.6) and at T1 the median HAL sum score was 74.2 (IQR 57.5-88.3). A functional decline was found in 35.6% of PWH, 55.8% remained stable and 8.7% improved. Among other variables, a BMI > 30 kg/m Conclusion: The majority of PWH remained stable in their perceived functional ability over mid-long term (median 3.5 years). However, about a third showed a clinical relevant decline in their functional ability.
MeSH term(s)	Adult ; Humans ; Hemophilia A/epidemiology ; Hemophilia B/complications ; Activities of Daily Living ; Hemorrhage/complications ; Synovitis/complications
Language	English
Publishing date	2023-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14783
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Zs.A 4249: 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)
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Article ; Online: The extent of unnecessary tooth loss due to extractions prior to radiotherapy based on radiation field and dose in patients with head and neck cancer.

Buurman, Doke J M / Speksnijder, Caroline M / Granzier, Marlies E / Timmer, Veronique C M L / Hoebers, Frank J P / Kessler, Peter

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 187, Page(s) 109847

Abstract: Background and purpose: Prior to radiotherapy (RT), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. To allow enough time for adequate wound healing prior to RT, decisions are made based on the estimated ... ...

Abstract	Background and purpose: Prior to radiotherapy (RT), teeth with poor prognosis that pose a risk for post-RT osteoradionecrosis (ORN) are removed. To allow enough time for adequate wound healing prior to RT, decisions are made based on the estimated radiation dose. This study aimed to gain insight into (1) the overall number of teeth extracted and (2) the patient and tumor characteristics associated with the number of redundantly extracted teeth. Materials and methods: Patients with head and neck cancer (HNC), treated with RT between 2015 and 2019, were included in this cross-sectional study. For each extracted tooth the radiation dose was calculated retrospectively. The cut-off point for valid extraction was set at ≥ 40 Gy in accordance with the national protocol. Potential factors for doses ≥ 40 Gy were identified, including age, sex, tumor location, tumor (T) and nodal stage (N), overall tumor stage and number of teeth extracted. Results: A total of 1759 teeth were removed from 358 patients. Of these 1759 teeth, 1274 (74%) appeared to have been removed redundantly, based on the mean dose (D Conclusion: To our knowledge this is the first study to provide insight into the amount of teeth redundantly extracted prior to RT and represents a step forward in de-escalating the damage to the masticatory system prior to RT.
MeSH term(s)	Humans ; Retrospective Studies ; Tooth Loss ; Cross-Sectional Studies ; Head and Neck Neoplasms/radiotherapy ; Tooth Extraction
Language	English
Publishing date	2023-08-04
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109847
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