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Article ; Online: A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.

Schiemsky, Toon / Van Hoovels, Lieve / Desmet, Koen J O / Phylipsen, Marion / Harteveld, Cornelis L / Kieffer, Davy M J

2015 Volume 39, Issue 6, Page(s) 435–437

Abstract: ... DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T ...

Abstract	We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.
MeSH term(s)	Amino Acid Substitution ; Codon ; DNA Mutational Analysis ; Erythrocyte Indices ; Female ; Gene Expression ; Genotype ; Glycated Hemoglobin A/genetics ; Glycated Hemoglobin A/metabolism ; Hemoglobin J/genetics ; Hemoglobin J/metabolism ; Hemoglobinopathies/diagnosis ; Hemoglobinopathies/genetics ; Humans ; Middle Aged ; Mutation ; Phenotype ; beta-Globins/genetics
Chemical Substances	Codon ; Glycated Hemoglobin A ; beta-Globins ; Hemoglobin J (58128-48-6) ; hemoglobin J-Amiens (73989-36-3)
Language	English
Publishing date	2015
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	750615-6
ISSN	1532-432X ; 0363-0269
ISSN (online)	1532-432X
ISSN	0363-0269
DOI	10.3109/03630269.2015.1079218
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Zs.A 1345: Show issues

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Article ; Online: The use of mixed reality technology within the donor collection experience.

Pandey, Suchitra / Goel, Ruchika / Kapral, Jennifer / Kieffer, Theodore / Kang, Jason / Shaffer, Hunter / Hermelin, Daniela / Hartwell, Beth

Transfusion

2024 Volume 64, Issue 2, Page(s) 315–324

Abstract: Background: Mixed reality (MR), a form of virtual reality (VR), provides an immersive and interactive experience for the user. Given VR's benefits in patients undergoing needle insertion procedures, MR's usability, impact on anxiety, and safety were ... ...

Abstract	Background: Mixed reality (MR), a form of virtual reality (VR), provides an immersive and interactive experience for the user. Given VR's benefits in patients undergoing needle insertion procedures, MR's usability, impact on anxiety, and safety were evaluated in the blood donation setting. Study design and methods: Whole blood donors ≥18 years old (yo) were enrolled at two blood centers and provided a MR headset with independently developed software to wear during blood donation. Pre- and post-donation questionnaires were conducted, and reaction data were reviewed. A post-study questionnaire was also completed by staff who assisted donors with MR. Descriptive statistics, bivariate analyses, and multinomial logistic regression were performed, and p values determined statistical significance between variables. Results: A total of 282 donors completed the study. 84% wanted to try MR because it seemed fun/different/cool/interesting, and most staff (69%) and donors (68%) found MR easy to use. Baseline subjective anxiety, reported by 50.3% (more often in females, first-time donors, and donors <20 yo), was reduced by MR in 68.4% of donors, and there was a 3.6 times higher odds of anxiety reduction with MR. 54% of donors with baseline anxiety would use MR again with the highest future interest in young donors. Donor reactions while using MR were mild and included pre-faint reactions and hematomas. Conclusion: This study demonstrates the potential of MR in reducing donor anxiety, its feasibility during blood donation, and its safety in blood donors. MR is an innovative technology that holds promise to increase donor engagement, satisfaction, and retention.
MeSH term(s)	Female ; Humans ; Adolescent ; Augmented Reality ; Blood Donors ; Anxiety/etiology ; Syncope ; Needles
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.17712
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Zs.A 284: Show issues

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Article ; Online: Thyroid Hormone Levels Correlate With the Maturation of Implanted Pancreatic Endoderm Cells in Patients With Type 1 Diabetes.

Ramzy, Adam / Saber, Nelly / Bruin, Jennifer E / Thompson, David M / Kim, Peter T W / Warnock, Garth L / Kieffer, Timothy J

The Journal of clinical endocrinology and metabolism

2023 Volume 109, Issue 2, Page(s) 413–423

Abstract: Background: Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical ... ...

Abstract	Background: Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells. Methods: We measured circulating triiodothyronine and thyroxine levels in all patients treated at 1 of the 7 sites of the ongoing clinical trial and determined if thyroid hormone levels were associated with the C-peptide or glucagon levels and cell fate of implanted PECs. Results: Both triiodothyronine and thyroxine levels were significantly associated with the proportion of cells that adopted an insulin-producing fate with a mature phenotype. Thyroid hormone levels were inversely correlated to circulating glucagon levels after implantation, suggesting that thyroid hormones lead PECs to favor an insulin-producing fate over a glucagon-producing fate. In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice. Conclusion: These data highlight the relevance of thyroid hormones in the context of PEC therapy in patients with type 1 diabetes and suggest that a thyroid hormone adjuvant therapy may optimize cell outcomes in some PEC recipients.
MeSH term(s)	Humans ; Mice ; Animals ; Diabetes Mellitus, Type 1/metabolism ; C-Peptide/metabolism ; Thyroxine/metabolism ; Triiodothyronine/metabolism ; Endoderm/metabolism ; Endoderm/transplantation ; Glucagon/metabolism
Chemical Substances	C-Peptide ; Thyroxine (Q51BO43MG4) ; Triiodothyronine (06LU7C9H1V) ; Glucagon (9007-92-5)
Language	English
Publishing date	2023-09-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad499
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Uh III Zs.134: Show issues

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Article ; Online: Real-time diffraction computed tomography data reduction.

Kieffer, J / Petitdemange, S / Vincent, T

Journal of synchrotron radiation

2018 Volume 25, Issue Pt 2, Page(s) 612–617

Abstract: Diffraction imaging is an X-ray imaging method which uses the crystallinity information (cell parameter, orientation) as a signal to create an image pixel by pixel: a pencil beam is raster-scanned onto a sample and the (powder) diffraction signal is ... ...

Abstract	Diffraction imaging is an X-ray imaging method which uses the crystallinity information (cell parameter, orientation) as a signal to create an image pixel by pixel: a pencil beam is raster-scanned onto a sample and the (powder) diffraction signal is recorded by a large area detector. With the flux provided by third-generation synchrotrons and the speed of hybrid pixel detectors, the acquisition speed of these experiments is now limited by the transfer rate to the local storage as the data reduction can hardly be performed in real time. This contribution presents the benchmarking of a typical data analysis pipeline for a diffraction imaging experiment like the ones performed at ESRF ID15a and proposes some disruptive techniques to decode CIF binary format images using the computational power of graphics cards to be able to perform data reduction in real time.
Language	English
Publishing date	2018-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2021413-3
ISSN	1600-5775 ; 0909-0495
ISSN (online)	1600-5775
ISSN	0909-0495
DOI	10.1107/S1600577518000607
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Article ; Online: Novel lipoprotein density profiling in laminitic, obese, and healthy horses.

Coleman, M C / Walzem, R L / Kieffer, A J / Minamoto, T / Suchodolski, J / Cohen, N D

Domestic animal endocrinology

2019 Volume 68, Page(s) 92–99

Abstract: Lipoproteins are water-miscible macromolecules enabling the transport of lipids in blood. In humans, altered proportions of lipoproteins are used to detect and classify metabolic diseases. Obesity and obesity-related comorbidities are common in horses. ... ...

Abstract	Lipoproteins are water-miscible macromolecules enabling the transport of lipids in blood. In humans, altered proportions of lipoproteins are used to detect and classify metabolic diseases. Obesity and obesity-related comorbidities are common in horses. The pathophysiology of obesity is poorly understood and likely multifactorial. Development of new diagnostic tests to identify horses at risk of developing obesity to implement preventative measures is critical; however, a necessary first step to accomplish this goal is to improve our understanding of the pathophysiology of disease. Thus, the objective of this study was to characterize and compare lipoprotein profiles of horses with normal and excess body conditions, with and without laminitis using a novel method of continuous lipoprotein density profiling (CLPDP). Comparisons were made between 4 groups of horses: (1) laminitic, obese horses (n = 66); (2) laminitic, nonobese horses (n = 35); (3) nonlaminitic, obese horses (n = 41); and (4) nonlaminitic, nonobese horses (n = 95). Lipoprotein profiling, including evaluation of triglyceride-rich lipoprotein (TRL), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) was performed using CLPDP, and all 4 groups were compared. A significant difference was observed among groups for the subfractions TRL, LDL1, LDL2, HDL2b, HDL2a, HDL3a, HDL3b, HDL3c, and total HDL. This is the first known description of CLPDP to characterize equine lipid profiles and holds promise as a useful method for lipid characterization of horses.
MeSH term(s)	Animals ; Female ; Foot Diseases/metabolism ; Foot Diseases/veterinary ; Hoof and Claw ; Horse Diseases/blood ; Horse Diseases/metabolism ; Horses ; Inflammation/metabolism ; Inflammation/veterinary ; Lipoproteins/blood ; Lipoproteins/metabolism ; Male ; Obesity/metabolism ; Obesity/veterinary ; Transcriptome
Chemical Substances	Lipoproteins
Language	English
Publishing date	2019-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	594468-5
ISSN	1879-0054 ; 0739-7240
ISSN (online)	1879-0054
ISSN	0739-7240
DOI	10.1016/j.domaniend.2018.11.003
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Zs.A 4204: Show issues

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Article: Performance of the time-resolved ultra-small-angle X-ray scattering beamline with the Extremely Brilliant Source.

Narayanan, Theyencheri / Sztucki, Michael / Zinn, Thomas / Kieffer, Jérôme / Homs-Puron, Alejandro / Gorini, Jacques / Van Vaerenbergh, Pierre / Boesecke, Peter

Journal of applied crystallography

2022 Volume 55, Issue Pt 1, Page(s) 98–111

Abstract: The new technical features and enhanced performance of the ID02 beamline with the Extremely Brilliant Source (EBS) at the ESRF are described. The beamline enables static and kinetic investigations of a broad range of systems from ångström to micrometre ... ...

Abstract	The new technical features and enhanced performance of the ID02 beamline with the Extremely Brilliant Source (EBS) at the ESRF are described. The beamline enables static and kinetic investigations of a broad range of systems from ångström to micrometre size scales and down to the sub-millisecond time range by combining different small-angle X-ray scattering techniques in a single instrument. In addition, a nearly coherent beam obtained in the high-resolution mode allows multispeckle X-ray photon correlation spectroscopy measurements down to the microsecond range over the ultra-small- and small-angle regions. While the scattering vector (of magnitude
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2020879-0
ISSN	1600-5767 ; 0021-8898
ISSN (online)	1600-5767
ISSN	0021-8898
DOI	10.1107/S1600576721012693
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Article ; Online: Impact on Health Care Utilization and Costs of a Medicaid Community Health Worker Program in Detroit, 2018-2020: A Randomized Program Evaluation.

Heisler, Michele / Lapidos, Adrienne / Kieffer, Edith / Henderson, James / Guzman, Rebeca / Cunmulaj, Jasmina / Wolfe, Jason / Meyer, Trish / Ayanian, John Z

American journal of public health

2022 Volume 112, Issue 5, Page(s) 766–775

Abstract: Objectives. ...

Abstract	Objectives.
MeSH term(s)	Community Health Workers ; Cost Savings ; Emergency Service, Hospital ; Health Care Costs ; Hospitalization ; Humans ; Medicaid ; Patient Acceptance of Health Care ; Program Evaluation ; United States
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	121100-6
ISSN	1541-0048 ; 0090-0036 ; 0002-9572
ISSN (online)	1541-0048
ISSN	0090-0036 ; 0002-9572
DOI	10.2105/AJPH.2021.306700
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Article ; Online: In vitro characterization of the full-length human dynein-1 cargo adaptor BicD2.

Fagiewicz, Robert / Crucifix, Corinne / Klos, Torben / Deville, Célia / Kieffer, Bruno / Nominé, Yves / Busselez, Johan / Rossolillo, Paola / Schmidt, Helgo

Structure (London, England : 1993)

2022 Volume 30, Issue 11, Page(s) 1470–1478.e3

Abstract: Cargo adaptors are crucial in coupling motor proteins with their respective cargos and regulatory proteins. BicD2 is a prominent example within the cargo adaptor family. BicD2 is able to recruit the microtubule motor dynein to RNA, viral particles, and ... ...

Abstract	Cargo adaptors are crucial in coupling motor proteins with their respective cargos and regulatory proteins. BicD2 is a prominent example within the cargo adaptor family. BicD2 is able to recruit the microtubule motor dynein to RNA, viral particles, and nuclei. The BicD2-mediated interaction between the nucleus and dynein is implicated in mitosis, interkinetic nuclear migration (INM) in radial glial progenitor cells, and neuron precursor migration during embryonic neocortex development. In vitro studies involving full-length cargo adaptors are difficult to perform due to the hydrophobic character, low-expression levels, and intrinsic flexibility of cargo adaptors. Here, we report the recombinant production of full-length human BicD2 and confirm its biochemical activity by interaction studies with RanBP2. We also describe pH-dependent conformational changes of BicD2 using cryoelectron microscopy (cryo-EM), template-free structure predictions, and biophysical tools. Our results will help define the biochemical parameters for the in vitro reconstitution of higher-order BicD2 protein complexes.
MeSH term(s)	Humans ; Dyneins/metabolism ; Dynactin Complex/metabolism ; Microtubule-Associated Proteins/metabolism ; Cryoelectron Microscopy ; Microtubules/metabolism
Chemical Substances	Dyneins (EC 3.6.4.2) ; Dynactin Complex ; Microtubule-Associated Proteins ; BICD2 protein, human
Language	English
Publishing date	2022-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2022.08.009
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Zs.A 4141: Show issues

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Article ; Online: Molecular and Clinical Portrait of HER2-low Invasive Lobular Carcinomas.

Djerroudi, Lounes / El Sabeh-Ayoun, Ahmad / Benoist, Camille / Pierron, Gaelle / Masliah-Planchon, Julien / Fuhrmann, Laetitia / Kieffer, Yann / Carton, Matthieu / Ramtohul, Toulsie / Callens, Celine / Renault, Victor / Bidard, François-Clément / Mechta-Grigoriou, Fatima / Vincent-Salomon, Anne

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 Volume 37, Issue 5, Page(s) 100463

Abstract: Invasive lobular carcinomas (ILCs) have a low frequency of ERBB2 amplification, therefore restricting the use of conventional anti-HER2 therapies for this histologic special type. Conversely, ILCs with low HER2 overexpression may represent a broader ... ...

Abstract	Invasive lobular carcinomas (ILCs) have a low frequency of ERBB2 amplification, therefore restricting the use of conventional anti-HER2 therapies for this histologic special type. Conversely, ILCs with low HER2 overexpression may represent a broader target for the use of emerging antibody drug conjugate therapies targeting HER2, since these treatments have proven effective in HER2-low breast cancers. Very scarce data about HER2-low ILCs have been so far published, although these tumors could have different prevalence and histomolecular specificities compared with invasive breast carcinoma of no special type (IBC-NST). Our aims in that context were to decipher the clinicopathological and molecular features of a large series of HER2-low ILCs. Comparative evaluation of HER2-low prevalence was done based on a retrospective series of 7970 patients from Institut Curie, with either primary invasive lobular (N = 1103) or no special type (N = 6867) invasive carcinoma. Clinicopathological and molecular analyses of HER2-zero, HER2-low, and HER2-positive ILCs were performed on a subgroup of 251 patients who underwent surgery for a primary ILC between 2005 and 2008. The mutational profile of these 251 cases was determined from RNAseq data. Compared with HER2-negative IBC-NSTs, the HER2-negative ILCs were found to display a higher frequency of HER2-zero cases (59.4% vs 53.7%) and a lower frequency of HER2-low (40.6% vs 46.3%) (P < .001). Clinicopathological features associated with HER2-low status (vs HER2-zero) in ILC were older age, postmenopausal status, nonclassic ILC histological types, higher grade, proliferation, and estrogen receptor expression levels. Survival curve analysis showed a significantly lower risk of local recurrence for HER2-low (vs HER2-zero) ILCs, but no association was found between HER2 status and either breast cancer-specific survival or distant metastasis-free interval. ERBB3 was the unique mutated gene exclusively associated with HER2-low ILCs yet being mutated at a low frequency (7.1%) (false discovery rate < 0.05). In conclusion, HER2-low ILCs exhibit their own particularities, both on clinical-pathological and molecular levels. Our findings call for larger multicenter validation studies.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100463
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Zs.A 2450: Show issues

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Article ; Online: Exploratory study: Evaluation of a symptom checker effectiveness for providing a diagnosis and evaluating the situation emergency compared to emergency physicians using simulated and standardized patients.

Abensur Vuillaume, Laure / Turpinier, Julien / Cipolat, Lauriane / Arnaud-Dépil-Duval / Dumontier, Thomas / Peschanski, Nicolas / Kieffer, Yann / Barbat, Boris / Riquier, Thomas / Dinot, Vincent / Galland, Joris

PloS one

2023 Volume 18, Issue 2, Page(s) e0277568

Abstract: Background: The overloading of health care systems is an international problem. In this context, new tools such as symptom checker (SC) are emerging to improve patient orientation and triage. This SC should be rigorously evaluated and we can take a cue ... ...

Abstract	Background: The overloading of health care systems is an international problem. In this context, new tools such as symptom checker (SC) are emerging to improve patient orientation and triage. This SC should be rigorously evaluated and we can take a cue from the way we evaluate medical students, using objective structured clinical examinations (OSCE) with simulated patients. Objective: The main objective of this study was to evaluate the efficiency of a symptom checker versus emergency physicians using OSCEs as an assessment method. Methods: We explored a method to evaluate the ability to set a diagnosis and evaluate the emergency of a situation with simulation. A panel of medical experts wrote 220 simulated patients cases. Each situation was played twice by an actor trained to the role: once for the SC, then for an emergency physician. Like a teleconsultation, only the patient's voice was accessible. We performed a prospective non-inferiority study. If primary analysis had failed to detect non-inferiority, we have planned a superiority analysis. Results: The SC established only 30% of the main diagnosis as the emergency physician found 81% of these. The emergency physician was also superior compared to the SC in the suggestion of secondary diagnosis (92% versus 52%). In the matter of patient triage (vital emergency or not), there is still a medical superiority (96% versus 71%). We prove a non-inferiority of the SC compared to the physician in terms of interviewing time. Conclusions and relevance: We should use simulated patients instead of clinical cases in order to evaluate the effectiveness of SCs.
MeSH term(s)	Humans ; Prospective Studies ; Triage/methods ; Physicians ; Voice ; Remote Consultation
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0277568
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