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Article ; Online: Fungal and bacterial gut microbiota differ between

Henderickx, Jannie G E / Crobach, Monique J T / Terveer, Elisabeth M / Smits, Wiep Klaas / Kuijper, Ed J / Zwittink, Romy D

Microbiome research reports

2023 Volume 3, Issue 1, Page(s) 8

Abstract: Aim: ...

Abstract	Aim:
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ISSN	2771-5965
ISSN (online)	2771-5965
DOI	10.20517/mrr.2023.52
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Article: Self-Supervised Learning Reveals Clinically Relevant Histomorphological Patterns for Therapeutic Strategies in Colon Cancer.

Liu, Bojing / Polack, Meaghan / Coudray, Nicolas / Quiros, Adalberto Claudio / Sakellaropoulos, Theodore / Crobach, Augustinus S L P / van Krieken, J Han J M / Yuan, Ke / Tollenaar, Rob A E M / Mesker, Wilma E / Tsirigos, Aristotelis

bioRxiv : the preprint server for biology

2024

Abstract: Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to ... ...

Abstract	Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival was confirmed in an independent clinical trial cohort (N=1213 WSIs). This unbiased atlas resulted in 47 HPCs displaying unique and sharing clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analysis of these HPCs, including immune landscape and gene set enrichment analysis, and association to clinical outcomes, we shed light on the factors influencing survival and responses to treatments like standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil new insights and aid decision-making and personalized treatments for colon cancer patients.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.26.582106
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Article: Endoglin and squamous cell carcinomas.

Hakuno, Sarah K / Janson, Stefanus G T / Trietsch, Marjolijn D / de Graaf, Manon / de Jonge-Muller, Eveline / Crobach, Stijn / Harryvan, Tom J / Boonstra, Jurjen J / Dinjens, Winand N M / Slingerland, Marije / Hawinkels, Lukas J A C

Frontiers in medicine

2023 Volume 10, Page(s) 1112573

Abstract: Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely ... ...

Abstract	Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely unknown. Therefore, we investigated SCC endoglin expression and function in three types of SCCs; head and neck (HNSCC), esophageal (ESCC) and vulvar (VSCC) cancers. Endoglin expression was evaluated in tumor specimens and 14 patient-derived cell lines. Next to being expressed on angiogenic endothelial cells, endoglin is selectively expressed by individual SCC cells in tumor nests. Patient derived HNSCC, ESCC and VSCC cell lines express varying levels of endoglin with high interpatient variation. To assess the function of endoglin in signaling of TGF-β ligands, endoglin was overexpressed or knocked out or the signaling was blocked using TRC105, an endoglin neutralizing antibody. The endoglin ligand BMP-9 induced strong phosphorylation of SMAD1 independent of expression of the type-I receptor ALK1. Interestingly, we observed that endoglin overexpression leads to strongly increased soluble endoglin levels, which in turn decreases BMP-9 signaling. On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.
Language	English
Publishing date	2023-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1112573
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Article ; Online: Use of very short answer questions compared to multiple choice questions in undergraduate medical students: An external validation study.

van Wijk, Elise V / Janse, Roemer J / Ruijter, Bastian N / Rohling, Jos H T / van der Kraan, Jolein / Crobach, Stijn / Jonge, Mario de / Beaufort, Arnout Jan de / Dekker, Friedo W / Langers, Alexandra M J

PloS one

2023 Volume 18, Issue 7, Page(s) e0288558

Abstract: Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open-ended questions requiring a very short answer, may ... ...

Abstract	Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open-ended questions requiring a very short answer, may circumvent these limitations. Although VSAQ use in medical assessment increases, almost all research on reliability and validity of VSAQs in medical education has been performed by a single research group with extensive experience in the development of VSAQs. Therefore, we aimed to validate previous findings about VSAQ reliability, discrimination, and acceptability in undergraduate medical students and teachers with limited experience in VSAQs development. To validate the results presented in previous studies, we partially replicated a previous study and extended results on student experiences. Dutch undergraduate medical students (n = 375) were randomized to VSAQs first and MCQs second or vice versa in a formative exam in two courses, to determine reliability, discrimination, and cueing. Acceptability for teachers (i.e., VSAQ review time) was determined in the summative exam. Reliability (Cronbach's α) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach's α was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (average Rir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was ±2 minutes on average. Positive cueing occurred more in MCQs than in VSAQs (20% vs. 4% and 20.8% vs. 8.3% of questions per person in both courses). This study validates the positive results regarding VSAQs reliability, discrimination, and acceptability in undergraduate medical students. Furthermore, we demonstrate that VSAQ use is reliable among teachers with limited experience in writing and marking VSAQs. The short learning curve for teachers, favourable marking time and applicability regardless of the topic suggest that VSAQs might also be valuable beyond medical assessment.
MeSH term(s)	Humans ; Students, Medical ; Reproducibility of Results ; Educational Measurement/methods ; Education, Medical, Undergraduate/methods ; Education, Medical
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0288558
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Article ; Online: Screening for Clostridioides difficile colonization at admission to the hospital: a multi-centre study.

Crobach, Monique J T / Hornung, Bastian V H / Verduin, Cees / Vos, Margreet C / Hopman, Joost / Kumar, Nitin / Harmanus, Celine / Sanders, Ingrid / Terveer, Elisabeth M / Stares, Mark D / Lawley, Trevor D / Kuijper, Ed J

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2023 Volume 29, Issue 7, Page(s) 891–896

Abstract: Objectives: To assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting.: Methods: A multi-centre study was conducted at four hospitals located across the Netherlands. Newly admitted ... ...

Abstract	Objectives: To assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting. Methods: A multi-centre study was conducted at four hospitals located across the Netherlands. Newly admitted patients were screened for CDC. The risk of development of Clostridioides difficile infection (CDI) during admission and 1-year follow-up was assessed in patients with and without colonization. C. difficile isolates from patients with colonization were compared with isolates from incident CDI cases using core genome multi-locus sequence typing to determine whether onwards transmission had occurred. Results: CDC was present in 108 of 2211 admissions (4.9%), whereas colonization with a toxigenic strain (toxigenic Clostridoides difficile colonization [tCDC]) was present in 68 of 2211 admissions (3.1%). Among these 108 patients with colonization, diverse PCR ribotypes were found and no 'hypervirulent' PCR ribotype 027 (RT027) was detected (95% CI, 0-0.028). None of the patients with colonization developed CDI during admission (0/49; 95% CI, 0-0.073) or 1-year follow-up (0/38; 95% CI, 0-0.93). Core genome multi-locus sequence typing identified six clusters with genetically related isolates from patients with tCDC and CDI; however, in these clusters, only one possible transmission event from a patient with tCDC to a patient with CDI was identified based on epidemiological data. Conclusion: In this endemic setting with a low prevalence of 'hypervirulent' strains, screening for CDC at admission did not detect any patients with CDC who progressed to symptomatic CDI and detected only one possible transmission event from a patient with colonization to a patient with CDI. Thus, screening for CDC at admission is not useful in this setting.
MeSH term(s)	Humans ; Clostridioides difficile/genetics ; Clostridioides/genetics ; Multilocus Sequence Typing ; Hospitalization ; Clostridium Infections/diagnosis ; Clostridium Infections/epidemiology ; Clostridium Infections/microbiology ; Hospitals ; Ribotyping
Language	English
Publishing date	2023-03-05
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2023.02.022
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Zs.A 4541: 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: Clinical consequences of diagnostic variability in the histopathological evaluation of early rectal cancer.

Smits, Lisanne J H / van Lieshout, Annabel S / Bosker, Robbert J I / Crobach, Stijn / de Graaf, Eelco J R / Hage, Mariska / Laclé, Miangela M / Moll, Freek C P / Moons, Leon M G / Peeters, Koen C M J / van Westreenen, Henderik L / van Grieken, Nicole C T / Tuynman, Jurriaan B

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2023 Volume 49, Issue 7, Page(s) 1291–1297

Abstract: Introduction: In early rectal cancer, organ sparing treatment strategies such as local excision have gained popularity. The necessity of radical surgery is based on the histopathological evaluation of the local excision specimen. This study aimed to ... ...

Abstract	Introduction: In early rectal cancer, organ sparing treatment strategies such as local excision have gained popularity. The necessity of radical surgery is based on the histopathological evaluation of the local excision specimen. This study aimed to describe diagnostic variability between pathologists, and its impact on treatment allocation in patients with locally excised early rectal cancer. Materials and methods: Patients with locally excised pT1-2 rectal cancer were included in this prospective cohort study. Both quantitative measures and histopathological risk factors (i.e. poor differentiation, deep submucosal invasion, and lymphatic- or venous invasion) were evaluated. Interobserver variability was reported by both percentages and Fleiss' Kappa- (ĸ) or intra-class correlation coefficients. Results: A total of 126 patients were included. Ninety-four percent of the original histopathological reports contained all required parameters. In 73 of the 126 (57.9%) patients, at least one discordant parameter was observed, which regarded histopathological risk factors for lymph node metastases in 36 patients (28.6%). Interobserver agreement among different variables varied between 74% and 95% or ĸ 0.530-0.962. The assessment of lymphovascular invasion showed discordances in 26% (ĸ = 0.530, 95% CI 0.375-0.684) of the cases. In fourteen (11%) patients, discordances led to a change in treatment strategy. Conclusion: This study demonstrated that there is substantial interobserver variability between pathologists, especially in the assessment of lymphovascular invasion. Pathologists play a key role in treatment allocation after local excision of early rectal cancer, therefore interobserver variability needs to be reduced to decrease the number of patients that are over- or undertreated.
MeSH term(s)	Humans ; Prospective Studies ; Neoplasm Staging ; Rectal Neoplasms/surgery ; Rectal Neoplasms/pathology ; Lymphatic Metastasis ; Digestive System Surgical Procedures
Language	English
Publishing date	2023-02-18
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2023.02.008
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Zs.A 1149: 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 549: Show issues

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Article ; Online: Effect of Detecting and Isolating Asymptomatic Clostridium difficile Carriers.

Crobach, Monique J T / Terveer, Elisabeth M / Kuijper, Ed J

JAMA internal medicine

2016 Volume 176, Issue 10, Page(s) 1572–1573

MeSH term(s)	Carrier State ; Clostridium Infections ; Clostridium difficile ; Enterocolitis, Pseudomembranous ; Feces ; Humans
Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2699338-7
ISSN	2168-6114 ; 2168-6106
ISSN (online)	2168-6114
ISSN	2168-6106
DOI	10.1001/jamainternmed.2016.5339
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Article ; Online: Carriage of three plasmids in a single human clinical isolate of Clostridioides difficile.

Roseboom, Anna M / Ducarmon, Quinten R / Hornung, Bastian V H / Harmanus, Céline / Crobach, Monique J T / Kuijper, Ed J / Vossen, Rolf H A M / Kloet, Susan L / Smits, Wiep Klaas

Plasmid

2022 Volume 125, Page(s) 102669

Abstract: A subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential importance, C. difficile plasmids remain poorly ... ...

Abstract	A subset of clinical isolates of Clostridioides difficile contains one or more plasmids and these plasmids can harbor virulence and antimicrobial resistance determinants. Despite their potential importance, C. difficile plasmids remain poorly characterized. Here, we provide the complete genome sequence of a human clinical isolate that carries three high-copy number plasmids from three different plasmid families that are therefore compatible. For two of these, we identify a region capable of sustaining plasmid replication in C. difficile that is also compatible with the plasmid pCD630 that is found in many laboratory strains. Together, our data advance our understanding of C. difficile plasmid biology.
MeSH term(s)	Humans ; Plasmids/genetics ; Clostridioides difficile/genetics ; Clostridioides/genetics ; Virulence ; Virulence Factors/genetics ; Anti-Bacterial Agents
Chemical Substances	Virulence Factors ; Anti-Bacterial Agents
Language	English
Publishing date	2022-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	282384-6
ISSN	1095-9890 ; 0147-619X
ISSN (online)	1095-9890
ISSN	0147-619X
DOI	10.1016/j.plasmid.2022.102669
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Article ; Online: Nucleic Acid Amplification Test Quantitation as Predictor of Toxin Presence in Clostridium difficile Infection.

Crobach, M J T / Duszenko, N / Terveer, E M / Verduin, C M / Kuijper, E J

Journal of clinical microbiology

2018 Volume 56, Issue 3

Abstract: Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) is among the most accurate methods ... ...

Abstract	Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) is among the most accurate methods for
MeSH term(s)	Algorithms ; Bacterial Proteins/analysis ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Toxins/analysis ; Clostridium Infections/diagnosis ; Clostridium difficile/genetics ; Clostridium difficile/immunology ; Clostridium difficile/isolation & purification ; Diagnostic Tests, Routine ; Enterotoxins/analysis ; Feces/chemistry ; Hospitals ; Humans ; Immunoenzyme Techniques/standards ; Netherlands ; Nucleic Acid Amplification Techniques/standards ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Enterotoxins ; tcdA protein, Clostridium difficile ; toxB protein, Clostridium difficile
Language	English
Publishing date	2018-02-22
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.01316-17
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Article: The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile

Crobach, Monique J. T. / Ducarmon, Quinten R. / Terveer, Elisabeth M. / Harmanus, Celine / Sanders, Ingrid M. J. G. / Verduin, Kees M. / Kuijper, Ed J. / Zwittink, Romy D.

Microorganisms. 2020 May 06, v. 8, no. 5

2020

Abstract: Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). ... ...

Abstract	Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p < 0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients’ gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile.
Keywords	Bacteroides ; Clostridium difficile ; Eubacterium hallii ; Veillonella ; adults ; genes ; intestinal microorganisms
Language	English
Dates of publication	2020-0506
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms8050677
Database	NAL-Catalogue (AGRICOLA)

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