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Article ; Online: Does cognitive dysfunction correlate with neurofilament light polypeptide levels in the CSF of patients with multiple sclerosis?

Thaleia Kalatha / Marianthi Arnaoutoglou / Theodoros Koukoulidis / Eleni Hatzifilippou / Emmanouil Bouras / Stavros Baloyannis / Effrosyni Koutsouraki

Journal of International Medical Research, Vol

2019 Volume 47

Abstract: Objective To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive ... ...

Abstract	Objective To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive dysfunction in MS. Methods This observational case–control study included patients with MS. CSF levels of NfL were determined using enzyme-linked immunosorbent assay. Cognitive function was measured with the Brief International Cognitive Assessment for MS (BICAMS) battery and Paced Auditory Serial Addition Test (PASAT3), standardized to the Greek population. Results Of 39 patients enrolled (aged 42.7 ± 13.6 years), 36% were classified as cognitively impaired according to BICAMS z-scores (–0.34 ± 1.13). Relapsing MS was significantly better than progressive forms regarding BICAMS z-score (mean difference [MD] 1.39; 95% confidence interval [CI] 0.54, 2.24), Symbol Digit Modality Test score (MD 1.73; 95% CI 0.46, 3.0) and Greek Verbal Learning Test (MD 1.77; 95% CI 0.82, 2.72). An inversely proportional association between CSF NfL levels and BICAMS z-scores was found in progressive forms of MS (r p = –0.944). Conclusions This study provides preliminary evidence for an association between CSF NfL levels and cognition in progressive forms of MS, which requires validation in larger samples.
Keywords	Medicine (General) ; R5-920
Subject code	616 ; 150
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer

Sarah J. Bowden / Triada Doulgeraki / Emmanouil Bouras / Georgios Markozannes / Antonios Athanasiou / Harriet Grout-Smith / Konstantinos S. Kechagias / Laura Burney Ellis / Verena Zuber / Marc Chadeau-Hyam / James M. Flanagan / Konstantinos K. Tsilidis / Ilkka Kalliala / Maria Kyrgiou

BMC Medicine, Vol 21, Iss 1, Pp 1-

an umbrella review and follow-up Mendelian randomisation studies

2023 Volume 15

Abstract: Abstract Background Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant ... ...

Abstract	Abstract Background Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associations remains unclear. Methods In this umbrella review, we searched electronic databases to identify meta-analyses of observational studies that evaluated risk or protective factors and the incidence of HPV infection, cervical intra-epithelial neoplasia (CIN), cervical cancer incidence and mortality. Following re-analysis, evidence was classified and graded based on a pre-defined set of statistical criteria. Quality was assessed with AMSTAR-2. For all associations graded as weak evidence or above, with available genetic instruments, we also performed Mendelian randomisation to examine the potential causal effect of modifiable exposures with risk of cervical cancer. The protocol for this study was registered on PROSPERO (CRD42020189995). Results We included 171 meta-analyses of different exposure contrasts from 50 studies. Systemic immunosuppression including HIV infection (RR = 2.20 (95% CI = 1.89–2.54)) and immunosuppressive medications for inflammatory bowel disease (RR = 1.33 (95% CI = 1.27–1.39)), as well as an altered vaginal microbiome (RR = 1.59 (95% CI = 1.40–1.81)), were supported by strong and highly suggestive evidence for an association with HPV persistence, CIN or cervical cancer. Smoking, number of sexual partners and young age at first pregnancy were supported by highly suggestive evidence and confirmed by Mendelian randomisation. Conclusions Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. Mendelian randomisation confirmed the link for genetically predicted lifetime ...
Keywords	HPV ; Cervical cancer ; Cervical intraepithelial neoplasia ; CIN ; Umbrella ; Mendelian randomisation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systematic Review Non-Vitamin K Oral Anticoagulants in Adults with Congenital Heart Disease

Nikolaos Stalikas / Ioannis Doundoulakis / Efstratios Karagiannidis / Emmanouil Bouras / Anastasios Kartas / Alexandra Frogoudaki / Haralambos Karvounis / Konstantinos Dimopoulos / George Giannakoulas

Journal of Clinical Medicine, Vol 9, Iss 1794, p

2020 Volume 1794

Abstract: Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised all studies on the safety and efficacy of non-vitamin-K oral anticoagulants (NOACs) ... ...

Abstract	Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised all studies on the safety and efficacy of non-vitamin-K oral anticoagulants (NOACs) in adult patients with various forms of congenital heart disease. PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were used, with duplicate extraction of data and risk of bias assessment. The Newcastle-Ottawa quality assessment scale was used to assess study quality. Three studies fulfilled the inclusion criteria and were analyzed. The total number of participants was 766, with a total follow-up of 923 patient-years. The majority of patients (77%) received a NOAC for atrial arrhythmias, while the remainder were prescribed NOACs for secondary (19%) or primary (4%) thromboprophylaxis. The annual rate of thromboembolic and major bleeding events was low: 0.98% (95% CI: 0.51–1.86) and 1.74% (95% CI: 0.86–3.49) respectively. In Fontan patients, the annual rate of thromboembolic and major bleeding events was 3.13% (95% CI: 1.18–8.03) and 3.17% (95% CI: 0.15–41.39) respectively. NOACs appear safe and effective in ACHD without mechanical prostheses. Additional studies are, however, needed to confirm their efficacy in complex ACHD, especially those with a Fontan-type circulation.
Keywords	congenital heart defects ; anticoagulants ; thromboembolism ; hemorrhage ; treatment efficacy ; patient safety ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MeinteR

Andigoni Malousi / Sofia Kouidou / Maria Tsagiopoulou / Nikos Papakonstantinou / Emmanouil Bouras / Elisavet Georgiou / Georgios Tzimagiorgis / Kostas Stamatopoulos

Scientific Reports, Vol 9, Iss 1, Pp 1-

A framework to prioritize DNA methylation aberrations based on conformational and cis-regulatory element enrichment

2019 Volume 12

Abstract: Abstract DNA methylation studies have been reformed with the advent of single-base resolution arrays and bisulfite sequencing methods, enabling deeper investigation of methylation-mediated mechanisms. In addition to these advancements, numerous ... ...

Abstract	Abstract DNA methylation studies have been reformed with the advent of single-base resolution arrays and bisulfite sequencing methods, enabling deeper investigation of methylation-mediated mechanisms. In addition to these advancements, numerous bioinformatics tools address important computational challenges, covering DNA methylation calling up to multi-modal interpretative analyses. However, contrary to the analytical frameworks that detect driver mutational signatures, the identification of putatively actionable epigenetic events remains an unmet need. The present work describes a novel computational framework, called MeinteR, that prioritizes critical DNA methylation events based on the following hypothesis: critical aberrations of DNA methylation more likely occur on a genomic substrate that is enriched in cis-acting regulatory elements with distinct structural characteristics, rather than in genomic “deserts”. In this context, the framework incorporates functional cis-elements, e.g. transcription factor binding sites, tentative splice sites, as well as conformational features, such as G-quadruplexes and palindromes, to identify critical epigenetic aberrations with potential implications on transcriptional regulation. The evaluation on multiple, public cancer datasets revealed significant associations between the highest-ranking loci with gene expression and known driver genes, enabling for the first time the computational identification of high impact epigenetic changes based on high-throughput DNA methylation data.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Is continuing medical education sufficient? Assessing the clinical nutrition knowledge of medical doctors

Grammatikopoulou, Maria G / Areti Katsouda / Eirini Kasapidou / Emmanouil Bouras / Kalliopi-Anna Poulia / Kyriaki Lekka / Kyriakos Tsantekidis / Michael Chourdakis

Nutrition. 2019 Jan., v. 57

2019

Abstract: Provision of nutritional support (NS) can improve disease outcome and shorten hospital length of stay. NS, often prescribed by medical doctors, requires adequate clinical nutrition (CN) expertise. The aim of this study was to investigate self-perceived ... ...

Abstract	Provision of nutritional support (NS) can improve disease outcome and shorten hospital length of stay. NS, often prescribed by medical doctors, requires adequate clinical nutrition (CN) expertise. The aim of this study was to investigate self-perceived and actual CN knowledge among medical doctors in Greece.Internal medicine physicians and surgical specialties (residents and specialized) were asked to self-evaluate their CN expertise, via a seven-item questionnaire and to complete a 20-question multiple-choice test on CN topics, with the aim of evaluating their actual CN knowledge. Participants were discouraged from accessing literature/information during the completion of either questionnaire.Of 182 invited medical doctors, 115 (50.4% surgical specialties) participated in the study (63.2% response rate). The majority of participants (65.2%) demonstrated inadequate CN knowledge, with 30.4% of those scoring low having a high self-perception of their CN expertise. Comparison of perceived and actual CN knowledge revealed that only 56.5% of the participants estimated their knowledge correctly. Those who had participated in CN continuous medical education courses demonstrated increased related expertise (P = 0.002).Medical doctors in Greece demonstrate low knowledge of fundamental CN principles, jeopardizing the provision of high-quality and efficient NS. Most importantly, the majority of participants overestimated their CN knowledge and prescribe artificial nutrition or participate in related decision making. Physicians’ CN knowledge should be enhanced accordingly, either by attending CN modules during their studies, by participating in basic and advanced courses or CN-specific continuous medical education, or both.
Keywords	clinical nutrition ; medical education ; medicine ; nutrition knowledge ; nutritional support ; physicians ; questionnaires ; self-perception ; Greece
Language	English
Dates of publication	2019-01
Size	p. 69-73.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/j.nut.2018.05.013
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Assessing the causal role of epigenetic clocks in the development of multiple cancers

Fernanda Morales Berstein / Daniel L McCartney / Ake T Lu / Konstantinos K Tsilidis / Emmanouil Bouras / Philip Haycock / Kimberley Burrows / Amanda I Phipps / Daniel D Buchanan / Iona Cheng / the PRACTICAL consortium / Richard M Martin / George Davey Smith / Caroline L Relton / Steve Horvath / Riccardo E Marioni / Tom G Richardson / Rebecca C Richmond

eLife, Vol

a Mendelian randomization study

2022 Volume 11

Abstract: Background: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker. Methods: We conducted a two-sample ... ...

Abstract	Background: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker. Methods: We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671–13,879; N controls = 173,493–372,016), FinnGen (N cases = 719–8401; N controls = 74,685–174,006) and several international cancer genetic consortia (N cases = 11,348–122,977; N controls = 15,861–105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach. Results: Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04–1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09–1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97–1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers. Conclusions: GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks ...
Keywords	cancer ; epigenetic age acceleration ; Mendelian randomization ; epigenetic clocks ; epidemiology ; DNA methylation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	150
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The two most popular malnutrition screening tools in the light of the new ESPEN consensus definition of the diagnostic criteria for malnutrition

Poulia, Kalliopi-Anna / Stanislaw Klek / Ioannis Doundoulakis / Emmanouil Bouras / Dimitrios Karayiannis / Aristea Baschali / Marili Passakiotou / Michael Chourdakis

Clinical nutrition. 2017 Aug., v. 36

2017

Abstract: The new definition of malnutrition in adults proposed recently by The European Society for Clinical Nutrition and Metabolism (ESPEN) changed the view on the issue and raised the question of the reliability of available diagnostic tools. Therefore, the ... ...

Abstract	The new definition of malnutrition in adults proposed recently by The European Society for Clinical Nutrition and Metabolism (ESPEN) changed the view on the issue and raised the question of the reliability of available diagnostic tools. Therefore, the aim of this study was to verify the accuracy of the two most commonly used screening tools by comparing their findings with the new ESPEN criteria.Nutritional screening was performed in 1146 (median age 60 years, interquartile range: 44â73 years, 617 males, 529 females) patients on admission to hospitals with two nutritional screening tools: Nutritional Risk Screening 2002 (NRS2002) and Malnutrition Universal Screening Tool (MUST). The screening results were then compared to the ESPEN new diagnostic criteria for malnutrition.According to the NRS2002 13.5% and 27.9% of the outpatients and hospitalized patients respectively were found to be at moderate/high risk of malnutrition. With the use of MUST 9.1% and 14.9% of the outpatients and hospitalized patients respectively were found to be at moderate/high risk of malnutrition. According to the ESPEN diagnostic criteria 6.4% and 11.3% of outpatients and hospitalized patients respectively were classified as malnourished. MUST was found to be better correlated to the latter for both outpatients (KÂ =Â 0.777, pÂ <Â 0.001) and hospitalized patients (KÂ =Â 0.843, pÂ <Â 0.001) as compared to NRS2002 (kÂ =Â 0.256, pÂ <Â 0.001 and kÂ =Â 0.228, pÂ <Â 0.001). ROC plots Area Under the Curve (AUC) was found to be higher for MUST compared to NRS2002 (0.964 vs. 0.695 for outpatients and 0.980 vs 0.686 for hospitalized patients respectively).To our knowledge, this study is the first to analyze the clinical value of a malnutrition screening tool in the light of the new ESPEN definition for malnutrition. According to our results, MUST was better correlated with ESPEN criteria for the definition of malnutrition, leading us to the conclusion that it can more efficiently identify the malnourished patients, during the screening process.
Keywords	adults ; clinical nutrition ; diagnostic techniques ; diet study techniques ; females ; hospitals ; males ; malnutrition ; metabolism ; patients ; risk ; risk screening ; screening
Language	English
Dates of publication	2017-08
Size	p. 1130-1135.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2016.07.014
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic

Afroditi Kanellopoulou / Fotios Koskeridis / Georgios Markozannes / Emmanouil Bouras / Chrysa Soutziou / Konstantinos Chaliasos / Michail T. Doumas / Dimitrios E. Sigounas / Vasilios T. Tzovaras / Agapios Panos / Yiolanda Stergiou / Kassiani Mellou / Dimitrios Papamichail / Eleni Aretouli / Dimitrios Chatzidimitriou / Fani Chatzopoulou / Eleni Bairaktari / Ioanna Tzoulaki / Evangelos Evangelou /

Evangelos C. Rizos / Evangelia Ntzani / Konstantinos Vakalis / Konstantinos K. Tsilidis

BMC Public Health, Vol 21, Iss 1, Pp 1-

results from the Epirus Health Study cohort

2021 Volume 14

Abstract: Abstract Background To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants. Methods The EHS is an ongoing and deeply-phenotyped ... ...

Abstract	Abstract Background To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants. Methods The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25–39, 40–49, 50–59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%. Results A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5, 10.0 and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value≤0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing. Conclusions High level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the ...
Keywords	COVID-19 ; Knowledge ; Trust in authorities ; Cohort study ; Epirus health study ; Exposure-wide association analysis ; Public aspects of medicine ; RA1-1270
Subject code	306
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Circulating inflammatory cytokines and risk of five cancers

Emmanouil Bouras / Ville Karhunen / Dipender Gill / Jian Huang / Philip C. Haycock / Marc J. Gunter / Mattias Johansson / Paul Brennan / Tim Key / Sarah J. Lewis / Richard M. Martin / Neil Murphy / Elizabeth A. Platz / Ruth Travis / James Yarmolinsky / Verena Zuber / Paul Martin / Michail Katsoulis / Heinz Freisling /

BMC Medicine, Vol 20, Iss 1, Pp 1-

a Mendelian randomization analysis

2022 Volume 15

Abstract: Abstract Background Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered ... ...

Abstract	Abstract Background Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. Methods Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). Results There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Conclusions Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.
Keywords	Cytokines ; Cancer ; Inflammation ; Mendelian randomisation ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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