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Article ; Online: Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition

Gerard Bryan Gonzales / Sarah De Saeger

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 10

Abstract: Abstract In this paper, the stability of the plasma metabolome at −20 °C for up to 30 days was evaluated using liquid chromatography-high resolution mass spectrometric metabolomics analysis. To follow the time-series deterioration of the plasma ... ...

Abstract	Abstract In this paper, the stability of the plasma metabolome at −20 °C for up to 30 days was evaluated using liquid chromatography-high resolution mass spectrometric metabolomics analysis. To follow the time-series deterioration of the plasma metabolome, the use of an elastic net regularized regression model for the prediction of storage time at −20 °C based on the plasma metabolomic profile, and the selection and ranking of metabolites with high temporal changes was demonstrated using the glmnet package in R. Out of 1229 (positive mode) and 1483 (negative mode) metabolite features, the elastic net model extracted 32 metabolites of interest in both positive and negative modes. L-gamma-glutamyl-L-(iso)leucine (tentative identification) was found to have the highest time-dependent change and significantly increased proportionally to the storage time of plasma at −20 °C (R2 = 0.6378 [positive mode], R2 = 0.7893 [negative mode], p-value < 0.00001). Based on the temporal profiles of the extracted metabolites by the model, results show only minimal deterioration of the plasma metabolome at −20 °C up to 1 month. However, majority of the changes appeared at around 12–15 days of storage. This allows scientists to better plan logistics and storage strategies for samples obtained from low-resource settings, where −80 °C storage is not guaranteed.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Gerard Bryan Gonzales / Sarah De Saeger

Scientific Reports, Vol 8, Iss 1, Pp 1-

Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition

2018 Volume 2

Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

Abstract	A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systemic inflammation is negatively associated with early post discharge growth following acute illness among severely malnourished children - a pilot study [version 2; peer review

James M. Njunge / Gerard Bryan Gonzales / Moses M. Ngari / Johnstone Thitiri / Robert H.J. Bandsma / James A. Berkley

Wellcome Open Research, Vol

2 approved]

2021 Volume 5

Abstract: Background: Rapid growth should occur among children with severe malnutrition (SM) with medical and nutritional management. Systemic inflammation (SI) is associated with death among children with SM and is negatively associated with linear growth. ... ...

Abstract	Background: Rapid growth should occur among children with severe malnutrition (SM) with medical and nutritional management. Systemic inflammation (SI) is associated with death among children with SM and is negatively associated with linear growth. However, the relationship between SI and weight gain during therapeutic feeding following acute illness is unknown. We hypothesised that growth post-hospital discharge is associated with SI among children with SM. Methods: We conducted secondary analysis of data from HIV-uninfected children with SM (n=98) who survived and were not readmitted to hospital during one year of follow-up. We examined the relationship between changes in absolute deficits in weight and mid-upper-arm circumference (MUAC) from enrolment at stabilisation to 60 days and one year later, and untargeted plasma proteome, targeted cytokines/chemokines, leptin, and soluble CD14 using multivariate regularized linear regression. Results: The mean change in absolute deficit in weight and MUAC was -0.50kg (standard deviation; SD±0.69) and -1.20cm (SD±0.89), respectively, from enrolment to 60 days later. During the same period, mean weight and MUAC gain was 3.3g/kg/day (SD±2.4) and 0.22mm/day (SD±0.2), respectively. Enrolment interleukins; IL17-alpha and IL-2, and serum amyloid P were negatively associated with weight and MUAC gain during 60 days. Lipopolysaccharide binding protein and complement component 2 were negatively associated with weight gain only. Leptin was positively associated with weight gain. Soluble CD14, beta-2 microglobulin, and macrophage inflammatory protein 1 beta were negatively associated with MUAC gain only. Glutathione peroxidase 3 was positively associated with weight and MUAC gain during one year. Conclusions: Early post-hospital discharge weight and MUAC gain were rapid and comparable to children with uncomplicated SM treated in the community. Higher concentrations of SI markers were associated with less weight and MUAC gain, suggesting inflammation negatively impacts recovery from wasting. This finding warrants further research on reducing inflammation on growth among children with SM.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Severe malnutrition or famine exposure in childhood and cardiometabolic non-communicable disease later in life

Marko Kerac / Melkamu Berhane / Alemseged Abdissa / Mubarek Abera / Natasha Lelijveld / Kelsey Grey / Gerard Bryan Gonzales / Debbie Thompson

BMJ Global Health, Vol 6, Iss

a systematic review

2021 Volume 3

Abstract: Introduction Child malnutrition (undernutrition) and adult non-communicable diseases (NCDs) are major global public health problems. While convincing evidence links prenatal malnutrition with increased risk of NCDs, less is known about the long-term ... ...

Abstract	Introduction Child malnutrition (undernutrition) and adult non-communicable diseases (NCDs) are major global public health problems. While convincing evidence links prenatal malnutrition with increased risk of NCDs, less is known about the long-term sequelae of malnutrition in childhood. We therefore examined evidence of associations between postnatal malnutrition, encompassing documented severe childhood malnutrition in low/middle-income countries (LMICs) or famine exposure, and later-life cardiometabolic NCDs.Methods Our peer-reviewed search strategy focused on ‘severe childhood malnutrition’, ‘LMICs’, ‘famine’, and ‘cardiometabolic NCDs’ to identify studies in Medline, Embase, Global Health, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. We synthesised results narratively and assessed study quality with the UK National Institute for Health and Care Excellence checklist.Results We identified 57 studies of cardiometabolic NCD outcomes in survivors of documented severe childhood malnutrition in LMICs (n=14) and historical famines (n=43). Exposure to severe malnutrition or famine in childhood was consistently associated with increased risk of cardiovascular disease (7/8 studies), hypertension (8/11), impaired glucose metabolism (15/24) and metabolic syndrome (6/6) in later life. Evidence for effects on lipid metabolism (6/11 null, 5/11 mixed findings), obesity (3/13 null, 5/13 increased risk, 5/13 decreased risk) and other outcomes was less consistent. Sex-specific differences were observed in some cohorts, with women consistently at higher risk of glucose metabolism disorders and metabolic syndrome.Conclusion Severe malnutrition or famine during childhood is associated with increased risk of cardiometabolic NCDs, suggesting that developmental plasticity extends beyond prenatal life. Severe malnutrition in childhood thus has serious implications not only for acute morbidity and mortality but also for survivors’ long-term health. Heterogeneity across studies, confounding by ...
Keywords	Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
Subject code	360
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prevalence of Fatigue and Unrecognized Depression in Patients with Inflammatory Bowel Disease in Remission under Immunosuppressants and Biologicals

Marie Truyens / Elodie De Ruyck / Gerard Bryan Gonzales / Simon Bos / Debby Laukens / Martine De Vos

Journal of Clinical Medicine, Vol 10, Iss 4107, p

2021 Volume 4107

Abstract: Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with ... ...

Abstract	Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with fatigue. Methods: IBD patients in clinical and biochemical remission under treatment with immunomodulators or biologicals were included. Fatigue, physical tiredness and depression were assessed using the fatigue Visual Analogue Scale (fVAS), the Shortened Fatigue Questionnaire (SFQ) and the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), respectively. Relevant clinical and biochemical parameters were included in regression analyses to identify factors associated with physical fatigue. Results: In total, 157 IBD patients were included. Up to 45.9% of patients reported fatigue, physical tiredness was observed in 51% and depression in 10.8%. The majority of patients with subclinical depression were fatigued. Female sex (OR = 4.17 [1.55–6.78], p = 0.002) was independently associated with physical fatigue. Transferrin saturation (OR = −0.11 [−0.22–−0.007], p = 0.037) and treatment with adalimumab (compared to infliximab, OR = −3.65 [−7.21–−0.08], p = 0.045) entailed a lower risk of fatigue. Conclusion: Fatigue is observed in about half of IBD patients in remission and can be a symptom of underlying undetected depression. Sex, transferrin saturation and medication were identified as independent risk factors.
Keywords	Crohn’s disease ; ulcerative colitis ; behavior ; depression ; NOD2 ; Lipocalin-2 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of integrin expression in the prediction of response to vedolizumab

Cara De Galan / Gerard Bryan Gonzales / Sophie Van Welden / Simon Jan Tavernier / Triana Lobaton / Wouter Van Moerkercke / Beatrijs Strubbe / Harald Peeters / Elisabeth Macken / Martine De Vos / Debby Laukens / Pieter Hindryckx

Clinical and Translational Medicine, Vol 12, Iss 4, Pp n/a-n/a (2022)

A prospective real‐life multicentre cohort study

2022

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nutritional Characterization of Street Food in Urban Turkmenistan, Central Asia

Gabriela Albuquerque / Sofia Sousa / Inês Lança de Morais / Marcello Gelormini / Carla Motta / Gerard Bryan Gonzales / Azat Ovezov / Albertino Damasceno / Pedro Moreira / João Breda / Nuno Lunet / Patrícia Padrão

Frontiers in Public Health, Vol

2022 Volume 10

Abstract: ObjectiveDescribing the availability and nutritional composition of the most commonly available street foods in Ashgabat, Turkmenistan.MethodsOne hundred sixty-one street food vending sites (six public markets) were assessed, through a collection of data ...

Abstract	ObjectiveDescribing the availability and nutritional composition of the most commonly available street foods in Ashgabat, Turkmenistan.MethodsOne hundred sixty-one street food vending sites (six public markets) were assessed, through a collection of data on vending sites' characteristics and food availability, and samples of commonly available foods (21 homemade; 11 industrial), for chemical analysis.ResultsFruit, beverages, and food other than fruit were available in 6.8, 29.2, and 91.9% of all vending sites, respectively. Regarding the latter, 52.7% of the vending sites sold only homemade products (main dishes, snacks, cakes, biscuits and pastries, bread, ice-cream chocolate and confectionery, savory pastries and sandwiches), 37.2% only industrial (ice-cream, chocolate and confectionery, cakes, biscuits and pastries, snacks, bread and savory pastries) and 10.1% both. Homemade foods presented significantly higher total fat [homemade 11.6 g (range 6.6–19.4 g); industrial 6.2 g (range 4.0–8.6 g), p = 0.001], monounsaturated, polyunsaturated and trans-fat, and sodium and potassium content per serving. Industrial wafers presented the highest mean saturated (11.8 g/serving) and trans-fat (2.32 g/serving) content. Homemade hamburgers presented the highest mean sodium content (1889 mg/serving).ConclusionsStrategies to encourage the production and sales of healthier street foods, especially homemade, are needed to promote healthier urban food environments in urban Turkmenistan.
Keywords	Central Asia ; food processing ; nutritional value ; ready-prepared foods ; street food ; Turkmenistan ; Public aspects of medicine ; RA1-1270
Subject code	910
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of albumin and the extracellular matrix on the pathophysiology of oedema formation in severe malnutrition

Gerard Bryan Gonzales / James M. Njunge / Bonface M Gichuki / Bijun Wen / Moses Ngari / Isabel Potani / Johnstone Thitiri / Debby Laukens / Wieger Voskuijl / Robert Bandsma / Jill Vanmassenhove / James A Berkley

EBioMedicine, Vol 79, Iss , Pp 103991- (2022)

2022

Abstract: Summary: Background: While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired ... ...

Abstract	Summary: Background: While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired lymphatic drainage. The mechanism of oedema formation, especially the primary role of hypoalbuminaemia, remains controversial. Here, we explored the roles of albumin and albumin-independent mechanisms in oedema formation among children with severe malnutrition (SM). Methods: We performed secondary analysis of data obtained from two independent clinical trials in Malawi and Kenya (NCT02246296 and NCT00934492). We then used an unconventional strategy of comparing children with kwashiorkor and marasmus by matching (discovery cohort, n = 144) and normalising (validation cohort, n = 98, 2 time points) for serum albumin. Untargeted proteomics was used in the discovery cohort to determine plausible albumin-independent mechanisms associated with oedema, which was validated using enzyme-linked immunosorbent assay and multiplex assays in the validation cohort. Findings: We demonstrated that low serum albumin is necessary but not sufficient to develop oedema in SM. We further found that markers of extracellular matrix (ECM) degradation rather than markers of EG degradation distinguished oedematous and non-oedematous children with SM. Interpretation: Our results show that oedema formation has both albumin-dependent and independent mechanisms. ECM integrity appears to have a greater role in oedema formation than EG shedding in SM. Funding: Research Foundation Flanders (FWO), Thrasher Foundation (15122 and 9403), VLIR-UOS-Ghent University Global Minds Fund, Bill & Melinda Gates Foundation (OPP1131320), MRC/DfID/Wellcome Trust Global Health Trials Scheme (MR/M007367/1), Canadian Institutes of Health Research (156307), Wellcome Trust (WT083579MA).
Keywords	Starling forces ; Extracellular matrix ; Endothelial glycocalyx ; Oedema ; Proteomics ; Severe malnutrition ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Childhood severe acute malnutrition is associated with metabolic changes in adulthood

Debbie S. Thompson / Celine Bourdon / Paraskevi Massara / Michael S. Boyne / Terrence E. Forrester / Gerard Bryan Gonzales / Robert H. J. Bandsma

JCI Insight, Vol 5, Iss

2020 Volume 24

Abstract: BACKGROUND Severe acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous ... ...

Abstract	BACKGROUND Severe acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODS This cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTS Seventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower β-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSION Adult SAM survivors have distinct metabolic profiles that suggest reduced β-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDING Health Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.
Keywords	Metabolism ; Medicine ; R
Subject code	360
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Childhood severe acute malnutrition is associated with metabolic changes in adulthood

Debbie S. Thompson / Celine Bourdon / Paraskevi Massara / Michael S. Boyne / Terrence E. Forrester / Gerard Bryan Gonzales / Robert H. J. Bandsma

JCI Insight, Vol 5, Iss

2020 Volume 24

Abstract	BACKGROUND Severe acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODS This cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTS Seventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower β-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSION Adult SAM survivors have distinct metabolic profiles that suggest reduced β-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDING Health Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.
Keywords	Metabolism ; Medicine ; R
Subject code	360
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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