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Does nutritional support prevent severe mucositis in patients with head and neck cancer treated with chemoradiotherapy? A systematic review and meta-analysis

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Clinical Nutrition ESPEN 2025年 66卷 547-555页

作者： Krzywon, Aleksandra Kotylak, Anna Rutkowski, Tomasz Department of Biostatistics and Bioinformatics Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland I Radiation and Clinical Oncology Department Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland Clinical Trials Support Centre Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland

Background: For patients with advanced head and neck cancer (HNC) chemoradiotherapy (CHRT) is the main treatment option. CHRT is a severe treatment with a high ratio of side effects which may be even more pronounced due to mucosities related malnutrition. Nutritional intervention like nutritional counseling (NC) and oral nutritional supplements (ONS) may prevent malnutrition. A systematic review and meta-analysis was performed to assess the effect of NC with or without ONS (NC±ONS) on CHRT-related grade ≥3 mucositis in patients with HNC undergoing CHRT. Methods: PubMed/MEDLINE, Web of Science, and Scopus were searched to identify randomized and non-randomized clinical studies of HNC patients undergoing CHRT, where mucositis grade ≥3 data were provided. Comparative and proportional meta-analyses were performed to calculate the odds ratio (OR) and incidence of a mucositis grade ≥3 in the included studies (%) with 95% confidence intervals (95% CI). Results: There were seven studies fulfilling inclusion criteria with 655 participants included. NC±ONS revealed no risk reduction of grade ≥3 mucositis (OR: 1.2, 95%CI: 0.7–1.9). The overall mucositis rate was 38.3% (95% CI: 24.8%–52.6%) and 32.8% (95% CI: 14.9%–53.5%) (P = 0.67) in NC+ONS and NC-ONS respectively. Conclusion: Despite the undeniable role of NC±ONS for patients with HNC undergoing CHRT, we found it insufficient to avoid grade ≥3 CHRT-related mucositis. Further research should be conducted to determine recomendations how to decrease the risk of oral mucosities and, in consequence, how to prevent malnutrition in patients with CHRT. © 2025 The Author(s)

关键词： Chemoradiotherapy Head and neck cancer Mucositis Nutritional counselling Oral nutritional supplements Toxicity

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Physiologically based serum ferritin thresholds for iron deficiency among women and children from Africa, Asia, Europe, and central America: a multinational comparative study

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The Lancet Global Health 2025年第5期13卷 e831-e842页

作者： Addo, O Yaw Mei, Zuguo Jefferds, Maria Elena D Jenkins, Mica Flores-Ayala, Rafael Williams, Anne M Young, Melissa Fox Luo, Hanqi Ko, Yi-An Papassotiriou, Ioannis Palmieri, Mireya Mesarina, Karla Bhutta, Zulfiqar Suchdev, Parminder S Brittenham, Gary M Nutrition Branch International Micronutrient Malnutrition Prevention and Control Program (IMMPaCt) Team National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) US Centers for Disease Control and Prevention Atlanta GA United States National Health and Nutrition Examination Survey Analysis Branch National Center for Health Statistics US Centers for Disease Control and Prevention Hyattsville MD United States Hubert Department of Global Health Emory University Rollins School of Public Health Atlanta GA United States Department of Biostatistics and Bioinformatics Emory University Rollins School of Public Health Atlanta GA United States Department of Paediatrics Emory University School of Medicine Atlanta GA United States First Department of Paediatrics National and Kapodistrian University of Athens School of Medicine Athens Greece Instituto de Nutrición de Centro América y Panamá – INCAP Guatemala City Guatemala Secretariat of Food and Nutrition Security (SESAN) Guatemala City Guatemala Institute for Global Health & Development The Aga Khan University Karachi Pakistan Division of Global Health Protection US Centers for Disease Control and Prevention Central America Regional Office Guatemala City Guatemala Department of Paediatrics College of Physicians and Surgeons Columbia University New York NY United States

Background: Diagnosis of iron deficiency commonly relies on measurement of serum ferritin concentrations. WHO guidelines identify serum ferritin thresholds for iron deficiency among healthy individuals of less than 15 μg/L for women and less than 12 μg/L for children under 5 years, based on expert opinion. We report thresholds for iron deficiency for apparently healthy non-pregnant women and young children based on physiological indicators. Methods: We performed secondary analyses of cross-sectional data from women (aged 15–49 years) and children (aged 6–59 months) from 12 countries in Africa, Asia, Europe, and central America from available surveys (2007–19). Using haemoglobin and soluble transferrin receptor concentrations as individual-level indicators of iron deficiency, we identified country-specific serum ferritin thresholds. We conducted multivariate meta-analysis using individual participant data to assess multinational heterogeneity and intercountry consistency. Findings: Data were collected from July, 2007 to March, 2019. 18 251 individuals (13 864 women and 4387 children) were included in the final analysis. The thresholds of pooled serum ferritin levels corresponding to the starting point of decline in circulating haemoglobin concentrations were 24·8 μg/L (95% CI 24·4–25·2) for women and 22·1 μg/L (20·8–23·4) for children based on the national survey data from 12 countries. The thresholds were consistent among countries (p_{heterogeneity}: women=0·73, children=0·43) but median serum ferritin concentrations and lower 5% reference ranges differed. In all countries, the prevalence of iron deficiency was higher using physiologically based thresholds than that using WHO current guidelines for women (36·0% [95% CI 25·3–46·8] vs 20·1% [11·5–28·7], p<0·0001) and for children (34·2% [24·3–44·1] vs 16·6% [11·2–22·0], p<0·0001). Interpretation: These results provide evidence that the prevalence of iron deficiency as indicated by physiological measures is su

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Robust inference in linear mixed model with skew normal-symmetric error

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Frontiers of Mathematics in China 2017年第6期12卷 1483-1500页

作者： Mixia WU Ye TIAN Aiyi LIU College of Applied Sciences Beijing University of Technology Beijing 100124 China Biostatistics and Bioinformatics Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development Bethesda MD 20892 USA

Linear mixed effects models with general skew normal-symmetric （SNS） error are considered and several properties of the SNS distributions are obtained. Under the SNS settings, ANOVA-type estimates of variance components in the model are unbiased, the ANOVA-type F-tests are exact F-tests in SNS setting, and the exact confidence intervals for fixed effects are constructed. Also the power of ANOVA-type F-tests for components are free of the skewing function if the random effects normally distributed. For illustration of the main results, simulation studies on the robustness of the models are given by comparisons of multivariate skew-normal, multivariate skew normal-Laplace, multivariate skew normal-uniform, multivariate skew normal-symmetric, and multivariate normal distributed errors. A real example is provided for the illustration of the proposed method.

关键词： Skew normal-symmetric (SNS) ANOVA-type F-test mixed effect

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Maximum Likelihood Estimation for Shape-restricted Single-index Hazard Models

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Journal of Data Science 2023年第4期21卷 681-695页

作者： Qin, Jing Sun, Yifei Yuan, Ao Huang, Chiung-Yu Biostatistics Research Branch National Institute of Allergy and Infectious Diseases Maryland United States Department of Biostatistics Mailman School of Public Health Columbia University New York United States Department of Biostatistics Bioinformatics & Biomathematics Georgetown University Washington DC United States Department of Epidemiology & Biostatistics University of California San Francisco California United States

Single-index models are becoming increasingly popular in many scientific applications as they offer the advantages of flexibility in regression modeling as well as interpretable covariate effects. In the context of survival analysis, the single-index hazards models are natural extensions of the Cox proportional hazards models. In this paper, we propose a novel estimation procedure for single-index hazard models under a monotone constraint of the index. We apply the profile likelihood method to obtain the semiparametric maximum likelihood estimator, where the novelty of the estimation procedure lies in estimating the unknown monotone link function by embedding the problem in isotonic regression with exponentially distributed random variables. The consistency of the proposed semiparametric maximum likelihood estimator is established under suitable regularity conditions. Numerical simulations are conducted to examine the finitesample performance of the proposed method. An analysis of breast cancer data is presented for illustration. © 2023 The Author(s).

关键词： isotonic regression pool-adjacent-violators algorithm profile likelihood semiparametric estimation

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Distance-Based Regression Analysis for Measuring Associations

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Journal of Systems Science & Complexity 2023年第1期36卷 393-411页

作者： SHI Yuke ZHANG Wei LIU Aiyi LI Qizhai LSC Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Biostatistics and Bioinformatics Branch Eunice Kennedy Shriver National Institute of Child Health Human Development National Institutes of HealthBethesdaMD 20847USA

Distance-based regression model,as a nonparametric multivariate method,has been widely used to detect the association between variations in a distance or dissimilarity matrix for outcomes and predictor variables of interest in genetic association studies,genomic analyses,and many other research *** on it,a pseudo-F statistic which partitions the variation in distance matrices is often constructed to achieve the *** the best of our knowledge,the statistical properties of the pseudo-F statistic has not yet been well established in the *** fill this gap,the authors study the asymptotic null distribution of the pseudo-F statistic and show that it is asymptotically equivalent to a mixture of chi-squared random *** that the pseudo-F test statistic has unsatisfactory power when the correlations of the response variables are large,the authors propose a square-root F-type test statistic which replaces the similarity matrix with its square *** asymptotic null distribution of the new test statistic and power of both tests are also *** studies are conducted to validate the asymptotic distributions of the tests and demonstrate that the proposed test has more robust power than the pseudo-F *** test statistics are exemplified with a gene expression dataset for a prostate cancer pathway.

关键词： Asymptotic distribution chi-squared-type mixture nonparametric test pseudo-F test similarity matrix

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A note on modeling placement values in the analysis of receiver operating characteristic curves

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biostatistics and Epidemiology 2021年第2期5卷 118-133页

作者： Chen, Zhen Ghosal, Soutik Biostatistics and Bioinformatics Branch Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD United States

Recent advances in receiver operating characteristic (ROC) curve analyses advocate modeling of placement value (PV), a quantity that measures the position of diseased test scores relative to the healthy population. Compared to traditional approaches, this PV-based alternative works directly with ROC curves and is attractive when assessing covariate effects on, or incorporating a priori constraints of, ROC curves. Several distributions can be used to model the PV, yet little guidelines exist in the literature on which to use. Through extensive simulation studies, we investigate several parametric models for PV when data are generated from a variety of mechanisms. We discuss the pros and cons of each of these models and illustrate their applications with data from a study of prenatal ultrasound examinations and large-for-gestational age birth. © 2020 International Biometric Society–Chinese Region.

关键词： AUC beta regression diagnostic accuracy large for gestational age ROC

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The Crosstalk Between Omental-Derived Adipose Stem Cells (O-ASC) And Ovarian Cancer Cells

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International Journal of Gynecological Cancer 2025年第2期35卷

作者： Alexander Jorge Cortez Agata Malgorzata Wilk Katarzyna Aleksandra Kujawa Magdalena Olbryt Sebastian Student Travis Solley Ann H. Klopp Joanna Syrkis Patrycja Jakubowska Katarzyna Marta Lisowska Department of Biostatistics and Bioinformatics Maria Sklodowska-Curie Institute Oncology Center Gliwice Branch Gliwice Poland Center for Translational Research and Molecular Biology of Cancer Maria Sklodowska-Curie Institute Oncology Center Gliwice Branch Gliwice Poland Faculty of Automated Control Electronics and Computer Science Silesian University of Technology Gliwice Poland Division of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston United States

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Approximating probabilities of correlated events

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Science China Mathematics 2010年第11期53卷 2937-2948页

作者： LI QiZhai1,2, ZHENG Gang3, LIU AiYi4, LI ZhaoHai2,5 & YU Kai2 1Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China 2biostatistics branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA 3Office of biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA 4biostatistics and bioinformatics branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA 5Department of Statistics, George Washington University, Washington, DC 20052, USA 1. Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 China2. Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD 20892 USA3. Office of Biostatistics Research National Heart Lung and Blood Institute Bethesda MD 20892 USA4. Biostatistics and Bioinformatics Branch National Institute of Child Health and Human Development Bethesda MD 20892 USA5. Department of Statistics George Washington University Washington DC 20052 USA

Efron (1997) considered several approximations of p-values for simultaneous hypothesis testing. An extension of his approaches is considered here to approximate various probabilities of correlated events. Compared with multiple-integrations, our proposed method, the parallelogram formulas, based on a one-dimensional integral, not only substantially reduces the computational complexity but also maintains good accuracy. Applications of the proposed method to genetic association studies and group sequential analysis are investigated in detail. Numerical results including real data analysis and simulation studies demonstrate that the proposed method performs well.

关键词： case-control group sequential test genetic association studies MAX parallelogram

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A new two-part test based on density ratio model for zero-inflated continuous distributions

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Applied Mathematics(A Journal of Chinese Universities) 2020年第2期35卷 203-219页

作者： LU Ya-hui LIU Ai-yi JIANG Meng-jie JIANG Tao School of Statistics and Mathematics Zhejiang Gongshang UniversityHangzhou 310018China Biostatistics and Bioinformatics Branch Eunice Kennedy Shriver National Institute of China Health and Human DevelopmentBethesdaMD 20817USA Hangzhou Commercial College Zhejiang Gongshang UniversityHangzhou 311508China

In this paper,we consider testing the hypothesis concerning the means of two independent semicontinuous distributions whose observations are zero-inflated,characterized by a sizable number of zeros and positive observations from a continuous *** continuous parts of the two semicontinuous distributions are assumed to follow a density ratio model.A new two-part test is developed for this kind of *** proposed test takes the sum of one test for equality of proportions of zero values and one conditional test for the continuous *** test is proved to follow a2 distribution with two degrees of *** studies show that the proposed test controls the type I error rates at the desired level,and is competitive to,and most of the time more powerful than two popular tests.A real data example from a dietary intervention study is used to illustrate the usefulness of the proposed test.

关键词： two-part test zero-in ated continuous distributions density ratio model

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HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines

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Cell Death and Disease 2025年第1期16卷 1-15页

作者： Gogler, Agnieszka Wilk, Agata Małgorzata Sojka, Damian Robert Adamiec-Organiściok, Małgorzata Matysiak, Natalia Kania, Daria Wiecha, Klaudia Małusecka, Ewa Cortez, Alexander Jorge Zamojski, Dawid Marczyk, Michał Mazurek, Agnieszka Maria Oziębło, Sylwia Scieglinska, Dorota Center for Translational Research and Molecular Biology of Cancer Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland Department of Biostatistics and Bioinformatics Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch Wybrzeze Armii Krajowej 15 Gliwice 44-102 Poland Department of Systems Biology and Engineering Silesian University of Technology Akademicka 16 Gliwice 44-100 Poland Department of Histology and Cell Pathology Faculty of Medical Sciences in Zabrze Medical University of Silesia in Katowice Jordana 19 Zabrze 41-808 Poland Department of Data Science and Engineering Silesian University of Technology Akademicka 16 Gliwice 44-100 Poland Genetic Laboratory Gyncentrum Sp. z o.o. Sosnowiec 41-208 Poland Yale Cancer Center Yale School of Medicine New Haven CT United States

Chaperone proteins constitute a molecular machinery that controls proteostasis. HSPA2 is a heat shock-non-inducible member of the human HSPA/HSP70 family, which includes several highly homologous chaperone proteins. HSPA2 exhibits a cell type-specific expression pattern in the testis, brain, and multilayered epithelia. It is a crucial male fertility-related factor, but its role in somatic cells is poorly understood. Previously, we found that HSPA2 deficiency can impair epidermal keratinocyte differentiation. In this study, we confirmed the crucial role of HSPA2 in keratinocyte differentiation by investigating immortalized keratinocytes cultured in a reconstructed human epidermis model. Moreover, we uncovered the influence of HSPA2 on immunomodulation. Transcriptomic analysis revealed that the total loss of HSPA2 affected the expression of genes related to keratinocyte differentiation and interleukin- and interferon-mediated signaling. The functional analysis confirmed bidirectional changes associated with the loss of HSPA2. The HSPA2 knockout in HaCaT and Ker-CT keratinocytes, but not HSPA2 overproduction, impaired granular layer development as evidenced by reduced levels of late keratinocyte differentiation markers, filaggrin and involucrin, along with structural abnormalities in the upper epidermal layer. Differentiation defects were accompanied by increased mRNA expression and extracellular secretion of keratinocyte-derived pro-inflammatory IL-6 cytokine and CCL2, CCL8, CXCL1, CXCL6, and CXCL10 chemokines. The loss of HSPA2 also led to increased expression of extracellular HSPA1 and interferon-stimulated genes and secretion of immune cell modulator SLAMF7. Knocking down HSPA1 expression in keratinocytes decreased the secretion of IL-6 and CCL5 release, suggesting extracellular HSPA1’s role in the HSPA2-regulated molecular network. To summarize, we uncovered the complex homeostatic role of HSPA2 in epidermal keratinocytes. Our results suggest that dysfunction in H

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