dataesr/scientific-paragraphs-categorization huggingface dataset:
Phenotyping foods at a more fine-grained level We have examined the association of anthropometric traits with food categories (benchmark) in the gender-specific cohorts, and with FGs (in the cohorts and in the subgroups). Our data showed The study of the main drivers for conflicting trends at the FI level also indicates that not all individual FI belonging to a higher level FG contribute to the contradictory effect observed at the FG level. Thus, fine mapping dietetrait association patterns for more fine-grained food items (e. g. , subdivide legumes into soybeans, and chickpeas etc. ) could, if consistently replicated, be one of initial steps towards designing a more personalized diet, compared to dietary macronutrient studies  [32, 33]. The growing differentiation and precision in the diet effect on complex traits such as obesity, diabetes, cardiovascular diseases and cancer may eventually reveal phenotypic impact or disease profiling of various diets, parallel to the nutrients based food categorization  [32, 33].
Conclusions In conclusion, we used data mining approaches to reveal relationships between dietary factors and anthropometric changes in middle aged Danish citizens. We identified subgroups that shared similar dietary, lifestyle and anthropometric profiles. The existence of conflicting rules manifested by specific co-intake patterns in given subgroups displaying other trends than in the gender-specific cohorts, implies a complex relationship between dietary and nondietary factors and anthropometric traits. The analysis of relationships between diet, non-dietary lifestyle, anthropometric traits, and genetics may eventually be carried out at the level of individuals, in analogy to the development within the general areas of precision medicine and pharmacogenomics [35e39]. Following this line of thought, our method is applicable as well in a clinical nutrition setting, where the focus is the nutrition in sick people, with the aim of supporting the cure or preventing the worsening of their condition, due to nutrition disorders induced by the loss of appetite that frequently accompany many different diseases.
For each olfactory test, the AUC of the four patients' groups was compared using Student test for independent samples. Pairwise comparisons were Bonferroni-corrected for multiple comparisons between the four groups. All statistical analyses were performed at 95% confidence interval (alpha = 5%). They were conducted using XLstat-Pro software. The effect sizes are reported as η2 or Cohen's d, for ANOVA and Student tests respectively. The statistics of the Tukey post hoc tests (p-values and effect sizes), the ROC curves and the optimal cutoff values for each olfactory test and groups of subjects are reported in S1-S13 Tables.
As for the Chapman Anhedonia Questionnaire, we did an Arabic translation and a back translation of this questionnaire. The results obtained in this study were gathered for the validation of the Arabic version of this questionnaire that is still in process. This study evaluated subjects with bipolar disorders. However, we didn't evaluate subjects in manic or hypomanic states. Studies have showed that bipolar subjects exhibit a characteristic magnification and persistence of their smell abilities in manic/hypomanic phases  [28, 29]. An evaluation of patients during these phases would have brought new data to our study and improved our understanding of olfactory changes in bipolar disorders. Subjects in our study had also different number of mood episodes and hospital admissions. Significant differences were seen between groups, and these variables may constitute a bias in the interpretation of olfactory differences.
A future study including subjects with the same number of mood episodes would provide more consistent and accurate data on olfactory function in depressive and euthymic states. Patients with severe cognitive impairment were excluded from the study because of their incapacity to complete the assessment. Therefore, severely depressed patients with cognitive impairment may have been excluded from this study, thus affecting its results. At last, we should mention that our sample was recruited from a clinical population in two hospital settings, and might not result of true randomization of subjects presenting with depressive symptoms in the general population. These biases should be acknowledged before generalizing the results of our study.
KEY POINTS Amino acid digestibility must be measured at the ileal level or using alternative procedures developed recently, in human and animal models. The amino acid bioavailability of legumes, refined and brown cereals, nuts, eggs, milk and meat with various treatments has recently been determined under various methodological conditions. The interindividual variability is inversely associated with digestibility and can be assumed as a marker of low amino acid bioavailability. In the case of gastric bypass, protein digestive efficiency is improved due to intestine hypertrophy, but metabolic bioavailability is paradoxically decreased. Limited data exist for other unhealthy gut conditions, although protein malabsorption has been quantified in pancreatic insufficiency and short bowel syndrome.
CONCLUSION The past few years have seen a renewed interest in protein and amino acid bioavailability in view of documenting the quality of plant and alternative proteins to animal proteins and, furthermore, to enrich the DIAAS database. As protein and amino acid digestibility are methodologically complex and invasive, many developments have been conducted to reduce the invasiveness or to improve the accuracy of data. In conditions of healthy gut functioning, the true digestibility depends on the protein source, animal more than plant protein, especially in the context of the food matrix where several values are below 75% for plants. Important interindividual variability is observed for low digestible protein but the reasons remain unknown. In abnormal gut functions, protein digestibility has been little-addressed and dedicated studies to determine protein malabsorption and the subsequent risk of protein malnutrition are required.
Background Excess male morbidity and mortality is well recognised in neonatal medicine and infant health. In contrast, within global nutrition, it is commonly assumed that girls are more at risk of experiencing undernutrition. We aimed to explore evidence for any male/female differences in child undernutrition using anthropometric case definitions and the reasons for differences observed. Methods We searched: Medline, Embase, Global health, Popline and Cochrane databases with no time limits applied. Eligible studies focused on children aged 0-59 months affected by undernutrition where sex was reported. In the meta-analysis, undernutrition-specific estimates were examined separately for wasting, stunting and underweight using a random-effects model. Results 74 studies were identified: 44/74 studies were included in the meta-analysis.
Likewise, the practical implications of these differences remain to be determined. On average, boys are slightly heavier and longer at birth and throughout infancy compared with girls, and more detailed studies have shown that the extra average weight of boys is primarily lean mass, whereas fat mass is more similar between the sexes. 16 17 To evaluate growth and nutritional status therefore, raw anthropometric data are conventionally converted to indices (eg, weight-for-age; weight-for-length, length-for-age) and expressed in comparison to reference populations as z-scores (SD scores, whereby +1 and -1 z-scores are one SD above and below the reference population median, respectively). Data published by WHO in 2006 represent a 'gold standard' of how children should grow and were developed from a globally representative reference population of healthy, breastfed children.
Search strategy Our search strategy captured the concepts of undernutrition, sex and gender. Detailed search terms are in box 1. Studies were identified by searching the Medline database using the above terms which were then adapted to Embase, Global health, Popline and Cochrane databases. No limits were applied for year of publication in order to capture historical publications on the subject. Studies were restricted to those that included terms for boy, girl, male, female, gender, or sex in the title or abstract, with the aim of filtering through the large body of literature that exists for undernutrition and capturing studies which either directly focused on sex and/or gender in the context of undernutrition or those which disaggregated and reported on it within main findings. As per the PRISMA recommendations, the search strategy was peer reviewed by a librarian.
Eligibility criteria Studies were included in the review if they met the following criteria: human studies, age range of 0-59 months, male and female participants, outcomes related to the prevalence or determinants of undernutrition, and related morbidity and mortality. Studies were eligible for inclusion in the meta-analysis if they presented data disaggregated by sex for both the overall sample and the outcome of interest (wasting, stunting, underweight), or relevant ORs. Studies of children over 59 months, non-English language, animal studies and studies on overweight/obesity and micronutrient deficiencies were excluded. Both peer-reviewed and grey literature were.
Data extraction All records identified through the search were imported into EndNote (EndNote V. X8, Clarivate Analytics). Duplicates were identified and removed. Initial screening was conducted by reading titles and abstracts to identify and remove studies which clearly did not fit our scope. Detailed review of the full text of all remaining results was conducted to determine which met the inclusion and exclusion criteria. When it was not clear how to classify an article, this was resolved through discussion and consensus with two or more authors. A data extraction template was piloted on a small number of articles before being finalised. Data were extracted on study characteristics and outcomes of interest. These included aims and types of studies, sample size, prevalence and male/female ORs for undernutrition, and explanations offered for any differences identified.
Risk of bias assessment We adapted the National Heart, Lung and Blood institute study quality assessment tools for Observational cohort and cross-sectional studies to assess the quality of studies,  20  and applied it to studies identified for the meta-analysis. Using this tool, we assessed data sources, a study's presentation of aims and objectives and target populations, the appropriateness of anthropometric methods and the presentation of results. We adapted the tool to assess if studies acknowledged sex differences in the discussion of results.
Study selection The study flow chart in figure 1 summarises our process of identifying studies. The final search of Embase, Global health, Popline and Cochrane databases conducted in March 2020 identified 34 270 studies, including both peer-reviewed studies and grey literature. In addition, 21 studies were found from other sources. After removing duplicates, 22 357 studies remained. Initial screening excluded 21 925 studies as they were unrelated to our review questions. Full texts of the 432 remaining studies were reviewed in detail to assess eligibility. At this stage, a further 358 studies were discarded as they did not meet the inclusion criteria, mostly because there was no mention of sex or gender in relation to undernutrition. Seventy-four studies were therefore included BMJ Global Health in the qualitative synthesis.
Study characteristics Table  1  shows the characteristics of each of the studies included in the review. The studies selected for the review varied widely in terms of aims and study design. Many were observational, assessing prevalence of undernutrition and related risk factors and many included secondary data analysis. The outcomes, both primary and secondary, also varied widely. The studies took place in more than 30 countries (some covered multiple countries). The studies were spread across Central Africa (3/74) East Africa (33/74), East Asia (1/74), North Africa (1/74), Oceania (1/74), South America (2/74), South Asia (10/74), South East Asia (9/74), South West Pacific (1/74), West Africa (8/74) and multiple countries (5/74). Where sample size was clearly stated, the included studies involved 3 361 736 participants.
Meta-analysis We identified 74 studies that had measured undernutrition in the form of wasting, stunting and underweight and reviewed them for inclusion in the meta-analysis. Forty-four studies included extractable data, fully disaggregated by sex and were therefore eligible for inclusion, 41 of these were cross-sectional and 3 were longitudinal (in which case the most recent prevalence data were used). Results from the analysis are presented in the forest plots in figure  2.
BMJ Global Health Interpretation of these findings into implications for practice and policy is limited at this stage but does warrant consideration and some degree of change. As a minimum, the systematic collection and reporting of disaggregated data by age and sex should be included in the design of programmes and assessments in all settings. Where differences are observed, particularly in programme admissions, these should be interpreted in light of sex differences in population burden in order to draw conclusions as to whether programmes are proving equally accessible to boys and girls, and then the potential causes of these differences should be considered and/or investigated. At present, boys' vulnerability to undernutrition is rarely a consideration in the design of nutrition programming, nor the formulation of policy.
Cell viability assay Cell viability and apoptosis were assessed using annexin V-APC/ 7-AAD staining (BD Biosciences). Fluorescence intensity was measured in a MACSQuant Analyzer (Miltenyi Biotech). Data were analyzed using Flow Jo software (version 10, Tree Star, Inc. ). Cell viability of treated cells was normalized to vehicle condition (i. e. cell viability of vehicle treated cells for each patient is set to 100% and all data were indicated relative to this value). In some experiment (when indicated, ex. in drugs combination experiments), cell viability was assessed using CellTiter-Glo Luminescent Cell Viability Assay Kit (Promega).
Drugs combination with AA study and synergism determination Synergism was evaluated with the Chou-Talalay Combination Index (CI) using the experimental design as recommended by Chou TC  [31]. Drugs were serially diluted in culture media and then cells were added to the media (in two replicates) and incubated for 24 h. Cells were seeded in 96-well plates at 1 × 10 5 cells per well. A constant molar ratio combination for drugs based on lethal concentration 50 (LC50) values was used. The cytotoxicity of these drugs or combinations was assessed by CellTiter-Glo assay (Promega). The combination indexes (CIs) and fraction affected (Fa) based on the Chou-Talalay method using CompuSyn software (CompuSyn Inc. Paramus, NJ, USA). CI values < 1 were considered as synergistic  [31]. For the data in Fig.
Statistical analysis Data were expressed as the mean ± standard error of the mean (SEM). The data are expressed as a percentage with respect to that of vehicle-treated cells (control), which was set to 100%. However, statistical analyses were done with absolute viability data. All statistical analyses were performed with GraphPad Prism® software (version 5. 0; GraphPad Software Inc. , San Diego, CA, USA). Statistical significance was assessed in a one-way analysis of variance. A two-sided paired t-test was used to detect significant differences between groups. The threshold for statistical significance difference was set to p < 0. 05 (* p values < 0. 05; ** p values < 0. 01 and ***p values < 0. 001). No blinding and no randomization of samples were applied.
Ascorbic acid induces redox alteration in OSU-CLL cell line Given that H 2 O 2 is membrane-permeant  [40] , we next measured levels of intracellular H 2 O 2 accumulation in two human cell lines (OSU-CLL  [28]  and JVM3  [41] ). As in the experiments on primary CLL cells, AA induced apoptosis in OSU-CLL cells, with an LC 50 of 243. 4 μM. In contrast, the JVM3 cell line was resistant to AA effects (Fig. 2a, b ). Mitochondrial superoxide radical levels were measured in a MitoSox flow cytometry assay. In OSU-CLL cells, the mean MitoSox fluorescence intensity was 38% higher for 250 μM AA than for the control (p < 0. 05) (Fig. 2c  and Fig. S2A ). This difference was not observed in the presence of 1 mM SP (data not shown). In treated JVM3 cells, the MitoSox level decreases by 30% after AA treatment (p < 0.
GAPDH in CLL B-cells from AA-sensitive patients (S-CLL B-cells) or AA-non-sensitive patients (NS-CLL B-cells) and B-cells from healthy donors (HD B-cells ). e: Catalase protein expression (normalized against β-actin) in HD B-cells and CLL B-cells (*: p < 0. 05, ***: p < 0. 001). f: Upper panel: Western blot and quantification of catalase protein levels following treatment of JVM3 cells for 48 h and 72 h with a control siRNA (siCtrl) or siRNA against catalase (siCAT). Relative catalase protein levels were quantified using ImageJ software. Lower panel: At 72 h, siRNA-transfected cells were treated by AA and cell viability was assessed after 24 h using the CellTiter-Glo Luminescent Cell Viability Assay Kit (n = 2 in duplicate). *: p < 0. 05, **: p < 0. 01. Data are presented as the mean ± SEM.
05) (Fig. 5d ). We then compared the effects of increasing concentrations of AA on CLL Bcell viability in the presence of 10% autologous serum. At a concentration of 500 μM, AA induced a high level of CLL B-cell deatheven in the presence of patient serum (p < 0. 01 vs. Ctrl) (Fig. 5e ). These data strongly suggest that components in the CLL patient's serum attenuate the AA's effects on leukemic cells. As CLL B-cells are in perpetual transition between normoxic compartment (the peripheral blood) and hypoxic tissues in lymph nodes and bone marrow, we next decided to study the impact of hypoxia on the cytotoxic effect of AA  [46, 48]. To address this question, we used cobalt chloride (CoCl 2 ) as a hypoxia-mimetic agent. OSU-CLL and JVM3 cell lines were pretreated with CoCl 2 for 24 h and then AA was added and cell viability was measured 24 h later.
S4B, C, D ). The combinations of these drugs with AA at the same doses had no significant impact on healthy donors' B-cells survival (Fig. S5 ). To study synergism between AA and CLL targeted therapies (ibrutinib, idelalisib and venetoclax), we used the Chou-Talalay method in a constant-ratio combination design  [31]. To identify synergistic effects, the combination index (CI) was calculated by the software Compusyn (CI < 1). The single-agent dose-effect curves of primary CLL Bcells from 6 patients are shown in Fig. S6. The combination index values calculated using the actual experimental data points showed synergistic interactions (CI < 1) between AA and all three drugs at AA dose of 250 μM or higher for all 6 patients (Fig. 6b ). For several patients, synergism was observed at 250 μM of AA but also at lower doses (Fig.
Discussion Despite major progress in treatment, CLL is still an incurable disease. We wondered whether oral supplementation with AA (vitamin C) would have an impact on CLL B-cell survival. To study this effect in vitro, we used   16 )) (*: p < 0. 05; **: p < 0. 01, ***: p < 0. 001). Cell viability was determined by an annexin V/7AAD staining. b: Synergistic efficacy of combination of AA and CLL targeted therapies in primary CLL B-cells. Left panels: Primary CLL cells (n = 6) were treated with ascorbic acid (AA) and ibrutinib or idelalisib or venetoclax for 24 h. CellTiter-Glo cell viability assay was performed to detect cell kill synergy. The curves show the dose-effect of single drugs and that of drugs combination. Each data point is the mean of six samples. Right panels: Tables show the combination index (CI) of each combination for each patient (P).
The CI values were calculated using the Chou-Talalay method by the software Compusyn. Fa: fraction affected (fraction of cells affected by a particular drug dose) recent knowledge from pharmacokinetic studies showing that oral administration of AA can achieve a plasma concentration of around 250 μM  [16, 18]. Using this concentration, we (i) provided mechanistic insights into the cytotoxic effect of AA on CLL B-cells, (ii) investigated the role of the CLL microenvironment in resistance to AA's effect, and (iii) suggested new therapeutic strategies. We showed that 250 μM AA selectively induced cell death in primary leukemic CLL B-cells by acting as a pro-oxidant and thus by leading to the release of H 2 O 2 into the extracellular medium. These results are in compliance with previous observations in other cancers  [5, 12, 14].
Acknowledgments The work performed in the authors' laboratories was supported by  CHU Amiens-Picardie  and UPJV. We thank all the physicians from the hematology department and the Cell therapy department at the  Centre Hospitalier Universitaire Amiens-Picardie  for providing samples from patients and healthy donors. We also thank the  Cancer United Research Associating Medicine, University and Society (CURAMUS) «INCA-DGOS-Inserm_12560»  and the  Fondation de France.
Considering this latter immune-modulatory role of TNF, combining TNF blocker and ICI has been tested. For instance, the Ségui's laboratory reported that TNFR1 mediates the Activation-Induced Cell Death (AICD) of CD8+ melanoma-specific tumour infiltrating lymphocytes (TILs)  [93]  and that combining anti-TNF and anti-PD-1 promotes the regression of murine melanoma  [94]. In accord, a phase 1b trial (NCT03293784) is ongoing combining anti-TNF and ICI for treatment of metastatic melanoma  [95]. This combination might be beneficial for patients suffering from other types of cancer (for example colon cancer), including via the ability of TNF blockers to reduce some adverse effects of ICI  [96]. Overall, rationale supports both blocking TNFR1 signalling or fine-tuning it for future anti-cancer therapies.
Together with CD95's role as a mediator of immune cells cytotoxicity, this argues for a potential anti-tumour role of this DR. Since the hepatotoxicity of some CD95 agonists was attributed to an antibody dependent cell-mediated cytotoxicity  [110] , non-antibody based CD95 agonists were developed. As such, APO010, an hexameric CD95L fusion (two CD95L extracellular domain trimers fused to the collagen domain of adiponectin)  [111]  displayed some efficiency in glioma models  [112, 113]. Detailed results from a clinical trial evaluating its tolerability and efficiency in patients with solid tumours (NCT00437736) are not available yet. However, when considering CD95 agonists as a single treatment, caution is warranted beyond the risk of hepatotoxicity since these might also drive tumour-promoting signals.
In primary glioma cells and glioblastoma cell lines CD95 induces migration by recruiting Yes in a caspase-independent manner, forming a protein complex initiating a PI3K/Akt/GSK3β pathway, which promotes Matrix MetealloProteinases (MMPs) up-regulation. Hence, in a syngeneic orthotopic model, the co-injection of glioma cells with a CD95L-neutralizing antibody reduces tumour invasion  [127]. In accord, blocking CD95 signal is one approach developed, for example, with APG101, consisting of the extracellular part of CD95 fused to an Fc domain. APG101 in combination with radiotherapy shows promising pre-clinical and Phase II clinical trial (NCT01071837) results for glioblastoma treatment  [128, 129]. Aberrantly increased CD95-driven apoptosis of erythroid progenitors contributes to myelodysplastic syndromes (MDS), which are characterised by haematopoiesis defects and can evolve in acute myeloid leukemia.