dataesr/scientific-paragraphs-categorization huggingface dataset:
Here, we take advantage of genome-wide genotype data from 1786 admixed Chileans and nationwide mortality data from 2007 to 2017 to investigate the relationship between ROH, genetic ancestry and child mortality in Chile. We use the PLINK software to calculate the sum length of runs of homozygosity (SROH) above 1. 5 Mb in each genome and the ADMIXTURE software to estimate the individual proportions of Aymara-Quechua, Mapuche-Huilliche, European and African ancestry  (36, 37). We assess the relationship between ROH, genetic ancestry and regionally aggregated mortality data by multiple linear regression to estimate the expected regional SROH and ancestry proportions, followed by multiple Poisson regression to quantify the association between regional mortality rates and the expected SROH and ancestry proportions.
As expected, Chileans in the fourth SROH quartile (33. 5-502 Mb) were on average shorter (-1. 32 cm, 95%CI: -2. 29 to -0. 35) than Chileans in the first SROH quartile (0-17. 5 Mb, Supplementary Material, Table  S2 ), adding plausibility to the rest of our findings. After examining the geographical distribution of SROH and ancestry proportions, the association between regionally aggregated mortality rates, SROH and ancestry proportions was quantified by multiple Poisson regression. To facilitate the interpretability of results, standardized mortality ratios (SMRs) are reported per Mb in SROH, and per 1% proportion of Aymara-Quechua and Mapuche-Huilliche ancestry. Only perinatal conditions (first character P or Q in the code of the 10th version of the International Classification of Diseases-ICD10) causing at least 200 deaths before the age of 5 years in Chile between 2007 and 2017 were considered, resulting in 23 investigated ICD10-categories.
The proportion of Mapuche-Huilliche ancestry was associated with an increased mortality due to other congenital malformations of brain (ICD-10 code Q04, 7% increased risk per 1% ancestry proportion, 95%CI: 2-12%) and with a decreased mortality due to Edwards syndrome and Patau syndrome (ICD-10 code Q91, 5% decreased risk per 1% ancestry proportion, 95%CI: -8 to -2%). To examine the robustness of the identified associations, we inspected visually the relationship between gender-specific mortality rates, SROH and ancestry, and performed genderstratified regression analyses. Figure  2A  shows the scatterplot for SROH and disorders related to short gestation and low birth weight, not elsewhere classified (ICD-10 code P07). Results are represented in red for young girls and blue for young boys.
The corresponding estimated SMRs are shown in Supplementary Material, Table  S3. Opposite associations were noticed for young girls (1% risk decrease) and young boys (3% risk increase per Mb in SROH). Results for young girls strongly depended on the data from De Maule region, which showed the highest average SROH (76. 2 Mb). However, effect estimates for males and females were even more different after exclusion of this high-leverage observation (6% risk decrease for young girls, data not shown). In contrast, consistent associations in young girls and boys were found for SROH and intracranial non-traumatic haemorrhage of foetus and newborn (ICD-10 code P52, Fig. 2B , the estimated SMR for young girls was 1. 01 after exclusion of the De Maule region, data not shown). Visual inspection of the remaining scatter plots revealed no apparent outliers or leverage points, and gender-stratified analyses revealed undifferentiated associations between Aymara-Quechua ancestry and respiratory distress of newborn (ICD-10 code P22, Fig.
Aymara-Quechua ancestry was also associated with an increased risk of child death due to anencephaly and similar malformations (ICD-10 code Q00), and Mapuche-Huilliche ancestry was associated with congenital malformations of brain (ICD-10 code Q04), which could point to a different completion of death certificates in the north and south of Chile. Anencephaly is known to be influenced by multiple risk factors including folic acid deficit, mutations in the genes of the folate pathway and exposure to a variety of toxins and contaminants. Folic acid supplementation could be particularly indicated to pregnant women with large proportions Downloaded from https://academic. oup. com/hmg/advance-article/doi/10. 1093/hmg/ddab302/6406904 by guest on 17 January 2022 of Native American ancestry, and the high levels of arsenic in drinking-water and copper mining in the north of Chile could contribute to the identified association with Aymara-Quechua ancestry.
Study participants and associated sociodemographic data The study comprised 1786 individuals who were recruited from 2010 to 2013; 39% of the study participants were women and the median age was 27 years. About two-thirds of the subjects were professional soldiers, with a relatively large proportion of men born in the south of Chile (Del Maule, Del Biobío and De la Araucanía regions). On the contrary, 60% of the women were recruited from the northern region De Arica y Parinacota, which was also the region, where the most participants were recruited from (42%), followed by Metropolitana de Santiago (18%), and Del Bío-Bío (9%). Since the majority of soldiers are typically recruited from among the middle classes, with minorities from the social elite and the lowest socioeconomic groups, this dataset represented the general Chilean population quite well.
Aggregated mortality data Aggregated mortality data were obtained from the Chilean Department of Statistics and Health information (www. deis. cl). Causes of death were grouped according to the 10th version of the International Classification of Diseases (www. who. int/classi fications/icd/, ICD10). We considered the first three characters of the ICD10 code and investigated perinatal conditions (first character P and Q). Only diseases causing at least 200 deaths before the age of 5 years in Chile between 2007 and 2017 were considered, resulting in 23 investigated ICD10-categories. From 2007 to 2017, Chile was divided into 15 regions, which are the country's first-level administrative division.
Genotyping and quality control Blood samples were collected by certified phlebotomists and trained nurses. DNA was extracted following standard laboratory procedures. Genotypes were available for 730 525 single nucleotide polymorphism (SNP) markers from the Illumina's Human610-Quad beadchip. Intentional duplicates, samples with sex information inconsistent with genotype data and related individuals with shared identity by descent proportion ≥0. 25 were removed. For the calling of ROH, variants with a minor allele frequency (MAF) under 5% and more than 3% missing genotypes across all individuals were excluded, leaving 593 740 SNPs for the subsequent ROH calling. For the genetic principal component and ancestry analyses, variants with an MAF under 5% and more than 5% missing genotypes were excluded.
Genetic principal component analysis and estimation of ancestry proportions Genetic principal component analyses were conducted using the eigenstrat function available at www. popgen. dk/software/inde x. php/Rscripts  (40). The ADMIXTURE software (version 1. 3) was used for supervised estimation of individual African, European, Northern Native Chilean and Southern Native Chilean ancestry components relying on reference individuals (37). Surrogates of African and European ancestry were 108 Yorubans in Ibadan, Nigeria, and 99 Utah residents with Northern and Western European ancestry as well as 107 individuals from Iberian populations in Spain from the 1000 Genome Project  (41).
Statistical analyses Data were analyzed using the R software environment for statistical computing and graphics (version 3. 6. 0). The relationship between the aggregated mortality data, SROH and Native American ancestry proportions was investigated in two stages. First, the expected regional SROH, Aymara-Quechua and Mapuche-Huilliche ancestry were estimated by multiple linear regression using the models E [X 1 |Z] = Z T d 1 , E [X 2 |Z] = Z T d 2 , E [X 3 |Z] = Z T d 3 , where the SROH (represented by X 1 ), the Aymara-Quechua ancestry proportion (represented by X 2 ) and the Mapuche-Huilliche ancestry proportion (represented by X 3 ) depended on the product of a design matrix Z times a fixed-effect vector d, which included the intercept and the response variables gender and region. Each model was run 15 times, altering each time the reference region.
Objective: The aim of this study was to assess incidence, causes and consequences of equipment failures in a high volume, advanced endoscopic surgery department. Methods: This is a prospectical observational single centre study between April and July of 2019 in the Gynecological surgery department of the Estaing University Hospital of Clermont-Ferrand, France. During the study period, 171 laparoscopies were observed. Data were collected real time by three supernumerary observers. Results: In total, 66 (38. 6%) laparoscopies were complicated by equipment failures. The bipolar cable and forceps accounted for 31% of the total amount of malfunctions in laparoscopy. Causes of malfunctions were in 45% due to the instrument per se and in 43% due to the incorrect combination of elements. Less commonly, the equipment was not available or a mismatched was reported.
Material and methods This is a prospective observational single-center study performed in the gynecological surgery department of the Estaing University Hospital of Clermont-Ferrand, France. All laparoscopic gynecological procedures performed between April and July 2019 were included, with the exclusion of emergency and trial procedures. Written consent was ruled out by the institutional review board for the observational study. Data were collected real time by three supernumerary observers. One observer was the leader, receiving direct training from the senior author, and was the one responsible for discussing unclear cases and intermediate data with the senior author. The other two observers were trained by the leader both with the support of the available literature for the methodology and demonstrative live sessions in the operative room.
Then, they collected pilot data for one week under the supervision of the leader, and finally started collecting independently. Data were always crosschecked between the three observers after the surgeries to avoid inter-observer bias. In case of doubt on objective issues, for example the type of instrument involved in the malfunction or the cause of the malfunction, the observer had to ask the scrubed nurse and/or the first surgeon in order to clarify the doubt. On contrary, to assess more subjective issues, such as human involvement and responsibilities, some cases were discussed with the senior author, who was not directly involved in the surgery. In this way, we tried at best to enhance data accuracy, reducing bias linked to impartiality and distortion of the information. The amount of procedures and failures was calculated in relation to the operator and the difficulty of the surgery, by dividing laparoscopies in 3 groups: (a) low difficulty, such as salpingectomy, annexectomy, ovarian cystectomy, explorative and fertility procedures; (b) medium difficulty, as hysterectomy and myomectomy; (c) high difficulty, including laparoscopic prolapsus surgeries, endometriosis and oncologic surgeries.
For each observed procedure, the following data were collected: -name and date of the procedure; -name of the first surgeon and first assistant; -duration of the procedure, from the incision to skin closure; -presence of one or more equipment failure, where the equipment fail-ure was defined as a problem of the endoscopic equipment resulting in a waste of time and a consequent measure of correction; -duration of each equipment failure, from the moment it has appeared to its resolution; -causes and consequences for each failure; -possible human error related to the failure. To achieve it, an equipment catalogue was created, inspired by the one published by  Wattiez et al. , 2008 [6] , and a specific data collection form was printed and delivered to the observers. Within the catalogue, equipment was divided into 4 categories: (a) fluid and gas circuit, including connections and fittings which could interfere with the fluid flow; (b) endoscopic instruments, such as forceps, scissors and even the small fittings that are not properly endoscopic but are however functional for the endoscopy, such as suspension/exposition devices and fascia closure devices; (c) electrical circuit, including bipolar forceps failing to conduct the electricity or cables and pedals; (d) video system devices, such as the optic and the camera which could be responsible of a dirty image or even a missed one.
Data Used in the Model Food consumption data were collected from the National Food and Physical Activity Consumption Survey (IAN-AF 2015-2016), a representative sample of the Portuguese general population aged between 3 months and 84 years old, with a total of 5811 participants  [20] [21] [22]. In this study, food consumption data from 779 children aged 6 to 36 months from the IAN-AF 2015-2016 sample was included. The sample size of participants was determined, considered in the power analysis, and presented in detail in the methodological publication of the IAN-AF 2015-2016 survey  [21]. Data on food consumption were collected according to European guidelines  [47]. For children aged under 10 years old, dietary intake was assessed by two non-consecutive one-day food diaries that were filled in by the main caregiver, followed by a face-to-face interview conducted with the caregivers to collect additional details on food description and quantification.
Between 2018 and 2019, the PNCA analyzed 50 samples of BC, corresponding to 30 different batches, for which 5 boxes were tested. Fourteen out of 150 samples had positive levels of B. cereus. For IC, data from another study carried out in Portugal in 2007 were applied, in which 35 samples were analyzed, including 15 positives  [37]. For both IC and BC, samples below the limit of detection (LOD) (<10 colony forming units (CFU)/g), were assumed to have 5 CFU/g. For BC, positive samples below 40 CFU/g were reported as <40 CFU/g in the database; these were assumed to have 25 CFU/g, i. e. , the median between 10 and 40. Regarding DALY, this metric combines information on disease incidence, severity, duration and mortality in one number and enables comparison across diseases  [51, 52]. The epidemiological and toxicological data used to derive the correspondent DALY are presented in Table  3.
Exposure Assessment, DALY Calculation and Integration of Risks and Benefits We applied different approaches for exposure and health impact assessment for each component-health effect pair. All models were developed and implemented in the @Risk ® software for Microsoft Excel version 6 (Palisade Corporation, Ithaca, NY, USA). We defined model variables as probabilistic distributions to quantify uncertainty. The approach applied for each component is described below and all models are documented in the Supplementary material (Table  S1 ). SPADE software  [55]  was used to estimate the intake distributions of total fiber, sodium and free sugars in the current and each alternative scenario.
We calculated the incidence and DALYs attributed to the change in IC and BC consumption in each scenario by multiplying incidence and DALY rates for DM2 and CVD for Portugal, obtained from the Global Burden of Disease 2017 study (GBD)  [53]  (Table  3 ), by the PIFs for each alternative scenario. A semi-quantitative analysis was performed for sodium and free sugars. The DRVs used were an upper-limit (UL) of 1500 mg/day for sodium  [58]  and a recommended intake (RI) of 5% and 10% of total energy intake (TEI) for free sugars  [19]. The prevalence of individuals above or below the DRVs was estimated for each scenario using SPADE software  [55].
Bacillus Cereus A beta distribution was used to approximate prevalence based on the percentage of positive values; it was expressed as a beta of "number of positive + 1; total sample-number of positive +1". For positive samples, to represent the level of B. cereus, a cumulative distribution was built for BC and a triangular one for IC. Simulations were run to represent the level of B. cereus in IC and BC, giving a value of 5 CFU/g when considered to be non-contaminated (<10 ufc/g) and selecting randomly for positive sample levels from the cumulative or uniform distribution of BC and IC, respectively. To estimate exposure to B. cereus (in CFU/day) through consumption of BC and IC in the considered population group, contamination data in CFU/g and consumption data in g/day were multiplied. This was done by multiple simulations to combine the different possible exposure values (observed for the reference scenario or estimated for alternative scenarios).
Regarding chemical contaminants, the literature review revealed the occurrence of mycotoxins  [5] [6] [7] [8] , heavy metals  [9, [11] [12] [13] 75] , acrylamide  [14] , furans  [15]  and PAHs  [16]  in breakfast cereals and infant cereals. The second step was conducted for the association "health effect-component" pairs and concerned the identification of potential health effects of each nutrient/contaminant/ microbiological agent identified. The selection of relevant health effects was based on official assessments by international authorities, regulatory agencies, food composition databases, and scientific papers available. Considered health effects included Diabetes Mellitus 2 and cardiovascular diseases, with an emphasis on evidence related to children  [76] [77] [78] [79] [80] [81] [82].
3, H  and J-L ). Therefore, T-bet-deficient CD4 + T cells overproduce Th2 cytokines in a T-bet-dependent manner. T-bet-deficient CD4 + T cells are epigenetically poised to promote Th2 skew We then investigated the molecular mechanism by which T-bet suppresses the expression of Th2 cytokines. Datasets from an omni-ATAC-seq experiment probing expanded CD4 + Th0 cells from healthy donors and from P, and P's cells complemented with EV or WT T-bet, were reanalyzed focusing on Th2 cellspecific difference  (Yang et al. , 2020). As T-bet deficiency unleashes Th2 cell production by disinhibition of GATA-3  (Hwang et al. , 2005) , we first focused on loci that were both differentially regulated in P in a T-bet-dependent manner and occupied by GATA-3 binding  (Yang et al. , 2020; Kanhere et al. , 2012).
ALEX allergen screen Allergy Explorer version 2. 0 (ALEX 2 ; Macro Array Diagnostics) was used to determine the levels of IgE against 282 allergens (156 extracts and 126 molecular allergens) according to the manufacturer's instructions. Briefly, plasma samples from P and controls were diluted 1:5 with a cross-reactive carbohydrate determinant inhibitor-containing diluent and incubated on the chip. Detection was performed by adding an alkaline phosphatase-conjugated anti-human IgE antibody (Ab). Raptor software (Macro Array Diagnostics) was used to quantify plasma IgE within a range of 0. 3-40 kU/liter. Values ≥0. 30 kU/liter were considered to be positive. Th2 cytokine determinations in TBX21-transduced primary CD4 + T cells This experiment was performed as previously described  (Yang et al.
(M-Q) T cell clones from memory CD4 + T cell libraries responsive to peptide pools from BCG (M), C. albicans (N), EBV (O), influenza A virus (P), or tetanus toxoid (Q) were subjected to Luminex assays to assess the levels of IL-17A. (R) T cell clones from memory CD4 + T cell libraries responsive to peptide pools from the pathogens indicated were subjected to Luminex assays to assess the levels of IL-22. (S) High levels of Th2 cytokines, UAI, and peripheral eosinophilia in the patient with inherited human T-bet deficiency. In F-R, bars represent the mean and SD. Dots represent individual T cell clones. Unpaired Student's t test was used in F-R. In F-R, *, P < 0. 05; **, P < 0. 01; ***, P < 0. 001; ****, P < 0. 0001. Data from A-E were summarized from a single experiment with library preparations from three controls (CTRLs) and independent repeats of libraries preparation from M/M and M/M complemented with EV or WT.
Examination of ILCs from peripheral blood of inherited T-bet deficiency Immunophenotyping of ILCs was performed in a recent publication, in which the staining and experimental procedures were described  (Yang et al. , 2020). Datasets from this published work were reanalyzed focusing on GATA-3 expression in ILCs, which was not done in the last publication. ILCP and ILC2, based on their surface markers described previously  (Yang et al. , 2020) , were gated, and intracellular expression of GATA-3-BUV395 was analyzed using FlowJo. Cytokine production by and ICS of PBMCs in response to prolonged stimulation with BCG-lysates BCG-lysates were prepared and provided by Dr. Carl F. Nathan (Weill Cornell Medicine, New York, NY). PBMCs from adult donors, the T-bet M/M P, and his relatives were resuspended at a density of 10 6 cells/ml.
Library quality was analyzed with a Bioanalyzer High Sensitivity DNA chip (Agilent). Sequencing was performed with Illumina NextSeq 500 in a 26-bp Read 1, 98-bp Read 2, and 8-bp Index 1 configuration. We obtained a mean of 23,283 reads per cell for the healthy donor and 89,076 reads per cell for P (TBX21 M/M). Reads were mapped onto the hg38 human reference genome assembly, and barcodes and UMIs were filtered and counted with CellRanger (v3. 0. 1). For each gene and cell, a list of UMI counts was obtained. The data were further analyzed with the Seurat v3 R package  (Stuart et al. , 2019). Cells with >10% mitochondrial genes or outside the [200, 5,000] interval of detected genes per cell were excluded. Normalization was performed by regularized negative binomial regression, with mitochondrial percentage included as an additional covariate  (Hafemeister and Satija, 2019).
Omni-ATAC-seq on CD4 + T cells and analysis The omni-ATAC-seq experiment was previously performed in a recent publication  (Yang et al. , 2020). Datasets were previously deposited at National Center for Biotechnology Information-Bioproject under accession no. PRJNA641463. Datasets were revisited in this study focusing on Th2 cell targets, which were not investigated in the previous report. Similar to a previous study  (Yang et al. , 2020) , T-bet chromatin immunoprecipitation sequencing (ChIP-seq) data in human Th1 cells (Sequence Read Archive accession no. SRR332104) and GATA-3 ChIP-seq data in human Th2 cells (Sequence Read Archive accession no. SRR332106), and their input controls were retrieved as unaligned sequences from the European Nucleotide Archive  (Kanhere et al. , 2012). Sequences were aligned with the hg38 genome from the Bsgenome.
Hsapiens. UCSC. hg38 Bioconductor package (version 1. 4. 1), with Rsubread's alignment method, and predicted fragment lengths calculated with the ChIPQC package  (Carroll et al. , 2014; Liao et al. , 2014; de Santiago and Carroll, 2018). Normalized, fragment-extended bigWigs signals were created with the rtracklayer package as previously reported  (Yang et al. , 2020). We focused on analyzing chromatin accessibility regions that were differentially regulated in the patient's CD4 + T cells (M/M) relative to controls but reversed by WT T-bet complementation (M/M + WT versus M/M + EV). For differential accessibility analysis, we imported raw ATAC-seq read counts into DESeq2 (version 1. 20. 0) and used a multifactorial generalized linear model to identify differential sites while accounting for cell type.