dataesr/scientific-paragraphs-categorization huggingface dataset:
Study Design The design and primary results of the EMPEROR-Preserved Trial (NCT03057951) have been recently reported. 6, 7   he study included HF patients with an LVEF >40% and New York Heart Association Class II-IV functional class. Study participants were randomized in a double-blind manner to receive placebo or empagliflozin 10 mg daily. The protocol required an NT-proBNP concentration >300 ng/L for participation; this concentration was increased to >900 ng/L in the presence of atrial fibrillation at baseline. The primary endpoint of EMPEROR-Preserved was time-to-first event in a composite of CV death or hospitalization for HF. The first secondary endpoint was the occurrence of all (first and recurrent) hospitalizations for HF. The second endpoint was the slope of the change in estimated glomerular filtration rate (eGFR) during double-blind treatment.
This approach allows for an understanding of the adjusted change in the geometric mean concentration (superior to arithmetic means for repeated measure comparisons over time) by expressing it as a ratio of the concentration at the present time point/concentration at baseline. To assess the association between change in NT-proBNP from baseline to week 12 and subsequent primary endpoint events occurring after the week 12, a landmark analysis was performed adjusted for same covariates as the Cox model, baseline log-transformed NT-proBNP and NT-proBNP relative change from baseline to week 12. All analyses were performed using SAS, version 9. 4 (SAS Institute). The P values reported are 2-sided with P<0. 05 considered statistically significant. No adjustments for multiple testing were made.
Physical Activity and Sedentary Time The levels of PA and ST were measured in baseline and final assessments with the tri-axis accelerometers in the GT3X activity monitor (ActiGraph LLC) as a valid objective measure  [29, 30]. Participants wore the accelerometer on the right side of the hip, adjusted with an elastic belt, during 7 consecutive whole days including day and night. They removed it only during the shower and aquatic activities. ActiLife Lite Pro software (version 6. 13. 4, ActiGraph LLC) was used to extract PA and ST values. Data were downloaded in 10-second epoch to measure PA and ST. Data collection was performed over 5 weekdays and 2 weekend days, and the first day of measure was excluded from the analysis. Corresponding to the French cultural schedule, PA and ST were analyzed for the whole day (6:00 AM to 11:59 PM) for weekdays and weekend days.
According to the optimal methodological approach for accelerometry, 2 conditions had to be met concerning the minimum wear time required to be considered as a valid measure: (1) participants had to wear the accelerometer at least 80% of the time between 6:00 AM and 11:59 PM and (2) 70% of participants had to wear the monitor during this period  [29]. To estimate usual PA and ST levels, wear-time had to be sufficient for a least 3 weekdays and 1 weekend to be considered valid  [30]. All the data were processed with the ActiLife software. We focused on 7 variables for the whole day in weekdays and weekend days: number of sedentary breaks occurring in the day, ST (minutes), light PA (minutes), moderate PA (minutes), moderate to vigorous PA (minutes), vigorous PA (minutes), very vigorous PA (minutes), and number of steps.
Sleep The ActiGraph GT3X activity monitor was used to measure sleep patterns. These measurements were conducted over the same period of time as the PA and ST. Participants were asked to wear the accelerometer on the right side of the hip even during the night. Sleep data were validated and analyzed if the total sleep period time was above 160 minutes per night with an estimated 90% wear time  [35, 36]. Data were analyzed only for participants having 3 nights validated on weekdays and 1 night validated on weekend days  [35]. Raw data were downloaded in 10-second epochs using the ActiLife software and reintegrated to 60 seconds to perform sleep pattern analysis. We then applied the Tudor-Locke algorithm developed automatically by the ActiLife software and validated  [37]. In contrast to previous algorithms, The  Tudor.
Statistics To further analyze changes in anthropometric values, physical fitness, objective and subjective PA and ST, sleep, and psychological variables, statistical comparisons might include (but will not be limited to) t tests, analysis of variance, Mann-Whitney U test, Kruskal-Wallis test, Pearson/Spearman correlation analyses, or linear and multiple regression analyses. Analyses will be performed using JASP software (version 0. 14. 1, JASP Team).
Background: Chemoradiotherapy alone is the standard treatment for locally advanced squamous cell anal carcinoma (SCAC). However, up to 50% of patients will experience recurrence; thus, there is a need for new treatments to improve outcomes. Modified docetaxel, cisplatin and 5-fluorouracil (mDCF) is a treatment option for first-line metastatic SCAC, having shown efficacy in the Epitopes-HPV01 and -02 trials (NCT01845779 and NCT02402842). mDCF treatment also plays a role in the modulation of anti-tumor immunity, suggesting it may be a good combination partner for immunotherapy in Frontiers in Oncology frontiersin. org 01.
This pivotal study will evaluate this combination in the locally advanced setting. Ancillary biomarker studies will contribute to the understanding of predictors of response or resistance to treatment. Clinical Trial Registration: https://clinicaltrials. gov/ct2/show/NCT04719988, identifier NCT04719988. KEYWORDS ezabenlimab, squamous, anal carcinoma, modified Docetaxel, Cisplatin, 5-Fluorouracil (DCF), Stage III.
Study design INTERACT-ION is a Phase II, open-label, pivotal, singlearm study of ezabenlimab and the mDCF regimen followed by chemoradiotherapy in patients with Stage III SCAC (NCT04719988). The study is sponsored by the Centre Hospitalier Universitaire de Besancon and will be conducted at twelve centers in France. Details of study sites can be obtained via www. clinicaltrials. gov. The study has received a favorable opinion from the Ethics Committee Sud-Mediterraneé I and authorization from the French National Agency for the Safety of Medicines and Health Products and will be conducted in accordance with Good Clinical Practice guidelines.
Response will be evaluated by the investigator per RECIST version 1. 1. For patients who discontinue treatment for reasons other than documented disease progression, loss to follow-up or consent withdrawal, tumor assessment must continue every 8 weeks during the first year and every 12 weeks thereafter until documented disease progression. Radiological assessments will be anonymized by the investigational centers and all imaging data will be collected at the end of the study for centralized review. Safety will be assessed throughout the study by evaluation of AEs, clinical safety laboratory tests (blood analysis, cardiac evaluation), vital signs, and physical examinations. Investigators will evaluate the intensity of AEs (per National Cancer Institute Common Terminology Criteria for Adverse Events version 5) and any causal relationship to study treatment.
Monitoring and safety As the safety profile of ezabenlimab and mDCF has not been evaluated in Stage III SCAC, semi-continuous monitoring for toxicity using a Pocock-type boundary will also be performed (targeted dose-limiting toxicity [DLT] rate: 0. 20). Any nonhematologic grade 4 toxicity lasting >1 week, any immune-related grade 3/4 toxicity lasting >1 week, and hyperprogression will be considered as DLTs. An independent Data Safety Monitoring Board (DSMB) will meet to monitor toxicities and review serious AEs every 6 months or if the DLT number exceeds the boundary limit.
Of note, two ongoing Phase III studies are assessing chemotherapy in combination with PD-1 inhibition. Firstly, the combination of carboplatin and paclitaxel with nivolumab will be assessed in approximately 205 treatment-naïve patients with metastatic anal cancer (NCT04444921). Secondly, the combination of carboplatin and paclitaxel with retifanlimab will be evaluated in around 300 patients with inoperable, locally recurrent or metastatic SCAC (NCT04472429). Both of these trials are currently recruiting patients. Additionally, the Phase II SCARCE trial (NCT03519295) is assessing mDCF in combination with the anti-PD-L1 antibody, atezolizumab  (9). The INTERACT-ION study, presented here, as well as the trials being conducted in the metastatic setting, should contribute further information on the treatment of locally advanced and metastatic SCAC, and the optimal chemotherapy regimens and immunotherapy combination partners.
Acknowledgments The authors received no direct compensation related to the development of the manuscript. The authors would like to thank  Dr Edward Espinal-Dominguez  for his contribution to an early draft of the manuscript. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by  Caroline Allinson and Hannah Simmons MSc of Ashfield MedComms , an  Ashfield Health Company , and was funded by  Boehringer Ingelheim.
Acknowledgements We thank the anonymous referees, whose comments have helped us to improve the presentation of the paper. This study was partially supported by  JSPS KAKENHI  Grant Numbers  JP19J21153  and  JP21K11881. This study was partially supported by the  French ANR  project  ANR-18-CE39-0019  ( MobiS5 ). Other programs also fund to write this paper, namely the  French government research program  " Investissements d'Avenir " through the  IDEX-ISITE initiative   16-IDEX-0001  (CAP.
S2 ). For modulation of the BA composition, foz/foz mice were randomized into 3 groups based on their body weight and glycemia and received a HFD or a HFD supplemented with 0. 03% or 0. 1% (w/w) DCA for 12 weeks, and were compared to WT mice fed a HFD for 12 weeks (n = 6-7/group). Body weight, glycemia and food intake were measured weekly. For sacrifice, mice were fasted for 12 hours then refed for 4 hours (to ensure synchronization for intestinal bile secretion) and anesthetized with ketamine-xylazine. Portal and systemic blood were collected in heparin-coated tubes and plasma stored at -80 C. Bile, liver and distal ileum were harvested, weighed, snap frozen in liquid nitrogen and stored at -80 C or fixed in 4% formalin. Animal care was provided in accordance with the guidelines for humane care for laboratory animals as per the European regulations and data reported in conformity with ARRIVE guidelines.
Statistical analysis Statistical analyses were performed using GraphPad Prism 8. Data are presented as mean ± standard deviation and graphed as individual dots as per the ARRIVE guidelines. Outliers were removed based on Grubbs' test. Normality was assessed using the Shapiro-Wilk test. When comparing 2 groups, an unpaired 2tailed t test or Mann-Whitney test were used to calculate significance. When comparing more than 2 groups, one-way or two-way ANOVA followed by post hoc Bonferroni correction or Kruskal-Wallis followed by Dunn's multiple comparisons test was used to calculate significance. For further details regarding the materials and methods used, please refer to the CTAT table and supplementary information.
Acknowledgments We thank  Natacha Feza-Bingi ,  Sébastien Meurice  and  Mathilde Beka  for animal breeding, genotyping, and care;  Boris Pirlot ,  Simon Ravau  and  Corinne Picalausa  for technical assistance; and  Paulina Henry  for help with histological analyses. We also thank  Amandine Descat  and  Emmanuelle Vallez  for their indispensable contribution to BA extraction and dosage.
| MATERIAL S AND ME THODS We performed a retrospective, multicentric observational study for excised atypical BCC lesions showing at least one of the revised seven-point checklist criteria at dermoscopy, compared with excised atypical MM lesions showing at least one BCC criteria at dermoscopy. This study was approved by the Ethics committee of Modena (protocol No 169/17). 14 ses were selected from dedicated databases at collaborating   S1. Cluster analysis was used to identify BCC and MM subgroups, to describe the most obvious features observed among this heterogeneous lesion cohort. According to the most obvious characteristics for each subgroup, descriptive names were arbitrarily given. The identification of "trump" dermoscopic features was identified based on multivariable analysis (outlined below).
1 in the rst group [n=9] and Delta and BA. 1 co-infection in the second group [n=9]) as well as a third group of COVID-19-naïve individuals who received three doses of the BNT162b2 vaccine (n=9) (Table  S1 ). Blood sampling was performed 6 months after breakthrough infection for infected individuals or after the third vaccine injection for COVID-19-naïve individuals (Table  S1 ). Statistical analyses were performed using the GraphPad Prism® software (version 8; GraphPad software, La Jolla, CA, USA). Participants were included from two clinical studies registered on ClinicalTrials. gov (NCT05060939, NCT04341142). Written informed consent was obtained from all participants and approval was obtained from the regional review board in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID-RCB 2020-A00932-37; ID-RCB 2021-A01877-34).
Authors contributions. S. T. A and A. B conceived the study. C. S; B. P; S. P and M. Y. N performed and interpreted experiments. B. L, A. B and L. J performed metagenomics analysis to identify viral strains. C. S wrote the initial draft, performed statistical analysis and generated gures. All authors read, edited and approved the nal manuscript. Data availability statement. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. GISAID accession numbers for the 19A, Delta, BA. 1, BA. 4 and BA. 5 strains used are EPI_ISL_1707038, EPI_ISL_1904989, EPI_ISL_7608613, EPI_ISL_12396843, and EPI_ISL_12852091, respectively.
Methods: We retrospectively analyzed between April 2020 and February 2021 200 records of divers suspected of COVID-19 contamination. Data collected included physical examination, ECG, blood biochemistry, chest CT scan and spirometry. Results: 145 PCR-positive subjects were included, representing 8. 5% of the total population of French military divers. Two divers were hospitalized, one for pericarditis and the other for non-hypoxemic pneumonia. For the other 143 divers, physical examination, electrocardiogram and blood biology showed no abnormalities. However 5 divers (3. 4%) had persistent subjective symptoms including fatigability, exertional dyspnea, dysesthesias and anosmia. 41 subjects (29%) had significant decreases in forced expiratory flows at 25-75% and 50% on spirometry (n = 20) or bilateral ground-glass opacities on chest CT scan (n = 24).
Data collection Data collected for each subject included FTD assessment results with age, biometric data, duration of symptoms, and type of symptoms. Results of additional tests included: -Blood sample: complete blood count, platelets, C-reactive protein (CRP), creatinine with calculation of glomerular filtration rate; -Electrocardiogram (ECG); -Spirometry: forced vital capacity (FVC, L), forced expiratory volume in one second (FEV1, L. sec -1), forced expiratory flow rates (FEF 25-75%,75%,50%,25%, L. sec-1) and ratio FEV1/FVC. All values were expressed as absolute values and as a percentage of the mean values predicted by the European Respiratory Society for standardized pulmonary function tests  (Graham et al. , 2019). For spirometry, post-COVID results were compared with pre-COVID assessments.
Statistical analysis All the statistical analysis performed with R statistical software. Demographic and descriptive data were expressed as mean (standard deviation, SD), median (interquartile range, IQR) or numbers and percentages where appropriate. Normality of distribution was checked before performing paired or unpaired parametric t tests to analyze spirometry on all 143 subjects or between the 3 groups of divers. For the 20 subjects with abnormal spirometry, a comparison of baseline, 1-month FTD assessment and 3-month control values was performed using the Kruskal-Wallis test followed by the Bonferroni-Dunn post hoc test. The level of significance was set at p < 0. 05.
Population characteristics Two hundred military divers were tested for COVID-19 infection between March 2020 and February 2021. Fifty-seven records were excluded due to missing data or negative PCR tests. Data from the remaining 145 records are examined in this study, representing approximately 8. 5% of the total French military diver population. All participants were male with a mean age of 33. 3 ± 7. 4 years and a BMI of 24. 8 ± 3. 2. 21% of subjects had a history of smoking and 9% were active smokers. During the study period, military divers were not yet vaccinated. 145 PCR-positive subjects were included, representing 8. 5% of the total population of French military divers. 143 divers were not hospitalized with 52 divers (36%) showing initial respiratory symptoms with dyspnea and cough (group 1), 70 divers (49%) showing only flu-like symptoms (fever, fatigue, body and muscle aches, headache, sore throat) and/or neurological disturbances such as loss of sense of smell/taste (group 2).
2017; DUCHON et al. 2021). These studies were pioneered and strongly driven by the use of the Ts(17  16 )65Dn/J (Ts65Dn) mouse line  (DAVISSON et al. 1990; DAVISSON et al. 1993; REEVES et al. 1995)  with more than 500 publications found in the PUBMED database  (April 2022). Originally, the Ts(17  16 )65Dn/J line was generated by the irradiation of DBA/2J males, then crossed with C57BL/6J females, with the progeny being checked for chromosomal abnormalities  (Davisson et al. , 1990; Davisson et al. , 1993). Translocations for mouse chromosome 16 (Mmu16 for Mus musculus) homologous to Hsa21 were then mated with the C57BL/6J x C3H/HeJ F1 hybrid line. The genetic background of B6C3HF1 was selected to obtain large litters and maintain higher transmission. The translocated minichromosome Ts(17.
RESULTS Structure of the Scaf8-Pde10a proximal region of mouse chromosome 17 Before creating the Ts66Yah model we looked at the Scaf8-Pde10a region. We found it quite rearranged in several mouse lines according to the mouse genome informatics database. In particular we closely investigated the corresponding segments in the DBA/2J line used to generate the first Ts65Dn chromosome, and also in C57BL/6J and C3H/HeJ (as a proxy) of the mouse lines used to breed the Ts65Dn mouse carriers. Overall, the region was globally conserved in its organization but several loci were affected (Fig. S1A ). More precisely, the Snx9 locus was different in size in the 3 models, and more perturbed in C3H/HeJ. Remarkably, the genetic interval encompassing Tulp4, Tmem181a and Sytl3 were not found in the DBA/2J genome and other loci for Rpsh3 and Rnaset2 were duplicated differently in the 3 genetic backgrounds (Fig.
For Ts65Dn, these CGH data have been previously published from the original "1924" Ts65Dn mouse line (DUCHON et al. 2011), however, they were reused in this study for comprehensive comparison with CGH data from Ts66Yah. For Ts65Dn, the CGH was undertaken using NimbleGen mouse HD2 oligonucleotide arrays. Comparative analysis was done using DNA extracts from one wild-type animal that were fluorescently labeled with Cy5 and from one animal bearing the duplication labeled with Cy3. After sonication and labeling, DNA was hybridized to the CGH array, followed by washing the slide according to the manufacturer's instructions (Roche NimbleGen, Madison, WI, USA). Slides were scanned using a G2565 scanner at 3-lm resolution (Agilent Technologies, Palo Alto, CA, USA), and array images were analyzed using NimbleScan v2.
Statistical analysis For each data set, we performed the Shapiro-Wilk test and Quantile-Quantile plots to analyze if the data were normally distributed and the Brown-Forsythe test to ascertain the homogeneity of variances. If the p-value was greater than the significance level (0. 05), we assumed the normality and equal variance. In this case, statistical significance of differences between groups was inferred by a two-tailed T test between genotype or ANOVA for repeated measures (MWM, FC). The post hoc tests (Tukey Test) were conducted only if F in RMANOVA achieved a 0. 05 level. In the case of datasets where the assumptions of normality or homogeneity of variances were not fulfilled, we did the Kruskal-Wallis non-parametric test. We performed a one sample two tail t-test respectively for the discrimination index (DI) of the NOR versus no discrimination (0%), or for the percentage of spontaneous alternation versus 50% (hazard) in the Y maze, or 25% (hazard) for the probe test in the MWM.
One Ts66Yah was excluded from Y maze experiment because the number of visited arms was less than 5 and one wt animal from Ts65Dn group in MWM PT reversal was excluded because he showed a floating behaviour for more than 90% of time. The figures and the statistical analysis for labo 2 were done using GraphPad Prism 9. The phenotypes were compared between genotypes in male and female mice separately. The comparisons between 2n and Ts66Yah mice were made using a two tailed t-test. The percentage of alternation and the discrimination index (NOR) was analyzed using a two tailed one-sample t-test. Identify further the explanatory phenotyping variables in the trisomic lines We used "Gdaphen" for "Genotype discrimination using phenotypic features". Gaphen is a R pipeline that allows the identification of the most important predictive qualitative and quantitative variables for genotype discrimination in phenotypic based datasets without any prior hypothesis (available on github https://github.
com/YaH44/GDAPHEN). More detailed are available in the supplementary data and in Muniz  Moreno et al (ref). Gdaphen is a R pipeline that allows the identification of the most important predictor qualitative and quantitative variables for genotype discrimination in animal models of different diseases. We used Gdaphen an unpublished R package developed in our lab (https://github. com/YaH44/GDAPHEN/releases/tag/Public) to identify the phenotypic explanatory variables of those recorded during the analysis more relevant to discriminate between genotypes mutant and wild-type from the Ts66Yah and Ts65Dn models. Moreover, we also identified which recorded variables were more relevant to discriminate between each specific model wild-types or mutants to more deeply understand the differences and similarities in the relevance of the alterations in the phenotypic characterization performed for those mice models.
Gdaphen takes as input data an excel table containing on the rows the info per animal and on each column all the variables recorded. As for some tests several variables were recorded, we grouped those variables with the same group label and identified the importance for the discrimination of i) each variable alone, ii) the overall contribution of the group. Pre-processing steps were carried out to get the data into shape for the analysis, after which Gdaphen was able to first identify the highly correlated variables (more than a r=0. 75) and remove them for downstream analysis. For example, in the sperm tests several variables measured for the test were highly correlated with each other. The sperm percentage of rapid cells and the percentage of cell motility showed a coefficient of correlation r=0.