dataesr/scientific-paragraphs-categorization huggingface dataset:
Therapeutic Strategies Based on CDA Expression Given the high heterogeneity of expression of CDA, different therapeutic strategies can be considered depending on the pathological context. Most cancers underexpress CDA compared to healthy tissues. 40, 91 Amor-Guéret and colleagues  40  focused on breast tumors that poorly express CDA due to DNA methylation. They showed that tumors with low CDA expression are more sensitive to aminoflavone derivative AFP464. Tissues that express higher levels of CDA are, however, resistant to these drugs, which would place CDA as a predictive biological marker of response. High-CDA-expressing tumors should be in theory more resistant to cytidine-based therapies. 3] [94] [95]  However, only a few clinical trials resulted from these studies. Phase I clinical trials studied the effects of 5-fluoro-2 0 -deoxcytidine with THU (ClinicalTrials.
gov: NCT00359606 and NCT01041443), and two phase II clinical trials were completed recently combining 5-fluoro-2 0 -deoxcytidine with THU and another combining THU and decitabine with nivolumab (ClinicalTrials. gov: NCT00978250 and NCT02664181), but none of them has shared the results yet. Another interesting hypothesis made by Amit and Gil 45 could be to target macrophages in order to reduce CDA levels and thus chemosensitize the tumor to gemcitabine. Zauri et al. 91  recently performed an elegant study, focusing on tissues that express high levels of CDA, including pancreatic cancer, in which CDA appears to be expressed mainly in epithelial tumor cells and not in the stroma. 96 They took advantage of CDA overexpression to metabolize synthetic deoxycytidine analogs to be inserted into DNA.
albicans  [30] , and homology arms of 30 bp resulted in almost a 100% gene-editing efficiency in Candida parapsilosis  [29]. Very often ADE2, a gene involved in the adenine biosynthetic pathway, is selected as proof of principle target when implementing CRISPR-Cas9 in a new species. In fact, ade2 mutants are easy to screen because the interruption of the pathway results in the accumulation of a red to pink pigment that colors the colonies. Finally, general recommendations for guide design to ensure efficiency and reduce off-target effects also apply to these fungi  [32]. Numerous guide-design software programs are now available, some allowing uploading of custom genomes, such as EUPaGDT (http://grna. ctegd. uga. edu) or CHOPCHOP (http://chopchop. cbu. uib. no/).
Hospitalisation was discussed with the oncologists who prescribed the drugs. If hospitalisation was necessary, the CNs recorded why and the outcomes of treatment. The CNs actively facilitated the patient's return home by calling all town caregivers. All direct or indirect actions were recorded on a computer spreadsheet. Clinical data were collected in accordance with French bioethics laws addressing patient information and consent. This project has been ethically approved by the relevant national authority: the National Institute of Cancer (INCa) and the Ministry of Health (no. DGOS/R3/2014/235-24 July 2014). Patients provided written (signed) informed consent to use their medical and administrative data.
Statistical analyses All data were collected and analysed using STATVIEW software (SAS Institute Inc. , Cary, NC, USA). Quantitative data are given as medians ± standard deviations (SDs) and qualitative results are numbers with percentages. The significance of between-group differences was evaluated using the Chi-square test. Means were compared using the nonparametric Mann-Whitney U-test for continuous variables and the Wilcoxon signed-rank test for categorical variables. A p-value < 0. 05 was taken to reflect significance.
Town-hospital links created by CNs At the first consultation, the CNs telephoned the patient's general practitioner (88%), town nurse (65%), and town pharmacist (84%). The combined median duration of all calls was 20 min (range 2-65 min). Letters and booklets were sent to general practitioners (Table  2 ). Of patients at high INCA-defined risk, 46 were referred to social services during initial consultations; some refused or claimed that assistance was already in place. The CNs also contacted hospital nurses, dieticians, psychologists, town laboratories, and hospital doctors and, also requested additional examinations (n = 72) (Table  2 ). During follow-up, CNs made threefold more calls than they received (2719 [median time 10 min; range 2-130 min] vs. 833). A total of 726 calls were to health professionals (Table  3 ) to discuss test results (419/1345 tests; 31%) and administrative data (67/168 datasets; 40%), and to seek medical information (44/74 questions; 60%).
This was created using the Weibull proportional hazards model by a pool of datasets of 12 European cohorts involving 205 178 persons undergoing baseline examination from 1967 to 1991 and crossed checked with Cox regression models. From the 7934 cardiovascular deaths 5652 deaths were attributed due to coronary heart disease. The SCORE risk charts are currently used in daily clinical practice in Europe in order to optimize individual cardiovascular screening and prevention including life style adjustment and preventive drug treatment  [16]. The current existing iatrogenic dose -effect relationships [3-9] focusses especially on relative risk which is unpractical in clinical practice, due to the heterogeneity of individual baseline lung cancer and cardiovascular risk factors. Our aim was to create clinical applicable risk charts focussing on absolute lung cancer and cardiovascular mortality risk in order to individualise breast radiotherapy and optimize lung cancer and cardiovascular mortality prevention and screening.
76 (95% confidence interval [CI], 0. 61 to 0. 94; P=0. 01) at 10 years. After breast RT no systemic screening is performed in order to identify cardiovascular morbidity or lung cancer. Our risk models might be helpful to identify patients that might benefit from such screening. These data emphasize the importance of lifestyle optimization including dietary patterns, physical activity and smoking cessation. Our risk charts provide long-term absolute risks, however when prevention is performed with life-style adjustment and/or medication (i. e. statins, etc), this will subsequently decrease the absolute risks presented in our charts and might therefore rebalance oncological gains versus iatrogenic effects by radiotherapeutic interventions. Moreover our risk charts enables to quantitatively estimate the individual advantage of smoking cessation on future lung cancer.
Moreover data on exposure to radon, asbestos, secondhand smoke, occupational carcinogens and history of adult pneumonia were not available. The PLCO trial  [13, 14]  had very few patients 80 year during follow up, therefore we didn't estimate the 20-year lung cancer risk in 60 year old patients. These results are putative due to the limitations of the individual trials (i. e. older data, no individual dosimetry, etc. ) and uncertainties based on the integration of the datasets. Currently, there are no large prospective datasets available with individual lung cancer and cardiovascular risk characteristics and dosimetric data for breast cancer patients receiving RT with decades of follow up. Prospective data collection is performed in order to validate these results.
All qPCRs were performed in a CFX96 RealTime System (Bio-Rad, Marnes-la-Coquette, France) and the results were analyzed using the CFX manager software (version 3. 1) (BioRad). For each sample, HVT load corresponded to the number of HVT genome copy number per 10 6 cells (meaning per 2 × 10 6 iNos copies). Data for a triplicate were ruled to be non-interpretable, when at least two Cq of a replicate showed variations greater than 0. 5 or when only one out of the three Cq was obtained, and that on two independent HVT qPCRs using the same DNA sample. Note that for iNos qPCR, all the results were interpretable.
Results We evaluated the persistence of HVT infection in feathers of four lines (Fayoumi, Fa; an egg layer line, He; Nunukan, Nu; and a parental broiler line, pH) vaccinated with HVT-ND at hatch. For that, we measured HVT loads by qPCR in growing feathers tips of forty birds (ten per line) from week 2 and every three weeks over 41 weeks. On 520 expected measures, 476 were obtained, after two imputations (Additional file 1). The 44 missing data were from week-24 birds, mostly due to the lack of growing feathers, especially in the pH line. The data were complete for 25 birds (Fa: 8, He: 8, Nu: 7, pH:3).
Antibody titers to NDV by hemagglutination inhibition (HI) and ELISA in each line over time Serum antibodies to NDV were titrated by HI and ELISA tests in order to evaluate maternally derived antibodies levels as well as the development and duration of the antibody response induced by rHVT-ND vaccination. No data were missing from the 720 expected data points, after a single imputation for lack of sample (H09/W02) (Additional file 1). We examined ND antibody titers in each line over time with both methods (Figure  4 ). The four lines had significantly different levels of maternally derived anti-NDV antibodies (statistical analysis not shown): negative by HI (≤ 2) to low by ELISA (1115) for Fa, low by HI (2) and moderate by ELISA (3631) for He, and high by HI (≥ 6) or moderate by ELISA (about 3880) for Nu and pH.
A relationship exists between HVT load in feathers and spleens MD vaccine are known to persist for several weeks in the spleen of vaccinated birds  [42, 43]. In order to examine whether HVT persistence in feathers was related to its persistence in the spleen, we quantified HVT loads in the spleen of each bird at week 41 by qPCR. Of the 40 data points expected, 3 were missing (Additional file 2). The median HVT loads (log) in the spleen were 3. 85, 3. 39, 3. 94, and 2. 92 for Nu, pH, Fa, and He lines, respectively (Figure  7 ). There were no significant differences in HVT loads in the spleen between the four lines using an ANOVA by permutations (p value = 0. 0597). Interestingly, four birds had null values (Nu03, He02, He03, He04) and were previously identified as controllers. Interestingly, two birds identified as feathers low producers, but not controllers, had the lowest HVT loads in the spleen (pH01, 64; Fa10, 92).
Acknowledgements We would like to thank  V. Nair  for the HVT BAC used as HVT standard in qPCR. We also greatly thank  M. Tixier-Boichard  and  E. Duval  for letting us use the Nu and pH+ lines. We acknowledge  Christophe Rat ,  Karine Anger  and  Harold Rigoreau  from the PEAT unit for their help with the animals. We also greatly thank  Vilmos Palya , director of the Scientific Support and  Investigation Unit at Ceva Phylaxia  for the management of antibody titrations and his comments on the manuscript. We thank  F. Paillard  for English editing of the manuscript. We are very grateful to the  ICSA/F2E  Carnot for funding the  MARDISHED  project.
Study design and subjects The Decubitus in Intensive Care Units study (DecubI-CUs) was a worldwide prospective, observational, 1-day point-prevalence study of pressure injuries among adult ICU patients with 12-weeks follow for survival status and length of hospital stay. All patients ≥ 18 years in ICU from 0:00 to 23:59:59 h on the study day were eligible; there were no exclusion criteria. DecubICUs was registered at ClinicalTrials. gov (NCT03270345).
Data collection Data were collected on 15 May 2018. Alternative dates were set for Nigeria, Brazil and Libya due to delayed ethics approval. Anonymous patient data were collected by case report form. They encompassed demographic and admission data, and physiological data pertaining to the study day, including the severity of disease assessment by the Simplified Acute Physiology Score II (SAPS II)  [21]. Pressure injury occurrence was measured by direct observation according to the international staging definitions  [1, 2]. Pressure injury risk was assessed by the Braden scale that combines 6 subscales: mobility, activity, sensory perception, skin moisture, nutritional state, and friction/shear, with lower scores reflecting higher risk  [22]. Follow-up data gathered were survival status, and length of ICU and hospital stay until hospital discharge or at 12 weeks following the study day  (7 August 2018).
Statistical analyses Analyses were performed at the patient level. Overall pressure injury prevalence was calculated as the proportion of the sample with at least one pressure injury on the study day, ICU-acquired prevalence as the proportion with at least one pressure injury acquired in ICU on the study day. Prevalence is reported as numbers (n) and percentages with 95% confidence intervals (CI). Continuous data are summarised by a median with interquartile range (IQR), categorical data as n (%). Univariate analyses used Chi square, Mann-Whitney U, and Kruskal-Wallis tests, as appropriate. Survival analysis was performed by Kaplan-Meier procedure (log-rank test). Associations with ICU-acquired pressure injuries were examined by generalized linear mixed-effects regression analysis with logit link function and a random effect for country.
All variables were included following an exploratory approach, irrespective of univariate analyses results. As analyses did not focus on a prediction but on the identification of associations, feature selection was not applied, particularly as the risk of overfitting was minimised given the limited number of covariates (n = 24 for pressure injury occurrence, n = 22 for hospital mortality) and the adequate dataset size (n = 13,254). Results are reported as odds ratios (OR) with 95% CIs. Statistical analysis was performed using IBM SPSS 24. 0 (IBM Corp. , NY, US) and R statistical software 3. 6. 1  [23].
Hospitals and patients We recruited 1117 ICUs in 90 countries (6 continents). Most were mixed medical-surgical units (n = 729; 65. 2%) and in university hospitals (n = 675; 60. 4%). Median (IQR) hospital and ICU capacities were 600 (329-1035) and 13 (8-20) beds, respectively; 1005 (89. 9%) data collectors had studied a training module on pressure injury staging, of which 920 (82. 3%) the module developed for this project. Participation rates and ICU characteristics are in Online Resources_6 and 7, respectively. Data from 13,254 patients were eligible for analysis. Their demographic characteristics are in Table  1 , completeness of data in Online Resource_8.
The major strength is that it is the first to present a worldwide picture of the epidemiology of pressure injuries in adult ICU patients and to map a high-risk profile based on a large global sample. It may act as an incentive for tackling this patient safety issue and provide local and regional baseline data for quality improvement programmes. Furthermore, pressure injuries staging was assessed by the gold standard of skin inspection by trained outcome assessors, and the study used a rigorous protocol with clear attention to detail in standardising the data collection process.
statistical analysis plan, and informed consent forms will be shared upon request with any researcher. Local DecubICUs investigators have the right to use the data collected from their respective units. National data can be obtained and used by the DecubICUs National Representatives upon proof of written consent from the local investigators. The complete DecubICUs database is only transferred to the primary investigators, SOL and SIB. They cannot share the database as they are bound to a broad variety of Data User Agreements. Information requests are to be addressed to stijn. blot@ ugent. be and sonia. labeau@hogent. be.
Step 1: extensive literature search for papers on paediatric tumours of interest PubMed is queried using specific keywords agreed upon by the initial two reviewers: ["paediatric cancer type" AND "target(s)/pathway"] and, in some cases, ["paediatric cancer type" AND "drug name"]. The scope of the TAR is limited to paediatric solid and brain tumour histologies (listed in Table  2 ). Based on the identified titles and abstracts, the reviewers independently decided which papers identified by the PubMed search merit inclusion in the downstream analysis. Papers addressing at least one of the corresponding critical appraisal questions for a specific PoC module (Table  1 ) were included; review articles were excluded. Reviewers agreed on a single list of PubMed   IDs (PMIDs) to upload to the R2 data application, which automatically links the PMIDs to the full texts of these relevant papers.
Discrepancies in 37 of the 106 data entries that were initially discordant between the first two reviewers (35%) were noted after the third review; all discrepancies were resolved after the final adjudication. No papers or entries were excluded during reviewer discussions and the final number of adjudicated data entries remained 338. Due to the multiple possible mechanisms of MDM2ep53 pathway dysregulation, the 'target/ pathway pattern module' (PoC 1; Tables  1  and 5 ) was further divided into subcategories to differentiate among (a) MDM2 amplification, (b) gain (either whole chromosome or focal) or overexpression and (c) expression (generally as determined by immunohistochemistry). In addition, the mutational status of TP53 reported in 12 recent studies subjecting paediatric tumour samples to next-generation sequencing was recorded as part of PoC module 1 (d).
Acknowledgements This project has received funding from the  Innovative Medicines Initiative 2 Joint Undertaking  under Grant Agreement No  116064. This Joint Undertaking receives support from the  European Union 's  Horizon 2020 research and innovation programme  and the  European Federation of Pharmaceutical Industries and Associations. Additional funding came from  KiKa (Children Cancer-free Foundation)  grant  189  and  PRE-DICTERC-2016-STG #716079.
Methods We retrospectively analyzed stroke among patients in Colmar Hospital with Covid-19 between March 3 and April 21, 2020. Colmar Hospital is a 1000-bed facility in northeastern France, a region in which a major outbreak of Covid-19 occurred during this period. A laboratory con rmed Covid-19 by a positive result of real-time reverse transcriptase polymerase chain reaction (PCR) for SARS-Cov-2 (nasopharyngeal swab, endotracheal aspirate, or sputum). We searched Colmar Hospital's database for all the patients with Covid-19 who had a stroke. The study was approved by the ethical committees of the odontology and pharmacy faculties and hospitals.
Acknowledgements The authors thank all the healthcare professionals who took care of the patients infected with SARS-Cov-2 at the  Civil Hospitals of Colmar. Authors' contribution GH, FS and MM conceived and designed the study, analysed and interpreted the data, drafted/revised the manuscript. GH, FS, SG, TB, CI, PA, CR, M-HA-D, MMZ and MM have collected the data, read and approved the manuscript.
Statistical analysis The data were analyzed offline with Clampfit (Molecular Devices), IGOR (Wavemetrics, Lake Oswego, OR, USA), Sig-maPlot (SPSS Science, Chicago, IL, USA), OriginPro (Origin-Lab Corporation, MA, USA), and ImageJ (National Institutes of Health). Conductance-voltage (G-V) curves for activation were derived from steady-state currents, converted to conductance, and then fitted by Boltzmann function: G/G max =1/(1 1 exp((V 2 V 1/2 )/k)), in which G max is the maximal conductance, V 1/2 is the voltage at which the conductance (G) is half the maximum conductance (G max ), and k is the slope factor. For dose-response analysis, the modified Hill equation was used: Y = A1 1 (A22A1)/(1 1 (EC 50 /[toxin]) nH ), in which n H is the Hill coefficient. All data are expressed as means 6 S.
Acknowledgments-We are grateful to our colleagues and members of  Yao lab  for comments and discussions. Author contributions-Y. W. , X. M. , C. P. , Q. H. , H. Z. , C. X. , B. Z. , D. L. , and J. Y. data curation; Y. W. , X. M. , C. P. , Q. H. , H. Z. , C. X. , B. Z. , D. L. , and J. Y. formal analysis; Y. W. , X. M. , C. P. , Q. H. , H. Z. , C. X. , B. Z. , D. L. , and J. Y. validation; Y. W. , X. M. , C. X. , D. L. , and J. Y. investigation; Y. W. , X. M. , C. P. , Q. H. , H. Z. , C. X. , B. Z. , D. L. , and J. Y. methodology; Y. W. , X. M. , and J. Y. writing-original draft; Y. W. , X. M. , and J. Y. writing-review and editing; C. X. and J. Y. resources; B. Z. and J. Y. software; J. Y. conceptualization; J. Y. supervision; J. Y. funding acquisition; J. Y. visualization; J. Y. project administration.
1a  and b ). Rabbits were sacrificed from D0 (i. e. the day of the surgery) to D42 by 4 ml intravenous pentobarbital. Samples were randomly divided in 2 groups, one for micro CT and one for histologic analysis. Analyses were performed by 2 operators. The microCT (Inveon ® , Siemens) was performed according to standards for bone characterization in the rodent  [10] , with the following parameters: magnification: high, 180 projections; binning 2, pixel size: 18. 76 mM, axial field of view 18 mm, transaxial field of view 28. 16 mm, scanning length 18 mm, voltage 80 kV, current 500 mA, exposure 770 ms and acquisition 30 min. A Hounsfield and density calibration was daily performed. The region of interest (ROI) was determined and analyzed thanks to ImageJ® software. BV/TV (percent bone volume), TbN (trabecular number) and TbSp (trabecular separation) were reported and analyzed thanks to ImageJ® software.
The bone mineral density (BMD) was also determined. Samples were fixed in 10% formalin, embedded in paraffin after slow decalcification in citric acid, sliced and finally stained with hematoxylin-eosin. Criteria for histological analysis were: number and aspect of bone cells (osteoblasts, osteocytes, and osteoclasts), number and aspect of vessels, fibrosis, necrosis, and aspect of bone structure. Cell count and vascular counts were performed in 4 fields and Â40 magnification. Statistical analysis was performed thanks to SPSS (IBM, Chicago). Standard deviation was calculated and a T test was performed to compare the two groups in terms of BMD, BV/TV, TbSp and TbN.
Study design and subject cohort The study was approved by the local ethics committee (Number: 10_18 B), and written informed consent was obtained from all participants prior to examination. Between May 2018 and October 2019, we included 19 patients (age 48. 1 ± 12. 7 years) with genetically confirmed FSHD. 12 ageand sex-matched volunteers (age 46. 6 ± 14. 2 years) were recruited as controls. Exclusion criteria were contraindications for MRI (e. g. , claustrophobia or metallic implants) and an age younger than 18. A neurologist scored manually the strength using the Medical Research Council grading system ranging from 0 (no muscle contraction) to 5 (maximal muscle strength) for the foot dorsal and plantar flexors  [23]. MR data were then acquired from the less affected leg or leg without any confounding factor such as former vein thrombosis or lymphatic fistula.
Data analysis For the semi-qualitative analysis, a radiologist with 6 years of experience in reading musculoskeletal MRIs evaluated eight different lower leg muscles: tibialis anterior, extensor halluces/digitorum, peroneus, tibialis posterior, gastrocnemius medialis, gastrocnemius lateralis, soleus, and flexor halluces/digitorum longus. The fat replacement of these muscles (fat score) was scored with an established five-point scale ranging from 0 (not-fat replaced) to 4 (completely fat replaced) by Goutallier et al. using the first echo of the multi-spin-echo sequence  [28]. Similarly, STIR-T 2 w intensity was rated on a five-point scale from 0, normal appearance, to 4, severe involvement of entire muscle, based on the scale described by Wang et al. [29]. All imaging slices of each muscle were considered for the grading.