dataesr/scientific-paragraphs-categorization huggingface dataset:
Our study data suggest significant withdrawal of primary prevention statins which are deemed unnecessary. Last but not the least, other wellfollowed recommendations concerned nicardipine and urapidil, which are classed as PIMs according to the EU(7)-PIM list. Similar results showing the beneficial impact of MRs on prescription quality have been suggested in other studies  [9, 10]. To our knowledge, this is the first French study to evaluate the positive impact of MR in NH, including almost 3000 residents who could be deemed representative of the older population in our region and France based on demographic data  [2, 3]. Among the NHs participating in the first MR, few of them (26%) responded to the second MR. Several factors could be used to determine NH participation in the MR. Our results suggest that the presence of an inhouse pharmacy and a coordinating physician could prompt participation.
To date, over 100 clinical trials investigating the use of CAR-T cells in MM have been registered at clinicaltrials. gov. Although several CD19-directed CAR-T cell products have been approved  (Ghobadi 2018; Yassine et al. 2020 ), CD19 surface expression on plasma cells is limited or absent, leading to uncertain efficacy in clinical trials that used anti-CD19 alone in patients with MM (Garfall et al. 2015, 2019). Using superresolution microscopy, CD19 can be detected on a large proportion of myeloma cells, which could explain the successful targeting and lysis of myeloma cells by CD19-detecting CAR-T cells  (Nerreter et al. 2019). Of note, some ongoing studies in which CD19 is targeted in combination with other antigens, especially BCMA, are being conducted  (Beauvais et al. 2020). BCMA-directed CAR-T cells have shown promising efficacy and safety profiles in various phase I/II clinical trials  (Munshi et al.
Based on data from 414 cats, the selected model (AICc weight = 0. 207) included the age of cats and their living environment/lifestyle to explain parasite prevalence (Table  3 ). We observed a signi cant decrease of parasite prevalence as cats aged, with 6 -24 months old cats having a lower prevalence than < 6 months old cats (OR = 0. 36 [0. 17, 0. 75] 95% CI ) and a higher prevalence than > 24 months old (OR = 4. 20 [2. 03; 9. 25] 95% CI ). Cats with access to outdoors in city and countryside had a higher prevalence of parasites compared to cats without access to outdoors (OR = 3. 89  [1. 50; 9. 95] 95% CI and 5. 34  [2. 67; 11. 34]  95% CI , respectively), and no differences were observed between cats with access to outdoors in city or countryside (P = 0. 453). Using a data subset including the previously selected variables in the multivariate model (age and living environment/lifestyle) and only cats > 6 months old (n = 367), we tested the in uence of the neutered/spayed status on parasite prevalence.
Acknowledgement The authors wish to thank the investigators ( Drs. Marx Dominique ,  Cauchy Alexandre ,  Arthur Labarre ,  Autenne Stéphanie ,  Roche Laurent ,  Christophe Soyer ,  Delphine Othenin ,  Olivier Reineau ,  Vincent Pouillaude ,  Mathilde Prévot ,  Lange Claire ,  Vaubourdolle Philippe ,  Melin Matthieu ,  Peyrac Pierre-Alain ,  Champeyroux Eric ,  Nello Cassandre ,  Garcia Julie ), the technicians of parasitology laboratories ( Slimania Benabed ,  Christiane Espie ,  Marie-Thérèse Poirel , and  Cecile Roux ), the veterinarians of the preventive medicine service of  VetAgro Sup  ( Drs. Lionel Zenner ,  Marie Abitbol ,  Florence Ayral ,  Ludovic Freyburger ,  Emmanuelle Gilot-Fromont ,  Angéli Kodjo ,  Maria-Halima Laaberki ,  Michel Pépin ,  Germain Rives ) and  Drs Gilles Bourdoiseau  and  Michel Franc , for their participation to the study.
However, in scenarios, such as a pandemic response, maximizing yields is also critical to meet high drug dosage requirements. Therefore, one of the runs of MERS-7. 7G6 was extended to 12 days to determine maximum titers for this molecule. A yield of 1. 74 g/ L was obtained for this antibody when the process was extended compared to 0. 77 ± 0. 06 g/L obtained for harvest on day 8. Material from all the 5 L batches was harvested, purified, and analyzed. PQAs were found to be as expected for the mAbs and bispecific products, with no aggregation or fragmentation issues observed for any of the tested molecules (data not shown). Additionally, analytical results for MERS-7. 7G6 showed consistent PQAs over the different batches (Figure  2  and Table  2 ), with minor differences observed in the level of the main G0F glycoform for material harvested after 12 days.
7G6) in a miniaturized bioreactor (Ambr® 15). The data confirmed consistent expression levels and product quality from passage 18 to passage 34. Scale-up and process consistency were thereafter assessed at a 5 L scale in bench-top bioreactors for the lead antibodies. Two antibodies, MERS-7. 7G6 and RVFV-107-104, showed promising expression levels, with titers of 0. 77 ± 0. 06 g/L and 1. 03 ± 0. 03 g/L at 8 days posttransfection, respectively. However, the two back-up antibodies, MERS-1. 6C7 and RVFV-107-150, showed lower expression levels, with titers of 0. 19 ± 0. 02 g/L and 0. 41 ± 0. 02 g/L at  8 days, respectively. The lower expression of these antibodies was consistent with the productivities observed during the early stages of the project (data not shown). Different expression levels for different antibodies of the same format are not unusual and have been previously reported.
23 Further work, such as gene sequence optimization, could be performed to improve expression. However, here the lower-expressing leads were down-selected based on a combination of potency and expression data. Process consistency was evaluated in a 5 L stirred-tank reactor using MERS-7. 7. G6 as the model antibody. Four independent runs for this antibody were carried out, resulting in an average maximum VCD of 6. 59 ± 0. 40 x 10 6 cells/mL and an average titer of 0. 77 ± 0. 06 g/L at 8 days post-transfection. PQAs were found to be consistent between the different batches and within the typical expected ranges for mAbs. These data confirm that a TGE process can be developed and controlled to enable product quality consistency from different batches, which is critical for preclinical and clinical studies.
The results of the in-vivo protection studies were in alignment with previously reported percentage survival for MERS-7. 7G6 where 80-100% percentage survival is  Raw values were modeled to a 4-parameter logistic fit, and analyses were run using Qubas software from Quantics. Two independent assays were run to provide two results for each sample from which a reportable result was calculated (% relative binding to reference standard). considered as protection. Different batches of RVFV-107-104 were also analyzed using a panel of in-vitro assays (ELISA, IFA, and VNT). The results confirmed that the material generated at the different scales efficiently recognized the native RVFV Gn protein to have potent neutralizing activity. In summary, we successfully demonstrated that our CHObased TGE system is capable of generating antibodies of consistent product quality at different scales and in different batches.
Binding assay The relative binding of MERS-7. 7G6 antibody was measured by using an electrochemiluminescence sandwich assay (Meso Scale Discovery technology, MSD). S1 spike protein was coated on assay plates at a fixed concentration and incubated overnight. MERS7. 7G was added as a serial dilution followed by a fixed concentration of anti-human IgG sulfo-tag secondary antibody (MSD, product ref. #D20JL-6). Raw data values were generated by reading on an MSD plate reader and analysis was performed using a 4-parameter logistic fit from which relativebinding percentages between reference standard and samples were generated using EC50 values.
Following incubation, the wells were washed again three times with PBST20, and submerged in VectaShield antifade mounting medium H-1000 (Vector Laboratories). Images were taken on an inverted widefield fluorescence microscope Axio Observer 7 (ZEISS, Germany) using appropriate filters and a 1. 3 NA 100x EC Plan-NEOFLUAR oil objective in combination with an AxioCam MRm CCD camera and ZEN 2. 6 Pro software (ZEISS, Germany).
Protection assay of MERS-CoV inoculated mice To evaluate the efficacy of the selected mAbs, 38 K18 TghDpp4-transgenic mice 20-30 weeks-old were administered after inoculation with MERS-CoV (5000 pfu/mouse), with the mAbs or negative controls. Mice were monitored daily for weight loss and survival. At selected intervals (0, 3, 6, and 10 days after inoculation), mice were bloodsampled. Three mice were sacrificed at 3 and 6 days postinoculation to collect lungs for viral titer (by plaque assay or qPCR) and histopathology and histochemistry (data not shown). This study received approval from the ethics committee at the National Center of Biotechnology (CNB-CSIC).
Acknowledgments The authors would like to thank  Dr. Michèle Bouloy  ( Institut Pasteur, France ) who kindly provided the  RVFV Clone 13. We also would like to thank all partners, scientists, post-docs, and graduate students involved in the  ZAPI  Project for their work and contributions, in particular:  Paul Varley ,  Dorota Kozub ,  Gary Pettman ,  Maiken Kristiansen ,  Aled Charles ,  Kieran Mistry ,  Ainul Zulkepli ,  Stephanie Davies ,  Katie Day ,  Sofia Ekizoglou ,  Peng Ke ,  Bradley Rawlins ,  Evangelia Ttofi ,  Tom Witkos ,  Chloe Parry (AstraZeneca) ,  Sandra van de Water  ( Wageningen Bioveterinary Research, the Netherlands ) and  Jean-Christophe Audonnet  ( Boehringer Ingelheim Animal Health, Global Innovation, France ; ZAPI coordinator).
Authorship Contribution: SL, JSG, ERM, CB and LP contributed to study design, study supervision, and data interpretation and wrote the paper. JSG is project manager of EPICOVIDEHA. LP is principal investigator of EPICOVIDEHA. All the authors recruited participants. All authors read and approved the final manuscript. Conflicts of interest: Sylvain Lamure declares miscellaneous support from Janssen, Gilead, Roche, Abbvie, Sanofi, Novartis, Actelion, Pfizer, some honorarium from Gilead and a pneumonia, severe for those with dyspnoea, respiratory frequency ≥ 30 breaths per min, SpO2 ≤ 93%, PaO 2 /FiO 2 < 300, or lung infiltrates > 50% on tomography, and critical for patients admitted in intensive care for respiratory failure, septic shock, or multiple organ dysfunction or failure.
some honorarium from  Gilead  and a research grant from  Janssen. Jon Salmanton-García  has received speaking honoraria from  Gilead Nordica , outside the submitted work. Rémy Duléry reports personal fees from  Takeda ,  Novartis , and Biotest and non-financial support from  Gilead  outside the submitted work. Caroline Besson  reports research funding from  Roche  and non-financial support from  Takeda  and  Roche. Monia Marchetti  is consultant for  Gilead. Martin Hoenigl  received research funding from  MSD ,  Astellas ,  Pfizer ,  Scynexis ,  F2G ,  Euroimmun ,  Gilead , and  NIH. board member of  Gilead Science, MSD ,  Pfizer , and has been speaker for  Gilead Sciences, MSD ,  Pfizer Pharmaceuticals , and  Astellas Pharma. Philipp Koehler reports grants or contracts from  German Federal Ministry of Research and Education (BMBF) B-FAST  ( Bundesweites Forschungsnetz Angewandte Surveillance und Testung ) and  NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network)  of the  Network University Medicine (NUM)  and the  State of North Rhine-Westphalia ;  Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.
In a cohort study including 111 patients with lymphoma hospitalized for COVID-19 in France, two patients (2%) had hairy cell leukemia (HCL) 9. Furthermore recent single case reports described either a concomitant diagnosis of COVID-19 and HCL 10 , and a critical COVID-19 in a context of HCL 11. In this study, we aim to report the characteristics and outcomes of patients with HCL and COVID-19 from the EPICOVIDEHA survey 12 , with a focus on patients with concomitant diagnosis of HCL and COVID-19. The EPICOVIDEHA registry is an online survey collecting cases of COVID-19 in the context of a haematological malignancy (HM) since April 2020, and the registration of new cases is still active. The survey is promoted by the European Hematology Association -Infectious Diseases Working Party (EHA-IDWP) and has been approved centrally by the Institutional Until January 26, 2022, 40 patients with HCL and COVID-19 were reported out of the 2 422 lymphoproliferative neoplasms in the database (1.
pdf by guest on 25 June 2022 Institute, Rome, Italy 7 Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy 8 Oncology Center, Mansoura University, Mansoura, Egypt Review Board and Ethics Committee of FondazionePoliclinico Universitario A. Gemelli -IRCCS -Università Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). The survey is registered on clinicaltrials. gov(NCT04733729). The data are collected online, on an electronic case report form available at www. clinicalsurveys. net(EFS Summer 2021, TIVIAN, Cologne, Germany). The following clinical and epidemiological data from patients with a laboratory-based diagnosis of SARS-CoV-2 infection are collected: underlying conditions before SARS-CoV-2, HM status and management before SARS-CoV-2 infection. The 7 cases diagnosed less than one month before Covid-19 were considered as concomitant.
Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and monosaccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome.
Material and methods A literature review was conducted using the electronic databases PubMed, EMBASE, and MEDLINE with the search terms 'endometriosis' (MeSH) and 'nutrition', 'lifestyle', 'diet', 'irritable bowel disease', 'physical activity', 'weight', or 'body mass index' (BMI). The review specifically evaluated articles published in the English language until February 2021. Multiple au-thors reviewed the papers and independently selected the articles included in this review.
Vietnam and Cameroon As part of the French National Agency for Research on AIDS and Viral Hepatitis ANRS 12229 PAANTHER 01 study (NCT01331811), CHIV with presumptive TB from Vietnam and Cameroon aged ≤13 years were enrolled between April 2011 and August 2013  [21]. All children underwent a medical history and TB symptoms assessment, physical examination, CXR, CBC, TST, and microbiologic testing for TB.
Kenya As part of the Pediatric Urgent Start of HAART (PUSH) trial (NCT02063880), which compared impact on mortality of early antiretroviral therapy (ART) initiation within 48 hours versus 7-14 days after enrollment between April 2013 and May 2015  [24] , children aged <12 years without central nervous system infection had complete medical history, physical examination, CBC, CXR, and microbiologic TB testing performed at enrollment. All children in the above cohorts were classified as having confirmed, unconfirmed, or unlikely TB using the Clinical Case Definitions for Classification of Intra-thoracic TB in Children 2015  [25]. Further details of the cohorts are reported in the Supplementary Methods.
Statistical Analysis To validate the findings from Kenya, data from the Vietnam/ Cameroon and South Africa cohorts were pooled to create a combined dataset and MLR was calculated using differential blood count for monocytes and lymphocytes at the initial diagnostic visit. A MLR value of ≥0. 378 was used to evaluate TB diagnosis using the previously defined cutoff in the Kenyan cohort  [19]. Microbiologically confirmed TB, either by mycobacterial culture or Xpert MTB/RIF (confirmed TB), versus unlikely TB was used as reference to calculate the sensitivity and specificity of MLR for TB diagnosis. To construct a diagnostic prediction score, we combined data from CHIV in the Kenyan, South African, Vietnam, and Cameroon cohorts. We restricted analysis to children with at least 1 of the following symptoms: cough for >2 weeks, fever for >2 weeks, failure to thrive, or reduced playfulness and blood samples collected within 7 days of starting TB treatment.
Multivariable logistic regression was performed with confirmed TB versus unlikely TB as the outcome. Predictor variables included TB-associated symptoms, TB contact history, CXR suggestive of TB (as a dichotomous outcome), TST ≥5 mm, MLR ≥0. 28, age in years (dichotomized at 4 years), and sex. The candidate variables selected for model building were based on clinical data that are commonly collected while assessing a TB patient in high-incidence, low-resource settings. CXR was defined as suggestive of TB if there was a positive response for any one of the radiographic features: presence of hilar or paratracheal lymphadenopathy, tracheal or bronchial compression, pleural effusion, consolidation, cavitation, or miliary pattern  [27]. For ease of use in clinical practice, we converted all continuous predictor variables into dichotomous variables using univariate receiver operating characteristic (ROC) curve analysis with the optimal cutoff based on the maximum value of Youden index, J (J = sensitivity + specificity -1).
Cohort Characteristics Of 663 children in the combined dataset from Vietnam, Cameroon, and South Africa, we excluded 71 children from the analysis because of missing MLR data. Sixty-two children from South Africa did not have blood samples collected within 7 days of starting TB treatment. These children did not differ demographically or clinically from the remaining 365 South African children who remained in the analytical dataset (Supplementary Table  1 ). Nine children from Vietnam and Cameroon did not have results for the blood counts recorded. The median age of the combined cohorts was 1. 9 (interquartile range [IQR], 0. 9-5. 3) years; 300 (50%) children were male. South African children were younger (median age, 1. 3 [IQR, 0. 7-2. 5] years) than children from Vietnam and Cameroon (median age, 5.
Deriving a Prediction Score for Diagnosis of TB in CHIV One hundred thirty-one CHIV from the Kenya cohort were added to the overall dataset, resulting in a total of 414 CHIV of whom 63 (15%) had confirmed TB and 163 (39%) had unconfirmed TB. Baseline characteristics of the cohort are shown in Supplementary Table  2. Since MLR had better performance among CHIV, we developed a prediction score for CHIV with confirmed and unlikely TB (n = 209). Using ROC curve analysis with Youden J, the best MLR cutoff was ≥0. 28 with sensitivity of 67% (95% CI, 54%-78%) and specificity of 68% (95% CI, 61%-75%). We also used Youden index to determine the optimal age cutoff of ≥4 versus <4 years. Using AIC values, the best model to predict active TB disease had the following variables: MLR ≥0. 28, age ≥4 years, TST ≥5 mm, contact history with a TB patient, fever for >2 weeks, and CXR suggestive of TB with an AUC of 0.
Acknowledgments This project has received funding from the  Investissement d'Avenir program , the  Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program  (grant  ANR-10-LABX-62-IBEID ), the  European Research Council  (No. 804744 ) and the  European Commission Seventh Framework Program  [FP7/2007-2013] for the  DENFREE  project under Grant Agreement no. 282378.
METHODS: In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis, we selected patients that underwent a RHC and/or CMR maximally 1. 5 years prior to an event (death or transplantation, N = 49). RESULTS: Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAHpatients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age.
Survival was defined as the time from the baseline measurements prior to initiation of treatment to a first event (death or transplantation) or to the censoring date. Of 49 patients that had an event (death or transplantation), a last RHC and/or CMR measurement was available with a maximum of 1. 5 years before the event. From these patients we collected RHC and CMR data at earlier time points during the disease. Lastly, in explanted and post-mortem RV tissue of male and female patients (N = 6) and controls (N = 6), we assessed histopathological differences. The Medical Ethics Review Committee of Amsterdam UMC did not consider the current study to fall within the scope of the Medical Research Involving Human Subjects (WMO), therefore informed consent was not required (approval number 2012288).
Finally, samples were coverslipped with ProLong Gold Antifade Mountant (Thermofisher Scientific). Cell apoptosis was assessed by Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay using the In situ cell death detection kit fluorescein (Roche) following manufacturer's protocol. Images were captured at 20x, 40x and 60x magnifications under a laser confocal microscope (Nikon A1R). Whole-slide image acquisition was performed on Vectra Polaris (Akoya) at 10x and 20x magnifications. Quantitative histological measurements (cardiomyocyte cross-sectional area, vessel density and apoptotic nuclei) were assessed through ImageJ analysis software (NIH) with at least 10 random fields averaged per patient.
Statistical analysis Data are presented as mean (standard deviation) or median [interquartile range]. Transplant-free differences in survival were assessed using Kaplan-Meier curves and log-rank test with Bonferroni-corrected pairwise comparison. We corrected the survival analysis for confounders including body mass index (BMI), treatment and comorbidities using cox regression analysis. For normally distributed continuous variables, group differences were assessed using one-way ANOVA and post-hoc unpaired t-tests with Bonferroni correction. For non-normally distributed data, logarithmic transformation was applied prior to testing or Kruskal-Wallis test and post-hoc testing with pairwise Mann -Whitney U-tests was performed. For categorical variables, group differences were assessed with Pearson's x2 test or Fisher's exact test.
Only RV afterload (mPAP, PVR, and Ea) was significantly higher in females ≤45years in comparison to females ≥55years and males (Figure  4B , Figure  S3 , Table  2 ). These data suggest a superior adaptation in females ≤45years, as they have a similar RVEF with a higher RV afterload, also reflected by the difference in RVEF » mPAP slope (Figure  4F ). Next, to investigate longitudinal differences in RV adaptation over time, we selected all patients with an event (defined as death or transplantation) and a CMR and/or RHC measurement max. 1. 5 years prior to the event (Table  S3 ). In addition, we analyzed CMR and/or RHC data at three earlier time points during the disease including baseline measurements. Median time from the last CMR and/or RHC measurement to the event was similar for all patients (females ≤45years: 0.