dataesr/scientific-paragraphs-categorization huggingface dataset:
Imaging and electrocardiographic parameters Echocardiography Due to low costs, as well as ease of image acquisition and interpretation, echocardiography is the universal imaging tool for cardiac amyloid assessment and plays a crucial role in monitoring disease progression  1  ; there is a need for clear and objective thresholds with regard to ATTR-CM progression criteria. Experts recommended that trends in disease progression should be identified and defined using serial measurements, and that findings should be interpreted in the context of other clinical examinations. RCT data may help to define thresholds for disease progression when long-term data on responders vs. non-responders becomes available. Due to the capacity for serial measurements, the panel recommended that physicians simultaneously collect a range of echocardiography parameters that provide meaningful indications of ATTR-CM worsening; for example, stroke volume, inferior vena cava diameter, Doppler assessment including E/e' and transmitral flow, global longitudinal strain (GLS) and pericardial effusion.
Based on clinical trial data in which 8% of patients experienced ≥2 mm increase in LV wall thickness,  36  experts agreed that this threshold was suggestive of disease progression, whereas changes of a lesser magnitude may represent measurement error. However, such changes occur slowly and so are less likely to be useful in guiding short-term management decisions. Confounders such as systemic hypertension should also be considered when assessing LV wall thickness. Routine measurement of LV systolic function should be assessed with ≥5% decreases in LV ejection fraction or as determined from the ATTR-ACT trial data. 13 Indeed, these measures may be better indicators of ATTR-CM progression than LV wall thickness. LV GLS has also been shown to diagnose LV dysfunction in ATTR-CM at the early stages of the disease  37  and to be diagnostically accurate when differentiating cardiac amyloidosis from other aetiologies.
Cardiovascular magnetic resonance and radionuclide imaging (nuclear cardiology) As a pivotal diagnostic tool in ATTR-CM, cardiovascular magnetic resonance (CMR) using native T1 mapping and T1 with late gadolinium enhancement (LGE) is used for tissue characterization and measurement of extracellular volume (ECV). 47 Cine CMR is also more reproducible and accurate for measuring both LV geometry and functional parameters than echo measurements. 7, 48, 49 CV has prognostic value in ATTR-CM,  50, 51  but its use as a measure of treatment response requires validation. Although CMR is contraindicated with some pacemakers, new conditional devices enable imaging where necessary. However, based on costs, availability, and the lack of serial data in ATTR-CM, CMR was not included in the progression criteria.
Treatment effects and transthyretin amyloid cardiomyopathy progression An additional factor when considering meaningful change is the potential delay in treatment effect, and this should be taken into account whilst the disease stabilizes, particularly during the initial 6-12-month interval after starting treatment. This recommendation underpins the importance of robust measures to discern between cardiac remodelling or lack of efficacy in patients with advanced-stage disease, and it is believed that imaging parameters may play a key role in this distinction in the future. Currently, long-term data in treated ATTR-CM patients are lacking, so clear endpoints indicating disease progression or stability are unknown. Findings from phase 3 trials, such as the ATTR-ACT study, may provide relevant endpoints for treatment goals  13  and long-term data will also inform these decisions.
Future studies To improve the management of patients with ATTR-CM, several studies assessing the relationship between patient outcome and progression help inform therapeutic decisions (Table  3 ). Therefore, a set of parameters measuring physical function, biomarkers and imaging should be categorized into different ATTR-CM disease stages based on their relationship with progression and survival. Data from placebo arms of RCTs will provide an opportunity to observe progressive changes in cardiac geometry and will allow a comparison of progressive changes in treated vs. untreated ATTR-CM patients. 10 Another area of future research includes the validation of systemic ATTR biomarkers for the production and plasma concentration of circulating TTR and unstable TTR. These include kinetic and peptide biomarkers that selectively bind to misfolded pathogenic oligomers in the serum; however, these are in the early stages of clinical investigation.
62 he experts propose that long-term studies in patients with ATTR-CM should explore global measurements of frailty, stratifying patients by age, severity and ATTR-CM phenotype. Ideally, multidimensional assessment of frailty should be incorporated into ongoing holistic assessment of ATTR-CM patients, but further studies are required to understand better how different frailty phenotypes influence disease progression. In a similar vein, owing to the typical late-stage diagnosis, the data to support these measures of progression tend to be from older patients; it is hoped that with improved diagnosis and awareness, disease progression in early-stage patients can be characterized. Assessment of cardiac progression in mixed ATTRv phenotype should be part of a multisystemic evaluation, in which progression, stability or improvement of other involved organs (i.
Conclusions A minimum set of parameters should be used to detect disease progression in patients diagnosed with ATTR-CM and these measures should be performed in a relatively short timeframe (6-12 months) after diagnosis or commencing treatment for ATTR-CM. Parameters should include the following: 1. Quantitation of functional decline (clinical and functional endpoints). 2. Quantitation of disease severity by biomarkers and laboratory markers. Upcoming data on non-treated patients will help to elucidate, refine and define these measurements. consultancy and speaker honoraria from Pfizer and Alnylam. P. M. E. has received consultancy fees from Pfizer, Alnylam, MyoKardia and Sanofi Genzyme and an unrestricted educational grant from Pfizer.
com under the Marie Skłodowska-Curie Grant Agreement 766214 (META-CAN), by La Ligue Contre le Cancer, le Cancéropole PACA, l'Inserm and the Agence Nationale de la Recherche (LABEX SIGNALIFE ANR-11-LABX-0028-01). JC obtained a grant from la Fondation ARC. J o u r n a l P r e -p r o o f.
II. THE BABAR DETECTOR AND DATASET The results presented here are based on the full data set collected with the BABAR detector at the PEP-II asymmetric-energy e + e -collider located at SLAC, and correspond to an integrated luminosity of 519 fb -1  [28]  recorded at center-of-mass energies at and near the Υ (nS) (n = 2, 3, 4) resonances. The BABAR detector is described in detail in ref. [29]. Charged particles are detected, and their momenta are measured, by means of a five-layer, double-sided microstrip detector and a 40layer drift chamber, both operating in the 1. 5 T magnetic field of a superconducting solenoid. Photons are measured and electrons are identified in a CsI(Tl) crystal electromagnetic calorimeter. Charged-particle identification is provided by the measurement of specific energy loss in the tracking devices, and by an internally reflecting, ring-imaging Cherenkov detector.
The pions tracking efficiency increases from 98% to 100% in the momentum range 0. 5-3 GeV/c while the average kaon identification efficiency is 84%. Muons and K 0 L mesons are detected in the instrumented flux return of the magnet. Monte Carlo (MC) simulated events  [30] , with reconstructed sample sizes of the order 10 3 times larger than the corresponding data samples, are used to evaluate the signal efficiency and to determine background features. Two-photon events are simulated using the GamGam MC generator  [31]. In this article, the inclusion of chargeconjugate processes is implied, unless stated otherwise.
The efficient production of milk is an important determinant of both, farm productivity and the environmental impact of intensive dairy systems. The objective of the present study was to use a large dataset of commercial dairy cows to determine the relationship among animal breed, Irish total merit index (Economic Breeding Index; EBI), parity, and production efficiency parameters, which included milk solids (MS) production per kg of midlactation bodyweight (MSperBW) and the estimated net energy requirement per kg of MS produced (ENperMS). Data from 80 different spring-calving commercial dairy herds located in southern Ireland comprising 20,051 cows across 34,002 lactations from Holstein-Friesian (HF) and Jersey × Holstein-Friesian crossbred (JFX) cows were accessible for the study across 4 years.
Data selection Data from 80 spring-calving commercial dairy herds located in southern Ireland were available from the Irish Cattle Breeding Federation database (http://www. icbf. com) for the years 2016 to 2019 inclusive. These herds were chosen as they had participated in whole herd milk recording and BW measurements during the time period. All of the herds comprised Holstein-Friesian and 64 out of the 80 herds had some Jersey × Holstein-Friesian crossbred dairy cattle as well as other dairy breeds. Therefore, two genetic groups were formed: HF and JFX. For HF,  a minimum of 75% of the breed proportion was Holstein-Friesian. On average, the HF cows were 92. 5% Holstein-Friesian and < 7% Jersey or other breeds. To define the JFX breed, cows had to have a minimum of 25% of the breed proportion as Jersey.
Data edits Data edits were applied to remove records of animals weighed at less than 750 days of age. Only records from animals weighed between 60 and 200 days in milk were retained to minimize the impact of changing post-calving body energy status on BW (De Vries and  Veerkamp, 2000; Berry et al. , 2006). Any individual BW or milk performance traits that exceeded 3 SDs from their respective mean values were considered outliers and were removed. The final dataset comprised 27,951 lactations from 16,898 HF and JFX cows across 80 commercial herds.
EBI and milk solids production The cows included in this study were of high genetic merit with an average EBI of €130 which is €26 greater than the current national average for herd EBI in Ireland (ICBF, 2019). The mean parental average genetic potential of HF and JFX are presented in Table  2 ; the animals in this study had higher sub-index (SI) values for milk (+€9), fertility (+€6) and maintenance (+€13) and lower SI values for beef (-€10) than the national average in Ireland  (ICBF, 2019). When compared to the HF, the JFX had a higher Milk SI and Maint SI. A detailed breakdown of the mean, and standard deviation (SD) estimates for 305-day lactation milk production, BW and production efficiency parameters for both breeds from the dataset is presented in Table  3. The mean milk yield, MS production, BW, MSperBW and ENperMS for the animals in the study was 5,992 kg, 491 kg, and 522 kg, 0.
Acknowledgments The authors acknowledge the financial support of the  Irish Dairy Levy Funding , the  Teagasc Walsh Scholarship, Research Stimulus Fund GREENBREED  and the  Science Foundation Ireland ,  Starting Investigator Research Grant ,  18/SIRG/5562. The technical assistance of  Jonathan Kenneally  (Teagasc) and  Declan Butler  ( Farm Business Advisors ) is also gratefully appreciated.
Purpose Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy. Methods A population-based study was conducted in North-eastern Italy, including 11. 7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo-or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region. Results Between 2010 and 2017 in North-eastern Italy, 24. 5% of women and 9. 8% of men received at least one TSH test yearly.
Materials and methods This population-based study was conducted to identify the frequency of thyroid examinations in North-eastern Italy, three administrative regions-Veneto, Emilia-Romagna, and Friuli Venezia Giulia-and two autonomous provinces-Trentino and Alto Adige (Table  1 ), for a total of 11. 7 million residents in 2017 (20% of the total Italian population, 5. 7 million men and 6. 0 million women). Well comparable and comprehensive regional health system databases are active in this part of Italy, including exhaustive information on medical prescriptions and procedures since the 1990s, and regional population-based cancer registries  [26]. The following databases collected by regional health authorities were examined: outpatient services databases; hospital discharge databases; and drug prescriptions databases (Online Appendix 1).
Prescriptions for TSH testing (ICD9-CM code 90. 42. 1)  [32] , neck ultrasound examinations (ICD9-CM codes 88. 71. For each individual only one procedure of TSH testing, neck ultrasound, thyroid FNA, and thyroidectomy per year was counted. In order to characterize the prevalence of people living with "chronic" thyroid dysfunction, including hyperthyroidism or hypothyroidism (for all reasons, including thyroidectomies), individuals with at least two prescriptions for thyroid (ATC code H03AA)  [34]  and anti-thyroid (code H03BB) preparations were identified in 2017 from the drug prescriptions databases. On account of the descriptive purpose of the present research and the demographic similarities of the examined regions, we computed only crude proportions and rates of selected examinations from 2010 to 2017, overall and by sex, calendar years, age, and region.
In women, a strong correlation also emerged for neck ultrasound (Spearman 0. 76), consistently with results in South Korea, where screening is the most important driver of the epidemic of thyroid cancer, particularly among females  [16]. The frequency of ultrasonography for thyroid screening reached coverage > 15% in some South Korean regions and is 3-to 4-fold higher than the frequency of neck ultrasound recorded in our study. No favourable effect of screening on thyroid cancer mortality emerged  [16, 20]. Strengths of the presents study include the populationbased design, the inclusion of a substantial part of Italian population, and the availability of data until 2017. Study limitations are the lack of linkage individuals for different tests performed, and of information on the determinants of examinations and their appropriateness according to current guidelines.
Acknowledgements The authors thank Mrs. Luigina Mei for editorial assistance. Members of the Diagnostic Examinations and Pathway of THyroid diseases (DEPTH) working group: Francesco Avossa (Epidemiological Department, Azienda Zero, Padua); Rossana De Palma (Emilia Romagna Region); Rosa Vattiato (Romagna Cancer Registry); Andrea Polverino (Trento Province); Fabio Vittadello (South Tyrol Cancer Registry); Federica Toffolutti, Giuseppe Fanetti (CRO, Aviano). This work was supported by the Italian Association for Cancer Research (AIRC) (Grant no. 16921) and by the Italian Ministry of Health (Ricerca Corrente, RCR-2020-23670066, Alliance Against Cancer: Overdiagnosis, overtreatment, and outcome in cancer patients,.
Acknowledgements The authors thank Mrs. Luigina Mei for editorial assistance. Members of the Diagnostic Examinations and Pathway of THyroid diseases (DEPTH) working group: Francesco Avossa (Epidemiological Department, Azienda Zero, Padua); Rossana De Palma (Emilia Romagna Region); Rosa Vattiato (Romagna Cancer Registry); Andrea Polverino (Trento Province); Fabio Vittadello (South Tyrol Cancer Registry); Federica Toffolutti, Giuseppe Fanetti (CRO, Aviano). This work was supported by the Italian Association for Cancer Research (AIRC) (Grant no. 16921) and by the Italian Ministry of Health (Ricerca Corrente, RCR-2020-23670066, Alliance Against Cancer: Overdiagnosis, overtreatment, and outcome in cancer patients, Funding.
3 g L À1 , dispersed with deionized water, and determined in triplicate. 2. 4. 4 X-ray diffraction patterns (XRD). XRD spectra were obtained for individual nanoparticles as well as their freezedried emulsions, and the data obtained from XRD were recorded every 10 min on a Bruker D8 Discover diffractometer. Cu-Ka1 radiation (Cu Ka1 ¼ 1. 5405 Å), produced in a sealed tube at 40 kV and 40 mA, was selected and parallelized using a Gobël mirror parallel optics system and collimated to produce a 500 mm beam diameter. The data were collected in the 2q ¼ 5-40 range. 2. 4. 5 Emulsion droplet size. Individual average droplet diameter of each emulsion aer re-suspension was measured by laser light scattering using a Horiba LA-960 particle size distribution analyzer (Kyoto, Japan). An analysis model was used with the refractive indices of 1.
Acknowledgements This work was carried out in the framework of cooperation between STDF, Egypt Grant No. 25275  and  Biopolymères Interactions Assemblages ,  INRAE, 44316 Nantes, France. We are equally grateful to  Emilie Perrin  and  Joëlle Davy  for their excellent technical assistance for TEM and SEM visualizations,  Genevieve Llamas  for granulometry, and  Bruno Pontoire  for XRD analysis. Also,  Tharwat I. Shaheen  would like to express his deep thanks to all the  INRAE  family, with special thanks to  I. Capron  for her support, guidance, time, and effective dedicated efforts.
Viral inocula from HBV genotype C and E were similarly prepared from the supernatant of a newly developed, stably transformed HepG2 cell lines. Briefly, cell lines were obtained by transfection of a linearized pcDNA3Neo-HBV plasmid containing 1. 35 genome unit of a consensus sequence of HBV genotype C or E (obtained from HBV database: https://hbvdb. lyon. inserm. fr accessed on 23 December 2021, sequences are available upon request) and a double-round selection under G418 (500 ng/mL) by colony cell cloning (very low density seeding in large flasks).
Funding: This work was supported by the  ANRS  (French national agency for research on AIDS and viral hepatitis) as well as financial support of  INSERM. M. D. received a PhD funding from  Lyon 1 Claude Bernard University, Ecole Normale Supérieure (ENS) Lyon  and  ANRS  ( ECTZ132570 ). Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
, 2011). In either case, investigations related to adaptation, especially of 'rapid' microevolution, are rare. Dunlop et al. (2017)  evaluated a relatively closed population (in the Laurentian Great Lakes) of sea lamprey for adaptation to lampricide resistance over a period of 57 years. Although they suggest the data must be interpreted with caution, they found no evidence for selection. Alternatively, Hess et al. (  2014 ) did report Pacific lamprey exhibiting signals of adaptive variation related to broad-scale geography and life history. Specific to climate change, there is little to no evidence of genetic adaptation to temperature or flow changes. The lack of examples of adaptation may be because the topic has not been investigated thoroughly yet or because such adaptations are rare, especially in migratory lampreys with a long life cycle.
Acknowledgements We acknowledge the contributions of  Hiroaki Arakawa  to the development of this paper. We thank the  Great Lakes Fishery Commission  for support to attend SLIS III and the productive discussions with SLIS III attendees which contributed to the development of this paper. We also thank the multiple reviewers whose comments greatly improved the paper. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of the  U. S. Fish and Wildlife Service. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
ACKNOWLEDGMENTS The authors acknowledge funding from  TopDyn ,  SFB TRR 146 ,  SFB TRR 173 Spin+X  (project  A01  # 268565370 ), and the  National Natural Science Foundation of China  (Grant No. 51771086 ). The experimental part of the project was additionally funded by the  Deutsche Forschungsgemeinschaft (DFG, German Research Foundation ) project No. 403502522  ( SPP 2137  Skyrmionics). We acknowledge financial support from the  Horizon   2020 Framework Programme  of the  European Commission  under  FET-Open Grant  No. 863155  ( s-Nebula ) and Grant No. 856538  ( ERC-SyG 3D MAGIC ). C. S. acknowledges additional financial support from the  China Scholarship Council  (Grant No. 201906180096 ) for a research stay at  Johannes Gutenberg University Mainz. N. K. , B. S. , R. M. R and M. K. gratefully acknowledge financial support by the  Graduate School of Excellence Materials Science in Mainz (MAINZ ,  GSC266 ).
Acknowledgments: Esr2 -/-, Esr1 -/-and AF2 0 ERα mice and the corresponding littermate WT mice were kindly provided by  Prof. P. Chambon  and  Dr. A. Krust  ( Institute of Genetics and Molecular and Cellular Biology, Strasbourg, France ). We thank  J. M. Foidart  and  Mithra Pharma  for providing Estetrol ( E4 ).
Source of funding: This work was supported in part by the  foundation for Medical Research (Fondation pour la Recherche Médicale ,  Mitoshear  project, contract  FRM -DPC20171138957 ), the  National Agency for Research (Agence Nationale de le Recherche ,  Estroshear  project, contract #  ANR-18-CE14-0016-01 ),  INSERM, University of Toulouse III , the  Fondation pour la Recherche Médicale  (Equipe FRM  DEQ20160334924 ), the  Fondation de France  (contract  00086486 ), the  Région Occitanie , and the  Institut Universitaire de France in Toulouse. JF was supported by the  Lefoulon-Delalande Foundation. CF and JR were supported by the  National Agency for Research (Agence Nationale de le Recherche ,  Estroshear  project, contract #  ANR-18-CE14-0016-01 ).
Study design Between January 2005 and March 2018, all adult patients (≥ 18 years of age) admitted in 11 French ICUs (cf. Additional files 1 and 2) for acute cholangitis were identified by searching hospital databases for codes K803 or K830 as a principal or associated diagnosis according to the International Classification of Diseases (10 th version). Acute cholangitis was defined by the association of fever, jaundice, imaging abnormalities and/or biliary obstruction, according to the International Guidelines  [6, 7].
Data collection Data were collected retrospectively by local investigators using electronic case report forms (eCRF) then centralized and anonymized. The following data were collected: age, gender, cardiovascular diseases (coronary artery diseases or chronic heart failure), hypertension, other comorbidities (e. g. diabetes mellitus, cancer, immune deficiency, cirrhosis, chronic renal failure), clinical symptoms (abdominal pain, jaundice, diarrhea, chills) at ICU admission. Disease severity was evaluated using the Simplified Acute Physiology Score (SAPS II), the Sequential Organ Failure Assessment (SOFA) score, and the use of organ support therapy. Specific AC-related parameters occurring during ICU stay were also recorded: presence of liver abscesses; parameters related to biliary drainage (method, time from admission), ERCP complications, microbial analysis, anti-microbial therapy.
Non-optimal biliary drainage was defined as persistent partial biliary obstruction after the first decompression procedure. Sepsis and septic shock were defined using the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)  [8]. Anti-microbial therapy was considered as appropriate if the first line therapy was active on the isolated pathogen (blood and/or biliary cultures) according to the EUCAST guidelines  [9]. All authors had access to the study data and reviewed and approved the final manuscript. Quality was assessed according to the STROBE checklist.