dataesr/scientific-paragraphs-categorization huggingface dataset:
Identification of patients with "possible" NDD-CKD using machine learning To complement the confirmed population of NDD-CKD patients identified by diagnostic codes and hospitalizations, a machine learning algorithm was developed to identify patients with "possible" NDD-CKD but who could not be captured using the case definition of NDD-CKD. Details of the machine learning algorithm have been described previously  [25]. Briefly, a "potential" NDD-CKD population was identified from the EGB database, comprising patients with a diagnosis of diabetes, cardiovascular disease, or hypertension or patients reimbursed for antihyperglycemic and/or hypertensive drugs during the inclusion period; only patients with �1 year of lookback or �2 years of follow-up were included for analysis (Fig 2B). A "possible" NDD-CKD population was then extracted from this "potential" NDD-CKD analysis population using an unsupervised machine learning algorithm (One Class Support Vector Machine, using scikit-learn Python 0.
Incidence and prevalence of anemia of NDD-CKD From 2015 to 2017, the incidence and prevalence of anemia among patients with NDD-CKD in the EGB database were stable (incidence: 108. 7-114. 7 per 1000 population; prevalence: 435. 7 -449. 5 per 1000 population) (Table  1 , main analysis). Furthermore, 69. 2% of prevalent NDD patients with anemia of CKD in the EGB population in 2017 had CKD stages 3-5 (Fig  3 ). When incidence and prevalence in the EGB population were used to approximate rates per year in the general French population, NDD-CKD and anemia of NDD-CKD incidence and prevalence were constant from 2015 to 2017 (Tables  2  and 3 ). In 2017, the incidence of NDD-CKD and anemia of NDD-CKD in the French population was 2. 3 and 0. 7 per 1000 population, respectively, and prevalence was 8.
Discussion This retrospective database study is the first to provide reliable estimates of incidence and prevalence of NDD-CKD and associated anemia in France. Nearly 10,000 adult patients with confirmed NDD-CKD were identified in the EGB database, around half of whom had evidence of anemia, as determined by codification of prescribed treatment for anemia or hospitalization with an anemia diagnosis, rather than a laboratory diagnosis. Despite differing definitions of anemia, this proportion of patients with anemia of CKD is consistent with published studies from other countries reporting anemia in approximately 40-60% of pre-dialysis CKD patients  [10, 11, [27] [28] [29] [30]. The estimated incidence and prevalence of NDD-CKD anemia among NDD-CKD patients from the database remained relatively stable between 2015 and 2017.
The annual incidence over this period was 108. 7-114. 7 per 1000 population, similar to the 2016 incidence (114 per 1000 population) reported for Italian patients with stage 3-5 NDD-CKD  [31]. Since the EGB is representative of the French population (in terms of age, sex, and healthcare consumption), the number of NDD-CKD patients in the EGB population was used to estimate NDD-CKD prevalence nationally. We estimate that there are almost 475,000 patients with a diagnosis of NDD-CKD in France. The unpredictable rate of CKD progression and the silent nature of early CKD stages makes early detection a challenge  [32]. Data from the Centers for Disease Control assessing undiagnosed CKD in the United States has shown that, even among adults at high risk (�15%) of kidney failure within 5 years, only 50% were aware of having CKD  [33].
Given that patients in this study with confirmed NDD-CKD were identified using hospital diagnosis or ALD codes, we expected that less severe stages of the disease (particularly stages 1-2) would be underestimated. Indeed, the Global Burden of Disease estimated that the global prevalence of CKD in 2017 was 9. 1% (including approximately 0. 05% for CKD patients with dialysis or kidney transplantation); of which, over half belonged to patients with CKD stages 1-2  [3]. By applying a machine learning tool, we estimated that there may be close to 1. 8 million patients in France with undiagnosed NDD-CKD (or otherwise not identified and captured in the EGB database) and, among these individuals, 332,939 may have associated anemia. While the total estimated number of diagnosed plus undiagnosed individuals with NDD-CKD (around 2.
26 million) in our study is less than that estimated by the Global Burden of Disease analysis for 2017 in France (~6 million people)  [3] , it aligns closely with the 2. 45 million estimated by a previous study (MONA LISA), which used prevalence data from cross-sectional surveys in adults aged 35-74. 9 years and standardized to the French population  [34]. Characterization of patients with confirmed NDD-CKD anemia revealed a median age of 83 years, which is older than that previously reported for dialysis-dependent CKD patients in France  [35, 36]. Since anemia is known to increase substantially with age  [37] , the older age profile of the NDD-CKD anemia population retrieved from the EGB database suggests the reliability of the data. However, as the study population included hospitalized patients with NDD-CKD, the age profile of these data could also reflect the fact that older patients are hospitalized more frequently than younger patients, and hence anemia was identified in a greater proportion of older patients.
The use of real-world data routinely collected from a large, nationally representative database  [17]  to provide real-world evidence for the incidence and prevalence of NDD-CKD anemia in France is a strength of our study. Furthermore, this study is the first of its kind in France to generate results indicating that a substantial proportion of French NDD-CKD patients is underdiagnosed and thus managed very late in their disease. The database also had several limitations. The EGB database did not include clinical laboratory/imaging data or outpatient medical diagnoses (e. g. , consultations or examinations); as such, the definitions used for CKD (by diagnostic codes and/or disease registration) and anemia (by treatment and/or hospital admission for anemia) could not use available laboratory data.
Treatments for anemia or anemia recorded during hospitalization may not have been caused by NDD-CKD (although we can confirm that chemotherapy was not a potential cause, as patients with a record of chemotherapy or recent hematological cancer were excluded from this study) and hence may have inflated the prevalence rates of NDD-CKD-related anemia reported herein. Furthermore, the EGB database did not capture diagnostic codes for outpatients, which may have meant that some patients predicted to have undiagnosed NDD-CKD by our machine learning model were already diagnosed. The database also captures all dispensed and reimbursed healthcare consumption; however, although not an objective of the current study, prescribed but non-reimbursed treatments are not included in the database, which precludes assessment of whether exposure to certain treatments fluctuated according to their compliance.
Drugs included in the Diagnosis-Related Group French hospital payment system  [40]  (based on the Groupe Homogène de Malades) were not identifiable and therefore were not available for analysis; this applied to intravenous iron therapy from 2014 onwards as well as any ESAs administered during a hospital stay, although subcutaneous ESA treatment administered in an outpatient setting was still captured. Additionally, over-the-counter drugs were not captured in the EGB database used in this study. As medications used in patients on dialysis are not captured in EGB, the target population included in this study was restricted to patients with NDD-CKD only. Lastly, estimates for overall CKD prevalence in France were derived from the GBD study in 2017  [3] , as more recent data are not yet available.
As a retrospective observational study that used pseudo-anonymized data derived from administrative claims database, bias may exist regarding diagnoses recorded in the database for long-term diseases and for hospital diagnoses. However, this should be minimized since long-term disease diagnoses were approved by the NHI, and diagnosis codes were chosen following national guidelines. Additionally, the inclusion of only patients having undergone a hospitalization involving CKD or who were on the long-term disease list could lead to enrichment of more severe or co-morbid patients and an underestimation of the confirmed NDD-CKD population. The NDD-CKD population may have been underestimated due to a limited lookback period. Patients with CKD stages 1 and 2 may also be less likely to be hospitalized and/or codified, and therefore be more likely to be under-represented, with the prevalence of patients in stages 3-5 being more reliable.
This is consistent with the lower number of confirmed NDD-CKD patients reported in our study versus our pre-study estimate, (although our estimate included both NDD and DD-CKD patients, S2 Table in S1 File). Finally, subclassification of CKD stage 3 patients into 3a and 3b was not reported in the database. The CKD stage was also only captured for approximately 4 out of 5 patients.
Paleomagnetism was measured on the same AMS plastic cube samples and using a superconductive magnetometer (2G-Enterprises, CA, US). We conducted step-wise alternating-field demagnetization during measurements of paleomagnetism. Since declination data are gradually shifted downward due to twisting to twisting during coring, magnetic north was corrected accordingly using the least-square method to reconstruct the in situ north direction of the core.
Magnetic Fabrics Most of the magnetic susceptibility values in the studied cores lie between 0. 1 Â 10 -3 and 1. 5 Â 10 -3 SI units. There are sharp peaks in the range of * 2. 0-3. 0 Â 10 -3 SI units in silt layers (Fig. 5 ). Paleomagnetic directions in all of the core samples were mostly stable from 50 to 800 G during the stepwise alteration of field demagnetization. In this study, we used declination and inclination data under 200 G conditions. Paleomagnetic inclinations are mostly 40-50°downward for the Brunhes chron, but those of 6K#1467MR vary from 70 to 5°downward. The magnetic susceptibility of the samples is 4-9 Â 10 -4 SI throughout the cores (Fig. 5 ). This range reflects differences in the content, type, and/or amount of magnetic mineral grains. Following  Tarling and Hrouda (1993) , the magnetic minerals contributing to the magnetic susceptibility and its anisotropy in our samples were assumed to be ferrimagnetic and paramagnetic mineral grains.
Therefore, we tilted the dataset of 6K#1467MR by 10°southward to adjust for the downslope gradient. As a result, the post-rotation plots are similar to those for 6K#1467MG (Fig. 6b ). According to  Kawamura et al. (2002) , the paleocurrent directions for 6K#1467MG and 6K#1467MR can be interpreted as indicating flow from north to south.
Acknowledgements We thank the captains, crew, shipboard scientists, and operation teams of the Shinkai 6500 submersible during the YK16-11 cruise. The authors gratefully acknowledge  Y. Yamamoto  ( Kochi University ) for help with the measurement of magnetic properties, and  M. Murayama ,  G. Uramoto , and  T. Matsuzaki  ( Kochi University ) for grain-size analyses. This study was performed under the cooperative research programs of the  Institute of Nature and Environmental Technology, Kanazawa University  (Acceptance No. 18026 ) and the  Center for Advanced Marine Core Research (CMCR), Kochi University  ( 17B062 ).
Purpose To perform a systematic review of literature specific to single-fraction stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS), maximum diameter ≥ 2. 5 cm and/or classified as Koos Grade IV, and to present consensus recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). Methods The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. We considered eligible prospective and retrospective studies, written in the English language, reporting treatment outcomes for large VS; SRS for large post-operative tumors were analyzed in aggregate and separately. Results 19 of the 229 studies initially identified met the final inclusion criteria. Overall crude rate of tumor control was 89% (93.
Inclusion criteria We included prospective and retrospective studies, written in the English language, reporting patients treated for a large VS with either upfront single fractions SRS or those treated with single fraction SRS following surgery to a residual or recurrent tumor. We abstracted data for large VS based on those tumors with a maximum diameter ≥ 2. 5 cm and/or classified as Koos Grade IV (large tumors with brainstem and cranial nerve displacement)  [10]. We initially identified 229 studies, of which after screening abstracts, 120 were excluded (Fig. 1 ). The remaining 109 studies were further screened with a detailed review of the published manuscript. We retained only those 19 articles that met our strict inclusion and exclusion criteria  [6, 8, [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26].
Acknowledgments The authors warmly thank  Dr Jean-Paul Concordet  for helpful advice about CRISPR-Cas9 strategy. We also thank  Dr Araksya Izmiryan ,  Dr Ahmed H. Y. Khedher  and  Prof. Denise Paulin  for their helpful discussions. This work was supported by  Association Française Contre les Myopathies  (contract numbers:  21833  and  22142 ),  Centre National de la Recherche Scientifique (CNRS) ,  Institut national de la santé et de la recherche médicale (Inserm) , and  Sorbonne Université. Caterina Gargano  was supported by a PhD student fellowship of  Sorbonne Université.
Future therapies Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell antigens, such as CD19, is being investigated for autoimmune diseases, including NMOSD  [2]. A phase I trial of CAR T-cell therapy targeting B-cell maturation antigen (BCMA) in 12 AQP4-IgG-positive NMOSD patients showed no attacks in 11 patients during a follow-up of 5. 5 months (median), with hematologic toxic side effects and cytokine release syndrome being reported as potential side effects  [184]. Other new drugs and new B-cell-or plasma-cell-directed therapies, such as ublituximab, T4406F telitacicept (B-lymphocyte stimulator blocker and proliferation-inducing ligand), bortezomib (proteasome inhibitor) and Bruton's tyrosine kinase inhibitor SHR1459  [59, 147, 254]  (clinicaltrials. gov), are being actively investigated for the prevention of attacks in AQP4-IgG-seropositive NMOSD.
VH reports no conflicts of interest. JH reports a grant for OCT research from the  Friedrich-Baur-Stiftung , personal fees and nonfinancial support from  Merck ,  Alexion ,  Novartis ,  Roche ,  Santhera ,  Biogen ,  Heidelberg Engineering , and  Sanofi Genzyme , and non-financial support from the  Guthy-Jackson Charitable Foundation ; JH is partially funded by the  German Federal Ministry of Education and Research  [grant numbers  01ZZ1603[A-D ] and  01ZZ1804[A-H ] (DIFUTURE)]. KH reports no conflicts of interest. MH reports no conflicts of interest. SJ reports no conflicts of interest. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from  Alexion ,  Almirall ,  Bayer ,  Biogen ,  Hexal ,  Horizon ,  Merck ,  Neuraxpharm ,  Sanofi , and  Roche/Chugai.
Acknowledgements The authors would like to thank  Dr Yong Chuan Tan  for his assistance in retrieving references and creating tables of the therapeutic agents and  Dr Gaetan Ligat  for assistance in drafting of Figures. SGL acknowledges the following grant support:  NMRC  grant  NMRC/TCR/014-NUHS/2015 ,  NMRC/CIRG/1351/2013 ,  NMRC/CSA-SI/0016/2017 ,  NMRC/CIRG/1479/2017  and  NMRC/OFLCG19May-0038. TFB acknowledges the following grant support:  European Union  ( EU H2020-HEPCAR #667273 ,  ERC-AdG -2014-HEPCIR # 671231 , the  French Cancer Agency  ( TheraHCC2. 0IHU201901299 ), the  ANRS  ( ECTZ103701 ,  131760 ,  104017 ,  ECTZ75178 ),  Inserm Plan Cancer   2019-2023 ,  IdEx Unistra  ( ANR-10-IDEX-0002 ),  SFRI-STRAT'US  ( ANR 20-SFRI-0012 ) and  EUR IMCBio  ( ANR-17-EURE-0023 ) under the framework of the  French Investments for the Future Program.
Acknowledgements. The authors wish to thank  A. Frishman ,  T. Grafke  and  Y. Duguet  for fruitful discussions, as well as the referees for their useful suggestions. Funding. The calculations for this work were performed using high performance computing resources provided by the  Grand Equipement National de Calcul Intensif at the Institut du Développement et des Ressources en Informatique Scientifique (IDRIS, CNRS)  through grant no. A0102A01119. This work was supported by a grant from the  Simons Foundation  (grant no. 662985 ). Declaration of interests. The authors report no conflict of interest.
FUNDING SUPPORT AND AUTHOR DISCLOSURES This work received support from  Centre National de la Recherche Scientifique  ( CNRS UMR 7339 ) and  France Life Imaging Network  ( ANR-11-INBS-0006 ). The author has reported that he has no relationships relevant to the contents of this paper to disclose. ADDRESS FOR CORRESPONDENCE:  Dr Frank Kober ,  Centre de Résonance Magnétique Biologique et Médicale, Aix-Marseille Université ,  Faculté de Médecine , 27  Boulevard Jean Moulin ,  13005   Marseille , France. E-mail: frank. kober@univ-amu. fr.
Background: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. Methods: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0. 3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA.
Like in non-RAO ischemic stroke, IVT was most effective when started within 4. 5 h after symptom onset. This was confirmed in an updated meta-analysis in 2020. 10  Concerning safety, less data is available. In a cohort study, 1 out of 25 RAO patients (4%) treated with IV alteplase developed asymptomatic intracranial hemorrhage (asICH), and in another safety and feasibility study, 1 out of 30 IVT treated patients (3%) developed asICH. 11  As total RAO patient numbers are low and mostly derived from smaller individual studies, we aimed to assess the safety and effectiveness of IVT in RAO patients within a larger multicenter cohort. To this end, we retrospectively analyzed the outcome of RAO patients treated with IVT from 10 European stroke centers within the multicenter IVT collaboration ThRombolysis in Ischemic Stroke Patients (TRISP).
Study population The data for this study was obtained from the TRISP (ThRombolysis in Ischemic Stroke Patients) collaboration containing >10,000 prospectively collected data sets of IVT treated patients from 20 European stroke centers. 12, 13  The locally obtained data was anonymized at the respective center, and then sent and pooled for analysis by the study coordinators in Zurich. We included data from all IVT treated RAO patients within the TRISP database and collected additional data of conservatively treated RAO patients in each center if available. Patients were included based on the diagnosis of RAO within the medical records, which was based on clinical parameters and ophthalmological exam performed by a trained ophthalmologist. Exclusion criteria were missing information about visual acuity (VA) at baseline and/or missing follow-up VA, as well as visual impairment at baseline of less than 0.
Patient data We analyzed baseline demographics, medical history and prior medication, RAO etiology, baseline and follow-up VA, safety parameters as well as symptom-to-needle time for the IVT group. VA was analyzed in logMAR equivalences. LogMAR is the logarithm of the Minimum Angle of Resolution. It is either derived directly by use of an Early Treatment Diabetic Retinopathy Study (ETDRS) vision test chart (also called logMAR chart) as opposed to the commonly used Snellen chart, or can be calculated from the results of measurement of the VA with a Snellen chart. In logMAR notation, lower numbers correspond to better vision, and higher numbers reflect a worse VA. A VA of six-sixths in the Snellen chart (i. e. being able to read six lines from 6 m on a Snellen chart) corresponds to a MAR of 1′ (1 min of arc) and would correspond to a VA in logMAR of zero.
Conclusion Our study provides real-life data from a large European cohort of IVT treated RAO patients. On follow up 3 months after RAO, vision was improved in 44. 7% of IVT and 38. 2% of non-IVT patients. While VR was not superior in IVT versus non-IVT patients, there is scope for benefit of IVT in RAO-patients. To facilitate further studies, outcome assessment in RAO patients should be standardized like for ischemic stroke in the brain. Based on our data, a randomized controlled trial assessing the benefit of IVT in RAO seems justified and participation in current clinical trials should be offered to RAO patients whenever possible. Ingelheim, Bayer, Pfizer and Daiichi Sankyo. His institution has received a grant from Boehringer Ingelheim for the ECASS-4 Study. RRL received funding for speaker honoraria from Pfizer, Boehringer Ingelheim, Biogen and Iscehma View.
Adverse effects, including abdominal pain and vomiting, were reported in 10% of patients. The use of WBI to clear ingested packets of illicit drugs in body packers represents a unique indication for this intervention. 24, 25 It is intuitive that hastening removal of packets of potentially lethal drugs from the GI tract before rupture, leakage and systemic absorption can occur would be advantageous. While a reduction in hospital length of stay has been demonstrated in this patient group (2. 1 days when treated with WBI vs 2. 8 days when treated with laxatives  24  ), there is again a lack of outcome data confirming clinical benefit. 24, 26, 27 Administration of WBI in this particular patient group is also frequently complicated by poor tolerability and treatment refusal. 24, 26 ministration of WBI is challenging to the inexperienced physician and not without risk.
However, the data coverage in the region is still thin: accessibility is limited, satellite sensors struggle with the high solar zenith angle, difficult surface and thermodynamic conditions, or clouds. Corresponding emission inventories and models differ significantly, in the distribution as well as in the amount of emissions. Based in Kiruna/Sweden, the French MAGIC initiative addressed these knowledge gaps by bringing together a multitude of instruments on three research aircraft (Safire ATR-42, BAS Twin Otter, DLR Cessna) and various other platforms for measurements in northern Scandinavia in August 2021. Here we focus on airborne in-situ measurements with the DLR Cessna. The suite of instruments aboard the aircraft included a meteorological sensor package, a Picarro, and an Aerodyne QCLS, providing CH 4 ,CO 2, C 2 H 6, 13 C(CH 4 ), temperature, H 2 O, 3d-wind, all along the flight track.