dataesr/scientific-paragraphs-categorization huggingface dataset:
To ensure transparency and replicability of the review, we developed a study protocol detailing our approach. All searches were conducted on July 20, 2018. The search string for ProQuest included both Medical Subject Headings terms and free-text terms. Text terms specifically searched in title or abstract, and included syntax, quotation marks and Boolean operators. Search terms for nAMD were combined with search terms for anti-VEGF therapy and study design. Conference abstracts published earlier than 2016, letters, and editorials were excluded from the search. The search terms for the individual conference databases included terms related to anti-VEGF treatments or the nAMD indication. The search terms used per data source are described in Additional Table  1. Given the nature of the analysis, an additional step was included.
Selection of studies and data extraction After all searches were completed, manuscript and conference abstract search hits were imported into a Microsoft Excel (Microsoft; Redmond, WA, USA) file, which was used as the basis to identify relevant publications following a population, intervention, comparator, outcomes, and study-design approach  [14]. The results were screened based on title/abstract followed by full-text review by one reviewer after the removal of duplicate publications. Publication eligibility was assessed based on the prespecified inclusion and exclusion criteria provided in Table  1. During both the title/abstract and full-text screening phase, reasons for exclusion were documented according to these predefined criteria. Studies reporting only clinical outcomes, such as change in the number of Early Treatment Diabetic Retinopathy Study (EDTRS) letters, were not included.
SLR results The SLR identified 2735 records. The database search identified 2230 publications (manuscripts) via Medline and EMBASE (via ProQuest). An additional 505 publications (conference abstracts) were identified from conference proceedings (ARVO, AAO, EURETINA, APAO, and ISPOR). The search for conference proceedings included the manual review of three abstract books from APAO, from which one study was identified and selected to be included in the analysis (Fig. 1 ). After removing 218 duplicates, the title and abstract of 2517 publications were screened for eligibility before moving to full-text screening. After screening, 2397 publications were excluded based on title and abstract. Of the remaining 120 publications, four were abstracts from conference proceedings and 116 were manuscripts.
The four abstracts were selected to be included in the analysis. Of the 116 manuscripts, 86 were excluded after review. Studies were excluded primarily because they did not report data on the outcomes of interest (62) or because of study design  (17). Thus, 30 manuscripts moved forward to full-text review. During the full-text review, the reference lists from the 30 manuscripts was revised using the same approach, and nine additional articles were identified. At the end of the review, 44 publications were selected (39 manuscripts and five conference abstracts) for extraction (Fig. 1 ). The final list of publications included in this review consists of 11 studies describing the impact of anti-VEGF therapy on vision-related outcomes, including blindness, other vision impairment outcomes, and the ability to drive; four studies (five publications) on the patients' overall quality of life (QoL); six studies on the depression or anxiety in patients receiving anti-VEGF treatment; nine studies on the risk for mortality, myocardial infarction, or stroke); and 13 studies on the impact of anti-VEGF therapy on costs.
Acknowledgements The authors thank  Jennifer Pluim  and  Georg-Alexander Pietsch  for their contribution to this project. Preliminary data from our systematic literature review were presented at the  International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Europe 2019 Meeting in Copenhagen, Denmark , 2-6 November 2019. The following authors report consulting fees, travel support, and financial and non-financial support outside the submitted work:  R. P. Finger -Bayer ,  Novartis ,  Novelion ,  Opthea , RetinaImplant, and  Santen ;  V. Daien -Alcon ,  Bayer ,  Horus ,  Novartis , and Thea;  B. M. Eldem -Alcon ,  Allergan Novartis, Bayer, Bausch & Lomb, Ophtotech ,  Pfizer ,  Roche ,  Sanofi ,  Santen ,  Servier , and  Thea; J. S. Talks -Allergan ,  Bayer , and  Novartis ;  J.
[41] Insurance Plan for Ontario and Canada VEGF drugs) in Canada (2007): (2005-2007) • Bevacizumab: $2,769,000 • Ranibizumab: $180,000,000 Fabiano et al. Patients from five Clinical Mean per-capita costs of 2536 € (treated < 1 year) [44] hospitals in Italy database treatment and specialist 1839 € (treated > 1 year) (2016).
The main factors associated with caregiver burden were age, financial issues, health status, daily care and coping strategies. The patients' health status was not associated with caregiver burden. Conclusions Some of the caregiver burden determinants might be modifiable. These findings should help healthcare workers and health-decision makers implement specific and appropriate interventions. trial registration number NCT02400528. ► This study explored, for the first time, the burden on the informal caregivers of polyhandicap (PLH) individuals cared for at home. ► This study was performed on a large sample allowing a high representativeness. ► These findings, based on a cross-sectional design, should be confirmed by longitudinal approaches. ► Based on a small sample size; our results may benefit from confirmation in a larger sample.
general procedure For each PLH individual included in the study, data were collected from medical records obtained by a dedicated clinical research assistant and were checked by the patient's referent physician. Next of kin (individuals to contact for any medical, administrative and social issues) were systematically identified in the medical record. From 19 March 2015 to 31 December 2016, a booklet, including self-administered questionnaires, was sent by mail to each next of kin. To optimise participation, a prepaid return envelope addressed to the coordination team send with the booklet.
Data collection Two sources of data were used: medical records and caregiver data. 1. Patient characteristics were collected from the medical records: -Sociodemographics: age and gender. -Aetiology: unknown versus known, progressive versus non-progressive disease. -Global health severity: severe for patients who met all the following criteria: motor handicap (paraparesia or tetraparesia and/or extrapyramidal syndrome and/or severe general hypotonia), IQ<25, FIM≤20, and GMFCS IV and V; less severe for patients who did not meet these criteria. cores ranged from 0 to 100. High scores reflected a high tendency to implement the corresponding coping strategies. -Burden: (i) specific ad hoc questions: number of children living at home, hours of daily caregiving and frequency of getting up during the night; (ii) self-perceived burden using the Caregiver Reaction Assessment (CRA) Scale,  18  a 24-item questionnaire describing five subscales: self-esteem (seven items), family support (five items), financial impact (three items), planning impact (five items) and health impact (four items).
In the models, each CRA score was considered to be a separate dependent variable. The independent variables relevant to the models were selected from the univariate analysis, based on a threshold p value of ≤0. 05. The final models produced standardised beta coefficients, which represented the change in the SD of the dependent variable (CRA) resulting from a change of one SD in the various independent variables. Statistical analyses were performed using SPSS N°22 software (IBM SPSS PASW Statistics). All tests were two-sided. The threshold for statistical significance was set at p<0. 05. Patient and public involvement Some parents of PLH patients were involved during the validation of the final data collection form to provide their opinions on the choice of questionnaires, understanding/formulation of the items, length of the form and so on.
10 The stingers of other hymenopterans (wasps, hornets) are different and have a pointed and grossly conical appearance. 10 They are smooth and are more commonly used as a hunting tool. They allow insects to inject like a needle and allow subsequent retraction of the sting. 10 o our knowledge, this is the first case describing a corneal bee sting in a cat. However, this lesion has been the subject of several reports in the human literature. The research of the keywords 'bee', 'sting' and 'cornea' in the PubMed Central database retrieved 24 publications since 2000 (19 single case reports and five case series, with a total number of 47 reported cases). Corneal bee stings are rare in humans with infectious, toxic and immunological complications added to the mechanical damage caused by stinger penetration.
Sample size The study sample size was calculated using the unmatched case-control study module of OpenEpi, version 3  [42]  with 90% power based on data from Thomas et al. [43]. Assuming a difference in DENV-infected female Aedes mosquitoes collected between dengue positive and dengue negative households, with an exposure of 10% of DENV-infected Aedes in the exposed group, and 1% of DENV-infected Aedes in the control group, the significance level was set at 5% (two-sided) and the ratio of control to case at 1. The result was a target sample size of 322 patients. To allow for a 15% loss at the household questionnaire stage, we increased the final sample to 370.
Household characteristics A questionnaire was used to collect data on house characteristics and socio-economic status, including monthly household income, possession of certain assets (e. g. , TV, air conditioner, car, or motorbike), and source of drinking and non-drinking water. Observations on the house included the number of rooms, wall and ceiling construction material, and presence or absence of eaves gaps. Housing was differentiated between those having a family living on one or two floors; other types of living conditions, such as apartments, townhouses, or multiple families living in separate houses grouped together. Mosquito control methods used in the household were divided as follows: (1) larval control, (2) adult mosquito control, (3) both the preceding, and (4) no control. The Premise Index was estimated based on the general condition of the house, the surrounding yard area and degree of shade  [47].
Data analysis Data analysis used R 3. 5. 1 software with the MASS, glm, and Rcmdr packages  [53, 54]. Figures were designed using ggplot2 and ggpbur packages  [55]. Map of study sites was built using QGis 3. 10 software and shapefiles were obtained from the Humanitarian Data Exchange project CC-BY 4. 0  [41]. Distribution of indices was visualized by kernel density estimate. Vector control measures, household observations and Premise Index are categorical variables. The study population was analyzed with descriptive statistics, and individuals' information and household characteristics were analyzed with the dengue case occurrence as categorical variables using univariable logistic regression. The socio-economic status (SES) of each patient was calculated as a score based on the household questionnaire (e.
Dengue cases, individual and household characteristics of the population All 396 patients informed about the study agreed to participate and were recruited. Some were excluded from the analysis because of missing entomological and household data, mostly because of limited capacity to follow-up multiple patients presenting at a facility on the same day (Fig 2 ). A total of 377 patients with complete entomological data were included in the final analysis, comprising 173 dengue cases and 204 controls (0. 85 case/control ratio). The participant ages ranged from 5 to 76 years with 190 (48%) females represented (Table  1 ). Almost half of the dengue cases were between 10 and 14 years of age resulting in 4. 28-fold higher odds for dengue infection than people aged greater than 25 years old (p<0. 001).
Moreover, the majority of those studies used immature Aedes indices to assess the infestation level (density) in the study area  [61, 62]. Nevertheless, a study in Sao Paulo, Brazil demonstrated a strong association between numbers of female Aedes collected over a fortnight and dengue incidence  [89]. Their findings were obtained after the re-introduction of DENV serotype 3, to which the majority of the population were susceptible, thus facilitating the assessment of entomological risk factors. The retrospective case-control design means the temporal sequence of events cannot be determined with accuracy. In particular, entomological and immunological data were collected following patient recruitment. Indeed, symptoms of dengue fever can appear as quickly as a few days after DENV transmission (typically incubation period between 4-7, up to 14 days), delaying the recruitment of patients and therefore the entomological collections.
Blinding procedure The main outcomes (AHA or Mini-AHA) will be rated from videos by external accredited/experienced raters unaware of group allocation or assessment interval. Analyses will be performed using study allocation codes. All kinematic analyses, as well as analysis of the neuroimaging data, will also be performed by an experienced rater unaware of group allocation or assessment interval. All data will be anonymized and storage within each site. At the end of the study, these anonymized data will be delivered for analysis.
This self-report questionnaire has been shown to be valid and reliable. The Canadian Occupational Performance Measure  [42]  (COPM) will be used to define therapeutic goals and to quantify the child's performance in relation to these goals, as well as the satisfaction of the parents regarding their achievement. The measure is administered via semi-structured interview and will be performed by a trained examiner. Neuroimaging (T0 and T2) MRI datasets will be collected in Saint-Luc University Hospital (Brussels), CHRU (Brest) and IRCCS Stella Maris (Pisa), using compatible scanners and standardized acquisition parameters to allow a pooled analysis. All children will undergo an MRI at T0 and T2. Before the scans, all participants will be checked to ensure they do not have any contraindications to MRI.
Acknowledgments The authors like to thank to " La Fondation Paralysie Cérébrale" (France)  for their support with this project. We thank  Johanna Robertson  for contributing to the formulation and writing of this project. Members of Early HABIT-ILE group :  Julie Paradis ,  Daniela Ebner-Karestinos ,  Geoffroy Saussez ,  Anne Klöcker ,  Rodolphe Bailly ,  Sandra Bouvier ,  Josselin Demas.
e. , an agonist of 5-HT4) can induce α-secretase and may exhibit positive outcomes in phase II clinical trial (NCT00693004) with an enhancement of the cognitive functions in AD individuals, though these experiments were not followed by additional studies  [120]. Epigallocatechin-gallate (EGCG), which is a polyphenolic compound extracted from green tea, induces α-secretase activity via the protein kinase C (PKC) signaling pathway and decreases cerebral amyloid deposition in AD mouse models  [121] [122] [123]. The benefits of this compound in AD are being studied in phase II/III trials (NCT00951834)  [123]. Bryostatin (i. e. , a strong modulator of PKC) can elevate the release of the α-secretase product, sAPPα. However, in a phase II study, bryostatin failed to show any significant cognitive or clinical benefit in a 12-week, double-blind, placebo-controlled study in 150 advanced AD patients  [124].
Reduction of the peripheral insulin resistance can be achieved by PPARγ agonists, including thiazolidinedione derivatives (i. e. , pioglitazone and rosiglitazone)  [132] , which can mediate aggravation of neuropathology of AD. This weakening of insulin sensitivity can help in proteolysis of Aβ. Nonetheless, pioglitazone failed to show cognitive or clinical benefits in a large prevention trial (NCT01931566) owing to the lack of efficacy of the drug and no safety concern  [133]. On the other hand, in 2 double-blind, placebo-controlled trials, rosiglitazone failed to show any clinically significant efficacy in cognition or global function in mild to moderate AD patients for 48 weeks  [134]. There is an ongoing investigation of several novel drugs. CTS-21166, which displays measurable brain penetration properties, lessened the plasma levels of Aβ and showed good tolerance in healthy individuals  [135] [136] [137].
The most probable mechanism of the effects of this antibody seems to be the binding to small plaques and stimulation of a phagocytic response by microglia  [247]. In clinical trials, when gantenerumab was administered to moderate AD individuals, it decreased the load of brain amyloid by up to 30% as estimated via a positron emission tomography scan, but 2 individuals experienced vasogenic cerebral edema in the high dose group  [248]. In a phase II/III clinical trial (NCT01760005), Hoffmann La-Roche is working together with Eli Lilly run by Washington University School of Medicine. A randomized clinical trial (DIAN-TU-001) aims to evaluate gantenerumab and Lilly's solanezumab in dominantly inherited AD patients (a rare, early-onset type of AD)  [249] [250] [251]. This clinical study is estimated to be finished in March 2021.
Aducanumab (BIIB037) is a human monoclonal antibody (mAb) that has the capacity to bind with various aggregated forms of Aβ such as, insoluble fibrils and soluble oligomers. However, it has been reported that this mAb does not bind with Aβ monomers. In an ongoing PRIME study (NCT01677572, phase Ib trial), aducanumab was shown to reduce Aβ plaques and slow the decline in clinical measures in prodromal or mild AD patients, with acceptable tolerability and safety  [255]. Nevertheless, a side effect called amyloid-related imaging abnormalities (ARIA) was also observed along with Aβ removal in a dose-dependent manner and was mainly reported in APOE4 carriers as compared to the non-carriers. Based on the findings of PRIME and observations from previous clinical trials in AD individuals, current phase III trials of aducanumab in early AD individuals including EMERGE (NCT02484547) and ENGAGE (NCT02477800) have been designed  [256, 257].
In addition, this mAb will also become the first therapeutic agent to confirm that Aβ clearance can lead to better clinical outcomes  [259]. BAN2401 is a humanized IgG1 version of the mouse monoclonal antibody mAb158 that has the capacity to bind with soluble and large Aβ protofibrils  [260]. It was observed that mAB158 can decrease Aβ protofibrils in CSF and brain of Tg-ArcSwe mouse models  [261]. Following experiments in mouse neuron-glial, co-cultures revealed that mAb158 might protect neurons (decrease toxicity of Aβ protofibrils) via resisting the pathological buildup of these protofibrils in astrocytes  [262]. In March 2014, this mAb was licensed to Eisai and collaboration was established with Biogen to develop BAN2401. In a different phase III trial (NCT03887455), the efficacy of BAN2401 is being evaluated in early AD patients  [263].
Results The structure of gdPT is nearly identical to that of PTx. The crystal structure of gdPT was solved at 2. 1 Å resolution (Protein Data Bank (PDB): 6RO0). The protein crystallized in a P2 1 2 1 2 1 space group with two gdPT molecules per asymmetric unit, consistent with the crystal formation reported for PTx  9, 24. We compared the structure of gdPT to the structure of PTx (PDB 1PRT)  9, 24. A schematic picture of the gdPT structure is shown in Fig. 1a  and shows the typical A-B structure previously reported for PTx with the enzymatic A-domain (S1) resting on top of a disc-like base formed by B-oligomer composed of subunit S2, S3, 2 copies of S4, and S5 (Fig. 1 ). The overall structure and the arrangement of the subunits comprising gdPT was determined to be nearly identical to that of the PTx (Fig.
Methods Materials. Purified PTx, PTd, and gdPT were produced by Sanofi Pasteur, Toronto (ON, Canada). Proteins were expressed in B pertussis and purified (~95%) by serial column chromatography following conventional purification protocols. gdPT was prepared at approximately 0. 5 mg/mL in 10 mM potassium phosphate buffer, 150 mM NaCl, and 5% glycerol pH 7. 0. PTx was prepared at approximately 0. 5 mg/mL in 75 mM potassium phosphate buffer and 225 mM NaCl at pH 7. 5. gdPT (R9K/E129G) crystallization, X-ray data collection, and structure refinement. Crystals of gdPT spontaneously grew at 5 °C in plastic bottles containing Fig. 7  gdPT induces an activated memory response in an autologous human whole-blood (hWB) culture. Mass cytometry was used to analyze wholeblood cells cultured for 7 days following stimulation with either PTd, gdPT, or a mock control (media alone).
0. 5 mg/mL of protein in 10 mM KPi pH 7, 150 mM NaCl, and 5% glycerol. Also, 25% glycerol was included as cryoprotectant prior freezing. X-ray diffraction data were collected at the European Synchrotron Radiation Facility Beamline ID30A-1 with a Pilatus 3 2 M detector: wavelength of data collection = 0. 966 Å, temperature of data collection = 100 °K, and beamline = ESRF Beamline MASSIF-1. Data were indexed/ integrated using autoPROC  40  , and molecular replacement was performed with Molrep  41  using PDB code: 1PRT as searching model. Model rebuilding was performed in Coot  42  , and refinement was completed using autoBUSTER (version 2. 11. 7. Global Phasing Ltd. , Cambridge, UK). Data collection and refinement statistics are listed in Table  1. Atomic coordinates have been deposited in the PDB under accession code 6RO0.
Non-deuterated digested peptides were identified by mass accuracy and MS/MS fragmentation (Waters HDMSe function) using the ProteinLynx Global Server software (Waters Corp. , MA, USA). Fragmentation (HDMSe) of non-deuterated peptides was activated in the transfer cell with the collision energy ramp from 15 to 65 V. The level of deuterium calculation on individual peptides was determined using the DynamX software (Waters Corp. , MA, USA). HDX data were analyzed by calculating and summing the difference in deuterium uptake for identical peptides between the two states, PTx and gdPT, at all the HDX mixing time points. The data are all shown with respect to gdPT. Hence, positive or negative values indicate an increase or decrease in deuterium uptake in gdPT, whereas neutral value indicates no difference of the peptides.
Cells were washed, counted, and resuspended in Maxpar® Cell Acquisition Solution containing 0. 1× EQ™ Four-Element Calibration Beads (Fluidigm). Cells were filtered through a 35-µm mesh cap immediately prior to acquisition. Approximately 200,000 events per sample were acquired on a Helios™ CyTOF® System (Fluidigm) and normalized in the CyTOF software version 6. 7. 1014. The hWB cells used for mass cytometry were obtained from the same healthy donor. Single-cell analysis: Data analysis was performed using Cytobank 53 by gating on intact cells based on the Cell-ID™ iridium DNA intercalators and live cells based on the Cell-ID™ rhodium DNA intercalator (Fluidigm). Manual gating on cell subset was performed according to Fluidigm recommended gating strategies (Supplementary Fig. 6 ). viSNE analysis was applied as a dimensionality reduction tool  54  reducing high parameter data down to two dimensions for easy visualization in Cytobank.
viSNE analysis was carried out on the CD45+CD66b-cell population, using 300,000 desired total events (equal event sampling was selected), 3000 iterations, a perplexity of 100, and a theta of 0. 5. Sun-burst plots were drawn using plotly package in the R software (Version 3. 6. 1; R Foundation for Statistical Computing, Austria). Statistics and reproducibility. The results are expressed as mean ± standard deviation (SD). Statistical analysis when comparing two groups was performed using Student's t test. When comparing data obtained from HDX experiments, a difference of 1. 5 Da and 3σ (3× standard deviation of a given peptide/time point over the five time course) was set as the significant threshold for increase and decrease in deuterium uptake.