dataesr/scientific-paragraphs-categorization huggingface dataset:
Fluorescent images of primary neurons were acquired on a Zeiss Apotome widefield microscope (Carl Zeiss, Inc. , White Plains, NY, USA) using the ZEN imaging software (Carl Zeiss, Inc. , White Plains, NY, USA). For Sholl analysis, neurons were imaged with a 20x objective lens at a single z-section to fully capture the dendritic tree. Dendritic complexity was analyzed at 50 µm increments from the cell soma using FIJI software (https://imagej. net/Fiji, accessed on 2016-2018) with the Concentric Circles plugin (ImageJ).
Generation of a Parp6 Knockout Mouse Line Using CRISPR-Cas9 Mutagenesis Parp6 is expressed preferentially in the mouse nervous system (www. informatics. jax. org and www. Biogps. org databases, accessed on 2015-2021). In the mouse brain, Parp6 is expressed almost exclusively in neurons (http://dropviz. org/ and https://amckenz. shinyapps. io/brain_gene_expression/, accessed on 2015-2021). shRNA-and miRNAbased knockdown experiments in rat hippocampal neurons in vitro and in vivo (using in utero electroporation of shRNA-based plasmids) demonstrate that PARP6 regulates dendritic arborization  [7]. To further study the role of Parp6 in the nervous system in vivo, we generated a Parp6 knockout mouse line using the CRISPR-Cas9 mutagenesis system, using a single-guide RNA (sgRNA) sequence corresponding to exon 18 in the C-terminal catalytic domain of Parp6 (Figure  1A ).
We next evaluated Parp6 protein levels in Parp6 WT , Parp6 HT , and Parp6 TR mouse brains by Western blotting. We used a Parp6 antibody generated by the Chang lab, which recognizes a region within the C-terminal catalytic domain of Parp6  [3]. We used this antibody because we found that all commercially available Parp6 antibodies were unreliable (data not shown). We first validated this antibody in rat cortical neurons transduced with a validated shRNA-based knockdown lentivirus that targeted Parp6  [7]  (Figure  2B ). We observed a complete loss in full-length Parp6 protein levels in Parp6 TR compared to Parp6 WT and Parp6 HT brain lysates (Figure  2C ). Because we do not have a Parp6 antibody that recognizes the N-terminal region, we cannot determine if Parp6 TR is actually expressed in the Parp6 TR mice.
Characterization of Parp6 TR Embryos and Few Surviving Adults In our previous studies, we found that Parp6 regulates dendrite morphogenesis in embryonic rat hippocampal neurons  [7] ; however, we did not examine axon outgrowth. Parp6 is not only expressed in central nervous system (CNS) neurons, but also in peripheral nervous system (PNS) neurons (e. g. , dorsal root ganglion and spinal cord cells) (www. Biogps. org, https://gp3. mpg. de and https://mouse. brain-map. org databases, accessed on 2015-2021). To examine peripheral nerve development, we performed whole mount immunolabeling for neurofilament medium chain (NF165) on embryonic day 12. 5 (E12. 5) Parp6 TR and Parp6 HT embryos (Figure  S2 ). Immunolabeled and cleared embryos were imaged and overall embryo development was quantified through eye and paw area measurements.
Peripheral nerve development was quantified through outgrowth measurements of the forepaw axon bundle and intercostal axon bundle outgrowth. No significant difference in overall development or axonal outgrowth was seen between Parp6 HT and Parp6 TR animals from multiple litters (Table  S5 ). We also compared Parp6 WT and We next evaluated Parp6 protein levels in Parp6 WT , Parp6 HT , and Parp6 TR mouse brains by Western blotting. We used a Parp6 antibody generated by the Chang lab, which recognizes a region within the C-terminal catalytic domain of Parp6  [3]. We used this antibody because we found that all commercially available Parp6 antibodies were unreliable (data not shown). We first validated this antibody in rat cortical neurons transduced with a validated shRNA-based knockdown lentivirus that targeted Parp6  [7]  (Figure  2B ).
Acknowledgments: We thank  OHSU Transgenic Mouse Models Shared Resource  for generation of the Parp6 TR mice. We thank  P. Chang  for the anti-Parp6 antibody,  Agnieszka Balkowiec  ( OHSU ) for help with the brain region dissections,  H. du Boise  for helping with the cloning of  C563R ,  R485H , and truncated versions of  Parp6 , and  Leomar Esteves  ( les83machines ) for assistance with the mp4 video. We thank  Larry David ,  Ashok Reddy , and  John Klimek  from  OHSU Proteomics  core for assistance with LC-MS/MS analysis.
The Foundation Fighting Blindness, a 501(c)(3) nonprofit organization, established an international consortium of inherited retinal disease specialists in 2016, with a mission to accelerate the development of treatments for rare, inherited retinal degenerations, such as retinitis pigmentosa, Stargardt disease, Leber congenital amaurosis, Usher syndrome, choroideremia, and achromatopsia. The Consortium accomplishes its mission by evaluating novel outcome measures, sharing standardized study protocols and datasets, and disseminating findings. Having established research infrastructure in the first 3 years, including 39 global research sites, the network is now poised to expand its infrastructure for trials of new therapies in partnership with industry. This model represents an innovative approach to overcome challenges of therapeutic development for rare diseases.
To be successful, they must identify suitable outcome measures and match them with their therapeutic strategy (including delivery to the appropriate retinal cell types) and the therapeutic goal (e. g. , slowing progression or improving vision). 2  The variety of promising treatment approaches is evident in the current therapeutic pipeline, ranging broadly from gene editing and augmentation for early stage disease; to neuroprotection for midstage disease; and to prosthetics, optogenetics, and cell therapy to restore some light sensation in late-stage disease. 3, 4 he Foundation's program of sponsored clinical studies began in 2010. It has led to the development of novel outcome measures and added greatly to our understanding of IRDs. The first study, a randomized clinical trial of valproic acid (NCT01233609) in individuals with autosomal dominant retinitis pigmentosa failed to demonstrate a treatment benefit, but was the basis for research that identified the area of the ellipsoid zone (intact photoreceptors), estimated from optical coherence tomography, as a sensitive and reliable outcome measure in retinitis pigmentosa.
5, 6 ] [9] [10]  The scientific output from this study, in the form of 22 publications and numerous downloads of study datasets, has generated significant industry interest and pointed the way to our most recent framework for collaborative clinical research. To extend the success of our early clinical studies, the Foundation established an international consortium of IRD specialists in 2016 (https://public. jaeb. org/ ffb), whose mission is to accelerate the development of treatments for IRDs. The Consortium is developing centers of excellence to participate in sponsored clinical studies that generate robust and high-quality data using standardized protocols. 4 Investigators from participating clinical centers collaborate to assess risk factors and develop outcome variables from prospective natural history studies of IRDs, using standardized protocols.
Using this information, the Consortium focuses on clinical trial development, including the development of hypotheses, creating study protocols, carrying out clinical trials, analyzing the data and publishing the results. As part of the Consortium's mission to stimulate further hypothesis generation and innovation, de-identified datasets will be archived in a central repository after study completion, and readily available to other researchers via a data transfer and processing agreement. Currently, the Consortium has 39 sites (28 in the United States) in 11 countries across North America, South America, Western Europe, and the Middle East. In addition to the sites, the research infrastructure includes a coordinating center, reading centers, technical experts, and oversight committees. All of these components have been developed through our experience launching 2 large multicenter natural history studies, Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A; NCT03146078) and Rate of Progression in EYS-related Retinal Degeneration (Pro-EYS; NCT04127006).
Second, we are focused on improving cost, efficiency, and quality because we have an obligation to donors who fund our work and because economics play a large role in determining whether sites can participate in research studies. Third, we are building avenues toward sustainability, which we view in terms of investigator engagement and project cofunding. We envision mutually beneficial partnerships of many forms, including early access to study datasets, joint development of novel outcome measures, and leveraging our entire research infrastructure to conduct clinical trials of novel treatments. Whatever form our partnerships take, the Consortium will remain open and flexible to conduct clinical trials of promising new therapies, even if they have not yet attracted industry funding. We have evolved over time in response to numerous challenges related to economics (e.
Acknowledgments Supported by funds from the  Foundation Fighting Blindness ,  Columbia ,  Maryland. David Birch  is supported by  NIH  Grant  EY009076. Jacque Duncan  is supported by an unrestricted Grant from  Research to Prevent Blindness  to UCSF and  NIH-NEI  core Grant  NEI-EY002162. Mark Pennesi  is supported by an unrestricted Grant from  RPB  to  Casey Eye Institute  and a core Grant  NIH P30EY010572. José-Alain Sahel  is supported by an unrestricted Grant from  RPB  to  UPMC Eye Center , a core Grant  NIH P30-EY08098 , the  ERC Synergy HELMHOLTZ  Grant and the  IHU FOReSIGHT Grant. Disclosure:  T. A. Durham , None;  J. L. Duncan ,  Acucela, Abbvie/Allergan, Inc. (F) ,  Biogen (F) , and consultant fees from  DTx Therapeutics (C) ,  Eloxx, Gyroscope (C) ,  ProQR Therapeutics, Inc. (C) ,  Spark Therapeutics, Inc.
Red cell membrane proteins were separated by SDS-PAGE. An 8µl of proteins of each sample was loaded in two different gels: the first gel was prepared using a 3. 5% to 17% gradient of acrylamide according to Fairbanks  [19] , and the second gel using a 5% to 15% linear gradient of acrylamide according to Laemmli's method  [20]. Gels were stained by Coomassie blue dye then scanned using a Bio-Rad GS-800 calibrated densitometer at a resolution of 36. 3 X 36. 3 microns. The gel images were analyzed by Bio-Rad's Quantity One software according to the manufacturer's instructions. The density of each protein band is expressed as a function of its optical density (OD) and its width in the gel after eliminating the background noise. To overcome possible errors in the amounts of proteins deposited in the gel, the density of each band is normalized as a function of the sum of the densities of all the bands detected in the track.
Statistical Analysis Statistical analysis was performed using GraphPad Prism version 5. 00 (GraphPad Software, San Diego California USA). The reference ranges and the cutoff values for HS diagnosis of all tests (EMA test, PT, CT, OFT, and EMPE test) were established according to the European Federation of Clinical Chemistry and Laboratory Medicine recommendation for the review of biological reference intervals in medical laboratories  [25]. Normally distributed data are expressed as means±SD [95% Confidence Interval] and compared pairwise by ANOVA test. The threshold of statistical significance was set at p<0. 05. The receiver operating characteristic (ROC) curve analysis was used to calculate the area under the curve (AUC) values for each test to discriminate patients with HS from patients with other types of anemia, and hence to evaluate the diagnostic performance of the method.
Conclusion Our study emphasizes that the EMA test is an efficient tool for HS diagnosis, notwithstanding the nature of the protein deficiency. A combination of the EMA test and the PT gives better results than any single test alone. The EMA test is highly recommended as a diagnostic tool for HS with the availability of a flow cytometer and should be always performed with 6 normal controls. In cases where a flow cytometer is not available, a combination of PT, CT, and incubated OFT are recommended and reached the sensitivity to detect HS. A predominant band 3 protein deficiency in HS Tunisian patients was detected using the EMPE test. We present a set of primary data of HS among Tunisians. Increasing the number of samples is required to strengthen the characterization of HS and related red blood cell membrane diseases at a cellular and molecular level.
Acknowledgements Author Contributions Conception: Salem Abbes. Acquisition, Analysis, and interpretation of data:  Nawel Trabelsi ,  Ghada Bouguerra ,  Faten Haddad ,  Imen Darragi ,  Imen Boudrigua ,  Dorra Chaouachi ,  Mbarka Barmat ,  Chaker Fouzai. Writing-original draft:  Nawel Trabelsi. Writing-review and editing:  Nawel Trabelsi ,  Ghada Bouguerra ,  Imen Kraiem. Agreement:  Salem Abbes ,  Samia Menif ,  Monia Ouederni ,  Mohamed Bejaoui.
Study design, settings, and participants The study was performed in a musculoskeletal and vocational rehabilitation centre. It was conducted in the same clinic and with the same patient profile as in the HFS-F validation study  [5]. Data were collected from patients aged 18 to 65 years who were French speakers and hospitalised from January 1, 2012 to January 31, 2019. The data collection has been prospective since 2012. Patients had various orthopaedic pathologies of the upper limb (shoulder, elbow, and hand) resulting from work, road, or domestic accidents. They had chronic pain for > 6 months. The exclusion criteria were: inability to read and understand the questionnaire in French; serious psychiatric disorders (psychosis, mood disorders, and post-traumatic stress disorder) and; brachial plexus-(or central nervous system)-associated pathologies.
The Stanton score for an item was the percentage of ''yes'' answers among the 6 experts, multiplied by 2 to obtain a score ranging from 0 to 2 (Table  1 ). Quantitative analyses: We collected HFS-F questionnaires from eligible inpatients hospitalised from January 1, 2012 to April 30, 2017, and performed several calculations. Item-to-total correlation: To estimate the representativeness of each item, we calculated the Pearson correlation coefficient between the item score and the overall assessment score  [24]. The Stanton score of an item depended on its correlation (r) with the global HFS score: ''0'' for r < 0. 4 and r > 0. 9 (low representativity or redundancy with other items), ''1'' for r = 0. 4 to 0. 59, and ''2'' for r = 0. 6 to 0. 9 (good representativity) (Table  1 ). Principal component analysis (PCA): This data analysis method consists of transforming variables linked to each other into new decorrelated variables (factors), allowing for reducing the number of variables.
Patients Details of the INFINITY registry have been published before. 16 In short, 10 European tertiary care centers provided individual patient data of consecutive patients treated with MT and received additional IAF (Supplementary Table  I ). Inclusion criteria were patients presenting with an internal carotid artery or middle cerebral artery (first or second segment) occlusion, who were treated with second-generation MT and intra-arterial (IA) urokinase or alteplase. A total of 311 patients were included in the registry. Consent was waived according to the retrospective nature of the work, or patients gave their written or oral consent, depending on the centers ethical and institutional guidelines. All centers obtained ethical approval from the respective local ethics committee. Functional outcome was assessed at 3 months using the modified Rankin Scale, with functional independence defined as modified Rankin Scale 2.
Statistical analysis Data are presented as median (interquartile range (IQR)) or % (n/N). Frequency comparisons were performed using Fisher's exact test. Non-normally distributed continuous or ordinally scaled variables were compared using Whitney-Mann U-test. For assessing associations between baseline variables and occurrence of early angiographic improvement, a multivariable logistic regression model was built, including age, sex, site of occlusion, and center together with all variables with p < 0. 20 in univariable comparison. Clinical regression models were generally adjusted for age, sex, admission NIHSS, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), symptom onset to reperfusion, and occlusion site, according to clinical importance. For assessing the heterogeneity of the clinical effect of EARI on the rate of functional independence, logistic regressions were ran in subgroups and interaction terms were calculated in the complete cohort.
METHODS The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. RESULTS There were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro-B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height.
Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing global disease registry for patients diagnosed with ATTRv amyloidosis and ATTRwt amyloidosis, and asymptomatic carriers of a pathogenic diseasecausing TTR genetic variant  (13). Because THAOS contains baseline and longitudinal data in a diverse global patient population with ATTR amyloidosis, the registry provides the opportunity to investigate the potential of association between sex and cardiac phenotype  (13). The objective of the present analysis was to investigate possible associations between sex and the genotype, phenotype, and degree of myocardial involvement in patients with ATTRv amyloidosis enrolled in THAOS. Sex-Related Cardiac Risk in ATTRv Amyloidosis  [14]   1 ).
Some data from studies in nonhuman animals are also consistent with this hypothesis: stimulation of mice with male sex hormones increases TTR synthesis in the liver and may constitute a risk factor for the development of ATTR amyloidosis  (18). In addition to the higher male prevalence in pa-    1. JACC: HEART FAILURE VOL. 9, NO. 10, 2021 Note that Karnofsky score was primarily collected as an imperfect measure of neurological disease progression, but it may also be impaired in patients with cardiac disease. Similarly, LVEF may be an imperfect measure of cardiac disease severity in patients with ATTR-CM because the majority of patients had preserved LVEF, with differences among patients who all have preserved LVEF less likely to be clinically meaningful. However, the lowest quartile in this analysis included patients with reduced and mildly reduced LVEF (range 17.
Abstract. The TOPAS  (Tikhonov regularised  Ozone Profile retrievAl with SCIATRAN) algorithm to retrieve vertical profiles of ozone from space-borne observations in nadirviewing geometry has been developed at the Institute of Environmental Physics (IUP) of the University of Bremen and applied to the TROPOspheric Monitoring Instrument (TROPOMI) L1B spectral data version 2. Spectral data between 270 and 329 nm are used for the retrieval. A recalibration of the measured radiances is done using ozone profiles from MLS/Aura. Studies with synthetic spectra show that individual profiles in the stratosphere can be retrieved with an uncertainty of about 10 %. In the troposphere, the retrieval errors are larger depending on the a priori profile used. The vertical resolution above 18 km is about 6-10 km, and it degrades to 15-25 km below.
The vertical resolution in the troposphere is strongly dependent on the solar zenith angle (SZA). The ozone profiles retrieved from TROPOMI with the TOPAS algorithm were validated using data from ozonesondes and stratospheric ozone lidars. Above 18 km, the comparison with sondes shows excellent agreement within less than ±5 % for all latitudes. The standard deviation of mean differences is about 10 %. Below 18 km, the relative mean deviation in the tropics and northern latitudes is still quite good, remaining within ±20 %. At south-ern latitudes, larger differences of up to +40 % occur between 10 and 15 km. The standard deviation is about 50 % between 7-18 km and about 25 % below 7 km. The validation of stratospheric ozone profiles with ground-based lidar measurements also shows very good agreement.
With the subsequent instruments SCIAMACHY (2002),  OMI (2004), and GOME-2 (2006) , the spatial resolution of the measurements was improved. Using the OPERA algorithm,  van Peet et al. (2013)  were able to determine ozone profiles using data from multiple instruments (GOME and GOME-2) with identical settings to obtain for the first time a merged time series, which required a subsequent correction of calibration offsets and a correction for degradation. Miles et al. (2015)  developed a retrieval algorithm for GOME-2, which consists of three steps and aims at an even more accurate determination of tropospheric ozone. In the first step, the stratospheric profile is determined from shorter wavelengths of the Hartley ozone absorption band (266-307 nm), in the second step the surface albedo is retrieved using the radiance at 336 nm, and in the last step, the tropospheric profile is retrieved only from the Huggins ozone band (323-335 nm).
For OMI,  Liu et al. (2010)  showed that ozone retrieval with good accuracy (up to 10 % in the troposphere) is possible after a spectral recalibration of the Level 1 data. With the launch of Sentinel 5 Precursor (S5P) in October 2017, the TROPOspheric Monitoring Instrument (TROPOMI) is another nadir-viewing spectrometer operating in the UV-Vis and SWIR spectral range. It is a followup of OMI and SCIAMACHY. Using TROPOMI data, it is possible to continue time series of past and current instruments into the future. The particular advantage of TROPOMI is its unprecedented spatial resolution of 28. 8×5. 6 km 2 in the UV1 band. The main objective of this study is the first evaluation of UV radiance data from TROPOMI for the ozone profile retrieval with the TOPAS (Tikhonov regularised Ozone Profile retrievAl with SCIATRAN) approach, which is the successor of the FURM (Full Retrieval Method) algorithm  (Hoogen et al.
Synthetic retrievals of ozone profiles One of the widely used approaches to check the selfconsistency of the retrieval, investigate its sensitivity, and estimate uncertainties and biases in the retrieved parameters is to undertake sensitivity studies. We call the data sets, used in these sensitivity studies, synthetic retrievals of ozone profiles. To this end, the radiances are simulated using the forward model for a representative set of geophysical scenarios. The retrieval algorithm then runs with the simulated radiances instead of the measured ones. The advantage of this approach it that the true state of the atmosphere is known, which is never the case for the real data. In this study, the radiances are simulated in the spectral range from 270 to 329 nm (TROPOMI UV1 and UV2 bands). The spectral resolution and sampling are set to 0.