dataesr/scientific-paragraphs-categorization huggingface dataset:
Finally, our research focuses on three types of BMR. Further research could therefore employ a more fine-grained operationalizations of BMR. Future research should follow on expanding the longitudinal setup of the database. The inclusion of lagged values of firm collaboration enabled us to develop insights explaining the consequences of collaboration over time, and to understand whether firm collaboration with partners persists and has short-and long-term implications. Using different lags for industries where R&D and knowledge collaboration effects are short-or long-term may allow further research to measure the inter-temporal dynamics of BMR. Further research may also entail a cross-country study in order to capture if and how differences in regulation and institutional environment across countries  (North, 1991)  change firms' BMR practices and the forms of engagement with their knowledge partners.
Department of Enterprise, Trade and Investment, (2018). UK Innovation Survey, 1994-2016: Secure Access. [data collection]. 6th Edition. UK Data Service. SN: 6699, http://doi. org/10. 5255/UKDA-SN-6699-6 hereinafter named UKIS-UK Innovation Survey (2002-2014). Source:Office for National Statistics. (2017). Business Structure Database, 1997-2017: Secure Access. [data collection]. 9th Edition. UK Data Service. SN: 6697, http://doi. org/10. 5255/UKDA-SN-6697-9, hereinafter named BSD-Business Register.
06 (. 03) year Foreign -0. 07 -0. 07 -0. 07 -0. 05 (0. 05) (0. 05) (0. 05) (0. 05) Reporting units 0. 01 (. 01) 0. 01 (. 01) 0. 01 (. 07) 0. 01 (. 01) Constant -2. 01*** -3. 01*** -2. 79*** -3. 04*** (0. 21) (0. 24) (0. 24) (0. 25) Industry controls No Yes Yes Yes City and year No Yes Yes Yes controls N 24,211 24,211 24,211 24,211 Log-likelihood -12490. 2 -9799. 3 -9729. 3 -9152. 2 Chi2 6592. 1 9025. 2 9136. 2 9069. 5 Note: reference category for legal status is Company (limited liability company), industry (mining), region (North East of England). Instead of industry dummies in this estimation employment (in logs is used). Robust standard errors are in parenthesis. Significance level: *p < 0. 05; **p < 0. 01, ***p < 0. 001. Source: UKIS-UK Innovation Survey; BSD-Business Structure Database.
13 -0. 15 (0. 08) (0. 08) (0. 08) (0. 09) Reporting units 0. 01 (. 01) -0. 01 (. 02) -0. 01 (. 06) -0. 01 (. 03) Constant -1. 39** -1. 23* -0. 98 -1. 22 (0. 48) (0. 60) (0. 63) (0. 69) Industry controls No Yes Yes Yes City and year No Yes Yes Yes controls N 24,211 24,211 24,211 24,211 Log-likelihood -3813. 2 -2405. 3 -2472. 3 -2468. 7 Chi2 1697. 5 1898. 5 1739. 6 1748. 6 Note: reference category for legal status is Company (limited liability company), industry (mining), region (North East of England). Instead of industry dummies in this estimation employment (in logs is used). Robust standard errors are in parenthesis. Significance level: *p < 0. 05; **p < 0. 01, ***p < 0. 001. Source: UKIS-UK Innovation survey; BSD-Business Structure Database.
04) (. 03) Foreign -0. 29** -0. 26** -0. 26** -0. 29** (0. 03) (0. 03) (0. 03) (0. 04) Reporting units 0. 01 (. 01) 0. 01 (. 01) 0. 01 (. 02) 0. 01 (. 02) Constant 1. 55*** 1. 52*** 1. 55*** 1. 56*** (0. 21) (0. 25) (0. 25) (0. 26) Industry controls No Yes Yes Yes City and year No Yes Yes Yes controls N 24,211 24,211 24,211 24,211 Log-likelihood -15818. 3 -11488. 2 -11494. 2 -11486. 7 Chi2 11477. 3 7467. 2 7453. 0 7463. 2 Note: reference category for legal status is Company (limited liability company), industry (mining), region (North East of England). Instead of industry dummies in this estimation employment (in logs is used). Robust standard errors are in parenthesis. Significance level: *p < 0. 05; **p < 0. 01, ***p < 0. 001. Source: UKIS-UK Innovation survey; BSD-Business Structure Database.
Introduction: AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema or macular edema secondary to retinal vein occlusion (RVO) in routine clinical practice. Here, we report the 24-month outcomes in the RVO cohort from France, Germany, Italy, and Taiwan. Methods: AURIGA (NCT03161912) was a prospective observational study. Eligible patients with RVO were enrolled for whom the decision to treat with IVT-AFL had already been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at Former employee: Kay D. Rittenhouse.
From baseline to M6, M12, and M24, treatment-naı ¨ve patients received a total of 4. 0 ± 1. 3, 5. 5 ± 2. 5, and 6. 9 ± 4. 2 injections, respectively, and previously treated patients received 3. 8 ± 1. 5, 5. 0 ± 2. 2, and 6. 3 ± 3. 7 injections, respectively. The safety profile of IVT-AFL was consistent with that of previous studies. Conclusions: In AURIGA, patients with RVO experienced clinically relevant functional and anatomic improvements following IVT-AFL treatment in routine clinical practice. These improvements were largely maintained in treatment-naı ¨ve patients over the 24-month study despite the decreasing treatment frequency, suggesting long-term durability of IVT-AFL treatment outcomes. Infographic available for this article. Trial Registration: ClinicalTrials. gov Identifier: NCT03161912 (May 19, 2017).
Whereas ranibizumab treatment of RVO has been evaluated in various studies of between 2 and 5 years in duration, robust longterm data on IVT-AFL are still needed, particularly in the treatment of BRVO  [5]. Observational studies produce key, realworld evidence (RWE) not only on the effectiveness and long-term safety of therapies, but also on other factors such as treatment patterns, disease progression, disease burden, and patient-reported outcomes  [21] [22] [23]. In RCTs, patients are enrolled according to specific criteria and there are strict treatment protocols. In contrast, RWE is typically gathered from more heterogenous patient cohorts (including patients with relevant comorbidities) who are treated according to physician discretion. RWE can, therefore, provide important insights pertinent to the management of disease in routine clinical practice.
Currently, limited RWE is available regarding the use of IVT-AFL in the treatment of RVO  [5]. The AURIGA study (NCT03161912) was a prospective observational study that evaluated the long-term effectiveness, treatment patterns, safety, and patient-reported outcomes of IVT-AFL treatment outside of RCT settings. Here, we report the primary endpoint and final, 24-month outcomes of AURIGA in treatmentnaı ¨ve and previously treated patients with macular edema secondary to RVO. AURIGA was the first large-scale, real-world study of IVT-AFL treatment in these patients, and the goal of the study was to gain robust insights to help guide the future clinical management of this disease.
Study Design AURIGA (NCT03161912) was a 24-month, prospective, multinational, observational study to assess the real-world effectiveness, treatment patterns, and safety of IVT-AFL in treatmentnaı ¨ve and previously treated patients with diabetic macular edema (DME) or macular edema secondary to RVO. Across both indications, the study enrolled a total of 2529 patients from 243 eye clinics and ophthalmology practices in 11 countries between November 24, 2017, and December 17, 2021. All treatment and monitoring decisions, including the initial decision to treat with IVT-AFL, were made by the attending physician according to their local practice and local marketing authorization. Sample size was calculated to enable sufficient precision in the assessment of the primary endpoint (mean change in visual acuity [VA] from baseline to month 12) by country and by cohort, and this resulted in a planned enrollment of 540 and 270 patients with treatmentnaı ¨ve and previously treated RVO, respectively (see Supplementary Methods in the electronic supplementary material for details).
All treatment and monitoring decisions were made at the discretion of the attending physician with consideration of the local IVT-AFL Summary of Product Characteristics (SmPC), and all treatments, visual acuity measurements, and anatomic assessments were performed according to routine clinical practice at each study site. Visual outcomes were preferably assessed using best-corrected visual acuity (BCVA) as evaluated with Early Treatment Diabetic Retinopathy Study (ETDRS) charts; where ETDRS charts were unavailable, BCVA was evaluated using other methods (e. g. , Snellen charts). In regions where BCVA was not part of the standard of care, conventional VA measurements were conducted and the data were later converted into ETDRS letter scores for statistical analysis  [24]. Central retinal thickness (CRT) was measured by time-domain or spectral-domain optical coherence tomography (SD-OCT) using the instrument available at each site, and data generated by time-domain optical coherence tomography were converted to SD-  OCT measurements for later analysis  [25].
Study Endpoints The study endpoints were assessed using data for each patient in the full analysis set (FAS) from visits closest to month 6 (150-210 days after baseline), month 12 (300-420 days after baseline), and month 24 (660-794 days after baseline). The FAS comprised all patients who received C 1 IVT-AFL injection within the study period and who underwent C 1 observation post-baseline. The primary endpoint of AURIGA was the mean change in VA from baseline to month 12. Secondary endpoints included the proportion of patients with prespecified VA gains and losses, mean change in CRT from baseline,.
VA visual acuity presence of retinal fluid, mean number of injections received, mean time in study, and mean number of visits of each type. All endpoints were assessed at months 6, 12, and 24. To evaluate the trend in VA and CRT over time, data collected for the FAS throughout the study were also analyzed at 4-weekly intervals (every 28 days) within a time window of ? 14/ -13 days. Further evaluations included a sensitivity analysis of the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on study outcomes, and an exploratory analysis of the impact of IVT-AFL treatment on resource usage and health-related quality of life. For the COVID-19 sensitivity analysis, the ''pre-COVID'' group included all patients who received their first IVT-AFL injection at least 360 days prior to the COVID-19 start date in the Only data from the study eye of each patient were used to evaluate the primary and secondary endpoints.
The mean (95% CI) change in CRT from baseline to month 24 was -247 (-267, -227) lm for the overall RVO treatment-naı ¨ve cohort and -147 (-192, -102) lm for the overall RVO previously treated cohort; there were no marked differences among countries in these data (data not shown). The presence of intraretinal fluid (IRF) and subretinal fluid (SRF) over the study period was also assessed in AURIGA. IRF was present at baseline in almost all treatment-naı ¨ve and previously treated patients with an SD-OCT assessment at this time point: 95. 3% (348/365) and 94. 4% (51/54) of patients, respectively (Figure  S2 ). By month 24, this proportion had decreased to 39. 9% (75/188) of treatment-naı ¨ve patients and 77. 8% (14/18) of previously treated patients assessed. In contrast, SRF was present in lower proportions of patients assessed at baseline compared with IRF: 53.
While acknowledging the low proportion of responses to the PRO questionnaires in AUR-IGA, such data can potentially provide key RWE and should be an avenue for further exploration. The safety profile of IVT-AFL was consistent with previous studies  [15, 18, 20, 34, 35]. One case of eye infection was reported; there were no other cases of intraocular inflammation, including endophthalmitis, nor were there any cases of retinal vasculitis. Retinal neovascularization occurred in one patient. The multiple strengths of the AURIGA study include the prospective design, the long-term study duration, the large number of patients enrolled, and the large number of centers participating across different countries. These factors enabled robust data collection from a heterogeneous group of patients across a variety of real-world settings.
Unlike within the setting of a controlled clinical trial, treatment and monitoring schedules in routine clinical practice can be highly variable, as these are at the discretion of the attending physician, and based on their clinical experience in managing the care of patients with RVO. Not all parameters are assessed at each visit, and not all patients attend each of the visits at key study time points. This results in missing data that may limit the interpretation of study endpoints. In AURIGA, this was particularly the case for the previously treated cohort, which was relatively small, and for specific analyses (e. g. , fluid persistence and patient-reported outcomes). Of note, fewer countries committed to enrolling previously treated than treatment-naı ¨ve patients, and the exclusion criteria of the study reduced the eligible patient population who could be enrolled in the previously treated cohort (i.
ACKNOWLEDGEMENTS The authors thank all the patients and clinical investigators who participated in the AURIGA study. Appendix III in the Supplementary Materials provides the list of AURIGA lead study investigators in each of the participating countries. The AURIGA study was sponsored by  Bayer AG, Leverkusen , Germany. Medical Writing, Editorial, and Other Assistance. Medical writing and editorial support for the preparation of this manuscript, under the guidance of the authors, was provided by  Natasha Beeton-Kempen, PhD , of  ApotheCom, UK , and was funded by  Bayer Consumer Care AG, Basel, Switzerland , in accordance with  Good Publication Practice (GPP)  standards (Ann Intern  Med 2022 ; 175:1298-1304 ).
Background: Current literature does not provide large-scale data regarding clinical outcomes of robot-assisted (RAPN) versus open (OPN) partial nephrectomy. Moreover, data assessing predictors of long-term oncologic outcomes after RAPN are scarce. Objective: To compare perioperative, functional, and oncologic outcomes of RAPN versus OPN, and to investigate the predictors of oncologic outcomes after RAPN. Design, setting, and participants: This study included 3467 patients treated with OPN (n = 1063) or RAPN (n = 2404) for a single cT 1-2 N 0 M 0 renal mass from 2004 to 2018 at nine high-volume European, North American, and Asian institutions. Outcome measurements and statistical analysis: The study outcomes were short-term postoperative, functional, and oncologic outcomes. Regression models investigated the effect of surgical approach (open vs Robot assisted) on study outcomes, and interaction tests were used for subgroup analyses.
However, common limitations of these papers are the relatively small sample size, missing information on surgeon's experience, and inclusion of patients treated mainly at European institutions. As a result, prospective, high-quality data on the comparison between RAPN and OPN are currently lacking. Among determinants of successful surgery, oncologic outcomes are the first matter of concern in cancer surgery. In this regard, evidence on the long-term oncologic outcomes of RAPN is scarce. Research questions such as whether RAPN might allow for similar long-term cancer control to OPN and what the meaningful prognosticators are for this patient population are often underinvestigated. Based on these premises and to address these voids, we built a large multi-institutional database with prospective data collection including patients treated with either OPN or RAPN at nine high-volume centers worldwide.
Data source and patient selection The current study relied on prospectively maintained databases from nine tertiary health care institutions worldwide, including 5032 patients treated with partial nephrectomy from 2004 to 2018 (complete inclusion/exclusion criteria are described in Supplementary Fig. 1 ). For the scope of this study, we focused on patients who underwent RAPN or OPN for a single cT 1-2 N 0 M 0 renal mass (n = 4201). We excluded 734 patients with missing information on tumor complexity, leaving 3467 (2404 RAPN and 1063 OPN) patients eligible for the analyses. The surgical approach was selected according to the surgeon's choice. Systemic staging was performed using conventional imaging (computed tomography/magnetic resonance imaging scan) according to internal practice at each treating institution.
The risk of complications according to each individual characteristic was computed for 3467 patients treated with RAPN or OPN using an interaction term between the characteristic of interest and surgical approach (robot assisted vs open) included in a multivariable regression model adjusted for age, PADUA score, clinical size, Charlson Comorbidity Index, and preoperative estimated glomerular filtration rate. [12, 24]. Whether this might apply to partial nephrectomya different operation, with wider variability and different challenges  [25] -is open to discussion and should be investigated in future studies. Oncologic control is always a concern in cancer surgery. In this regard, our data showed that oncologic outcomes, including surgical margins rates, were not different between patients receiving RAPN and OPN.
Conclusions We compared the outcomes of RAPN and OPN in one of the largest series on partial nephrectomy. While cancer control and long-term renal function did not differ between the techniques, we found that the intra-and postoperative morbidity-especially in terms of complications-were lower after RAPN than after OPN. Our predictive models allow surgeons to estimate the risk of adverse oncologic outcomes after RAPN with optimal predictive accuracy, with relevant implications for preoperative counseling and follow-up after surgery. The global setting of the study, the relatively long follow-up, and the large population with thorough clinical data collection (including contemporary patients treated in the postdissemination era of RAPN) are unique strengths of this study and support the validity of the observed findings.
Whether Doppler ultrasonography helps to refine the diagnosis of cirrhosis for patients classified F34 by our study algorithm needs to be evaluated. Consensus reading of liver biopsies was performed in the UK cohort (PB, VP), but histological reading in the French centres was performed by the local pathologist (SM, BL, NS). Nevertheless, these pathologists were all experts specialized in hepatology with at least 20 years of experience. Previous studies have shown that inter-observer reproducibility for fibrosis staging is much better, even excellent, when performed by experts  [24] [25] [26]. Our study algorithm and risk prediction charts have been developed in datasets coming from tertiary care centres and are therefore well suited for use in the context of liver clinics. With the growing awareness of the disease and further widespread use of non-invasive tests, one can expect our tools to disseminate to settings where the prevalence of cirrhosis is lower, such as diabetology clinics.
Exclusion criteria for the present study were liver biopsy length < 10 mm, VCTE failure, and missing blood markers for fibrosis tests calculation. All patients came from hepatology clinics and none of the biopsies were performed during bariatric surgery. Data from the four cohorts were pooled in an excel file (Excel v2303, Microsoft, Redmond, WA, USA). The three French cohorts were not part of the development of the fibrosis tests evaluated in this study, whereas the UK cohort was part of the multicentre set in which Agile3+ and Agile4 fibrosis tests were developed. In addition, morphometry data (area of fibrosis) was only available for patients included from the Angers centre. We therefore decided to pool the UK and Bordeaux cohorts as a derivation set for our study, and the Angers and Grenoble cohorts as a validation set.
Acknowledgements This work received grant support from  Intercept , delivered to  Angers University Hospital (JB). Philip N Newsome  was supported by the  Birmingham NIHR Biomedical Research Centre. This paper presents independent research supported in part by  National institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS foundation Trust  and the  University of Birmingham. (Grant reference number:  BRC-1215-20009 ). The views expressed are those of author(s) and not necessarily those of NIHR or the department of Health and Social care. We thank  Marc de Saint Loup ,  Sandra Girre , and  Audrey Morisset  for data collection and database construction.
Data availability Data that support the findings of this study come from four independent cohorts in different countries (France, UK). Angers cohort (France) -Individual deidentified participant data (including data dictionaries) that underlies the results reported in this article are available from the principal investigator of the cohort (Pr Jerome Boursier, JeBoursier@chu-angers. fr). No additional document will be shared. Data will be available immediately following publication, with no end date. Researchers who provide a methodologically sound proposal will be required to sign a data access agreement, and will only be allowed to carry out the objectives of the approved proposal. Bordeaux cohort (France) -Individual deidentified participant data (including data dictionaries) that underlies the results reported in this article are available from the principal investigator of the cohort (Pr Victor de Ledinghen, victor.
Data processing and statistical analysis First, to evaluate potential significant differences in the MY adj90d, PP adj90d and FP adj90d estimations between the animals subjected to the NPR (n = 20) and those in the control group (n = 20), a multivariate general linear model (GLM) was performed using SPSS software  (IBM Corp, 2019). The model included the nutritional challenge (NPR vs. C) group as a fixed effect. Second, for the data collected for local and systemic indicator traits of inflammation in the 24 animals subjected to the experimental inflammatory challenge (13 NPR vs. 11C) and after assessing the normality of the distributions using the Shapiro-Wilk test (IBM Corp, 2019) (data not shown), nonparametric methods were considered for further analyses. For the SCC trait, we considered a logarithmic transformation (logSCC).
The ratio transformation was also applied to the 11 measurements collected for each systemic phenotype, the rectal T ra , and the 14 plasma biomarker concentration values. To analyse the relative importance of the different studied traits throughout the inflammatory challenge, we performed 17 generalised linear model (GzLM) analyses using SPSS software  (IBM Corp, 2019). The model included the fixed effects on the 11 considered sample collection times (-24 h, 0 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h, and 144 h) and the challenge (NPR vs. C) group. For the statistical significance level to be considered in the GzLM analysis, a Bonferroni correction considering the number of independent traits analysed as determined by a principal component analysis was performed. Hence, for a total of ten independent traits that were found to explain 90% of the total phenotypic variance, the considered significance threshold was defined as P ≤ 0.
005. An additional analysis was performed for the plasma biomarker concentration records using sparse partial least squares-discriminant analysis (sPLS-DA)  (Lê Cao et al. , 2011). In this analysis, the independent variables (X) considered were the ratio traits of the 14 biomarkers analysed at each time point (154 biomarker measurements), and the dependent variable (Y) was a single qualitative variable representing the NPR and C groups. The sPLS-DA identified a small subset of variables that best discriminates the two groups. A threefold repeated 50 times cross-validation procedure was performed to determine the number of components to retain and the optimal number of explanatory variables. The "mixOmics" package  (Rohart et al. , 2017)  of R software was used to represent the dispersion and discrimination of the samples and plot the results.