dataesr/scientific-paragraphs-categorization huggingface dataset:
METHODS • STUDY DESIGN: We studied 2700 consecutive penetrating, anterior lamellar and endothelial keratoplasties carried out between December 1992 and June 2022 at National Eye Hospital, Paris, France. Data were retrospectively analyzed. From 1992 to 2001, all patients had undergone full-thickness penetrating keratoplasty. Between 2002 and 2022, patients with corneal diseases sparing, or only moderately affecting, the corneal endothelium underwent deep anterior lamellar keratoplasty whenever feasible. From 2006 to 2022, patients with endothelial diseases underwent Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) or Descemet Membrane Endothelial Keratoplasty (DMEK) when no stromal fibrosis was discernable on slitlamp examination. Recipient rejection risk was determined as follows: highrisk corresponding to vascularized corneas (2 or more quadrants of corneal vascularization) or a history of irreversible corneal allograft rejection in the operated eye.
Phase and Composition Characterization 2. 3. 1. X-ray Diffraction The presence of crystalline phases in all obtained samples was examined by using X-ray powder diffractometry (XRD). XRD was performed using PANalytical Aeris diffractometer (The Netherlands) and accompanying analyses were performed with suitable software (X'Pert Data Collector, X'Pert Data Viewer, X'PertHighScore and the International Centre for Diffraction Data PDF-2 (ICDD) database). To obtain the XRD pattern, the following parameters were used: 40 kV and 15 mA, step size 0. 0435 • , within 2θ range from 3 • to 60 • , time per step 299. 575 s. The quantitative amount of the observed phases was determined with the Rietveld refinement procedure by using Profex software  [36]. For crystalline phase identification following, ICDD entries were used-#026-1056 for OCP, #01-072-1243 for hydroxyapatite (HAp), #009-0077 for DCPD, and #009-0348 for α-TCP.
Phase and Composition Characterization Prior to starting the OCP synthesis, thermal transformation of ACP (SSA 72 ± 14 m 2 /g, d 0. 5 = 75 ± 5 µm) to α-TCP was confirmed using XRD analysis (Figure  S2 ). Characteristic maxima of α-TCP were in accordance with the reference XRD pattern provided by the ICDD (Figure  S2a ). FTIR and Raman spectroscopy analyses efficiently followed the XRD data, with specific α-TCP bands clearly discernible in the spectrum (Figure  S2d, e ). The median particle size (d 0. 5 ) determined by the laser diffraction granulometry was 37 ± 3 µm (Figure  S2f ), while the specific surface area was 8. 8 ± 0. 2 m 2 /g. SEM micrographs displayed the morphology of α-TCP aggregates (Figure  S2b, c ). The starting precursor for OCP was quantified and the powder was composed of 99% α-TCP (based on the Rietveld calculation, Profex software).
While research on bapineuzumab was terminated due to safety concerns  [81] [82] [83] , clinical trials with solanezumab  [73]  and crenezumab  [84]  were stopped because of the absence of cognitive or functional improvement. Concerning gantenerumab, a phase III clinical trial is still ongoing (NCT03444870, NCT03443973, NCT03887455)  [85] [86] [87]. To date, aducanumab (Aduhelm TM )  [88]  obtained controversial approval from the FDA  [89]  but was rejected by the EMA. This provisional regulatory decision was taken under an accelerated approval pathway. It requires the validation of clinical benefit in a post-approval trial to be held  [90, 91]. Aducanumab was demonstrated to reduce both Aβ and Tau aggregates  [88, 92, 93]  and to improve cognitive deficits in the early stages of the pathology  [89] , representing a hope to slow down the progression of AD.
Prasinezumab was the first to undergo clinical studies in 2017. Phase I and 1b trials in healthy and mild idiopathic PD patients treated with prasinezumab showed favorable results regarding safety, tolerability, and pharmacokinetics. The treatment reduced the level of free α-synuclein in the blood. Besides, no serious adverse effects nor immunogenicity were observed  [109, 110]. However, the results of the phase II trial (NCT03100149) are less positive  [111]. No significant changes were seen in the symptoms of PD nor the imaging measures of the disease's progression. However, despite this failure, studies on safety and efficacy in early-stage PD patients are continuing (phase 2b; NCT04777331)  [112]. Cinpanemab was also reported as negative after a phase II trial (NCT03318523)  [108]. Several adverse effects were observed and led its developer to discontinue the study  [108].
Regarding the third antibody MEDI1341, it is currently in a phase I trial (NCT04449484)  [113]. In the same idea of targeting α-synuclein aggregates, VHHs have been generated; however, the strategy is different. Here, the authors try to target intracellular α-synuclein oligomers  [114]. Moreover, to do so, they use genetic material to express the VHHs directly in the cytoplasm. Since this review focuses on purified sdAbs administered extracellularly, we will not develop this administration technique for antibody fragments. However, it is interesting to know that the VHH PFFNB2, for example, specifically binds to α-synuclein preformed fibrils and does not recognize the monomers in vitro. It can also significantly dissociate the fibrils. Its expression in animals prevented the spreading of the α-synuclein pathology to the cortex  [114]  (Table  5 ).
Funding: This research was funded by  Centre National de la Recherche Scientifique (CNRS)  and  Institut National de la Santé et de la Recherche Médicale  (INSERM). P. R. was supported by the  French National Research Agency (ANR)  (grants  ANR-15-CE18-0020-01 ,  ANR-20-CE18-0011-01  and  ANR-20-CE44-0006-02 ). J. -P. P. was supported by the  Fondation pour la Recherche Médicale  (équipe DEQ20170336747). M. E. T. and P. -A. L. were supported by a doctoral and a postdoctoral fellowship, respectively, from  LabEx MAbImprove  (grant  NR-10-LABX-5301 ).
Data collection and regulatory aspects Data were retrospectively collected from the medical records. The initial disease stage was defined according to the Union for International Cancer Control TMN 7th version. Follow-up radiology and nuclear medicine images were used to identify relapses. Relapses were classified into tumor, lymph node in the treatment field, lymph node out of the field, and metastasis. In cases of isolated local or locoregional relapse, the images were compared with the radiotherapy treatment plans. Out-of-field node relapses were considered as such in cases of localization entirely outside the CTV and were divided into two categories (adjacent and nonadjacent) by using the thoracic anatomy atlas of Chapet et al. (33)  INF was specifically studied. Due to the difficulty in distinguishing a single metastasis from a second lung cancer, relapse as a single nodule was classified as metastatic relapse.
Toxicities were recorded during treatment and at each follow-up visit and defined according to the Common Terminology Criteria for Adverse Events (CTCAE) v5. 0. The study complies with the "reference methodology" MR004 adopted by the French Data Protection Authority. The patients granted consent to the use of their clinical data for research purposes. The study was approved by an international review board (CEC-2022-004). No funding was received for the study.
(36). To obtain comparable data, only patients with stage IIIA or IIIB disease were included in the analysis. We estimated the coordinates of the survival curve using the Datathief tool  (37)  and then generated individual survival data. The one-sample log-rank test was used to compare the two curves. We first approximated the data extracted from Bradley et al. using a parametric distribution according to a log-normal distribution. We then calculated the cumulative hazard function and applied it to the data. Estimates were provided with their 95% confidence intervals (95% CI). Analyses were performed using STATA software (version 17. 0; StataCorp. LLC, College Station, TX, USA).
Comparison to literature data For this analysis, 57 patients with stage IIIA or IIIB disease were included and compared with patients from the 60 Gy subgroup of  the RTOG 0617 study. The two OS curves are shown in Figure  3. The p value of the one-sample log-rank test was 0. 94. Therefore, we cannot conclude that the survival observed in our study was better than that in the 60 Gy subgroup of the RTOG 0617 study.
clinicaltrials. gov/ct2/show/NCT03988816, accessed on 1 July 2023). However, the use of Roflumilast is limited by class-related side effects, such as nausea, diarrhea, weight loss and abdominal pain, resulting in both substantial treatment discontinuation in clinical practice and withdrawal from clinical trials. This has prompted the search for PDE4 inhibitors to be administered by inhalation to reduce the systemic exposure (and thus optimize drug safety) and maximize the therapeutic effect in the lung  [10]. Tanimilast (international non-proprietary name of CHF6001) is an example of a novel inhaled PDE4 inhibitor that has progressed to clinical studies in COPD and asthma  [11]. Tanimilast showed antiinflammatory properties in various inflammatory cells, including leukocytes derived from asthma and COPD patients, as well as in experimental rodent models of pulmonary inflammation  [11] [12] [13].
Inhaled Tanimilast has reached phase III clinical development by showing promising pharmacodynamic results associated with a good tolerability and safety profile, with no evidence of PDE4 inhibitor class-related side effects  [11]. Apremilast is currently under clinical evaluation as a therapy to mitigate the severe inflammatory reactions associated with COVID-19 pneumonia (https://classic. clinicaltrials. gov/ct2/show/NCT04590586, accessed on 1 July 2023). Additionally, a number of molecules are currently under clinical trial for the treatment of respiratory diseases, as recently reviewed in several works  [4, 7, [14] [15] [16]  and briefly summarized in Table  1. Several clinical trials for the treatment of COPD and psoriasis were terminated due to adverse events, mainly affecting the gastrointestinal tract, which were caused, at least in part, by poor selectivity versus the different PDE4 subfamilies.
BI 1015550 Boehringer Ingelheim International Idiopathic Pulmonary Fibrosis III NCT05321069 Evaluate long-term efficacy and safety of BI 1015550. Apremilast (Otezla) Amgen COVID-19 III NCT04590586 Efficacy and safety of Apremilast as add-on to standard of care in hospitalized patients. Cilomilast (Ariflo) GSK COPD III NCT00103922 Completed 24-week study for safety and efficacy in COPD patients (development terminated). GSK256066 (inhaled) GSK COPD II NCT00549679 Safety and tolerability in mild to moderate COPD patients (development terminated). Tetomilast (OPC-6535) Otsuka Pharmaceutical COPD II NCT00917150 24-month study for efficacy and safety of OPC-6535 in COPD patients (last update 2021). 14-week study for safety and efficacy of a Oglemilast Forest Laboratories COPD II NCT00671073 range of Oglemilast doses (last update 2019).
Materials and Methods We conducted a retrospective cohort study of patients with EOC. The data were issued from a French multicenter database composed of thirteen hospital centers (FRANCOGYN research group). This database included patients with EOC of any FIGO stage between July 2000 and December 2020. The study was approved by the Institutional Ethics Committee of the National College of French Gynecologists and Obstetricians (CNGOF) (CEROG #2022-GYN-0803)  [11].
Care Management Socio-demographic, clinical, biological and imaging data were collected for all patients. The diagnosis of EOC was based on pathological examination from a radio-guided or a surgical biopsy. An initial laparoscopy evaluation was used to define the peritoneal carcinomatosis index (PCI) and the Fagotti score  [15, 16]. Three treatment regimens were discussed, according to the current recommendations: primary cytoreductive surgery (PCS), neoadjuvant chemotherapy with interval cytoreductive surgery (NACT-IS) and chemotherapy alone (CTA)  [17] [18] [19] [20]. The surgical goal was the absence of gross residual disease  [21, 22]. Residual disease was defined at the end of the intervention and separated in complete resection, residual disease < 10 mm and residual disease ≥ 10 mm  [23].
Descriptive Analysis of the Population Between 2000 and 2020, 2252 patients from the FRANCOGYN cohort were managed for an EOC, all FIGO stages combined. Of these, 307 (13. 6%) were included in our study: 98 (31. 9%) in the FIGO IVA group and 209 (68. 1%) in the FIGO IVB group. A flow chart of the study is shown in Figure  1. curves was performed by a log-rank test. All statistical analyses were p Excel database (Microsoft, Redmond, WA, USA) and RStudio softwar.
Due to the retrospective n the data concerning the tumor histology of 13 patients (6 patients wi and 7 patients with FIGO stage IVB) could not be specified beyond ep enocarcinoma. More than half of the stage IVB patients had concomita ment. Of the 209 stage IVB patients, 102 had parenchymal metastasis, had intrahepatic metastasis and 43 (21. 3%) patients had extrahepat volvement (brain, pancreatic, splenic, transmural involvement of the most 70% of stage IVB patients had lymph node involvement, mos The main patient characteristics are detailed in Table  1. FIGO IVA patients were significantly older than FIGO IVB patients (p = 0. 03) and therefore significantly more postmenopausal (p < 0. 005). The American Society of Anesthesiologists (ASA) score was used to assess the preoperative health status of patients.
Patients were assigned a score ranging from 1 to 6 if they were in good general condition (ASA 1), had moderate (ASA 2), severe (ASA 3) or life-threatening (ASA 4) organ dysfunction, with a life expectancy of less than 24 h (ASA 5), or in a state of encephalic death (ASA 6). The mode of discovery of EOC was similar for stage IVA and stage IVB patients. Due to the retrospective nature of our study, the data concerning the tumor histology of 13 patients (6 patients with FIGO stage IVA and 7 patients with FIGO stage IVB) could not be specified beyond epithelial ovarian adenocarcinoma. More than half of the stage IVB patients had concomitant pleural involvement. Of the 209 stage IVB patients, 102 had parenchymal metastasis, 73 (36. 1%) patients had intrahepatic metastasis and 43 (21. 3%) patients had extrahepatic parenchymal involvement (brain, pancreatic, splenic, transmural involvement of the digestive tract).
Study Design PAOLA-1 (ClinicalTrials. gov identifier: NCT02477644) was a phase III, randomized, double-blind, international trial (primary data cutoff: March 22, 2019); the study design, patient inclusion criteria, and HRD testing methodology have been previously described in detail. 4 Briefly, adults with newly diagnosed advanced (stage III-IV) high-grade serous or endometrioid OC, primary peritoneal cancer, or fallopian tube cancer who had no evidence of disease or clinical complete or partial response after first-line treatment with platinum-based chemotherapy plus bevacizumab were randomly assigned (2:1) to receive either maintenance olaparib (300 mg twice a day) plus bevacizumab (15 mg/kg every 3 weeks) or maintenance placebo plus bevacizumab.
Before primary data cutoff, a subgroup of patients with a non-BRCA HRRm was determined using a predefined panel of 13 genes involved in HRR. To investigate whether expanding the gene panel to a larger number of genes involved in HRR improved the predictive value of non-BRCA HRRm, an expanded panel, including five additional genes involved in HRR, was formed. Further post hoc analyses using a restricted panel of five selected HRR genes with the highest median GIS and additional published gene panels (those used in Study 19, 8 NOVA,  9  and.
Knowledge Generated In PAOLA-1, non-BRCA HRRm captured a small proportion of HRD-positive tumors. Non-BRCA HRRm gene panels were not predictive of progression-free survival benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab, irrespective of the gene panel tested. Relevance Current gene panels exploring non-BRCA HRRm should not be considered a substitute for HRD determined by BRCA mutation status and genomic instability testing in newly diagnosed advanced OC. ARIEL3 10 trials) were also conducted. Where published gene panels were assessed, analysis was limited to genes also included in the 108-gene panel defined by Myriad: this gene panel, and the HRR genes included in each panel are shown in the Data Supplement. Mutation prevalence was evaluated for individual genes; patients with mutations in more than one HRR gene were classified as having cooccurring HRR gene mutations.
For the analyses in non-BRCA HRRm subgroups reported herein, tumors were analyzed using the MyChoice HRD Plus assay (Myriad Genetic Laboratories Inc, Salt Lake City, UT). HRD-positive status was defined as a GIS of ≥ 42 on the basis of this assay. HRD-negative status was defined as a GIS of , 42 and the absence of a tumor mutation in BRCA1/2 on the basis of this assay. HRD-unknown were cases where a GIS could not be determined. This GIS encompasses LOH, telomeric allelic imbalance, and large-scale state transitions. Detailed methods specific to the MyChoice HRD Plus assay, including Myriad genetic variant classification and genespecific zygosity assessment, are shown in the Data Supplement. PFS was defined as the time from random assignment until investigator-assessed disease progression (modified RECIST version 1.
ACKNOWLEDGMENT We thank the patients and families for making this trial possible and the investigators and clinical study teams who participated in this trial. Support with statistical analysis was provided by  Phil Rowe , MSc, at  AstraZeneca. Medical writing support was provided by  Adam Gill , MRes, at  Cence , funded by  AstraZeneca  and  Merck Sharp & Dohme LLC  (a subsidiary of  Merck & Co. Inc. , Rahway, NJ, USA ).
DATA SHARING STATEMENT Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data-sharing policy described at https://astrazenecagrouptrials. pharmacm. com/ST/Submission/ Disclosure. Data for studies directly listed on Vivli can be requested through Vivli at www. vivli. org. Data for studies not listed on Vivli could be requested through Vivli at https://vivli. org/members/enquiries-aboutstudies-not-listed-on-the-vivli-platform/. AstraZeneca Vivli member page is also available outlining further details: https://vivli. org/ourmember/ astrazeneca/.
-RNA extraction, cDNA synthesis and RT-qPCR Extracted RNA was checked for purity and concentration using the Nanodrop 2000. For RNA extracted from neonatal microglia or tissue, cDNA was synthesised from 1 µg of RNA with M-MuLV reverse transcriptase (Invitrogen) and random hexamers as specified by the manufacturer. cDNA was diluted 1:10 prior to qPCR. qPCR master mix was composed of QuantiFast SYBR Green PCR kit (Qiagen) and forward and reverse primers (1 µM) for the relevant gene of interest. Primer sequences used are provided in Table  1. qPCR was performed for 40 cycles using the Corbett Rotor-Gene 6000 (Qiagen) and quantified using the standard curve method using Rotorgene Q series software (v2. 3. 1). Genes of interest were normalised to either 18S or βactin (in vitro), or the geometric mean of β-actin and cyclophilin (in vivo) as was determined by the stability of the respective housekeeping genes using NormFinder  (Andersen et al.
-Untargeted lipidomics Primary microglia (neonatal) were seeded at 2x10 6 in 150 mm uncoated glass dishes. After 24 h treatment (control, ATGListatin, LPS +/-ATGListatin), cells were dissociated for 5 min with trypsin (0. 05%) and DNAse I. Digestion was neutralized with 10% BSA in ice cold PBS, and cells were pelleted at 600 g for 10 minutes. Cells were resuspended in PBS and counted with a hemocytometer. 1. 11x10 6 cells were taken for further processing and 10% of sample taken for protein quantification. The remaining 90% were pelleted at 600 g for 10 minutes, supernatant aspirated and pellet snap-frozen in liquid nitrogen and stored at -80 °C until analysis. Lipid extraction, sample and data analysis were performed using a previously validated untargeted lipidomic workflow  (Forest et al.
, 2018; Lefort et al. , 2023; Ruiz et al. , 2019). In brief, lipids were extracted from microglia pellets and spiked with six internal standards: LPC 13:0, PC19:0/19:0, PC14:0/14:0, PS12:0/12:0, PG15:0/15:0, and PE17:0/17:0 (Avanti Polar Lipids). Protein concentration was determined using BioRad Bradford dye-binding method as described in section 2. 4. LPS. In addition, we used data alignment with our in-house database, which contains > 500 unique lipids with previously determined MS/MS spectra, for the remaining features. Side chains are indicated when annotated using MS/MS with certitude. When not identified, we only mentioned the total number of carbons and double bounds.
ACKNOWLEDGEMENTS We are grateful to  Dr Grant Mitchell  for the ATGL-floxed mice. We thank the  CRCHUM cytometry core facility  for their help with FACS studies. This work was supported by grants from the  National Natural Sciences and Engineering Research Council (NSERC ,  RGPIN/04798 ), the  Canadian Institutes of Health Research (CIHR ,  PJT153035 ) and  Réseau de recherche en santé cardiométabolique , diabète & obésité from  Fonds de Recherche Québec-Santé (CMDO-FRQS)  to T. A. , and grants from  Fondation pour la Recherche Médicale (FRM) ,  Fédération pour la Recherche sur le Cerveau (FRC)  and  Institut Benjamin Delessert  to X. F. A. C. was supported.
Type of study We conducted semi-structured in-depth interviews using an interview guide with open questions. In order to obtain qualitative data on the experience of infertility in the context of deep infiltrating endometriosis, the questions were mainly about the experience and understanding of the disease in the professional sphere: the way in which the pain symptoms and infertility are perceived by work colleagues, subordinates and superiors; the possible hindrance to hiring; the repercussions on the quality of work; the justification for absences (absenteeism); and the loss of productivity (in connection with presenteeism). Among unemployed women, we also studied the extent to which their pathology could be an obstacle to returning to work.
Unfortunately, the majority of elderly patients with DLBCL and high risk of CNS relapse may not be able to bene t from being treated with R-ACVBP or other regimens more aggressive than R-CHOP because of toxicities precluding their routine administration to older and un t patients (18, 31). Despite improved overall survival rates reported for younger patients with aaIPI of 1, R-ACVBP was associated with signi cantly increased hematological toxicity (18). It must be weighed up individually whether the potential bene t of preventing CNS relapse justi es more treatment-related toxicity. Therefore, the search for better diagnostic and prognostic markers as well as optimizing systemic therapy including new drugs with less toxicity crossing the BBB must continue  (32, 33). A GLA phase II study investigating R-CHOEP plus the BTK-inhibitor ibrutinib in young, high-risk DLBCL patients completed patient accrual and awaits analysis (EudraCT-No.
Additionally, HLCA automated the data pre-processing steps to set up label propagation achieving >60% correct annotations compared with manual annotation. This label propagation works well for single-nucleus, single-cell and various sampling methods, and it is applicable to both healthy and diseased states in most instances. Label propagation was able to extend the HLCA to 2. 2 million cells and 444 individuals from 46 studies, which can function as a universal transcriptomic reference for healthy lung, and can identify disease-affected cell states and gene signatures. Next, Alexandra Firsova (Stockholm, Sweden) introduced the power of spatial transcriptomics in healthy and diseased tissue to extend the HLCA with details relating to lung region. Serial sections obtained from five different regions of the respiratory tract (trachea, proximal large airway and three locations of the parenchyma) from five healthy, 10 asthmatic and 20 COPD donor lungs were studied.