dataesr/scientific-paragraphs-categorization huggingface dataset:
As of January 2023, IMGT/mAb-DB contains 1,342 entries: 1,167 IG, 65 CPCA, 61 RPI, 44 FPIA and 5 TR from several clinical domains. In the field of oncology, IMGT/mAb-DB has 530 mAbs, with assigned INN names, in different clinical trials. Among these mAbs, 54 have been approved by the U. S. Food and Drug Administration (FDA) and/ or European Medicines Agency (EMA). Regarding immune checkpoint molecules, IMGT/mAb-DB includes 148 mAbs targeting an IC with an assigned INN name, of which nine have been approved by FDA and/or EMA. Sources of data managed in IMGT/mAb-DB are extracted from INN/WHO Proposed and Recommended lists. These lists provide, for each mAb, an INN definition based on the amino acid (AA) sequences and biochemical properties of the mAb chains, domains and regions. The AA sequences are analyzed and stored in IMGT/2Dstructure-DB  (8) , which is linked to IMGT/mAb-DB.
Acknowledgments We are very grateful to  Marie-Paule Lefranc , IMGT ® founder in 1989, which conceived IMGT/mAb-DB and for her continuous contribution to IMGT ®. We thank all internship students that worked on this project, specifically  Christos Chatzopoulos ,  Evangelia Valliou ,  Grasila Oye-Ndo  and  Layla Barbar. We thank  Souphatta Sasorith ,  Meĺissa Cambon  and  Karima Cherouali  for their contribution to the database development and its feeding. We thank all members of the IMGT ® team for their expertise and constant motivation. We thank  Zhanna Santybayeva  ( illustration4science ) for producing the animated video and the graphical abstract for this publication. IMGT ® is a registered trademark of CNRS. IMGT ® is a member of the  Confederation of Laboratories for Artificial Intelligence Research in Europe (CLAIRE ).
Funding IMGT® is granted access to the  High Performance Computing (HPC) resources of Meso@LR  and of the  Centre Informatique National de l'Enseignement Superieur (CINES) , to  Tres Grand Centre de Calcul (TGCC) of the Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) and Institut du developpement et des ressources en informatique scientifique (IDRIS) [036029  ( 2010-2023 )] made by  GENCI  ( Grand Equipement National de Calcul Intensif ). IMGT® is currently supported by the  Centre National de la Recherche Scientifique (CNRS)  and the  University of Montpellier. AK's thesis is funded by the  Occitanie Region, Subvention d'Investissement, Allocations de Recherche Doctorales 2020.
Study design JAVELIN IL-12 (NCT02994953 ) was an open-label, multicenter, dose-finding, phase Ib trial with a consecutive parallel-group expansion conducted at 33 sites in North America and Europe. In the dose-escalation part, sequential cohorts of patients received combination therapy with M9241 plus avelumab in a modified 3+3 design to determine the maximum tolerated dose, defined as the maximal dose at which no more than one of six evaluable patients experienced a dose-limiting toxicity (DLT). Patients in the dose-escalation cohorts received one of four ascending dose levels (DLs) of M9241 subcutaneously every 4 weeks (Q4W) plus avelumab 10 mg/kg intravenously every 2 weeks (Q2W). For DL1-DL4, patients received M9241 at 4, 8, 12, and 16. 8 µg/kg, respectively. For DL5, patients received M9241 at 16.
RNA was analyzed using the nCounter PanCancer Immune Profiling panel (NanoString Technologies, Seattle, Washington, USA), per the manufacturer's protocol. Genes with p<0. 05 and >1. 5-fold change after treatment were analyzed for enrichment of pathways using Ingenuity Pathway Analysis software (Redwood City, California, USA). Changes in immune parameters between two time points were assessed for statistical significance using a Wilcoxon signed-rank test. Blood-based PD-L1 gene expression was assessed in the dose-escalation part using samples from baseline and during treatment; total RNA was extracted using the PAXgene Blood miRNA Kit, and PD-L1 gene expression was detected by using a validated digital droplet PCR method. TaqMan assays containing primer and probe sets were selected based on coverage of the PD-L1 gene and were tested for linearity and efficiency using real-time quantitative PCR.
Dose-escalation part Patients Of a total of 41 screened patients, 36 were enrolled across the five dose groups. At final analysis (data cutoff: November 20, 2020), 36 patients with various solid tumors had received ≥1 dose of M9241 plus avelumab. The primary tumor sites for these patients are reported in online supplemental table S1. Most patients were male and White, and all had an ECOG PS of 0 or 1 (table  1 ). All patients had discontinued study treatment at the data cut-off. The most common reasons for treatment discontinuation were disease progression (M9241, 52. 8%; avelumab, 50. 0%) and AEs (M9241, 30. 6%; avelumab, 33. 3%) (figure  1 ). One patient (2. 8%) who had a complete response with M9241 8 µg/kg plus avelumab discontinued both study drugs per protocol; on disease reoccurrence, this patient subsequently reinitiated both study drugs.
Biomarker analyses In total, 27 patients were analyzed for changes in serum analytes, 135 immune cell subsets, and gene expression. A time-dependent induction in serum levels of IFN-γ was observed after M9241 administration (figure  4A ). IFN-γ levels increased at day 2 of both cycles 1 and 2 and    Analyses of classic PBMC subsets showed a reduction in conventional and plasmacytoid dendritic cells after the first M9241 dose, which returned to baseline levels after the second dose (online supplemental figure  S2A ). Analyses of refined immune cell subsets reflective of increased CD8 + T-cell and NK-cell activity were also seen (online supplemental figure  S2B ). No significant dose-dependent differences were observed in immune cell subsets. A time-dependent induction in PD-L1 gene expression in peripheral blood was observed following M9241 administration in combination with avelumab (data for DL5 are not available because of limited samples) (online supplemental figure  S3 ).
Dose-expansion part Patients After the RP2D was determined, enrollment began of patients with advanced or metastatic UC in a doseexpansion cohort. Of a total of 26 screened patients, 16 were enrolled. At final analysis (data cut-off: November 6, 2020), 16 patients with advanced UC had received ≥1 dose of M9241 plus avelumab at the RP2D. Of these, six patients (37. 5%) had upper-tract tumors and 10 (62. 5%) had lower-tract tumors. The median time since first diagnosis was 1. 6 years (range, 0. 3-12. 3); the median time since metastatic diagnosis was 0. 7 years (range, 0. 1-6. 1); and the median time since last disease progression was Open access 1. 5 years (range, 0. 9-2. 8). Most patients were male and White, and all had an ECOG PS of 0 or 1 (table  1 ). Baseline PD-L1 status for patients in this part is summarized in online supplemental table  S2.
Safety All 16 patients had ≥1 AE of any grade; 14 (87. 5%) had a grade ≥3 AE (table  2 ). TRAEs of any grade occurred in 15 patients (93. 8%); the most common (≥25% of patients) were fever (50. 0%), nausea (37. 5%), anemia (31. 3%), asthenia (31. 3%), chills (31. 3%), and hyperthermia (25. 0%). Grade ≥3 TRAEs occurred in eight patients (50. 0%): anemia (18. 8%), increase in gamma-glutamyl transferase (12. 5%), lymphopenia (12. 5%), neutropenia (12. 5%), fever (12. 5%), hepatocellular injury (6. 3%), The solid lines depict the median (50%) prediction using a population pharmacokinetic model for monotherapy (10 mg/kg Q2W for DL1-DL4, 800 mg QW for 12 weeks then Q2W thereafter for DL5); the dotted lines depict 5% and 95% predictions using the population pharmacokinetic model. (B) The data points show individual patient values, and the horizontal lines show medians; avelumab monotherapy data (red) were taken from the UC cohorts of the JAVELIN Solid Tumor trial (dose, 10 mg/kg Q2W).
Acknowledgements The authors thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers. Contributors Study concept: JSc and JLG; study design: JSc, XW, YV, FB, and JLG; data collection: JSt, AR, MMar, RKP, JSc, RND,  Y-TT , XW, and YV; data analysis: JSt, JSc, RND,  Y-TT , XW, YV, FB, AS, SC, and JLG; data interpretation: JSt, AR, MMar, RKP, JSc, RND,  Y-TT , XW, YV, FB, AS, SC, and JLG. All authors drafted the manuscript and approved the content of the final version of the manuscript. JLG is the guarantor for this article. Funding This trial was sponsored by  Merck  ( CrossRef Funder   ID 10. 13039/100009945 ) as part of an alliance between  Merck  and  Pfizer. This trial was partly funded by the  Center for Immuno-Oncology ,  National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Subjects Patients registered on LT waiting for decompensated cirrhosis or for cirrhosis complicated with hepatocellular carcinoma list at Lyon University Hospital (France) were prospectively enrolled. All patients were eligible to a standard immunosuppressive protocol with administration of simulect (day 0 and day 4), corticoids (at least 7 days), tacrolimus and mycophenolate mofetil. Exclusion criteria were as follows: patients requiring multi-organ transplant, patients treated with immunosuppressors (including patients with history of previous LT) and patients without underlying cirrhosis. This protocol is an ancillary study from EdMonHG study (N °ID-RCB 2019-A00954-53, CT identifier: NCT03995537). Patients reported in this study were included from January 2022 to September 2022. Peripheral blood samples were collected once at enrolment (within 3 months before LT).
Following LT, samples were collected twice a week for 1 month or until the occurrence of infection and/or acute cellular rejection. Post-LT time points were grouped as follows: day 1 to day 3 (D1-D3), day 4 to day 6 (D4-D6), day 7 to day 13 (D7-D13), day 14 to day 20 (D14-D20), day 21 to day 27 (D21-D27) and day 28 to day 31 (D28-D31). Before LT, all clinical data related to cirrhosis severity and aetiologies were collected. All relevant clinical and biological data occurring during and after transplant surgery were recorded. Acute decompensation (AD) of cirrhosis was defined by the acute development of one or more major complications of liver disease (i. e. , ascites, hepatic encephalopathy, gastrointestinal haemorrhage and/or bacterial infections)  (Moreau et al. , 2013). ACLF stage in pre-LT patients were defined according to Moreau's criteria  (Moreau et al.
For skin cryosections, samples were snap frozen and stored at -80 °C. Cryosections were cut in OCT at 7 μm thickness on Epredia CryoStar NX50 at -20°C chamber temperature and mounted onto lysinecoated Superfrost slides (VWR). Sections were fixed for 20 min in 4% ParaFormAldehyde (PFA) at RT prior to immunostaining. For paraffin embedded sections, tissue samples were fixed in 4% PFA overnight at 4 °C then stored at 4 °C in 100% Ethanol. They were then embedded in paraffin. Paraffin blocks were then sectioned at 7 μm thickness and mounted onto Lysine-coated slides and stained with Haematoxylin and Eosin (H&E) at the Histology Facility at University of Bristol. Epidermal thickness measurement: Pictures of skin sections stained with H&E as above were taken with 5X objective on Zeiss Apotome Axio Observer (Carl Zeiss) using the tile function of Zeiss Zen Blue software.
Antibodies: The following primary antibodies were used: anti-P-MLKL (Abcam, 187091), anti-mIL-33 (R&D System, AF3626), anti-mTNF (BD Pharmingen, 559064), anti-cleaved caspase-3 (R&D Systems), anti-RIPK3 (Abcam, ), anti-Krt14 (Neomarkers), anti-Krt10, Krt6 and loricrin (Biolegend), anti-CD3 (Agilent), anti-F4/80 (BD Biosciences, T45-2342) and anti-Gr1 (BD Biosciences, RB6-8c5). As secondary antibodies donkey-anti-mouse 488 AlexaFluor  (1:2000) , goat anti-rabbit 488, goat anti-rabbit 594, donkey anti-rat 594 and donkey anti-goat 594 were used in combination with DAPI as counterstaining for DNA. Fluorescent images were acquired on a Zeiss LSM800 confocal laser scanning microscope using ZEN 2. 6 Software. DAPI was purchased from Sigma. Slides were mounted in fluorescence mounting solution Vectashield (H-1000, Vectastain Laboratories Inc.
For anti-cleaved caspase-3 and anti-RIPK3 immunostainings, sections were permeabilized using 1/100 trypsin solution in water for 30 min at 37 °C prior to immunostaining. Primary antibodies were diluted 1/1000 and 1/100 respectively in PBS-T 10% goat serum. then incubated the following day with secondary antibody Alexa 594 anti-Rabbit, stained with DAPI (Sigma), then mounted in Vectashield. Fluorescent images were acquired on a Zeiss LSM800 confocal laser scanning microscope using ZEN 2. 6 Software. Epidermal markers immunostainings: For epidermal differentiation markers, formalin-fixed paraffin-embedded sections underwent deparaffinization and rehydration steps using xylene and successive baths of 90%, 75% and 50% ethanol. Heat-induced antigen retrieval using citrate buffer ph 6 was performed for 20 min.
Acknowledgments We thank  Dr. Stephen Hedrick  ( UCSD, U. S. A. ) for kindly providing caspase-8 Flox mice. We thank  Pr. Daniel Pinschewer  ( University of Basel, Switzerland ) for kindly providing the St2-/-mice. We thank  Pr. Andrew McKenzie  ( MRC, Cambridge, UK ) and  Dr. James MacLaren  ( Cardiff University, UK ) for kindly providing the IL-33-/-citrine reporter mouse. We thank  Dr. Timothy Hughes  and  Dr. Wiola Zelek  for helpful discussions. We thank  Michelle Somerville  for helpful support with the imaging facility. We thank  Pr. B. Paul Morgan  for helpful discussions and continuous support. Funding:  MRC NIRG  Grant  MR/R009252/1  to  MCB UKRI  CoA funding to  MCB Cardiff University   Research Fellowship  to  MCB   European Skin Research Foundation Grant  to  MCB Versus Arthritis  Grant  20016  to  EHC ALOCA  funding to  LM INSERM  funding to AB and MB.
Parsaclisib, a selective inhibitor to PI3Kdelta, showed therapeutic effects in both antibody transfer-induced MMP and immunization-induced EBA, but not in autoantibody-induced EBA. These data indicated that cutaneous kinase activity of inflamed skin may correlate with treatment outcomes following PI3Kdelta inhibition in experimental mouse models of pemphigoid diseases. IgG levels are maintained by IgG-recycling neonatal Fc-receptor (FcRn). To assess the impact of FcRn antagonism by efgartigimod on pemphigus-related immunological parameters, Maho-Vaillant et al. examined pemphigus patients during and after treatment with efgartigimod in combination with prednisolone. The treatment resulted in reduction of both total IgG and autoreactive IgG antibody levels. In several patients, autoreactive antibody levels remained low after stopping the efgartigimod treatment.
Data collection Patients' follow-up lasted one year after CABM. At 12 months, a telephone call was made by a trained researcher to ask patients about their health status and subjective HRQOL. When it was not possible to interview the patients directly, interviews were addressed to 1)patient's proxies and 2)general practitioner. In case of non-response, the phone call was repeated 3 times in a period of 3 weeks; in case of failure after 3 phone call attempts, vital status was obtained using the French Epidemiology Centre on Medical Causes of Death (CepiDc) database. Data collected at hospitalization time. During the initial meningitis hospitalization, background characteristics, health status and clinical course were recorded electronically in the case report form. The presence of a pre-existing hearing impairment and headache were also collected at the time of hospitalization.
Data collected one year after CABM. At one year after CABM, disability outcome was assessed according to the GOS in its French version  [18]. We considered GOS scores related to vegetative state, severe disability and moderate disability (scores from 2 to 4 in the initial scale) as unfavourable disability outcomes and a score of 5, corresponding to a good recovery, as a favourable outcome  [1]. Patients were also asked about eventual incident hearing disorders at 12 months from meningitis. Thus, hearing impairment has been grouped into 3 categories: 1) no hearing impairment, 2)hearing impairment prior to meningitis, 3)onset of hearing impairment since meningitis. A reassessment of eventual headaches at 12 months post-CABM was also performed to detect onset of headaches since meningitis. Thus, headache were grouped into 2 categories: 1)no headache, disappearance of headaches at 12 months, constant or decreasing intensity from before meningitis to 12 months, 2)onset of headaches at 12 months or worsening intensity at 12 months.
We selected variables associated with outcome variables at a threshold of 20% (p<0. 20) for multivariate analysis, we also included in final regression analysis potential confounding variables (mainly sociodemographic variables). To analyze the relationship of sociodemographic factors, medical data (medical background and CABM clinical course) and CABM impairments at 12 months (GOS, headache, hearing impairment) on the four WHOQOL-Bref domains, hierarchical multivariate linear regression analyses were performed. We chose to use the linear score, but we could have used a threshold as used in some works. However, to our knowledge, there is no validated threshold for identifying people with impaired QOL when using the WHOQOL scale. For each independent variable of the model, unstandardized coefficients with their associated p-value were presented.
Determination coefficients (R 2 ) showing the explained difference in variance of QOL's domains explained by each group of associated variables was presented, as well as statistical significance of the R 2 improvement with an analysis of variance (ANOVA). Linear regression assumptions were checked, as well as multicolinearity issues. The level of significance for the multivariate model and ANOVA was set at the 5% p-value threshold. Analyses were performed by using RStudio 1. 2. 5033 software  [21]. Ethics and regulatory issues. This study was registered at clinicaltrials. gov (identifier: NCT01730690) and received ethics approval by the "Comitede Protection des Personnes Ile de France CPP 4" (IRB 00003835) (2012-16NI), and the "Commission Nationale de l'Informatique et des Libertes" (CNIL) (EGY/FLR/AR128794).
Baseline and outcome characteristics A total of 533 CABM patients were included in the study, 94 did not survive at 12 months. Among the 439 survivors, 284 patients (i. e. our study population) answered the questionnaire at 12-month follow-up (Fig 1 ); 89. 5% (248/277) of patients answered the questionnaire by themselves, for 8. 3% (23/277) of patients, data were obtained through proxies or general practitioners, and for 2. 2% (6/277), patients were helped by a proxy to answer. Male gender (p = 0. 048), excessive alcoholic consumption (p = 0. 028), and unemployed people (p = 0. 044) at inclusion were significantly less likely to be represented in the 284 patients who were successfully contacted for this study (data not shown). Among   1 ). At 12-month follow-up, 31% (86/277) of participants had an unfavourable disability outcome (GOS score <5), 21.
Strengths and limitations We identified several limitations in our study. First, we collected data related to QOL only at 12 months. Then we did not have data regarding QOL at baseline, preventing us from making an intra-subject comparison between baseline and 12 months. It might also be interesting to have a longer-term follow-up of CABM patients to have more information on the support to be recommended. Second, since the findings were based on self-report measures collected by phone, it may have introduced a response bias, social desirability bias, even though questionnaires were anonymous and standardized. Moreover, questionnaires could be answered by proxies or by general practitioners that may have introduced a measurement bias, but fortunately this only concerns very few patients. Regarding our QOL models, except for physical health, variables included in models explain a relatively small proportion of the variance in QOL.
Acknowledgments COMBAT STUDY GROUP Principal investigator: Xavier DUVAL Steering Committee:  Bruno HOEN ,  Bruno MOURVILLIER ,  Marie-Ce  ´cile  PLOY ,  Sarah TUBIANA ,  Emmanuelle VARON. Scientific  committee: steering committee and the following members Francois CARON,  Pierre-Edouard BOLLAERT ,  Olivier GAILLOT ,  Muhamed-Kheir TAHA ,  Claire POYART ,  Stephane BONACORSI , Francois VANDENESCH,  Emmanuelle CAMBAU ,  Marc LECUIT ,  Alain GRAVET ,  Bruno FRACHET ,  Thomas DEBROUCKER ,  Daniel LEVY BRUHL ,  Francois RAFFI ,  Marie PREAU.
Method: We conducted a prospective cohort study during the 2017-2018 seasonal influenza epidemic, on the GrippeNet. fr electronic platform, which allows the collection of epidemiological crowdsourced data on ILI, directly from the French general population. The immunocompromised population were adults treated with systemic corticosteroids, immunosuppressants, and/or biologics for an autoimmune or chronic inflammatory disease, recruited directly on GrippeNet. fr and also among patients of the departments of a single university hospital that were asked to incorporate GrippeNet. fr. The general population consisted of adults reporting none of the above treatments or diseases participating in GrippeNet. fr. The incidence of ILI was estimated on a weekly basis and compared between the immunocompromised population and the general population, during the seasonal influenza epidemic.
| METHODS We conducted a crowdsourced cohort study, based on the use of GrippeNet. fr (https://www. grippenet. fr/), a French online influenza surveillance system integrated into a larger European platform (called InfluenzaNet), running since 2012. 16 GrippeNet. fr participants are volunteers recruited from the general French population through communication actions (Internet, radio, television, etc. ). Individuals register directly on the GrippeNet. fr website with an e-mail address. This electronic platform allows the collection of epidemiological data on ILI directly from the population each winter period. This study was conducted during the 2017-2018 GrippeNet. fr season, spanning from November 22, 2017, to April 29, 2018.
| Data collection After registration on the GrippeNet. fr platform, an inclusion questionnaire was sent to the participants, documenting the following parameters: age, gender, height and weight, level of education, living area, household composition, comorbidities, and influenza vaccination status (according to the national French recommendations, an influenza vaccination voucher, allowing free vaccination, is sent to individuals with at least one of the following characteristics: age ≥65 years, some chronic underlying diseases including autoimmune or chronic inflammatory diseases on immunosuppressive therapy). Once the inclusion survey was filled, a reminder e-mail was sent each week to all participants, from November 2017 to April 2018, asking them to complete a weekly questionnaire and informing them on influenza trends throughout the season.
| Data analyses Demographic and clinical characteristics were described in both the immunocompromised and the general populations. The two cohorts were compared using the Fisher test or the chi-squared test, with an alpha risk of 5%. A calculation power was computed in order to determine the minimum number of individuals needed to detect a significant difference of 5%, using a one-sided test. Since about 28% of GrippeNet. fr participants reports an ILI episode each season,  17  it would be necessary to include at least 52 immunocompromised patients, if we assume that they are twice as likely to have an ILI compared to the general population.
Data from the French Sentinelles network (www. sentiweb. fr) were used to identify the 2017-2018 influenza seasonal epidemic period. 19 e Sentinelles network conducts primary care ILI surveillance, thanks to data collected from GPs consultations. It is a referral network for the detection of winter influenza epidemics and has been previously used as a validation tool for GrippeNet. fr incidence estimations. 18, 19.