dataesr/scientific-paragraphs-categorization huggingface dataset:
Funding This was supported by  Institut National de la Santé et de la Recherche Médicale (Inserm) ,  Sorbonne Université ,  Fondation Association pour la Recherche sur le Cancer (ARC , n°  PJA 20191209801 ), and the  Center for Interdisciplinary Research in Biology (CIRB)  at the  Collège de France. The light-sheet microscope used in this work was funded by the  Leducq foundation. LL was supported rst by a fellowship from the  French Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation (Doctoral School Physiology Physiopathology & Therapeutics  ( ED394 ),  Sorbonne Université ) and then by a fellowship from " La Ligue Nationale contre le Cancer ". CR was supported by a fellowship from " La Ligue Nationale contre le Cancer ". SA was supported by the " Agence Nationale pour la Recherche ".
4c ). However, in contrast to what we observed in MAPKi-treated cells, the decrease in the intracellular concentration of Glu and Asp that was induced by Gln depletion was associated with an enrichment of the G/C-ending codons (i. e. , GAG and GAC) and not the A/T-ending codons (i. e. , GAA and GAT) (Fig. 4c ). These results suggested that the decrease in amino acid bioavailability is not sufficient to explain codon-selective effects in agreement with previous reports (see Introduction). Since aminoacyl-tRNA synthetases contribute to codon-selective effects, we inspected our RNA-seq datasets and we found that the expression level of several aminoacyl-tRNA synthetases varied in response to MAPKi treatment or in response to Gln depletion. Among these, we focused on the EPRS1 aminoacyl-tRNA synthetase, which loads Glu onto the corresponding tRNAs, because the expression level of EPRS1 was repressed in response to MAPKi but increased in response to Gln depletion, as validated by RT-qPCR (Supplementary Fig.
4c ). To test the potential role of EPRS1 on codon-selective effects, A375 cells were cultured in the absence or presence of Gln and in the absence or presence of EPRS1 (Supplementary Table  1 ). EPRS1 depletion abolished the codon-selective effect of Gln depletion with respect to the enrichment of the GAG codon to the advantage of the GAA codon suggesting that EPRS1 could at least in part participate to the codon-selective effect observed after Gln depletion (Fig. 4d ). We also observed in our datasets that some enzymes that can modulate codon-selective effects by biochemically modifying tRNAs (see Introduction) were differentially expressed in MAPKitreated cells as compared to control cells. Among these, CTU2 caught our attention for three reasons: i) CTU2 expression was decreased in MAPKi-treated cells (Supplementary Fig.
removed using the program MarkDuplicates from picard toolkit version 2. 18. 11 (Picard Toolkit 2019. Broad Institute, GitHub Repository. https://broadinstitute. github. io/picard/) with the parameters VALIDATION_STRINGENCY=LENIENT REMOVE_DUPLICATES=true. Then, the number of mapped reads within each files were recovered using idxstats commands of samtools v1. 11. Each bam file was subsampled, using samtools v1. 11, to have approximately the same number of mapped reads as in the smallest bam file. The command mpileup of the program bcftools v1. 16 was used to produce bcf files using the following options: -I -d 10000 -O b -a AD. The mpileup was only performed on human exonic regions. SNP and unchanging nucleotide positions were next called using the command call from bcftools and the parameters -A -V indels -m -O b.
Limitations This study has a number of limitations. All registry research introduces selection bias and other inherent limitations, including potential issues with data completeness, recruitment-and enrollment strategies, and confounding variables, both known and unknown  29. Specifically, the @neurIST database has unique limitations because of the nature of IA diseases, including underdiagnosis, heterogeneity of presentation and natural history. Indeed, a certain number of patients was excluded from further analysis due to incomplete data. Furthermore, studies reporting on interrater agreement regarding IAs diagnosis report relatively low agreement rates for IA neck diameter, characterization of IA morphology and -multiplicity  39, 40. Data derived from the registry are also likely to be enriched with patients with symptomatic IAs who seek care.
Acknowledgments Data were collected starting in 2006 in the context of the EU project @neurIST and SystemsX. ch initiative AneuX evaluated by the  Swiss National Science Foundation. The data is hosted by the  Swiss Bioinformatics Institute  in the context of the Aneurysm Data Bank. The authors would like to thank  Vitor Mendes Pereira ,  Daniel Rüfenacht  and  Norman Juchler  for helping with data collection, harmonization, and processing.
Funding The author(s) disclosed receipt of the following financial support for the research, and/or publication of this article: T. W. was supported by the  OPO Foundation , the  Swiss Cancer Research foundation  ( KFS-3880-02-2016-R ,  KFS-4758-02-2019-R ), the  Stiftung zur Krebsbekämpfung , the  Kurt und Senta Herrmann Foundation, Forschungskredit of the University of Zurich , the  Zurich Cancer League , the  Theodor und Ida Herzog Egli Foundation , the  Novartis Foundation for Medical-Biological Research  and the  HOPE Foundation. P. M. was supported by the  Canadian Institutes of Health Research. P. B. and B. R. K. were supported by grants from the  Swiss SystemsX. ch initiative  evaluated by the  Swiss National Science Foundation (AneuX) , a  CONFIRM grant  of the  Fondation privée des HUG , the  Swiss Heart Foundation  and the  Fondation Carlos et Elsie De Reuter.
Sample analysis a. Assessment of differences due to incomplete datasets 79 of 228 included participants did not ll the T2 assessment, representing a rate of 34. 7% of subjects with incomplete datasets. It's worthwhile to note that almost all the participants who did not ful ll the questionnaires nevertheless completed the program (missing data are mainly due to organizational errors in the recall strategies to obtain the questionnaires from the participants). At baseline, these subjects did not differ signi cantly from the 149 subjects with complete datasets in terms of participant and loved one gender (X²=2. 39, p = 0. 12; N = 228, X²=0. 86 p = 0. 35 respectively), duration of symptoms (F = 0. 11 p = 0. 74), age of the caregiver (F = 3. 68, p = 0. 06) and in terms of burden (IEQ : F = 2. 03, p = 0.
Acknowledgements: We would like to express our gratitude to  Marie-Paule de Valdivia  ( LCSW, MBA ) for the training of the leaders of the program and for her long-standing support to the implementation of the program. We also would like to thank all  Family Connections®  leaders for their commitment and all the participants for their valuable feedbacks. We would like to thank the  Family Connections study group  for their implication in the development of the project. The Family Connections study group:  Mario Speranza ,  Sophie Bluteau-Blin ,  Véronique Brand-Arpon ,  Olivier Clément ,  Satchel Cohen ,  Karen Dieben ,  Déborah Ducasse ,  Amaury Durpoix ,  Clementine Estric ,.
Consent for publication: Not applicable Competing interests: The authors declare that they have no competing interests Funding: No funding was provided for the realization of this study Authors' contributions: SC wrote the nal manuscript; VS, MS, SC and NP elaborated the study design; MS and SC conducted statistical analysis and interpreted the results. HT and UK reviewed the statistical procedures. UK contributed to the elaboration of the conceptual framework and the discussion of the results. All authors read and approved the nal manuscript. Florence Guenot, Emmanuelle Jeker, Stephane Kolly, Uëli Kramer, Emilie Olié, Nader Perroud, Virginie Salamin, Hervé Tissot, Julie Vitrolles, Luisa Weiner,  Sebastien Weibel.
The relationship between MB and hypoxia is poorly known. The four different subgroups  [3] [4] [5] [6]  of medulloblastomas are not similarly located in the cerebellum and access to oxygen is different between the four groups of MB (Fig. 1a ). To assess the impact that this oxygen heterogeneity might have on the different MB groups, we analyzed the expression of 19 HIF-1 target genes (Tf, Ho1, Ccl2, Oas2, Lox, Igf2, Slc2a1, Epo, Il2ra, Gpnmb, bFgf, Ak3, Hk1, Myl3, Cxcl16, Igfbp2, Murc, Des and Ccl5) from the Affymetrix Human Gene 1. 1 ST array profiling of 763 primary medulloblastoma samples (GSE85217)  7. Group 4, SHH Group and Wnt Group MBs express these genes most strongly compared to Group 3 MB (Fig. 1b ). From these data and in order to understand the molecular mechanisms that govern these differences, we focused on the Group 3 MB, the group with a very poor prognosis, using HDMB-03 and D-458 cell lines, and the Non-Group 3 MB, with an intermediate prognosis, using DAOY and ONS-76 cell lines.
While Ard1 expression was repressed in Hx in DAOY, ONS-76 and HDMB-03 cells, again, we found that ARD1 expression, already very high in Nx, was not altered in Hx in D-458 cells (Fig. 2h ). However, invalidation of Ard1 by siRNA did not stabilize HIF-1 (data not shown). Interestingly, significantly higher expressions of Egln1, Egln3 and Naa10 were detected in Group 3 MB than in the Non-Group 3 using the R2: Genomics analysis and visualization platform (Suppl. Figure  8h-i ). Egln3 and Egln1 mRNA expression were also found to be significantly upregulated using the GSE85217 microarray (Suppl. Figure  8k ). Taken together, these results strongly suggest that Group 3 MB cells have nonfunctional HIF-1 resulting from post-translational modifications of HIF-1, methylation in the HDMB-03 cells and high destabilization in D-458 cells, and thus that the response of Group 3 MB cells to the hypoxic microenvironment relies essentially on HIF-2.
However, HIF-2 is a formidable player in maintaining stem cells in an undifferentiated state via genes like Oct4, Sox and Nanog  17, 18. In physioxia or hypoxia where Oct4 would be induced, the cells would then have a strong stem cell potential even though these cells would be "adult". Since hypoxia occurs as early as the embryonic state  19  , we can propose that HIF-2 may be the primary origin of oncogenic evolution of Group 3 MB. If the uniqueness of HIF-2 is an extraordinary advantage for the Group 3 MB tumor cell, then it becomes a perfect target to block MB tumor growth. We used PT2385, which is in phase II for ccRCC (https://clinicaltrials. gov/ct2/show/NCT03108066) but also for glioblastoma (https://clinicaltrials. gov/ct2/show/NCT03216499). Very promising results have been obtained, suggesting similar results would be possible for Group 3 MB patients.
Other more efficient inhibitors identified recently, such as PT2399 or PT2977, could certainly provide stronger therapeutic responses. HIF-2 inhibition could then not only partially block metabolism but also affect particular stem cells. However, unlike ccRCC, it was the combination of PT2385 with Metf that had a very strong impact on cell growth and death. Here we have proven the concept that the best targeted therapy comes from a better molecular knowledge. It seems clear that this "hypoxic" approach will reveal other potential therapeutic targets and allow new drug combinations to be found, to provide the most specific and personalized therapeutic response possible. (b) Heatmap of the RNA expression of genes from GSE85217 with 763 primary samples from MB patients from Group 3, Group 4, SHH Group and WNT Group MB  7.
Single Cell Data Availability The RNA-Seq data discussed in B. Manoranjan's publication (PMID: 32859895) have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE131473. The scRNA-seq data have been deposited in CReSCENT (https://crescent. cloud/; CRES-P22) and processed data is uploaded on the Broad Institute Single Cell Portal https://singlecell. broadinstitute. org/single_cell/study/SCP840.
Acknowledgments This work was supported by a grant from  La Fondation Flavien , the  Fondation ARC pour la recherche sur le Cancer and La Ligue contre le Cancer. Y. Guo  is supported by the  Chinese Ministry of Research. I. Ben-Sahra  is supported by the  NIH   R00-CA194192  and  LAM Foundation  grants. F. Bost  and  N. M. Mazure  are CNRS investigators. Metabolomics services were performed by the  Metabolomics Core Facility at Robert H. Lurie Comprehensive Cancer Center of Northwestern University  and the  Beth Israel Deaconess Medical Center Mass Spectrometry Facility of Harvard Medical School. Armenise ,  AIRC , CARITRO and EMBO to L. T. We sincerely thank the  GIS-IBISA multi-sites platform Microscopy Imagery Côte d'Azur (MICA) , and particularly the imaging site of C3M (INSERM U1065) supported by  INSERM ,  Cancéropôle PACA ,  Conseil Régional, Conseil Départemental , and  IBISA.
Similarly, although RV global longitudinal strain (GLS) assessed by 2D speckle tracking echocardiography (STE) is more sensitive than conventional parameters in detecting changes in RV function  28  , it only reflects RV global longitudinal systolic function  29. Thus, 3D echocardiography and cardiac magnetic resonance (CMR) can provide additional high-quality data to assess the RV in TOF. In 2008, Sheehan et al. published the first threedimensional (3D) shape analysis by CMR in patients with rTOF and chronic PR. They showed that rTOF patients had larger RV cross-sectional areas, a more rectangular RV shape, a broader apex, and basal bulging compared to controls. When analysing the contribution of different segments to the total RV surface, they found that the septum occupied a smaller fraction of the total RV surface, suggesting that free wall dilatation contributed more to global RV dilatation than the septum  30.
Introduction The current standard of care for first-line (1L) treatment of patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) is up to six cycles of platinumbased chemotherapy  [1] [2] [3]. Given the cumulative toxicities associated with platinum-based chemotherapy and/or decline in performance status, a substantial proportion of patients are unable to receive six cycles and treatment with more than six cycles is generally not recommended  [1] [2] [3] [4]. The optimal duration of 1L chemotherapy is unknown and has not been evaluated in a prospective trial. However, a retrospective international database study reported no significant difference in overall survival (OS) between subgroups of patients with advanced UC who received three to five cycles (median, four cycles) and those who received six to nine cycles (median, six cycles) of 1L chemotherapy  [4].
Overall, the safety profile of avelumab 1L maintenance was similar across all subgroups examined and was consistent with the results from previous avelumab monotherapy studies  [10]. HRs for OS with avelumab 1L maintenance versus BSC alone across all subgroups defined by the duration of 1L chemotherapy (0. 63-0. 79) and in patients who had received four or six cycles of chemotherapy (0. 69 and 0. 66, respectively) were generally consistent with the HR in the overall population (0. 69)  [7]. The HR in patients who received five cycles of chemotherapy was 0. 98; how-ever, this subgroup was small (16% of patients). Additionally, the number of cycles was estimated from the data derived from the records of 1L chemotherapy; hence, the actual number of cycles might differ slightly from the estimates, and caution is needed when interpreting these findings.
Nonetheless, results from analyses by both the duration of prior chemotherapy and the estimated number   of cycles suggest that avelumab 1L maintenance can be administered after four to six cycles of 1L chemotherapy depending on individual patient needs. This trial did not assess the outcomes after fewer than four or more than six cycles of 1L chemotherapy. Other observational studies of avelumab 1L maintenance treatment in a real-world setting are ongoing, for example, in the USA, France, and Germany (PATRIOT II  [14] , AVENANCE [15], and AVENUE [16], respectively), which may provide relevant insights. In addition, a randomized, phase 2 trial (DISCUS; EudraCT 2021-001975-17) is comparing the impact on quality of life of three versus six cycles of 1L platinum-based chemotherapy followed by avelumab maintenance.
10  Despite this, WHOcc has been able to secure a number of isolates from the country that have been subsequently characterised. Recent data from the country has indicated an increase in suspected meningitis across three governorates in the region. 11  Established meningitis reporting is in place in the Republic of Turkiye (Turkey), Qatar, the Kingdom of Saudi Arabia (KSA), Lebanon, Cyprus, Oman, Jordan, Iraq, Bahrain, Kuwait, Palestine, and the United Arab Emirates (UAE). Cases are typically reported to a national center for disease control (CDC) or Government ministry. 12  The robustness of such reporting mechanisms vary and their completeness is not evaluated. For instance, in Iraq and Lebanon, a paper-based notification system is used; these case report forms will include information on patient demographic data, clinical presentation, vaccination status, laboratory confirmation, and clinical outcomes.
Qatar have made progress in moving away from a paperbased report system, with the introduction of the Surveillance & Vaccine Electronic System (SAVES) in 2020. 13  In establishing an electronic-based notification network, real-time laboratory notifications of confirmed cases have increased. In the UAE, any suspected case of bacterial meningitis is reported to the relevant Emirates' Department of Health, as well as the national Ministry of Health and Prevention. Public health specialists from the Emirates' local CDC will conduct a face-to-face investigation for each case, collating information on clinical presentation, potential source of infection, vaccination status, and disease outcome among other data. The country also has a dedicated national antimicrobial resistance surveillance database.
More recent data has indicated a shift in the age distribution of IMD cases in KSA. 15  During the period 2012-2021, 48 IMD cases were reported to the MoH, with 33% occurring in those < 5 years and 33% in those aged between 5 and 14 years. 15  IMD cases have also been reported in Turkiye; a significant proportion of cases were reported in those < 1 year (34. 8%) and those aged between 1 and 4 years (27%) (2015-2018). 25  In a study from 2007 in the UAE, 35% of bacterial meningitis cases reported in Al-Ain were caused by N. meningitidis. 26  Of these cases, the majority were recorded in the 21-30 (10 cases) and 31-40 age groups (5 cases). IMD case numbers peaked in 2001 (during the period 2000-2005). In a separate analysis, 48 IMD cases were reported to the MoH in UAE in 2008, with 79% occurring in those aged 15-44 years.
Acknowledgements Medical writing support for the development of this manuscript, under the direction of the authors, was provided by  Matthew Gunther  of  Ashfield MedComms , an  Inizio company. Medical writing support was funded by  Sanofi Vaccines. The authors would like to thank  Naif K. Alharbi  and  Pasi Penttinen  from the  Gulf Centres for Disease Prevention and Control  for their contributions to the GMI meeting and their insights. All authors discussed and agreed to the objectives of this manuscript and contributed throughout its production. All authors read and approved the final manuscript.
Xilian Bai performs contract research on behalf of UKHSA for GSK, PATH, Pfizer and Sanofi Pasteur. Ray Borrow performs contract research on behalf of UKHSA for GSK, PATH, Pfizer and Sanofi Pasteur. Ener Cagri Dinleyici performs contract work for the Eskisehir Osmangazi University funded by GSK, Sanofi Pasteur and Pfizer. Jay Lucidarme performs contract research on behalf of UKHSA for GSK, PATH, Pfizer and Sanofi Pasteur. Marco A. P. Sáfadi reports research grants and personal fees for advisory boards from GSK, Pfizer, and Sanofi. Vinny Smith and Claire Wright work for the MRF that receives grants and/or sponsorship from GSK, PATH, Pfizer, Sanofi, Bill and Melinda Gates Foundation, and Serum Institute of India. M. K. Taha performs contract work for the Institut Pasteur funded by GSK, Pfizer and Sanofi Pasteur.
Diagnostic capacity of VEGF to discriminate different peri-implant conditions with respective diagnostic ranges was assessed using C4. 5 decision trees  [34] , while the diagnostic performance parameters (accuracy, sensitivity and specificity were estimated using logistic regression. Area under ROC curve (AUC) was used for predictive model evaluation. Data analysis was performed using commercial softwares (SPSS v. 25. 0; SPSS Inc. , Chicago, IL, USA; MATLAB, MathWorks, Natick, MA, USA). The present study was reported according to the STROBE guidelines.
Sections were stained with haematoxylin-eosin or IHC using commercially available antibodies for VEGF (1:100, sc-7269, Santa Cruz Biotechnology, USA) and IHC detection kit (DAKO; Dako Dual Endogenous Enzyme Block; EnVision System-HRP; DAB, DakoCytomation, Glostrup, Denmark) following standard diagnostic protocols and manufacturer's instructions. Slides were counterstained with haematoxylin, manually dehydrated, mounted and cover slipped. Sections were examined by an experienced blinded pathologist using bright-field microscopy (BX50 Olympus, Inc, Japan) equipped with imaging system (Q-500 MC; Leica, Wetzlar, Germany). VEGF-positive cells were quantified using NIH ImageJ software (NIH, Bethesda, Maryland; https://imagej. nih. gov/ij/) in aid of IHC profiler plugin  [35]. VEGF was quantified in 4-5 fields/sample (300 × 200 µm) at x40 magnification, values were averaged per sample and expressed as proportion of positive cells.
Phylogenetic analysis Sequences generated during the present study and those from the literature were concatenated to generate a dataset of 55 filarial species and a total of 3695 bp. Each locus was aligned independently with SATe-II  (Liu et al. , 2012). For each gene, the best-fitting substitution model was determined using the corrected version of the Akaike Information Criterion (AICc) in JModelTest v2. 1. 10 analyses  (Guindon and Gascuel, 2003) : TVM+Γ was the best fit for 12S rDNA; TVMef+I+Γ for 18S rDNA; TPM3+I+Γ for 28S rDNA; TIM1+I+Γ for cox1; TN93+I+Γ for hsp70; TN93+I+Γ for myoHC and TPM3uf+Γ for rbp1. To root the trees, two species were included as outgroup: Protospirura muricola Gedoelst, 1916 (Spirurida: Spiruridae) and Filaria latala  Chabaud & Mohammad, 1989 (Spirurida: Filariidae).
Additional molecular analyses We determined partial sequences of the mitochondrial cox1 and 12S rRNA genes of four females (ID nos. M1 and M2 from Johor; G3 and G4 from Selangor). DNA extraction, PCR amplification and sequencing were performed as described previously  (Casiraghi et al. , 2001; Agatsuma et al. , 2005; Uni et al. , 2017). We also cloned the PCR products of the ITS1 region into pGEM-T vectors and determined the sequences of the recombinant plasmid  (Saijuntha et al. , 2018). Phylogenetic trees of the nucleotide sequences of the cox1, 12S rRNA genes and the ITS1 region of M. (Tup. ) dunni were constructed using the maximum-likelihood method in MEGA7 with 1000 bootstrap replicates  (Kumar et al. , 2016). Sequence data were deposited in the GenBank database. The lengths of the sequence datasets used for the analyses were as follows: cox1, 393 bp; 12S rDNA, 304 bp; and ITS1, 866 bp.