dataesr/scientific-paragraphs-categorization huggingface dataset:
Another application of convolutional neural networks is exhibited in  [175]  for the accurate estimation of the heat generation rate and voltage distribution of Li-ion batteries in the context of EVs. As indicated in  [176] , heat generation rate estimation is a very important factor for accurate and timely decision-making within the framework of effective BMS of high-performance EVs, where a novel physics-informed neural network is employed and validated in a diverse range of driving conditions. The performance and scalability of deep models is, however, dependent on the diversity and quality of the training dataset, which is the major shortcoming beside the computational burden associated with the training phase. Distinctly, the data-driven models can be integrated with classical electrochemical perceptions; some examples are presented in the recent literature where data-driven electrothermal models are proposed with the aim of estimating battery degradation, modeling SoH, and predicting the effect of temperature on battery performance.
A recent retrospective analysis of a French nationwide hospital database estimated the incidence of newly diagnosed iCCA as 1,825 patients per year (3650 new cases between 2014 and 2015)  [23]. The study investigators noted this was higher than the incidence of iCCA recorded in earlier French registry studies  [24]. As BTC is generally diagnosed at an advanced stage, with limited therapeutic options available, it is associated with a poor prognosis. The ENSCCA registry, a multicenter observational study of 2234 patients with a histologically proven diagnosis of CCA between 2010 and 2019 in 26 hospitals and 11 European countries (iCCA: 1243; pCCA: 592; dCCA: 399), showed that at diagnosis, 42. 2% of patients had local disease, 29. 4% had locally advanced disease, and 28. 4% had metastatic disease  [25].
An ongoing French phase 2 trial (GEMOXIA-02; NCT03364530) is evaluating HAI gemcitabine plus oxaliplatin in patients with iCCA who failed prior first-line systemic chemotherapy. A US phase 2 trial (NCT04251715) is currently recruiting patients with liver-dominant, unresectable iCCA to investigate the efficacy and safety of induction systemic chemotherapy with modified FOLFIRINOX (mFOLFIRINOX; oxaliplatin, irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV)), followed by HAI with floxuridine and dexamethasone given concurrently with systemic modified FOLFIRI (irinotecan, 5-FU, and LV). Other loco-regional treatments include external beam radiation therapy (EBRT), including stereotactic body radiotherapy, which delivers high-dose radiation beams to a tumor with high precision while limiting toxicity to surrounding tissue  [49].
8 months and 12. 5 months, respectively  [68]. In a US study, cisplatin, gemcitabine, and nanoparticle albuminbound-paclitaxel provided an ORR of 45%, a median PFS of 11. 8 months, and a median OS of 19. 2 months (95% CI: 13. 2 to not estimable)  [62]. This regimen is currently being compared with CisGem in the US SWOG-1815 phase 3 study (NCT03768414). GEMOX was developed in France and has historically been the preferred regimen in our country for the treatment Table  1  Selected trials investigating therapies for first-line use in patients with advanced biliary tract cancers 5-FU 5-fluorouracil, CAPOX capecitabine + oxaliplatin, CI confidence interval, CisGem cisplatin + gemcitabine, ECOG PS Eastern Cooperative Oncology group performance status, GBC gallbladder cancer, GEMOX gemcitabine + oxaliplatin, HR hazard ratio, LV leucovorin, mFOL-FIRINOX oxaliplatin irinotecan and infusional 5-FU, m median, mo month, nal-IRI nanoliposomal irinotecan, ORR objective response rate, OS overall survival, PFS progression-free survival, R randomized, y year a The GERCOR study investigated first-, second-and third-line use; however, only group A patients received only first-line use and results presented in the paper are not separated out by treatment stage, hence only results for Group A are presented here b Included patients with GBC only of advanced BTC after the results of a phase 2 study  [56] ; however, CisGem is increasingly used in routine practice  [60, [69] [70] [71] [72] [73].
Second-Line and The NIFTY results suggest that the Nal-IRI-5-FU-LV regimen is a promising second-line treatment option; however, these findings were not confirmed in a Western population. NALIRICC (NCT03043547) was a randomized phase 2 study that compared the efficacy and safety of Nal-IRI-5-FU-LV with that of 5-FU-LV in German patients with metastatic BTC who had progressed after first-line gemcitabine-based therapy  [78]. The results of this study (presented at the 2022 ESMO conference) showed that, despite an improved ORR in the Nal-IRI-5-FU-LV arm (14. 3% vs. 3. 9%), there was no difference in median PFS (the primary endpoint) between patients receiving Nal-IRI-5-FU-LV and those receiving 5-FU-LV (2. 8 vs. 2. 3 months). Moreover, median OS tended to be longer in the group receiving 5-FU-LV than in those receiving Nal-IRI-5-FU-LV (8.
7%, DCR was 82. 5%, median PFS was 8. 9 months, and median OS was 20 months, with 12-month PFS and OS rates of 35. 4% and 73. 1%, respectively  [108]. Futibatinib had a tolerable safety profile, with hyperphosphatemia being the most common adverse event (85%). Another FGFR inhibitor, erdafitinib, is currently under investigation in a phase 2a study to assess its efficacy and safety in Asian patients with advanced CCA who have FGFR alterations  [109]. Interim findings showed, in addition to an acceptable safety profile, six partial responses and four stable disease responses in the 12 evaluable patients treated with erdafitinib (ORR of 50% and DCR of 83. 3%). Of the ten patients who were FGFR-positive, the ORR was 60% and the DCR was 100%. Several ongoing phase 3 studies are comparing FGFR inhibition with pemigatinib (FIGHT-302; NCT03656536), infigratinib (PROOF; NCT03773302), or futibatinib (FOENIX-CCA3; NCT04093362) to CisGem as first-line therapy for patients with advanced iCCA harboring FGFR2 rearrangements.
Of the 34 patients enrolled, ten patients had a partial response and 17 had stable disease, to give an ORR (primary study endpoint) of 29. 4% (95% CI: 16. 7-46. 3) and a DCR of 79. 4% (95% CI: 62. 9-89. 9). Median PFS was 5. 1 (95% CI: 3. 6-6. 7) months and median OS was 10. 7 (95% CI: 7. 9-not reached) months. Zanidatamab is a bispecific HER2-targeted antibody that is accessible in France via an early access program. A phase 1 study, investigating the safety and preliminary efficacy of zanidatamab in BTC patients with centrally confirmed HER2 overexpression has demonstrated acceptable tolerability and promising and durable anti-tumor activity with this agent  [129]. In this non-randomized, multicenter study, eight of the 17 patients evaluable for response had a response (ORR: 47%; 95% CI: 23-72); further randomized clinical trials are ongoing in this population (NCT04466891).
BRAF V600E Mutation The prevalence of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in patients with BTC is relatively low, with the vast majority being BRAFV600E (~ 3%)  [133]. The combination of dabrafenib (a BRAF inhibitor) and trametinib (a mitogen-activated protein kinase (MEK) inhibitor) is under investigation in the Rare Oncology Agnostic Research (ROAR; NCT02034110) basket trial as a potential regimen for patients with BRAFV600E-mutated, advanced BTC. This is a phase 2, open-label, single-arm, multicenter trial. An investigator-assessed objective response was observed in 22 of the 43 evaluable patients to date, with an ORR of 51% (95% CI: 36-67%)  [134]. Of note, these results support "classical" BRAF therapeutic manipulation in BRAFV600E-mutated BTC, i. e. , BRAF inhibition potentiated by downstream MEK inhibition without the need for negative feedback loop inhibition via an epidermal growth factor receptor inhibitor such as in advanced colorectal cancer.
This rating supports the use of targeted therapy in this group, albeit without the same level of evidence as ivosidenib. Other rankings for less common mutations include MSI-H and NTRK (both with a rating of IC), as well as BRAF, which has a ranking of IIB. Certain genomic alterations, such as HER2, were not listed, but could be now considered as IIB due to specific trial data  [127]. This highlights the importance of genetic sequencing of tumor samples, which is recommended by the French and ESMO guidelines  [42, 55, 120] , to identify patients who may benefit from targeted therapy, to screen patients for inclusion in clinical trials, and to further drug research and capture valuable data. An improved understanding of genetic alterations and their possible associations will lead to better treatments.
Single-arm studies investigating therapies for iCCA include the MATCH Screening trial (NCT02465060), which is investigating the multi-targeted receptor tyrosine kinase inhibitor sunitinib, among other targeted therapies, as a possible treatment for patients with advanced, refractory solid tumors, including iCCA. Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations occur with widely varying frequencies among solid cancers from 0% to up to 90% of pancreatic cancers, but only a minority are KRAS G12C mutations. In the phase 2 KRYSTAL-1 trial (NCT05162443), four (50%) of the eight pretreated patients with BTC experienced a partial response with adagrasib, a KRAS G12C-selective inhibitor  [143]. Enrollment in this study continues, and an early access program has been initiated in patient populations with KRAS G12C-mutant solid tumors.
9% of patients received adjuvant therapy. Interestingly, the proportion of patients receiving BSC decreased between 1976 and 2005, and the proportion of patients receiving palliative chemo- therapy and/or radiotherapy, as well as curative-intent resec- tion, increased over this period [7]. However, this shift has somewhat plateaued more recently, as attested by the above- mentioned French nation-wide hospital database study of 3650 newly diagnosed iCCA cases (assessed between 2014 and 2015), in which 11. 2% of patients underwent surgery, 23. 8% received chemotherapy, and 65. 0% received BSC [23]. Patient care was mainly provided by general hospitals (59. 8%), rather than university hospitals (15. 0%) and private (19. 2%) or cancer centers (6. 0%). In all, 28. 4% of patients were admitted via the emergency room.
CisGem for patients with 300 a NCT03773302 advanced CCA with FGFR2 gene fusions/trans- locations FIGHT-302 3 Pemigatinib FGFR Pemigatinib vs. CisGem for patients with 432 NCT03656536 advanced CCA with FGFR2 rearrangements ZWI-ZW25-201 2/3 Zanidatamab HER2 Zanidatamab + standard first-line combina- 362 NCT03929666 tion chemotherapy for patients with advanced HER2-expressing gastrointestinal cancers including BTC a Estimated enrollment b Trial prematurely stopped for commercial reasons.
2021 [168] mumab with or without paclitaxel NCT04720131 2 39 Camrelizumab + apatinib + PD-L1 + multi-kinase BTC NCT04720131 capecitabine NCT03092895 2 152 SHR-1210 + apatinib vs. PD-L1 + multi-kinase Primary liver cancer or NCT03092895 FOLFOX or GemOx BTC BTC biliary tract cancer, CCA cholangiocarcinoma, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, FOLFOX leucovorin + 5-fluorouracil + oxaliplatin, GemOx, gemcitabine + oxaliplatin, HDAC1/3 histone deacetylases 1/3, HIF-2α hypoxia inducible factor-like factor 2α, PD-1, programmed cell death protein 1, PD-L1 programmed cell death ligand 1, R randomized, TGF-βR transforming growth factor beta receptor.
Statistical analyses were conducted to evaluate the difference between ASD patients with and without respiratory complications using SPSS version 28. Chi-square and Student's T-tests for categorical and continuous variables, respectively. Odds ratios were calculated to compare the risk factors in these groups. Results: 171 adult patients with ASD with operative management of acute cervical fractures were included. Four patients did not meet inclusion criteria. 12. 3% were intubated on scene, 9. 9% in the ED-ICU, and 77. 8% in the operative room. Intubation technique used was 18. 1% direct laryngoscopy, 40. 9% videolaryngoscopy, 28. 1% fiberoptic, and other 12. 9%. A total of 70 patients had 86 respiratory complications including: 15% with pneumonia, 19% with respiratory failure/distress, 8% tracheostomy placement, 4% with pneumothorax, and 3.
Strains and Culture Conditions Two different parental strains were used in this study: - The Scedosporium apiospermum wild-type strain deposited at the BCCM/IHEM cult collection (Brussels, Belgium) under the accession number IHEM 14462 (WT 144 was isolated in 1998 from a sputum sample of a CF patient. The genome of this str has been sequenced and annotated  [30] ; -A non-homologous end joining-deficient strain (ΔKU70) previously obtained fr the WT 14462 strain  [33]. All strains were conserved frozen at -80 °C and cultured at 37 °C. Fungi were r tinely maintained by passage on supplemented potato dextrose agar plus 0. 5% chlora phenicol supplemented with phleomycin (20 µ g/mL) for the culture of the ΔKU70 stra Hygromycin B (50 µ g/mL) was also added to the culture medium of the PIG1-disrup strains to maintain the selection pressure.
Strains and Culture Conditions Two different parental strains were used in this study: - The Scedosporium apiospermum wild-type strain deposited at the BCCM/IHEM culture collection (Brussels, Belgium) under the accession number IHEM 14462 (WT 14462) was isolated in 1998 from a sputum sample of a CF patient. The genome of this strain has been sequenced and annotated  [30] ; -A non-homologous end joining-deficient strain (∆KU70) previously obtained from the WT 14462 strain  [33]. All strains were conserved frozen at -80 • C and cultured at 37 • C. Fungi were routinely maintained by passage on supplemented potato dextrose agar plus 0. 5% chloramphenicol supplemented with phleomycin (20 µg/mL) for the culture of the ∆KU70 strains. Hygromycin B (50 µg/mL) was also added to the culture medium of the PIG1-disrupted strains to maintain the selection pressure.
Directional libraries were prepared from rRNA-depleted RNA using the TruSeq Stranded mRNA sample Preparation Kit following the manufacturer's instructions (Illumina, Evry-Courcouronnes, France). Libraries were checked for quality on Bioanalyser DNA chips (Agilent, Les Ulis, France) and quantified using the fluorescent-based quantification Qubit dsDNA HS Assay Kit. RNA sequencing was performed on the Illumina NextSeq 500 platform using a High Output Kit (75 cycles). RNA-seq analysis was performed using Sequana 0. 12. 7  [40]. In particular, we used the RNA-seq pipeline 0. 15. 0 (https://github. com/sequana/sequana_rnaseq) built on top of Snakemake 6. 7. 0  [41]. Reads were trimmed from adapters using fastp 0. 20. 1  [42]  and mapped to the S. apiospermum reference genome (GCF_000732125. 1) using STAR 2.
Additionally, Interproscan (https://www. ebi. ac. uk/, accessed on 1 April 2022) was used for the functional analysis of proteins, classifying them into families and predicting domains based on several databases, including the Pfam, CDD, and Panther databases. For quantitative real-time PCR analysis, RNA was reverse transcribed to cDNA using a high-capacity cDNA reverse transcription kit (Applied Biosystems, Illkirch-Graffenstaden, France) according to the manufacturer's instructions. Quantitative PCR amplifications were carried out in duplicate using PowerUp SYBR ® green PCR master mix (Applied Biosystems), 0. 3 µM primers, and 2 µL of cDNA in a final volume of 10 µL, in 384-well optical plates, using a CFX384 OPUS TM real-time PCR detection system (Bio-Rad, Marnesla-Coquette, France). Gene-specific primers (Table  S1 ) were synthesized by Eurogentec.
Cells were stained for viability using the LIVE/DEAD™ Fixable Yellow Dead Cell Stain Kit (ThermoFisher Scientific) for 30 min at RT, protected from light. After washing, Fc receptors were blocked with Fc-R Blocking Reagent (Miltenyi) for 10 min at 4 • C and marked with anti-CD11b/Mac1 (Mouse antihuman, BD horizon) for 15 min at 4 • C, washed twice with PBS-2% SVF, fixed with 4% PFA, and analyzed on a LSRFortessa TM cytometer (BD Biosciences) to quantify the percentage of macrophages with ingested conidia. Data were analyzed using Flowlogic software according to the gating process previously designed to remove dead macrophages and distinguish between the CD11b + /FITC -population (non-infected macrophages) and the double-positive CD11b + /FITC + population (macrophages with adherent and/or ingested conidia)  [47].
Cytokine Assays Primary macrophages were plated in 24-well plates at 10 6 cells/mL and incubated with 10 7 (MOI 10:1) live conidia in complete RPMI for 12 h at 37 • C in 5% CO 2. Supernatants were then collected and immediately stored at -80 • C. Pro-inflammatory cytokines were measured using a 13 plex-bead-based immunoassay LEGENDplex ® multi-analyte flow assay (BioLegend, Paris, France) according to the manufacturer's instructions. Cytokine concentrations were determined using standard curves obtained using recombinant cytokine standards provided in the kit. Samples were analyzed on a LSRFortessa TM cytometer (BD Biosciences) and the data processed using the online platform provided by the kit manufacturer.
Statistical Analysis All experiments were performed in triplicate or quadruplicate at least three times independently. Data are expressed as the mean ± standard error of the mean (SEM). Statistical analysis was performed using GraphPad Prism software (GraphPad Software, Inc. , La Jolla, CA, USA). A one-way analysis of variance Kruskall-Wallis test or a Mann-Whitney test were used to evaluate differences between strains. In all analyses, p-values ≤ 0. 05 were considered statistically significant.
Transcriptomic Analysis of M1 Transformant We next conducted a comparative transcriptomic analysis between the MI strain and its parental ∆KU70 strain to understand the involvement of the transcription factor PIG1 in melanin biosynthesis and the phenotypic characteristics described above, especially relative to the morphogenesis of the S. apiospermum cell wall. Mycelia were harvested from YPDA medium after 30 h of incubation and RNA extracted and purified for transcriptome sequencing. In total, eight biological samples (four biological replicates) were thus sequenced by next-generation sequencing. After a stringent quality check and data cleaning, 9. 4 to 15 million assigned reads were obtained for each sample (Table  S2 ), which were further spliced into 10,919 assembled unigenes. In addition to biostatistical quality controls, RNA-seq based differential gene expression data were further validated by RT-qPCR for eight selected representative genes, resulting in an excellent agreement between the fold change values determined by global sequencing and specific qPCR (Table  2 ).
(c) Cytokine release in culture supernatants from macrophages incubated with conidia for 12 h (MOI 10:1). Concentrations were determined using a 13 plex-bead-based LEGENDplex ® multianalyte flow assay. A non-infected (NI) condition was included in each experiment. Data are from three independent experiments. * p < 0. 05, ** p < 0. 01, *** p < 0. 001 (Kruskall-Wallis test) T: transformant derived from the WT strain; M1 and M2: transformants derived from the ∆KU70 strain. The inflammatory macrophage response to the PIG1-deficient strains was also indirectly evaluated by measuring the level of various pro-inflammatory cytokines released within 12 h post-infection. Although there was a trend toward increasing IL-1β release by M1-and M2-infected macrophages, the IL-18 concentration increased by a factor of 1.
The reduction in conidia survival was calculated relative to control conidia as: 100*((% of live conidia among control conidia-% of live conidia among cell-exposed conidia)/% of live conidia among control conidia). (c) Cytokine release in culture supernatants from macrophages incubated with conidia for 12 h (MOI 10:1). Concentrations were determined using a 13 plex-bead-based LEGENDplex ® multianalyte flow assay. A non-infected (NI) condition was included in each experiment. Data are from three independent experiments. * p < 0. 05, ** p < 0. 01, *** p < 0. 001 (Kruskall-Wallis test) T: transformant derived from the WT strain; M1 and M2: transformants derived from the ΔKU70 strain.
The Fermi Large Area Telescope (LAT) lightcurve repository (LCR) is a publicly available, continually updated library of gamma-ray lightcurves of variable Fermi-LAT sources generated over multiple timescales. The Fermi-LAT LCR aims to provide publication-quality lightcurves binned on timescales of 3, 7, and 30 days for 1525 sources deemed variable in the source catalog of the first 10 yr of Fermi-LAT observations. The repository consists of lightcurves generated through full likelihood analyses that model the sources and the surrounding region, providing fluxes and photon indices for each time bin. The LCR is intended as a resource for the time-domain and multimessenger communities by allowing users to search LAT data quickly to identify correlated variability and flaring emission episodes from gamma-ray sources.
To address this need, we developed the Fermi-LAT Lightcurve Repository (LCR; Kocevski 2021), 75  consisting of a public database of lightcurves for variable Fermi-LAT sources on a variety of timescales. The repository provides publicationquality lightcurves on timescales of 3 days, 7 days (weekly), and 30 days (monthly) for 1525 sources deemed variable in the 4FGL-DR2 catalog  (Ballet et al. 2020). The repository consists of lightcurves generated through full likelihood analyses of the sources and surrounding regions, providing flux and spectral index measurements for each time bin. Hosted at NASA's Fermi Science Support Center (FSSC), the LCR provides users with on-demand access to these lightcurves, which are continually updated as new data become available. The repository is a new resource to the time-domain and multimessenger communities for associating and monitoring LAT sources, in particular facilitating identification of time intervals with high fluence or flux.
This paper is organized as follows. In Section 2 we describe the gamma-ray sources included in the LCR. Section 3 is devoted to the description and discussion of the automated data analysis employed by the repository. We discuss analysis caveats and data usage best practices in Section 4. We briefly summarize and conclude in Section 5. We provide a Quick Guide in the Appendix with the aim to help familiarize users with the LCR data portal.
Note that energy dispersion is neglected in the unbinned analysis mode. This is not expected to impact the quality of the analysis. However, repeating the analysis with a binned likelihood approach would return mostly insignificant differences in the results. For each source and time bin, photons are selected from a circular region of interest (ROI) of radius 12°centered on the location of the target source. The ROIs are analyzed separately. By contrast, for the standard FGL catalogs, fluxes and spectral parameters of multiple sources are extracted from the same ROI. The size of the ROI is conservatively chosen to be as large as the 95% containment radius of the LAT energydependent point-spread function (PSF) at 100 MeV. Additional data selection cuts are imposed to exclude photons associated with regions and periods of known solar flares and gamma-ray bursts (GRBs).