dataesr/scientific-paragraphs-categorization huggingface dataset:
Obesity in dogs is associated with a wide diversity of disease types, ranging for example from metabolic such as diabetes mellitus  (26) , to orthopedic  (19) , and cancer  (53) , some of which might impact lifespan. In terms of the relationship between body condition and disease, obesity is likely to be a causative risk factor for many of these conditions e. g. , diabetes, but it can be a consequence of some other diseases such as hyperadrenocorticism and hypothyroidism  (54) (55) (56). Obesity could also be an unrelated comorbidity that exacerbates the severity and/or prognosis of another condition, or contributes to a decision on euthanasia. It is not possible to attribute adiposity in our study as a cause of reduced LE birth , but since the database included both healthy and diseased animals it is feasible that it played an indirect role through disease association.
A further consideration is that we used the median BCS over a pet's medical history in the database to reflect its weight status over life. This approach could lead to misinterpretation in cases where an age-related disease affected BCS. For example, if an animal with a BCS of 5 in the first third of its life contracted a disease in the second third of its life that led to a reduction in BCS to BCS 3, and with disease progression this declined to BCS 1 in the last third of its life, the animal would nevertheless be analyzed in the median BCS 3 category. Less than ideal median BCS (1 and 2) was associated with much lower life expectancy than an ideal or obese median BCS. In adult dogs, underweight is a general signalment for serious illness or a poor prognostic factor for diagnosed disease.
Increasing awareness of obesity and its health implications in pets could also have driven greater proactivity in interventions to treat obesity-associated diseases. Our clinical dataset relied upon owners visiting a veterinarian, and the animal having a recorded BCS. There may be different thresholds of bodyweight loss or bodyweight gain that would prompt owners to seek veterinary advice. Delaying a visit until a dog or cat has reached an extreme BCS will worsen the prognosis for the underlying etiology. The decision of an owner to opt for the euthanasia of their dog or cat might also vary by BCS and thereby impact life expectancy. Pet lifestyle can impact survival for medical and non-medical reasons. An indoor lifestyle is associated with feline obesity at 1 year of age  (66) , and outdoor access poses a greater risk of road traffic accidents  (46).
Strengths and limitations of the study This study benefited from a large dataset of 8. 9 million dogs and 2. 4 million cats, which is more than 10-fold greater than the dataset used to generate life expectancy tables for Japanese dogs (13) and 100-fold greater than the dataset for life expectancy study of dogs in the UK. The database was large enough for a sub-analysis by BCS, and CIs remained modest with the exception of LE birth for cats with BCS 5, and life expectancy for dogs and cats with BCS 5 over the age interval 14-15 years, likely due to the small number of obese animals in these age intervals. Limitations that should be considered include the retrospective nature of the study design, a degree of uncertainty of pet age for dogs and cats acquired as rescued animals or adopted from animal shelters, and the inherent limitations of body condition scoring.
Differences in life expectancies between breeds within body size were not captured. The intent was to maintain accuracy in life expectancy tables while recognizing the large size differences between breeds. As population numbers were low for many of the more than 300 breeds in our dataset, we favored statistical accuracy over breed differences. Parallel analyses of health status, recorded causality of death, or reason for euthanasia were beyond the scope of this study and this limited the interpretation of differences between subpopulations. Most pets that visit Banfield Pet Hospitals have veterinary care as part of an Optimal Wellness Plan, which is a suite of pre-paid services focused on preventive health care, routine diagnostic testing, comprehensive physical examination, and unlimited clinic visits.
Wellness Plans could result in a pet being seen more frequently and having an earlier diagnosis and treatment of chronic conditions; they might also drive a proactive reduction in risk factors for disease and improvement in prognosis for disease at diagnosis. Conversely, the use of medical records results in missed visits by animals never presented to veterinary clinics. A major statistical consideration with databases involving millions of individuals is that tests are often highly significant. A widely used method for assessing the standard error of life expectancy is to use the variance of the conditional probability of death. To address the issue of having such large populations, instead of implementing this method we used Monte Carlo simulations to sample dead populations and recalculated life expectancies 1.
10 6 times. This mitigated the issue, but statistical significances were still high whatever significance level. A complementary strategy would have been to sample the mid-year population in the Monte Carlo simulation. The analyses presented do not extend to estimations of disability free life expectancy, healthy life expectancy or healthy life years lost. A method has been developed for this  (74)  and applied to life expectancy data from dogs in the UK  (15)  and Japan  (13)  for different breeds and cross-breed dogs  (75). The Banfield database provides additional opportunities to explore healthy life expectancy and specific disease-associated life expectancy in future work.
Cross-sectional µCT The right femora with surrounding soft tissue were stored at -20°C after dissection. The soft tissue was removed before imaging the whole bone with a Skyscan 1176 scanner  (Bruker-microCT, Kontich, Belgium). Images were acquired using the following settings: 9 µm isotropic voxel, 0. 5 mm aluminum filter, 50 kV voltage, 500µA current, 1000 ms exposure time, rotation 0. 6 degrees and frame averaging = 1. 3D images were reconstructed with the SkyScan software program NRecon  (Bruker, version 1. 7. 4. 6) , with 20% beam hardening correction, at Gaussian smoothing = 1 (sigma = 0. 5, and support = 3). Bone mineral density (BMD) calibration 2mm -diameter phantoms in pairs with calcium hydroxyapatite concentration of 0. 25 and 0. 75 g/cm 3 were acquired with attenuation coefficient (AC), which were 0.
If data did not follow a normal distribution, and to determine confidence intervals  (Henderson, 2005) , the Bootstrapped ANOVA analysis was performed with the "ANOVA. boot" function, followed by pairwise comparisons with the "wild. boot" function included in the "lmboot" package to present 95% CI and p-values. Data were randomly resampled 1000 times because, given the characteristics of the data, that number of replicates maximized accuracy in the prediction of mean differences, standard error of mean difference, and power  (Pattengale et al. , 2010). The bias-corrected and accelerated confidence interval was used  (Efron, 1987). p-values were followed by Benjamini-Hochberg procedure for multiple comparisons. A nominal p-value of 0. 05 was considered statistical significance. Besides p-values, 95% confidence intervals (95% CI) are reported in the representation of evidence of effect  (Nguyen, 2020).
Acknowledgments The authors thank the staff of  PLEXAN (Platform for Animal Experimentation and Analysis, Medical School, Saint-Etienne, France)  for supervision of animal care and Stansea for providing nacre powder. We gratefully thank  Dr. Luc Malaval  in our group for contributing to the present study with critical comments on the manuscript. We thank also our staff,  Mrs. Stéphanie Mundweiler  for checking the form of manuscript before submission.
Methods Literature search was conducted using the keywords and MeSH terms 'Anchusa strigosa Banks & Sol. '2023, "A. strigosa," AND ("phytochemical content," "pharmacological properties, or activities, or effects, or roles," "anti-inflammatory," "antioxidant," "anticancer," "ethnopharmacology," "traditional uses," "medicinal uses," "antimicrobial," "antibacterial," or "antifungal") in major scientific literature databases such as PubMed, Scopus, ScienceDirect, SciFinder, Medicinal and Aromatic Plants Abstracts, Dr. Duke's Phytochemical and Ethnobotanical Databases, Chemical Abstracts, and Henriette′s Herbal Homepage. Google and Google Scholar were also used for general web searches. The search period covered articles published between 1984 and 2023. The search yielded 23 research articles on A.
In this study, we took advantage of multiple long read sequencing datasets to generate a new female assembly close to chromosome scale and integrate it with genetic maps. This revealed a highly uneven recombination landscape throughout the S. latifolia genome, with peripheral recombination in all chromosomes. Extensive pericentromeric recombination suppression (PRS) in females is particularly pronounced on the X chromosome, where it has likely contributed to evolution of sex chromosomes by facilitating or even causing the expansion of the nonrecombining region on the Y chromosome (NRY). Furthermore, the PRS on the X chromosome significantly affects the patterns of genetic diversity and divergence in the sex-linked genes that have previously been attributed to Y chromosome degeneration.
Materials availability This study did not generate new unique reagents. conditions: FPKM>3, blastp hits with >30% identity and >100 alignment length, containing at least one Pfam domain and Augustus_transcript Support_percentage > 50. Secondly, the IGV-GSAman software (https://gitee. com/CJchen/IGV-sRNA) was used to manually correct and filter out the genes that included TE sequences in coding regions. Finally, the completeness of genome annotation was evaluated by BUSCO.
miRNA annotation For miRNA annotation, the plant miRNAs downloaded from the publicly available database miRBase (most recent access 5 July 2018, http://www. mirbase. org/) were aligned to S. latifolia female genome using bowtie  89  as described previously. 98  The mapping results were filtered with PERL script filter_alignments. pl from the miRDP1. 3 package. 90  The miRDeep-P program, 90 a plant-seecific scoring system explicitly anticipating miRNAs for plants, was used to trim, filter and identification of new miRNAs.
Transposable element (TE) annotation The EDTA v1. 9. 6 de novo annotation tool  91  was used to annotate LTR, terminal inverted repeat, and Helitron elements. For EDTA, the following parameters were used in addition to defaults: -step all, -species others, -sensitive 0, -anno 1, and -threads 4. Sequences with multiple paralogs were mapped back to the genome and manually extended to determine the full-length boundary of each TE. A total of 15,560 full-length, representative Copia and Gypsy copies were successfully annotated. The significance of difference in TE abundance between autosomes and the X chromosome was tested with R package ggpubr (version 0. 4. 0). Significance was tested using the two-sided Mann-Whitney-Wilcoxon test with multiple comparison. P. adjust homl method was used to adjust the P values.
Data and code availability The S. latifolia female genome assembly and annotation have been deposited to Genome Warehouse (GWH) database in BIG data Center (https://ngdc. cncb. ac. cn/gwh/) under accession number GWHCBIJ00000000 and BioProject accession PRJCA014197. The PacBio and Hi-C data have been uploaded to NCBI Sequence Read Archive (SRA) database as Bioproject PRJNA952727.
METHOD DETAILS Genome sequencing and assembly PacBio library construction and sequencing of the female genome DNA for sequencing was extracted from young leaves of female S. latifolia plants. Genomic DNA was sheared and size-selection was carried out using BluePippin system. SMRTbell libraries were constructed according to the protocol from PacBio. Subsequently, 104. 9 Gb of sequence data were generated with the PacBio Sequel IIe System. PacBio high-quality HiFi reads was generated from subreads by CCS software (v6. 4, https://github. com/PacificBiosciences/ccs). HiFi reads were assembled using hifiasm software  81  with default parameters, which yielded a 2. 64 Gb long contig-level genome assembly (Table  S2 ).
In the NCT02511106 trial, osimertinib therapy has significantly increased the duration of progression-free survival (PFS)  [16]. As the cfDNA concentration in the bloodstream has been suggested to be related to the tumor burden, it appears particularly important to develop extremely sensitive methods to demonstrate the presence of molecular alterations, especially for peri-operative targeted therapies  [17, 18]. In this study, we reported an ultra-sensitive high-throughput targeted DNA sequencing method (Plasma-SeqSensei™ SOLID CANCER IVD kit) for cfDNA identification, in terms of high clinical sensitivity detection of targeted somatic alterations. Clinical performance was assessed by comparing the Plasma OncoBEAM TM EGFR V2 assay or our custom validated NGS routine assay with the Plasma-SeqSensei™ SOLID CANCER IVD assay for 212 cfDNA clinical samples collected at Lyon University Hospital (LHU, France).
OncoBEAM TM EGFR V2 Kit for DNA Exploration CfDNA was analyzed using the OncoBEAM TM EGFR V2 kit (Sysmex Inostics, Hamburg, Germany, Cat No ZR150220), according to the manufacturer's instructions. The OncoBEAM TM EGFR V2 kit is able to detect 36 alterations, including p. G719X, p. L858R, and p. L861Q alterations, as well as 27 of the deletions in Exon 19, p. T790M, and p. C797S EGFR resistance mutations. The analysis was performed using Sysmex Inostics software (FCS Express 5 Flow v. 5. 01. 0082) dedicated to BEAMing technology  [20].
Description of the Patient Cohort To compare clinical performances of the assays, we performed molecular profiling on paired plasma samples. We did not include clinical data in this study testing clinical performance. The cfDNA molecular profiles are reported in Table  1. We analyzed 215 somatic alterations identified by at least one of the three assays in 123 plasma samples. Additionally, 89 samples showed no somatic alterations in the limited panel coverages of the three assays. There were some samples with co-alterations (two alterations or more per sample, see Table  S4 ). Lacking residual biological materials, 82 samples were excluded from the Plasma OncoBEAM TM EGFR V2 analysis. A total of 130 samples were analyzed with the Plasma OncoBEAM TM EGFR V2 assay, and 209 samples were analyzed with our custom validated NGS routine assay.
One limitation of the Plasma-SeqSensei™ SOLID CANCER IVD kit is the non-detection of insertion into the ERBB2 gene, which is addressed by some drugs currently clinical trials. This is supported by the clinical need for identifying patients with EGFR sensitizing alterations to benefit from osimertinib in early NSCLC stages (ADAURA, NCT02511106). Accordingly, it is important to use ultra-sensitive molecular NGS assays, which do not sacrifice specificity, for patients with non-contributive tissue molecular analysis. Tissue sample analysis is mandatory for verifying cancer types identified only via histological analysis, determining to the choice of clinical management and treatments. Therefore, although molecular tissue analysis remains the reference for cancer diagnosis, the rapid selection required for administering targeted therapies can be better achieved via cfDNA testing.
b. Set the Ti:sapphire excitation laser (Chameleon Ultra II, Coherent) at 920 nm. Note: GCaMP fluorescence is isolated using a bandpass filter (510/25). Images are acquired through a GaAsP PMT (H7422-40, Hamamatsu) using a 16X immersion objective (NIKON, NA 0. 8 for a total duration of 33 min or 15000 frames). c. Record with Imspector software (LaVision BioTec), the fluorescence activity from a 400 mm 3 400 mm field of view at 9 Hz with a 1. 85 ms dwell time per pixel (2 mm/pixel). Note: Imaging fields of view are selected from the dorsal CA1 area and maximize the number of imaged neurons in the stratum pyramidale. Note: For further details on the use of Imspector software, please refer to Figure  17  in this article. 10 d. To synchronize 2p images with the behavior, record the camera exposure time, and image triggered signals using a 1440A Digidata (Axon Instrument, 50 kHz sampling) and the AxoScope 10 software (Axon Instrument).
Analysis of two photon calcium imaging data Timing: 2 h This section describes the steps to preprocess and analyze the experimental data. 37. Motion correction and Segmentation (Figure  5,  Step #1). a. Motion correction. To correct the possible motion artifacts occurring during the imaging session, we use custom MATLAB codes (adapted from Miri et al. 11  ) available at GitLab. 12  Note: For this step, movies need to be in tiff. format. Note: This step can also be performed using the Suite2p algorithm which uses. tiff movies as an input. In brief, for each recording session, a subset of frames is selected as a reference and the shifts in the x and y axes are corrected with a rigid and / or non-rigid method. b. Segmentation (cell detection and variation of fluorescence extraction). i. Install Suite2p 13 following the instructions.
This toolbox is designed to infer neuronal activity exclusively based on calcium imaging recordings (i. e. , movies). The performance of this toolbox is impressive not only on developing hippocampus datasets, but also on recordings from other cortical areas, such as the barrel cortex. 2  It particularly excels in cases involving overlapping co-active cells, a common occurrence in densely packed layers like the CA1 pyramidal layer. Furthermore, DeepCINAC 2 has been trained to predict interneuron activity without any specific labeling to identify interneurons. Since the algorithm is already published and available online, we will not detail how to infer activity with DeepCINAC; rather we invite you to follow the tutorial online on the GitLab page 20 in demos. The code outputs a binary array with the activity of all cells as a function of time, with 1 if the cell is active at the current frame, 0 otherwise.
(Figure  5  Step# 2). Note: When used locally, the code needs to access the GPU to perform the prediction of activity, therefore, follow the instructions in the ''inferring neuronal activity'' section on the GitLab page. 20  The activity can also be predicted online on Google Colab. CRITICAL: At the end of this step, it's important to create a temporary Neurodata Without Borders  21, 22  (NWB) file (see below) to move to the next steps. The activity can also be predicted online on Google Colab. 39. Behavioral annotation. CICADA and BADASS GUI. Note: The goal of our experiment is to link neuronal activity (Steps #1 and #2) with pups' behavior. To do so, we developed a graphical user interface (GUI) named CICADA (Calcium Imaging Complete Automated Data Analysis). This GUI accepts as inputs any NWB file to perform any kind of analysis.
One example is BADASS (Behavioral Analysis of Data And Some Surprises) analysis that we use to manually annotate animal behavior during our imaging session (Figure  5  Step #3). To install and run it, refer to the instructions and the video on the GitLab repository. 23  Note: NWB formatting (not specific to this experiment): We decided to use NWB (Neurodata Without Border, Kavli Foundation) files as a data standard to share and store our data (including metadata). NWB files are similar to a container storing collections of data, including the raw data and the results of the preprocessing steps above. (Figure  5  Step #1+Step #2). These datasets are stored with the metadata describing each experimental condition or preprocessing parameters. Regardless of their content, for example two-photon imaging data or extracellular recordings data, NWB files are organized following a similar structure.
21, 22  40. Final NWB file and analysis. a. Final NWB file. The final NWB gathers the content of the temporary version, namely the segmentation and the activity predictions (Figure  5  step #1, step #2) and the manual annotation performed in BADASS GUI (Figure  5  step #3) as well as the raw data. This final version is used as the input to CICADA GUI to perform analyses (see below). b. Data analysis in CICADA. To link pups' behavior to neuronal activity, analyses such as Peri Movement Time Histogram (PMTH) or displaying the raster with the behavior epochs are performed on the final NWB. The outputs of such analyses are displayed on Figure  5  step #4. Note: This entire step-by-step analysis pipeline is specific to our data which includes two photon calcium imaging and behavioral recordings.
On the other hand, in utero electroporation is quite a long and invasive technique compared to P0 injections. Moreover, it has been suggested that virus injection or plasmid electroporation at early stages of neuronal differentiation or migration is irreversibly toxic to neurons. 30  Regarding the analysis, a significant limitation of DeepCINAC is that it was exclusively trained using movies from developing pups expressing GCaMP6s. Despite demonstrating the algorithm's effectiveness in various brain regions and with different indicators, 2 it is not justifiable to assume its universal applicability across all brain regions and indicators without further training with appropriate datasets.
Whole Exome Sequencing and Sanger Direct Sequencing For 17 participants of the Hmong family (I-1, I-5, I-7, I-8, I-9, I-10, I-11, II-2, II-6, II-8, II-9, II-10, II-11, II-12, II-13, II-14, and II-15), the genomic DNA samples were subjected to exome capture using the SureSelect V6+UTR-post kit (Agilent Technologies, Santa Clara, CA, USA). The captured DNA underwent high throughput sequencing using the Illumina HiSeq platform (Illumina, San Diego, CA, USA). All prepared flow cells were run using pairedend 150-basepair reads. Reads were aligned to the human reference sequences (GRCh37) in the Burrows-Wheeler Alignment (BWA) tool version 0. 7. 17 to generated BAM files  [51]. Using Genome Analysis Toolkit (GATK) version 3. 8. 1 software (Broad Institute, Cambridge, MA, USA) [52], both single nucleotide variants (SNVs) and small insertions/deletions (Indels) were identified in individual genome variant call format (gVCF) files.
Then, the genotyped data of all samples were called by GenotypeGVCFs, and high-quality variants were obtained after a variant quality score recalibration (VQSR) step following the GATK best practice. All variants were assigned their pathogenic effect scores using the variant effect predictor (VEP) tool version 99  [53] , as well as cross-checking against the database for nonsynonymous SNPs' functional predictions (dbNSFP), version 3. 5a  [54]. General variant filtering was completed by (1) excluding the intron, intergenic and non-coding regions, (2) excluding synonymous variants, and (3) excluding common variants with allele frequencies of 1000 Genome project (http://www. 1000genomes. org/ accessed on 8 January 2022), gnomAD exome and gnomAD genome (https://gnomad. broadinstitute. org/ accessed on 8 January 2022) greater than 0.
Sequencher 4. 8 Sequence analysis software (Genecodes, Ann Arbor, Michigan, United States of America) was used to analyze variant presence. Amino acid sequences of the protein in various vertebrate species were aligned with PLALINE multiple sequence alignment software (https://www. ibi. vu. nl/programs/ pralinewww/ accessed on 8 January 2022) to calculate conservation consistency. Mu-tationTaster (http://www. mutationtaster. org/ accessed on 8 January 2022), PolyPhen-2 (http://genetics. bwh. harvard. edu/pph2/ accessed on 8 January 2022), and sorting intolerant from tolerant (SIFT) software (http://provean. jcvi. org/index. php/ accessed on 8 January 2022) were used to predict the functional effects of the mutation.