dataesr/scientific-paragraphs-categorization huggingface dataset:
Limitations and future perspectives As our analyses involved a relatively limited sample of 29 HCs and 34 patients with ET, our results should be viewed as preliminary until they can be replicated in future studies focusing on larger cohorts. It will also be important to consider a clinically broader set of patients, instead of only severely impacted drug-resistant individuals as here. Doing so is likely to reveal further types of heterogeneity in the data. Our modelling approach could also be refined in several ways if larger datasets are considered: first, as alluded to above, the existence of multimodal data organization could then be probed for cluster numbers larger than 2. Second, more morphometric features could be jointly analyzed, as a larger sample size enables the accurate estimation of a larger array of parameters.
However, RiPP posttranlational modifications of ribosomic all L-AA peptides into D-containing epimeric forms are known and may not be as rare as once thought. With the massive progress made in bioinformatic scanning of the genetic code for a vastly increasing number of living animals and plants, the biosynthetic gene cluster code needed to produce a given peptide or even protein can be calculated and searched within databases in a short time  [150]. The software ant-iSMASH searching for antibiotics and secondary metabolite biosynthetic gene clusters is freely available at https:// antis mash. secon darym etabo lites. org/  [154]. In most cases, the biological activity of the D-containing natural products is completely different of that of the analogous all-L containing stereoisomer. This greatly helps in locating the D-AA(s) in the peptide chain using organic synthesis followed by biological tests.
Methods / Design Design This is a hybrid effectiveness implementation Type III study,  14  using mixed methods approach for data collection. It's multi-country, conducted across three continents (Africa, Asia, and Central America), and registered in the ClinicalTrials. gov registry -ID# NCT05133661 (24/11/2021). The implementation research conceptual framework was modelled on the approach described by Proctor et. al, is shown in Fig. 1. 15  Speci cally, we closely observe and study locally relevant contexts and processes, to understand the implementation of services and client outcomes. The primary outcome is the proportion of HPV positive women (general population and WLHIV) who undergo treatment for precancerous cervical lesions within three months of screening -the optimal time for quality services.
Cost data -In addition to the client exit interview cost data, additional data are being collected through time-and-motion observation to document inputs at service delivery (e. g. staff time, supplies, number of procedures per day, laboratory-related processes etc. ). Project nancial records for 2022-23 will be analysed. The cost database will be maintained using a modi ed version of the C4P costing tool. 17  Recruitment and Consent: Written informed consent will be obtained from each study participant in accordance with the approved study protocol and documents, prior to data collection. For women recruited in study sites, service providers introduce the study to potential study participants and those who meet the basic criteria (e. g. age, not pregnant, no history of hysterectomy), and are interested in learning more about the study, will be referred to a research assistant for further screening and consenting prior to enrolment.
Data collection and timeline The overall duration of the study in each country is estimated to be 18 months, with countries starting and ending at different times depending on when relevant ethical clearance and other preparatory activities are completed. Figure  2  summarizes the data collection schedule through both approaches. Quantitative data are collected using tablets loaded with the CommCare application (https://www. dimagi. com/commcare/), and uploaded on a central server hosted by Amazon Web Services. This allows for online entry of data in real-time and retrieval. Data are stored in password protected les or on a part of the server where access can be limited to study staff. Qualitative data are collected by experienced qualitative researchers and audio recorded (audio, MP3 format or equivalent) and note taken.
For qualitative data, the audio recordings are stored in locked cabinets and will be destroyed at the end of the study after veri cation and data analysis is completed. Only study staff directly involved in collecting, transcribing, or analyzing the qualitative data have access to the recordings. The transcribed electronic versions of the recordings, without personal identi ers, will retained with other study data for 5 years after the end of the study. Consent forms will be kept for the same period to allow respondents to exercise their right of access.
Data analysis plan Descriptive and logistic regression analysis will be conducted for quantitative data to answer the primary and secondary research questions. Additionally, secondary analysis of service delivery data, including laboratory services, will be conducted to determine key parameters such as turnaround time for HPV test results and promptness of treatment where indicated. Cost analysis will determine the unit cost of providing the services as well as user costs. Speci cally, cost per woman screened, per woman screenedand-treated, and per delivery component will be reported, by month, year and facility type. Aggregated site-speci c, country-speci c and project level costs will also be reported. Where comparison is possible to provide insights into cost e ciencies, they will be reported.
Anonymized out-of-pocket costs will be consolidated in a separate dataset and also analysed with descriptive statistics. KIIs and IDIs data will be transcribed from the audio-recordings and the notes taken, and for recordings in a local language, translated and back translated. Atlas ti. 8 software will be used for analysis. A coding frame will then be developed using a grounded theoretical approach. The emerging themes will be iteratively developed by repeatedly analysing data collected from participant categories. Verbatim text generated alongside the code matrix will be used to support the emerging thematic framework.
Acknowledgements The authors would like to thank and acknowledge Expertise France and Jhpiego co-investigators to the study,  Eric Fleutelot ,  Jean-Claude Comoé Kouassi ,  Somesh Kumar ,  Ana Maria Rodas , and  Linda Traore. The authors recognize the Study Coordinators and Data Collectors/Research Assistants in each country for their contributions thus far. We also thank  Unitaid  for their vision and investment, as well as their inputs along with the global Scienti  c Steering Committee  into this protocol and implementation. We also appreciate and thank the  Ministries and Departments of Health in Burkina Faso, Cote d'Ivoire, Guatemala  and the Philippines and the country level Implementation Research  Advisory Groups  for their leadership to support the scale up of HPV self-sampling, HPV testing, and thermal ablation treatment in their respective countries.
Images were processed using FIJI (ImageJ) software (v1. 53f). Turbidity measurements were also used to characterize the saltand light-dependent phase behavior of DD and azoTAB. Here, freshly made samples were added to a 384-well plate and incubated for ~5 min, then the absorbance at 700 nm was measured on a Molecular Device SpectraMax Paradigm microplate reader using SoftMax Pro software (v6. 2. 2), and a reference value (corresponding to 25 μL of pure water) was subtracted. Cycles of UV and blue light were performed by irradiating the samples for 15 min using alternating UV and blue LED (Thorlabs, Inc): the samples were irradiated for 15 min under UV light using an LED operating at 365 nm, then the absorbance was measured and the samples were irradiated for 15 min under blue light with an LED operating at 450 nm, and the turbidity monitored at 700 nm after each irradiation.
Polyacrylamide gel electrophoresis Ligation products analysis was performed using 15% denaturing polyacrylamide gels (20 cm wide × 16 cm high) containing 8. 3 M urea and run in 1× TBE for 3 h at a constant power of 32 W. Equal DNA masses from each sample, 0. 5 μg, were loaded in the gels. Gels were stained with 1× SYBR Gold for 20 min with gentle agitation. Ladders used in gels were composed of an equal mass mixture of 12-, 24-, 48-, and 96-mer DNA sequences, corresponding to 1-, 2-, 4-, and 8-times repetitions of the DD sequence, respectively, unless otherwise specified. Uncropped gels are shown in a Source Data file. Gel image analysis was carried out with FIJI (ImageJ) software (v1. 53f) using a custom MATLAB (MathWorks) script. Estimations of the ligation product distributions from gel band intensities were performed by measuring the profile peaks areas normalized on the sum of the area of the peaks.
Fluorescence recovery after photobleaching Fluorescence recovery after photobleaching (FRAP) experiments were performed on a Leica DMI8 scanning laser confocal microscope equipped with a ×25 water immersion objective (HC FLUO-TAR L, 0. 95 NA). Coacervate samples were prepared by doping DD solutions with 1:1000 Cy5-labeled DD oligomers (Integrated DNA Technologies). Images were analyzed by the Leica LAS X software (v 3. 5. 7. 23225). The normalized FRAP intensity I FRAP (t) was calculated as [S(t) -B(t)]/[C(t) -B(t)], where S(t), C(t), and B(t) are the fluorescence intensity measured in circular ROIs with the same diameter (2-5 μm) inside the bleached coacervate area (sample, S), non-bleached coacervate region (control, C), and non-bleached supernatant (background, B). I FRAP (t) was fitted with a monoexponential growth function A.
Acknowledgements We thank  D. Cuvelier  and  F. Giavazzi  for the use of their microscopes during parts of this study,  P. Nghe  laboratory at  ESPCI  for support for gel electrophoresis, and  M. Todisco  for useful discussions. We are indebted to  J. -P. Douliez ,  J. -C. Baret ,  T. Bellini , and  A. Griffiths  for critical reading of the manuscript and stimulating discussions. T. P. F. is supported by a  Junior Research Chair fellowship  from  IPGG  ( Laboratoire d'Excellence, "Investissement d'avenir" program   ANR-10-IDEX-0001-02 PSL  and  ANR-10-LABX-31 ),  ANR-10-EQPX-34  and  IPGG AAP High Risk2020  grant. N. M. acknowledges funding from  IdEx Bordeaux  ( ANR-10-IDEX-03-02 ), an " Investissement d′Avenir" program  of the French government managed by the  French Agence Nationale de la Recherche ,  Région Nouvelle-Aquitaine  ( AAPR 2020-2019-8330510 ), the  French Agence Nationale de la Recherche  under the project  LASCO2  ( ANR-21-CE06-0022-01 ), and support by the  Univ.
The SLPC contained in the food supplement SPIR-ULYSAT ® (produced by AlgoSource) has already been tested for metabolic syndrome (NCT02817620). Studies of SPIRULYSAT ® in the murine model of non-alcoholic steatohepatitis have shown very strong anti-oxidant activity  [9]. The SLPC used in this protocol will be five times more concentrated but is still produced by the same laboratory (PHYCOCARE ® ). In brief, firstly, it is generally accepted that no pharmacologic agent has been definitively shown to prevent platinum salt-induced neurotoxicity  [10]. Secondly, although duloxetine, a non-selective serotonin reuptake inhibitor antidepressant with non-opioid pain-relieving properties, has been shown to be effective in ameliorating neuropathic pain, clinical experience has not, to date, validated the trial data  [11].
Concealment mechanisms {16b} Randomization will be carried out using EnnovClinical software, the e-CRF of CHU Nantes, by connecting to the website at https:// nantes-lrsy. ennov. com/ Ennov Clini cal/ login. The connection will be made using a login, a password, and a study number, issued by a data manager from the Sponsor Department. The enrolment number and randomization arm will be assigned automatically. Subjects are randomized into blocks as the allocation progresses. A block, generated as already said by SAS, being a subgroup of a predetermined size within which there is a random allocation of patients.
Data management {19} An eCRF will be drawn up for each subject. Subjects will be identified using a code which should be the only information featuring in the eCRF, enabling a retrospective link with the patient. The investigator will also encode the patient data in any documents that may be in their possession (EDX, questionnaires) and attached to the eCRF. At the end of the study, the CRF database and the safety database will be reconciled before the databases are locked. Similarly, an annual reconciliation will be carried out when updating the Annual Safety Report.
Confidentiality {27} Each patient's medical data will only be provided to the sponsor or any person duly authorized by the sponsor and, where applicable, to authorized health authorities, under conditions of confidentiality. The sponsor and the supervisory authorities may request direct access to medical records for the purposes of verification of the procedures and/or data in respect of the clinical trial, within the limits authorized by legislation and regulations. The data compiled during the trial may be processed electronically in compliance with CNIL requirements. CNIL is an independent administrative regulatory body whose mission is to ensure that data privacy legislation is applied to the collection, storage, and use of personal data. Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} Not applicable as no biological specimens were collected as part of this trial.
Statistical methods for primary and secondary outcomes {20a} Descriptive analyses will be conducted for all variables collected. Point estimates and 95% confidence intervals will be calculated for qualitative and quantitative variables. For estimates obtained using a small sample, the medians and interquartile intervals (for quantitative variables) and exact confidence interval (for qualitative variables) will be provided. All analyses will be performed with the use of R software (version 4. 0) or SAS software (version 9. 4). To fulfill the main objective of this study, the prevalence of neurotoxicity of grade 2 or above in both arms will be estimated using linear mixed regression, taking into account the center effect (random effect). The second step will be to adjust this estimate based on known risk factors (gender, age, etc.
Adverse event reporting and harms {22} All subjects will be followed up for adverse event collection, through self-reporting in the patient's diary and monthly, at the time of the visit, based on clinical and biological examination. Neurological toxicity will also be monitored by EDX. In addition, between visits, as well as all subjects receiving chemotherapy, patients are asked to contact the clinical team in case of difficulties or toxicity. The expected ARs are associated with: ▪ PHYCOCARE ® Spirulina has been the subject of preclinical and clinical studies. Preclinical data have not shown toxicity of spirulina at high doses (for administered doses up to 30g/kg/day or ad libitum in mice). In the numerous clinical studies carried out at doses of up to 19g/day of dry spirulina, only a few gastrointestinal (moderate vomiting and diarrhea episode) and headache-type adverse effects linked to the consumption of spirulina have been reported.
90 (https://github. com/rrwick/Bandage). Additionally, we uploaded the sequencing reads to BugSeq (https://bugseq. com/academic) for automated functional annotation of the plasmid genomes including resistance gene detection against a curated plasmid database  31. Here, the IncN plasmid was identified as the carrier of the KPC-2 and KPC-14 genes respectively. To assess similarity between the IncN plasmids and the KPC-2 and KPC-14.
Acknowledgements We thank the laboratory technicians, especially  Jacqueline Meindl , and physicians at the  Institute of Medical Microbiology at the Technical University Munich  for their support with phenotypic species identification, susceptibility testing, and sample storage and retrieval. We thank  Sam Chorlton  for helpful discussions on the BugSeq platform. We thank  Niels Pfennigwerth  from the  German National Reference Center for Gram-Negative Bacteria  for his work on identifying the novel KPC-159 subtype. We thank  Dr. Youssef Hamway  for his help with laboratory work and conceptualization of the study. This project was funded by a  Helmholtz Principal Investigator Grant  awarded to LU.
Bioinformatics and genetic analysis European seabass and gilthead seabream crtam sequences were identified in RNA-seq studies carried out in our laboratory and further confirmed within the European seabass genome project (http://seabass. mpipz. mpg. de/) and assembled reference genome of gilthead seabream (GCA_900880675. 1, NCBI Genome), while seabass and seabream cadm1a and cadm1b were obtained from the Ensembl database (https://www. ensembl. org/index. html). Exon-intron structure was generated by the Exon-Intron Graphic Maker (http://wormweb. org/exonintron). Genomic synteny was performed in Genomicus 101. 01. Predicted proteins were used for multiple sequence alignments using the CLUSTALW program and phylogenetic analysis were performed with MEGA software version 6  [17]. Protein domain architecture was searched by InterPro (https://www.
Genomic organization Within the genome databases, we found complete sequences for crtam, as well as two cadm1 forms, a and b, in both fish species. A summary of the genomic, mRNA and protein molecules is presented in Table  2. Analysis of the genomic structure predicts the presence of 11 exons in seabass and seabream for crtam, 12 in seabass and 9 in seabream for camd1a and 11 in both species for cadm1b (Fig. 1a , Table  2 ). Even the genomic structure might show some variations between the two fish species, their synteny present a good conservation of organization in the genome from Actinopterygii ancestor (Fig. 1b ). Curiously, cadm1a is preceded by ncam1a whilst camd1b is by ncam1b suggesting that these genes duplicated and evolved together. mRNA transcripts resulting from these genes contained a complete open reading frame (ORF), except the partial cadm1a of seabass, with little variations between the two species though the 3 ′ and 5' UTRs were variable in length (Table  2 ).
Acknowledgements This work was funded by  Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación  ( MCIN/AEI/10. 13039/501100011033 , grant  PID2019-105522GB-I00  to AC) and  Fundación Séneca de la Región de Murcia (Grupo de Excelencia  grant number:  19883/GERM/15 ). C. González-Fernández  is contracted with the  Spanish national  postdoctoral program  Juan de la Cierva -Incorporación with number  JC2019-040510-I.
All the crosses had high levels of spore viability (>94% of the spores were viable, n = 43, 37, and 41 tetrads, respectively), suggesting that meiosis was unaffected by the heterozygous mutations (Tables S7, S8, and S9). Two tetrads gave incomplete sequencing data and were dismissed, providing a final dataset of 90 tetrads (29, 30, and 31 tetrads, for populations Pombe2_Tet, Pombe4_Tet, and Pombe9_Tet, respectively. Table  S1 ). To define the informative SNPs for each population, we deep-sequenced the parental genomes (25-91x, Table  S2 ), and identified 161, 121 and 172 well-supported and randomly distributed mutation markers that provided good coverage of the three chromosomes (Table  S3 ; Figure  S1 ). The median/mean inter-marker distance is 56/83 kb and corresponds to the resolution at which recombination sites could be detected and assigned (equivalent to 7.
21 and 0. 17, in 100 kb and in 200 kb window size, respectively) despite the existence of DNA double-strand break hotspots at higher resolution. 28, 47  Gene conversions in S. Pombe In addition to COs, we identified a total of 66 gene conversions (GCs) characterized by a 3:1 segregation profile of a single SNP, which corresponds to an average of 0. 7 per tetrad (Figures  2C, 2E,  and S3 ). Among them, 37 GCs were flanked by a CO event (Table  S4 ) and could be either associated to the CO, or be an independent NCO recombination event in the same interval (median size = 134 kb). We thus estimated that between 29 and 66 NCOs were detected in our dataset. In total, we analyzed the segregation of 13,975 SNPs in 90 tetrads, which resulted in an estimation of an average NCO conversion rate of 0. 21-0.
We divided each chromosome in intervals of fixed size ($200 kb in Figures  4C  and S13G-S13I ), and calculated the CoC for all pairs of intervals. A CoC curve is obtained by plotting the mean CoC for pairs of intervals separated by a given distance versus this distance (Figures  4C  and S12 ). In presence of interference, the CoC curve is expected to deviate from 1, approaching zero for short inter-interval distances. We found that the CoC curves are flat (close to 1) for each chromosome, when considering intervals size of 200 kb or more, supporting an absence of CO interference in S. pombe at this scale which represents 4-8% of the chromosome length (Figures  4C, S12 , and S13G-S13I). It should be noted that because of limited resolution of CO positions (median resolution $113 kb, Figure  S2 ), these global CoC curves, using the entire dataset, cannot exclude CO interference acting at shorter physical distances.
High quality EMS-induced mutation marker calling The reference genome and genomic annotations of the fission yeast Schizosaccharomyces pombe were downloaded from the PomBase database (https://www. pombase. org). 64, 65  The whole genome resequencing short reads of parental samples of the three independent populations (Pombe2_Tet, Pombe4_Tet and Pombe9_Tet, Table  S2 ) were aligned to the reference genome using BWA v0. 7. 15-r1140  55  with the default parameters. A command set of Sambamba v0. 6. 8  56  was used to format the read alignment file. The variant calling and filtering processes were largely performed following a previously described pipeline. 45, 57, [66] [67] [68]  First, variations were called for each individual parental sample by inGAP-family. 57  Then, non-allelic, low-quality and artificial variants were selected and filtered by checking the effects of tandem repeats, small indels and structural variations predicted by Tandem Repeats Finder v4.
CO and chromatid interference analysis To simulate the CO landscape in the absence of interference, COs were randomly sampled in the genomic range of first and last markers in the population along chromosomes. To match the contribution of COs per chromosome and tetrad, we kept the exact same sample size in the simulation. The distances between simulated COs were calculated as the observed dataset. The CoC analysis was performed using MADpattern v. 1. 1 (https://github. com/mwhite4/MADpatterns). 12, 50  For the chromatid interference analysis, the Chi-Square test of goodness-of-fit was performed to evaluate the deviation from the random 1:2:1 ratio for each observed 2C:3C:4C ratio, using the chisq. test function (stats v3. 6. 2 package) in R environment. Adjacent double COs were not included in the CO and chromatid interference analysis.
ACKNOWLEDGMENTS We thank the anonymous reviewers for their comments and suggestions to improve the manuscript. We would like to thank the  Max Planck Genome center  for library preparation and sequencing. We thank  Neysan Donnelly  for proofreading the manuscript. This work was supported by core funding from the  Max Planck Society  and an  Alexander von Humboldt Fellowship  to Q. L. B. L. lab was supported by the  ANR  grant  ANR-18-CE12-0013-01.