dataesr/scientific-paragraphs-categorization huggingface dataset:
CMA (Chromosomal MicroArray) and Fluorescence In Situ Hybridization (FISH) analysis In brief, for all foetal samples, oligonucleotide aCGH was performed using the Agilent Human Genome CGH microarray 180 K, with 13 kb genome-wide median probe spacing (Agilent Technologies, Santa Clara, CA, USA). The experiments were performed according to the manufacturer's protocol. Patients' gDNAs were obtained from total blood (for parents), and from chorionic villi, amniotic fluid or frozen tissues (for the foetuses) using a Prepito instrument  (PerkinElmer Inc. , Turku, Finland). Images were analysed using Agilent Feature Extraction Software version 10. 7. 3. 1. A graphic overview and analysis of the data were obtained using Agilent CytoGenomics software version 3. 0. 6. 6. The probes were mapped using the GRCh37 genome version.
Aberrant signals including five or more adjacent probes were considered as genomic aberrations and were retained for further study. FISH analysis, using the Vysis LSI TUPLE / LSI ARSA Probe Set (Abbott Laboratories. Abbott Park, Illinois, U. S. A), was performed to confirm the 22q11. 2 typical duplication in the propositus and to study the possibility of inheritance when parental samples were available. In-house BAC probes were used to study atypical 22q11 duplications that were not targeted by the TUPLE1 probe, along with other CNVs when necessary, according to the CMA results. A final classification of the variants was based on data found in the literature and international CNV databases (DECIPHER, DGV, gnomAD), and on inheritance and gene content of the CNV, in accordance with recommendations by the French aCGH network (AChro-Puce).
Cytogenetic studies Twelve foetuses carrying duplications at the 22q11 locus, were included in this work. Most of these duplications were inherited from an apparently healthy parent (Table  1 , Table  2  and Supplementary   Table 2 ). Six duplications were typical (between LCR-A and LCR-D, foetuses F1 to F6, Figure  1 ) and 6 were considered as atypical duplications (foetuses F7 to F12, Figure  1 ). All breakpoints of atypical duplications took place in the LCR-rich sequences. A second CNV considered as pathogenic or VOUS was diagnosed for 3 foetuses (foetuses F9, F10 and F12, Supplementary Table  2 ). All the clinical and cytogenetic data for the 12 foetuses reported here can be found in the DECIPHER database at the following reference numbers: 433453 (F1), 433454 (F2), 433455 (F3), 433456 (F4), 433457 (F5), 433459 (F6), 433441 (F7), 433443 (F8), 433446 (F9), 433450 (F10), 433451 (F11), 433452 (F12).
This the injected cells. To exclude this possibility, a control group consisting of a DSO/DWEK procedure with and without ROCK inhibitor may be considered in future studies. There are currently three ongoing clinical trials using cell injection of primary cultured human CECs worldwide, which will soon provide valuable new data to advance towards the implementation of this technology in the therapeutic setting. These comprise a phase I clinical trial (identification number NCT04191629) which studies the delivery of primary cultured CECs with ferromagnetic beads in Mexico, and two phase III clinical trials (identification numbers UMIN000034334 and UMIN000012534) to further study CEC injection in Japan.
, 2020)  and amniotic membranes did not fully revert corneal edema in cats  (Fan et al. , 2013). There is currently an ongoing phase I clinical trial in Singapore (identification number NCT04319848) for delivering primary cultured CECs using decellularized and modified human corneal stromal carriers to patients suffering from corneal endothelial disease. This study is at an early recruitment phase and more information will be available in the coming years. The attraction of using biological scaffolds rests with their somatic origin, as there is no better biocompatibility than that of a native tissue. Nevertheless, biological carriers present some other hurdles. Generating CEC carriers from donor tissue will always be dependent on donor availability and require adequate tissue banking. Countries lacking this infrastructure may have difficulties in using tissue-derived CEC carriers.
Mehta and colleagues were the first to report the use of acellular corneal endothelial graft substitutes in 2017  (Bhogal et al. , 2017). In their study, the corneal endothelium was stripped off rabbit eyes and decellularized human Descemet's membrane was introduced similarly to a DMEK procedure, a process called Descemet membrane transfer. The animal group receiving allogenic decellularized Descemet's membrane showed an increased corneal endothelial migration and a faster edema reduction compared to the control group which did not received an allogeneic transplant (Fig. 11 ). There is currently an ongoing clinical trial in Singapore studying such technique in humans (identification number NCT03275896). The first clinical results were recently published, and the first transplantation of a 4 mm diameter decellularized Descemet's membrane into a patient was successful in improving the patient's best-corrected Snellen visial acquity from 6/18 to 6/7.
This figure was obtained from  He et al. , (2016a). Licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4. 0 International License (CC BY-NC-ND 4. 0) https://creativecommons. org/licenses/by-nc-nd/4. 0/. reverse corneal endothelial disease. There is currently an ongoing randomized multi-center clinical trial (identification number NCT03069521) aimed to evaluate if a Contomac Ci26-based implant (EndoArt), is successful in reversing corneal edema and promoting sight recovery. The EndoArt implant was designed to prevent fluid infiltration into the cornea, thereby preventing and reversing corneal edema. While the data on this study are still restricted, preliminary results from eight patients with chronic corneal edema are encouraging  (Daphna and Marcovich, 2020). Out of these eight patients, seven presented a reduction of corneal edema and recovery of transparency after EndoArt implantation.
Drug There are currently four ongoing phase II, randomized and doubleblinded clinical trials using topical delivery of Ripasudil for treating FECD. A first study in Germany (identification number NCT03575130) will involve 21 participants and study the topical delivery of ripasudil 0. 4% eye drops after a DWEK procedure six times per day for 2-4 weeks. The control group will undergo a DWEK procedure and will be treated with placebo artificial tears. A second clinical trial in the United States (identification number NCT03813056) will involve 72 participants and will study the benefits of Ripasudil 0. 4% eye drops delivered six times per day for 2-4 weeks after a DMEK procedure. The control group will undergo a DMEK procedure and will be treated with placebo artificial tears. A third study (identification number NCT03249337) will compare Ripasudil dosing regimen of 3 times a day with 6 times a day in patients who underwent a DSO/DWEK procedure for FECD.
Finally, a fourth international multicenter trial (identification number NCT04250207) will involve 60 participants and will study the topical delivery of two different doses of Ripasudil (K-321 solution) eye drops after a DWEK procedure on FECD patients. Half the controls that will undergo DWEK will receive placebo only and the other half will receive twice daily placebo and twice daily Ripasudil. These studies will give more insight into the use of ROCK inhibitors for treating corneal endothelial disease. To date, ROCK inhibitors have been the most studied drugs for treating corneal endothelial disease, but there is also promising research exploring other pharmacological tools to promote corneal endothelial regeneration. Different growth factors such as epidermal growth factor  (Hoppenreijs et al.
, 1992) , platelet-derived growth factor  (Hoppenreijs et al. , 1994)  and fibroblast growth factors  (Lu et al. , 2006)  have been studied to promote migration and proliferation of CECs for tissue regeneration. Nevertheless, their potential benefit comes with the risk of causing an undesired EndMT  (Roy et al. , 2015; Wendt et al. , 2012). Research in this field identified an engineered FGF-1 molecule, TTHX1114  (Xia et al. , 2012) , which has shown potential in vitro and in vivo to trigger corneal endothelial regeneration without any relevant side effects (United States patent registry number US, 2016/0263. 190 A1). There is currently an ongoing phase I/II clinical trial in the United States (identification number NCT04520321) studying the safety and efficacy of TTHX1114 for treating corneal endothelial disease.
Standard PCR, Sequencing, and Phylogenetic Analysis Standard PCR was performed using a thermal cycler (Applied Biosystems, Paris, France) on the samples that were positive in qPCR, and then sequencing to identify the microorganism species. Samples that were negative for R. africae but positive for Rickettsia spp. were subjected to standard PCR to amplify a 632-bp fragment of the ompA gene  [34, 36]. The amplicons were sequenced, assembled, and compared to GenBank entries sequences by a BLAST search to identify the Rickettsia species. For sequences with a low percentage identity with the corresponding sequences in GenBank, PCR targeting a second gene (gltA) was used to amplify a 700 bp DNA fragment, followed by sequencing. Samples that were positive for the Anaplasmataceae family were subjected to amplifying and sequencing of 520 bp fragment of the 23S rRNA gene  [32].
The samples positive for Borrelia spp. under qPCR were subjected to amplifying and sequencing of a 300 bp fragment of the flagellin (FlaB) gene  [40]. Samples that were Piroplasmida-positive following qPCR were subjected to amplifying and sequencing of a 969 bp fragment of the 18S rRNA gene  [29]. The obtained sequences were assembled and analysed using the CromasPro software (version 1. 7. 7) (Technelysium Pty. Ltd. , Tewantin, Australia) and were then blasted against the reference sequences available in GenBank (http://blast. ncbi. nlm. nih. gov/ accessed on 20 July 2021). Sequences from microorganisms were aligned using the BioEdit v 7. 2. 5. 0 software (University of North Texas, Denton, TX, USA). The aligned sequences were imported into TOPALi v2. 5 software (Biomathematics and Statistics Scotland, Edinburgh, UK) and phylogenetic trees were constructed using TOPALi v2.
The BLAST analyses showed that 17 (48. 6%) sequences were 99-100% identical to Rickettsia massiliae (MH549236, MN811608), and 14 (40%) sequences were 99-100% identical to the Rickettsia aeschlimannii (MH932060, MK922621). Similarly, two (5. 7%) sequences were 99. 49% identical to Candidatus Rickettsia barbariae (KU645284). In contrast, two (5. 7%) sequences of Rickettsia sp. were 97. 88% and 97. 92% identical to Rickettsia slovaca (MZ851192) using the ompA gene. When the citrate synthase (gltA) gene was targeted for the same samples, the obtained sequences were 98. 09% identical to those of Rickettsia parkeri (CP040325). The sequences of the latter species have been deposited in GenBank as Rickettsia sp. under the numbers: OP223189, OP223190, OP223191, and OP223192. Rickettsia massiliae was detected in Rh.
lunulatus and Rh. muhsamae. Rickettsia aeschlimannii was observed in Hy. rufipes, Hy. Truncatum, and Rh. sanguineus. Candidatus Rickettsia barbariae was detected in Rh. muhsamae. Finally, Rickettsia sp. was detected in two Rh. lunulatus ticks (Table  4 ). A total of 141 (35. 3%) ticks tested positive by qPCR for bacteria from the Anaplasmataceae family. The amplification of the 23S rRNA gene and sequencing were successful for only 46 (32. 6%) samples. The BLAST analysis showed that 19 (41. 3%) of the obtained sequences were 98-100% identical to Candidatus Ehrlichia rustica (KT364330, MN614109), ten (21. 7%) sequences were 99-100% identical to Candidatus Ehrlichia urmitei (GenBank KT364334). Six (13%) sequences were 99-100% identical to sequence of A. marginale (CP023731), six (13%) sequences were 99-100% identical to an uncultured Ehrlichia sp.
(MW850476, MK942565), and two (4. 3%) sequences were 98. 72% and 98. 74% identical to A. platys (MN626395). Similarly, two sequences were 100% and 99. 58% identical to E. ruminantium (CR925677) and A. centrale (MH321193), respectively. One sequence of Wolbachia sp. from Ha. leachi was 99. 78% identical to Wolbachia pipientis (KT827385) for the first hit and other Wolbachia from Mycopsylla fici deposited in GenBank as "endosymbiont" (KT273261). Candidatus Ehrlichia rustica was detected in Rh. lunulatus, Rh. Microplus, and Haemaphysalis sp. ; Candidatus Ehrlichia urmitei were found in Rh. microplus. Uncultured Ehrlichia sp. were detected in Rh. microplus, Rh. lunulatus, Rh. Sanguinues, and Haemaphysalis sp. ; Anaplasma marginale were detected in Rh. microplus and Haemaphysalis sp. ; A. platys in Rh.
Unfortunately, we could not amplify these positive samples using standard PCR. Finally, 29 co-infections (7. 3%, 29/399) were detected. Most co-infections (72. 4%, 21/29) involved the presence of Rickettsia spp. in Am. variegatum ticks. Eleven co-infections (38%, 11/29) were observed with R. africae, of which nine of the eleven were R. africae with Anaplasma spp. and two of the eleven were R. africae and Piroplasmida. Other co-infections were Rickettsia sp. plus Anaplasma spp. (  No bacterial DNA was identified in I. rasus, Rh. Annulatus, and Rh. decoloratus ticks. Two phylogenetic trees of Rickettsiae and Anaplasmataceae were constructed from the partial sequences of the ompA gene and the 23S rRNA gene sequences of our amplicons, respectively. These phylogenetic trees showed that sequences of the microorganisms detected in this study are close to their homologues available is GenBank, except for two sequences of Rickettsia sp.
(Figures  2  and 3 ). No bacterial DNA was identified in I. rasus, Rh. Annulatus, and Rh. decoloratus ticks. Two phylogenetic trees of Rickettsiae and Anaplasmataceae were constructed from the partial sequences of the ompA gene and the 23S rRNA gene sequences of our amplicons, respectively. These phylogenetic trees showed that sequences of the microorganisms detected in this study are close to their homologues available is GenBank, except for two sequences of Rickettsia sp. (Figures  2  and 3 ).
Funding: This study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the French National Research Agency under the "Investissements d'avenir" programme, reference ANR-10-IAHU-03, the Région Provence Alpes Côte d'Azur and European ERDF PRIMI funding. Y. N. -Y. received a Ph. D. scholarship grant from IHU Méditerranée Infection. The funders had no role in the study design, data collection, and analysis; decision to publish; or preparation of the manuscript. Institutional Review Board Statement: Permission to undertake the study was obtained from the Western Regional Delegation of the Ministry of Livestock, Animal Husbandry and Fisheries in Cameroon, reference number 21/20/L/RO/DREPIA-O/SRAG.
Cytogenetic characteristics of patients were performed with FISH technique searching for 17p deletion, t(4;14), and t(11;14) translocations. Daratumumab was used in front line in the "Cassiopeia" study (NCT02541383) or in relapse at the dose of 16 mg/kg either in monotherapy or in combination with PI or IMiD. Daratumumab was administered intravenously once per week (days 1, 8, 15 and 22) during cycles 1 and 2, once every 2 weeks (on day 1) during cycles 3 to 6, and once every 4 weeks thereafter. In the second group, patients received a treatment combining either Alkylating agent, IMiD, or PI, without daratumumab. Research and identi cation of anti-HLA antibodies were carried out in the immunology laboratory of Saint Louis Hospital in Paris using the Luminex technology and the screening kit for anti-HLA antibodies for class I and for class II (ref LSM12, One Lambda, Canoga Park, CA).
A phase 1-2 study (NCT04204980) is underway on the use of daratumumab to desensitize highly immunized patients awaiting kidney transplantation. The rst step is a dose escalated step from 4 mg/kg to 16 mg/kg. For the second step, patients will receive daratumumab at a dose of 16 mg/kg weekly for 8 weeks. A remaining open question is the optimal dose and schedule of daratumumab for this particular purpose. In fact, the monoclonal anti-CD20 antibody rituximab is used at different doses in lymphoproliferative syndromes and in dysimmune pathologies  (19) ,  (20). In conclusion, this study couldn't nd a signi cant effect of daratumumab to lower HLA antibody. The association of chemotherapy in both group is an important bias. We nd nevertheless a quicker clearance of anti-HLA in daratumumab group.
The pUL51 finalmodel was analyzed and aligned with the atomic coordinates of the monomeric HSV-1 terminase complex (PDB: 6M5R). Results: Among the 16 strains from treated-patients with LMV, 4 never described substitutions in pUL51 (D12E, 17del, A95V, V113L) were highlighted. These substitutions had no impact on viral fitness. Only UL51-A95V conferred 13. 8-fold increased LMV resistance level by itself (IC50 = 29. 246 ± 0. 788). Conclusion: As an isolated mutation in pUL51 in a clinical isolate can lead to LMV resistance, genotyping for resistance should involve sequencing of the pUL51, pUL56 and pUL89 genes. With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.
Next generation sequencing and data analysis UL51 gene coding sequence was amplified by nested PCR for 24 clinical samples from naïve patients and 16 from LMV-treated patients. Viral DNA was isolated from the 32 clinical isolates by the Hirt method  (Hirt, 1967). The flowchart of the experiments is presented in Fig. 1. A depletion of human DNA was then performed using the NEBNextR Microbiome DNA Enrichment kit (New England Biolabs, Ipswich, USA). Before analysis, all DNAs were purified using magnetic beads (Agencourt AMPure XP) and fragmented using the Ion Xpress Plus DNA Fragment Library Preparation kit (ThermoFisher Scientific, Waltham, USA). Barcodes adapters were ligated to fragment ends and 250 bp fragments were collected. Libraries were PCR amplified, then sequenced either on Ion Proton or S5 machine using Ion Sequencing kit (Thermo-Fisher Scientific, Waltham, USA).
Polymorphism and heatmap generation The binary heatmap provides a data matrix where the colors give an overview of mutational differences between strains. Briefly, the strains groups were extracted from the base dataset and each mutation is recorded in a dummy variable. The base dataset is converted into a 2dimensional matrix (x, y) with y ordered by the strain and x by the amino acids id. The binary heatmap is plotted showing mutations in saddle brown and absence of a mutation in peach puff. Python 3. 9. 6 engine is used to generate this binary heatmap  (Muller et al. , 2021).
Tridimensional structure alignment The atomic coordinates of the monomeric HSV-1 terminase complex (PDB: 6M5R) are separated in 3 chains. Chain A corresponds to pUL15 from amino acid T35 to T727, chain B to pUL28 from amino acid A2 to R775 and chain C to pUL33 from amino acid T12 to R129. Atomic coordinates of the chain C were extracted from the text file (PDB: 6M5R) with notepad++ (8. 1. 9. ) and were saved in a new file (. txt). The HCMV-pUL51 modelling structure and the new file containing atomic positions of pUL33 from amino acid T12 to R129 were both imported in VMD 1. 9. 4. Analyses were performed using "MultiSeq" analyses. From "Sequence Alignment" function, structures were aligned with "Stamp Structural Alignment". Both structures are represented with the drawing method "NewCartoon".
Root Mean Square Deviation (RMSD) score of atomic position was analyzed in Excel (Fig. S1 ). In the same way, HCMV-pUL51 modelling structure was aligned with HSV-1 pUL33 structure in the whole HSV-1 terminase complex (PDB: 6M5R). The Chain C of HSV-1 terminase complex was selected to do "Sequence alignment" and "Stamp Structural Alignment".
Identification of polymorphisms The UL51 sequencing results of reference strains AD169, Towne and Toledo were identical to the sequences found in the GenBank (accession number FJ527563. 1, GQ121041. 1, GU937742) by both methods used (Sanger and NGS). Thus, inter-assay reproducibility was 100%. Among the 56 LMV-naïve strains, 14 amino acid polymorphisms were distributed across pUL51 (Fig. 2 ). Only one substitution (S153P) was also present in the reference strains Towne, Toledo, Davis and Merlin but not in AD169. The main identity of the HCMV isolates was 98. 96% (range 97. 45%-100%) and the mean number of polymorphisms per isolates was 1. 6 (range 0-4). Analysis of polymorphisms repartition through pUL51 revealed a huge concentration of amino acid substitution in a Nterminal part. Single nucleotide polymorphisms (SNPs) of 56 LMV-naïve strains did not concern the C-terminal part except for the S153P substitution found also in reference strains Towne, Toledo, Davis and Merlin.
Tridimensional modelling of pUL51 and alignment with pUL33 from the terminase complex of HSV-1 To identify the tridimensional amino acids position, protein modelling was performed with I-TASSER. The predicted secondary structure is mainly composed of helices on the C-terminal part. The N-terminal part is mostly composed of coils, with some helices. The I-TASSER report suggested the presence of a possible ligand binding sites in the C-terminal part. These initial structural data were consistent with the "conclusions" drawn from polymorphism analysis and alignments. The threedimensional structure of the HSV-1 packaging complex was elucidated in 2020 by cryo-electron microscopy  (Yang et al. , 2020). In order to validate the modelling of pUL51 determined by I-TASSER, structure alignment was performed after the pUL33 coordinates extraction from the PDB file (PDB: 6M5R).
More often during this period, the acquired habits are accompanied until adulthood, making this time of great importance for preventive intervention  [5]. The prevalence of adolescent SU is rampant and creates a conundrum for medical professionals. Initiation of SU at an early age has been associated with long-term physical, behavioral, social, and health risks  [6, 7]. SU may lead to neurological changes and behavioral consequences that differ from those that happen in adults due to rapid brain development and maturity during this tenuous period  [1]. Research based on a postmortem database introduces a complementary and different perspective on SU. It includes those persons who do not usually participate in self-reporting studies, and the results depend on actual toxicological analysis; the results of the measurements could temporally connect the toxic substance effect and the fatality  [8].
The prevalence of adolescent SU is rampant and creates a conundrum for medical professionals. Initiation of SU at an early age has been associated with long-term physical, behavioral, social, and health risks  [6, 7]. SU may lead to neurological changes and behavioral consequences that differ from those that happen in adults due to rapid brain development and maturity during this tenuous period  [1]. Research based on a postmortem database introduces a complementary and different perspective on SU. It includes those persons who do not usually participate in self-reporting studies, and the results depend on actual toxicological analysis; the results of the measurements could temporally connect the toxic substance effect and the fatality  [8]. Deceased adolescents offer a picture of the substance-related fatalities which may be helpful to estimate the SU problem in a certain population, identify trends in drug use patterns, and cause of death among the substance users.