Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Fujiwara, Y. Funatsu, N. Hasegawa, T. Betsuyaku (2013) Modulation of murine macrophage TLR7/8-mediated cytokine expression by mesenchymal stem cell-conditioned medium. 2013: 264260. 7. Baker, N. , L. B. Boyette, R. S. Tuan (2015) Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone 70: 37-47. 8. Bernardo, M. E. , N. Zaffaroni, F. . Moretta, D. Montagna, R. Maccario, R. Villa, M. G. Daidone, O. Zuffardi, F. Locatelli (2007) Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. 67: 9142-9149. 9. Bianco, P. , P. G. Robey, P. J. Simmons (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell 2: 313-319. 10. Bidic, S. M. , J. W. Calvert, K. Marra, P. Kumta, P. Campbell, R. Mitchell, W. Wigginton, J. O. Hollinger, L. Weiss, M. P. Mooney (2003) Rabbit calvarial wound healing by means of seeded Caprotite scaffolds. J 82: 131-135. 11. Bigham-Sadegh, A. , A. Oryan (2015) Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures. J 12: 238-247. 12. (2014) Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review. Ther 16: 432. 13. Bose, S. , M. Roy, A. Bandyopadhyay (2012) Recent advances in bone tissue engineering scaffolds. 30: 546-554. 14. Cao, Z. , C. Dou, S. Dong (2014) Scaffolding biomaterials for cartilage regeneration. J Nanomater 2014: 8. 15.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: However, success did not come overnight but was the result of a step-by-step escalation in both understanding the molecular mechanisms of HCV replication and in the therapeutic approaches which started at the end of the 1980s, before the discovery of HCV, with IFN alpha affording a response rate of less than 15%[1]. The addition of ribavirin to IFN increased the success rate to about 30%, and then treatment moved into the era of the long-acting pegylated IFNs (pegIFNs). PegIFN plus ribavirin was the standard therapy for about 10 years during which the overall therapeutic success increased to 50%[2]. However, IFN-based treatment was associated with a significant number of severe side effects that limited its use considerably. Many other factors conspired to limit the therapeutic response, further hampering the use of IFN. These included host factors, such as age, body mass index, level of liver fibrosis and steatosis, insulin resistance, ethnicity, the genetic background such as the polymorphism of interleukin-28B, and viral factors, namely HCV genotype and levels. Furthermore, IFN-based regimens required a long therapeutic course, which reduced the adherence to treatment. The year 2011 marked the beginning of the era of oral direct-acting antiviral drugs (DAAs). The scenery was complex with the first-generation DAAs, the NS3-A4 protease inhibitors boceprevir and telaprevir, which were approved in combination with pegIFNs and ribavirin for HCV genotype 1 treatment[3]. Although this triple therapy afforded a higher sustained virological response (SVR) rate than pegIFN plus ribavirin, the treatment was short-lived because of the dependence on IFN due to the low barrier to resistance of these first-generation DAAs. Moreover, the use of these DAAs was aggravated by a high rate of serious adverse events and by the scanty possibility to treat patients with advanced liver disease. Fortunately, the research moved fast and new oral were devised, several of which had proved highly effective in a combined regimen, and finally approved for use in clinical practice (Table 1). Several other DAAs are currently in the drug development pipeline. Figure 1 shows the crucial milestones in the chronic hepatitis C treatment evolution, from IFN-based regimens to all-oral IFN-free combinations.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: More importantly, individual copies of a TE are separated by, on average, twice as many mutations as they are from the original sequence approached by a consensus, improving sensitivity dramatically. we now provide both profile HMM and auxiliary consensus sequence models for each family in the database. Both are derived from a single seed alignment, allowing for provenance to be maintained and both models to be simultaneously improved. Most importantly, Dfam maintains a correspondence between consensus and HMM positions so that alignments produced by either may be compared directly. In Dfam, consensus sequences are generated for each family using a caller that we originally employed to build many of the consensus sequences for Repbase. It assigns the base with the highest score using a log-odds substitution matrix that reflects neutral substitution patterns in a genome, including e. g. the strong GC- > AT bias in mammals. It also infers ancestral CpG sites by accounting for the frequency of TG and CA dimers in neighboring columns [17]. Classification systemWithout classification, a TE library is of limited use. While entries in Dfam have always been classified, in this release series we developed a new classification system for repetitive sequences in eukaryotic genomes. In addition, an interactive tool was developed for the website to assist in exploring the new system in the form of an identification key (Fig. 2). Fig. 2Dfam TE classification system and visualization tool. a A small portion of the Dfam TE classification tree depicted using the dynamic visualization found at the Dfam website. Filled in circles represent internal nodes of the tree while hollow circles are leaf nodes in the classification tree. A classification is specified by concatenating the path through the classification tree. For example, the classification “Interspersed_Repeat;Unknown” is highlighted in the tree. b In addition, wherever possible a mapping is provided between classification systems. classification for the L1 group of LINEs is shown with the equivalent classifications in several other systemsFull size imageClassification of TEs poses specific problems that may prevent a universal solution to be found [18]. A purely cladistic approach is impossible as TEs are polyphyletic (they have many independent origins) and because their relationship is reticulated (sections of TEs can have entirely different evolutionary histories, due to recombinations, gene captures and nested insertions). Classic SINEs, which have originated many times from fortuitous positioning of an internal promoter (e.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Caplan, A. I. , S. P. Bruder (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Med 7: 259-264. 16. Carrion, F. A. , F. E. Figueroa (2011) Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue? 2: 23. 17. Castelo-. Buongusto, C. A. Martinusso, A. do Rosario Jr, S. A. Souza, B. Gutfilen, L. M. Fonseca, C. Elia, K. Madi, A. Schanaider, M. I. Rossi, H. S. Souza (2012) Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis. PLoS One 7: 14. 18. Chabner, K. T. , G. B. Adams, J. Qiu, M. (2004) Direct vascular delivery of primitive hematopoietic cells to bone marrow improves localization but not engraftment. Blood 103: 4685-4686. 19. (2010) Mesenchymal stem cell-encapsulated collagen microspheres for bone tissue engineering. Methods 16: 225-235. 20. Chen, W. J. , S. Jingushi, I. Aoyama, J. Anzai, G. Hirata, M. Tamura, Y. Iwamoto (2004) Effects of FGF-2 on metaphyseal fracture repair in rabbit tibiae. J Metab 22: 303-309. 21. . Ahn (2014) Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Med 46: e70. 22. Choi, H. , R. H. Lee, N. Bazhanov, J. Y. Oh, D. J.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Table 1 Direct-acting antiviral agents approved for the treatment of hepatitis C virus in interferon-sparing regimens. 3-4ASecond-wave, first generationGenotypes 1 and 4ParitaprevirNS3-4ASecond-wave, first generationGenotypes 1 and 4SofosbuvirNucleoside/nucleotideNucleotide analoguePangenotypeanaloguesDasabuvirNon-nucleoside inhibitors of the -dependentPalm domain I inhibitorGenotype 1RNA polymeraseDaclatasvirNS5A inhibitorsFirst-generationPangenotypeLedipasvirNS5A inhibitorsFirst-generationGenotypes 1, 3, 4, 5, and 6OmbitasvirNS5A inhibitorsFirst-generationGenotypes 1 and 4 DAAs: Direct-acting antiviral agents; HCV: virus. Open in 1 Milestones in the chronic hepatitis C treatment evolution, from interferon-based regimens to all-oral interferon-free combinations, and the respective sustained virologic response rates. IFN: Interferon; SVR: Sustained virologic response. The first therapeutic strategy with the new DAAs approved in 2014 was pegIFN plus ribavirin plus sofosbuvir, a nucleoside analogue acting as a false substrate for HCV to stop viral RNA synthesis. Sofosbuvir is active against all HCV genotypes and has a high barrier to resistance. A phase III trial[4] using the triple regimen showed an SVR of 89% and 96% for HCV genotype 1 and 4, respectively, and a phase II trial[5] in treatment-experienced patients showed an SVR of 96% and 83% in genotype 2 and 3, respectively. In the same year, based on the data of phase III studies[6,7], another triple regimen with pegIFN plus ribavirin and simeprevir, a first-generation NS3-4A protease inhibitor, was approved for the treatment of HCV genotype 1 and 4. The two trials reported an SVR of 80% and showed that in HCV genotype 1a carrying the mutation Q80K in the NS3 protease sequence the response rate was significantly impaired.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: g. in a small RNA gene) and the 3′ fragment of an active LINE [15, 19] provide an example for both these issues. Nevertheless, most currently-used classification systems for eukaryotic TEs are very similar and are based on hybrids of cladistic, mechanistic, and structural approaches. In 1989, introduced an early classification with just four classes [20]. His basic division between TEs that transpose via an RNA intermediate (class I) and those that “transpose directly from DNA to DNA” (class II) is still used by most. Considering the fundamental impact of the trans-activity of class II proteins on their transcripts and the cis -activity of class I proteins on their genomic copies, this is indeed a primary division (Fig. 1). At the time, very few types of eukaryotic TEs were known, and his further divisions of class I elements into those with and without long terminal repeats (LTRs), and divisions of class II elements into those with short and long terminal inverted repeats (TIRs) has not survived the onslaught of new data, although LTR and non-LTR (LINE) elements still form valid clades, at least from the reverse-transcriptase point of view [21]. When we introduced RepeatMasker in 1995, we needed a succinct classification to fit in the slightly modified cross_match format [22] that we used to annotate genomic DNA. We chose a three-level form coded as “level1/level2-level3” (e. g. “DNA/hAT-Charlie”). We adopted Finnegan’s and class II (“DNA”) divisions and added SINE and a number of non-TE classes for the first divisions, the three class I elements reflecting a bias towards the frequency of elements encountered in the human and other mammalian genomes. Second and third divisions represent clades of elements based on reverse transcriptase (RT) or transposases phylogenies. Non-autonomous elements whose movement depends upon the coding capacity of autonomous elements, were grouped within the autonomous elements’ classification, based on similarities of the LTRs or TIRs in the absence of any coding sequence. Entries in Repbase more or less inherited this simple classification hierarchy. In later years, attempts were made to reflect as much as possible of the classification in the name of the elements [23].

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Prockop (2011) Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages. Blood 118: 330-338. 23. Connolly, J. F. (1998) Clinical use of marrow osteoprogenitor cells to stimulate osteogenesis. 355: S257-S266. 24. Connolly, J. F. , R. Shindell (1986) Percutaneous marrow injection for an ununited tibia. J 71: 105-107. 25. Cui, L. -l. , E. Kerkelä, A. Bakreen, F. Nitzsche, A. Andrzejewska, A. Nowakowski, M. Janowski, P. Walczak, J. Boltze, B. Lukomska, J. Jolkkonen (2015) The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity. 6: 11. 26. Das, A. , D. A. Barker, T. Wang, C. M. Lau, Y. Lin, E. A. Botchwey (2014) Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair. PLoS One 9: e101276. 27. Datta, N. , Q. P. Pham, U. (2006) In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. 103: 2488-2493. 28. de Girolamo, L. , E. Lucarelli, G. . Biagi, A. T. Brini, G. D'Amico, F. Fagioli, I. Ferrero, F. Locatelli, R. Maccario, M. Marazzi, O. Parolini, A. Pessina, M. L. Torre, G; Group (2013) Mesenchymal stem/stromal cells: a new “cells as drugs” paradigm: efficacy and critical aspects in cell therapy.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: The year 2014 also marked the beginning of the end of the IFN era and the triumph of the all-oral IFN-free regimens, which were highly effective and safe and afforded treatment also for patients with advanced cirrhosis. Phase III studies[8,9] showed that the combination sofosbuvir plus ribavirin for 12 wk for HCV genotype 2 achieved an SVR from 88% to 100% depending on whether the patients were treatment-naïve or -experienced and on the absence or presence of cirrhosis, and for 24 wk for genotype 3, achieving an SVR from 60% to 94%, with the poorest results in therapy-experienced cirrhotic patients. The treatment of genotype 3 can be shortened to 12 wk by adding pegIFN to sofosbuvir and ribavirin. A phase III trial[10] showed that the combination sofosbuvir plus daclatasvir, a “pan-genotypic” first-generation NS5A inhibitor, taken for 12 wk produced an SVR in genotype 3-infected patients of 90% for previously untreated patients and 86% for prior non-responders. Thus, at present, this combination seems to be the best option for the treatment of genotype 3 infection. The combination sofosbivir plus daclatasvir also showed good results in HCV genotype 1, 2, 4, 5 and 6. The regimen sofosbuvir plus simeprevir has been approved for treatment of HCV genotypes 1 and 4. A phase II study[11] showed an SVR of 93%-96% in treatment-naïve and -experienced patients treated for 12 wk. For HCV genotype 1a the Q80K substitution did not seem to influence the response rate of the sofosbuvir and simeprevir combination. In early 2015 the combination of sofosbuvir and ledipasvir, a first-generation NS5A inhibitor, in a single pill to be administered once a day was available for the treatment of HCV genotypes 1, 3 and 4. The SVR after 12 wk of treatment was as high as 99%[12,13]. Importantly, it was shown that the treatment could be shortened to 8 wk with an SVR of 94%[14].

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: The classification system suggested in 2007 by researchers with a primarily plant genomics background [24] has the same basis in Finnegan and follows a similar logic; in order to display compact classification on an annotation line, they suggested a three-letter class-order-superfamily code to add to each “family” classification. The “subfamily” was suggested to be used in the TE’s name itself. Our classification, like those before, combines a mechanistic, cladistic and structural approach. Where possible, the relationship of the RT in class I elements and transposase, helicase, or DNA polymerase in class II elements guides the tree. While non-autonomous LTR elements tend to remain dependent on the autonomous element from which they formed and can be classified with these, LINE-dependent non-autonomous elements have a variety of origins. They are separated by those with a small RNA derived pol III internal promoter (the SINEs) and other elements. The latter category is a grab bag of sorts, classified by the type of LINE they depend upon, and contains elements mostly consisting of LINE-material to hodgepodges like SVA [25]. The modular, classic SINEs are organized by their 5′ small RNA-derived, core, and 3′ LINE-derived modules. Class II elements are divided in the four fundamental mechanisms of propagation so far known in eukaryotes, “cut-and-paste” via a linear or circular dsDNA, “rolling circle”, and “self-synthesizing” groups, after which the phylogenetic relationship of the transposase, recombinase, helicase, or DNA polymerase, respectively, takes over. Like non-autonomous LTR elements, most non-autonomous DNA transposons can be classified based on their TIR combined with their target site duplication (TSD) pattern. We therefore do not provide structural categories like LARD (large LTR retrotransposon derivatives) or MITE (miniature inverted–repeat transposable elements).

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Drobnic, G. Vunjak-Novakovic (2008) Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Ther 3: 254-264. 46. Gamradt, S. C. , N. (2006) Tracking expression of virally mediated BMP-2 in gene therapy for bone repair. 450: 238-245. 47. Gentile, P. , A. Orlandi, M. G. Scioli, C. Di Pasquali, I. Bocchini, V. Cervelli (2012) Concise review: adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical implications for tissue engineering therapies in regenerative surgery. 1: 230-236. 48. Gimbel, M. , R. K. Ashley, M. . Heller, L. Wilson, H. K. Kawamoto, J. P. Bradley (2007) Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix. J 18: 895-901. 49. Giuliani, N. , G. Lisignoli, M. Magnani, C. Racano, M. Bolzoni, B. Dalla Palma, A. Spolzino, C. Manferdini, C. Abati, D. Toscani, A. Facchini, F. Aversa (2013) New insights into osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells and their potential clinical applications for bone regeneration in pediatric orthopaedics. Int 2013: 312501. 50. Glenn, J. D. , K. A. Whartenby (2014) Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. 6: 526-539. 51. Gomez-Barrena, E. , P. Rosset, I. Muller, R. Giordano, C. Bunu, P. Layrolle, Y. T. Konttinen, F. P. Luyten (2011) Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology. J Med 15: 1266-1286. 52. Gordon, J.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Patients with genotypes 5 and 6 have also been treated successfully. The first IFN-free triple combination approved for HCV genotype 1 was ritonavir-boosted paritaprevir and ombitasvir in one pill, and dasabuvir. Several phase III studies[15-18] showed an SVR from 95% to 100%. High SVR rates were also reported for patients with HCV genotype 4 without adding dasabuvir. All the above-mentioned data are awaiting solid confirmation from the real world. The early real-life data presented seem to confirm the trial results, albeit with a slightly lower SVR[19]. Further studies are necessary to evaluate the effect of treatment in patients with advanced liver disease as well as on the development of hepatocellular carcinoma (HCC). To this regard, preliminary studies seem to indicate that cirrhotic patients should undergo a close follow-up after HCV clearance by DAAs due to the residual possibility of developing HCC. In addition, considering the widespread use, the possibility to shorten the treatment duration should be evaluated. Overall, the data on safety seem to indicate good tolerability for all of the above combinations. Moreover, it seems that there are no absolute contra-indications to the use of these approved DAAs. However, it is necessary to be prudent with the use of sofosbuvir for patients with severe renal impairment. In addition, the triple combination of ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir has not yet been adequately evaluated in patients with Child-decompensated cirrhosis and is contraindicated in patients with Child-decompensated cirrhosis. Furthermore, the pharmacokinetics and safety of simeprevir for decompensated cirrhosis have not yet been fully evaluated, and it induces increased bilirubin levels in about 10% of cases. At present, considering the scanty data on the safety of DAAs in advanced liver cirrhosis, they must be used with extreme caution in this subgroup of patients. Moreover, if DAAs are administered to patients taking other drugs, it is mandatory that the drug-to-drug interaction be taken into account[20].

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: classification system does not display a ranked hierarchy as there will never be satisfying definitions for what a class, order, family or subfamily of TEs constitutes, while with the addition of new elements and growing knowledge of their relationship, the number of branches, and therefore subdivisions, along some parts of the tree will remain in flux (see 1 and Table S1). Wicker et al. proposed to define a family as a group of TEs that can be aligned over at least 80 bp and show 80% + identity covering 80% or more of the alignment [24]. Meant as a pragmatic definition, it has been pointed out that applying it would lead “to an unpredictable mix of monophyletic, paraphyletic and polyphyletic groups” [26]. Strictly following this rule will also not be practical, as, for example, newly identified TEs intermediate between known families will force these to be merged over time and the aforementioned reticulate relationship of TEs could join radically different TEs in one family. Also, some of the ranks are already in use for other purposes: the term “family” is often used for any group of aligned TE copies for which a consensus or HMM has been derived and, in animal TE annotation, “subfamilies” either indicate subsets of class I TE copies that share multiple co-segregating differences from the rest (Fig. 1) or sets of particular internal deletion products of an autonomous class II transposon. With its lack of taxonomic ranks, our schema avoids these issues. TEs may also be classified by their transposition mechanism and classification systems based on the mechanism of integration and chemistry of the transposition reaction have been proposed [27, 28]. These have the benefit of being able to integrate the wide variety of TEs active in prokaryotes, but are somewhat hampered by the lack of knowledge on the details of transposition by new, bioinformatically discovered TEs. Furthermore, written specifically to include prokaryotic TEs, the mechanistic classifications do not have the fundamental division in cis-active and trans-active elements, brought about by the separation of transcription and translation in eukaryotes.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: A. , M. Q. Hassan, M. Koss, M. Montecino, L. Selleri, A. J. van (2011) Epigenetic regulation of early osteogenesis and mineralized tissue formation by a HOXA10-PBX1-associated complex. Organs 194: 146-150. 53. Granero-Moltó, F. , J. A. Weis, M. I. Miga, B. Landis, T. J. Myers, L. O'Rear, L. . Spagnoli (2009) Regenerative effects of transplanted mesenchymal stem cells in fracture healing. 27: 1887-1898. 54. Grayson, W. L. , B. A. Bunnell, E. Martin, T. Frazier, B. P. Hung, J. M. Gimble (2015) Stromal cells and stem cells in clinical bone regeneration. Endocrinol 11: 140-150. 55. Grellier, M. , L. Bordenave, J. Amedee (2009) Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering. 27: 562-571. 56. Guo, X. , H. Park, G. Liu, W. Liu, Y. Cao, Y. Tabata, F. K. Kasper, A. G. Mikos (2009) In vitro generation of an osteochondral construct using injectable hydrogel composites encapsulating rabbit marrow mesenchymal stem cells. Biomaterials 30: 2741-2752. 57. Hauzeur, J. P. , V. Gangji (2010) Phases 1-3 clinical trials using adult stem cells in osteonecrosis and nonunion fractures. Int 26: 410170. 58. Hayashi, O. , Y. Katsube, M. Hirose, H. Ohgushi, H. Ito (2008) Comparison of osteogenic ability of rat mesenchymal stem cells from bone marrow, periosteum, and adipose tissue. Int 82: 238-247. 59. He, X. , R. Dziak, X. Yuan, K. Mao, R.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: the basis of the solid data from the trials on the efficacy and safety of all-oral INF-free combinations, the scientific community is euphoric about the elimination and even eradication of chronic hepatitis C. Therefore, now that we have a cure, the question is: In the real world, can we meet the conditions to make the dream come true? At the present, considering that HCV infection and its treatment are tremendously complex situations, the answer cannot be directly affirmative because of the many conditions, not impossible to overcome, that hamper the fulfillment of the dream. These conditions are linked to the elevated cost of drugs, to the access and delivery of care, to the epidemiology of HCV and to the political commitments to be undertaken. The current high cost of the new all-oral regimen allows access to treatment only for a restricted number of HCV-infected patients; at present, many countries have chosen to treat only patients with advanced liver diseases. The high treatment costs can only be justified by the need to recuperate the research and development costs of the drugs; it has been estimated that the predicted manufacturing costs of range from $100 to $270 per person for a 12-wk treatment course[21]. Thus, action strategies should be evaluated with the aim to reducing the price of the new drugs and allowing extensive access to the new treatments not only in high- but also in middle- and low-income countries, where the highest prevalence of HCV infection is concentrated. By extending access to treatment, a double advantage can be achieved: First, it will enable the drug companies to recover their costs sooner, and second, it will allow substantial individual and public health benefits by reducing both the hepatic and extrahepatic HCV-associated pathologies and the spread of HCV infection worldwide. Global negotiations should be undertaken to include state authorities, drug companies, healthcare authorities and the scientific communities to reduce the cost of treatment, thereby extending access to more patients and preventing the spread of HCV infection. In this respect, the policies adopted by Egypt and India have obtained a price reduction that will allow widespread treatment of HCV-infected patients. Alternatively, it will be necessary to wait 15 years for generic drugs, the time required for drug patents to expire.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: While the focus of the RepeatMasker/Repbase/Wicker classification on eukaryotes and on reverse transcriptase phylogeny has been criticized [29], a unified eukaryotic/prokaryotic TE classification would be unwieldy. In the future, we will explore the use of an independent classification for prokaryotic TEs. A TE family can be classified as belonging to any node in the classification tree by concatenating the names along the path from the root to the designated node. For example, the highlighted node in Fig. 2 is referenced with the string “Interspersed_repeat;Unknown”. This enables partial classifications to be made and node labels to be reused. All classifications are linked to the corresponding RepeatMasker, Repbase, Wicker-et-al. or Curcio-Derbyshire classification, where they are available. While most interspersed repeats identified by de novo repeat finding programs are derived from TEs, alternative origins include (i) simple tandem repeats, originating independently at many sites, (ii) long tandem repeats like satellites, found at multiple (sub)telomeric and centromeric sites, (iii) segmental duplications, (iv) common coding motifs like zinc fingers, and (v) gene families. In mammals, the most common non-TE source of interspersed repeats are retro(pseudo)genes that have been accidently copied by the LINE1-mechanism; some small structural RNAs occur with over a thousand copies [30]. While our classification system includes these categories for annotation purposes, most of these entries should not be part of Dfam. Satellites and small structural RNAs are included in Dfam, but shorter tandem repeats are better detected by specialized programs like TRF [31] and ULTRA [32] and the inclusion of segmental duplications, cellular transcripts or coding regions would lead to much false annotation. Transposon terminiMost methods to categorize newly identified TEs are pipelines that rely heavily on finding homology to existing classified TEs [17, 33,34,35]. When a curated library of a related species exists, near-full-length matches at the DNA level are often found that allow proper class assignment. A translated comparison to a TE protein database can classify many models with (remnants of) coding sequence.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Genco, M. Swihart, D. Sarkar, C. Li, C. Wang, L. Lu, S. Andreadis, S. Yang (2013) BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects. PLoS One 8: e60473. 60. (1990) Percutaneous bone marrow grafting of delayed union and nonunion in cancer patients. 256: 280-285. 61. Hermund, N. U. , A. Stavropoulos, O. Donatsky, H. Nielsen, C. Clausen, J. Reibel, B. Pakkenberg, P. Holmstrup (2012) Reimplantation of cultivated human bone cells from the posterior maxilla for sinus floor augmentation: histological results from a randomized controlled clinical trial. 23: 1031-1037. 62. Hernigou, P. , F. Beaujean (2002) Treatment of osteonecrosis with autologous bone marrow grafting. 405: 14-23. 63. Hernigou, P. , G. Mathieu, A. Poignard, O. Manicom, F. Beaujean, H. Rouard (2006) Percutaneous autologous bone-marrow grafting for nonunions: surgical technique. J 88(suppl 1): 322-327. 64. Hipp, J. , A. Atala (2004) Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy. J 1: 3. 65. . Muul, T. Hofmann (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. 99: 8932-8937. 66. . Neel, M. Sussman, P. (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. 5: 309-313. 67. (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97: 1227-1231. 68. Houlden, H. , P.

Output: corroborate


Input: Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: If this should occur, the question that everyone should ask themselves is: Is it ethical to let someone die of hepatitis C when effective treatment is available but is inaccessible due to the high cost, especially since we know that treatments can be produced at a very low cost? At present, of the estimated 150-200 million HCV-infected subjects worldwide, only the tip of the iceberg is really known. Consequently, if we presume today that the drug costs could be reduced, we would be able to treat only the prevalent cases of HCV. To achieve the elimination of HCV infection another two conditions have to be considered, the cases that are unaware of their HCV status and the incident cases. As a substantial number of countries do not have a screening program, it is critical to start adequate screening programs to identify subjects to be treated. Furthermore, the spread of HCV infection must be taken in hand to identify incident cases. Therefore, marginalized populations, drug users and intra-family spread of the infection must be monitored. To this regard, the current costs for both the epidemiological and pre-treatment screening is high. To ensure widespread treatment with the new it is necessary to reduce the costs of diagnostic tests and, perhaps, determine only the HCV genotype to detect viremic subjects and decide the best therapeutic approach. A further critical point is the delivery of treatment. At present, due to the high cost and the complexity of therapy, treatment is confined to specialist care centers to administer the drugs. However, for several reasons, these centers are not accessible to all infected subjects and in order to implement a successful HCV elimination program, non-specialists in primary care settings could deliver treatment. Due to the complexity of treatment, to be sure that an effective regimen is delivered, specialist supervision in the primary care should be given. could be a model for the management of HCV[22,23] where the decisions on treatment could be made using communication technologies. fantastic race for effective treatment for HCV has reached the final straight and the finishing line that marks the fulfillment of the dream can be clearly seen. Although the reality has exceeded all expectations, the do not appear to be ready to take on the challenge for victory.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: However, due to the recombinant and modular tendencies of TEs, sequence homology is not always sufficient evidence for classification, especially if similarities are fragmentary or weak. For example, many non-autonomous class I and II elements carry insertions or fragments of non-related TEs, while a model matching the 3′ end of a LINE element may represent a SINE instead. Even functional TE coding regions can be misleading as related proteins have been repurposed in disparate TEs; for example, the transposases of the cut-and-paste Ginger transposons are closely related to the integrases of both Gypsy retrotransposons and Maverick/polinton self-synthesizing elements [36, 37]. Needless to say, TEs without (remnant) coding sequence or related entries in the database will remain unclassified using this method alone. There are fortunately other characteristics and sequence features of TEs that can confirm the mechanism by which the element propagated, and in turn, how it should be classified. Clusters of copies with co-segregating mutations generally imply that the TE is a class I element, and, given enough copies, their complete absence suggests a class II element. A simple-repeat tail and TSDs of variable length indicate movement via target-primed reverse transcription, which requires the protein products of LINEs. When models have TG…CA termini and carry a poly-adenylation signal, while their copies are flanked by 4–6 bp TSDs, they likely represent solitary LTRs, which, through homologous recombination, can vastly outnumber complete LTR elements in a genome. In our experience, many models that resist automatic categorization represent non-autonomous class II elements that actually can be classified in detail based on the pattern of the terminal 20–50 bp. This is particularly true for the ubiquitous TIR transposons: their transposases specifically recognize and bind the terminal sequences, to the point that these are sufficient for an element to retain or obtain mobility [38, 39]. As a result, transposons with similar transposases (the basis of their classification) have similar termini.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Charlton, D. Singh (2007) Neurology and orthopaedics. J Psychiatry 78: 224-232. 69. Huang, S. , L. Xu, Y. Zhang, Y. Sun, G. Li (2015) Systemic and local administration of allogeneic bone marrow derived mesenchymal stem cells promotes fracture healing in rats. 24: 2643-2655. 70. Jr, N. Anderson, K. Chambers (1995) Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects. 80: 24-27. 71. Izadpanah, R. , B. A. Bunnell (2008) Gene delivery to mesenchymal stem cells. Biol 449: 153-167. 72. van Gool (2013) Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Biol 91: 32-39. 73. Jafarian, M. , M. B. Eslaminejad, A. Khojasteh, F. Mashhadi Abbas, M. M. Dehghan, R. Hassanizadeh, B. Houshmand (2008) Marrow-derived mesenchymal stem cells-directed bone regeneration in the dog mandible: a comparison between biphasic calcium phosphate and natural bone mineral. 105: e14-e24. 74. Janowski, M. , A. Lyczek, C. Engels, J. Xu, B. Lukomska, J. W. Bulte, P. Walczak (2013) Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation. J 33: 921-927. 75. Jones, E. A. , A. English, K. . Emery, D. McGonagle (2004) Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. 50: 817-827. 76. Jurgens, W. J. , R. J. Kroeze, B. Zandieh-Doulabi, A. van van Milligen, M. J. Ritt, M. N.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: Go to 5804. DOI: 10. 19080/CTOIJ. 2018. 11. 555804 Go to 0. 5%-1% of all mammary carcinomas. Even though it has a non-aggressive biological behaviour and a notable long-term prognosis, there is no general agreement in terms of therapeutic management, the tendency being to avoid adjuvant therapies such as radiotherapy. Case Report: A caucasian woman of 75 yr, started with the appearance of a painless right breast node, with no other symptoms. Diagnostics confirmed a malignant node in the right breast, classified as 4. The patient underwent a core needle biopsy and the histological study revealed a papillary neoplasia. The tumor board decided to perform lumpectomy and sentinel node biopsy with a final pathologic result of encapsulated papillary carcinoma, with positive hormone receptors, HER2 negative, Ki67=40%, no lympho-vascular nor perineural invasion and negative sentinel lymph node. The patient was referred to radiation oncology department to evaluate adjuvant treatment. After reviewing the literature about pure IPC, with no in situ or intraductal component, no adjuvant therapies were performed. The patient was then referred to gynecology department for close follow-up. Nowadays, at 10 months follow-up she has a good performance status with no evidence of disease. Keywords: Carcinoma; Adjuvant Treatment; Lumpectomy; Radiotherapy; Go to 0. 5% and 1% of all mammary carcinomas [1-4]. In the last WHO classification we can find the IPC divided in 4 subgroups: intraductal papilloma, intraductal papillary carcinoma, encapsulated papillary carcinoma and solid papillary carcinoma [5]. Over the last years this type of tumor has been found with other names too and has even been classified differently, however the fact that this type of disease has an indolent course and a good prognosis has remained consistent. Despite this last assertion, it is no completely exempt of the possibility of turning into a disseminated disease. IPC is found more frequently among postmenopausal women, with a mean age around 67 years old, predominantly in caucasians [6-12].

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: While these terminal homologies are too short to appear significant in a whole database search, they can be found by comparing the 30–60 bp termini of new elements to the 30–60 bp termini of all classified class II elements and filtering the output by orientation and position. Characteristic TSDs can cement classification. Over the years, we classified thousands of short sequences in Repbase this way, including ancient elements that were active in the common ancestor of all amniotes. In Dfam, we now provide terminal sequence signatures for 64 categories of class II elements, for use in classifying new TE models. To create these signatures, we lined up the 5′ and 3′ 60 bp of all members of a particular type that seem to have clearly defined ends (e. g. as indicated by the presence of the expected TSDs, Fig. 3). Minor modifications were made to some of the nearly 12,000 remaining consensus sequences in order to have each start at the true beginning or end of the TE. This most commonly involved removing (partial) target site duplications or adding one or more Ns when comparison to others showed the sequence to be short. The alignments are ungapped, however, and it is possible that more signal can be obtained by allowing a few indels. We used HMMER (hmmbuild) to develop HMMs for the 5′ ends, the 3′ ends, and, in case of TIRs, the combined termini. Fig. 3Generation of HMMs and sequence LOGOs for DNA transposon termini. The first/last 60 bp of family consensi belonging to a single classification of DNA Transposons are piled up and aligned (without gaps) by hand. Profile HMMs are developed for each end and for the combination of the two to determine if a stronger signal may be obtained in that fashion. Finally, LOGOs are generated for each HMM and displayed on the Dfam websiteFull size imageThe LOGOs of the termini can be viewed on the “Classifications” page on the Dfam website, and are organized by class II subclasses (e. g. , Crypton, Helitron, TIR, etc. ). This allows for easy visualization of the base conservation at each position in the terminal sequences and comparisons between the 5′ and 3′ termini.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Helder (2013) One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study. Access 2: 315-325. 77. Kadiyala, S. , (1997) Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. 6: 125-134. 78. Kaigler, D. , G. . (2013) Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. 22: 767-777. 79. Kean, T. J. , P. Lin, A. I. Caplan, J. E. Dennis (2013) MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Int 2013: 732742. 80. Kim, J. ,. Choi, Y. Park, K. Sun, S. J. Hwang (2010) In vivo evaluation of MMP sensitive high-molecular weight HA-based hydrogels for bone tissue engineering. J 95: 673-681. 81. Kim, J. ,. Tae, I. Noh, S. H. Lee, Y. Park, K. Sun (2007) Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 28: 1830-1837. 82. (2011) Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow. J Sci 41: 192-200. 83. (2009) A multi-center, randomized, clinical study to compare the effect and safety of autologous cultured osteoblast (Ossron) injection to treat fractures. BMC 10: 20. 84. Kitaori, T. , H. Ito, E. M. Schwarz, R. Tsutsumi, H. Yoshitomi, S. Oishi, M. Nakano, N. Fujii, T. Nagasawa, T. Nakamura (2009) Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: The clinical presentation is variable, and it is possible to find asymptomatic patients, woman with a palpable node in an otherwise normal breast or even becoming manifest in the form of a swelling breast due to the presence of a large intracystic mass. Histologically, this tumor is usually described as an encysted lesion, containing nodules of papillary carcinoma surrounded by a thick fibrous capsule [2,4,6]. As in addition, and being more accurate with its histologic features, in the 4th WHO classification, IPC was considered more as a less aggressive variant of papillary carcinoma, due to its lack of myoepithelial layer [8,9]. Regarding the radiological features, the tumor can be found in a mammographic image as a round, oval lesion or as a circumscribed lobulated mass (in consequence of the appearance of a dilated duct) [7-8]. Given the rarity of the disease and the lack of agreement in terms of histologic classification, there is no general consensus about the management of patients with this type of pathology. In spite of these inconsistencies, and taking into account its indolent course, the WHO working group recommends classifying them, and therefore managing them, as a Tis (in situ carcinomas), as long as they do not have clear invasive component [5,9,13]. Here we present the case of a woman diagnosed with pure IPC of the breast that is followed by a literature review focused on this subtype of papillary carcinoma with the aim of proposing a therapeutic management of these rare tumors. Go to 0. The patient was then moved to the radiation oncology department to consider the possibility of breast radiotherapy as adjuvant treatment. Given the rarity of the case and following review of the literature published on this histological subtype (pure intracystic papillary carcinoma, with no component of in situ nor intraductal carcinoma), mostly given by case reports or retrospective series, we concluded that this was a very noninvasive type of cancer where, in women over 50 years of age, no adjuvant therapies (radiotherapy and/or hormone therapy) may be indicated as it would not increase local control or the overall survival. We spoke to the patient and family about this matter, and in consensus we reached the decision of therapeutic abstention and close follow-up by Gynecology department.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: The full set of profiles may be downloaded and will be updated as new elements are added to each class. Dfam growthThe development of a curated TE library for a given species is a specialized and mostly manual task that has only incrementally improved since the inception of TE databases. We recognize that as reference genome sequencing increases at a faster rate, and until automated curation methods improve, uncurated datasets (mostly de novo generated TE libraries) will far outpace the development of curated libraries. There are some advantages to making uncurated datasets available through a resource such as Dfam: (1) they can be used as simple genome masking libraries, and the fragmentation and redundancy that are the hallmark of datasets derived from de novo discovery tools are not detrimental in that context, (2) cataloging uncurated families provides a shared starting point for community curation efforts, and (3) these datasets will provide a resource for developing per-family and per-library quality metrics as well as improved automated curation tools. In the latest release of Dfam we have added support for uncurated datasets, denoting these families using the new accession prefix “DR” and limiting/altering the analysis and metadata displayed for these families (Fig. 4). For instance, a DR family has both a consensus and a profile HMM generated for it, but does not have rigorously characterized false discovery rate thresholds as for curated families [3] due to the lack of pre-calculated assembly annotations. However, uncurated families do contain provenance for the seed alignment, standard metadata (description, classification, taxa, 3. 3. A subset of species are named and species-rich groups are collapsed into triangles, with the number of species indicated. Major branch points have been labeled according to the NCBI taxonomy. Branching times and order of the tree are roughly following that of the OneZoom project [40] with modifications based on more specific research; for example, the branching order within the birds is according to Prum et al. [41]Full size imageDue to the scale of the dataset, only minimal prefiltering of the families was performed before import. Families with > 80% tandemly repetitive sequence and less than 100 bp of contiguous non tandemly repetitive sequence (according to TRF) were removed. This filtered 894 families.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: 60: 813-823. 85. . Cui (2015) Interactions between MSCs and immune cells: implications for bone healing. J 2015: 17. 86. Krebsbach, P. H. , M. H. Mankani, K. Satomura, S. A. Kuznetsov, P. G. Robey (1998) Repair of craniotomy defects using bone marrow stromal cells. Transplantation 66: 1272-1278. 87. Le Blanc, K. , C. Gotherstrom, O. Ringden, M. Hassan, R. McMahon, E. Horwitz, G. Anneren, O. Axelsson, J. Nunn, U. Ewald, S. Norden-Lindeberg, M. Jansson, A. Dalton, E. Astrom, M. Westgren (2005) Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation 79: 1607-1614. 88. (2011) Direct deposited porous scaffolds of calcium phosphate cement with alginate for drug delivery and bone tissue engineering. 7: 3178-3186. 89. . Shin (2010) Control of osteogenic differentiation and mineralization of human mesenchymal stem cells on composite nanofibers containing poly[lactic-co-(glycolic acid)] and hydroxyapatite. 10: 173-182. 90. (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103: 1669-1675. 91. . Ylostalo, B. L. Larson, L. Semprun-Prieto, P. Delafontaine, D. J. Prockop (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell 5: 54-63. 92. Levi, B. , A. W. James, E. R. Nelson, S. Li, M. Peng, G. W. Commons, M. Lee, B. Wu, M. T.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: At the last followup visit (10 months after diagnosis) no evidence of disease has been found. Go to 5. 8% of the total) had a loco-regional relapse and only 9 patients overall (1. 9%) suffered metastasis. Additionally, the percentage of survival related to the disease was 99. 4%. In particular, in the study by Solorzano et al. [11], no differences were found in the rate of local recurrence or death due to disease when analyzing the type of surgery (mastectomy or conservative surgery) or the associated use of adjuvant radiotherapy. They concluded that the decision about adjuvant therapy in these cases should be based on the presence of associated lesions, such as an in situ or invasive intraductal component, and that the benefit of radiotherapy in patients with pure IPC was unclear. In another study performed by Fayanju et al. [9], after studying the data of 45 patients with IPC, the conclusion was that patients with pure IPC received less adjuvant therapies (radiotherapy and hormone therapy) compared to patients with IPC associated with an intraductal or invasive component. When clinicians have to decide about the therapeutic approach, patient age is also taken into account, with patients under 50 being more suitable for radiotherapy as compared to older ones. Another factor considered is the type of surgery performed, since the few patients who underwent a mastectomy did not receive adjuvant radiotherapy, but those who had undergone a more conservative surgery in some cases received adjuvant radiotherapy. Despite this, it was found that no patient with pure IPC who had undergone a more conservative surgery had relapse due to it, corroborating what had been seen in other studies, that a mastectomy is not necessary in the treatment of pure IPC and that any adjuvant treatment should be tailored to patient’s histology in order to ensure the excellent outcome expected for these neoplasms. Hence, adjuvant radiotherapy and/or hormone therapy should be considered both for patients with IPC associated with in situ component or microinvasion and for patients under 50 with pure IPC. Esposito et al. [14], in their study of 27 patients suffering from IPC, confirmed that IPCs have an excellent prognosis and so local treatment alone may be sufficient to control the disease. Finally, in another retrospective study performed by Rakha et al.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: TRF was run with a maximum period of 20 bp to preserve common and complex satellite sequences in the dataset. The number of TE models in Dfam has grown from 6915 to 273,655, largely because of the RepeatModeler libraries for 336 additional species contributed by the EBI. Table S2 contains statistics for these EBI additions alone. 116 bony fish, 133 bird and 47 mammalian species form the bulk of the additions, and numbers for these clades alone are displayed in the table. A generally higher variety of recognizable TEs in fish and lower variety in birds is reflected in the data: bony fish (35% of the new species) contributed 58. 4% of the added models, while mammals and birds (14 and 40% of the new species) each contributed about 9. 3% of the new models (Table S2). The remaining 10% of the EBI dataset, and therefore 23% of the TE diversity, belong to other groups outside of bony fish, mammals, and birds that include: plants, cartilaginous fish, turtles and lizards. An analysis of the TE classes and superfamilies in each of the aforementioned clades depicted that bony fish contribute a large number of models across class II TE superfamilies, and are consequently enriched for class II TEs (2 and Table S2). Birds and mammals contribute to and are enriched for LINEs (CR1 and L1, respectively), in addition to endogenous retrovirus (ERV)-like LTR elements. The EBI dataset confirms large-scale patterns visible in addition to providing data regarding TE expansion for individual organisms. Examples of the seed alignments generated as part of the aforementioned pipeline can be observed in Fig. 6. The seed alignment for any model provides researchers with a wealth of information including sequence coverage, length, and number of sequences contributing to the model. From a curator’s perspective, information like divergence patterns and blocks of seemingly truncated sequences are also evident. For example, a block of sequences in an LTR alignment that show a different divergence pattern and/or appears to be truncated at the same position relative to the consensus sequence are likely to indicate a subfamily structure within the model (Fig. 6a, red box). This alignment pattern reflects the biology of the TE, as LTR sequences regularly recombine their 5′ and 3′ ends to form new families [43].

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Longaker (2010) Human adipose-derived stromal cells stimulate autogenous skeletal repair via paracrine hedgehog signaling with calvarial osteoblasts. Dev 20: 243-257. 93. Levi, B. , M. T. Longaker (2011) Adipose derived stromal cells for skeletal regenerative medicine. 29: 576-582. 94. Li, F. , N. Whyte, C. Niyibizi (2012) Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrine activities on exogenous MSCs: implications for paracrine activities in bone regeneration. 426: 475-479. 95. Li, H. , K. Dai, T. Tang, X. Zhang, M. Yan, J. Lou (2007) Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2. 356: 836-842. 96. Liao, J. , X. Guo, D. Nelson, F. K. Kasper, A. G. Mikos (2010) Modulation of osteogenic properties of biodegradable polymer/extracellular matrix scaffolds generated with a flow perfusion bioreactor. 6: 2386-2393. 97. Liebergall, M. , J. Schroeder, R. Mosheiff, Z. Gazit, Z. Yoram, L. Rasooly, A. Daskal, A. Khoury, Y. Weil, S. Beyth (2013) Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. 21: 1631-1638. 98. Lotfy, A. , M. Salama, F. Zahran, E. Jones, A. Badawy, M. Sobh (2014) Characterization of mesenchymal stem cells derived from rat bone marrow and adipose tissue: a comparative study. 7: 135-142. 99. Luo, Y. , M. S. Shoichet (2004) Light-activated immobilization of biomolecules to agarose hydrogels for controlled cellular response. Biomacromolecules 5: 2315-2323. 100. Mallela, J. , S.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: [8] with data from 207 patients with IPC, it was concluded that IPC is a carcinoma with a very favourable prognosis and that moderate local treatment, with an addition of hormone therapy in selected cases, is sufficient for an optimal outcome. In general terms, many of these studies agreed to conclude that pure IPC variant has an indolent course with a very good prognosis even in those patients in whom the management is only surgical, without the association of adjuvant therapies. In addition, the absence of axillary lymph node involvement in this type of patients excludes the need to carry out axillary staging procedures [1,17-19]. However, some authors consider the procedure of sentinel lymph node biopsy as a prudent approach, given the uncertainty concerning the intraductal vs. invasive nature of IPC [20-23]. More recently, in 2016, a retrospective analysis was published, based on data from the SEER (Surveillance, Epidemiology, and End Results) database, including 2649 patients diagnosed with IPC [24], where the authors concluded that overall, IPC has a very good prognosis and that survival is improved in caucasian patients and in patients who receive radiation therapy, but two important limitations in this study were the inability to specifically assess whether patients had pure IPC or the presence of an invasive component and the fact that the effect of administration of other adjuvant therapies (such as hormone therapy) could not be assessed as these variables are not captured within the database. Go to 19. (1967) Intracystic carcinoma of the female breast. Obstet 124(1): 93-98. (1958) Intracystic carcinoma of the breast. Obstet 106(3): 347-352. (1992) Tumors of the mammary gland. 3rd (edn), Institute of 219. (2012) WHO classification of tumors of the breast. Lyon: for Research on Cancer, Lyon, France. (2008) Intracystic papillary carcinoma: a review of 917 cases. Cancer 113(5): 916–920. (1995) Papillary carcinoma of the breast: imaging findings. Roentgenol 164(2): 321-326. van (2011) Encapsulated papillary carcinoma of the breast: an invasive tumor with excellent prognosis. 35(8): 1093–1103.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: Similarly, blocks of outwardly truncated sequences close to the 5′ end in an L1 seed alignment reflect a tendency for differing patterns present in the 5′ UTR regions [44] (Fig. 6b). Closer inspection of these sequence blocks within the alignment is warranted to determine if a subfamily structure is present. Fig. 6Seed alignment examples from raw Dfam 3. 3 entries. A) ERV1 (LTR) (DR0086957. 1; Eulemur macaco (black lemur)). The red bracket indicates a group of sequences differing in length and divergence patterns. 506 sequences contribute to the seed alignment for this 503 bp model. B) L1 sequence (DR0215804. 1; Phyllostomus discolor (pale spear-nosed bat)). The red brackets indicate two groups of sequences that differ in their 5′ alignment. One thousand one hundred eighty-six sequences contribute to the seed alignment for this 7353 bp model. Each sequence is represented by a single row (sorted by start position) where the color gradient indicates alignment quality (red = low; blue = high) over 10 bp non-overlapping windows. The solid green shape over the two seed alignments indicate the coverage along the model consensus sequence. Note: the two panels differ in scaleFull size imageBy providing the RepeatModeler output for the additional 336 species, Dfam encourages the TE community to lend their expertise, thus improving this dataset so that it moves from a raw dataset to a highly curated one. We are working on providing tools for the community to curate and improve upon these and existing curated datasets. Architectural and Interface improvementsThe architecture of Dfam was refactored in Dfam 3. 0 to prepare the resource for housing TE families, seed alignments, and sequence models at scale. website ( has been updated to provide both (i) a front end intended for human interaction through a web browser (the ‘portal’) and (ii) an API served over HTTP to support programmatic access to Dfam data. The source code for both projects is available on GitHub ( and released under the CC0 public domain dedication. The API uses computer-friendly data formats such as JSON and tab-separated values (as appropriate), which makes it more suitable as a data source for community-developed tools than the human-oriented format of the website.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Tatullo (2015b) Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells. J 94: 843-852. 108. Marrelli, M. , M. Tatullo (2013) Influence of PRF in the healing of bone and gingival tissues: clinical and histological evaluations. Sci 17: 1958-1962. 109. Mathieu, P. S. , E. G. Loboa (2012) Cytoskeletal and focal adhesion influences on mesenchymal stem cell shape, mechanical properties, and differentiation down osteogenic, adipogenic, and chondrogenic pathways. B Rev 18: 436-444. 110. Mehta, M. , K. Schmidt-Bleek, G. N. Duda, D. J. Mooney (2012) Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. 64: 1257-1276. 111. Meier, R. P. , Y. D. Muller, P. Morel, C. Gonelle-Gispert, L. H. Buhler (2013) Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence? Res 11: 1348-1364. 112. Melek, L. N. (2015) Tissue engineering in oral and maxillofacial reconstruction. J 12: 211-223. 113. (2015) Posterior partially edentulous jaws, planning a rehabilitation with dental implants. 3: 65-76. 114. Moreau, J. L. , H. H. Xu (2009) Mesenchymal stem cell proliferation and differentiation on an injectable calcium phosphate-chitosan composite scaffold. Biomaterials 30: 2675-2682. 115. Moshiri, A. , A. Oryan (2013) Role of platelet-rich plasma in soft and hard connective tissue healing: an evidence-based review from basic to clinical application. 2: 6. 116. Moshiri, A. , A. Oryan, A. Meimandi-Parizi (2015a) Synthesis, development, characterization and effectiveness of bovine pure platelet gel-collagen-polydioxanone bioactive graft on tendon healing.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: (2007) Therapeutic management of intracystic papillary carcinoma of the breast: the roles of radiation and endocrine therapy. Surg 194(4): 497-500. (1999) Treatment and outcome of intracystic papillary carcinoma of the breast. Surg 86(10): 1274. (2002) Treatment and outcome of patients with intracystic papillary carcinoma of the breast. Surg 184(4): 364–368. (1998) Intracystic (encysted) papillary carcinoma of the breast: a clinical, pathological, and immunohistochemical study. 29: 1097-1104. (2009) Encapsulated apocrine papillary carcinoma of the breast-a tumour of uncertain malignant potential: report of five cases. Virchows Arch. 455(6): 477-483. (2009) Are encapsulated papillary carcinomas of the breast in situ or invasive? A basement membrane study of 27 cases. 131: 228-242. (2008) Papillary lesions of the breast: Selected diagnostic and management issues. Histopathology 52(1): 20-29. Collins L, O’ (2012) Encapsulated papillary carcinoma. In: van de Vijver MJ, editors. WHO classification of tumors of the breast. for Research on Cancer, Lyon, France, 107. Collins L, O’ (2012) Encapsulated papillary carcinoma. In: van de Vijver MJ, editors. WHO classification of tumors of the breast. for Research on Cancer, Lyon, France, 107. (1983) Immunohistochemical analysis of benign and malignant papillary lesions of the breast. 7(5): 451-461. (1998) Recent patterns of hormone replacement therapy use in a large managed care organization. J 7: 1017-1026. (1994) Intraductal (intracystic) papillary carcinoma of the breast and its variants: A clinicopathological study of 77 cases. 25(8): 802-809. -Tanaka S, et al. (2009) Clinical and pathological features of intracystic papillary carcinoma of the breast. 39(1): 5-8. (2009) Breast intracystic papillary carcinoma: An update. 15(6): 639-644.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: The portal has gained several significant new features. To support the massive scale of family data we replaced the old one-page-per-letter approach to family organization with a “Browse” page that supports sorting and filtering on multiple criteria such as name, classification, taxon, or keywords. Some similar filters have also been added to the “Relationships” tab to restrict results to related species. The “Features” tab has been added to the per-family page to display curated features (binding sites, hand-curated coding sequences etc), as well as blastx matches against other known TE protein sequences. The architectural changes also facilitated the merger of Dfam and Dfam_consensus [45], creating a single resource for both consensus and HMM sequence models for each family. During the merger, Dfam inherited the seed alignment visualization from Dfam_consensus. This visualization shows both coverage (how many representatives cover each portion of the alignment) and the conservation patterns within the alignment, shown as a heatmap indicating how closely each member aligns to the consensus (as seen in Fig. 6). Dfam also now includes an authentication system and public data submission system; this is the first step in a planned development of a curation workbench that will provide users with tools to edit and curate data uploaded by themselves or (eventually) others. Software/tool distribution improvementsOne of the main hurdles with using bioinformatic pipelines and tools is the complexity of the installation and configuration necessary to use them. Software containers are an increasingly popular way to tackle this problem, by delivering an executable user environment that comes with pre-installed and pre-configured software packages. In order to support community curation efforts we have developed containers for Docker and Singularity, housing pre-installed versions of our latest tools (e. g. ) and dependencies as well as external open-source tools (e. g. HMMER, mafft, cdhit, TRF). More information along with instructions for use are available at As part of our outreach efforts, we will be eliciting recommendations for including additional packages in future releases. Notably these containers include FamDB, a new HDF5-based Dfam export format and associated query tools for offline access to Dfam.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: J Med 19: 1308-1332. 117. Moshiri, A. , M. Shahrezaee, B. Shekarchi, A. Oryan, K. Azma (2015b) Three-dimensional porous Gelapin-Simvastatin scaffolds promoted bone defect healing in rabbits. Int 96: 552-564. 118. 'Brien (2010) The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials 31: 461-466. 119. Murphy, M. B. , K. Moncivais, A. I. Caplan (2013) Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Med 45: e54. 120. Murrell, W. D. , A. W. Anz, H. (2015) Regenerative treatments to enhance orthopedic surgical outcome. 7(suppl 4): S41-S52. 121. Nanes, M. S. (2003) Tumor necrosis factor-α: molecular and cellular mechanisms in skeletal pathology. Gene 321: 1-15. 122. Nsair, A. , W. R. MacLellan (2011) Induced pluripotent stem cells for regenerative cardiovascular therapies and biomedical discovery. 63: 324-330. 123. Olmsted-Davis, E. , F. H. Gannon, M. Ozen, M. M. Ittmann, Z. -Dilling, S. Schumara- (2007) Hypoxic adipocytes pattern early heterotopic bone formation. Pathol 170: 620-632. 124. Oryan, A. , S. Alidadi, A. Moshiri, A. Bigham- Sadegh (2014a) Bone morphogenetic proteins: a powerful osteoinductive compound with non-negligible side effects and limitations. Biofactors 40: 459-481. 125. Oryan, A. , S. Alidadi, A. Moshiri, N. Maffulli (2014b) Bone regenerative medicine: classic options, novel strategies, and future directions. J Res 9: 9-18. 126. Oryan, A. , A. Kamali, A.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: com Received: May 9, 2024Revised: June 7, 2024Accepted: June 18, 2024Published online: August 6, 2024Processing time: 53 Days and 21. 8 sign is a specific electrocardiographic manifestation of ostium secundum atrial septal defects (ASDs), which is associated with the severity of the left-to-right shunt. Herein, we reported a case of selective his bundle pacing (S-HBP) that eliminated crochetage sign in a patient with ostium secundum ASD. 77-year-old man was admitted with a 2-year history of chest tightness and shortness of breath. Transthoracic echocardiography revealed an ostium secundum ASD. Twelve-lead electrocardiogram revealed atrial fibrillation with a prolonged relative risk interval, incomplete right bundle branch block, and crochetage sign. The patient was diagnosed with an ostium secundum ASD, atrial fibrillation with a second-degree atrioventricular block, and heart failure. The patient was treated with selective his bundle pacemaker implantation. After the procedure, crochetage sign disappeared during his bundle pacing on the electrocardiogram. -HBP eliminated crochetage sign on electrocardiogram. Crochetage sign may be a manifestation of a conduction system disorder. Key Words: Crochetage sign; Atrial septal defect; Pacemaker; Selective his bundle pacing; Case report Core Tip: Crochetage sign is a characteristic electrocardiographic manifestation seen in patients with ostium secundum atrial septal defects. We reported the case of a patient with secundum atrial septal defect, atrial fibrillation, and second-degree atrioventricular block who received selective his bundle pacing (S-HBP) treatment. Subsequently, crochetage sign was eliminated by S-HBP. Crochetage sign may indicate a conduction system disease. Citation:. Selective his bundle pacing eliminates crochetage sign: A case report. 2024; 12(22): 5276-5282 URL: DOI: an incidence of 6%-10% after birth, atrial septal defect (ASD) is one of the most prevalent congenital heart diseases, with secundum ASD being the most common[1].

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: FamDB files contain family consensi/HMMs and the NCBI Taxonomy data related to these families in a format that allows for fast offline access from the command line. The current release of FamDB includes all Dfam consensus sequences, HMMs, metadata, and 61,003 taxa from NCBI’s taxonomy database [46] related to these families. Lookups for information on a single taxon or family complete in about a second; extraction of consensus sequences () or HMMs for all TE families found in Human (including ancestral repeats) complete in about 3 to 4 s. Due to indexing, the run time for data queries is largely independent of the total number of TEs in the database: it takes about the same amount of time to extract the human library from a FamDB file including only the curated subset of Dfam (6915 entries) as for the full database (273,655). Future challenges/directionsThe curation of multi-species TE databases involves many manual tasks (e. g. defragmentation, classification validation, lineage assignment) and many subjective decisions (e. g. redundancy removal, pseudogene removal, subfamily characterization) that have not been universally standardized into protocols. With the growth of uncurated TE libraries and their inclusion in databases such as Dfam, it has become necessary to develop protocols for many of these tasks and to consider the challenges introduced by this data growth. Here, we discuss two of these topics that we will be focusing on in the near term. SubfamiliesWhen a family is believed to exhibit subfamily structure, there are a variety of methods available to cluster the family copies into subfamily groups. A subfamily structure is suspected when there is a wide divergence distribution of family members, or directly observing distinct groups of co-segregating subsequences in a seed alignment. Wicker used the aforementioned 80/80/80 rule to cluster sequences into subfamilies: sequences are clustered such that all members of the subfamily share at least 80% sequence identity and at least 80% sequence coverage with length greater than 80 bp. A strategy to define subfamilies was used in the analysis of bread wheat subgenomes by applying a 90/90 or 95/95 rule in which 90 or 95% sequence identity and 90 or 95% sequence coverage was used to cluster sequences into subfamilies [47, 48].

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Moshiri (2015) Potential mechanisms and applications of statins on osteogenesis: current modalities, conflicts and future directions. J 215: 12-24. 127. Oryan, A. , A. Moshiri (2013) Tissue engineering: alternative option in managing large and massive tissue deficits. Surg 1: e101. 128. Otsuru, S. , K. Tamai, T. Yamazaki, H. Yoshikawa, Y. Kaneda (2007) Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice. 354: 453-458. 129. Pak, J. , J. H. Lee, S. H. Lee (2014) Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells. Int 436029: 30. 130. Papandreou, I. , R. A. Cairns, L. Fontana, A. L. Lim, N. C. Denko (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. 3: 187-197. 131. Park, S. H. , A. Tofighi, X. Wang, M. Strunk, T. Ricketts, J. Chang, D. L. Kaplan (2011) Calcium phosphate combination biomaterials as human mesenchymal stem cell delivery vehicles for bone repair. 97: 235-244. 132. Pelegrine, A. A. , C. E. da Costa, M. E. Correa, J. F. Marques Jr. (2010) Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft. 21: 535-542. 133. Peng, F. , H. Wu, Y. Zheng, X. Xu, J. Yu (2012) The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Sci 27: 645-653. 134. . (2009) Analysis of the osteoinductive capacity and angiogenicity of an in vitro generated extracellular matrix. J 88: 295-303. 135.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: AV nodal conduction disorders are uncommon in other forms of ASD[8]. The incidence of heart block in patients with ASD is unclear, and ASD with high-grade AV block is relatively uncommon[11]. Our patient had a second-degree AVB and atrial fibrillation, which are rare. His bundle pacing was then performed. The postoperative ECG revealed an isoelectric interval in all 12 leads, with the pacing spike to QRS onset equaling the native HV interval (35–55 ms). The QRS morphology was identical to that of the intrinsic rhythm, confirming S-HBP. Crochetage sign refers to the presence of a notch in the initial 80 ms of the QRS complex in leads II, III and aVF, which resembles the shape of a crochet needle[12]. This sign is most frequently observed in individuals with ASD and can also be observed in other disorders such as patent foramen ovale (PFO), pulmonary embolism, and RV hypertrophy[11]. Recent research has revealed that, crochetage sign combined with RBBB and TTE had good performance for PFO prediction, with an accuracy, sensitivity, and specificity of 0. 712, 0. 801, and 0. 439, respectively[13]. In the initial published research on crochetage, 73% of patients with ASD showed this pattern[14]. Crochetage sign is considered a characteristic presentation of secundum ASDs. When the pattern is seen in all three inferior leads, the specificity of this sign ranges from 92% to 100%[3]. The presence of a RBBB on the ECG considerably increases the specificity and sensitivity of crochetage sign for the diagnosis of ASD[3]. It has also been associated with the severity of the left-to-right shunt, and patients with ASD sizes of ≥ 5 mm showed a higher incidence of crochetage sign[6]. Because of its high sensitivity and specificity in diagnosing ASD, crochetage sign is a useful diagnostic tool[12]. Moreover, a retrospective clinical study demonstrated that the presence of crochetage sign was an independent predictor for late atrial arrhythmia among patients with secundum ASD who received transcatheter closure[15]. The underlying electrophysiological mechanism of crochetage sign is not fully understood, but many researchers believe that it is related to delayed RV depolarization due to RV volume overload[15].

Output: pass


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: However, further testing should be completed to determine if this type of threshold accurately splits sequences into subfamilies of all TE types across a wide array of species. The methods used to develop subfamily models vary widely, from the manual clustering of copies in a multiple sequence alignment by eye, to automated clustering algorithms [49], and network-based approaches [50]. Wildly different subfamily sets can be produced by these alternative methods, or even by using slightly different parameterizations within one method. The large number of fine-grained subfamilies produced by some of these methods is not of practical use for identifying copies of the superfamily in a genome or specifically labeling individual copies confidently [51] with current sequence similarity search algorithms. Still, in aggregate the tree structure and subfamily membership are valuable datasets for studying family evolution and databases can play a role in the standardisation of this data. For future releases of Dfam we will explore ways to set a minimum sequence distance threshold for inclusion in Dfam as a subfamily. The threshold should reflect the current sensitivity and specificity of both HMM and consensus based search algorithms and act on the detailed subfamily tree to cluster closely-related subfamilies (lumping their copies together). The original detailed tree structure and individual copy membership need not be lost (Fig. 7), but stored alongside the superfamily as a combination of newick data and fine-scale seed alignment sequence subfamily labels for further study and use. Fig. 7Database subfamily representation. Proposed database representation for TE subfamilies maintaining a detailed phylogenetic structure while reducing the representative models for practical genome-scale annotation. The TE seed alignment (1) from a family with evidence of subfamily structure is analysed by a clustering method to produce a detailed subfamily structure and membership (2). Sequence models are developed for subfamilies and lumped (3) if model performance isn’t improved by the subdivision of two or more subfamilies. The lumped families and their corresponding seed alignments are added to the database (4) with metadata holding the detailed tree structure and seed sequence membership for each subfamilyFull size imageRedundancy/fragmentation detectionIdeally, a TE database should contain a single full-length entry for each transposing family. Unfortunately that overly simple definition doesn’t account for the fine detail of subfamily expansions, recombinations, deletion products, and mosaicism exhibited by many TE families.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: (2009) Differential mobilization of subsets of progenitor cells from the bone marrow. Cell 4: 62-72. 136. Pittet, M. J. , M. Nahrendorf, F. K. Swirski (2014) The journey from stem cell to macrophage. Ann NY 1319: 1-18. 137. Poser, L. , R. Matthys, P. Schawalder, S. Pearce, M. Alini, S. Zeiter (2014) A standardized critical size defect model in normal and osteoporotic rats to evaluate bone tissue engineered constructs. Int 2014: 11348635. 138. Qin, X. , R. M. Raj, X. F. Liao, W. Shi, B. . Zhou (2014a) Using rigidly fixed autogenous tooth graft to repair bone defect: an animal model. 30: 380-384. 139. Qin, Y. , J. Guan, C. Zhang (2014b) Mesenchymal stem cells: mechanisms and role in bone regeneration. J 90: 643-647. 140. Radice, M. , P. Brun, R. Cortivo, R. Scapinelli, C. Battaliard, G. Abatangelo (2000) Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Res 50: 101-109. 141. Rauh, J. , F. Milan, K. P. Gunther, M. Stiehler (2011) Bioreactor systems for bone tissue engineering. B Rev 17: 263-280. 142. Raynaud, C. M. , A. Rafii (2013) The necessity of a systematic approach for the use of MSCs in the clinical setting. Int 2013: 892340. 143. Reiser, J. , X. Y. Zhang, C. S. Hemenway, D. Mondal, L. Pradhan, V. F. (2005) Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases. 5: 1571-1584. 144. Rickert, D. , S. Sauerbier, H. Nagursky, D.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: Crochetage sign disappears in approximately 50% of patients after successful correction of ASD using percutaneous or surgical procedures[3,6]. Interestingly, in our case, crochetage sign disappeared on the ECG after S-HBP; however, the patient had not undergone atrial septal closure. We concluded that crochetage sign may be a manifestation of conduction system impairment. Based on the theory of longitudinal dissociation in the his bundle, conduction impairment may originate within the proximal his bundle because the pacing exceeded the injury level, and conduction through the His-Purkinje system was recovered, thus eliminating crochetage sign[16]. exact mechanism underlying the development of crochetage sign has not yet been elucidated. Some patients with ASD closure experience crochetage signs that disappear from their ECG. Here, we report the case of a patient with ASD whose crochetage sign disappeared after selective his bundle pacing. Subsequently, we deduced that crochetage sign could be a manifestation of a cardiac conduction system injury. Future research is needed to explore the mechanism behind crochetage sign. and peer review: Unsolicited 1. . Atrial septal defects - clinical manifestations, echo assessment, and intervention. Insights Cardiol. 2014;8:93-98. [PubMed] [DOI] [Cited in This 2. 9] [Analysis (0)] 2. Bayar N, Arslan Ş, Köklü üçükseymen S. The importance of electrocardiographic findings in the diagnosis of atrial septal defect. Kardiol Pol. 2015;73:331-336. [PubMed] [DOI] [Cited in This 0. 8] [Analysis (0)] 3. Heller J, Hagège. "Crochetage" (notch) on R wave in inferior limb leads: a new independent electrocardiographic sign of atrial septal defect. J Cardiol. 1996;27:877-882. [PubMed] [DOI] [Cited in This 1. 6] [Analysis (0)] 4. . the Way. . 2023;13:101814. [PubMed] [DOI] [Cited in This 5. . 'Crochetage' sign of atrial septal defect. QJM. 2020;113:133-134.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: These processes lead to necessary redundancy in a library. Another form of redundancy, that is not desirable, is the direct result of (1) re-detection of ancestral families in the de novo analysis of two or more related species, (2) the confounding effects of sequence variation on de novo detection methods leading to rediscovery, and (3) inadequate clustering in pipelines that run multiple discovery methods and merge the results (Fig. 8). In addition, differences in the representative set of TE copies, in the alignment parameters, and the selection of model building parameters will lead to subtle differences between models generated for the same family; making automatic redundancy detection difficult. Fig. 8Redundancy/Fragmentation removal challenges. Both inter- and intra-library redundancy is present in de novo datasets and are currently resolved through manual curation. Interlibrary redundancy is often the result of unresolved subfamily structure (e. g. internal deletion products of DNA transposons) that confounds discovery and produces both redundant and fragmented families. Intra library redundancy is an inherent aspect analyzing a single species in isolation. For each new species these ancestral families need to be resolved by comparison to existing families, and by considering presence at orthologous sitesFull size imageThrough the expansion of the Dfam database via the addition of diverse sets of species and their associated TEs, it will become necessary to detect redundancy automatically. One approach would be to use a comparative genomics approach to assess TE insertions at orthologous sites to resolve interspecies redundancies while improving the taxonomic labels for each family (Fig. 8). Fragmentation is an additional problem apparent in most de novo datasets. In some cases this directly relates to the structure of the observed TE copies appearing as distinct patterns within a genome (e. g. full length LTRs with internal sequence, and solo LTRs) or coverage bias in a families copies (e. g 5′ end of LINE families). In either case joining these fragments into a complete family is the desired result. Fragmentation is often identified during manual curation as a family fragment is extended and subsequently matched to another fragment in the library over the extended region. Another approach would be to use genome annotations for the uncurated library to identify significant collinearity among family pairs and automatically group families together.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Menne, A. Vissink, G. M. Raghoebar (2011) Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial. 22: 251-258. 145. Robey, P. G. (2011) Cell sources for bone regeneration: the good, the bad, and the ugly (but promising). B Rev 17: 423-430. 146. . Ylostalo, K. Coble, R. H. Rosa Jr, D. J. Prockop (2011) Action at a distance: systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-α stimulated gene/protein 6. 29: 1572-1579. 147. Rokn, A. , A. R. Ghahroudi, S. Hemati, A. Soolari (2011) Comparison of peri-implant bone loss and survival of maxillary intrasinus and extrasinus implants after 2 years. J Dent 8: 130-137. 148. Roy, S. , J. Driggs, H. Elgharably, S. Biswas, M. Findley, S. Khanna, U. Gnyawali, V. K. Bergdall, C. K. Sen (2011) Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation. Regen 19: 753-766. 149. Santos, J. L. , D. Pandita, J. . Tomas (2011) Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration. Ther 11: 46-57. 150. Sarkar, S. K. , B. T. Lee (2015) Hard tissue regeneration using bone substitutes: an update on innovations in materials. 30: 279-293. 151. Sauerbier, S. , D. Rickert, R. Gutwald, H. Nagursky, T. Oshima, S. P. Xavier, J. Christmann, P. Kurz, D. Menne, A. Vissink, G.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: Log in or new issue alertsGet alerts Submit a your Email address: Subscribe to e2019. | DOI: 10. 4103/ijo. IJO_1905_18 Abstract Purpose: This study evaluated the efficacy of retrobulbar ropivacaine plus dexmedetomidine compared with systemic fentanyl in pediatric vitreoretinal (VR) surgery. Methods: This prospective double-blind, randomized controlled study was performed in 60 children undergoing VR surgery, age from 2 to 7 years. After general anesthesia, the following procedure was administrated: (1) retrobulbar block with 0. 5% ropivacaine plus dexmedetomidine 1 μg/kg (group RD, n = 20), (2) retrobulbar block with 0. 5% ropivacaine (group RB, n = 20), and (3) control group with general anesthesia only (group F, n = 20). Hemodynamics, postoperative pain scores, anesthetics consumption (remifentanil, propofol, fentanyl), and emergence agitation were recorded. Results: Respiratory depression was observed in 7 of the 20 patients in group F after the laryngeal mask airway was removed in the operating room, compared with none in groups RD and RB. All patients in group F required intraoperative rescue fentanyl (average intraoperative fentanyl consumption, 26. 6 ± 12. 6 μg per patient). Some rescue fentanyl was required in group RB (three patients required one dose of rescue fentanyl). Patients in group RD required none. Groups RD and RB reported lower pain scores than group F at 4 h postoperatively (RD group: P < 0. 001; RB group: P =0. 002); pain scores in group RD were lower than that in group F at 6 h postoperatively (P < 0. 001). Conclusion: Retrobulbar dexmedetomidine as an adjuvant to ropivacaine is a safe and effective alternative to systemic fentanyl. This regimen provides better pain management, hemodynamic stability, and stress response suppression in pediatric VR surgery. Postoperative opioid-induced respiratory depression is the main cause of death and brain damage in the perioperativeperiod. [12] Regional anesthesia combined with general anesthesia decreased opioid-related adverse events in major pediatric surgeries.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: ConclusionThe new Dfam release has expanded the number and scope of species included in the database, allowing for enhanced genome annotation while fostering the development of highly curated TE libraries for use in research. In addition, a unified eukaryotic TE classification scheme and HMMs for DNA transposon termini now on Dfam, provide additional details for researchers to utilize in their TE research. Combined with an expanded TE library, the new database architecture, improved interfaces, and simplified software distribution, Dfam offers a collaborative platform for the TE research community. Collaborative efforts and increased datasets will be necessary to tackle problems such as those mentioned above: subfamily identification, library redundancy and fragmentation. We invite the TE research community to provide feedback on the challenges discussed here and to join us in these efforts to further Dfam development. Availability of data and materials The datasets generated during and/or analyzed during the current study are available at the Dfam portal: Software generated for this project is located in the Dfam consortium repository: 10. 9. CAS 82. 31. CAS 2013. 22. 5. 9. 33. 31. 1996. 8. 10. 5. 8. 91. 7. 19. 64. 7. 97. 414. 82. 71. 276. 77. 69. 109. 921. 80. 46. PubMed Pub20. 30. 1929. 3. 93. 301. 1. Genes Dev. 1996;10:755–61. 1406. 73. 8. 1283. 9416. 2017. p. 18–23. 1. 2939. FundingThis work is funded by NHGRI grant # U24 HG010136, and NHGRI grant # RO1 HG002939. Author informationAuthors and AffiliationsInstitute for Systems Biology, Seattle, WA, 98109, & Arian F. SmitUniversity of Montana, Missoula, MT, 59812, USATravis J. WheelerAuthorsJessica StorerView author publicationsYou can also search for this author in PubMed 3. x. AS developed the classification system and performed the transposon termini analysis. JS, AS curated Dfam families. JS, RH, and AS were major contributors in writing the manuscript. All authors read and approved the final manuscript. Corresponding authorsCorrespondence to Jessica Storer, or Arian F. Smit.

Output: pass


Input: Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Raghoebar, R. Schmelzeisen, W. Wagner, F. P. Koch (2011) Bone marrow concentrate and bovine bone mineral for sinus floor augmentation: a controlled, randomized, single-blinded clinical and histological trial - per-protocol analysis. A 17: 2187-2197. 152. Sauerbier, S. , A. Stricker, J. Kuschnierz, F. Buhler, T. Oshima, S. P. Xavier, R. Schmelzeisen, R. Gutwald (2010) In vivo comparison of hard tissue regeneration with human mesenchymal stem cells processed with either the method or the BMAC method. C Methods 16: 215-223. 153. Schmidt-Bleek, K. , H. Schell, J. Lienau, N. Schulz, P. Hoff, M. Pfaff, G. Schmidt, C. Martin, C. Perka, F. Buttgereit, H. D. Volk, G. Duda (2014) Initial immune reaction and angiogenesis in bone healing. J 8: 120-130. 154. Seamon, J. , X. Wang, F. Cui, T. Keller, A. S. Dighe, G. Balian, Q. Cui (2013) Adenoviral delivery of the VEGF and BMP-6 genes to rat mesenchymal stem cells potentiates osteogenesis. Res 2013: 737580. 155. Shao, J. , W. Zhang, T. Yang (2015) Using mesenchymal stem cells as a therapy for bone regeneration and repairing. 48: 62. 156. Simmons, C. A. , E. Alsberg, S. Hsiong, W. J. Kim, D. J. Mooney (2004) Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone 35: 562-569. 157. Smadja, D. M. , C. d'Audigier, C. L. Guerin, L. Mauge, B. Dizier, J. S. Silvestre, L.

Output: corroborate


Input: Claim: Nanotechnology eliminates the need for surgery in all medical cases. [SEP] Text: [34] Surgical stress associated with pediatric strabismus and vitreoretinal (VR) surgery has been reported. [56] Our hypothesis is retrobulbar dexmedetomidine, which is commonly used in China, could reduce the need of fentanyl and pain scores, meanwhile prolong the duration of analgesia. Thus, we administrated 1 μg/kg dexmedetomidine with retrobulbar block according to a previous study. [7] study was approved by the hospital's Ethics Committee. Written consents were obtained from the parents of the participating patients. Patients of of Anesthesiologists physical status I to II, age 2–7 years, who underwent elective VR surgery at our hospital, were selected for the study. All surgeries were performed vitrectomy without scleral buckling. Exclusion criteria include consent not obtained, upper airway infection, allergy to anesthetics, and eye tumors or infections. Sixty patients were randomized to receive general anesthesia plus retrobulbar dexmedetomidine (group RD) or retrobulbar block (group RB), or general anesthesia alone (group F). The randomization was performed in a 1:1:1 ratio using SPSS 25. 0 (IBM Inc. , ). A nurse, not involving in patient management, prepared all the anesthetics. The parent, investigator, and anesthesiologist were blinded to the group assignments. After induction, 1 mL of venous blood was withdrawn to test the baseline stress response biomarkers. An intravenous infusion of 2–4 mL/kg/h Ringer's lactate was maintained during the surgery. The patients were monitored by electrocardiography, pulse oximetry (SPO2), heart rate (HR), noninvasive blood pressure (BP), capnography (ETCO2), and bispectral index (BIS). General anesthesia was induced with propofol 3 mg/kg, rocuronium 0. 6 mg/kg, and remifentanil 3 μg/kg in all the three groups. A laryngeal mask airway (LMA) was inserted to secure the airway. Patients in group RD were administered retrobulbar block with 0. 5% ropivacaine 0. 1 mL/kg plus dexmedetomidine 1 μg/kg and group RB with 0. 5% ropivacaine 0.

Output: contrast


Input: Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: Extensive sequence-influenced DNA methylation polymorphism in the human genome access Published: 24 May 2010 Extensive sequence-influenced DNA methylation polymorphism in the human genome Asaf Hellman1 & Andrew Chess2,3 Epigenetics & Chromatin 0. 16% of SNPs [2], and another study suggested that 1. 5% of SNPs could affect local methylation [3]. Thus, the extent to which SNPs may direct methylation remains unclear. Other studies in humans have focused on an imprinted locus [4, 5] or examined CpG islands [6], and a recent study on F1 mice focused on regions preselected to have strain-specific differences in gene expression [7]. We report our analyses of DNA methylation at over 100,000 CpGs distributed throughout the genome, and our investigation into the dependence of DNA methylation on nearby sequence polymorphisms. Results and DiscussionTo explore the potential effect of polymorphisms on local DNA methylation, we performed numerous comparisons of monoallelic methylation patterns in pairs of related and unrelated individuals. Methylation of the two alleles was measured using a SNP mapping array (250 K array; ), with pre-digestion of the DNA with a cocktail of methylation-sensitive restriction endonucleases (MSREs) before PCR amplification of amplicons ranging in size from 100, to 1,100 bp (average 677 bp) [8] and subsequent detection of SNPs present on the amplicons. After all known MSRE site polymorphisms were filtered out, 110,883 amplicons were available for assessment of DNA methylation. As shown in Figure 1a, a heterozygous SNP present on an amplicon that has methylation present on only one of the two alleles will lead to a 'homozygous' call after MSRE treatment. Therefore, by looking for cases in which the genotype is heterozygous (in regular genomic DNA) and MSRE-pretreated DNA yields a homozygous call, amplicons with monoallelic methylation can be identified. Figure 1Genome-scale assessment of allelic DNA methylation patterns. (a) Representative amplicon (defined by sites). The 'B' allele has a methylated CpG (red filled oval) within a methylation-sensitive restriction enzyme (MSRE).

Output: pass