Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Therefore, MSCs make an indirect contribution to osteoblast cell differentiation and bone regeneration. An interesting experimental study showed that transplanted MSCs contribute to fracture healing by expressing BMP-2, which induces bone and cartilage formation [Granero-Moltó et al. , 2009]. Some of the mechanisms of MSC action on bone regeneration and repair are illustrated in Figure 3. Fig. 3View largeDownload slideSome mechanisms of MSC action on bone reconstruction and repair. The beneficial effects of MSCs include immunomodulatory effects, stimulation of angiogenesis, antiapoptotic effects in osteoblastic lineage cells, recruitment of host MSCs/progenitor cells, and stimulation of their differentiation into osteoblasts. Fig. 3View largeDownload slideSome mechanisms of MSC action on bone reconstruction and repair. The beneficial effects of MSCs include immunomodulatory effects, stimulation of angiogenesis, antiapoptotic effects in osteoblastic lineage cells, recruitment of host MSCs/progenitor cells, and stimulation of their differentiation into osteoblasts. Close modal of MSCs for So far, several different approaches have been utilized to deliver MSCs into the injured area of the bone (i. e. , bone defects) [Bernardo et al. , 2007; Sorrell et al. , 2009; Lee et al. , 2010; Achille et al. , 2011]. The most common method for using MSCs is direct injection [Chabner et al. , 2004]. Some studies have also shown that seeding MSCs on biocompatible scaffolds could be an attractive candidate for treating nonunion fractures [Oryan et al. , 2014b]. In general, MSCs can be applied through systemic and local injections or by tissue engineering approaches. injection of MSCs has been used in the treatment of osteoporosis and fracture healing for many years [Huang et al. , 2015]. Several factors are involved in order to achieve more successful results from cell therapy in bone healing. These include the vehicle and type of cells, cell concentration, differentiating status of the cells, treatment period, and route of administration [Granero-Moltó et al. , 2009]. [SEP] Justify:

Output: The text corroborates the claim by detailing how mesenchymal stem cells (MSCs) contribute to bone regeneration and repair through various mechanisms such as stimulating osteoblast differentiation and promoting fracture healing. It mentions that MSCs have been used in therapies for conditions like osteoporosis and fracture healing, directly supporting the idea of using stem cells in regenerative medicine to repair damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Guidance on rosiglitazone for type 2 diabetes mellitus. for Clinical Excellence, 2000. ↵Cohen D. Insiders criticise FDA’s decision not to withdraw rosiglitazone. BMJ2010;341:c5333. ↵. The record on rosiglitazone and the risk of myocardial infarction. N Med2007;357:67-9. doi:10. 1056/NEJMe078116 pmid:17551162. of Science↵ PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PR(PROspective pioglitmacroVascular Events): a randomised controlled trial. Lancet2005;366:1279-89. doi:10. 1016/S0140-6736(05)67528-9 pmid:16214598. of Science↵Scheen AJ. Outcomes and lessons from the PROactive study. Clin Pract2012;98:175-86. doi:10. 1016/j. diabres. 2012. 09. 001 pmid:23020930. ↵. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA2007;298:1180-8. doi:10. 1001/jama. 298. 10. 1180 pmid:17848652. of Science↵. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ2009;339:b2942. OpenUrlAbstract/↵Graham DJ, Ouellet- Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA2010;304:411-8. doi:10. 1001/jama. 2010. 920 pmid:20584880. of Science↵ Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care2011;34:916-22. doi:10. 2337/dc10-1068 pmid:21447663. [SEP] Justify:

Output: The text contrasts the claim by discussing various studies and observations related to the risks associated with treatments like rosiglitazone and pioglitazone, indicating that there are notable adverse cardiovascular events and risks, such as myocardial infarction and bladder cancer, linked to these treatments. This suggests that not all treatments, including those enhanced by nanotechnology, are risk-free.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: The clonal precursor of the leukemic stem cell is not the clone with most representation in the pHSC pool, but rather the clone with epigenomic bias towards the leukemic regulatory program, as depicted by related color schemes. (B) deconvolutes AML clonal heterogeneity. Heteroplasmic mtDNA mutations in three cell populations from patients SU070 are shown. Mutations sites (in rows) in each FACS-sorted cell population (in columns) are shown, with size of each circle representing its VAF. Several mtDNA mutations (sites shown in purple) are detected in pHSCs and transmitted to LSCs and blasts, confirming those pHSC clones at the apex of leukemia lineage. LSCs accumulated additional mtDNA mutations (sites shown in green) and are transmitted to leukemic blasts in patient SU070. Allele frequency, sequencing depth and annotation of the variant allele are shown in Figure 2—figure supplement 1 and Supplementary file 2. (C) Same plot as (B) shown for patient SU353. In addition to the shared mtDNA mutations in pand blasts (purple), two pHSCs-specific mtDNA mutations are also detected (yellow). Allele frequency, sequencing depth and annotation of the variant allele are shown in Figure 2—figure supplement 1 and Supplementary file 2. (D) Heteroplasmic mutations in single pHSCs from one patient reveal clonal heterogeneity. Each column is a mtDNA nucleotide position; each row is one cell. Blue color indicates the presence of the mtDNA variant. Shown are cells with any mtDNA mutation detected, or cells with more than 40X coverage of the mitochondrial genome without any detected mutation(pHSC with WT mtDNA). The number of cells in each clonotype are indicated on the right. (E) Landscape of single-cell chromatin accessibility of blood progenitor and leukemic cells in patient SU353. tSNE map using bias-corrected deviations from chromatin accessibility showing cluster of AML blasts, LSCs, pHSCs and normal HSC, colored by cell types. (F) Chromatin accessibility of the FOS:JUN binding motif across the same single cells. tSNE map colored by deviation z-score for motif associated to FOS:JUN, the most variable TF motif. (G) pHSC clones possess distinct epigenomic signatures. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses leukemic stem cells, mtDNA mutations, and chromatin accessibility without any mention of the Human Genome Project or the mapping of human DNA sequences.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Bone marrow-derived MSCs and adipose tissue-derived MSCs (ADMSCs) are the most applicable type of MSCs that have been used in bone regenerative medicine. Among these, the stromal vascular fraction (SVF) is a component of adipose tissue that has attracted much attention recently, specifically for the use of this fabulous extraction in bone and cartilage defects [Jurgens et al. , 2013]. SVF of adipose tissue is a rich source of preadipocytes, MSCs, different types of progenitor and inflammatory cells, and cytokines, which are extracted by the processing of body fat [Gentile et al. , 2012]. Evidence from experimental and clinical studies has shown that SVF is more effective in bone and cartilage healing than ADMSCs alone. It is believed that the more advantageous effects of SVF may be a reflection of different growth promotion factors and cytokines, which not only support the proliferation, differentiation, and viability of ADMSCs, but also play a critical role in the tissue repair process [Pak et al. , 2014]. SVF can be easily collected and enriched with platelet-rich plasma [Moshiri and Oryan, 2013]. In addition, ADMSCs in SVF can be activated by photostimulation with low-level lasers and light-emitting diodes [Peng et al. , 2012]. Similar to drug studies, there is an effective cell dose (ECD) for stem cell therapy, which is defined as the minimum cell number required to discern a remarkable therapeutic effect [Horwitz et al. , 2002]. In clinical trials that have focused on bone regenerative medicine, the MSC dose per person is determined as a mean of 1. 86 × 108 cells, or is based on body weight, calculated as a mean of 6. 64 × 106 cells/kg. However, there is no precise available ECD for the treatment of bone defects and disorders, meaning further studies are needed to illustrate a guideline in this regard. It is important to select an appropriate route of administration for MSC therapy in order to improve bone healing. Intravascular injection of MSCs (including intravenous, IV, and intra-arterial, IA, cell delivery) has been used by many clinicians in bone defects and some promising results have been reported [Horwitz et al. , 1999, 2001; et al. [SEP] Justify:

Output: The text corroborates the claim by detailing the use of mesenchymal stem cells (MSCs), specifically bone marrow-derived MSCs and adipose tissue-derived MSCs (ADMSCs), in bone regenerative medicine. It explains how SVF, a component of adipose tissue, is significant in repairing bone and cartilage defects and highlights the efficacy of MSCs in promoting healing processes in damaged tissues. This aligns directly with the claim regarding the application of stem cells in regenerative medicine for tissue repair.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: OpenUrlAbstract/↵ Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the Association (ADA) and the for the Study of Diabetes (EASD). Diabetologia2012;55:1577-96. doi:10. 1007/s00125-012-2534-0 pmid:22526604. of Science↵. Safety of dipeptidyl peptidase 4 inhibitors: a perspective review. Drug Saf2014;5:138-46. doi:10. 1177/2042098614523031 pmid:25083269. OpenUrlAbstract/↵. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Med2013;369:1327-35. doi:10. 1056/NEJMoa1305889 pmid:23992602. of Science↵Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. J Med2015;373:232-42. ↵ Sitagliptin and the risk of hospitalization for heart failure: a population-based study. Cardiol2014;177:86-90. doi:10. 1016/j. ijcard. 2014. 09. 038 pmid:25499347. ↵-. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ2013;346:f2267. doi:10. 1136/bmj. f2267 pmid:23618722. OpenUrlAbstract/↵. Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis. Cardiovasc Diabetol2013;12:3. doi:10. 1186/1475-2840-12-3 pmid:23286208. ↵. Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Med2007;147:578-81. doi:10. 7326/0003-4819-147-8-200710160-00182 pmid:17679700. of Science↵. Challenges in meta-analysis of randomized clinical trials for rare harmful cardiovascular events: the case of rosiglitazone. J2008;156:23-30. [SEP] Justify:

Output: The text discusses safety and risks associated with treatments, particularly focusing on diabetes medications and their cardiovascular implications. It highlights 'uncertain effects' and 'challenges in meta-analysis of randomized clinical trials for rare harmful cardiovascular events,' which suggests that not all treatments (specifically those referred to in the text) can be considered completely risk-free. This indicates a contrast to the claim that all treatments using nanotechnology are risk-free.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: Clone 1 that gives rise to the AML has a chromatin accessibility profile that more resembles LSCs and leukemic blasts. ‘WT’ pHSC refers to the pHSC with WT mtDNA. Clonotype information from is overlaid on the tSNE map defined by TF motif deviations, and colored by different lineal sub-populations defined by mtDNA mutations. (H) Quantitation of distinct single-cell chromatin accessibility at FOS:JUN motifs among different pHSC clones defined by EMBLE. Clone 1 pHSCs tend to down regulate FOS:JUN accessibility, while clone 2 pHSC shows substantially greater cell-to-cell variability. pHSCs with no detectable mtDNA variants and normal HSCs are shown for comparison. TF deviation of single cells (black dots) is shown on the distribution box-plot. The statistical significant were indicated by ‘*” when p<0. 05, ‘**” when p<0. 01(Wilcoxon rank-sum test). Figure 2—figure supplement 1 Download asset Open asset Heteroplasmic mtDNA mutations detected in bulk ATAC-seq from AML patients. (A) The number of heteroplasmic variants detected using ATAC-seq data from normal primary blood cells and cancer cells from AML patients. (B) The number of mtDNA variants identified from normal and cancer samples in different substitution classes are shown as a bar plot. Mutations from normal (gray) and cancer (yellow) samples are separated. > T and T > C signature in mtDNA mutations has been observed in previous studies and it's equivalent to the one that has been operating during the evolution of human germline mtDNAs. (C) Annotation of mtDNA mutations and the proportion of mutations in coding and non-coding regions. Coding mutations are divided into synonymous, nonsynonymous, and gain of stop codon. Heteroplasmic mutations detected from cancer samples show a similar distribution as those from normal samples, with a slightly higher proportion falling within coding regions. (D) Heteroplasmic mutations in three cell stages for each AML patient. Variant alleles (in rows) in each cell population (in columns) are shown with a circle, with size indicating their variant allele frequency. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on chromatin accessibility, mtDNA mutations in AML patients, and related statistical analyses. It does not mention the Human Genome Project or the mapping of human DNA sequences.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: , 2005]. Intravascular delivery of MSCs is the most common systemic method that is minimally invasive and has the potential for a broad distribution of cells throughout the body. Despite the suggested beneficial effectiveness of an IV injection method on bone repair, some drawbacks have been reported previously, such as significant entrapment of cells after passing through the lungs and formation of vascular microemboli [Castelo-Branco et al. , 2012]. This effect in IV delivery of MSCs is called the pulmonary first pass effect [Fischer et al. , 2009]. However, some investigations have suggested that MSCs trapped inside the lungs can potentially have therapeutic effects [Lee et al. , 2009; Choi et al. , 2011; Roddy et al. , 2011]. Alternatively, MSCs can be systemically delivered by IA injection that overcomes the drawbacks of an IV delivery method. The pulmonary first pass effect of IV injection is bypassed by an IA route of administration. In addition, the ECD can be decreased by simply switching from IV to IA delivery due to the bypassing of the lungs and lower risk of cellular embolism. However, cellular embolism has also been reported with the IA delivery route of bone marrow stromal cells (BMSCs) in rats, which is related to the cell dose and infusion velocity [Cui et al. , 2015]. Overall, use of a local delivery route for MSC transplantation has been suggested because many researchers believe that after systemic infusion virtually all MSCs are trapped in the lungs and rapidly disappear. The occurrence of some cells in extravascular spaces is most likely due to the vascular leakage created by the injury. A comparison of IV and IA delivery of MSCs is provided in Figure 4. Fig. 4View largeDownload slideBioluminescence imaging of the IV and IA route of cell delivery in rats. Rats were irradiated unilaterally (white arrow) before IV (a) or IA (b) injection with 1 × 106 BMC9 MSCs expressing a luciferase reporter [Kean et al. , 2013]. Copyright© 2013 Thomas J. Kean et al. This is an open access 0. 4 mL (12 × 106 cells) and fibrin was prepared and injected locally into the fracture site. Eventually, a significant fracture healing acceleration was observed. [SEP] Justify:

Output: The text corroborates the claim by discussing the use of mesenchymal stem cells (MSCs) in various delivery methods for repairing bone injuries. It mentions that local delivery of stem cells has been suggested for their transplantation, which supports the idea that stem cells are utilized in regenerative medicine to facilitate tissue repair. The information provided about the efficacy of different injection methods, such as IV (intravascular) and IA (intra-arterial) delivery of MSCs, further substantiates the claim regarding the role of stem cells in regenerative applications.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: doi:10. 1016/j. ahj. 2008. 03. 002 pmid:18585493. of Science↵Department of Health and for and Research. Guidance for industry: diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008. ↵. Guideline on clinical investigation of medicinal products in the treatment of diabetes mellitus. 2010. ↵Bell DS. Do sulfonylurea drugs increase the risk of cardiac events? CMAJ2006;174:185-6. doi:10. 1503/cmaj. 051237 pmid:16415463. ↵Hippisley-Cox J, Coupland C. Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care. BMJ2016;352:i1450. doi:10. 1136/bmj. i1450 pmid:27029547. OpenUrlAbstract/↵Wikipedia. Readcodes 2015 J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ2005;330:1366-74. doi:10. 1136/bmj. 330. 7504. 1366 pmid:15947398. OpenUrlAbstract/↵Hippisley-. Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ2005;331:1310-6. doi:10. 1136/bmj. 331. 7528. 1310 pmid:16322018. OpenUrlAbstract/↵Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ2010;340:c2197. doi:10. 1136/bmj. c2197 pmid:20488911. OpenUrlAbstract/↵Parker C, Coupland C, Hippisley-Cox J. [SEP] Justify:

Output: The text lists multiple studies and guidelines that discuss various treatments and their associated risks, suggesting that not all treatments, including those that could involve nanotechnology, are without risk. Specifically, the mention of cardiovascular risks and adverse outcomes related to different medical therapies indicates that treatments, irrespective of technology, may pose certain dangers.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: Sequencing depth of the variant allele is indicated by the color of the circle (in log2 scale). pHSC-specific mutation sites are in red. Allele frequency and annotation of mtDNA mutations were shown in Supplementary file 2 (E) Heteroplasmic mutations in two cell stages for each AML patient. Variant alleles (in rows) in each cell population (in columns) are shown with a circle, with size indicating their variant allele frequency. Sequencing depth of the variant allele is indicated by the color of the circle (in log2 scale). pHSC-specific mutation sites are in red. Allele frequency and annotation of mtDNA mutations were shown in Supplementary file 2. Figure 2—figure supplement 2 Download asset Open asset Single cell chromatin accessibility. (A) Phylogenetic relationship of cells from SU353 was inferred using the Neighbor-Joining method. The phylogenetic tree is drawn to scale, with branch lengths in the units of the number of base difference per site. The clade in purple matched to clone 1 and the clade in yellow matched to clone 2 in Figure 2D. The cell type and mtDNA variants in each single cell are shown on the right. 229 single cells with at least one of the six heteroplasmic mtDNA mutations were included. (B) Heat map showing clusters of pHSCs from SU353 and normal HSCs from a healthy donor, based on the z-score of TF deviation. The Z-score deviation is shown for individual cells (columns) for each TF (rows). Clone information is shown on the top of the heat map. Top 50 most variable motifs were used in this heat map. (C) Volcano plot showing the difference in chromatin accessibility for transcription factor binding motifs between Clone 1 and Clone 2. The x-axis shows the mean difference of bias-corrected deviations and the y-axis shows the p-value (in log10 scale). The most significant differential motifs are annotated with TF names. (D) Same as in (C) for Clone 1 vs. WT cells. (E) Same as in (C) for Clone 2 vs. WT cells. No significantly differential motifs were detected. Figure 2—figure supplement 3 Download asset Open asset for pHSCs. Scheme of FACS sorting of the pHSC population from AML patient SU353. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses details about allele frequencies, mutation sites, and chromatin accessibility in single cells, without mentioning the Human Genome Project or human DNA mapping.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: This is the only published clinical trial that has used differentiated MSCs in long bone fracture healing [Kim et al. , 2009]. In the field of stem cell therapy, considerable clinical information about the myriad possibilities are available for consideration. Many registered international or national clinical trials have been conducted to investigate the role of MSCs in long bone defect healing. However, so far almost none of them have reported their results, with only a few providing initial information about their research. This review used available information in clinical trial databases such as the ( the ClinicalTrials. gov database ( the ( and the Australian and clinical trials registry (www. anzctr. org. au/). In order to show the current status of clinical MSC therapy for bone repair, the available clinical trials are listed in Table 3. All the clinical trials related with MSCs and long bone defects cited in clinical trial registries were included, and those labeled as “unknown status,” “withdraw,” or “not yet recruiting” were excluded. Finally, 16 clinical trials related to long bone fracture, delayed union or nonunion, and MSC therapy were identified that were cited in clinical trial registries as completed (10 of them) or recruiting patients. These trials used MSCs for treating long bone fracture/nonunion via different procedures, including direct injection/implantation of the MSCs with or without scaffolds/matrices. They can be classified into 3 groups to allow for a comparative analysis. The first group, with 4 clinical trials (3 completed), used local injection of MSCs without in vitro culture and expansion, and none of these trials have been published so far. The second group (5 clinical trials, 2 completed, none published) used expanded MSCs by local injection in the defect site. The third group consisted of 8 trials intending to test MSCs with bone substitutes. Just 1 among the completed trails has published the results [Liebergall et al. , 2013]. Table 3Randomized clinical trials using MSCs to treat long bone defects View largeNeedless to say, the main criticism of these completed clinical trials is their failure to report results. This may reflect: (1) lack of expected results (e. g. , beneficial effects of MSCs on bone regeneration), (2) inconsistency in results, (3) the need to conduct further phases of study, or (4) other unknown reasons. [SEP] Justify:

Output: The text corroborates the claim by detailing the use of mesenchymal stem cells (MSCs) in various clinical trials focused on healing long bone fractures and nonunions. It discusses specific procedures employing MSCs for treatment, highlighting their role in regenerative medicine aimed at repairing damaged tissues, thus supporting the claim.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ2010;341:c4245. doi:10. 1136/bmj. c4245 pmid:20858909. OpenUrlAbstract/↵Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to bisphosphonates and risk of gastrointestinal cancers: series of nested case-control studies with QResearch and CPRD data. BMJ2013;346:f114. doi:10. 1136/bmj. f114 pmid:23325866. OpenUrlAbstract/↵-Cox J. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ2015;350:h517. doi:10. 1136/bmj. h517 pmid:25693810. OpenUrlAbstract/↵Hippisley-Cox J, Pringle M. Prevalence, care, and outcomes for patients with diet-controlled diabetes in general practice: cross sectional survey. Lancet2004;364:423-8. doi:10. 1016/S0140-6736(04)16765-2 pmid:15288740. of Science↵ The incident user design in comparative effectiveness research. Saf2013;22:1-6. doi:10. 1002/pds. 3334 pmid:23023988. ↵Hippisley- Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ2008;336:1475-82. doi:10. 1136/bmj. 39609. 449676. 25 pmid:18573856. OpenUrlAbstract/↵ UK Study (UKDPS) Group. A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the Study (UKPDS) (UKPDS no. 68). Diabetologia2004;47:1747-59. doi:10. 1007/s00125-004-1527-z pmid:15517152. of Science↵. . [SEP] Justify:

Output: The text contrasts the claim by referencing studies that highlight risks associated with various treatments, such as antipsychotic drugs and the potential for venous thromboembolism, bisphosphonates and gastrointestinal cancers, and antidepressants' risks of suicidal behavior. These examples suggest that not all treatments, including those potentially involving nanotechnology, are devoid of risks.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: community resource of transposable element families, sequence models, and genome annotations access Published: 12 January 2021 community resource of transposable element families, sequence models, and genome annotations Jessica Storer1, : orcid. org/0000-0001-9261-38211, Jeb Rosen1, Travis J. Wheeler2 & …Arian F. Smit1 Show authors Mobile DNA 3. 0–3. 3 releases of Dfam ( represent an evolution from a proof-of-principle collection of transposable element families in model organisms into a community resource for a broad range of species, and for both curated and uncurated datasets. In addition, releases since Dfam 3. 0 provide auxiliary consensus sequence models, transposable element protein alignments, and a formalized classification system to support the growing diversity of organisms represented in the resource. The latest release includes 266,740 new de novo generated transposable element families from 336 species contributed by the EBI. This expansion demonstrates the utility of many of Dfam’s new features and provides insight into the long term challenges ahead for improving de novo generated transposable element datasets. IntroductionSignificant portions of many genomes are composed of transposable element (TE) copies. TE-derived sequence decays in the genome over time, making its discovery and characterization challenging. However, accurate annotation and description of these elements is crucial in understanding their impact on the genome in which they reside and the evolution of a species as a whole. The influence of TEs on the genome and/or species can be direct, such as insertions into coding regions, exaptation to new functions, or chromosomal rearrangements as a consequence of non-homologous recombination, or indirect, as with an “arms race” between the host and resident parasite. TE instances have long been identified in genomes through a combination of two complementary strategies: de novo detection, and database-driven annotation. In de novo detection, a variety of methods are used to recognize and categorize remnants of TE activity. The families identified in this fashion are typically further curated and cataloged in databases such as Dfam. In database-driven annotation each sequence in that database is aligned to the genome being annotated, with the best-scoring alignment determining the label of the genomic sequence. Such databases have long used consensus sequences to represent each family. [SEP] Justify:

Output: The text is irrelevant to the claim about the Human Genome Project because it focuses on transposable elements and genome annotations rather than mapping the entire human DNA sequence. It discusses the Dfam database and methods for detecting transposable elements, without mentioning the Human Genome Project or its findings.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Analysis showed that only gene-transduced MSCs could induce osteogenesis in vivo, whereas adenoviral vector or nontransduced MSCs alone did not induce osteogenesis. The osteogenic genes can also be transduced to MSCs using a gene-activated matrix (GAM). GAM is one of the tissue engineering approaches that consists of collagenous scaffold impregnated with plasmid DNA encoding osteogenic genes. When GAM is inserted into a bone defect, host MSCs entering the scaffold are transfected by plasmid and consequently secrete the osteogenic gene product. The usefulness of GAM in bone tissue regeneration was investigated by Umebayashi et al. [2015]. GAM with atelocollagen containing cDNA of BMP4 (pBMP4) or Runx2 (pRunx2) was transplanted into the cranial bone surface under the periosteum of F344 rats. At 2, 4, and 8 weeks after surgery, the results showed that the bone induction effect of GAM is dose-dependent and bone formation was detectable in specimens containing 1 mg of pBMP4 or pRunx2 at 8 weeks. Epigenetic regulation and RNA interference are major strategies routinely used to modify genes. Gordon et al. [2011] showed that loss of the PBX1 (pre-B-cell leukemia homeobox 1) gene from the osterix promoter is associated with an increase in the recruitment of histone acetylases (p300). Based on this result, it was proposed that PBX1 plays a central role in weakening the activity of the HOXA10 (homeobox A10) gene as an activator of osteoblast-related genes and functions to establish the appropriate timing of gene expression during osteogenesis. Furthermore, Zeng et al. [2012] found that knockdown of BMPR-2 by RNA interference inhibits osteogenic differentiation of ADMSCs. Although promising results have been generated in the experimental studies, gene-manipulated MSC transplantation for treating bone injuries in humans has limited application and its safety and efficacy need to be elucidated in the near future. In addition, developing clinical grade vectors is a very complex process and does not seem to be cost effective. Genetic modification strategies of MSCs for bone healing are shown in Figures 5 and 6. Fig. [SEP] Justify:

Output: The text corroborates the claim by discussing how gene-transduced mesenchymal stem cells (MSCs) can induce osteogenesis in vivo. It explains the process by which these genetically modified MSCs can repair damaged bone tissues, particularly through the use of gene-activated matrices (GAM). The experiments cited demonstrate how MSCs, when transduced with specific osteogenic genes, contribute to bone tissue regeneration, directly supporting the claim about the use of stem cells in regenerative medicine.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: 2. 147 pmid:12090408. of Science↵ Effect of dipeptidyl peptidase-4 inhibitor on all-cause mortality and coronary revascularization in diabetic patients. J Cardiovasc Ultrasound2015;23:233-43. doi:10. 4250/jcu. 2015. 23. 4. 233 pmid:26755932. ↵ Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Cardiol2012;110:826-33. doi:10. 1016/j. amjcard. 2012. 04. 061 pmid:22703861. ↵. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Res Opin2011;27(Suppl 3):57-64. doi:10. 1185/03007995. 2011. 602964 pmid:22106978. ↵. A multicenter observational study of incretin-based drugs and heart failure. N Med2016;374:1145-54. doi:10. 1056/NEJMoa1506115 pmid:27007958. ↵ Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Med2016;164:705-14. doi:10. 7326/M15-2568 pmid:27110660. ↵ A nomogram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients. BMJ Open2015;5:e005892. doi:10. 1136/bmjopen-2014-005892 pmid:25687897. OpenUrlAbstract/↵. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Endocrinol2015;3:43-51. doi:10. 1016/S2213-8587(14)70213-X pmid:25466239. ↵Majeed A. Sources, uses, strengths and limitations of data collected in primary care in England. Q2004;(21):5-14. [SEP] Justify:

Output: The text contrasts the claim by highlighting that various medical treatments, including those associated with dipeptidyl peptidase-4 inhibitors, have undergone rigorous analysis and raised safety concerns. The mention of studies and meta-analyses indicates that there are significant considerations regarding cardiovascular risk and other health impacts, undermining the claim that all nanotechnology treatments are risk-free.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: However, such searches tend to miss highly-diverged sequences, prompting us to explore the utility of profile methods [1, 2] to increase sensitivity. In 2012, we released Dfam [3], a database of TE families from the human genome in which each family was represented by a multiple sequence alignment (MSA) and a profile hidden Markov model (HMM). Profile HMMs [4, 5] yield sensitivity gains in part by modeling the position-specific residue and indel (insertion and deletion) variability found in family MSAs. The first release of Dfam was based on the design of similar databases of protein (Pfam) and RNA (Rfam) families [6, 7]. In addition to improving annotation sensitivity through the use of profile HMMs, Dfam demonstrated decreased false discovery rates through rigorously defined thresholds [8]. An additional advantage of these databases is the preservation of a multiple sequence alignment of representative family members, the seed alignment. The seed alignment is model-agnostic, provides details on coverage and fragmentation, and supplies essential provenance for the family. Subsequent releases of Dfam refined the prototype database and modestly expanded the curated libraries to five model organisms (4150 families). In 2018, Dfam received funding to move from a proof-of-principle to a production community resource by (1) scaling the system architecture, (2) supporting multiple model types (HMMs and consensus sequences) derived from the seed alignment, (3) improving annotation speed and quality, and most importantly (4) engaging the community in its further development. In this paper we will describe accomplishments represented in the latest release series (Dfam 3. 0 through 3. 3) and the challenges that lay ahead. These accomplishments include support for consensus models, a hierarchical TE classification system with an interactive explorer, a TE termini library encompassing various DNA transposon classes, and a framework for “uncurated” or “raw” data sets in Dfam alongside the existing curated data sets. Dfam 3. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the Human Genome Project since it discusses the Dfam database and its enhancements rather than providing information about the mapping of the entire sequence of human DNA. There is no mention of the Human Genome Project or its accomplishments within the provided text.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: 5View largeDownload slideDifferent approaches in gene-modified MSCs. Fig. 5View largeDownload slideDifferent approaches in gene-modified MSCs. Close modal Fig. 6View largeDownload slideThe gene delivery process for MSCs: (1) the carrier or nanop4. Table 4A useful guide for MSC therapy research View largeThe healing rate increases in close relation with the implanted MSC concentration [Wu et al. , 2007]. Concentrated MSCs can be mixed with a synthetic or natural osteoconductive matrix [Bornes et al. , 2014]. As a novel strategy for MSC therapy in fracture healing, combination therapy might be used in the future. In this approach, MSCs can be implanted with a biodegradable scaffold in the fracture site and 1-2 weeks later osteoinductive genes can be injected locally at the site of implantation. Another way to achieve this goal is a reversed procedure. The various MSC delivery approaches are shown in Figure 7. Fig. 7View largeDownload slideMSC delivery approaches. Systemic delivery of MSCs (a), osteoinductive genes (b), and gene-modified MSCs (c) by injection into the circulatory system. Local delivery of MSCs with or without culture media (d), osteoinductive genes (e), and gene-modified MSCs with or without growth factors (f) by direct injection at the fracture site. Local delivery of MSCs (g), osteoinductive genes (h), and MSCs with osteoinductive genes (i) by incorporation in scaffolds, which are implanted at the fracture site. Combination therapy: MSCs are implanted with scaffolds in the fracture site and osteoinductive genes are injected locally at the site of implantation 1-2 weeks later (j). By an alternative method, osteoinductive genes with scaffolds can be implanted in the fracture site and MSCs injected locally at the site of implantation 1-2 weeks later (k). Fig. 7View largeDownload slideMSC delivery approaches. Systemic delivery of MSCs (a), osteoinductive genes (b), and gene-modified MSCs (c) by injection into the circulatory system. [SEP] Justify:

Output: The text corroborates the claim by discussing various approaches related to the use of mesenchymal stem cells (MSCs) in therapeutic strategies for fracture healing. It highlights how MSCs can be implanted with osteoconductive matrices and describes combination therapy that leverages MSCs to facilitate tissue repair. This aligns well with the notion of using stem cells in regenerative medicine to repair damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: English 简体中文 6Publishing-Submit a Manuscript F6Publishing-世界华人消化杂志在线投稿 is committed to discovery and dissemination of knowledge About the a All 10. 4254/wjh. v7. i22. 2363] of This 2. it of This 4. 0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Counts in Google of This 2015. Published by Group Inc. All rights reserved. Hepatol. Oct 8, 2015; 7(22): 2363-2368 Published online Oct 8, 2015. doi: 10. 4254/wjh. v7. i22. 2363 All-oral interferon-free treatments: The end of hepatitis C virus story, the dream and the reality of Medical, Surgical, Neurological, Geriatric and Metabolic Sciences, of Naples, 80100 number: $[] Author contributions: Adinolfi LE and conceive and wrote the paper. Conflict-of-interest statement: The authors do not have conflict of interest. Open-Access: This 4. 0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: to: of Medical, Surgical, Neurological, Geriatric and Metabolic Sciences, of 80100 Naples, Italy. luigielio. adinolfi@unina2. it Telephone: +39-823-690642 Fax: +39-823-690642 Received: May 27, 2015Peer-review started: May 28, 2015First decision: July 27, 2015Revised: August 14, 2015Accepted: September 16, 20154. 1 The year 2014 marked the beginning of the end of the interferon era and the triumph of the all-oral interferon-free regimens for treatment of hepatitis C virus (HCV) infection. These innovative therapies are safe and yield a cure rate of over 90%. [SEP] Justify:

Output: The text contrasts the claim by stating 'These innovative therapies are safe,' which suggests that while the therapies may be safe, it does not imply they are completely risk-free. Therefore, the assertion that all treatments using nanotechnology are completely risk-free is rebutted.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: 3 currently houses 273,655 families: 112,455 retrotransposons, 101,711 DNA transposons, and 59,489 other repeats that include interspersed repeats of unknown origin, satellite regions and/or other non-TE entries to avoid annotating non-coding RNA genes as TEs. At present, Dfam’s coverage of organismal diversity is smaller than that of Repbase, owing to Repbase being a closed database and having two decades longer to accumulate data; with the development of an open framework for community contribution, the pace of data acquisition in Dfam is expected to close that gap quickly. Consensus modelsWhile the use of HMMs allows for improved detection of TE copies in genomes, most sequence analysis algorithms (Smith-Waterman, Needleman-Wunsch etc. ) and popular sequence analysis tools (etc. ) act directly on string representations of sequences (e. g. consensus sequences). Likewise, programs used to define new TEs (de-novo repeat finders), to extend fragmented models, to unravel the relationship of related TEs, to classify elements or to describe biological features like exons are not typically able to generate or take advantage of HMMs directly. Each TE model in Dfam therefore should be accompanied by a simple sequence model; a consensus sequence derived from the seed alignment is the logical candidate. The use of a consensus sequence as a first-order model for sequence families has a rich history of demonstrated utility [2, 9,10,11]. A consensus is typically made by considering the occupancy and composition of columns in a multiple sequence alignment of TE copies. A basic consensus caller might assign for any given column the majority nucleotide found in the column regardless of occupancy (the number of homologous nucleotides in the column vs the number of gaps). A more sophisticated caller would account for gaps and make base calls reflecting the observed rates of substitutions in the given genome. Most TE-derived sequences are under no functional constraint and accumulate mutations in a random and neutral fashion. Given this random noise, an informed consensus for a sufficient number of properly aligned copies may be expected to reproduce the original active TE sequence. [SEP] Justify:

Output: The text discusses the Dfam database and its various models related to transposable elements within genomes, but it does not address or provide any information regarding the Human Genome Project or its mapping of the human DNA sequence. Therefore, the text is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Local delivery of MSCs with or without culture media (d), osteoinductive genes (e), and gene-modified MSCs with or without growth factors (f) by direct injection at the fracture site. Local delivery of MSCs (g), osteoinductive genes (h), and MSCs with osteoinductive genes (i) by incorporation in scaffolds, which are implanted at the fracture site. Combination therapy: MSCs are implanted with scaffolds in the fracture site and osteoinductive genes are injected locally at the site of implantation 1-2 weeks later (j). By an alternative method, osteoinductive genes with scaffolds can be implanted in the fracture site and MSCs injected locally at the site of implantation 1-2 weeks later (k). Close modal Another challenge for bone regenerative medicine at this early stage is the isolation of a specific category of cells from donors with different individual genetic profiles due to patient variability [Nsair and MacLellan, 2011]. Moreover, different biomaterials that have been used for the scaffolding of MSCs raise technical challenges (i. e. , the type of material, the special effect on bone, the effect on MSCs) [Gomez-Barrena et al. , 2011]. It is important to prepare biodegradable scaffolds with osteoinductive properties; their application can provide a 3D environment for MSCs at the site of the defect in which they promote angiogenesis and can contribute to the healing process [Cao et al. , 2014]. Finally, differentiation of the MSCs into preosteogenic cells is not fully supported by the in vivo release of osteogenic factors. Thus, by using the appropriate scaffold in an alternative approach, such problems may be solved. Furthermore, MSCs can be used together with PRP and different growth/healing promotive factors in order to improve their beneficial effects on bone healing. However, it is very difficult to conclude which elements are particularly critical and effective in stem cell therapy for bone healing because of the lack of comparative and randomized clinical studies [Evans et al. , 2006]. The implementation of accurate clinical trials may help to further define and spread these therapies as a standardized cost-beneficial procedure for bone regeneration cell therapy, if their safety and efficacy is proven. [SEP] Justify:

Output: The text corroborates the claim by discussing various methods of using mesenchymal stem cells (MSCs) in bone regenerative medicine. It details the local delivery of MSCs, the use of scaffolds, and the combination of MSCs with osteoinductive genes to promote bone healing. This highlights the role of stem cells in regenerative medicine, particularly in repairing damaged tissues such as bone, thus supporting the claim.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: The scientific hepatology community is euphoric about the possibility of elimination and even eradication of HCV infection. However, the current high cost of the new all-oral regimens allows access to treatment only for a restricted number of HCV-infected patients. In addition, many other conditions such as modality of access and delivery of care, inadequate knowledge of HCV epidemiology and political commitments to be undertaken, hamper the fulfillment of the dream to eliminate the virus. Since, such conditions are not impossible to overcome, a global urgent effort must be made to allow a widespread access to the new treatments which will permit in the next years to avoid million of HCV-related deaths. Key Words: Sofosbuvir; Simeprevir; New-oral hepatitis C virus treatments; Paritaprevir; Dasabuvir; Daclatasvir; Ledipasvir; tip: It is begun the era of all-oral direct-acting antiviral drugs for hepatitis C virus (HCV) treatment allowing interferon-free therapeutic regimens. These regimens are safe and yield cure rate greater than 90%. The therapeutic success has posed the basis for HCV elimination, although, confirmation are waiting from real world. However, many conditions hinder the fulfillment of the dream. These conditions are the excessive cost of drugs, the access and delivery of care, the epidemiology of HCV and the political commitments. Thus, an urgent effort must be done to make accessible on large-scale all-oral anti-HCV therapies allowing saving millions of lives. Citation: Adinolfi LE, Guerrera B. All-oral interferon-free treatments: The end of hepatitis C virus story, the dream and the reality. Hepatol 2015; 7(22): 2363-2368 URL: DOI: the years 2014-2015 the scientific hepatology community virtually laid the milestone that could mark the beginning of the end of the hepatitis C virus (HCV) story. The milestone marked the advent of the first new oral drugs approved for HCV treatment, namely sofosbuvir and simeprevir, which were quickly followed by several others allowing interferon (IFN)-free therapeutic regimens. These innovative therapies, which yield a cure rate of over 90%, have been approved in many regions of the world, including Europe and the United States. [SEP] Justify:

Output: The text contrasts the claim by indicating that while new antiviral treatments for HCV have a high cure rate and are generally considered safe, it discusses various conditions—such as excessive cost, access issues, and knowledge gaps—that hinder widespread treatment. This suggests that not all treatments, particularly those involving new technologies like nanotechnology as implied in the claim, can be assumed to be risk-free, as there are numerous factors that may impact their safety and accessibility.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: This bears out particularly well for most “class II elements” or “DNA transposons” in eukaryotes; due to the trans-activity of the transposase on the genomic copies, these do not tend to evolve during their short life in a genome, and thus create copies that have a star-like phylogenetic relationship to the original sequence (Fig. 1) [12]. The situation is more complicated for most class I elements, which duplicate via a reverse transcription step; thanks to the cis-activity of the reverse transcriptase on its own mRNA, they may evolve, e. g. to escape the host’s defense mechanisms, and propagate in a genome for hundreds of millions of years. For these elements, careful clustering of copies into so-called subfamilies will result in a series of interrelated consensus sequences that can be interpreted as snapshots of the TE sequence during its evolution, though each may still be a composition of divergent active elements. Fig. 1Typical phylogenetic structure of retroposon and DNA transposon families. After multiple mutations have occurred in the evolving class I TE, the relative ordering of copies may be distinguished by these changes as they cosegregate. The presence of such clusters or “subfamilies” of TE copies is a good indication that they arose via retrotranspositionFull size imageThe concept that consensus sequences approach the original TE sequence has been demonstrated by the resurrection of recently extinct TEs through modification of a dead copy to the consensus [13, 14] and by the recovery of expected sequence features for ancient elements. For example, the consensus sequences of many coding TEs that were active > 100 MYA in our genome contain full-length ORFs [15], despite the fact that their individual copies have accumulated so many mutations that they on average share less than half the original nucleotides with each other and often cannot be pairwise aligned. was initiated as a reference database containing (single copy) prototypes of genomic interspersed repetitive DNA [16], we began developing consensus sequence representations by 1994 [11]. Not only did this endeavor explain the biological origin of most repetitive DNA, the use of consensus sequences rather than genomic copies improved the detection of older and therefore more diverged copies as well. A collection of genomic copies has redundancy and contains low complexity sequences like simple repeats expanded in individual copies, both of which result in lower specificity. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the evolution of transposable elements and their phylogenetic relationships without mentioning the Human Genome Project or its mapping of human DNA. There is no indication in the text that relates to the specifics of the Genetic mapping conducted by the Human Genome Project.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text supports the claim as it references multiple studies about mesenchymal stem cells, which are a type of stem cell used in regenerative medicine for their potential to assist in tissue repair and regeneration. The inclusion of various scholarly articles discussing stem cell applications and their properties strongly corroborates the assertion that stem cells play a role in regenerative medicine.


Input: Task: contrast the claim using the given text. 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. [SEP] Justify:

Output: The text contrasts the claim by highlighting that previous treatments, including those based on interferon (IFN), were associated with significant severe side effects that limited their use. It discusses the complexities and risks involved in treatments for hepatitis C, emphasizing that the success and safety of these treatments evolved over time, but side effects and treatment limitations were present. The mention of high rates of serious adverse events in the context of direct-acting antiviral drugs (DAAs) suggests that treatments, including those involving nanotechnology, cannot be considered completely risk-free.


Input: Task: pass the claim using the given text. 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. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the Human Genome Project's mapping of the entire human DNA sequence. Instead, it discusses various aspects of transposable elements (TEs), their classification, and associated evolutionary considerations, without mentioning the Human Genome Project or its achievements.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text corroborates the claim by discussing several studies and articles related to mesenchymal stem cells, which are a type of stem cell used in various medical applications, including regenerative medicine. The mention of their role in treatment for conditions such as systemic lupus erythematosus and their effects in colitis suggest their utility in repairing damaged tissues.


Input: Task: contrast the claim using the given text. 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. [SEP] Justify:

Output: The text contrasts the claim by discussing various direct-acting antiviral agents (DAAs) that are used in hepatitis C treatment, highlighting specific regimens and their sustained virologic response rates. It implies that, while these treatments can be effective, there are nuances and potential risks associated (e.g., response rates can vary based on patient mutations, as indicated by the lower response rate in patients with the Q80K mutation). This suggests that not all treatments are 'completely risk-free,' contradicting the claim.


Input: Task: pass the claim using the given text. 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]. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the Human Genome Project mapping human DNA. It discusses classification systems for eukaryotic transposable elements (TEs) and does not provide any information or evidence about the Human Genome Project or the mapping of human DNA.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text corroborates the claim as it discusses various studies and clinical uses of mesenchymal stem cells (MSCs) and their role in regenerative medicine, particularly mentioning the effectiveness associated with osteogenesis and skeletal repair. This aligns well with the claim that stem cells are used to repair damaged tissues, indicating their significant role in regenerative therapies.


Input: Task: contrast the claim using the given text. 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]. [SEP] Justify:

Output: The text contrasts the claim by discussing various treatments for Hepatitis C (HCV) and their effectiveness, but does not address the concept of risk or safety related to nanotechnology. While it highlights the efficacy of certain drug combinations, it implies that not all treatment approaches are guaranteed to be risk-free or effective, especially when mentioning the variability in sustained virological response (SVR) rates among different patient groups.


Input: Task: pass the claim using the given text. 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). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses a classification system in plant genomics and the relationships of transposable elements, which does not address the mapping of the human DNA sequence conducted by the Human Genome Project.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text provides multiple references to studies and articles that discuss the use of stem cells in various regenerative medicine applications, such as bone repair and tissue engineering. For example, it mentions 'Reduced morbidity with bone marrow stem cells in a resorbable matrix' and 'New insights into osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells,' both of which support the claim that stem cells are utilized in regenerative medicine to repair damaged tissues.


Input: Task: contrast the claim using the given text. 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]. [SEP] Justify:

Output: The text contrasts the claim by indicating various risks and precautions associated with the use of direct-acting antivirals (DAAs) in treating Hepatitis C. It highlights that while the data on safety indicate good tolerability, there are specific concerns such as the need for close follow-up in cirrhotic patients and contraindications in patients with Child-decompensated cirrhosis. Additionally, it mentions the necessity for caution with certain patients, particularly those with severe renal impairment. This suggests that not all treatments, including those potentially utilizing nanotechnology, can be considered completely risk-free.


Input: Task: pass the claim using the given text. 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. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the Human Genome Project and its mapping of human DNA. Instead, it discusses classification systems for transposable elements (TEs) and their hierarchical organization, which does not relate to the mapping of human DNA by the Human Genome Project.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text corroborates the claim by providing multiple references to studies that discuss the regenerative effects of various types of stem cells, particularly mesenchymal stem cells, in the context of tissue repair and healing. For example, it mentions a study on the 'regenerative effects of transplanted mesenchymal stem cells in fracture healing' which directly supports the idea that stem cells are used in regenerative medicine to repair damaged tissues.


Input: Task: contrast the claim using the given text. 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. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and challenges associated with HCV treatment, including high costs and restricted access, which imply that treatments, potentially including those using nanotechnology, may carry risks and are not universally accessible or risk-free. The mention of various conditions that hamper the fulfillment of treatment access indicates that not all treatments can be regarded as completely risk-free, especially considering economic and healthcare system barriers.


Input: Task: pass the claim using the given text. 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. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses classifications of transposable elements (TEs) and does not provide any information regarding the mapping of the human DNA sequence by the Human Genome Project. It focuses on classification systems and methods to identify TEs without addressing the broader context of human genome mapping.


Input: Task: corroborate the claim using the given text. 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. [SEP] Justify:

Output: The text provides multiple references and studies that suggest the application of stem cells, specifically mesenchymal stem cells (MSCs), in various contexts of regenerative medicine and tissue repair. For instance, it mentions the genetically engineered MSCs promoting bone regeneration and autologous bone marrow grafting used for treating osteonecrosis, indicating a clear link to the use of stem cells in repairing damaged tissues.


Input: Task: contrast the claim using the given text. 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. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and challenges associated with the treatment of hepatitis C, including high costs and the necessity for specialist supervision, indicating that treatments are not risk-free and depend on numerous factors such as accessibility and monitoring of at-risk populations.


Input: Task: pass the claim using the given text. 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. [SEP] Justify:

Output: The text does not address the claim about the Human Genome Project and its mapping of human DNA. Instead, it discusses transposable elements (TEs) and their classification based on various genetic sequences and characteristics. Therefore, the text is irrelevant to the claim.