Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: For example, if a patient was prescribed metformin alone on entry to the cohort for 12 months and then was prescribed both glitazones and metformin for a further 24 months and then had a treatment free period for six months until they were censored, they would have three treatment periods (metformin only for 12 months, metformin and glitazones for 24 months, and no treatment for six months). We determined the duration of each treatment period by calculating the number of days between the earliest issue date and the latest issue date plus 90 days for the type of treatment prescribed. If another treatment was added before the initial treatment was stopped then we calculated the duration of the treatment period on the initial treatment alone to be the number of days between the earliest issue date for the initial treatment and the earliest issue date for the next treatment. We added 90 days to the last prescription date as an estimate of the date on which the patient stopped treatment (the “stop date”), we made this assumption to allow for events that occur during a withdrawal period to be attributed to the drug rather than being counted as unexposed time. For the analysis, we used six binary exposure variables for each treatment period to indicate treatment with any of the diabetes drugs, grouped into six drug classes—glitazones (including rosiglitazone and pioglitazone), gliptins, metformin, sulphonylureas, insulin, and other oral diabetes drugs (including α-glucosidase inhibitors, sodium-glucose cotransporter 2 inhibitors, glinides, guar). This accounted for patients receiving different combinations of these drugs during a treatment period. To further assess associations for different specific treatment combinations (such as dual treatment with metformin and glitazones) we also categorised treatments during each treatment period into one categorical variable with 21 mutually exclusive treatment categories, including a no current treatment group and 20 categories for monotherapy, dual treatment, and triple combinations of drugs. Confounding variablesWe considered confounding variables that were likely to be associated with the risk of the complications from diabetes20 37 38 39 40 or with the likelihood of receiving treatment with different diabetes drugs. [SEP] Justify:

Output: The text contrasts the claim by describing a detailed methodology for assessing treatment periods and associated risks related to various diabetes medications. It highlights the importance of considering various treatment combinations and confounding variables that might affect the outcomes, implicitly suggesting that treatments, including those potentially involving nanotechnology, are not devoid of risk.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Οι πληθυσμοί των ελληνικών νησιών τοποθετούνται κοντά στη ρίζα του δέντρου όπως ορίζεται από τα είδη Gir και Yak, ενώ οι φυλές της ηπειρωτικής χώρας μοιράζονται μια κοινή ιστορική προέλευση με την Buša. [SEP] Justify:

Output: The text does not address the claim regarding genetic markers and inheritance patterns. Instead, it describes the geographical placement and historical origins of certain populations without mentioning genetic markers, making it 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: Thus glandular stem cells should enable a glandular stem cell cardiomyoplasty which combines an expected regenerative potential of transformed adult glandular stem cells into cardiomyocytes within the myocardium with the potential of a hypercapillarized latissimus dorsi muscle (LDM) wrapped around the heart for stem cell nutrition and girdling. Advertisement 1. Association, -2009Updates, Dallas, Texas2. BeyerM. 1997Cardiomyopexy-current status of an indirect revascularization method. Z Kardiol; 86:Suppl 1125132 3. BeyerM. BeyerU. MierdlS. SirchJ. vonBehren. H. HannekumA. 1994Indirect myocardial revascularization--an experimental study in the dog. Cardiothorac Surg; 8557562 4. CarpentierA. ChachquesJ. C. 1985Myocardial substitution with stimulated skeletal muscle:first successful clinical case. Lancet;1:1267 EOF 5. ChiuR. C. J. 2005Tolerance” in stem cell Transplantation: Potential for “universa Donors” in myocardial regenerative therapy. J of Heart and Lung Transplant; 24511516 6. ChoiY. TaM. AtoufF. LumelskyN. 2004Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny. Stem Cells; 22107010847. DawsonJ. M. HudlickaO. 1989The effect of long-term activity on the microvasculature of rat glycolytic muscle. Microcirc; 8538. GuanK. et al. 2006Pluripotency of spermatogonial stem cells from adult mouse testis. Nature [online March]15 9. GuldnerN. W. KlapprothP. SchwarzP. O. et al. 2009Bio-technologies for glandular stem cell cardiomyopexy. Ann. Anatomy;191455010. . et al. 1994Dynamic training of skeletal muscle ventricles. A method to increase muscular power for cardiac assistance. Circulation; 8910321040 11. GuldnerN. W. KajahnKlinger. [SEP] Justify:

Output: The text corroborates the claim by discussing how glandular stem cells have the potential to be utilized in a cardiomyoplasty procedure that aims to repair damaged heart tissues by transforming these stem cells into cardiomyocytes within the myocardium. This aligns directly with the idea that stem cells are employed 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: Statistical analysisproportional hazards models we assessed the associations between the six different classes of diabetes drugs and risk of each of our three outcomes, adjusting for potential confounding variables. Rather than using a competing risks analysis we used the Cox model as it is considered more appropriate for analyses of causes such as in this study, whereas competing risks analyses tend to be more useful for prediction modelling or estimating absolute risks. 42 43 44 To account for patients starting and stopping different diabetes treatments and changing between treatments, we included use of different diabetes drugs as time varying exposures. In the analysis, we calculated unadjusted and adjusted hazard ratios for the six different classes of diabetes drug (each as a binary variable indicating use or no use), with adjustment for the confounding variables and the other classes of diabetes drugs. We also calculated unadjusted and adjusted hazard ratios for the mutually exclusive treatment combinations comparing each treatment category with no current treatment. To determine whether there were significant differences between classes or individual drugs, we carried out Wald’s tests. We tested for interactions between the six different drug classes and age, sex, haemoglobin A1c, and body mass index. We used multiple imputation with chained equations to replace missing values for continuous values and smoking status and used these values in our main analyses. 45 46 47 We did this for each of the study outcomes and in the imputation model included the censoring indicator for the outcome, the log of survival time, all the confounding variables, and the diabetes drug treatment variables. Before imputation we log transformed body mass index, haemoglobin A1c, creatinine level, and cholesterol to high density lipoprotein cholesterol ratio, as they had skewed distributions. We carried out five imputations, and combined the results using Rubin’s rules. To evaluate the robustness of our results and assess the impact of confounding variables we added the confounding variables to our model in blocks and compared the adjusted hazard ratios. Box 1 lists the models we assessed. [SEP] Justify:

Output: The text contrasts the claim by discussing statistical analysis of diabetes drug classes, indicating that the study assesses risks associated with different treatments. It implies a consideration of risk factors and does not support the idea that any treatment, including those potentially involving nanotechnology, is completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Οι μη εποπτευόμενες αναλύσεις ομαδοποίησης και η ανάλυση D-statistics παρείχαν ισχυρές ενδείξεις για την παρουσία γονιδίων του Bos indicus σε όλες σχεδόν τις τοπικές φυλές βοοειδών που ερευνήθηκαν κατά μήκος της διαδρομής από την Ανατολή μέχρι τις νότιες παρυφές των Άλπεων, καθώς και στις περισσότερες φυλές βοοειδών κατά μήκος της χερσονήσου των Απεννίνων προς τους πρόποδες των Άλπεων. [SEP] Justify:

Output: The text discusses analyses related to the genetic markers of the Bos indicus breed across various local cattle populations but does not specifically address the capability of genetic markers to trace inheritance patterns in populations. Therefore, it 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: M. SieversH. H. KruseC. 2006Autonomously contracting human cardiomyocytes generated from adult pancreatic stem cells and enhanced in co-cultures with myocardial biopsies. Artif Organs; 2911586612. GuldnerN. W. KlapprothP. GrossherrM. et al. 2001Biomechanical hearts: muscular blood pumps, performed in a 1-step operation, and trained under support of clenbuterol. Circulation;104717722 13. GuldnerN. W. KlapprothP. GrossherrM. et al. 2000Clenbuterol-supported dynamic training of skeletal muscle ventricles against systemic load: a key for powerful circulatory assist? Circulation;1012213221914. HagègeA. A. DesnosM. FernandezF. BesseB. MirochnikN. CastaldoM. ChachquesJ. C. CarpentierA. GuérotC. 1995Clinical study of the effects of latissimus dorsi muscle flap stimulation after cardiomyoplasty. Circulation,; 92(9 Suppl): II21021515. HeschelerJ. FleischmannB. K. LentiniS. MaltsevV. A. RohwedelJ. WobusA. M. 1997Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis. Cardiovasc Res. ; 3614916216. HudlickaO. TylerK. R. 1984The effect of long-term high frequency stimulation on capillary density and fibre types in rabbit fast muscles. J Physiol; 35343544517. KawamotoA. TkebichavaT. YamaguchiJ. 2003Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neo-vascularization of myocardial ischemia. Circulation; 10746146818. AAKocherSchuster. MJSzabolesTakuma. S. GurkhoffD. WangJ. et al. [SEP] Justify:

Output: The text lists various studies and clinical trials that involve the use of stem cells and their applications in regenerative medicine, specifically mentioning the generation of cardiomyocytes from adult pancreatic stem cells, which supports the claim that stem cells are utilized in repairing damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Box 1: Types of models used in studyModel A: diabetes drug classes adjusted for age, sex, ethnicity, deprivation, calendar year, duration of diabetes, plus other diabetes drugsModel B: model A plus comorbidities (hypertension, cardiovascular disease, heart failure, atrial fibrillation, chronic kidney disease, rheumatoid arthritis, valvular heart disease, peripheral vascular disease) plus previous complications (hypoglycaemia, hyperglycaemia, amputation, severe kidney failure, blindness) plus use of other drugs (statins, aspirin, anticoagulants, thiazides, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers)(primary analysis model): model B plus clinical values (body mass index, cholesterol to high density lipoprotein cholesterol ratio, systolic blood pressure, serum creatinine level, haemoglobin A1c)Model D: model C plus interaction termsModel E: treatment combinations categorical variable plus confounders in model C (models compared with no treatment and with metformin monotherapy)Model F: model C with prevalent users of sulphonylureas excludedModel G: model E with prevalent users of sulphonylureas excludedWe also carried out a sensitivity analysis where we excluded prevalent users of sulphonylureas from the study cohort so that the hazard ratios for sulphonylureas are based on incident users, and we fitted the models F and G (see box 1). We used all the available data in the database to maximise the power and generalisability of the results. P values less than 0. 01 (two tailed) were considered as significant and hazard ratios of 1. 10 or more or 0. 90 or less as clinically important. STATA (version 13. 1) was used for all analyses. Patient involvementPatients were not involved in setting the research question, in the outcome measures, in the design, or in the implementation of the study. Patient representatives from the QResearch advisory board have written the information for patients on the QResearch website about the use of the database for research. They have also advised on dissemination, including the use of lay summaries describing the research and its results. ResultsOverall, 1243 practices contributing to QResearch in England met the inclusion criteria. A cohort of 601 405 patients aged 25-84 years with diabetes was identified (fig 1⇓). [SEP] Justify:

Output: The text contrasts the claim by not addressing nanotechnology directly, but it highlights various complex models and treatments that involve comorbidities and patient demographics. The mention of sensitivity analyses and exclusion of prevalent users suggests that there are inherent risks and considerations in treatments, indicating that not all treatments are risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Οι πληθυσμοί βοοειδών της Κύπρου, του Καστελόριζου και του Αγαθονησίου παρουσίασαν υψηλά επίπεδα παρουσίας του Bos indicus, παρόμοια με αυτά των ανατολικών φυλών. [SEP] Justify:

Output: The text does not relate to the claim about using genetic markers to trace inheritance patterns. It discusses the presence of Bos indicus in specific populations without addressing genetic markers or inheritance patterns.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: 2001Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodelling and improves cardiac function. Nat Med,; 743043619. KruseC. BirthM. RohwedelI. AssmuthK. GoepelA. WedelT. 2004Pluripotency of adult stem cells derived from human and rat pancreas. A; 115 20. KruseC. BirthM. RohwedelI. AssmuthK. GoepelA. WedelT. 2004Pluripotency of adult stem cells derived from human and rat pancreas. A; 11521. MakinoS. FukudaK. MiyoshiS. KomadaF. K. PanJ. SanoM. TakahashiT. HoriS. AbeH. HataJ. UmezawaA. OgawaS. 1999Cardiomyocytes can be generated from marrow stromal cells in vitro J Clin Invest; 10369770522. JDMannionBlood. V. BaileyW. et al. 1996The effect of basic fibroblast growth factor on the blood flow and morphologic features of a latissimus dorsi cardiomyoplasty. J Surg; 111192823. JDMannionBuckman. P. D. MagnoM. G. Di MeoF. 1992Collateral blood flow from skeletal muscle to normal myocardium. J Surg Res; 5357858724. JDMannionMagno. M. BuckmanP. et al. 1993Techniques to enhance extramyocardial collateral blood flow after a cardiomyoplasty. Ann Surg; 21854455325. ,1993Acute electrical stimulation increases extramyocardial collateral blood flow after a cardiomyoplasty. Surg; 561351826. Mathieu Costello1996Capillary-to-fibre surface ratio in rat fast-twitch hindlimb muscles after chronic electrical stimulation. J Appl Physiol; 80390490927. OrlicD. KajsturajJ. ChimentiS. AndersonS. M. LiB. PickelJ. Mc KayR. et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential uses of human bone-marrow-derived angioblasts and adult stem cells in the context of myocardial repair. It specifically mentions how these stem cells can prevent cardiomyocyte apoptosis, reduce remodeling, and improve cardiac function, which aligns well with the idea of using 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: Overall, at least 82% of patients had complete data for each clinical value across all drug groups. Apart from higher mean levels of haemoglobin A1c in patients before use of insulin or the group of other diabetes drugs, and higher levels of creatinine among those prescribed sulphonylureas or insulin, the mean values were similar across the six groups. Supplementary table 1 shows mean values before starting the 20 different treatment combinations. The mean values for haemoglobin A1c tended to be higher for patients starting triple treatment (as high values tend to trigger changes in treatment). Table 2 Recorded clinical values before starting drugs or at study entry for prevalent usersView this table:View popupView inlineRisks associated with use of each diabetes drug groupTable 3⇓ shows the number of incident cases of each outcome for patients’ periods of use of each of the six treatment groups during follow-up. Importantly, the treatment groups in table 3⇓ are not mutually exclusive—for example, the rows for glitazones include any use of glitazones, whether as monotherapy, dual treatment, or triple treatment. Similarly, the adjusted hazard ratios for model C shown in table 3⇓ give an overall risk for the use of each drug group compared with non-use of that drug group, having adjusted for use of other diabetes drugs and the potential confounders listed in the footnote. Table 3 Adjusted hazard ratio (95% confidence intervals) for each outcome by use of diabetes drug (model C)View this table:View popupView inlineFor our main exposures of interest we found that compared with non-use, glitazones were significantly associated with a 23% decreased risk of all cause mortality, a 26% decreased risk of heart failure, and a 25% decreased risk of cardiovascular disease; and compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant association with risk of cardiovascular disease. [SEP] Justify:

Output: The text contrasts the claim by discussing various diabetes drug groups and their associated risks and benefits, including adjusted hazard ratios for outcomes such as all cause mortality and heart failure. The mention of risks connected with different treatment groups indicates that treatments, even if they involve advanced technologies like nanotechnology, are not without risks, thereby challenging the assertion that all treatments using this technology are completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Όλες οι φυλές της Κύπρου και της Ελλάδας που ερευνήθηκαν παρουσιάζουν ένα πολύπλοκο γονιδιωματικό μωσαϊκό ως αποτέλεσμα ιστορικών και πρόσφατων γεγονότων πρόσμιξης μεταξύ γειτονικών φυλών μιας γεωγραφικής έκτασης που εκτείνεται σε όλη την περιοχή της Νοτιοανατολικής Ευρώπης, συμπεριλαμβανομένης της Ευρωπαϊκής Ασίας. [SEP] Justify:

Output: The text discusses the genetic makeup of populations in Cyprus and Greece, highlighting a complex genomic mosaic resulting from historical and recent admixture events. However, it does not specifically address the use of genetic markers to trace inheritance patterns, making it 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: 2001Bone marrow cells regenerate infarcted myocardium. Nature. ;41070170528. Planat-BenardV. MenardC. AndreM. PuceatM. PerezA. Garcia-VerdugoJ. PenicaudCasteilla. L(2004Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res; 9422322929. PuissantB. BarreauC. BourinPh. ClavelC. BousquetCh. TaureauCh. 2005Immunmodulary effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Haematol,); 12911812930. SalmonsS. . HastingsM. HooperT. L. 1998Morphological and functional evidence, and clinical importance, of vascular anastomoses in the latissimus dorsi muscle of the sheep. J Anat; 19319310431. SeabergM. 2004Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat biotech [online March] 110 32. 2006Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab Invest; 861415333. SkorjancD. JaschinskiF. HeineG. PetteD. 1998Sequential increases in capillarization and mitochondrial enzymes in low-frequency-stimulated rabbit muscle. Physiol; 274810818 34. StammC. WestphalB. KleineH. D. et al. 2003Autologous bone marrow stem-cell transplantation for myocardial regeneration. Lancet; 361454635. SteinhoffG. Choi-HY. StammC. 2006Intramyocardial bone marrow stem cell treatment for myocardial regeneration. J; Suppl:323936. WangT. XuZ. JiangW. MaA. 2005Cell-to-cell contact induces mesenchymal stem cell to differenciate into cardiomyocyte and smooth muscle cell. Cardiol. Aug 22; [Epup ahead of print]. 37. Wollert KC and Drexler H2005Clinical applications of stem cells for the heart, Circ. [SEP] Justify:

Output: The text supports the claim by providing multiple examples and studies related to the use of stem cells for regenerative purposes. For instance, it mentions 'Autologous bone marrow stem-cell transplantation for myocardial regeneration' which indicates the application of stem cells in repairing heart tissues. Additionally, it references 'spontaneous cardiomyocyte differentiation from adipose tissue stroma cells', which further corroborates the role of stem cells in the regeneration of damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: 7 million person years free of use of any diabetes drug. The table shows the number of events for each clinical outcome for each of the treatment categories. Table 4 Number of incident events for each outcome and person years of exposure to mutually exclusive treatment groupsView this table:View popupView inlineTable 5⇓ shows the corresponding adjusted hazard ratios for each treatment group category compared with no current treatment. The key significant findings are (all compared with periods of no diabetes drug treatment):Table 5 Adjusted hazard ratio (95% confidence intervals) for each outcome (model F)View this table:View popupView inline• There were no significant associations between monotherapy with gliptins and risk of any of the three outcomes. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause mortality). • Monotherapy with glitazones was associated with a 50% decreased risk of heart failure. Dual treatment with metformin and glitazones was associated with a decreased risk of all three outcomes (reductions of 50% for heart failure, 54% for cardiovascular disease, and 45% for all cause mortality). Dual treatment with sulphonylureas and glitazones was associated with a decreased risk of two outcomes (reductions of 35% for heart failure and 25% for cardiovascular disease). Triple treatment with metformin, sulphonylureas, and glitazones was associated with a decreased risk of all three outcomes (reductions of 46% for heart failure, 41% for cardiovascular disease, and 56% for all cause mortality). Table 6⇓ shows the results for the different treatment combinations compared with metformin treatment alone (rather than compared with periods of no treatment as previously). [SEP] Justify:

Output: The text contrasts the claim by outlining various treatment outcomes related to diabetes drugs, indicating that different treatment combinations have varying risks associated with them. For instance, it mentions results like 'dual treatment with gliptins and metformin was associated with a decreased risk,' showing that not all treatments can be deemed risk-free. This implies a level of risk is present in treatments, specifically those relating to diabetes, thus contradicting the notion that all nanotechnology-based treatments are completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Αν και η συμβολή ορισμένων ηπειρωτικών φυλών στη δεξαμενή γενετικής ποικιλότητας φαίνεται σημαντική, ορισμένες νησιωτικές και κατακερματισμένες φυλές της ηπειρωτικής χώρας υποφέρουν από σοβαρή μείωση του μεγέθους του πληθυσμού τους και απώλειας αλληλομόρφων λόγω της τυχαίας γενετικής παρέκκλισης. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the genetic diversity contributions of certain continental and island populations and issues related to population size reduction, without mentioning genetic markers or tracing inheritance patterns.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: Close navigation menu 83. 83. Download citation file: Ris (Zotero) toolbar search Menu toolbar search search input Search input auto suggest filter your search and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects. Journal Section: Editor's choice Keywords: Mesenchymal stem cells, Bone regeneration, Bone tissue engineering has a self-repair ability so that it can repair itself when the nature and extent of injury is not large, chronic, severe, and complicated. Bone healing is a complex process of overlapping phases, including inflammation, repair, and remodeling that involves the many intracellular signaling pathways which are responsible for regeneration of the new bone with the help of surrounding tissues [Oryan and Moshiri, 2013; Oryan et al. , 2014b; Moshiri et al. , 2015b]. Bone healing is not always completely satisfactory, and many reasons might be responsible for its failure. [SEP] Justify:

Output: The text corroborates the claim by providing specific information about the application of mesenchymal stem cells (MSCs) in bone repair and regeneration. It emphasizes that MSCs, which are multipotent stem cells, are increasingly being utilized in regenerative medicine to improve outcomes in treating bone injuries, particularly large bone defects. The discussion around MSC therapy's potential roles in bone repair aligns with the assertion that stem cells are indeed used for repairing damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: The key findings for our two exposures of interest are:Table 6 Adjusted hazard ratios (95% confidence intervals) for each outcome (model F) compared with monotherapy with metforminView this table:View popupView inline• Monotherapy with gliptins was associated with a 50% increased risk of cardiovascular disease and an 86% increased risk of all cause mortality; dual treatment with metformin and gliptins was associated with a decreased risk of two outcomes (reductions of 13% for cardiovascular disease and 20% for all cause mortality); dual treatment with sulphonylureas and gliptins was associated with a 44% increased risk of all cause mortality and a borderline 27% increased risk of cardiovascular disease; triple treatment with metformin, sulphonylureas, and gliptins was associated with a 24% decreased risk of all cause mortality compared with metformin alone. • Monotherapy with glitazones was not associated with an increased or decreased risk of any outcome compared with metformin alone; dual treatment with metformin and glitazones was associated with a decreased risk of two outcomes (reductions of 26% for heart failure and 40% for cardiovascular disease) and a borderline 14% decreased risk in all cause mortality; dual treatment with sulphonylureas and glitazones was associated with a 50% increased risk of all cause mortality; triple treatment with metformin, sulphonylureas, and glitazones was associated with a decreased risk of all three outcomes (reductions of 21% for heart failure, 22% for cardiovascular disease, and 32% for all cause mortality) compared with metformin alone. Supplementary table 3 shows the results for the different treatment combinations compared with periods of no treatment, having dropped prevalent users of sulphonylureas at study entry (model G). Incident use of sulphonlyureas, whether alone or in combination with insulin as dual or triple treatment, was associated with a substantial increased risk of all cause mortality of 50%, 171%, and 87%, respectively. Monotherapy with sulphonylureas was associated with a 12% increased risk of cardiovascular disease and a 16% increased risk of heart failure. Triple treatment with sulphonlyureas, metformin, and insulin was associated with a 42% increased risk of heart failure. [SEP] Justify:

Output: The text contrasts the claim by detailing various treatment outcomes, including instances of increased risk associated with certain medications. It states that monotherapy with gliptins and sulphonylureas increases the risk of cardiovascular diseases and all-cause mortality, emphasizing that certain treatments do carry significant risks. Thus, it provides evidence that not all treatments, potentially including those involving nanotechnology, are risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Τα προγράμματα γενετικής διατήρησης, που θα μπορούσαν να εφαρμοστούν για τη προστασία των τοπικών φυλών, θα πρέπει να αποτελούν έναν συμβιβασμό μεταξύ του εφικτού και του επιθυμητού και να επικεντρώνονται όχι μόνο στις φυλές της ηπειρωτικής χώρας που έχουν υψηλά επίπεδα ποικιλομορφίας αλλά να διερευνούν και τις δυνατότητες διατήρησης των νησιωτικών φυλών. περισσότερα Περίληψη σε άλλη γλώσσα The autochthonous cattle population of Greece is like that bred throughout the and they consist of the Brachyceros (“Shorthorn”) and the Podolian or Steppe type. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses genetic conservation programs for local livestock breeds in Greece and does not mention genetic markers or inheritance patterns at all.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: These include those injuries that cause large bone defects to occur and develop, such as necrosis, tumors (e. g. , osteosarcoma), high-energy traumas, and compound-, multiple-, gunshot-, open-, comminuted-, and osteoporosis-related fractures [Frohlich et al. , 2008; Amini et al. , 2012; Oryan et al. , 2015]. This failed healing process can eventually lead to the formation of malunions, delayed unions, nonunions, and osteomyelitis. Today, the correction of bone regeneration impairment has been achieved by advances in healing process management. Using the latest equipment and surgical techniques, better protocols and more effective rehabilitation procedures have contributed to a better prognosis for bone healing [Houlden et al. , 2007; Moshiri et al. , 2015b]. Despite these advancements, malunions, delayed unions, or nonunions occur and persist in clinical cases where the osteogenesis and subsequent bone remodeling are impaired, particularly in those involving large bone defects [Oryan et al. , 2014b]. In order to improve and accelerate the healing process, several options are currently available in clinical practice [Amini et al. , 2012]. First of all, after the diseased bony tissue has been removed and the remaining bones fixed, the resulting defect should be reconstructed and filled with various grafts and materials [Amini et al. , 2012; Oryan et al. , 2014b; Moshiri et al. , 2015b]. An ideal bone graft substitute should have certain properties, including osteoconduction, osteoinduction, osteoincorporation, osteointegration, and osteogenesis [Oryan et al. , 2014a]. Despite several efforts that have been made to invent and characterize various bone graft substitutes and engineered tissue scaffolds, none could be globally accepted as an ideal alternative option to autografts due to the low ability of the bone substitutes to enhance osteoinduction and osteogenesis [Zomorodian and Eslaminejad, 2012; Mallick and Cox, 2013; Bigham-Sadegh and Oryan, 2015]. Stem cell therapy, as one of the methods used in the bone repair process, has been developed over the last 2 decades [Giuliani et al. , 2013]. [SEP] Justify:

Output: The text corroborates the claim by stating that 'Stem cell therapy, as one of the methods used in the bone repair process, has been developed over the last 2 decades,' which indicates that stem cells play a role in regenerative medicine specifically aimed at repairing damaged tissues.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Overall, the adjusted hazard ratios for glitazones and gliptins were similar to those in table 5⇑, except confidence intervals were wider, and there was no longer a significant decrease in risk of heart failure and cardiovascular disease among people prescribed dual treatment with sulphonylureas and glitazones. DiscussionWe have conducted a large cohort study of risks for cardiovascular disease, heart failure, and all cause mortality associated with different diabetes drugs in people with type 2 diabetes attending for routine clinical care in the UK. Our companion paper27 presented the corresponding analysis for other complications of diabetes, including blindness, amputation, severe kidney failure, hyperglycaemia, and hypoglycaemia. The approach we have taken allows assessment of the relative benefits and hazards of diabetes drugs in a real world clinical setting for a range of clinically important outcomes. It enables analysis of treatment periods that are substantially longer than those reported in clinical trials,9 including more events than in previous similar observational studies. 5 12We have found clinically relevant differences between different diabetes drugs (alone and in combination) in the risk of three key outcomes—heart failure, cardiovascular disease, and death—in people with type 2 diabetes. Compared with non-use, use of glitazones was significantly associated with a decreased risk of all three outcomes (all cause mortality; heart failure, and cardiovascular disease), whereas use of gliptins was significantly associated with a decreased risk of two outcomes (all cause mortality and heart failure) but no significant change in risk of cardiovascular disease. Compared with periods of no treatment, dual treatment (ie, metformin and gliptins or metformin and glitazones) was associated with a decreased risk of all three outcomes, as was triple treatment with metformin, sulphonylureas, and either gliptins or glitazones. However, since the use of gliptins and glitazones is usually recommended as a second line treatment in combination with other agents such as metformin, the clinical question is whether the addition of gliptins or glitazones to metformin monotherapy is associated with net benefit or net harm. Compared with metformin monotherapy, dual treatment (metformin and glitazones) and triple treatment (metformin, sulphonylureas, and glitazones) were associated with decreased risk of all three outcomes (see table 6⇑). [SEP] Justify:

Output: The text contrasts the claim by discussing the risks associated with various diabetes treatments, indicating that not all treatments, including those that involve advanced technologies, are risk-free. It reveals that there are clinically relevant differences in treatment outcomes, including risks of heart failure and cardiovascular disease, thus highlighting that treatments, including those using nanotechnology, may have associated risks.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Conservation programs that are a compromise between what is feasible and what is desirable should focus not only on the highly diverse mainland breeds but also promote and explore the conservation possibilities for island breeds. περισσότερα Διαβάστε τη διατριβή (Online) Κατεβάστε τη διατριβή σε μορφή PDF (15. 82 MB) (Η υπηρεσία είναι διαθέσιμη μετά από δωρεάν εγγραφή) Δηλώνω ότι έλαβα γνώση και ανεπιφύλακτα συμφωνώ και αποδέχομαι τους Όρους Χρήσης του Εθνικού Αρχείου Διδακτορικών Διατριβών, καθώς και της Κατέβασμα αρχείου PDF Όλα τα τεκμήρια στο ΕΑΔΔ προστατεύονται από πνευματικά δικαιώματα. DOI10. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses conservation programs for mainland and island breeds without mentioning genetic markers or inheritance patterns. There is no information in the text that relates to the assertion of how genetic markers could trace inheritance in populations.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: The involvement of mesenchymal stem cells (MSCs) in the bone healing process is critical, in particular for difficult nonunion fractures resulting from trauma, blood insufficiency, and other conditions [Grayson et al. , 2015; Melek, 2015]. The reparative process of bone regeneration is initiated by MSCs with the formation of soft and hard calluses. Bone remodeling can eventually start after the gap has been filled by this process. Modern strategies of tissue engineering and regenerative medicine (TERM) utilize tissue scaffolds, healing promotive factors (e. g. , growth factors such as BMP-2), and MSCs to improve bone repair and regeneration. Most in vitro and many in vivo studies have suggested that the MSCs have the potential to increase osteoinduction and osteogenesis [Li et al. , 2007; Otsuru et al. , 2007; Hayashi et al. , 2008; Pitchford et al. , 2009; de Girolamo et al. , 2013]. However, little proof is available from the standard clinical trials. In addition, some controversies are apparent between the results and conclusions of the studies, making them difficult to interpret. In order to achieve successful results, an understanding of several mechanisms related to MSCs, such as homing, differentiation, apoptosis, and inflammation, together with various current and future options for which MSCs may be used, is necessary to determine the outcome of cell therapy [Qin et al. , 2014b]. In this review we summarize recent advances in understanding of the mechanisms of MSCs in bone repair. Moreover, we update the most important delivery approaches of MSCs in bone TERM. We also review the reported effects of MSC therapy on bone healing in various clinical trials according to the site of damage. The side effects of this therapy are also illustrated to help readers to draw better conclusions regarding its use. Finally, we discuss the role of TERM approaches in bone healing and illustrate the prospects and directions for the future of MSC-related research. Mechanisms of MSC Action in Characteristics of are multipotent stromal cells present in most adult connective tissues. They have been extensively studied because of their ability to differentiate into multiple cell types [Eslaminejad and Nadri, 2009; Eslaminejad et al. , 2009]. Friedenstein et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the critical involvement of mesenchymal stem cells (MSCs) in the bone healing process, specifically noting their role in repairing difficult nonunion fractures and initiating the reparative process in bone regeneration. It mentions modern strategies in regenerative medicine that utilize MSCs along with tissue scaffolds and growth factors to enhance bone repair and suggests that MSCs have the potential to improve osteoinduction and osteogenesis based on various studies.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Dual treatment (metformin and gliptins) was associated with a decreased risk of cardiovascular disease and all cause mortality compared with metformin monotherapy. Triple treatment (metformin, sulphonylureas, and gliptins) was associated with a 24% reduced risk of all cause mortality (see table 6⇑). GliptinsOur study included over 70 000 person years of exposure to gliptins from over 32 500 patients, which represents one of the largest studies to date, with over four times more gliptin users than in the observational study by Eurich et al. 20 Our results differ from those reported by Eurich et al, since we found that use of gliptins compared with non-use was associated with a reduction in all cause mortality. We also found that dual treatment (metformin and gliptins) and triple treatment (metformin, sulphonylureas, and gliptins) seems to be associated with a lower risk of all cause mortality compared with monotherapy with metformin. The median duration of use of gliptins in our study was 5. 7 years, compared with 2. 5 years in the study by Eurich et al,20 and the mean age of our cohort was 63 years compared with 52 years. 20 We also had more events and more statistical power—there were 996 deaths during 71 524 person years of exposure to gliptins in our study compared with 32 deaths during 11 307 person years in the study by Eurich et al. 20 Our findings of a reduction in risk of all cause mortality are relatively novel and deserve further investigation, especially as there was no overall reduction in cardiovascular events. Our results are consistent with another recent real world observational study, which found gliptins associated with reduced all cause mortality. 48 Park et al hypothesised that their findings might reflect reduced hypoglycaemic events, although their study, like ours, was observational and susceptible to unmeasured confounding. 48 In our companion paper, we reported reduced risks of hypoglycaemia among gliptin users compared with non-users, which is broadly consistent with this hypothesis. [SEP] Justify:

Output: The text contrasts the claim by discussing the risks associated with treatments, specifically mentioning that gliptins are subjected to observational studies that are 'susceptible to unmeasured confounding.' This indicates that there are potential risks involved with the use of gliptins and suggests that treatments involving technology, such as gliptins, cannot be deemed completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: 12681/eadd/56176 Διεύθυνση Handle ND56176 Εναλλακτικός τίτλοςGenetic identification of Greek bovine breeds/populations using molecular markers ΣυγγραφέαςΠαπαχρήστου, Δημήτριος (Πατρώνυμο: Αναστάσιος) Ημερομηνία2023 ΊδρυμαΓεωπονικό Πανεπιστήμιο Αθηνών. Σχολή Επιστημών των Ζώων. Τμήμα Επιστήμης Ζωικής Παραγωγής. [SEP] Justify:

Output: The text is irrelevant to the claim as it primarily consists of bibliographic information regarding a publication and does not discuss the use of genetic markers for tracing inheritance patterns in populations.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: [1970] demonstrated a rare population of plastic-adherent cells in bone marrow (approx. 1 in 10,000 nucleated cells) that were able to form a spindle-shaped cell morphology and round-shaped colonies. These cell clones expanded into round-shaped fibroblastoid colonies, which are termed colony-forming unit-fibroblasts, or CFU-Fs. Some of the colonies could differentiate into bone, cartilage, or adipose tissue [Bianco et al. , 2008]. Other research groups extended these initial observations through the study of the proliferative abilities and phenotypic characteristics of CFU-Fs [Caplan and Bruder, 2001; Eslaminejad and Taghiyar, 2010; Eslaminejad et al. , 2011; Lotfy et al. , 2014; Baker et al. , 2015]. MSCs have been widely used in stem cell transplantation, tissue engineering, gene therapy, and immunotherapy [Reiser et al. , 2005; Marion and Mao, 2006; Zhao et al. , 2016]. These cells express CD105, CD73, and CD90, and are not able to express CD45, CD34, CD14, or CD11b, CD79α or CD19 antigens. In addition, they are able to differentiate into at least 3 cell lineages in vitro, including chondroblasts, osteoblasts, and adipocytes [Eslaminejad et al. , 2007; Wyse et al. , 2014]. MSCs can migrate to defect sites and facilitate bone regeneration, but the fundamental mechanisms in this process remain unclear. In regenerative medicine, among all types of stem cells, MSCs are the most commonly used stem cells because of their beneficial properties [Murphy et al. , 2013]. The advantages and disadvantages of different types of MSCs are listed in Table 1. MSC populations and maintenance of their homeostasis are established in MSC niches [Ehninger and Trumpp, 2011]. Niches are specific anatomic locations that regulate tissue generation, maintenance, and repair by MSCs [Glenn and Whartenby, 2014]. The niche has a dual role by which it saves MSCs from depletion and also protects the host from overexuberant MSC proliferation. [SEP] Justify:

Output: The text corroborates the claim by detailing the role of mesenchymal stem cells (MSCs) in regenerative medicine. It notes that MSCs are widely used for tissue engineering and repair and can migrate to defect sites to facilitate bone regeneration. Additionally, the mention of their ability to differentiate into various cell lineages such as chondroblasts, osteoblasts, and adipocytes supports 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: 27Our results are also broadly consistent with recent non-inferiority trials18 and meta-analyses of randomised controlled trials, reporting that various gliptins (alogliptin, dutogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin) are associated with statistically significant 30-60% reductions in major adverse cardiac events and non-significant 33% and 48% reductions in all cause and cardiovascular death compared with other active drugs or placebo treatment. 49 50 However, Monami et al urge caution in interpreting the results because the events were not the principle endpoints, the trial duration was short, and the characteristics of patients could be different from those of patients in routine clinical practice. 50 We found an inverse association for gliptins, with a 15% lower risk of heart failure, whereas trials did not find such a strong benefit. This may reflect residual confounding owing to the observational study design or differences in study duration. However, our findings are consistent with the recently published multicentre nested case-control study,51 which also reported a 14-18% lower risk of hospital admission for heart failure with gliptins compared with other diabetes drugs. It is also consistent with a new user cohort study, which did not find a higher risk of heart failure among patients prescribed gliptins compared with other diabetes drugs. 52Some of the differences in results between our observational study and earlier clinical trials may reflect the type of gliptin studied—80% of patients prescribed gliptins were prescribed sitagliptin in our study compared with saxagliptin in some of the trials. Currently there are too few patients prescribed linagliptin, saxagliptin, and vildagliptin to support separate analyses by individual drug, which is a limitation of the study as there may be differences between individual gliptins and their effect on haemoglobin A1c. 53 However, the numbers of people taking different types of gliptin is likely to increase over time, and further analyses can be undertaken once more data have accrued. GlitazonesOur study included over 55 000 person years of exposure to glitazones arising from 21 308 patients. [SEP] Justify:

Output: The text contrasts the claim by highlighting the need for caution in interpreting results from trials involving treatments, specifically gliptins, as mentioned by Monami et al who urge caution due to factors such as short trial duration and patient characteristics differing from routine clinical practice. This suggests that there are risks related to treatments which undermines the assertion that treatments using nanotechnology are completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: Εργαστήριο Γενικής & Ειδικής Ζωοτεχνίας Εξεταστική επιτροπήΜπιζέλης ΙωσήφΚουτσούλη ΠαναγιώταMedugorac IvicaΚομινάκης ΑντώνιοςΜπεμπέλη ΠηνελόπηΠαφίλης ΠαναγιώτηςΜπουγιούκος Κωνσταντίνος Επιστημονικό πεδίοΓεωπονικές Επιστήμες και Κτηνιατρική ➨ Επιστήμη Ζωικής Παραγωγής ➨ Επιστήμη ζωικής παραγωγής Λέξεις-κλειδιάΕλληνικές φυλές βοοειδών; Γενετική ποικιλομορφία; Γενετική δομή ΧώραΕλλάδα ΓλώσσαΑγγλικά Άλλα στοιχείαεικ. , πιν. [SEP] Justify:

Output: The text does not provide any relevant information about genetic markers or their application in tracing inheritance patterns. Instead, it includes a list of names and keywords related to agricultural sciences without discussing 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: In fact, it controls the balanced response of MSCs to the necessary requirements of the body [Glenn and Whartenby, 2014]. It may also preclude aberrant function on MSCs or other targets that cause malfunctions. MSC niches are located adjacent to vessel walls, on the endosteal surfaces of trabecular bone, umbilical cord blood (vein, arteries, Wharton jelly, and lining membrane) [Lee et al. , 2004], dental tissues (dental pulp, exfoliated deciduous teeth, periodontal ligament, apical papilla, dental follicle, and periapical cyst-MSCs [Kim et al. , 2011; Marrelli et al. , 2015b], adipose tissue [Zuk et al. , 2002], and synovium (synovial membrane and fluid) [Jones et al. , 2004]. The sources of MSCs are shown in Figure 1. Table 1Advantages and disadvantages of different types of MSlargeFig. 1View largeDownload slideSources of MSCs. Fig. 1View largeDownload slideSources of MSCs. Close modal MSCs and Blood clotting and inflammatory reactions are 2 immediate responses when bone fractures occur. In fact, inflammation can initiate the cascades and pathways for bone regeneration by producing chemotactic factors [Jacobs et al. , 2013]. In the second phase of inflammation (chronic phase), chronic inflammatory cells, particularly the macrophages and lymphocytes, enter the injured site. The role of macrophages and T helper lymphocytes should be highlighted. Macrophages have many important roles during bone healing. They not only phagocytize the necrotic tissues, micro-organisms, and hematoma, but also release several beneficial cytokines and growth factors that facilitate the transition from the inflammatory stage to the reparative phase of bone healing. There are at least 2 important inflammatory behaviors in response to exogenous cell/graft/scaffold/matrix implantation. In the type I response, the lymphocyte T helper type I cells trigger macrophage type I cells, which causes an inflammatory reaction to occur. This type results in graft/cell rejection. [SEP] Justify:

Output: The text corroborates the claim by discussing the important roles of mesenchymal stem cells (MSCs) in responding to inflammatory processes during tissue repair, particularly in bone healing. It mentions how inflammation initiates pathways for bone regeneration and highlights the function of macrophages in clearing necrotic tissues and facilitating healing, which aligns with the broader concept of stem cells being utilized for regenerative medicine.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: The predominant glitazone was pioglitazone, which was prescribed to 90% of glitazone users, and hence our results most closely reflect associations for pioglitazone rather than rosiglitazone (withdrawn in the UK in 2010). Our study is substantially larger than a previous UK study of 92 000 people with diabetes, which finished in 20054 and includes newer drugs available over the past decade. It supplements information from the Canadian study,12 of people aged 66 and over which compared three outcomes (heart failure, myocardial infarction, and death) among 16 951 users of pioglitazone compared with 22 785 users of rosiglitazone between 2002 and 2008. Our study is more recent and includes more patients prescribed pioglitazone over a longer duration (mean exposure of 4. 5 years in our study compared with 294 days). It also includes more events—the Canadian study12 included 461 cases of heart failure, 273 of myocardial infarction, and 377 deaths. We have found significant reductions in two outcomes—cardiovascular disease and all cause mortality—among users of glitazones compared with non-users (table 3⇑). This reduction is similar in magnitude to that reported in clinical trials and meta-analyses of pioglitazone. 9 11 In 2007, Lincoff et al reported a meta-analysis of 19 trials of pioglitazone with a treatment duration ranging from four months to 3. 5 years. 11 The results showed an 18% decreased risk of their composite primary outcome (risk of death, myocardial infarction, or stroke). However, we have reported a decreased risk of heart failure among users of glitazones compared with non-users. This contrasts with the increase in heart failure that occurred in other studies, without an associated increase in mortality. 9 11 The authors of the PROactive study partially attributed this finding to a diagnostic bias due to the increase of oedema in the pioglitazone group. 9 Our observational study differs from the clinical trial not only in design, size, and setting but also in the calendar time during which it was conducted and in the selection of patients. For example, the PROactive study9 selectively recruited high risk patients with pre-existing macrovascular disease, whereas our study included a more representative population from primary care. [SEP] Justify:

Output: The text contrasts the claim by discussing the outcomes associated with the use of pioglitazone and rosiglitazone, specifically highlighting differences in the prevalence of heart failure and mortality rates among users compared to non-users. It implies that while glitazones may have benefits, there are risks involved, especially since the study notes a previous increase in heart failure linked to rosiglitazone without a corresponding increase in mortality. This indicates that treatments, particularly those related to diabetes medications in this context, are not without risk, thus opposing the idea that all nanotechnology treatments are completely risk-free.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: , χαρτ. , σχημ. , γραφ. Στατιστικά χρήσης ΠΡΟΒΟΛΕΣ Αφορά στις μοναδικές επισκέψεις της διδακτορικής διατριβής για την χρονική περίοδο 07/2018 - 07/2023. Πηγή: Google Analytics. ΞΕΦΥΛΛΙΣΜΑΤΑ Αφορά στο άνοιγμα του online αναγνώστη για την χρονική περίοδο 07/2018 - 07/2023. Πηγή: Google Analytics. ΜΕΤΑΦΟΡΤΩΣΕΙΣ Αφορά στο σύνολο των μεταφορτώσων του αρχείου της διδακτορικής διατριβής. Πηγή: Εθνικό Αρχείο Διδακτορικών Διατριβών. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses usage statistics of a doctoral thesis and metrics related to it, without mentioning genetic markers or inheritance patterns.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: , 2013]. The antiapoptotic effect of MSCs could also accelerate the process of bone healing. It has been suggested that faster bone healing with MSC transplantation may be especially correlated with lower levels of TNF-α expression in the callus [Kovach et al. , 2015]. This may favor bone formation since it has been reported that TNF-α can have proapoptotic effects on osteoblasts. MSCs and we know, angiogenesis is a very important factor for bone formation and it is logical to speculate that angiogenesis also contributes to bone regeneration and repair. In this regard, many studies have attempted to incorporate angiogenic factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, insulin-like growth factor, platelet-derived growth factor, and bone morphogenetic proteins (BMPs) into scaffolds to improve the bone healing process [Chen et al. , 2004; Simmons et al. , 2004; Formiga et al. , 2010]. The process of angiogenesis involves a complex interaction between endothelial cells and the corresponding microenvironment, including endothelial cell survival, proliferation, migration, tube formation, and maturation. In previous in vivo studies, the angiogenic activity of MSCs has been suggested to contribute to their regenerative capability [Smadja et al. , 2012; Manieri et al. , 2015]. The angiogenesis could be increased with the help of their paracrine signal. The microenvironment of the damaged tissue changes due to the angiogenesis, which then benefits osteogenesis [et al. , 2011]. Some biomatrices, such as platelet-rich fibrin (PRF), play critical roles as a biological niche in stimulating the resident MSCs in the angiogenesis process. PRF (fibrin sealant or fibrin glue) is the second-generation plasma-rich plasma (PRP), which is an improved version of the traditionally prepared PRP. PRF significantly enhances the healing of soft and hard tissues and is widely used in regenerative dentistry. The PRF not only enhances the healing process through reducing bone resorption, but it also promotes neoangiogenesis in the defect site of oral bone [Marrelli and Tatullo, 2013]. [SEP] Justify:

Output: The text corroborates the claim by discussing the regenerative capabilities of mesenchymal stem cells (MSCs) in the context of bone healing. It specifically mentions that MSCs have an antiapoptotic effect that can accelerate bone healing, which is essential in the context of regenerative medicine. The mention of angiogenesis and factors that contribute to both bone healing and regeneration further supports the role of stem cells in repairing damaged tissues, as enhanced angiogenic activity is linked to their regenerative capability.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: Two thirds of patients in the PROactive study9 had evidence of myocardial infarction or stroke compared with 14% in our study. It is also possible that, given the growing concerns about rosiglitazone and its subsequent withdrawal, patients with symptoms or signs suggestive of early heart failure (such as breathlessness or oedema) in our study might not have been prescribed pioglitazone or might have switched to another diabetes drug. Other diabetes drugsAlthough our research question focuses on associations between gliptins and glitazones and adverse clinical outcomes, for comparison we have results for other diabetes drugs. Overall, metformin monotherapy was associated with reduced risks of all cause mortality, heart failure, and cardiovascular disease compared with non-use. This is important because metformin is generally recommended as the first line diabetes drug and is commonly used in combinations with other drugs. Sulphonylureas were associated with an increased risk of all cause mortality both in the main analysis and in the sensitivity analyses restricted to new users of sulphonylureas. Monotherapy with sulphonylureas was also associated with an increased risk of cardiovascular disease and as triple treatment with metformin and insulin was associated with an increased risk of heart failure compared with metformin alone. These unfavourable results are consistent with some studies linking sulphonylureas with increased adverse cardiovascular events,5 but not all studies. 26 Further research into the safety of sulphonylureas compared with other types of diabetes drugs is warranted. However, this research needs to distinguish between individual types of sulphonylureas, as different individual drugs have different mortality risks. 54As in our companion paper,27 we excluded prevalent users of insulin at baseline but included in the analysis those patients subsequently prescribed insulin because insulin is part of the treatment ladder and some of these people will also have had other drugs of interest during follow-up. Although insulin was not the primary drug of interest, patients prescribed insulin had higher risks of all three outcomes, despite adjustment for higher levels of comorbidity. It is unlikely that this increased risk was a direct result of treatment with insulin. Instead, residual confounding and reverse causality could have occurred—that is, the insulin treated group was at much higher risk of complications than the groups treated with diet or oral drugs, and these result in their apparently worse outcomes and not their treatment with insulin. [SEP] Justify:

Output: The text contrasts the claim by indicating that there are significant risks associated with various diabetes treatments, particularly highlighting that sulphonylureas are linked with increased mortality and cardiovascular disease risks. This suggests that not all treatments, including those potentially utilizing nanotechnology, are completely risk-free, contradicting the claim's assertion.


Input: Task: pass the claim using the given text. Claim: Genetic markers can be used to trace inheritance patterns in populations. [SEP] Text: ΧΡΗΣΤΕΣ Αφορά στους συνδεδεμένους στο σύστημα χρήστες οι οποίοι έχουν αλληλεπιδράσει με τη διδακτορική διατριβή. Ως επί το πλείστον, αφορά τις μεταφορτώσεις. Πηγή: Εθνικό Αρχείο Διδακτορικών Διατριβών. "Γενετική ταυτοποίηση των αυτόχθονων πληθυσμών βοοειδών με τη χρήση μοριακών δεικτών" Πληκτρολογήστε το κείμενο της εικόνας! [SEP] Justify:

Output: The text does not address the claim directly, discussing instead users interacting with a doctoral thesis and mentioning genetic identification of indigenous cattle populations without explicitly tying to inheritance patterns in human populations.


Input: Task: corroborate the claim using the given text. Claim: Stem cells are used in regenerative medicine to repair damaged tissues. [SEP] Text: It has been shown that the angiogenic activity of PRF is due to the slow and steady release of growth factors such as VEGF, which is primarily responsible for endothelial cell proliferation via the extracellular signal-regulated kinase activation pathway [Roy et al. , 2011]. MSC Homing and Recruitment to Many challenges are involved in the healing of critical-sized bone defects (CSDs). In bone, CSD is the term used for any orthopedic defect that will not heal without intervention and where nonunion would subsequently occur [Poser et al. , 2014]. Basically, there are 3 main reasons for the occurrence of nonunions, including a lack of MSC migration into the defect site, insufficient numbers of osteoblast progenitor cells (MSCs) in the CSD, and failure to differentiate into osteoblasts or the wrong differentiation of MSCs [Wang et al. , 2009]. As the first step of the chain in the treatment of nonunions, many researchers attempt to recruit MSCs to the defect site. The exact mechanism of MSC homing to the injury site is still not clear; however, chemotactic factors released at the site of the bone defect must play an essential role in MSC homing and recruitment. It is known that MSCs express at least 19 chemokine receptors [Li et al. , 2012]. Specific chemokine receptors (e. g. , CCR1, CCR7, CCR9, CXCR4, CXCR5, and CXCR6) are important mediators in this matter, and among them CXCR4 and its ligand (CXCL12 or stromal-derived factor 1; SDF1) are the most widely investigated mediators in the MSC recruitment process [Kitaori et al. , 2009]. A localized hypoxic condition occurs in the initial stage of fracture due to vascular damage that acts as a useful recruitment factor and regulatory stimulus for MSCs and other progenitor cells [Mehta et al. , 2012; Toupadakis et al. , 2012]. It has also been suggested that new bone formation occurs under hypoxic conditions [Olmsted-Davis et al. , 2007]. [SEP] Justify:

Output: The text supports the claim by discussing the role of mesenchymal stem cells (MSCs) in the healing of critical-sized bone defects (CSDs). It describes how MSCs are involved in the recruitment process to the defect site, highlighting their significance in regenerative medicine for repairing damaged tissues, particularly in the context of bone healing. The mention of factors that affect MSC homing, and their expression of chemokine receptors further illustrates their critical role in tissue repair.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: For example, in table 2⇑, the insulin treated group had the highest haemoglobin A1c and creatinine values before treatment, although both factors were adjusted for in the analyses. An alternative explanation could be that patients with symptoms that indicated cardiovascular disease or heart failure were prescribed insulin rather than glitazones or gliptins before subsequently having a diagnosis of these conditions. Strengths and limitations of this studyGeneralisabilityThis is a large study based on an ethnically diverse contemporaneous, representative population of people with type 2 diabetes during an eight year study period. We included all eligible patients to minimise selection bias. Hence we think the results are likely to be generalisable to similar populations of people with type 2 diabetes. Although our observational study has limitations inherent in its design, it also has advantages over meta-analyses of clinical trials as these tend to be limited by ascertainment and reporting of events, short follow-up, lack of time to event data, and insufficient power to report on rare cardiovascular events. 23Clinical outcomesStrengths of our analysis are the inclusion of hard clinical endpoints of cardiovascular disease, heart failure, and death based on clinical diagnoses recorded on at least one of three linked electronic data sources. Use of all three linked data sources was designed to minimise under-ascertainment of outcomes, which would otherwise lead to under-estimation of absolute risks. The cardiovascular disease and heart failure outcomes are based on clinical diagnoses made by the treating clinician rather than formally adjudicated events as would occur in a clinical trial. Although it is possible that some patients were recorded as having heart failure or cardiovascular disease who did not have this condition, such misclassification will not have affected the mortality outcome. UK general practices have good levels of accuracy and completeness in recording clinical diagnoses and prescribed drugs. 55 Also, the diagnostic validity of such diagnoses in general practice has been shown to be high. 56 Possible ascertainment bias of outcomes is unlikely to vary according to the type of diabetes drug prescribed so would not explain the associations we found. Exposure to diabetes drugsWe had detailed information on use of diabetes drugs prescribed throughout the follow-up period, enabling us to develop a detailed categorisation of drug exposure time into 21 different treatment groups, including combinations of treatments. Recording of prescriptions issued in UK general practices has high levels of completeness. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and limitations of studying treatment effects, specifically focusing on diabetes drugs and their associated outcomes. It highlights that while treatments are prescribed, the observational study design has limitations that could affect the perceived risks, such as potential misclassification of patients' conditions and the challenges in assessing absolute risks. This suggests that treatments, including those potentially involving nanotechnology, may carry risks that are not fully understood or documented.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to and Genomics Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial for Regulomes, United States; School of Medicine, United States; Apr 8, 2019 Open access Copyright information Version of RecordApril 17, 2019 Accepted ManuscriptApril 9, 2019 Accepted ManuscriptApril 8, 2019 Open annotations (there are currently 0 annotations on this page). 12,455 views 1,543 downloads 102 5105. Copy to clipboard Download BibTeX Download. RIS Full text Figures and data Peer review Side by side files 2 figures and 4 additional files 1 with 5 supplements Download asset Open asset reveals cell lineage from mtDNA mutations. (A) workflow. Usings standard ATAC-seq data as input (left), an SNV calling step was added to enumerate all single nucleotide variants in mtDNA (middle). identifies heteroplasmic mtDNA mutations in single cells, groups mutations into diagnostic sets, and infers cell lineage based on mtDNA variants, and overlays clonotype information on epigenomic profile of the same cells (right). (B) ATAC-seq enriches for mtDNA reads compared to whole exome sequencing (WES), low coverage whole genome sequence (WGS_L), or PCR-free, high-coverage whole genome sequence (WGS_H). (C) Bimodal distribution of variant allele frequency (VAF) of mtDNA mutations discovered using ATAC-seq. Yellow bar presents the homoplastic variants that can distinguish different individuals. Heteroplasmic variants can distinguish clonal cell populations within one individual. (D) Two possible models for 25% mtin bulk: Homoplastic variants in a small proportion of cells (top) or heteroplasmic variants in nearly every single cell (bottom). Blue cells: cells with mutated mtDNA, blue dots: mtDNA with mutated allele. (E) VAF of mtDNA mutations in single cell ATAC-seq data of human B cells. Each dot presents the VAF (y-axis) in single cells, and rotated kernel density on each side presents their distribution. The x-axis indicates the mutation site (the nucleotide position in mitochondrial genome). (F) mtDNA mutations in human AML. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the Human Genome Project mapping human DNA. It discusses research on mitochondrial DNA mutations and lineage tracing without mentioning 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: Hypoxia can express special genes that increase cell survival under low oxygen tension and induce the reestablishment of blood vessels for oxygen delivery [Papandreou et al. , 2006]. In addition, hypoxia by the expression of the hypoxia-inducible factor 1-α (HIF-1α) subunit transcription factor may induce the upregulation of SDF1 and ultimately regulate the homing of progenitor cells. The SDF1/CXCR4 (CXC chemokine receptor R4) axis is thought to be a master mediator of MSC recruitment and migration [Yellowley, 2013]. Because of the hypoxic condition at the injured (fracture) site, it is possible that the expression of chemokines such as SDF1 is regulated by hypoxia and HIF-1α. The homing of leukocytes and their role in transporting hematopoietic precursors in tissues are very similar to mechanisms that govern the migration of MSCs [Trautmann et al. , 2014] (Fig. 2). It has been discovered that mobilization of MSCs to the site of fracture, where they are thought to contribute to the regeneration of bone, is mainly facilitated through paracrine support of angiogenic factors (e. g. ). Furthermore, secretion of angiogenic factors in injured tissue could be due to the activation of HIFs [Mallela et al. , 2013]. MSCs can also recruit the other MSCs or progenitor cells towards the injury/defect site via paracrine effects [Shao et al. , 2015]. Fig. 2View largeDownload slideMSC homing to the fracture site. HIF-1α may increase the transcription of CXCL12 (SDF1) production in the cells of damaged bone. In normoxia conditions, HIF-1α is hydroxylated by the activity of prolyl hydroxylase domain protein 2 (PHD2), leading to HIF-1α binding to the von Hippel-Lindau protein (VHL) and subsequent ubiquitination (Ub) and proteasomal degradation. Otherwise, in hypoxia (low O2), due to a reduction of PHD2 activity, HIF-1α levels are stabilized and migrate into the nucleus to form a complex with HIF-1β. [SEP] Justify:

Output: The text corroborates the claim by discussing the role of MSCs (mesenchymal stem cells) in the regeneration of bone at fracture sites. It mentions that the mobilization of MSCs to injury areas is facilitated through paracrine support of angiogenic factors and that they contribute to the regeneration of bone. This supports the idea that stem cells are involved in regenerative medicine, specifically in repairing damaged tissues like bone.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: 57 We ascertained patient characteristics, concurrent drugs, clinical values, and diagnoses at the beginning of each treatment period. This enabled us to account for switching between different treatments or treatment combinations, making adjustments for a large number of potential confounders. We undertook a time varying analysis, which analysed different types of monotherapy, dual treatment, and triple treatment over the study period. This reflects real world prescribing patterns over a long duration, allowing multiple comparisons not only between drugs but also between different combinations of drugs compared with untreated periods of time (diet only treatment). Our study analysed prescribed drugs rather than the drug actually taken by the patients, although renewal of prescriptions is likely to indicate drug use, as patients need to initiate repeat prescriptions. This could result in misclassification of exposure if patients were prescribed drugs that they did not actually take and could underestimate associations between use of diabetes drugs and clinical outcomes. Unlike previous studies, we have included comparisons of risk against periods of no treatment,5 which is important as about 40% of people with type 2 diabetes are managed without diabetes drugs throughout follow-up. Limitations include lack of analyses for different subtypes of each type of drug and for different dose levels. Assessment of other types of biasOther types of bias that can affect observational studies include recall bias, indication bias, and channelling bias. Recall bias will not have occurred as data on prescriptions for diabetes drugs and confounding variables were recorded before the clinical outcomes. We restricted the study population to people with type 2 diabetes to limit indication bias (ie, bias that occurs when people are prescribed drugs for a condition that is itself associated with the risk of the adverse event under consideration). We used an incident user design to reduce, but not eliminate, confounding and biases that can otherwise arise from adjustment for intermediate characteristics in the causal path. 36 There were some differences at baseline between patients prescribed different treatment groups (tables 1 and 2⇓), although these were predominantly increased levels of comorbidities for insulin and lower levels of concurrent use of drugs (such as statins and aspirin) for metformin. To reduce channelling bias (where the choice of a particular drug is influenced by patient characteristics), we adjusted for a wide range of potential confounding variables. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and potential biases in observational studies of drug treatments, indicating that there are inherent risks and confounding factors associated with treatment evaluations. The mention of biases such as recall, indication, and channelling bias suggests that treatments are not without risk or complications, which directly opposes the claim that all treatments using nanotechnology (and, by extension, all treatments) are 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: Each row in the heap map is a single cell (LSC or AML blast); each column is a heteroplasmic mtDNA mutation. Blue color indicates the mtDNA variant is detected (>1 reads); white color indicates no mutation. The nucleotide position in mitochondrial genome for each mutation is indicated. (G) Combined set of heteroplasmic mtDNA mutations improve cell lineage assignment in single cells. Cells were first separated into bins according to their mtDNA coverage (x-axis). The detection rate (y-axis) for each site (indicated by different color and shape) is calculated with the number of cells with that mutations divided by total number of cells in that bin. The detection rate of combining four sites (black line, ) is substantially increased. (H) Quantitation of mtDNA mutation detection rate as a function of sequencing depth and number of single cells. Cells were sorted in descending order by their sequencing depth and grouped into bins (10% of cells in each row). Distribution of sequencing depth is shown on the left panel. The black line and dark blue shade indicate mean ± standard deviation, respectively. The light blue shade indicates remaining value of the bin. Cells with or without mtDNA variants are shown in blue and orange on the right panel, respectively. Figure 1—figure supplement 1 Download asset Open asset workflow for SNP calling and lineage inference. (A) Workflow for mitochondrial DNA variant calling from ATAC-seq data. This workflow was applied to both bulk and single cell ATAC-seq. The steps indicated with dotted lines were not applied to single-cell data. (B) Workflow for inferring lineage relationships from single-cell ATAC-seq data. BAM files from single cells were first merged and confident mtDNA variants were called. Mutated alleles from these variant sites were then counted for each single cell. The cell lineage was then inferred from mtDNA variants and analyzed alongside the chromatin profile for each cell. Figure 1—figure supplement 2 Download asset Open asset mtDNA coverage and variants from different sequencing libraries from GM12878 human B cells. (A) Mitochondrial genome coverage from each of four different sequencing libraries including WGS_H (high coverage PCR-free whole genome sequencing), WGS_L (low coverage whole genome sequencing), WES(whole exome sequencing), ATAC-seq. axis shows coverage scaled in log10. [SEP] Justify:

Output: The text does not directly address or provide information relevant to the claim regarding the Human Genome Project's mapping of the entire human DNA sequence. Instead, it focuses on mitochondrial DNA mutations and methods for lineage inference from single-cell ATAC-seq data. Therefore, it 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: HIF-1α then binds to the hypoxia-responsive element (HRE) on the promoter of the CXCL12 gene with the cooperation of the transcriptional coactivating CREB-binding protein (CBP). This cascade can drive the upregulation of CXCL12 levels at the site of injury and promotes the migration of MSCs from the blood circulation to the defect site. The CXCL12 ligand binds to its receptor CXCR4 on circulating cells and converts cell surface integrins to a high-affinity state. This process is necessary for the binding of MSCs to vascular endothelial cells. MSCs then migrate through the endothelium towards the CXCL12 gradient. This process of chemokine-mediated cell extravasation is very similar to leukocyte transmigration. Fig. 2View largeDownload slideMSC homing to the fracture site. HIF-1α may increase the transcription of CXCL12 (SDF1) production in the cells of damaged bone. In normoxia conditions, HIF-1α is hydroxylated by the activity of prolyl hydroxylase domain protein 2 (PHD2), leading to HIF-1α binding to the von Hippel-Lindau protein (VHL) and subsequent ubiquitination (Ub) and proteasomal degradation. Otherwise, in hypoxia (low O2), due to a reduction of PHD2 activity, HIF-1α levels are stabilized and migrate into the nucleus to form a complex with HIF-1β. HIF-1α then binds to the hypoxia-responsive element (HRE) on the promoter of the CXCL12 gene with the cooperation of the transcriptional coactivating CREB-binding protein (CBP). This cascade can drive the upregulation of CXCL12 levels at the site of injury and promotes the migration of MSCs from the blood circulation to the defect site. The CXCL12 ligand binds to its receptor CXCR4 on circulating cells and converts cell surface integrins to a high-affinity state. This process is necessary for the binding of MSCs to vascular endothelial cells. MSCs then migrate through the endothelium towards the CXCL12 gradient. [SEP] Justify:

Output: The text corroborates the claim by describing the process through which mesenchymal stem cells (MSCs) migrate to injury sites within the body. It indicates that CXCL12 levels are upregulated in damaged tissues, which promotes the migration of MSCs to these sites, suggesting a role for stem cells in tissue repair and highlighting their usefulness in regenerative medicine.


Input: Task: contrast the claim using the given text. Claim: All treatments using nanotechnology are completely risk-free. [SEP] Text: This included demographic characteristics (age, sex, ethnicity, and deprivation), different comorbidities, clinical values (including haemoglobin A1c, body mass index, blood pressure, creatinine level, and cholesterol to high density lipoprotein cholesterol ratio), and concurrent drugs. However, we are unable to exclude the possibility of residual confounding because other unmeasured patient characteristics might have affected the selection of diabetes drug treatment. Although randomised controlled trials of diabetes drugs are not influenced by residual confounding, they tend to be small, of short duration, and might not report on relevant clinical outcomes. An alternative design would be an observational study of a cohort of patients specifically assembled for the purpose rather than using routinely collected data as in our study. Studies using routinely collected data are susceptible to missing data, although in our study over 99% of patients had smoking status recorded, 87% had ethnic group recorded, and over 82% had complete data for all five clinical values (table 2⇑). We also used multiple imputation to deal with missing data. Other problems with routine data include coding errors and variable timing between measurements of risk factors because of differences in when patients present to their general practitioner. Advantages of using routinely collected data rather than a purposeful cohort include size, efficiency, better generalisability, and less susceptibility to selection bias or attrition bias. We fitted several different models and carried out sensitivity analyses that showed some heterogeneity of results with variations in point estimates. The results are therefore sensitive to the assumptions made in the study design and modelling and have uncertainty; however, our findings were generally consistent across the different analyses for glitazones and gliptins. ConclusionsWe have found clinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality between different diabetes drugs alone and in combination compared with no drug treatment. Overall, use of gliptins or glitazones was associated with a decreased risk of heart failure, cardiovascular disease, and all cause mortality compared with non-use of these drugs. These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, may have implications for prescribing of diabetes drugs. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and potential issues related to the selection of diabetes drug treatments, including residual confounding, small sample sizes, and the issues with data quality. It highlights that the results are sensitive to assumptions made in the study design and modelling, indicating that there are uncertainties and risks involved in treatments that are not 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: 43M paired-end ATAC-seq reads (2 × 50 bp) yielded the same coverage of mtDNA as 747M paired-end reads (2 × 250 bp) from WGS-H data. (B) Comparison of variants detected in sequencing data from four different library preparations. The number of variants detected in each library is shown on the bottom left. The intersection of different libraries (bottom-right) and the number of variants are shown on the top. Homoplasmic variants are in yellow and heteroplasmic variants are in blue. (C) Heteroplasmic mtDNA mutations detected by WGS_H (in blue) and ATAC-seq (in red). axis is the position of the mutation on mitochondrial genome and Y axis is the variant allele frequency in percentage. Figure 1—figure supplement 3 Download asset Open asset Heteroplasmic mtDNA mutation in K562 cells. (A) Percentage of mtDNA reads in ATAC-seq and whole genome sequence(WGS) libraries from human K562 cells. Four millions mtDNA reads from 32 millions total mapped reads in ATAC, seven millions mtDNA reads from 1775 millions total reads in WGS. (B) The average coverage of the mitochondrial genome in ATAC and WGS from K562 cells. (C) Number of heterplasmic mtDNA mutations detected in ATAC and WGS. The intersection size represents mutations detected by single or both methods. (D) Variant allele frequency of mtDNA mutations and their correlation between ATAC and WGS. The red dots indicate the mutations detected by both ATAC and WGS, with the same criteria. The black dots indicate the mutations detected by ATAC or WGS only. Figure 1—figure supplement 4 Download asset Open asset Heteroplasmic variants in single cells from AML blasts and LSCs (SU353). (A) Heatmap showing variant mitochrondrial sites (columns) in each AML blast from patient SU353(rows). The color represents the number of reads supporting the variant allele (log2(depth)). The first two sites are negative controls, which are detected in pHSCs only. (B) Bar plot showing the number of cells in which we detect each mitochondrial variant. The last bar shows the number of cells with any one of the four variants detected. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses technical details related to mtDNA sequencing and variants in specific cell types, without addressing or mentioning the mapping of the entire human DNA sequence 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: This process of chemokine-mediated cell extravasation is very similar to leukocyte transmigration. Close modal Some studies have focused on the recruitment of MSCs to the bone defect site for treating the nonunions. Das et al. [2014] showed that FTY720 (a small molecule) enhances MSC recruitment to the calvarial defect of rats, thus promoting skeletal repair. They suggested that sustained release of FTY720 from injected microspheres used alone or in combination with rhBMP-2 improves the recruitment of MSCs and subsequently increases bone repair. Zwingenberger et al. [2014] showed that SDF-1α mediates stem cell mobilization and enhances BMP-2-induced bone regeneration in CSDs. They implanted adenovirally activated fat tissue grafts expressing SDF-1α and/or BMP-2 at the defect site in the treatment group. CT-scans and histological analysis confirmed a higher degree of bone healing in the BMP-2 and SDF-1α combined group compared with the negative control group. In this area, another investigation showed that cobalt can activate HIF-α, through which it contributes to the recruitment of MSCs for the initiation of the bone healing process [Wu et al. , 2012]. With these promising results, endogenous MSC recruitment into the bone injury/defect site via small molecules or protein mobilizing factors could be another interesting field for researchers working on stem cell-based therapy in bone regeneration. MSCs and Differentiation of have great potential to differentiate into various cell types, such as osteoblasts, and it has also been hypothesized that MSC transplantation would induce tissue regeneration by replacing cells in the injured site, the incidence of MSC engraftment has remained surprisingly low. Accumulating evidence indicates that the general therapeutic effects of MSCs are due to their ability to support a regenerative microenvironment rather than their capacity to differentiate and incorporate into the host tissue [Horwitz et al. , 2002; Amin et al. , 2014]. As previously mentioned, MSCs reduce the TNF-α level at the injured site. Another important effect of TNF-α is the blockage of osteoblast differentiation, which occurs by inhibiting the expression of 2 essential transcription factors for bone formation: Runx2 and its downstream target, osterix [Nanes, 2003]. [SEP] Justify:

Output: The text corroborates the claim by discussing the use of mesenchymal stem cells (MSCs) in the context of bone regeneration and healing. It mentions studies where MSCs are recruited to bone defect sites and how factors like FTY720 and SDF-1α enhance this recruitment, promoting skeletal repair. Additionally, it indicates that MSCs have great potential to differentiate into cell types such as osteoblasts and contributes to a regenerative microenvironment, thereby supporting the idea 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: What is already known on this topicCardiovascular disease and heart failure are major causes of morbidity and mortality in people with type 2 diabetesSeveral diabetes drugs have been associated with an unexpected increased risk of heart failure during clinical trials and post-marketing surveillance raising concerns about overall risks and benefitsThere is a need to quantify risks of clinical outcomes in large representative populations of people with type 2 diabetes prescribed these drugs over longer periodsWhat this study addsClinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality were found between different diabetes drugs alone and in combinationCompared with non-use of gliptins, gliptin use was significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular diseaseCompared with non-use of glitazones, glitazones were significantly associated with a 23% decreased risk of all cause mortality, a 26% decreased risk of heart failure, and a 25% decreased risk of cardiovascular diseaseFootnotesWe acknowledge the contribution of the practices that contribute to QResearch and (EMIS), and the University of Nottingham for expertise in establishing, developing, and supporting the database. The data from hospital episode statistics used in this analysis are re-used by permission from the Health and who retain the copyright. We thank the Office for for providing the mortality data. ONS bear no responsibility for the analysis or interpretation of the data. Contributors: JH-C initiated the study, undertook the literature review, data extraction, data manipulation, and primary data analysis, and wrote the first draft of the paper. CC contributed to the design, analysis, data manipulation, interpretation, and drafting of the paper. JH-C had access to all the data for this project. JH-C is the guarantorFunding: This study received no external funding. Competing interests: All authors have completed the ICMJE uniform disclosure form at www. icmje. org/coi_disclosure. pdf (available on request from the corresponding author) and declare: JH-C is professor of clinical epidemiology at the University of Nottingham and codirector of QResearch, a not-for-profit organisation, which is a joint partnership between the University of Nottingham and (leading commercial supplier of IT for 60% of general practices in the UK). [SEP] Justify:

Output: The text contrasts the claim by discussing the risks associated with certain diabetes drugs, indicating that not all treatments, including those that may involve nanotechnology, are completely risk-free. It highlights significant risks, such as an increased risk of heart failure, showing that the claim is too absolute and does not account for the potential dangers associated with such treatments.


Input: Task: pass the claim using the given text. Claim: The Human Genome Project mapped the entire sequence of human DNA. [SEP] Text: (C) The top right shows the number of cells with each different combination of variants detected. The number of cells is shown on top of the bar. The combination of variants detected is annotated below the bar. The total number of cells with each variant site detected is shown to the left. The average coverage of the mitochondrial genome for each intersection group is shown below. (D) VAF of mtDNA variants. The x-axis indicates the variant site notated by the nucleotide position in the mitochondrial genome. Each dot represents the VAF (y-axis) in single cells and the rotated kernel density on each side shows their distribution. (E–H) Same as (A–D), for leukemia stem cells (LSCs) from patient SU353. Figure 1—figure supplement 5 Download asset Open asset Heteroplasmic variants in single cells from AML blasts and LSCs (SU070). (A–D) Same as Figure 1—figure supplement 3A–D for AML blasts from SU070. (E–H) Same as Figure 1—figure supplement 3A–D for LSCs from SU070. (I) Quantification of the detection rate for each heteroplasmic variant from mtDNA. Cells (both LSCs and AML blasts) were first separated into bins according to their coverage of mtDNA (x-axis). The detection rate (y-axis) for each site (notated by different color and shape) is calculated as the number of cells with that variant detected divided by the total number of cells in that bin. (J) Quantitation of mtDNA mutation detection rate as a function of sequencing depth and the number of single cells. Cells were sorted in descending order by their sequencing depth and grouped into bins (10% cells in each row). Distribution of sequencing depth is shown on the left panel. Cells with or without mtDNA mutations are shown in blue or orange, respectively. Figure 2 with 4 supplements Download asset Open asset Clonal evolution of pre-leukemic HSCs inferred from joint lineage tracing and single cell chromatin accessibility. (A) Lineage hierarchy in acute myeloid leukemia based on and prior genetic information. mtDNA mutations reveals pHSC clonal heterogeneity. [SEP] Justify:

Output: The text provided does not address the claim regarding the Human Genome Project and its mapping of the entire sequence of human DNA. Instead, it focuses on the detection and analysis of mitochondrial DNA variants in cells, particularly related to leukemia, which is unrelated to the overarching goal of the Human Genome Project.