Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: 3i, BioCanRx) provide support and regulatory advice as a component of existing agreements with groups like Medicine by and ThéCell (i. e. free to researchers), while industry must maintain infrastructure and regulatory groups (i. e. out-of-pocket expenses). In this role, groups like CellCAN act as conduits between the Cells, Tissue and (CMF) stakeholders and regulators while providing an outlet for to address regulatory concerns and clarifications around the expectations for CTAs. Perhaps then, a way to alleviate financial burdens would be to encourage academia to better prepare and organize so as to increase awareness of such services and ensure that research groups get the support they need. In the same vein, the substantial regulatory requirements surrounding clinical translation that burden academic institutions require careful advanced planning and proper attribution of resources to increase overall efficiencies in progressing through the clinical trials pipeline and meet the safety and efficacy criteria prior to approval and marketing [63]. Other factors intrinsically linked to international multi-centre trials in the context of regenerative medicine are cultural and logistical disparities between the different institutions involved. These issues must be considered when planning clinical trials and developing uniform procedures [22]. For example, the information to be transmitted to participants, as well as the quality and availability of infrastructures, vary from country to country [60]. Clinician-researchers should also be aware of different health insurance requirements and availability in different countries that may affect the financial sustainability of the research project [22]. Another challenge stems from obtaining REB approval and subsequently coordinating various agreements. The REB approval process, requirements and privacy issues are unique to each country and may vary by institution, which hinders multi-centre clinical trials if all sites are not able to obtain approvals in a timely manner. As well, site-specific issues may arise, for example, executing quality agreements between manufacturing sites. Finally, as mentioned above, unproven therapies are on the rise [64]. This increase is reportedly the result of onerous regulations that have led to only a small number of approved stem cell therapies making it to the US market [29], with prohibitively expensive price tags [21]. Conversely, one may also argue that the regulations are not truly onerous but rather appropriately balance the potential risks of the therapy through an independent third party (i. e. drugs/products that do not meet regulatory standards should not be offered to the public).

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: : Effect of protopanaxatriol ginsenosides on the blood pressure and endothelial dysfuction in the aorta of spontaneously hypertensive rats, Korean J. Ginseng Sci. 21, 119-124 (1997) Anderson, K. E. : Pharmacology of penile erection. Pharmacol. Rev. 53, 417-450 (2001) Rajfer, J. , Aronson, W. J. and Bush, P. A. : Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to noradrenergic, noncholineregic neurotransmission. New Engl. J. Med. 326, 90-94 (1992) Choi, Y. D, Ma, S. Y. , Shin, J. S. and Choi, H. K. : Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle. Korean J. Ginseng Sci. 20, 133 (1996) Choi, Y. D. , Xin, Z. C. and Choi, H. K. : Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle. Int. J. Impot. Res. 10, 37-43 (1998) Choi H. K. , Seong, D. H. and Ra, K. H. : Clinical efficacy of Korean red ginseng for erectile dysfunction. Int. J. Impot. Res. 7, 181-186 (1995) Cashen, D. E. , MacIntyre, D. E. and Martin, W. J. : Effects of sildensfil on erectile activity inmice lacking neuronal or endothelial nitric oxide synthase. Br. J. Pharmacol. 136, 693-700 (2002) Lugnier, C. and Kim, N. D. : Cyclic nucleotide phosphodiesterases as possible targets for ginsenosides, Advances in ginseng research Proceedings of the 7th International symposium on Ginseng, Society of Ginseng, 10. 1016/S0378-8741(01)00217-3 Maffei, F. R. , Carini, M. , Aldini, G. , Berti, F. and Rossoni, G.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: land-use proportions must be positive and add to 1) and to represent assumed physical or legal restrictions (e. g. no farming in PAs). Finally, restored native vegetation is allocated according to the specific scenario being run. In the case of the FC, FC + SFR and FCZD scenarios, the amount of restoration required by the spatial distribution of environmental debts (in legal reserves (LRs) and areas of permanent preservation (APPs)) is allocated following three criteria, the distribution of existing native vegetation (i. e. new growth is near old growth), hydrography (i. e. vegetation tends to concentrate around water bodies) and pasture (i. e. vegetation will tend to grow over former pasture), with no order of priority among them. To this end, gravity functions are constructed for each criterion, and, after normalization, multiplied together into a single cost function. In the case of the FC + CEZ scenario, restoration concentrates at anthropized areas inside or at the near vicinity of CEZs. Further details on the downscaling methodology can be found in the SM. 2. 4. Simulation scenariosUnder various preservation/restoration policy limitations, five scenarios are used to capture anthropization in CEZs. Table 2 provides a summary of all scenarios. The BAU scenario maintains existing rates of native vegetation conversion to pasture and agriculture across Brazil's major biomes, with no restoration of illegally deforested areas, and little illegal deforestation control, which is calibrated by means of a probability of enforcement (see SM). Key parts of Brazil's FC are enforced in the FC scenario, including a deforestation prohibition on farms' LRs and permanent protection areas (APPs) after 2000, and mandatory restoration of illegally deforested areas of native vegetation after 2020. The FC + SFR (FC plus small farms restoration) scenario is based on the FC but includes mandatory restoration of illegally deforested areas prior to 2008 that were exempted from mandatory restoration by the Brazilian Parliament's small farms amnesty. The FC + CEZ scenario is essentially the FC scenario with a different restoration requirement: any places within unprotected CEZs that had experienced some degree of anthropization by 2020 must be restored. Note that there can be legal deforestation inside unprotected CEZs in the FC + CEZ, just like in the FC and FC + SFR scenarios.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: They act as a barometer to determine if a given drug/product has demonstrated enough evidence of safety to move towards the market; therefore, the critique should be on the difficulty in establishing this evidence that holds upmarket approvals and not on onerous regulations. Moreover, there is a gap in oversight and the enforcement of such mechanisms that often leads to exploitation [65]. Thus, efforts are being made to strengthen regulatory oversight and discourage clinics from marketing therapies that lack an evidentiary basis [66]. As outlined in the for Research’s (ISSCR) 2016 Guidelines for stem cell research and clinical translation, “all research involving clinical applications of stem cell-based interventions must be subject to prospective review, approval and ongoing monitoring by independent human subjects review committees” (p. 19) [67]. This recognizes the value and importance of independent research oversight in ensuring the ethical conduct of research, the protection of human participants and the generation of credible data. ConclusionsWe propose the following initiatives as a way of addressing and perhaps overcoming the limitations and barriers to initiating multi-centre RMCTs, from both national and international perspectives: 1. International coordination in the harmonization of existing regulatory requirements and pathways. A first step forward would be to focus on the clarification and standardization of the terminology currently used and outlined in the regulatory process, as there exist variations in the critical definitions used in cellular therapies (e. g. minimal manipulation, homologous versus non-homologous use) [24]. From there, a consensus strategy could be built to enable the harmonization and prioritization of tasks along with a push for global standards. Such a process will be time-consuming, as there is a need to adjust to varying criteria, which “necessitates far-reaching forms of scientific self-governance, training and procedural adjustments in participating clinical trial sites” (p. 305) [56]. An approach that consolidates or decreases the number of initiatives would enable the focus to be on improved and streamlined coordination. 2. Oversight could be provided by international authorities (e. g. ISSCR and the for Cellular Therapy) so as to counteract the diversification of regulation, despite their non-binding nature. 3. Development of an international approach for ethics approvals of multi-centre clinical trials that build on the principle of mutual recognition [68, 69].

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: elicits Th1 and Th2 immune responses to ovalbumin in mice. Vaccine 2007;25:161-169. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Med 1999;340:448-454. . Nitric oxide, chronic infl ammation and autoimmunity. 2007;111:1-5. . Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from infl ammation to autoimmunity and tissue damage/remodeling. 2010;233:267-285. . Panax ginseng ameliorates airway infl ammation in an ovalbumin-sensitized mouse allergic asthma model. J Ethnopharmacol 2011;136:230-235. . Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice. 2010;10:45. . Ginseng ameliorates chronic histopathologic changes in a murine model of asthma. Proc 2008;29:493-498. . Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model. 2009;150:32-42. . Suppression of local infl ammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia. Neuroscience 2012;202:342-351. . Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model. 2007;26:785-791. . Red ginseng saponin extract attenuates murine collagen-induced arthritis by reducing pro-infl ammatory responses and matrix metalloproteinase-3 expression. Bull 2010;33:604-610. . Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Bull 2006;29:1862-1867. . Anti-inflammatory and anti-oxidative effects of Korean red ginseng extract in human keratinocytes. 2011;11:42-49. -. Red ginseng inhibits scratching behavior associated with atopic dermatitis in experimental animal models.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: Finally, in addition to the FC requirements, the FCZD scenario contains a zero-deforestation strategy in the Cerrado beginning in 2025. Table 2. Scenario assumptions. Main assumptions for the various scenarios, including governance (illegal deforestation control (IDC) and native vegetation restoration), and zero-deforestation policy (ZD). ScenariosDeforestation controlRestorationAtl. ForestAmazonCerradoRest of ++(2025)Full IDCYes3. Results3. 1. Anthropization of unprotected CEZs by 2020Table 3 presents the level of anthropization (in Mha and %) inside unprotected CEZs by 2020, estimated from Map4. 1 data. In Brazil, CEZs cover 341 Mha, 57% (194 Mha) of which legally protected by Brazil's network of PAs. Of the 137. 6 Mha of CEZs outside PAs (i. e. unprotected), 10. 2 Mha (6. 9%) have already suffered some degree of anthropization by 2020. In the largest Brazilian biomes, the level of CEZ anthropization is 12. 3% (3. 55 Mha) in the Cerrado, 3. 3% (3. 38 Mha) in the Amazon, 35. 7% (2. 34 Mha) in the and 10. 4% (0. 63 Mha) in the Caatinga. At level 1, the highest conservation priority level globally (see section 2), 12. 7% (6. 68 Mha) of unprotected CEZs in Brazil had been anthropized by 2020. Figure 1(a) presents the spatial distribution of anthropization inside unprotected CEZs by 2020. Red pixels indicate where anthropization exceeds 20% of the pixel area. Observe that in the Amazon anthropization areas inside unprotected CEZs follow the pattern of the main rivers (specially, the Amazon) and of the main roads that cross the biome. In the Cerrado, most anthropization is concentrated in the region, and in the biome's east and northwest regions, along the borders with the and the Amazon, respectively.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Such an approach could take the form of a submission template containing all required information common to each institution involved while allowing specific additions to be made by way of appendices. This would maximize transparency and lead to a more simplified and streamlined approach to REB approvals while reducing the duplication of efforts. 4. Creation of an interactive online educational platform for knowledge mobilization containing information on the regulatory requirements and procedures for CTAs on a large number of countries, so as to centralize and facilitate access to such information by researchers. Researchers from different countries looking to conduct multi-centre clinical trials could communicate and discuss the feasibility of proposed trials. For example, under the new EU Regulation (Regulation (EU) No 536/2014), a publicly accessible EU database and portal will be created to act as a one-stop-shop for all CTAs [70]. This will be set up and managed by the EMA, and the Member States, thus addressing the diversity of infrastructure requirements and systems in place in different countries. Of note, however, is that the European system may be difficult to translate into either the Canadian or US contexts due to the lack of an equivalent authority. 5. Initiate dialogue with regulatory entities early in the process in order to collect all necessary information regarding criteria, safety and efficacy standards, and assure timely turnover of CTAs. This can be spearheaded by national regulatory authorities as they ensure that the scientific expertise and staffing needed to assure timely assessment of CTAs is in place. Organizations such as CellCAN and the and Committee have created meetings for open dialogue with regulators from each jurisdiction (and the US FDA, respectively) that allow cell therapy stakeholders to concert efforts and address other pressing issues facing the RMCT sector with a united front. Furthermore, by establishing an advanced dialogue with regulatory agencies, basic researchers and clinician-researchers will be able to receive support, information and guidance early on. 6. Clarification and re-examination of the boundaries between research and innovation are necessary. Research comprises the necessary building blocks and foundational work for scientific breakthroughs. Yet, the path from research to innovation is evolving. This research branding of the clinical trials pipeline is not a new paradigm. The same held true for previous generations of ground-breaking cellular therapies such as bone marrow transplantation when it was first used in the clinic in the 1970s and now considered a routine medical procedure [71].

Output: pass


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: J 2012;118:391-400. Korean red ginseng extract ameliorates skin lesions in NC/Nga mice: an atopic dermatitis model. J Ethnopharmacol 2011;133:810-817. . Inhibitory effects of ginsenoside Rb1 on atopic dermatitis-like skin lesions in mice. J 2010;34: 363-368. . Efficacy of Korean red ginseng in the treatment of atopic dermatitis. J 2011;35: 149-154. Gonzalez-. Plant antimicrobial agents and their effects on plant and human pathogens. 2009;10:3400-3419. . Ginseng treatment enhances bacterial clearance and decreases lung pathology in athymic rats with chronic P. aeruginosa pneumonia. APMIS 1997;105:438-444. . Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats. Chemother 1997;41:961-964. Pizarro-Cerda J, Cossart P. Bacterial adhesion and entry into host cells. Cell 2006;124:715-727. . Inhibition of pathogen adhesion to host cells by polysaccharides from Panax ginseng. Biochem 2009;73:209-212. . Pectin-like acidic polysaccharide from Panax ginseng with selective antiadhesive activity against pathogenic bacteria. 2006;341:1154-1163. . Antimicrobial polyacetylenes from Panax ginseng hairy root culture. Bull (Tokyo) 2012;60:377-380. . Inhibition of Helicobacter pylori adhesion to human gastric adenocarcinoma epithelial cells by acidic polysaccharides from Artemisia capillaris and Panax ginseng. 2004;70:615-619. . Rescue of Helicobacter pylori-induced cytotoxicity by red ginseng. Sci 2005;50:1218-1227. øiby N. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection. APMIS 1996;104:350-354. .

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: This result can be explained by the fact that the spatial distribution of restored vegetation under the FC and FC + SFR (and, also, FCZD) scenarios follows from FC legal requirements (restoration of LRs and APPs), which are blind to the location of CEZs. To address this issue, in the FC + CEZ scenario, we prioritize restoration of areas within unprotected CEZs that have already been anthropized by 2020 (red pixels in figure 1(a)). Compared to 2020, this strategy decreases anthropization by −3. 27 Mha (−2. 2%) in 2050, the best result among all scenarios. However, it is important to note that more restoration may result, through displacement of agricultural activity, in more loss of biodiversity-rich, old-growth native vegetation areas. This explains why by 2050 the percentage of old-growth native vegetation inside unprotected CEZs in the FC + CEZ scenario is the smallest among all FC-based scenarios (figure 2). The FCZD scenario is an attempt to mitigate this problem by introducing a zero-deforestation policy in the Cerrado, the most threatened biome, from 2026 onward. This scenario permits to maintain a large share of Brazil's old-growth native vegetation inside unprotected CEZs, while keeping almost constant the level of anthropization between 2020 and 2050. Reset image size Figure 2. Percentage of anthropized area, and old-growth and restored native vegetation areas inside unprotected CEZs between by 2050, for all scenarios, in %. Download figure:Standard image High-resolution image 3. 2. 2. Biome levelUnder the BAU scenario, the Cerrado and the Amazon biomes are the most vulnerable. In the Cerrado, anthropization level inside unprotected CEZs increases to 31. 9% (8. 9 Mha) in 2050, mostly inside the region (7. 42 Mha). In comparison, in the Amazon, where the network of PAs covers more than 50% of the biome, anthropization level remains relatively low (10. 5%). However, in terms of area, accumulated anthropization in the Amazon inside unprotected CEZs reaches 10. 66 Mha, a larger area than in the Cerrado. Overall, under the BAU scenario, these two biomes account for more than 97% of the anthropization projected to occur inside unprotected CEZs in Brazil between 2020 and 2050.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Although the traditional clinical trials model is still the most used approach, there are ways of making innovative therapies available (e. g. hospital exemption or compassionate treatment) [59]. As such, traditional boundaries must also be revisited in light of this evolution. These initiatives are important because cell-based therapies hold promising clinical applications for the treatment and prevention of a wide range of diseases and conditions. Nevertheless, there remain important barriers and ELSI issues associated with initiating such trials that need to be addressed. As such, there is a need to propose a way to bridge the regulatory gaps so as to facilitate multi-centre RMCTs. This will enable collaborative efforts to collect the necessary safety and efficacy evidence by providing a larger sample of participants, while pooling resources (i. e. protocols, personnel and costs). Ultimately, this will favour the acceleration of cell-based therapies into the clinic. AbbreviationsATMP: Advanced therapy medicinal products CBER: Center for TA: Clinical trial application CTO: Cells, tissues and organs CTP: Cell and tissue product ELSI: Ethical, legal and social issues EMA: Agency F&DR: Food and FDA: Food and HCT/P: Human cell and tissue-based product ISSCR: for : cell therapy for Sclerosis patients PHSA: : Research ethics board RMAT: Regenerative medicine advanced therapies RMCT: Regenerative medicine clinical trial TGA: Administration 21. 2017. Accessed 11 June 2018--Parton S, A, et al. The global cell therapy industry continues to rise during the second and third quarters of 2012. Cell. 2012;11(6):735–9. 64. 70. 2018. [Available from: Touré. Bridging stem cell research and medicine: a learning health system. Regen Med. 2018;13(6):741-752. 1395. 2018. 23. 2009. p. 115–26. 6. 2012. 2018. Program (CNTRP). updates 14 December 2016. Accessed 11 June 2018. Meinert CL, Tonascia S. Single-center versus multicenter trials. In: Meinert CL, editor. Clinical trials: design, conduct and analysis. New York: Press; 1986. p. 23–9. 75. 9. 819. 97. 609. 8. 14. 90. 2017. Accessed 8 Mar 2018.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection. Phytomedicine 2010;17:1040-1046. . Efficacy and safety of the standardised ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold. 1996;22:65-72. . Dual functions of ginsenosides in protecting human endothelial cells against influenza H9N2-induced inflammation and apoptosis. J Ethnopharmacol 2011;137:1542-1546. . Human infection with infl uenza H9N2. Lancet 1999;354:916-917. . Effect of oral administration of Korean red ginseng on influenza A (H1N1) virus infection. J 2011;35:104-110. . Ginseng and Salviae herbs play a role as immune activators and modulate immune responses during influenza virus infection. Vaccine 2007;25:272-282. . Emerging concepts in the immunopathogenesis of AIDS. Med 2009;60:471-484. Weiss RA. How does HIV cause AIDS? Science 1993;260:1273-1279. . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. . N Med 1998;338:853-860. . Beneficial effects of a combination of Korean red ginseng and highly active antiretroviral therapy in human immunodeficiency virus type 1-infected patients. Immunol 2009;16:1127-1131. Geffi n. Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors. 2000;16:1855-1868. . Frequent gross deletion in the HIV type 1 nef gene in hemophiliacs treated with Korean red ginseng: inhibition of detection by highly active antiretroviral therapy. 2009;25:419-424. . High frequency of grossly deleted nef genes in HIV-1 infected long-term slow progressors treated with Korean red ginseng. Curr HIV Res 2006;4:447-457. . Dosage and duration effects of Korean red ginseng intake on frequency of gross deletions in the nef gene.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: In fact, this result corresponds to anthropization that happened before the implementation of the zero-deforestation policy in 2025. With its policy of CEZ-targeted restoration, the FC + CEZ achieves contradictory results in the Cerrado biome: −1. 6% reduction on the level of anthropization but with the smallest area of old-growth native vegetation after the BAU scenario. Caatinga's arid climate reduces its aptitude for large-scale agricultural activity. Caatinga is also relatively less protected by the environmental legislation than its neighboring biomes, the Cerrado and the Atlantic Forest. In this context, the FC + CEZ scenario is the only one that performs well, managing to reduce the level of anthropization inside unprotected CEZs by −4. 7% (−0. 28 Mha), between 2020 and 2050. Finally, it is worth mentioning that, regardless the scenario and region. 3. 2. 3. Conservation versus productionNaturally, policies like the ones modeled by our scenarios, in addition to their positive impacts on the environment, may also affect agricultural production. In figure 3, we present the percentage of gain or loss (in volume) by 2050, relative to the BAU scenario, of the production of beef and soybeans, used here as proxies of Brazil's agribusiness sector dynamism. These results are compared to two proxies of conservation: the total area of native vegetation and the total area of native vegetation inside unprotected CEZs, in Brazil and its four largest biomes (plus the region). Reset image size Figure 3. Percentage of gain or loss relative to the BAU scenario of beef and soybeans production (in volume), total native vegetation area, and native vegetation area inside unprotected CEZs by 2050, for all scenarios. Download figure:Standard image High-resolution image At the country level, we observe that policies to preserve and restore Brazil's CEZs, at least the ones represented by our scenarios, incur in production losses due to higher restrictions on access to land for agricultural expansion. For the FCZD scenario, for an increase of 17% of native vegetation area inside unprotected CEZs, there is a loss of approximately 15% in the beef production and of 7% in the soybeans production, relative to the BAU scenario by 2050. Losses and gains of the same magnitude are obtained with the FC, FC + SFR and FC + CEZ scenarios.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Give us a call: +91-9541745472 of Journal of of of in Clinical and Journal of of of Microbiology and Journal of Surgery and Journal of Gynecology & Guidelines for for Editor-in-chief Guidelines for indexing and cells: in to 13. Received Date: May 23, 2020, | Published Date: June 10, 2020 Copyright© 2020 genesis pub by Kumar PKR. CC BY-NC-ND 4. 0 DEED. This is an open-access 4. 0 International License. , This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation. DOI: specific set of cells from stem cells is a scientific miracle. These stem cells help in rebuilding damaged and diseased tissues, and also help in formation of any type of cells. One type of stem cell called Mesenchymal stem cells (MSC) has the ability to differentiate into non lineage cells namely glia and neural stem cells. Several research indicates neural mechanism for neuroglia has its specification. These neural mechanism show interconnected components of cell signalling. Furthermore they highlight the signalling pathways inside neurons. Most dependent cells of these pathways are ligands and cellular architecture flowing on these ligands. The limit to understanding this architecture ends with neurosphere, spheroid structure and organoids. Sometimes injuries in brain are devastating and there is no cure in sight. The symptoms also show complications in neural regeneration. Local environment factors effects loss of neurons. This review focuses more on therapeutic solutions to cure damaged neurons and give more attention to glial cells. The regeneration of stem cells in its various forms are now put to effective use for both neuroglia and neuronal replacements. cells; Neural stem cells; Nerve cells cells are present in large numbers in the central nervous system (CNS), they help in maintaining balance, forming myelin, and provides support and protection to neurons. There has been a significant progress in glial formation and repair, stem cells provides valuable solution to the problem [1] (Figure 1). Figure 1: Shows the glial cells structure during activation [2]. There are three different types of glial cells. The astrocytes, oligodendrocytes and microglia [3] (Figure 2). Figure 2: Shows the glial cells and its types [3].

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: J 2010;34:219-226. . High frequency of gross deletions in 5' LTR/gag and nef genes in patients infected with CRF02_AG of HIV type 1 who survived for over 20 years: an association with Korean red ginseng. 2009;25:535-541. . Frequent genetic defects in the HIV-1 5'LTR/gag gene in hemophiliacs treated with Korean red ginseng: decreased detection of genetic defects by highly active antiretroviral therapy. J 2011;35:413-420. . High frequency of gross deletions in the 5' LTR and gag regions in HIV type 1-infected longterm survivors treated with Korean red ginseng. 2008;24:181-193. . Antiviral effect of Korean red ginseng extract and ginsenosides on murine norovirus and feline calicivirus as surrogates for human norovirus. J 2011;35:429-435. . Inhibitory effect of ginseng polysaccharides on rotavirus infection. J 2004;14:202-204. O'. Recent advances in the discovery and delivery of vaccine adjuvants. 2003;2:727-735. McElrath MJ. Selection of potent immunological adjuvants for vaccine construction. Biol 1995;6:375-385. Singh M, O'Hagan DT. Recent advances in veterinary vaccine adjuvants. Parasitol 2003;33:469-478. Song X, Hu S. Adjuvant activities of saponins from traditional Chinese medicinal herbs. Vaccine 2009;27:4883-4890. . Recent advances on ginseng research in China. J Ethnopharmacol 1992;36:27-38. Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice. Vaccine 2007;25:1114-1120. . Enhancement of immune responses to infl uenza vaccine (H3N2) by ginsenoside Re. 2010;10:351-356. . Amplified immune response by ginsenoside-based nanop2311. .

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: At the regional level, the picture is more complex due to production and deforestation leakages across biomes. In the Cerrado, for the FCZD scenario, losses in beef and soybeans production are, respectively, 18% and 10%, but the environmental gains are impressive, ranging from around 35% for native vegetation to more than 70% for native vegetation inside CEZs (respectively, 48% and 92% in the region). In the Atlantic Forest, compared to BAU, losses in beef production, seen in the Cerrado, are replaced by gains of up to 15%, depending on the scenario. Moreover, the variation in native vegetation area inside unprotected CEZs is still positive, reaching 42% in the FC + CEZ scenario, and 20% in the FCZD. In the Amazon, losses relative to BAU on the soy production are the smallest (there is even some gain for the FC and FCZD scenarios) but are the highest on the beef production among all biomes. In the Caatinga biome, a biome with low agricultural output, our scenarios produce no production losses but also no environmental gains relative to BAU. The exception is the FC + CEZ, with a gain by 2050 of 7% and 13% in the area of native vegetation and of native vegetation inside CEZs, respectively. 4. DiscussionMore than half of Brazil's 1172 endangered species are placed on the [3] due to the ongoing reduction in size, extent, and/or quality of their habitats as a result of the expansion of the agricultural activity [3, 22]. In this context, it makes sense to preserve and restore CEZs, which by construction are biodiversity-rich areas, until recently relatively spared by human activities like agriculture. However, from the above presented results, it is clear that keeping the current situation represented by the BAU scenario (almost no illegal deforestation control, and no restoration of illegally deforested areas), Brazil is in route to loose a large share of its unprotected CEZs in the coming decades, with dire consequences for its biodiversity and other ecosystem services. The election and inauguration of Inácio Lula da Silva (January 2023), who pledged a fundamental departure from his predecessor's environmental policies, provides some cause for optimism. In terms of its legal framework, Brazil already possesses, if there is political will, some of the means for quick action.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: It is important to understand glial cells in order to solve the neurological disease [4]. MSCs have potential ability to help in neural cells formation. But majority of tests have proved iHPSC (induced human pleuripotent stem cells ) have the capacity to generate glial cells and neural stem cells [5]. Neurons have unique characteristics to communicate via chemical synapsis. Glial cells clean up after this mess, the task peculiar to the star shaped astrocytes [6]. Glial cells thereafter communicate through non lineage cells, called synaptic communication. The components of synaptic cells form the target organ in the periphery such as muscle cells and glial part[7]. The glial part forms the entire synapse involving perineural nets which is densely arranged extracellular matrix firmly holding the synapse. There is consistence in the multiple role of glial cells, thus increasing in number of these cells outnumbering neurons. They also act as oligodendrite progenitor cells in brain cells proliferation[8]. This is the immature step of neural generation. Why it is called immature is because of one sided support to progenitor cells division. The cell NG2 glia has three purpose, one to hold the progenitors and others synapsis. An intriguing question is, the pro-genesis is remodelling of synaptic connections of glia that contributes to the performance of astrocytes in formation of nerve cells [9] (Figure 3). Figure 3: Shows glia cells and its division into neural cells [10]. This review has lot of queries answered on role of glial cells in development of brain, glial cells act as progenitor, evidence of radial glia cells, glial cells and CNS and emergence of progenitors [11]. most prominent role of glial cells is structure maintanance and bonding. The term nerve cement was promulgated a century ago and neuroglia arrived from that. Glial cells play almost all the role in brain including CNS functions, development, injury and curing diseases [12]. With knowledge of glial cell types, NG2-glia or polydendrocytes had been identified as oligodendrocyte progenitor cells. In addition there are few other glia cells such as Muller glia in retina and Bergmann glia in cerebellum [13] (Figure 4).

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: Ginsenosides Rg1 and Re act as adjuvant via TLR4 signaling pathway. Vaccine 2012;30:4106-4112. . Ginsenoside Rg1 and aluminum hydroxide synergistically promote immune responses to ovalbumin in BALB/c mice. Immunol 2008;15:303-307. Cited by A 14-week randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy and safety of ginseng polysaccharide (Y-75) vol. 12, 10. 1186/s12967-014-0283-1 Ginseng and Combination to Chemotherapy: A vol. 2014, 10. 1155/2014/168940 Herbal medicines for cancer cachexia: protocol for a systematic review vol. 4, 10. 1136/bmjopen-2014-005016 of ginsenosides in sulphur-fumigated and non-fumigated ginseng by ultra performance liquid chromatography quadruple time-of-flight mass spectrometry based chemical profiling approach vol. 7, 10. 1002/dta. 1675 Characterization of a Ginsenoside-Transforming β-glucosidase from Paenibacillus mucilaginosus and for of F2 vol. 9, 10. 1371/journal. pone. 0085727 recipe induces apoptosis in HepG2 cells via P38 MAPK activation and the mitochondria-dependent apoptotic pathway vol. 9, 10. 3892/mmr. 2014. 2138 Identification and Characterization of a Ginsenoside-Transforming β-Glucosidase from Pseudonocardia sp. Gsoil 1536 and for of Rg2(S) vol. 9, 10. 1371/journal. pone. 0096914 Renoprotective effect of red ginseng in gentamicin-induced acute kidney injury vol. 94, 10. 1038/labinvest. 2014. 101 Development of in for Predicting P-Based on a Two-for to vol. 12, 10. 1021/acs. molpharmaceut. 5b00465 Negative regulation of the inflammasome: keeping inflammation under control vol. 265, 10. 1111/imr. 12294 and Anxiety in Chinese Medicine: A Perspective vol. 07, 10.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: The FC, which is the primary legal document governing the protection and restoration of native vegetation on rural private lands in Brazil, has been promulgated in 2012. Since 2017, the government also oversees the for Recovery (), which has the stated goal of achieving the 12 Mha restoration objective announced in Brazil's NDC and pledge. Indeed, our results with the FC scenario show that truly enforcing Brazil's FC is capable in the Amazon and the biomes to stop or even revert the loss of native vegetation inside unprotected CEZs. The code requires landowners to conserve and restore native vegetation inside APPs and LRs. LRs account for more than one-third of the country's original vegetation and contribute to biodiversity preservation [23]. In the Amazon, LRs cover up to 80% of total property area, explaining why the FC scenario fared well in maintaining the biome's unprotected CEZs, with fewer than 2 Mha (out of 95 Mha) anthropized in three decades. Since protected and unprotected CEZs together cover 67% of the Amazon, enforcing the FC represents a great step towards the overall conservation of the biome. The situation is different in the biome. Although landowners are required to protect only 20% of their properties as LR, the is protected by federal law 11. 428/2006, which imposed since 2006 a de facto ban on deforestation in the biome. By 2050, 0. 7 Mha of will be recovered inside unprotected CEZs. However, this good result may hide the destruction of older forests and their replacement by younger ones [35]. In two biomes, the Caatinga and, above all, the Cerrado, the FC scenario alone was not able to stop the destruction of native vegetation inside unprotected CEZs. In other words, these two biomes require the creation (and the effective implementation) of additional, specific policies. Ideally, these policies should combine targeted restoration, as in the FC + CEZ or FC + SFR scenarios, with increased protection against deforestation, as in the FCZD. Targeted restoration (i. e. outside the FC framework) may need to be undertaken as part of a program that pays landowners directly for restored ecological services. The REDD+ (from Deforestation and Forest Degradation) system is a well-known example. + Strategy (+) was introduced in 2016, and focuses on initiatives that prevent deforestation and support forest recovery and conservation.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Several studies have suggested that human neurogenesis is different from rodent [14]. Due to differences in neuroanatomy, profound results are inadequate to cure human cells. Hence the concept called iHPSC was discovered. pluripotent stem(iHPSC) cells is an in-vitro success in curing brain injury[15]. It has been a valuable tool for modelling diseases, mapping development of CNS and treasuring the CNS cures. iHPSCs were derived from transcriptional factors of cells. They can be obtained in large numbers from human blood cells, skin fibroblasts and somatic cells [16]. Figure 4: Suggests the iPSCs method of drug development for brain cure. They are the solution to formation of neural cells which helps on replacing damaged tissues and cells. However there are hurdles to this formation. It is the microenvironment that prevents or rather restricts the formation of neural cells [17]. The balance of microenvironment is crucial for regeneration of brain cells. Glial cells volunteers to maintain the homeostasis of microenvironment. The communication between glial cels and neural cells is important for regeneration. Stem cells are blessed with characteristics for formation of any cell or any bodily organ [18]. Neural stem cells already present in subventricular region generates new neurons, some present in hippocampus region generate astroglia. Since these neural stem cells has limited capacity to produce glial cells, stem cells is often the best alternate during disease and damage [19]. Adult stem cells from mesoderm layer differentiate into neuron and glial cells under the influence of growth inducers. MSCs differentiation helps in neuron functions and also glial cells transformation for regeneration therapies. Many studies have suggested that MSCs help in treatment of several brain injuries including Alzheimers, Amyotrophic lateral sclerosis, cerebral palsy and Parkinsons diseases. These cells have the ability to exert paracrine effects inducing protein in impaired glia for repair [19-21] (Figure 5). Figure 5: Shows MSC in neural environment [20]. MSC plays an effective role in neural cells MSCs are abundant in the adipose tissues but have less significance in placenta. They harvest less; hence biological and chemical inducers are used to derive MsC from bone marrow. The results have shown these derived MSC has better regeneration capacity in animal model [22] (Figure 6).

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 4236/cm. 2016. 73012 in RAW 264. 7 cells vol. 17, 10. 4142/jvs. 2016. 17. 3. 315 Overexpression of Panax ginseng sesquiterpene synthase gene confers tolerance against Pseudomonas syringae pv. tomato in Arabidopsis thaliana vol. 22, 10. 1007/s12298-016-0384-9 strain TH-10a vol. 46, 10. 1080/10826068. 2015. 1031391 vol. 48, 10. 1111/are. 13072 Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection vol. 68, 10. 1111/jphp. 12529 Effect of SRD-P401 on the Discomfort of Neck and/or vol. 08, 10. 4236/ajps. 2017. 85070 Growth of via Inducing Mitochondria- Function vol. 16, 10. 1177/1534735416654761 1/vol. 2017, 10. 1155/2017/7171404 Production in Cultures of Cultivated in Bioreactors vol. 22, 10. 3390/molecules22060880 T Helper Subsets: A Crucial to vol. 23, 10. 1089/act. 2017. 29103. eya leaves suppress inflammatory - mediators production via blockade of NF-κB activation in macrophages vol. 45, 10. 1080/21691401. 2016. 1228661 Synergistic production of 20(S)-protopanaxadiol from protopanaxadiol-type ginsenosides by β-glycosidases from Dictyoglomus turgidum and Caldicellulosiruptor bescii vol. 7, 10. 1186/s13568-017-0524-9 Provides a View of the Panax ginseng Transcriptome vol. 8, 10. 3390/genes8090228 Inhibition of in HepG2 Cells by GINST-Decreasing HMG--Kinase vol. 82, 10. 1111/1750-3841. 13828 Effects of ginsenosides on regulatory T cell differentiation 10.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: Currently, national funds such as the Amazon and the form the backbone of the + financial architecture [13]. In the Caatinga biome, the FC + CEZ scenario allows by 2050 the restoration of almost half (0. 38 Mha) of the area already anthropized by 2020. In the Cerrado, currently the epicenter of Brazil's agrobusiness expansion, 8. 9 out 28. 4 Mha of native vegetation inside unprotected CEZs may be anthropized between 2020 and 2050, according to the BAU scenario. In the FC + CEZ scenario, this loss is transformed into a net gain of 0. 45 Mha. However, as a side effect, the FC + CEZ scenario generates an increased loss of biodiversity-rich, old-growth native vegetation areas, which are replaced by restored areas elsewhere. Overall, only the FCZD scenario permitted to effectively protect the biome, and its threatened biodiversity. Basically, the FCZD scenario extends to the Cerrado from 2026 onwards the same level of protection granted by law to the in 2006. This initiative may be politically and economically difficult to implement biome-wide (not to mention Brazil-wide). Zeroing or even slowing deforestation requires advances in frontier governance, law enforcement, and mechanisms for punishing deforesters, and persuasive measures to engage producers [27, 28]. An alternative approach would be to extend the zero-deforestation policy initially to the region, which covers 36% of the Cerrado but contains within its borders 64% of the biome's unprotected CEZs. Private-sector initiatives, like the in the Amazon [39], to combat deforestation and the conversion of native vegetation into pasture or cropland could also be an option, but implementing a similar agreement in the Cerrado faces major political and geographical obstacles [28]. The creation of new PAs to avoid the collapse of key ecosystem services, or the habitat loss of critically endangered species, although not the focus of this study (PAs are public land), should also be considered as a policy option. Creating PAs for strict protection or sustainable use at all CEZ locations would most likely be the optimal scenario. This measure would add 137. 6 million ha (42.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: MSc are successfully obtained by adjusting the cell culture and use growth hormones for neural differentiation. The changes in components are observed through cell conditions in brain, absorption and secretion of components by various inducers [23]. Figure 6: Shows presence of MSC in glial cell [22]. in per knowledge glial cell types have been playing a part in nerve regeneration. Main part of brain is the CNS which contains the grey matter and white matter [24]. Astrocytes of glial cells are abundant in them. They act as support for neurons and play a part in homeostasis. Astrocytes also harbour receptors and transporters which is the main role of homeostasis. The surface contains K+ channel, helps in regulating potassium levels and aquaporin receptors regulated osmosis changes. Astrocytes interlinks gap junctions due to presence of glucose receptors, glutamate, glutamate aspartate and glutamate transporter 1. Calcium is the one transported into these gaps to release the neurotransmitters from astrocytes [25]. Hence it is called gliotransmission. This transmission plays a crucial in receiving inputs from neurons. The biochemical support for blood brain barrier and ion balance are done by astrocytes. After the brain injury, the signalling pathways are activated by the reactive astrocytes. Glial scar formation might stop axonal growth, inhibiting factor interleukins produced by the astrocytes protects the neurons. Hence there is a dynamic signalling taking place in the inflammatory function and produces notch in the pathway modulating the axon growth [26]. The myelinating cells in white matter and grey matter in CNS is the oligodendrocytes. Myelin sheets plays effective role in axon survival and are believed to regulate environment where neurons are present. Basically both oligodendrocytes and neurons play mutual role. Former provides structural and neuroprotection to axons and latter provides maturation to oligodeendrocytes [27]. Nerve glial antigen 2 cells help in co-localising oligodendrocyte precursor cells. They contain dividing cells in high numbers which expresses ion channels and conduct electric current. They have self-propagating ability and differentiate into oligodendrocyte cells, potentially useful for cellular therapy of brain injury [28] (Figure 6,7). Figure 6: Shows the work of glial cells in brain [28].

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 1007/s10068-017-0255-3 of in High-Fat Diet-vol. 17, 10. 1089/jmf. 2014. 0016 Immunomodulatory effects of selected Malaysian plants on the CD18/11a expression and phagocytosis activities of leukocytes vol. 5, 10. 1016/S2221-1691(15)30170-2 in rats with estrogen decline using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry vol. 9, 10. 1039/C7FO01680H Ginsenoside F1 Activity of NK Cells via Insulin-Factor-1-vol. 9, 10. 3389/fimmu. 2018. 02785 -Mix on Lipopolysaccharide-Stimulated RAW 264. 7 Cells vol. 21, 10. 1089/jmf. 2018. 4180 Lam. heartwood inhibit the innate immune responses of human phagocytes vol. 70, 10. 1111/jphp. 12952 Ginsenosides from Korean red ginseng modulate T cell function via the regulation of NF-AT-mediated IL-2 production 10. 1007/s10068-018-0428-8 Metabolomics reveals immunomodulation as a possible mechanism for the antibiotic effect of Persicaria capitata (Buch. -Ham. ex D. Don) H. Gross vol. 14, 10. 1007/s11306-018-1388-y Identification of candidate UDP-glycosyltransferases involved in protopanaxadiol-type ginsenoside biosynthesis in Panax ginseng vol. 8, 10. 1038/s41598-018-30262-7 Alkaloids and in and Application to Pharmacokinetics of Shen-vol. 2018, 10. 1155/2018/5107083 extracts on rats vol. 9, 10. 1039/C8FO00025-and 2,4,6-Trinitrobenzenesulfonic Acid-in Mice by Activation and T vol. 46, 10. 1142/S0192415X18500945 the for vol. 2019, 10. 1155/2019/6908716 Chemical composition characteristics of Korean straight ginseng products vol. 1, 10. 1016/j. jef.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: 1 million ha outside the Amazon) to the country's public network of PAs. However, the proportional financial implications in terms of land expropriation and management, and commensurate political and social repercussions in terms of land use limitations should also be considered. More realistically, given Cerrado's critical situation [43], the creation of conservation areas at all level 1, unprotected CEZs would bring a much needed respite to this hotspot of biodiversity by adding 28. 4 Mha to the current network (17. 5 Mha, excluding indigenous lands) of PAs in this biome. A similar measure in the Caatinga, would add 3. 6 Mha of protected land to the biome. Summarizing, the complexity and magnitude of the task of protecting and restoring Brazil's unprotected CEZs requires a mix of additional policies, like targeted restoration, zero-deforestation, creation of PAs, built upon the existing legal framework defined by the (strictly enforced) FC. Naturally, the policies investigated here may also imply in production losses relative to the BAU scenario, as they more or less restrict access to land. Therefore, a careful political negotiation is needed to find the best balance between conservation measures and the economic interests of land owners. At stake are biodiversity conservation, climate change, food and energy production, and social justice in Brazil. Note that previous studies ([4–7, 10, 32, 36–38, 42, 43, 47]), using different methodologies, and with different goals, arrive to similar findings: deforestation is a threat to Brazil's rich biodiversity, be it a whole biome, a class or a single species; Brazil's current environmental legal framework needs improvements; and a compromise between agricultural production and preservation/restoration is possible. Finally, it is important to note that, per construction, CEZs are a subset of the larger set of conservation priority zones (CPZs), which includes disturbed and undisturbed biodiversity-rich areas, and covers 89. 1% of the Brazilian territory [51]. Since, with the exception of the FC-CEZ restoration strategy, all our scenarios (BAU included) do not depend on the location of both CPZs and CEZs (see table 2), most of the qualitative findings discussed in this section are also applicable to CPZs. 5.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Figure 7: Shows environment of glial cells in CNS [29]. neurogenesis, macroglia containing astrocytes and oligodendrocytes undergo asymmetric division to form glial-restricted progenitors [30] (Figure 8). Figure 8: Explains the process for stem cell therapy for brain injury [30]. and its cells have not reached its full potential in treatment of nervous system. Most fascinating studies often establish greater results, such fascination is the stem cell treatment of nervous cells [31]. The animal models often expedite clinical trials resulting in compounding results. They help in determining the site delivery, dosage, transplantation time and safety of the experiments. Most specific of them all are the cell types to choose from, either iPHSC [32]. But the source basically varies from each cell type. Bone marrow tailor made to suit the cells to form organs. More often fetal cells are more preferred than adult cells. Imaging techniques have helped in tracking the cells, most common used are magnetic imaging resonance, positron emission tomography and bioluminescence [33]. The most common problem of regeneration is the rejection of graft cells. But the for rejection solution lies in stem cells itself, induced pluripotent stem cells are used, giving an edge over ethical issues. Future studies can all underline the genetic profile of diseased cells and carve a necessary cell to treat damaged neurons [34-36]. creates appropriate environment for glial cells to regenerate. But potential harmful effects have sidelined the studies for further development of nerve cells. Natural products such as hydrogen sulfide is important to control activation of microglia in CNS. Microglia has two effects, one it protects neurons and second transplantation of nerve cells. During injury microglia benefits neuronal stem cells. Since glial cells are the cellular components of environment surrounding neurons, their types play a major role in neural regeneration. Glial cells often create scar formation, but technology driven stem cells find various ways to convert these into neural cells. Glial scar often has its potential, they repair, inhibit and potentially regenerate CNS injured tissue. NG2 helps to proliferate, survive and differentiate stem cells in the brain, target the injured region and cure them. In conclusion appropriate control of glial cells can help in survival and efficient function of neural stem cells. These glial cells can be the future of treatment of CNS injuries and diseases.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 2014. 11. 007 Ginseng pharmacology: a new paradigm based on gintonin-lysophosphatidic acid receptor interactions vol. 6, pp. None, 2012, 인삼 지상부를 첨가한 사료 급여가 닭에서 나타내는 효과 vol. 55, 10. 14405/kjvr. 2015. 55. 1. 1 vol. 22, 10. 18787/jr. 2015. 22. 2. 63 on System by of Panax ginseng in Relapse-Autoimmune Encephalomyelitis-Induced SJL/J Mice vol. 44, 10. 1142/s0192415x16500610 Use of Gold Nanop10. 4014/jmb. 1604. 04034 In situ preparation of water-soluble ginsenoside Rh2-entrapped bovine serum albumin nanop10. 2147/ijn. s125154 Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus vol. 41, 10. 1016/j. jgr. 2016. 08. 010 Towards natural mimetics of metformin and rapamycin vol. 9, 10. 18632/aging. 101319 Investigation of Herb-between and five CYP Substrates by LC-MS/MS vol. 8, 10. 5478/msl. 2017. 8. 4. 98 Stimulation of Function by Panax ginseng after vol. 66, 10. 1021/acs. jafc. 8b00152 Effect of Asterias amurensis through NF-κB and MAPK Pathways on RAW 264. 7 Cells vol. 28, 10. 4014/jmb. 1709. 09005 Medicine in Multiple Sclerosis: Theory and Practice vol. 4, 10. 1007/s40495-018-0158-x Role of inflammasome regulation on immune modulators vol. 32, 10. 7555/jbr. 32. 20170120 Optimization of ginseng hairy roots culture and its ginsenoside analysis vol. 35, 10.

Output: pass


Input: Claim: Offsetting policies may require developers to restore or protect similar ecosystems. [SEP] Text: Wealthier countries will have to cut emissions more quickly, making reductions by 2030 beyond those currently proposed20,21 and reaching net-zero emissions before 2050. Similar targets and emergency action are needed for biodiversity loss and the wider destruction of the natural world. To achieve these targets, governments must make fundamental changes to how our societies and economies are organised and how we live. The current strategy of encouraging markets to swap dirty for cleaner technologies is not enough. Governments must intervene to support the redesign of transport systems, cities, production and distribution of food, markets for financial investments, health systems, and much more. Global coordination is needed to ensure that the rush for cleaner technologies does not come at the cost of more environmental destruction and human exploitation. Many governments met the threat of the covid-19 pandemic with unprecedented funding. The environmental crisis demands a similar emergency response. Huge investment will be needed, beyond what is being considered or delivered anywhere in the world. But such investments will produce huge positive health and economic outcomes. These include high quality jobs, reduced air pollution, increased physical activity, and improved housing and diet. Better air quality alone would realise health benefits that easily offset the global costs of emissions reductions. 22 These measures will also improve the social and economic determinants of health, the poor state of which may have made populations more vulnerable to the covid-19 pandemic. 23 But the changes cannot be achieved through a return to damaging austerity policies or the continuation of the large inequalities of wealth and power within and between countries. Cooperation hinges on wealthy nations doing more In particular, countries that have disproportionately created the environmental crisis must do more to support low- and middle-income countries to build cleaner, healthier, and more resilient societies. High income countries must meet and go beyond their outstanding commitment to provide $100bn a year, making up for any shortfall in 2020 and increasing contributions to and beyond 2025. Funding must be equally split between mitigation and adaptation, including improving the resilience of health systems. Financing should be through grants rather than loans, building local capabilities and truly empowering communities, and should come alongside forgiving large debts, which constrain the agency of so many low-income countries. Additional funding must be marshalled to compensate for inevitable loss and damage caused by the consequences of the environmental crisis. As health professionals, we must do all we can to aid the transition to a sustainable, fairer, resilient, and healthier world.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: Since the discovery if iPSC, many disorders of CNS has been cured. It is clear that glial cells has contributed towards stem cell regeneration in CNS and are indispensable asset to brain homeostasis, disease cure, development and function of nerve cells. Along with fast paced progress of stem cells and cell replacement therapy, hiPSC derived glial cells will play crucial role on clinical treatment of neurological diseases. 293. e9. (2015) Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. . 10:e0116933. . (2009) Neuroscience: glia - more than just brain glue. Nature. 457(7230):675-7. . (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Neurosci. 7(3):194-206. (2001) An inwardly rectifying K(+) channel, Kir4. 1, expressed in astrocytes surrounds synapses and blood vessels in brain. Physiol. 281(3):C922-C931. -(1997) Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci. 17(1):171-180. . (1995) The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia. 14:43-54. Abbott NJ. (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat. 200(6):629-38. . (2011) Oligodendrocyte fate after spinal cord injury. Neurotherapeutics. 8(2):262. (2013) Metabolic aspects of neuron-oligodendrocyte-astrocyte interactions. (Lausanne). 4:54. van der Valk P. (2010) Inflammation in neurodegenerative diseases. Immunology. 129:154-169. . (2015) Adult mammalian neural stem cells and neurogenesis: Five decades later. Cell. 17(4):385-95. (2001) Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng. 72:211-28.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 12925/jkocs. 2018. 35. 4. 995 Mapping a novel positive allosteric modulator binding site in the central vestibule region of human P2X7 vol. 9, pp. None, 2019, Electrodeposition of Ginseng/Poly(lactic-co-glycolic Acid) on 316L at Parameters vol. 67, 10. 1248/cpb. c18-00847 of for IBD vol. 2019, pp. None, 2012, Dish to Patient: and Mechanism of Action for Antimicrobial and Products vol. 10, pp. None, 2012, A on the Effects of of Panax ginseng on the of Cyclophosphamide-Mice vol. 24, 10. 3390/molecules24061096 Immune-enhancing effects of a traditional herbal prescription, Kyung-Ok-Ko vol. 34, 10. 6116/kjh. 2019. 34. 2. 41 : Preparation, Phytochemistry and vol. 24, 10. 3390/molecules24101856 of the Metabolomes among the of Panax ginseng, Panax quinquefolius, and Panax notoginseng by UHPLC/IM-QTOF-HDMSE-Analysis vol. 24, 10. 3390/molecules24112188 Integration of Data-(DDA) and Data-Independent High-Definition MSE (HDMSE) for the and Characterization of Multicomponents from Panax japonicus by UHPLC/I vol. 24, 10. 3390/molecules24152708 Pharmacological effects of ginseng on infectious diseases vol. 27, 10. 1007/s10787-019-00630-4 Ginsenoside Rh2 reverses cyclophosphamide‐induced immune deficiency by regulating fatty acid metabolism vol. 106, 10. 1002/jlb. 2a0419-117r Development of a Validated UPLC-MS/MS Method for from Species vol. 24, 10. 3390/molecules24224065 A case of cancer patient treated by monotherapy vol. 40, 10. 13048/jkm.

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: Figures AbstractAttempts to meet biodiversity goals through application of the mitigation hierarchy have gained wide traction globally with increased development of public policy, lending standards, and corporate practices. With interest in biodiversity offsets increasing in Latin America, we seek to strengthen the basis for policy development through a review of major environmental licensing policy frameworks in and Venezuela. Here we focused our review on an examination of national level policies to evaluate to which degree current provisions promote positive environmental outcomes. All the surveyed countries have national-level Assessment laws or regulations that cover the habitats present in their territories. Although most countries enable the use of offsets only Brazil, Colombia, Mexico and Peru explicitly require their implementation. Our review has shown that while advancing quite detailed offset policies, most countries do not seem to have strong requirements regarding impact avoidance. Despite this deficiency most countries have a strong foundation from which to develop policy for biodiversity offsets, but several issues require further guidance, including how best to: (1) ensure conformance with the mitigation hierarchy; (2) identify the most environmentally preferable offsets within a landscape context; (3) determine appropriate mitigation replacement ratios; and (4) ensure appropriate time and effort is given to monitor offset performance. Citation: (2014) for in Latin America. 9(9): e107144. Clinton N. Jenkins, Instituto de Pesquisas Ecológicas, BrazilReceived: February 18, 2014; Accepted: August 13, 2014; Published: September 5, 2014Copyright: © 2014 Villarroya et al. This is an open-access 1. Countries selected for the study (in color). In dark grey, countries for which offset frameworks have been established. Countries' names have been abbreviated to the codes set by ISO 3166. MethodsWe focused our review on national (federal) level policies to assess how current requirements would affect implementation of the mitigation hierarchy and promote positive environmental outcomes. State and provincial policies have not been included in this study. Although they are necessary to respond to local environmental contexts, the paper focuses on national policies because (a) the constitution of Chile, Colombia, Peru only allow for all laws to be established at the national level [17]–[19]. In addition in Venezuela environmental laws are only made at the national level [20]. Decisions on environmental licensing in Mexico are context dependent with large scale impacts (e. g.

Output: corroborate


Input: Claim: Regenerative medicine can cure any disease with stem cell therapy. [SEP] Text: (2007) Stem cells and neurological diseases. Cell Proliferation. 41:94-114 (2018) Stem cells: A promising candidate to treat neurological disorders. Res. 13(7):1294-1304. Barres BA. (2008). The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 60(3):430-40. (2012). Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Med. 367:795-804. Bjartmar C, D. (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Neurol. 14(3), 271-8. -Hoberg M, Jin L, et al. (1994) Localization of neuronal and glial glutamate transporters. Neuron. 13(3):713-25. Baumann N, Pham-Dinh D. (2001) Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev. 81(2):871-927. (2008)NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci. 11:1392-1401. . (2004) NG2-positive cells in the mouse white and grey matter display distinct physiological properties. J Physiol. 561:109-122. . (2008) Expression of the receptor for advanced glycation end products in oligodendrocytes in response to oxidative stress. J Neurosci Res. 86(11):2414-22. Bonifati DM, Kishore U. (2007) Role of complement in neurodegeneration and neuroinflammtion. Mol Immunol. 44(5):999-1010. (2018) Methods of mesenchymal stem cell homing to the blood-brain barrier. Biol. 1842:81-91. (2015) Cell-based therapy for traumatic brain injury. Anaesth. 115(2):203-212. . (2014) In vitro and in vivo neurogenic potential of mesenchymal stem cells isolated from different sources. J Biosci. 391:157-169.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 19044 In-depth profiling, characterization, and comparison of the ginsenosides among three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. by ultra-high performance liquid ch vol. 411, 10. 1007/s00216-019-02180-8 A Review of in Cardiovascular Disorders: Benefits and Risks vol. 48, 10. 1142/s0192415x20500147 Peptides as for Authentication of Mountain- of -HRMS vol. 68, 10. 1021/acs. jafc. 9b05568 Gintonin-Stress-through LPA Receptor vol. 25, 10. 3390/molecules25051019 Ginsenoside Rg1 Acts as a with Anti-without Regeneration in vol. 9, 10. 3390/cells9051107 Characteristics of Panax ginseng Cultivars in Korea and China vol. 25, 10. 3390/molecules25112635 Effects of on and DHEA Levels in Healthy Females: Study vol. 12, 10. 3390/nu12061582 Characterization of red ginseng–drug interaction by CYP3A activity increased in high dose administration in mice vol. 41, 10. 1002/bdd. 2246 Ginseng integrative supplementation for seasonal acute upper respiratory infections: A systematic review and meta-analysis vol. 52, pp. None, 2012, of Oils vol. 10, 10. 3390/biom10081139 Physiological responses and ginsenoside production of Panax ginseng seedlings grown under various ratios of red to blue light-emitting diodes vol. 61, 10. 1007/s13580-020-00255-5 Research Quality-Modeling for Comparison of the of Black and vol. 12, 10. 3390/nu12092590 Immunomodulatory effects of fermented Platycodon grandiflorum extract through NF-κB signaling in RAW 264. 7 cells vol. 14, 10. 4162/nrp. 2020. 14. 5. 453 Synergistic anti-liver cancer effects of curcumin and total ginsenosides vol. 12, 10. 4251/wjgo. v12. i10.

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: We also paid attention to sector-specific policies, since it is common to find specifications on how EIA shall be carried out for certain types of development (i. e. mining) projects, or require specific mitigation measures for particular types of development. In addition we also examined habitat/area-specific policies (e. g. wetlands), since sometimes they include provisions related to impact mitigation [26]. Although our analysis examined some aspects of the EIA process it was not intended as a detailed review of these procedures. Impact assessments are highly technical processes, whose success depends on the quality of the regulatory requirements, availability of analytical tools and technical capacity. Here we focused on aspects of EIA that we think influence implementation of the mitigation hierarchy. Moreover several publications have conducted broader analysis of EIA process in the region, including operational and implementation issues [27]–[31]. In addition a recent review by Reid et al. (in prep. ) analyzes the SEA procedures in the region. To evaluate mitigation frameworks as the basis for offset practices, our assessment is focused on regulatory features directly related to impact mitigation, mainly: impact evaluation and the use of the mitigation hierarchy. The aim is to assess to what extent the reviewed policies set requirements that may eventually promote solid mitigation practices. This portion of our analysis serves as the starting point for the more detailed review of offset frameworks, see below. To standardize the review as much as possible, we have defined a set of questions that have been answered for each country on a yes/no basis, depending on the contents of their laws and regulations (1. Current policies reviewed for the selected offset frameworks. Brazil projects subject to environmental licensing must offset their impacts on environmental assets. Impacts on (Law 9985 of 2000), caves (Decree 6640 of 2006) and coastal native vegetation (Decree 5300 of 2004) shall always be offset, although the environmental authority (IBAMA) may require the developer to offset any other residual impacts identified. In addition to these laws, Law 12651 of 2012 (on the Protection of Native Vegetation) regulates offsets for impacts to native vegetation, although these are not required for obtaining an environmental license so we will not examine it in this paper. In this case, our review will focus on the framework first set by Law 9985 of 2000 (see Table 1).

Output: corroborate


Input: Claim: Regenerative medicine has no ethical or medical risks. [SEP] Text: Clinical trial and regulatory paradigm for testing and market approval of offer different clinical trial structures for assessing non-traditional medical therapies [65]. The most appropriate trial structure and preclinical testing requirements for a new therapy can be discussed with the FDA. However, the guidelines and regulations often lag behind current scientific knowledge. While clinical trials for SCTCs are not unique, being similar to stem cell trials and organ transplants, these trial structures may still not be optimal. Clearer guidance on trial structure and preclinical testing requirements would assist researchers and clinicians in developing new therapies. It would also ensure the risks to trial participants are minimised and the trial benefits are maximised. The following recommendations are applicable to clinical trials of both stem cell and SCTC therapies. The relevance of animal studies for stem cell and SCTC therapy is largely unknown. Some animals have greater abilities to regenerate tissue and have different immune systems, vasculature and nerve growth, physiology and metabolism to humans. Subsequently, the survival, integration and function of animal or human stem cells and SCTCs implanted into an animal model may be very different from in a human. Traditional preclinical studies on animals and cell lines assess the efficacy, toxicity, dose response, pharmacokinetics, pharmacodynamics and mode of action of a therapy, and are used to guide which parameters to monitor, who are the most eligible patients, and what is the best treatment delivery method for first-in-human studies. The first-in-human studies are then used to validate any preclinical studies and better define the phase 1 trial structure. However, the high level of uncertainty of preclinical data relevance of risk and benefit to first-in-human trial participants places them at very high risk of harm. Yet positive data from preclinical studies may give clinicians and review boards a false understanding of treatment risk and benefit. This may lead to overly enthusiastic portrayal of the treatment to potential trial participants, generating a false hope of therapeutic benefit and low treatment risk [66]. It may also needlessly harm large numbers of animals testing potential therapies which have low relevance to humans. What details can be obtained from a preclinical study of stem cell and SCTC therapy? Current FDA guidelines for preclinical assessment of gene and cellular therapies include investigating the animals immune response, the animal and implanted tissue survival, stem cell proliferation, differentiation, engraftment and migration, and determining a suitable initial cell dosage level [38, 39].

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: 1091 Lactobacillus fermentum KP-3-fermented ginseng ameliorates alcohol-induced liver disease in C57BL/6N mice through the AMPK and MAPK pathways vol. 11, 10. 1039/d0fo02396e A Proliferation-Regulation in by Panax ginseng vol. 68, 10. 1007/s00005-020-00597-z alleviates immunoparalysis of CLP mice by degrading CHOP through interacting with FBXO15 vol. 10, 10. 1038/s41598-020-76285-x A comprehensive review of COVID-19 characteristics vol. 22, 10. 1186/s12575-020-00128-2 Comparative assessment of antimicrobial and antioxidant activity between whole plant and parts of Sphaeranthus indicus Linn. (Asteraceae) vol. 6, pp. None, 2012, Effect of Oil on after Treatment with Lipopolysaccharide vol. 33, 10. 5021/ad. 2021. 33. 3. 245 Heracleum moellendorffii root extracts exert immunostimulatory activity through TLR2/4‐dependent MAPK activation in mouse macrophages, RAW264. 7 cells vol. 9, 10. 1002/fsn3. 2020 Composition, Antioxidant and in of Panax ginseng Extracted in vol. 11, 10. 3390/app11010093 of Ginsenosides, the Components of Ginseng vol. 2021, pp. None, 2021, Immuno-enhancement effects of Ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial vol. 45, 10. 1016/j. jgr. 2020. 08. 003 of from Panax ginseng C. A. Meyer and Ostrea gigas Thunberg on in vol. 18, 10. 3390/ijerph18052349 Activities of Arginyl-Fructose (AF) and AF-Products in In-Vitro and In-Models vol. 26, 10.

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: projects subject to EIA must offset their impacts on terrestrial ecosystems (as regulated by Resolution 1517 of 2012) and freshwater (Law 99 of 1993, Decree 1900 of 2006 and Decree 1933 of 1994). In addition there are some offset requirements for impacts to forests (Decree 1791 of 1996) as well as several specific activities (Resolutions that implement TORs for elaborating EISs, see Table S1). However, these latter policies only address a few aspects related to offset implementation, so they cannot be considered equal to the 2012 law focused on terrestrial ecosystems. For this country we will focus the review on this 2012 framework (see Table 1). the of 2003 requires offsets for impacts that result in land-use change to forested areas. The recently enacted Act (2013) also requires offsets, but only when impacts are not predicted or approved in the EIA and are deemed an environmental offence. Since this is not a part of the environmental licensing process we have not included it in our assessment. The general law on ecological balance and environmental protection of 1988 (most commonly known as the ) also enables the use of offsets as does the -120--2011 which makes some provisions for offsets related to mining projects. Neither of these two laws can be considered a specific offset framework since they only enable the use of offsets but do not make any specific requirements or guidance for when or how they should be used. a new law about to be passed requires offsets for certain projects subject to EIA, and provides details on how such measures shall be implemented. Although the law is not currently enacted, we have included it in this study since it establishes a new offset framework that is different from the other country level programs. Offset design is a complex process that entails multiple challenges. Several principles have been outlined to guide this process, the most widespread being the ones set by the Business and Programme (BBOP) [32]. However, applying theoretical guidance into practice often proves difficult, as when trying to translate best practice principles into effective policy requirements. Several challenges, which may be especially tricky for policy making, have been identified and discussed in the scientific literature (see [33], [34]). We want to contribute to this discussion by evaluating how the selected policies deal with these challenges, and how the theory we know may help improving legal frameworks. Following the approach outlined in McKenney and Kiesecker 2010 [33] and Bull et al.

Output: corroborate


Input: Claim: Regenerative medicine has no ethical or medical risks. [SEP] Text: The animal testing should achieve an understanding of the biological plausibility of the therapy with characterisation including morphology, functional and animal behavioural changes. Safety should be assessed by toxicology studies. And if a scaffold is implanted, it should be adequately characterized for composition, degradation profile, biomechanical performance, and biocompatibility. Where appropriate, a preclinical study for stem cell and SCTC therapy should define the cell source, differentiation method, tissue plating, culture timing and media composition; it should demonstrate consistent tissue yield, purity and phenotype. Animal studies should assess the impact of incorrect tissue placement, orientation and composition on tissue and animal survival and function. The effect of necrotic tissue and cysts should be determined and the impact on tissue and animal survival when vasculature fails to grow into the implanted tissue. Changes in tissue maturity, structure, function, survival and integration should be assessed over long-term implantation. Different aged animals may be implanted to determine the impact on tissue development. And biofluid samples may be assessed for changes after implantation. Implanted animals should also be given other disease-specific standard treatments such as immunosuppressants, drugs or electrical stimulation to determine the impact on implanted tissue function and survival, and changes to the other treatments performance. These preclinical studies will provide some guidance on how a stem cell or SCTC will perform in a first-in-human study. However, due to differences in genetics and target tissue, the function may vary in every person. These studies also have limited benefit in understanding how autologous tissue will function. The poor relevance of the animal studies to humans precludes the need to test every autologous tissue before clinical use. Preclinical studies would only be required before a first-in-human clinical trial for a particular tissue protocol. Once a stem cell or SCTC therapy has proceeded to a clinical trial, how should the trial be structured? Trials will likely need to incorporate efficacy as well as safety endpoints in ways that are fair and respectful to research trial participants [67]. The question is how to manage uncertainties related to risk of harm, in particular with custom made tissues. Does a precautionary approach to the risk-benefit ratio work? Autologous SCTCs may be fabricated on a tailor-made ‘per-patient’ basis, and so a precautionary approach might be less relevant.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: Neuroprotective effects of ginsenosides. Exp (Wars) 2006;66:369-375. . Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS 2007;13:381-404. . Ginsenosides and their CNS targets. CNS 2011;17:761-768. . Neuroprotection in progressive brain disorders. 2003;5:576-580. . Strategies for the protection of dopaminergic neurons against neurotoxicity. 2000;2:99-114. de. Staging of brain pathology related to sporadic Parkinson's disease. 2003;24:197-211. Schapira AH. Molecular and clinical pathways to neuroprotection of dopaminergic drugs in Parkinson disease. Neurology 2009;72(7 Suppl):S44-S50. . Mechanisms underlying infl ammation in neurodegeneration. Cell 2010;140:918-934. . Protection against 1-methyl- 4-phenylpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng C. A. Meyer) in SH-SY5Y cells. J Ethnopharmacol 2011;135:34-42. . Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease. 2003;184:521-529. . Rg1 reduces nigral iron levels of MPTP-treated C57BL6 mice by regulating certain iron transport proteins. 2009;54:43-48. . Rg1 protects the MPP+-treated MES23. 5 cells via attenuating DMT1 up-regulation and cellular iron uptake. Neuropharmacology 2010;58:488-494. . Rg1 protects iron-induced neurotoxicity through antioxidant and iron regulatory proteins in 6-OHDA-treated MES23. 5 cells. J 2010;111:1537-1545. Rouault TA, Cooperman S. Brain iron metabolism. Neurol 2006;13:142-148. . Iron elevations in the aging Parkinsonian brain: a consequence of impaired iron homeostasis? J Neurochem 2010;112:332-339. .

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: survival rates for reforestation activities). S4 for details. Offsets: Although most countries enable the use of offsets only Brazil, Colombia, Mexico and Peru explicitly require their implementation for specific impacts. some basic provisions are established in the national EIA regulation (see Decree 40 of 2013), although more specific guidance is being developed by the Ministry of the Environment. Detailed guidance is provided by Brazil, Colombia, Mexico and Peru all of which have specific regulations regarding offsets. These countries all include regulations that are already implemented or in the case of Peru are about to be passed into law. None of these regulations is sector-specific. and Mexican policies are aimed at impacts to specific natural assets, Colombia and Peru have a broader scope. For more details see section on offsets below. Monitoring: While all countries require the use of EIA and many have requirements that emphasize the use of offsets few have explicit language requiring monitoring of development impacts and mitigation activities. Some countries add provisions specific to particular sectors explicitly requiring post-project monitoring, but such information is lacking in most general-scoped EIA policies. Several of the documents that make provisions for monitoring require specific activities to be included in the plan (schedule, indicators, human resources, etc. ). Some policies state when the monitoring activities should be performed (e. g. construction and closure phases), but only three documents were found to set the duration of monitoring activities, which ranged from 3 to 10 years after the completion of the project or implementation of the mitigation activities (S5 for details). by country. Brazilian and Mexican schemes are the first for which specific offset policies were enacted and in turn include a relatively high number of policy documents (especially in the Brazilian case). In marked contrast the Colombian and Peruvian frameworks are recent, and have few policy related documents (1 and Figure 4). Here we consider the aspects of country-level offset policies highlighting aspects that promote conservation outcomes. Table 3 summarizes the results that are described below with more detail. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageFigure 4. Number of policies related to each country's offset framework issued per year. Includes both current and revoked policies. Countries' names have been abbreviated to the codes set by ISO 3166. Download: PPTPowerPoint slidePNGlarger imageTIFForiginal imageTable 3. Summary of results of the review of offset frameworks by country.

Output: corroborate


Input: Claim: Regenerative medicine has no ethical or medical risks. [SEP] Text: As such, it would be of limited clinical value and unethical to first test safety in a randomised clinical trial on a different population of non-specific subjects. This may entail that fabricating unique personalised SCTC treatments on demand from one’s own stem cells will unlikely require a prior randomized safety and efficacy trial on other patients as the relevance is limited, aside from standardised criteria and protocols for building the tissues. Accordingly, a patient waiting for a SCTC would likely serve as their own test subject or a ‘guinea pig’ for their therapy [67]. Where possible, there should be a standardisation of primary and secondary endpoints for different regenerative medicine targets to enable comparison of safety and efficacy. Patient recruitment should be staggered with an individual patient implanted first, the risks and benefits of the stem cell or SCTC therapy monitored over a sufficiently long time period [68]. If the treatment was successful, a second patient can be enrolled. If the treatment was not successful, then the protocol may be modified to address any known issues before enrolling a second patient. Given the unknowns surrounding both benefits and iatrogenic harms, patient selection should favour those with no other treatment options. At the conclusion of the trial, all data should be published so that no other patients are needlessly harmed in similar future trials and the knowledge obtained from the patients provides benefit to society. Trial participants should be made aware of sponsors that have not published previous trial data, as this may suggest their involvement will lead to no benefit to society. Our previous work on restructuring clinical trials based on treatment risk provides further information and examples to aid IRBs in evaluating the risk and efficacy of a novel therapy [68]. The risk of neural and reproductive regenerative medicine therapies is greater than other tissues, which may suggest they should not be assessed initially. However, trial sponsors are not organised to assess new medical therapies beginning with the lowest risk. Trial sponsors will likely target diseases with greater prevalence in first world countries. The cost of SCTC therapy is very high, so it may not receive reimbursement. This raises concerns around equity of trial and treatment access. Where possible, stem cell and SCTC therapy should be provided through the public health care system to ensure equal access regardless of patient or disease. The choice of population group for enrolling in a clinical trial is also complicated.

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: J Ethnopharmacol 2007;111:458-463. . Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. J Ethnopharmacol 2008;115:441-448. Heneka MT, O'Banion MK. Inflammatory processes in Alzheimer's disease. J Neuroimmunol 2007;184:69-91. . Potential effects of microglial activation induced by ginsenoside Rg3 in rat primary culture: enhancement of type A Receptor expression. Res 2005;28:1164-1169. . Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin. J 2009;61:375-380. . Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes. 2008;434:1-5. Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affi nity. 2012;33:151-162. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J 2012; Epub ahead of print. . Mitochondria in Huntington's disease. Acta 2010;1802:52-61. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Research Group. Cell 1993;72:971-983. Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease. 2004;187:150-159. . Imaging microglial activation in Huntington's disease. Bull 2007;72:148-151. Leegwater-Kim J, Cha JH. The paradigm of Huntington's disease: therapeutic opportunities in neurodegeneration. NeuroRx 2004;1:128-138.

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: Brazil all projects subject to EIA can utilize offsets and those EIAs shown to cause negative impacts on protected areas must implement offsets according to the scheme set by Law 9985. The effective implementation of the offsets can be carried out either by the developer (20 of 2011, 1. 3 to 1∶6) that are calculated according to eight criteria: ecosystem type, degree of conservation, presence of endangered or threatened species, affected ecosystem services, proximity to protected areas, project characteristics ( = how its design affects the area), degree to which soil and vegetation resources are affected, and benefits the project will bring to the area (environmental, or social). These ratios are used to calculate the payment that the developer must make to the (Agreement of 2011). Equivalence: in-kind offsets are explicitly prioritized in the Colombian and Peruvian frameworks, and each country uses a different method for calculating the equivalency between impacts and offsets. In the case of Colombia, offsets are required to match impacted ecosystems [36]. The new law in Peru does not include a detailed calculation system but defines a list of variables (e. g. type of habitat impacted, priority areas for conservation and ecosystem services,) that will have to be considered when selecting area to be used for offsets(see Annex II of the Law). approach includes calculations of how much money developers shall put towards offsets depending on the significance of the impacts resulting from the development activities (Decree 4340 of 2002, Decree 6848 of 2009), but there is no way of assessing the equivalence between impacted assets and offset measures. Offset Timing: provisions regarding when offsets are implemented are not present in all the reviewed frameworks, and when they are they tend to be somewhat ambiguous. In Brazil, time limits for proving offset implementation or payment are conditioned to the signed terms of commitment. But that date is not clear so there is no way of knowing if offsets are implemented before or after the project impacts occur. offsets shall be implemented when environmental license is approved, which probably means before the project impacts occur, although this is not completely clear. Time lag: none of the reviewed Latin-American frameworks includes provisions regarding time lags, although in the case of Peru the implementation of a national network of conservation banks, where offsets credits are generated before impacts are incurred, could help address this issue. Offsets longevity: both Colombia and Peru clearly state the minimum duration of offsets.

Output: corroborate


Input: Claim: Regenerative medicine has no ethical or medical risks. [SEP] Text: Due to differences in disease presentation, treatment risk and methodology, it is not possible to provide a blanket rule for patient selection and recruitment of every stem cell and SCTC trial. Patients requiring tissue replacement may suffer degenerative disease or severe trauma with no treatment, including significant mental trauma, and may be desperate for a therapeutic option. And there is the possibility of testing underage patients or those with mental disabilities that affect their ability to provide informed consent. Certain diseases are less likely to include people that are underage or have mental disabilities and should be the initial target for testing stem cell and SCTC therapies. Further discussion over the choice of patients for first-in-human clinical trials of high-risk therapies is detailed in reference [68]. While there is guidance to protect patients enrolling in a clinical trial, the principle investigator takes responsibility for conducting ethical research and is accountable for noncompliance and misconduct. The specific responsibilities for principle investigators, sponsors, IRBs, trial participants and regulatory agencies are numerous and further information can be obtained from other sources [69,70,71].

Output: contrast


Input: Claim: Ginseng is known for its potential adaptogenic effects. [SEP] Text: Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacology 2005;48:743-756. . Ginsenosides protect striatal neurons in a cellular model of Huntington's disease. J 2009;87:1904-1912. . Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 1993;13:4181-4192. . 3-Nitropropionic acid animal model and Huntington's disease. Rev 1997;21:289-293. Kim SU, de Vellis J. Microglia in health and disease. J 2005;81:302-313. . Anti-infl ammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol 2009;209:40-49. . Anti-infl ammatory mechanism of ginsenoside Rh1 in lipopolysaccharidestimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase-1 expression. J Neurochem 2010;115:1668-1680. Mulder DW. Clinical limits of amyotrophic lateral sclerosis. 1982;36:15-22. . Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. J Neurosci 2001;21:9246-9254. . Onset and progression in inherited ALS determined by motor neurons and microglia. Science 2006;312:1389-1392. . Caspase-1 and -3 are sequentially activated in motor neuron death in Cu, Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. 2000;97:13901-13906. Rowland LP. Amyotrophic lateral sclerosis: theories and therapies. 1994;35:129-130. . Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. J Neurosci 2007;27:9201-9219. . Amyotrophic lateral sclerosis. 2009;4:3. .

Output: pass


Input: Claim: Some countries mandate biodiversity offsets as part of environmental regulation. [SEP] Text: offsets should last at least for the length of the project, while in Peru they are required to match the duration of the impacts. Although the topic is not specifically addressed in Brazil, benefits can be considered permanent since they benefit the of Protected Areas. Uncertainty: none of the reviewed Latin-American offset frameworks includes provisions regarding uncertainty, although in the case of Peru the implementation of a national network of conservation banks would help address this issue. Thresholds: only Colombia has set clear limits as to what can be offset. Additionality: only Peru explicitly requires demonstrable gains that ensure that the offsetting process results in additional conservation outcomes. Linking offsets to landscape-level conservation goals: Colombia is the country that clearly establishes the link between offsets and broader conservation plans, although Brazil also requires measures to benefit the System. Peru includes some broad guidance on this issue, although specifics have not been set yet, probably because they will be developed in forthcoming regulatory guidance. Monitoring: provisions regarding post-implementation monitoring of offsets are scarce, and only Colombia requires results to be compared against the area ecological baseline. In Mexico, the is responsible for supervising offset project implementation and that they meet the agreed terms. None of the frameworks establishes specific time requirements for monitoring. DiscussionPrevious studies by Tanaka in 2010 [38] and Consultancy in 2013 [39] identified 56 countries in the world that have or are developing national legislation or policies around offsets. America five territories required the use of offsets (Brazil, Colombia, French Guiana, Mexico and Paraguay), nine enabled the use of this tool (and Venezuela), and three were developing policies related to offsets (Bahamas, Chile, Belize and Peru). Our review of environmental licensing and offset policy frameworks in and Venezuela shows that these systems have been evolving recently (see Figure 2), although not yet adequate in all cases. We have found significant variation on how EIAs are utilized, the importance of adhering to the mitigation hierarchy, offset goals and approaches for addressing key challenges to implementing offsets.

Output: corroborate