Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: In that work, the authors clearly state that in vivo cortisol treatment had no synergistic effect with TH in inducing metamorphosis. Moreover, in Senegalensis, the sole pre-otic CRH neuron number decreases during metamorphosis, further arguing that, at least in flatfish, cortisol is not involved in flatfish metamorphosis (PMID: 25575457). We will do our best to improve the clarity of the revised manuscript to avoid any misunderstanding about our claims. However, we would like to point out the semantic shift in the reviewer first sentence: Indeed “being involved” is not the same as “cortisol alone does not induce”. In ref 20 the authors explicitly wrote that “Cortisol further enhanced the effects of both T4 and T3, but was ineffective in the absence of thyroid hormones” and in our view this indeed corresponds to ”being involved in metamorphosis”. We are not claiming that cortisol alone is involved in metamorphosis as the reviewer suggests, but simply that there is a possible involvement of cortisol together with TH in metamorphosis. We stand on this claim as we indeed observed an activation of corticoid pathway genes around D32, which is sufficient to say it is involved. We do agree that functional experiments will be needed to properly demonstrate the involvement of corticoids in grouper metamorphosis, but this was not possible in the current study as it would imply to set up a full grouper life cycle in lab conditions which is impossible for the scope of this manuscript. We also mentioned in the discussion that the role of corticoids in fish larval development is still debated, and we agree that this remains a contentious issue. We have clarified the Discussion on this point (lines 375-376, lines 439-464). We wrote that “There is contrasting evidence of communication between these two pathways during teleost fish larval development with some data suggesting a synergic and other an antagonistic relationship. In terms of synergy, an increase in cortisol level concomitantly with an increase in TH levels has been observed in flatfish [26], golden sea bream [64] and silver sea bream [65]. Cortisol was also shown to enhance in vitro the action of TH on fin ray resorption (phenomenon occurring during flatfish metamorphosis) in flounder[27]. [SEP] Justify:

Output: The text provided focuses on the role of cortisol and thyroid hormones in the metamorphosis of flatfish, specifically discussing their effects and interactions. It does not mention insects or the process of complete metamorphosis in insects. Therefore, it is irrelevant to the claim about insects undergoing complete metamorphosis.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: to stroke, we implanted Wistar rats (n = 14) with pineal microdialysis probes and determined baseline melatonin secretion patterns. Since this is an outbred population, we observed a range of MT-on and melatonin offset (MT-off) times (Figure 1), defined by the interval between time of dark onset and time when the melatonin rhythm reached 20% of its nightly maximum. The variation of MT-on and MT-off within the cohort has been described previously [19]. Melatonin duration was calculated as the time difference between MT-on and MT-off. Although there was variation within the cohort of circadian profiles, individual rats prior to stroke showed virtually no day-to-day variation in MT-on, MT-off, or melatonin duration over more than three days of baseline observation, as described previously (14). Figure 1 Baseline melatonin profiles for rats prior to MCAo. Melatonin profiles were obtained for all animals prior to MCAo to determine baseline timing. Measurements were made for up to six days, and, in all cases, the daily melatonin timing was stable. Therefore, only a single day's tracing of each individual is shown in this composite illustration. Animals exhibit a wide range of timing profiles. There is a broader range of MT-on times compared to MT-off times. The melatonin duration is defined as the time between the MT-on and MT-off. The MT-on is defined as the time when melatonin rises to 20% of the daily maximum (set to 100%). The MT-off is defined as the time when the melatonin level falls to 20% of the daily maximum. The gray shaded area represents time of lights off. MCAo surgery was then performed on these animals. All surgeries were initiated between 12:15 h and 14:34 h during the day. Rats were then placed back on microdialysis to measure post-surgical circadian melatonin profiles. We could not record melatonin secretion from one animal, and it was excluded from analysis. Two animals did not show changes in melatonin secretion after MCAo. Eleven of the remaining 13 rats exhibited temporal shifts in melatonin secretion, beginning with the first night after MCAo (Day 0); a representative rat is shown in Figure 2A. These rats demonstrated clear brain infarctions of the cortex and basal ganglia, demonstrated by TTC staining (Figure 2A). [SEP] Justify:

Output: The text corroborates the claim by detailing an experiment where Wistar rats exhibited changes in circadian melatonin profiles after a stroke (MCAo). The variation in melatonin secretion patterns, particularly the temporal shifts noted in 11 out of 13 rats after the surgery, indicates disruption of circadian rhythms, which can be associated with health issues such as stroke-induced effects on the brain.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: In addition, no human C-peptides were detected in the supernatant of dgHPSCs-ERRγ and dgHPSCs-Insulin, respectively. To our knowledge, this is the first time to discover that human pluripotent stem cells overexpression ERRγ can efficiently synthesize and secrete human insulin at the pluripotent stem cell state, and do not need to differentiate into β-like cells. Transplantation of dgHPSCs-ERRγ can replace exogenous insulin administration, efficiently reduce the blood glucose levels and increase C-peptide secretion The tested results were showed in Table 3, and the patient did twice tests at January 19th of 2018 before receiving stem cell transplantation and at March 7th of 2018 after five times transplantations, respectively. The patient stopped daily insulin injection at January 19th of 2018, and went to the of to test his fasting blood glucose, glycosylated haemoglobin, fasting insulin, and fasting C-peptide. The results showed that, without the exogenous insulin administration, the patient’s fasting blood glucose gradually increased from around 7mmol/L (with daily insulin injection) up to 9. 46mmol/L in the morning of January 19th of 2018 (at January 18th of 2018, the patient injected insulin twice, morning and night, 12U, respectively). With daily injection of insulin, his glycosylated hemoglubin value was 6. 0%, and the fasting insulin and C-peptide were 59. 88pmol/L and 0. 584nmol/L, respectively (Table 2). After receiving dgHPSCs-ERRγ cell transplantations, the patient could totally give up exogenous insulin administration, and maintained his fasting glucose level around 11. 23mmol/L (compared with his fasting glucose levels above 13mmol/L in 2013 before treatment with insulin administration), and his glycosylated hemoglubin value about 8. 3%, respectively. Surprisingly, his fasting C-peptide levels increased from 0. 584nmol/L up to 0. 890nmol/L, which is the hallmark for the repairing of the functions of pancreatic β cells. [SEP] Justify:

Output: The text contrasts the claim by detailing a case study involving human pluripotent stem cells that replaced insulin therapy in a patient rather than curing all injuries or regenerating all types of tissue instantly. It underscores the gradual improvement in the patient’s condition, indicating that while stem cells have a beneficial effect, they do not achieve immediate or universal tissue regeneration.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: It has also been shown that cortisol regulates local T3 bioavailability in the juvenile sole via regulation of deiodinase 2 in an organ-specific manner [66]. On the antagonistic side, it has been shown that experimentally induced hyperthyroidism in common carp decreases cortisol levels[67], whereas cortisol exposure decreases TH levels in European eel [68]. Given this scattered evidence, the existence of a crosstalk active during teleost larval development and metamorphosis has never been formally demonstrated. The results we obtained in grouper are clearly indicating that HPI axis is activated during both early development and metamorphosis and that cortisol synthesis is activated during early development. This may suggest that in some aspect, cortisol synthesis could work in concert with TH, as has been shown in several different contexts in amphibians [25], but functional experiments need to be conducted to confirm this hypothesis. ” In the revised manuscript, we have also added the interesting case of the Senegal sole mentioned by the reviewer. In the last revision, we had also added that our results “brought a first insight into the potential role of corticoids in the metamorphosis of E. malabaricus and call for functional experiments directly testing a possible synergy” meaning that we clearly acknowledge that we are only revealing a hypothesis that remains to be tested. We later follow up with a discussion about the most novel observation and focus of our study, the increase in THs and cortisol during early development, which was unexpected and very intriguing. Again, these results suggest that there might be a link between the two, as has been shown in amphibians. This is typically the kind of results that should encourage more investigations into other fish species. Indeed, this has been pointed out by other authors and in particular by (probably the foremost expert on this topic) in Crespi and Denver 2012: “Elevation in HPA/I axis activity has been described prior to Metamorphosis in amphibians and fish, birth in mammals (reviewed in Crespi & Denver 2005a; Wada 2008)”. B. Denver also adds that: “Experiments in which GCs were elevated prior to metamorphosis or prior to hatching or birth (e. g. Weiss, Johnston & Moore 2007) or inhibited by treatments with GC synthesis blockers (e. g. metyrapone) or receptor antagonists (e. g. [SEP] Justify:

Output: The text does not address the claim about insects undergoing complete metamorphosis. Instead, it discusses the role of cortisol in the metamorphosis of fish, particularly in terms of hormonal regulation and development processes. The focus is on teleosts and amphibians, with no information provided about insects or their metamorphic stages.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Figure 2 Effect of MCAo on rhythmic secretion of melatonin. Melatonin secretion was measured in animals before and after surgery. Representative animals undergoing MCAo (A) and sham surgery (B) are shown. Tracings represent daily melatonin profiles superimposed upon the time of the day, with the gray shaded area representing lights off. Each day is demonstrated in a different color. D-2 and D-1 are two and one day before surgery. D0 is the day of the surgery, which was performed in the daytime. Days one to four (D1 to D4) are post-operative days. MCAo caused an advance of MT-on that persisted through four days of monitoring (A). MCAo slightly delayed the MT-off. Due to technical reasons, the data for the third postoperative day was lost (D3*). TTC stained brain sections are displayed to demonstrate that MCAo induces cortical and subcortical infarction. Sham surgery (B) did not affect MT-on or MT-off timing and did not cause brain infarction. We also performed sham MCAo (control) surgery on six rats that were analyzed by pineal microdialysis. These rats had pre-surgical melatonin profiles that were similar to the rats with MCAo. All six rats exhibited identical timing of melatonin secretion before and after control surgery; a representative animal is shown in Figure 2B; as expected, TTC staining of control brains showed no infarction. We examined the entire cohort of animals that exhibited melatonin shifts to attempt to identify trends in circadian behavior. Figure 3 shows the MT-on and MT-off profiles for this set of rats. Surprisingly, the pattern of circadian phase shifts in melatonin secretion showed a heterogenous amplitude and direction of change. In general, however, the MT-on shifts were more pronounced than MT-off shifts. The duration of melatonin secretion also exhibited significant differences after stroke in these animals (Figure 4). The changes in melatonin duration varied in direction and amplitude. When daily shifts of MT-on were averaged following stroke surgery (a measure of deviation from baseline – see methods), we observed a significant difference (p < 0. 02) between sham and MCAo treated animals (Figure 5). [SEP] Justify:

Output: The text corroborates the claim by providing evidence that disruption to normal patterns of melatonin secretion occurs after MCAo (Middle Cerebral Artery Occlusion), which suggests a disruption in circadian rhythms. The mention of 'MT-on shifts' and their changes indicate that the surgical procedure affected the normal circadian rhythm of melatonin production, thus supporting the claim that disruptions can lead to health issues.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: In addition, the daily monitoring of fingertip capillary blood glucose revealed that the effect of decreasing blood glucose by dgHPSCs-ERRγ cell transplantation could maintained at least for one and half months (Table 3). The exact duration of the effects of stem cell transplantations still needs to be determined further because the patient will take the second course of treatment using stem cell transplantation afterwards. The glucose challenge tests before and after stem cell transplantations did not show significant improvements both for insulin and C-peptide secretions (Table 2). These data demonstrated that transplantations of dgHPSCs-ERRγ cells could potentially replace exogenous insulin administration and restore the functions of the patient’s pancreatic β cells. The follow-up visit of the patient The patient reported that he had a transient fever after the transplantations of about 1x108 cells, and the body temperature reached up to 37°C. The fever faded away next day. 26 of 2018, about 50 days after the last transplantation, the patient described that he felt stronger physically, and his knees felt much better, he could exercise much longer than before and did not feel tired. His gross amount of food per meal did not change, but his body weight decreased slightly. In a word, his overall physical conditions were improved obviously. 2 diabetes is an increasing threat to human health span, and diabetes incidence and prevalence increase with the age. Approximately 25. 9% of Americans of 65 years or older have diabetes, whereas, 9. 3% of those in the general population. 3 In addition, diabetes is a major risk factor for premature onset of multiple age-related conditions, including renal dysfunction, cardiovascular disease, stroke, impaired wound healing, infection, depression, and cognitive decline. 25–27 Although, almost one hundred years ago, Banting et al. ,1 confirmed that administration of exogenous insulin can decrease blood glucose levels and improve the symptoms of diabetes, the administration of exogenous insulin cannot maintain blood glucose levels within the narrow physiological range and further protect from development of various diabetic complications, because normal pancreatic β cells adjust insulin secretion continually in response to varying blood glucose levels. 2 Therefore, to develop novel strategies for diabetes treatment to restore the normal functions of pancreatic β cells is critical to finally cure diabetes and protect from diabetic complications development. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and current understanding of stem cell transplantation, particularly in relation to its effects on diabetes. It highlights that while there have been improvements in the patient's conditions following stem cell treatment, such as reduced blood glucose levels and enhanced physical abilities, the effects are not instant nor do they cure all injuries. The text points out that the duration of effects and need for further treatment are still under evaluation, which contradicts the claim that stem cells can regenerate any type of tissue instantly.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: RU486, Glennemeir & Denver 2002) demonstrate that GCs play a causal role in precipitating these life-history transitions (also reviewed in Crespi & Denver 2005a; Wada 2008). ” We believe the reviewer will be convinced by these elements coming from a colleague unanimously respected in the field. Furthermore, the authors need to recognise that the transcriptomic analysis is whole-body and that HPA axis genes are upregulated, which does not mean they are involved in regulating the HPT axis. The authors do not show that in thyrotrophs, any CRH receptor is expressed or in any other HPT axis-relevant cells and that changes in these genes correlate with changes in TSH expression. An in-situ hybridisation experiment showing co-expression on thyrotrophs of HPA genes and TSH could be a good start. However, the best scenario would be conducting cortisol treatment experiments to see if this hormone affects grouper metamorphosis. We agree that functional experiments are needed to validate our hypothesis. As the early peaks of expression levels observed for many genes were very intriguing for us, we did carry out thyroid hormones and goitrogenic treatment on young grouper larvae to test their effect on the morphological changes. Unfortunately, such experiments, already tricky on metamorphosing larvae, are even more risky on such tiny individuals just after hatching and we encountered high mortality rates. We must add that because we cannot establish a full grouper life cycle under lab conditions, we have done these experiments in the context of a commercial husbandry system in Japan, which while excellent limits the scope of possible experiments. We were thus not able to provide functional validation of our hypothesis. Such experiments will be a full project in itself, requiring setting up a rearing system suitable for both larval survival and economical constraints related to drug treatments. We were further limited by the spawning times of the grouper in the operational aquaculture farm, which are limited to a short time during each year. So even if we strongly agree with the necessity of conducting such experiments, we think that this is not in the scope of the present paper, but something future research can explore. High TSH and Tg levels usually parallel whole-body TH levels during teleost metamorphosis. [SEP] Justify:

Output: The text does not address the claim regarding the complete metamorphosis of insects. Instead, it discusses hormone effects and experimental approaches related to metamorphosis in grouper larvae, without any reference to insects or their metamorphic processes. Therefore, it is deemed irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: However, in animals for which we had daily data for extended periods, the MT-on and melatonin duration demonstrate highly dynamic day-to-day changes after stroke (Figures 8A and 8B); the change in MT-on and melatonin duration from day-to-day exhibited an alternating pattern, seeming to oscillate after stroke, albeit with progressively decreasing amplitude. The waning of day-to-day changes suggests that over time, the melatonin onset and duration are reaching equilibrium at a new set point. As on the first day after MCAo, MT-on and melatonin duration changes over the course of a few days correlate well with each other, indicating that the main determinant of melatonin duration changes after stroke is the MT-on shift (Figure 8C). Figure 8 Day to day changes in MT parameters after stroke. The day-to-day changes in MT-on and melatonin duration were defined as the change in melatonin timing compared to the time on the previous day. As expected, on Day -1, there is no shift since the melatonin rhythm is stable. However, on Day 0 (the day of the stroke) there is a change in the melatonin timing compared to before stroke. Only five animals, represented by different colors, were used for this analysis. Other animals in the study could not be used because of gaps in data. (A) MT-on changes markedly in most animals from day-to-day. In all animals, there is a remarkable oscillation of the daily changes in melatonin timing. In general, the amplitude of the oscillation decreases over time. (B) A similar trend is seen with the daily change in melatonin duration. (C) There is a strong relationship between the daily shift in MT-on and melatonin duration among most animals. The r2 coefficients (for each animal) were: 0. 85 (ID2658), 0. 56 (ID2833), 0. 15 (ID2839), 0. 92 (ID2892), and 0. 99 (ID2900). To determine whether circadian melatonin shifts were related to the degree of infarction, we computed the area of brain infarction using established morphometric methods. The range in infarction volume was typical of stroke studies (30% +/-15%). [SEP] Justify:

Output: The text corroborates the claim as it discusses the changes in melatonin timing and duration after a stroke, indicating an alteration in circadian rhythms. The mention of 'day-to-day changes in MT-on and melatonin duration' reflects how the circadian rhythm has been disrupted due to the stroke, supporting the idea that such disruptions are significant and can relate to health conditions.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: To date, different protocols are reported for in vitro differentiation and production of pancreatic β cells from hESCs and hiPSCs. Transplantations of these β cells produced can decrease the blood glucose levels of the animal models, and elongate their life spans. Although these results are encouraging and promising, these protocols are complicated and time consuming. 4–16 Worth of particular note, to our knowledge, there are no successful reports for clinically treatment of human diabetes patients using in vitro differentiated pancreatic β cells thus far. ERRγ is a master regulator of β cell maturation in vivo, and in vitro overexpression of ERRγ in human iPSC-derived β-like cells can give rise to functional and transplantable glucose-responsive cells capable of restoring glucose hemeostasis in type 1 diabetic mouse models. More importantly, these transplanted β-like cells can control blood glucose levels in recipient mice chronically up to 56 days. 16 Surprisingly, we found that our transduced dgHPSCs-ERRγ cells could secrete insulin into cell culture supernatant, and the concentration of secreted insulin in the supernatant was 30. 84µIU/ml. Since our transduction format was performed in 50ml volume, in theory, our transduced cells could continually secrete about 1,542µIU insulin into the recipient blood after intravenous transplantation. Furthermore, we found that the patient’s fasting blood C-peptide is 0. 890nmol/L after stem cell transplantations, much higher than 0. 584nmol/L before those transplantations. Consequently, the fasting blood insulin concentration is 53. 06pmol/L after transplantations, which is slightly lower than 59. 88pmol/L before transplantations, with the exogenous insulin injection of 24IU daily before the test. These data demonstrated that the transplantation of dgHPSCs-ERRγ cells not only can decrease the blood glucose levels, but also increase the secretion of C-peptide by the pancreatic β cells, which is the hallmark for the improvement of the β cells functions. Therefore, we believe that the transplanted dgHPSCs-ERRγ cells can potentially differentiate into functional pancreatic β cells and further restore the injured patient’s pancreatic β cell’s normal functions. [SEP] Justify:

Output: The text contrasts the claim by highlighting that while stem cell transplantation shows promise in specific contexts, such as differentiating into pancreatic β cells to manage diabetes, these processes are complicated and time-consuming. Specifically, it notes, 'these protocols are complicated and time consuming' and 'to our knowledge, there are no successful reports for clinically treatment of human diabetes patients using in vitro differentiated pancreatic β cells thus far.' This demonstrates that the ability of stem cells is not instantaneous, and there are significant limitations in their application for curing injuries.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: However, in this study, high Tg expression levels are only achieved at the juvenile stage, whereas high TSH is achieved at D32, and at the juvenile stage, they are already at their lowest levels. This is exactly our point. We observe two peaks in TSH expression, one at D3 and one at D32. The peak at D3 coincides with high thyroid hormone levels on the same day, and while we have not measured TH at D32, existing literature shows that there is a peak in TH during that time (e. g. , de Jesus et al. , 1998). Similarly, there is a small peak of Tg at D3. Our manuscript focused more on the upregulation of these genes at D3, which has not been reported before in the literature and raised the question of the role of TH so early in the larval development, outside of the metamorphosis period. Regarding the respective levels of TSH and Tg, we first would like to add that their respective order of appearance before metamorphosis (TSH at D32, Tg after) is consistent with what we would expect. We agree however that the strong increase of Tg and TPO expression is later than expected. Therefore, we have added the following sentence in lines 212 to 216: “The respective order of appearance of TSH and Tg (TSH at D32, Tg after) is consistent with what we would expect but a bit later than expected given the morphologicl transformation. It would be interesting to revisit this in a future series of experiments, with tighter temporal sampling to study how gene expression and morphological transformation aligned. “. It is very difficult to conclude anything with the TH and cortisol levels measurements. The authors only measured up until D10, whereas they argue that metamorphosis occurs at D32. In this way, these measurements could be more helpful if they focus on the correct developmental time. The data is irrelevant to their hypothesis. [SEP] Justify:

Output: The text does not address the claim about insects undergoing complete metamorphosis or the processes involved in larval stages. Instead, it discusses gene expression levels and timing in relation to thyroid hormone during the development of a juvenile stage. As such, it does not provide relevant information regarding metamorphosis and is therefore considered irrelevant.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: We could not identify a correlation between the degree of damage and either the direction or the amplitude of initial changes in MT-on, MT-off, and melatonin duration (Figure 9). Figure 9 Infarct volume and its relationship to shift in MT timing. Infarct volumes for all animals undergoing MCAo were computed. Each rat's infarct volume was plotted against the Day 0 shift in MT-on, melatonin duration, or MT-off relative to the baseline time before stroke. There was no linear relationship between infarct volume and any of the quantitative measures of circadian changes. The r2 values are shown; no relationship was found. Melatonin production in the pineal gland is controlled by a number of brain structures that include the SCN, paraventricular nucleus of the hypothalamus (PVN), and intermediolateral nucleus of the spinal cord (IML). In addition, the thalamic intergeniculate leaflet (IGL) [20] modulates SCN activity, which may affect melatonin output. Additionally, structures such as caudate putaman (CPu) and parietal cortex are involved in locomotor rhythm generation that can be dissociated from the SCN signals [21], and may be affected in animals after stroke. To determine whether specific regions affected by MCAo were responsible for melatonin rhythm disruption, we examined lesion sites of MCAo-treated animals. Of the animals that exhibited shifts in melatonin rhythms, only one showed injury near the SCN and only three animals showed infarctions of the IGL. None of the animals had injury to the PVN or IML. This indicates that injury to these structures cannot account for the change in melatonin timing after stroke. On the other hand, all animals had significant injury to the CPu, and all but two animals had cortical injury. Thus, CPu stroke is sufficient by itself to disrupt normal melatonin rhythms. is the first study to our knowledge that demonstrates an effect of stroke on diurnal melatonin secretion in experimental animals. Our experiments unequivocally demonstrate that ischemic strokes in rats disrupt the timing of melatonin onset and/or offset, which are the most consistent and direct markers of circadian timing. We also demonstrate that pineal microdialysis is a highly sensitive method for the study of modulation of the circadian pacemaker by disease states. [SEP] Justify:

Output: The text corroborates the claim by providing evidence that ischemic strokes in rats disrupt the timing of melatonin secretion, which is a direct marker of circadian timing. The statement 'Our experiments unequivocally demonstrate that ischemic strokes in rats disrupt the timing of melatonin onset and/or offset, which are the most consistent and direct markers of circadian timing' supports the notion that disruption of circadian rhythms can lead to health issues.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Although the patient’s blood glucose, C-peptide and glycosylated haemoglobin levels are still higher than normal physiological range, with continued transplantation of these stem cells, it is very promising to totally restore the normal functions of pancreatic β cells, and effectively cure type 2 diabetes and possibly prevent and reverse diabetic complications. There are two milestone works in differentiating hESCs/hiPSCs into functional pancreatic β cells in vitro by using 11 different factors or overexpressing ERRγ, respectively. 4,16 The produced functional adult pancreatic β-like cells share the common characteristics with bona fide pancreatic β cells, which include: 1) expressing markers found in mature β cells; 2) fluxing Ca2+ in response to glucose; 3) packaging insulin into secretory granules; 4) secreting quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro; 5) secreting human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner; 6) transplantation of these cells ameliorates the hyperglucemia in diabetic mice. 4,16 Compared with these two important works, our strategy reported here have the following advantages. Firstly, our method can directly produce and secrete human insulin into the patient blood without the use of the complicated and time-consuming in vitro differentiation procedure. Secondly, our method can reduce the patient’s blood glucose levels and stop exogenous insulin administration immediately after transplantation. In addition, our method can improve the patient’s symptoms physically and mentally, not only by decreasing the glucose levels and improving glucose metabolism, but, more importantly, also by repairing the damaged tissues and organs, and further preventing the development of diabetic complications and even reversing the existed complications potentially. Furthermore, in our strategy, we use directly generated human pluripotent stem cells derived hADSCs without any genetic modifications, therefore, our stem cells are much safer than other reports. 4–16 Finally, we directly use our strategy to treat volunteered type 2 diabetes patient, and to our knowledge, this is the first report to directly use human pluripotent stem cells overexpressing ERRγ to treat human diabetes. As for the physical and mental improvements of the patient after stem cell transplantations, it is beyond the words to describe the overall beneficial effects, including the strengthened muscles and the knees, and the vitality of the patient. [SEP] Justify:

Output: The text contrasts the claim by clarifying the limitations of stem cell therapy. While it discusses the potential of stem cells to restore pancreatic β cells and improve conditions like type 2 diabetes, it emphasizes that these results are not immediate nor universal for all injuries. The details of the ongoing process needed for stem cells to reach a functional state, along with the reference to specific factors needed for differentiation, suggest that stem cells do not regenerate any tissue instantly, as implied by the claim.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: We respectfully disagree with the reviewer, considering that 1) TH levels have already been investigated in groupers coinciding with pigmentation changes and fin rays resorption (Figure 4 in de Jesus et al, 1998), 2) there is also evidence in numerous fish species that TH level increase is concomitant with increase of TH related genes, and 3) we observed in our data an increase in the expression of TH related genes as well as pigmentation changes and fin rays resorption. Based on our experience in fish metamorphosis and the literature we can say confidently that those observations indicate that metamorphosis is occurring between D32 and the juvenile stage. This clearly shows that our inference is correct. Additionally, we would like to reemphasize that from our experience in several fish species transcriptomic data are more robust and precise than hormone measurements. However, as we were surprised by the activation of TH and corticoid pathway genes very early in the larval development (at D3), which is clearly outside of the metamorphosis period, we decided to measure TH and cortisol levels during this period of time to determine if whether or not there this surprising early activation was indeed corresponding to an increase in both TH and cortisol. As such observation has never been made in other teleost species (to our knowledge), and as we were wondering if gene activation was accompanied by hormonal increase, the measurements we did for TH and cortisol between D1 and D10 are relevant. In order to clarify our message further, we have changed some of the mentions of “metamorphosis” to “larval development” throughout the manuscript and added other improvements to avoid any confusion between the two periods we are studying: early larval development (between D1 and D10) and metamorphosis (between D32 and juvenile stage). Moreover, as stated in the previous review, a classical sign of teleost metamorphosis is the upregulation of TSHb and Tg, which does not occur at D32 therefore, it is very hard for me to accept that this is the metamorphic stage. With the lack of TH measurements, I cannot agree with the authors. I think this has to be toned down and made clear in the manuscript that D32 might be a putative metamorphic climax but that several aspects of biology work against it. Moreover, in D10, the authors show the highest cortisol level and lowest T4 and T3 levels. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the metamorphosis of fish, particularly concerning thyroid hormone levels and gene expression during different developmental stages. It does not mention insects or the specific process of complete metamorphosis as it pertains to them.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Our prospective study design using pineal microdialysis overcomes methodological limitations encountered in human studies and in animal studies that utilize other circadian markers. Human studies are confounded by the inability to measure pre-stroke circadian parameters, heterogeneity of stroke location, pre-existing medical conditions, medications, neurological disability and the unavoidable environmental variation required for medical care. As discussed above, melatonin is superior to wheel running activity, core body temperature, and heart rate as a marker for animal circadian timing; in addition, melatonin is commonly used as a clock marker in human studies [15]. In agreement with the human study by Beloosesky et al[10], we show that in the acute phase of stroke, melatonin rhythms are still present, but that the phase of melatonin rhythms is shifted. Importantly, our experiments give us added temporal resolution to quantify circadian changes and to observe unique patterns of clock plasticity after stroke. Our ability to examine individual melatonin profiles reveals that there is dramatic heterogeneity in the response of melatonin after stroke that cannot be detected in human cohort observations. We detected oscillatory behaviors in the MT-on alteration and the melatonin duration change, which suggests that a neuronal mechanism of non-pineal origin could be responsible for reestablishing the steady state after ischemic stress. The oscillatory melatonin rhythm demonstrates that in the days after stroke, the circadian rhythm is unstable. However, the oscillations dampen over days, suggesting that the rhythm will ultimately reach an equilibrium state with a stable melatonin rhythm similar to the pre-stroke rhythm. Our finding that stroke induces changes in melatonin secretion for several days differs from the previous human studies [10]; we believe that our results may be due to our ability to sample melatonin with higher temporal resolution (20 minute vs. 240 minute increments) directly from the pineal gland (versus a urinary metabolite). We were surprised by the heterogeneity of melatonin responses to stroke. Our data shows that the heterogeneity is not related to a pre-existing circadian phenotype and is not a result of differential damage to the hypothalamus, which is spared in this model of stroke. There may be several explanations for the heterogeneous effects of stroke on circadian rhythms. We speculate that diffusely distributed cortical and subcortical neurons exert distinct effects on different sets of hypothalamic neurons. [SEP] Justify:

Output: The text corroborates the claim by discussing how changes in melatonin secretion following a stroke result in unstable circadian rhythms. It explains that the acute phase after a stroke leads to dramatic alterations in melatonin rhythms, which in turn indicates disruptions in circadian rhythms. Moreover, it suggests that these oscillations in melatonin and inconsistencies in circadian patterns may lead to health issues associated with stroke recovery, supporting the idea that disturbances in circadian rhythms can indeed be linked to health consequences.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: All these changes indicate the positive effects of stem cell therapy. Therefore, our preliminary investigations laid an important foundation for stem cell therapy for human diabetes diseases. work reported here demonstrated the following conclusions: Human pluripotent stem cells can be generated directly from human adipose-derived stem cells without the need of any genetic modifications. Human pluripotent stem cells overexpressing ERRγ can produce and secrete human insulin into cell culture medium in vitro immediately after transduction and do not need to differentiate into functional pancreatic β-like cells. Transplantation of these stem cells can reduce patient’s blood glucose levels, increase C-peptide levels, and replace exogenous insulin administrations. Transplantation of these cells can improve the patient symptoms greatly physically and mentally. Our strategy reported here potentially can prevent the development of diabetic complications and even reverse the existed complications with more transplantations approval and consent to participate Described in Statement of ethical approval section. Consent for publication All the participated patients were consent for the publication of this work. Availability of supporting data The datasets generated and/or analysed during the current study are not publicly available due to the protection of the confidential information of the participated patients but are available from the corresponding author on reasonable request. Author’s contribution T W and G Z instructed and supervised the whole experimental and clinical work. X W and X C performed the vector construction. B Z and L Z charged the lentiviral transduction. and X Y did the cell culture. and Y M worked on the clinical treatments of the cells. All the authors discussed, wrote, read and approved the final manuscripts. authors wish to thank the nurses in our hospital for their help and caring of the patients during the clinical treatments. Conflict of interest The author declares they have no competing interests. 146. Minami K, Seino S. Current status of regeneration of pancreatic β-cells. J Diabetes Investig. 2013;4(2):131–141. Cellular senescence in Type 2 Diabetes: a therapeutic opportunity. Diabetes. 2015;64(7):2289–2298. ürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014;159(2):428–439. Cell aggregation optimizes the differentiation of human ESCs and iPSCs into pancreatic bud-like progenitor cells. Res. 2015;14(2):185–197. [SEP] Justify:

Output: The text contrasts the claim by highlighting that while stem cells can have positive therapeutic effects, the processes described are not instant. The text discusses how human pluripotent stem cells can potentially improve the symptoms of diabetes rather than regenerate any type of tissue instantly and cure all injuries as stated in the claim. The mention of the need for transplantation and the conditions under which these stem cells operate indicates that the healing process is complex and not instant.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: As we may have arrived at the explanation of this hypothesis too rapidly without setting up the context well enough, we have made changes to the introduction and discussion. Even though this is a solid technical paper and the data obtained is excellent, the conclusions drawn by the authors are not supported by their data, and at least hormonal levels should be present in parallel to the transcriptomic data. Furthermore, toning down some affirmations or even considering the different hypotheses available that are different from the ones suggested would be very positive. We thank the reviewer for acknowledging the solidity of the method of our paper and the quality of the results. We agree that there were several parts where our message was unclear. We have addressed these points in the revised version of the manuscript to make sure there is no more confusion between the two distinct periods we studied in this paper (early larval development and metamorphosis). We also made sure that our claims about TH/corticoids interaction during both periods remain hypothetical as we cannot yet, despite trials, sustain them with functional experiment. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the context and methodological issues of a scientific paper without mentioning the process of complete metamorphosis in insects or any relevant details regarding larval stages.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Broadly distributed circadian controlling neurons may be responsible for the highly variable changes in melatonin secretion due to the stochastic nature of stroke injury, which is in the same general territory, but varies subtly from animal to animal. Alternatively, since stroke causes massive releases of glutamate into the brain, it is possible that glutamate diffusion into the hypothalamus results in the disruption of hypothalamic clock neurons. The regional spread and timing of glutamate release into the hypothalamus may differ between individuals, resulting in individual-specific patterns of circadian disruption. It is noteworthy that Wang et al. [5] described abnormalities in the circadian rhythms of stroke patients which were quantitatively dependent on the distance of the infarct from the hypothalamus. Finally, novel genetic polymorphisms in outbred Wistar rats may impact the responses of SCN neurons to cortical and basal ganglial injury. In addition to the and IML are important brain structures controlling melatonin production. Only one rat (ID2658) showed lesion near the SCN, whereas none of the MCAo treated rats showed detectable injury in the PVN region. MCAo surgery is known to spare the spinal cord where IML is found. Thus, direct neuronal defects in melatonin rhythm-generating machinery in the brain can be ruled out as the cause of the melatonin rhythm disruptions seen in our studies. Since brain structures such as IGL [20] and Raphe nuclei send projections to the SCN, injury in these regions could potentially affect melatonin output. Upon careful examination, however, none of the rats had lesions in the Raphe nuclei and only three rats (ID2658, ID2639, and ID2896) showed lesion near the IGL. There were no common features of melatonin shifts in rats with IGL lesions compared to those with intact IGL. Previous study also demonstrated involvement of CPu and parietal cortex in locomotor rhythm regulation that can be dissociated from the SCN [21]. In the same study, melatonin rhythms were shown to be phase aligned with the SCN clock gene expression and were not affected by the free-running locomotor rhythms induced by drug treatment [21]. MCAo treated rats in our cohort showed lesions in both CPu (11 of 11 rats) and parietal cortex (8 of 11), two structures that are most consistently affected in this model of stroke. [SEP] Justify:

Output: The text corroborates the claim by discussing how injuries such as strokes can lead to disruptions in circadian rhythms. It mentions how alterations in melatonin secretion and circadian rhythm abnormalities in stroke patients are connected to various neurological mechanisms. Specifically, it notes that circadian disruptions can arise due to the uptick of glutamate in the brain and its effects on hypothalamic clock neurons, which play a crucial role in regulating circadian rhythms. Thus, the findings highlight that the disruption of circadian rhythms, as seen in stroke cases, can indeed lead to health issues.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: D' Production of pancreatic hormone expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006;24(11):1392–1401. Stage-specific signaling through TGF-β family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development. 2011;138(5):861–871. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008;26(4):443–452. Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nat Biotechnol. 2011;29(8):750–756. Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes. 2012;61(8):2016–2029. Enrichment of human embryonic stem cell derived NKX6. 1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. Stem Cells. 2013;31(11):2432–2442. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014;32(11):1121–1133. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS One. 2012;7(5):e37004. Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice. Diabetologia. 2013;56(9):1987–1998. Role of BMP signalling in pancreatic progenitor differentiation from human embryonic stem cells. Rev. 2013;9(5):569–577. ERRγ is required for the metabolic maturation of therapeutically functional glucose-responsive β cells. Cell Metab. 2016;23(4):622–634. Human adipose tissue is a source of multipotent stem cells. Cell. 2002;13(12):4279–4295. Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. . 106(37):15720–1525. [SEP] Justify:

Output: The text contrasts the claim by providing a detailed account of research on pancreatic cells derived from human embryonic stem cells, which does not imply that stem cells can regenerate any type of tissue instantly. Instead, it outlines specific studies showing that such stem cells can generate insulin-secreting cells to treat diabetes, indicating a specialized and not instantaneous regenerative capacity.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: The circuitry of the MB is known at the EM level for both the larva (Eichler et al. , 2017) and adult (Zheng et al. , 2018; Li et al. , 2020). The core of the MB is a set of hundreds (larva) to thousands (adult) of small neurons called Kenyon cells (Figure 2A and B). Their dendrites project into calyx neuropil, which receives primarily olfactory input via antennal lobe projection neurons, and into accessory calyx neuropils that receive visual and thermal information (Li et al. , 2020; Eichler et al. , 2017). The bundled axons of the Kenyon cells extend down the peduncle and into the vertical and medial lobes. The mature, adult MB has three major classes of Kenyon cells: the γ neurons made during embryogenesis and early larval life, the α'β' cells generated late in larval life, and the αβneurons born through early and mid-metamorphosis (Lee et al. , 1999). There is considerable complexity within each of these major Kenyon cell classes (Eichler et al. , 2017; Li et al. , 2020), but overall, their axons form three medial lobes (γ, β', β) and two vertical lobes (α, α') (Figure 2B). Unlike the adult, the MB of the larva contains only modified γ Kenyon cells whose axons form a vertical and a medial lobe (Figure 2A). Figure 2 Download asset Open asset The organization and development of the larval and adult mushroom bodies (MBs). (A) The larval MB has a core of γ Kenyon neurons whose dendrites project to the calyx (CA) neuropil and whose axons extend through the peduncle and bifurcate into a vertical and medial lobe. Projections from three clusters of aminergic neurons, the 1, and PAM clusters divide the axon array into 10 computational compartments: IP and LP: intermediate and lower peduncle; LA: lateral 2. pptx Download elife-80594-fig2-data1-v2. [SEP] Justify:

Output: The text does not directly address the claim about insects and complete metamorphosis. Instead, it focuses on the anatomical and cellular details of the mushroom bodies (MBs) in larvae and adults, specifically referencing Kenyon cells and their structures during different life stages. While it mentions larva and adult stages, it does not confirm or refute the claim regarding the metamorphosis process.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: These results suggest that stroke may unmask interactions between the parietal/CPu locomotor rhythm generating system and other SCN-driven rhythms by yet unidentified mechanisms. Our studies confirm the influence of the cortex and basal ganglia on circadian rhythms. In fact, extrahypothalamic mechanisms of circadian disruption have been described in preclinical models of Huntington's disease [22] and Alzheimer's disease [23]. Thus, uncovering the mechanisms of how brain dysfunction outside the retinohypothalamic pathway impacts circadian timekeeping may ultimately lead to strategies to reduce the morbidity of many neurological disorders. Our model of measuring pineal melatonin after stroke may be useful in deciphering these mechanisms, since it is quantitative and capable of detecting longitudinal changes in the same animals. Competing interests The authors declare that they have no competing interests. Authors' contributions HM designed and performed stroke surgery and performed analysis of circadian and stroke data. TL performed microdialysis surgery and melatonin measurements and analyzed melatonin data. JB directed the melatonin measurement studies, analyzed microdialysis data, edited the manuscript, and designed the figures. MMW directed the stroke experiments, analyzed data, and wrote the manuscript. All authors read and approved the final version of this 1. [PubMed] DOI: and Hirata, K (2002). Alteration of circadian periodicity in core body temperatures of patients with acute stroke Neurosci 56: 221–222, [PubMed] DOI: Sander, D and Klingelhofer, J (1994). Changes of circadian blood pressure patterns after hemodynamic and thromboembolic brain infarction Stroke 25: 1730–1737. [PubMed] and Ibaragi, K (2002). Circadian variation of blood pressure and neurohumoral factors during the acute phase of stroke Hypertens 24: 109–114, [PubMed] DOI: and Tseng, YZ (1997). Abnormal circadian blood pressure changes in patients with acute cerebrovascular disorders J Assoc 96: 710–717. [PubMed] and Barreca, T (1994). Twenty-four-hour beta-endorphin secretory pattern in stroke patients Stroke 25: 2142–2145. [PubMed] Jovicic, A, Ivanisevic, V and Nikolajevic, R (1991). [SEP] Justify:

Output: The text corroborates the claim by discussing the influence of brain dysfunction on circadian rhythms, specifically noting that disruption of these rhythms may be linked to neurological disorders. It mentions 'extrahypothalamic mechanisms of circadian disruption' and the analysis of how brain dysfunction can impact 'circadian timekeeping,' indicating that disruptions in circadian rhythms due to health issues such as stroke could potentially lead to further morbidities.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: pptx Figure 2—source data 2 Examples of the adult anatomies of larval neurons DAN-c1 and DAN-d1 obtained by flip-switch-mediated immortalization of expression of lines MB586B and MB328B, respectively, late in larval life. Download elife-80594-fig2-data2-v2. pptx Figure 2—source data 3 Examples of the adult anatomy of larval neuron OAN-e1 obtained by flip-switch-mediated immortalization of expression of lines SS21716 and SS01958 late in larval life. Download elife-80594-fig2-data3-v2. pptx Figure 2—source data 4 Examples of the adult anatomies of larval neurons MBIN-l1 and DAN-f1 obtained by flip-switch-mediated immortalization of expression of stable spilt lines late in larval life. The anatomy of the adult form of MBIN-l1 was revealed using lines SS04484 and SS01624; that of DAN-f1 using lines MB065B and MB145B. Download elife-80594-fig2-data4-v2. pptx Figure 2—source data 5 Examples of the adult anatomies of larval neurons DAN-g1 and OAN-g1 obtained by flip-switch-mediated immortalization of expression of stable spilt lines late in larval life. The anatomy of the adult form of DAN-g1 was revealed using lines SS017164 and SS01755; that of OAN-g1 using lines SS20844 and SS4268. Download elife-80594-fig2-data5-v2. pptx Figure 2—source data 6 Table showing the success rate for maintaining expression of the various larval neurons through metamorphosis. Download elife-80594-fig2-data6-v2. xlsx The MB receives flows of sensory information through projection neurons to the calyx, but our study focused on the sets of MB input neurons (MBINs) and output neurons (MBONs) that innervate the peduncle and lobes (Figure 2A and B). [SEP] Justify:

Output: The text passes on the claim as it does not directly address the process of complete metamorphosis in insects or mention the transition through larval stages. It focuses on specific examples of adult anatomies of larval neurons and other technical details without discussing insect development stages.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Circadian variations of platelet aggregability and fibrinolytic activity in patients with ischemic stroke 64: 487–491, [PubMed] DOI: Culebras, A and Miller, M (1984). Dissociated patterns of nocturnal prolactin, cortisol, and growth hormone secretion after stroke Neurology 34: 631–636. [PubMed] and Xie, BL (1990). Acute cerebral hemorrhage changes the nocturnal surge of plasma melatonin in humans J 9: 193–208, [PubMed] DOI: and Zisapel, N (2002). Melatonin rhythms in stroke patients 319: 103–106, [PubMed] DOI: Dall'Aglio, P (1999). Disruption of nocturnal melatonin rhythm and immunological involvement in ischaemic stroke patients Immunol 50: 228–231, [PubMed] DOI: and Bassetti, CL (2006). Sleep EEG changes after middle cerebral artery infarcts in mice: different effects of striatal and cortical lesions Sleep 29: 1339–1344. [PubMed] and Tomita, T (2001). Disturbance of circadian rhythm in heart rate, blood pressure and locomotive activity at the stroke-onset in malignant stroke-prone spontaneously hypertensive rats Pharmacol 85: 197–202, [PubMed] DOI: Borjigin, J and Liu, T (2008). Application of long-term microdialysis in circadian rhythm research Behav 90: 148–155, [PubMed] DOI: and Kronauer, RE (2002). Comparisons of the variability of three markers of the human circadian pacemaker J 17: 181–193, [PubMed] DOI: and Sack, RL (1999). The endogenous melatonin profile as a marker for circadian phase position J 14: 227–236, [PubMed] DOI: Memezawa, H, Smith, ML and Siesjo, BK (1992). Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats Stroke 23: 552–559. [PubMed] and Cummins, R (1989). Reversible middle cerebral artery occlusion without craniectomy in rats Stroke 20: 84–91. [PubMed] Liu, T and Borjigin, J (2006). [SEP] Justify:

Output: The text corroborates the claim by discussing various studies that demonstrate disruptions in circadian rhythms—such as alterations in melatonin levels and disturbances in sleep patterns—are associated with health issues, specifically in patients who have suffered from ischemic stroke and other cerebrovascular conditions. For example, it references the 'disruption of nocturnal melatonin rhythm' and its 'immunological involvement in ischaemic stroke patients,' indicating a link between circadian disruption and health complications.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Additionally, stem cell biology has become a growing interest of many medical researchers because stem cells have the capacity to renew themselves as well as differentiate multiple cell types [5]. In the skin, most stem cells are located within the hair follicle bulge [6]. Stem cells repair a wound by giving rise to daughter skin cells, which migrate to the epidermis [7]. These stem cells do not normally supply cells to the epidermis, but only do so after epidermal injury [7]. Severe burns are a highly common soft tissue injury that cause extensive damage to the skin. Severe burns often result in unsatisfactory functional and cosmetic healing [8]. They are a devastating trauma which requires specialized, immediate care [9]. Stem cell therapy is an indicated treatment for severe burns because of the potential for enhanced wound healing, replaced skin, and perfect skin regeneration [9]. Burns also present systemic effects such as inflammation, hypermetabolism and immunosuppression which may be combatted with stem cell therapy [9]. Stem cell therapy is a viable treatment because it is efficient, high-quality therapeutic treatment for skin burns that carries a potential to address systemic effects of burn injury such as hypermetabolism and inflammation [9]. There are three major pathways through which stem cells accelerate burn wound healing: granulation tissue formation, collagen deposition, and by inducing neo-angiogenesis. They modulate the inflammatory response and reduce the risk of infection. They can regenerate skin appendages and halt the zone of stasis in acute burn injury [10]. skin is the body’s largest organ, and it is quite complex. It not only serves as a barrier to the outside world, but also functions in immune inflammatory processes. The skin’s structure includes the epidermis, or top layer, the dermis, or middle layer, and most internally, there is subcutaneous fat. The epidermis is the outermost layer of the skin and it acts as a wall to restrict access to the inside of the body. It consists primarily of keratinocytes with tight connections to form the stratum corneum, a critical piece of the barrier of the epidermis. The basement membrane separates the dermis from the epidermis. It is comprised of a thin layer of extracellular matrix proteins. The dermis is a more flexible and elastic layer than the epidermis and is also made up of extracellular matrix proteins. [SEP] Justify:

Output: The text contrasts the claim by detailing the specific context in which stem cells operate, particularly in relation to skin injuries and burns. It emphasizes that stem cell therapy can enhance wound healing and skin regeneration, but does not support the notion that stem cells can regenerate any type of tissue instantly or cure all injuries. The description of stem cell functions in wound healing is specific to burn injuries and does not imply universal instant regeneration across all tissue types.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: In both larvae and adults, these neurons divide the lobes into non-overlapping compartments (Figure 2C) that have a common microcircuit motif (Figure 2D; Eichler et al. , 2017; Zheng et al. , 2018). Each compartment is defined by the axonal tuft of an aminergic input cell that synapses onto Kenyon cell axons and onto a dedicated MBON(s). cell axons synapse onto each other and the MBONs but also feed back onto the MBINs (Figure 2D). The majority of the MBINs are dopaminergic neurons (DANs) but a few are octopaminergic neurons (OANs). Most DANs come from two clusters, the protocerebral anterior medial (PAM) cluster, which primarily encodes reward, and the protocerebral posterior lateral 1 (PPL1) cluster, which mainly encodes punishment (Saumweber et al. , 2018; Cognigni et al. , 2018; Eichler et al. , 2017; Eschbach et al. , 2020). Depending on their compartment, the MBONs are cholinergic, GABAergic, or glutaminergic. Interestingly, stimulation of the MBONs from PPL1-supplied compartments generally evokes approach behavior while stimulation of those from PAM supplied compartments evokes avoidance (Owald et al. , 2015; Cognigni et al. , 2018). Consequently, pairing punishment with a particular odor reduces the drive on MBONs that promote attraction. Behavior is therefore guided by a balance of avoidance versus attractive influences and the inhibition of neurons mediating one behavior then favors the opposite behavioral state (Thum and Gerber, 2019; Cognigni et al. , 2018). The functions of some compartments, though, are complex because of extensive interconnections amongst MBONs and feedback from MBONs back to various MBINs (e. g. , Eschbach et al. , 2020; Li et al. , 2020). While serving similar functions of mediating associative learning, the larval and adult MB differ in a couple of ways. The larval MB has 10 compartments plus the calyx (Saumweber et al. , 2018; Eichler et al. , 2017), while the adult has 16 (Aso et al. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the functional differences in the mushroom body (MB) between larval and adult stages of insects, including details about neurons and behavior, without mentioning the process of complete metamorphosis or the transition through larval stages.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Journal of Circadian RhythmsStart SubmissionBecome a ReviewerReading: Metastasis of Promoted by Disruption due to Light/and its Prevention by in MiceDownloadPDF (US English)XML (US English)Alt. DisplayShareShareResearch 0. 3 % quercetin significantly inhibited distant lymph node metastasis, particularly metastasis to the iliac and kidney lymph nodes. Our results contribute to our understandings of the effects of the external light environment on breast cancer metastasis and provide a glimpse into potential protective effects of dietary quercetin on light/dark disturbance-induced metastasis. Keywords:light/dark shiftcircadian rhythmbreast cancerlymph node metastasisquercetinYear: 2021Page/10. 5334/jcr. 203Submitted on Nov 7, 2020Accepted on Jan 31, 2021Published on Feb 18, 20214. 0 1. mammalian circadian system controls various physiological functions including body temperature, hormone secretion, blood pressure, and sugar metabolism, and is affected by the master clock [1, 2, 3, 4, 5]. The master clock synchronizes the rhythm of peripheral clocks to the time of the external environment (i. e. , a 24-hour cycle) through stimulation by the light signal received by the eye [6, 7, 8]. In other words, the light environment surrounding mammals is an important input signal for controlling circadian rhythm. Clock genes controlling biological rhythms interact with each other, and each has its own circadian rhythm [9]. It has been reported that BMAL1, a clock gene, has an antitumor effect on ovarian cancer, colon cancer, and head and neck squamous cell carcinoma [10, 11, 12]. Another study showed that PER2 is associated with the development of breast cancer [13]. Night and shift workers are inevitably exposed to light at night. Our group previously reported that nocturnal light exposure disturbed the regular expression rhythms of clock genes such as PER2, BMAL1, and CRY2 [5]. The increase in the incidence and mortality rate of breast cancer in women is a worldwide problem. An epidemiological survey of cancer mortality, morbidity, and survival years, conducted in 195 countries and territories from 1990 to 2015 reported that breast cancer is the most common cancer in women (2. 4 million cases) [14]. [SEP] Justify:

Output: The text corroborates the claim through its detailed discussion on the disruption of circadian rhythms due to light exposure, especially in night and shift workers. It mentions that nocturnal light exposure disturbed the regular expression rhythms of clock genes, which are crucial in various physiological functions. The mention of health issues such as increased incidence and mortality rates of breast cancer in women, linked to disturbances in circadian rhythms, supports the claim that such disruptions can lead to health issues.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Finally, the subcutaneous fat layer consists of adipocytes, and also houses blood vessels, nerves, and lymphatic vessels [4]. Burn wounds include multiple mechanisms of injury which lead to similar results. Scalds are common type of thermal injury seen in children and the elderly population and they result from hot liquid spills or hot bathing water. These injuries typically cause superficial dermal burns. Another common mechanism of thermal injury is a flame burn which tends to cause deep dermal or full thickness burns. A smaller number of burns are caused via electrocution. This occurs when an electrical current travels through the body and the tissue through which it travels may face extensive damages. The depth of these wounds is determined by heat levels reached, and therefore relies on the voltage of the electrical current. This leads to a concern for cardiac abnormalities and requires extensive monitoring during treatment. Finally, chemical injuries result from accidental exposure to corrosive chemical agents and these wounds are typically deep [11]. There are three degrees of burns. First-degree burns are only injuries to the superficial epidermis. For these burns, only mild treatments are necessary, and risks are relatively low. Second-degree burns destroy the epidermis and damage the dermis; dermal damage can either be superficial or deep. There is a greater risk of hypertrophic scarring with these as well as the deeper third- and fourth degree burns which penetrate into subcutaneous fat and muscle, respectively [12] (Figure 1). Figure 1: Depicts depth levels of different burn wound degrees [13]. Once a burn reaches 30% of total body surface area (TBSA), a systemic effect is seen in the body. Cardiovascular changes involve increased capillary permeability, which results in the loss of proteins and fluids to the interstitial space [11]. Fluid loss also occurs from the burn wound itself and these result in systemic hypotension [11]. Hypovolemia then leads to decreased perfusion and oxygen delivery [12]. Additionally, in severe burns, respiratory distress syndrome can occur because of bronchoconstriction [11]. The cell basal metabolic rate will also increase to as much as three times its normal rate which exacerbates the hypoperfusion and requires early medical intervention through enteral feeding to reduce catabolism [11]. Lastly included in the systemic response are immunological alterations including non-specific down regulation of the immune response which affects multiple cell pathways [11]. (Figure 2). [SEP] Justify:

Output: The text contrasts the claim by detailing various types of burn injuries and their complexities, indicating that treatment for such injuries is not immediate or straightforward, undermining the idea that stem cells can cure all injuries instantly. It discusses different degrees of burns, their systemic effects, and the need for medical intervention, suggesting that the regeneration of tissue is not as simple or instant as the claim suggests.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: These two designations, however, likely are the two extremes along a continuum of change. Figure 3 and Table 1 summarize the fates of the larval MBINs (Saumweber et al. , 2018). We lacked suitable lines for the two octopaminergic neurons that innervate the calyx compartment (OAN-a1 and -a2). However, these cells have a very similar anatomy to the two adult OA-VUM2a neurons (Busch et al. , 2009), leading us to conclude that they are the same neurons. We experimentally established the fates of 13 of the remaining 14 larval MBINs. These cells either trans-differentiate, remodel, or degenerate. Trans-differentiation was the fate of one MBIN innervating the LA compartment and all those innervating the vertical lobe compartments, UVL and IVL, and the intermediate peduncle (IP) compartment (Figure 3). The most extreme change was evident for MBINs-b1 and -b2; they withdraw from the larval intermediate peduncle and become sexually dimorphic neurons that innervate the adult optic lobes (Figure 3B, Figure 3—figure supplement 1A and B). We named their adult form PAL-OL because they are found in the protocerebral anterior lateral (PAL) cluster of adult aminergic neurons described by Mao and Davis, 2009. The three vertical lobe MBINs (OAN-e1, MBIN-e2, and DAN-f1) are members of the PPL1 group (Saumweber et al. , 2018). We lacked a line to determine the fate of MBIN-e2, but OAN-e1 reorganizes to innervate the neuropil shell surrounding the MB lobes (as PPL1-SMP; Figure 3—figure supplement 1C) and DAN-f1 forms bilateral arbors in the adult superior medial protocerebrum as PPL1-bi-SMP (Figure 3—figure supplement 1D). [SEP] Justify:

Output: The text discusses the development and fate of specific neurons in the larval and adult stages of certain organisms, with details on trans-differentiation and remodeling of neuron types, but it does not address insect metamorphosis or any stages of life cycles. Therefore, it is irrelevant to the claim regarding insects and metamorphosis.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Another study conducted a follow-up survey of female nurses for 10 years and revealed that night or shift work was associated with an increased risk of breast cancer [15]. Furthermore, other epidemiological studies also demonstrated that the potential risk of breast cancer increased in women engaged in shift work [16, 17]. Under these circumstances, shift work that results in circadian disruption was categorized as “Group 2A” because it was determined to be probably carcinogenic in the carcinogenic risk assessment by for Research on Cancer (IARC) in 2007. However, the mechanism of increased risk of breast cancer by shift work remains unclear, and there have been few in vivo studies conducted to definitively associate the two factors. It is known that the survival rate of breast cancer patients markedly decreases as tumor stage progresses, particularly regarding the occurrence of metastasis [18]. Cancer cell migration from breast tissue to lymph nodes can be an important process in breast cancer progression. It has been reported that noradrenaline (NA) contributes to the acquisition of breast cancer cell invasiveness and escape pathways of cancer cells [19, 20], although NA is secreted through the activation of the sympathetic nervous system and has a role in the recruitment of lymphocytes to lymph nodes to enhance the body’s defense functions [21]. In our previous studies, it was shown that light exposure during the dark phase activates the stress response pathways and increases secretion of stress hormones adrenaline and NA [5, 22]. Hence, internal desynchronization and stress responses caused by disruption of the light environment may affect breast cancer progression and metastasis. We report here that we investigated the influence of circadian rhythm disruption by light/dark shifts on breast cancer development, especially metastasis, using BALB/c mice transplanted with BJMC3879Luc2 mouse breast cancer cells. We used a light/dark shift cycle pattern that imitated the rotating two-shift work pattern adopted in several types of workplaces, such as production industries, fire departments, and medical institutions [23, 24, 25]. To clearly disrupt the circadian rhythms of the mice, we chose a radical shift pattern: 12:12 light:dark inverted every two days. BJMC3879Luc2 cells are estrogen receptor positive breast cancer cells derived from metastatic foci within lymph node and lung, and they show a high metastatic potential to lymph nodes and lung [26]. [SEP] Justify:

Output: The text corroborates the claim by discussing the relationship between shift work, which disrupts circadian rhythms, and an increased risk of breast cancer. It states that shift work is categorized as ‘Group 2A’ in the carcinogenic risk assessment and highlights how internal desynchronization from light exposure can affect cancer progression. This clearly supports the idea that disruption of circadian rhythms can lead to health issues, specifically in the context of cancer.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Figure 2: Depicts systemic changes that occur as the result of a burn injury 11]. Successful healing after a burn injury is related to burn size and depth, as well as confounding factors of the patient such as age, mechanism of injury, and other comorbidities [12]. In this case, success is measured by healing time and scar quality [14]. Furthermore, burns may present a progressive expansion of necrosis into the zone of stasis, which is an area of initially viable tissue that is not harmed until the burn progresses [15]. Success may also be found in preventing the expansion of this necrotic tissue and allowing for viable tissue to remain [15]. There are also three phases during wound healing: inflammation, proliferation, and remodeling; these phases may be referenced in (Table 1) 5]. These processes are highly regulated by growth factors, cytokines, chemokines and cells [5]. Proper wound treatment involves maintaining an appropriate environment, infection control, and debriding the tissue [5]. Every phase in wound healing is mediated by stem cell proliferation and signaling [16]. Therefore, impaired stem cell functioning leaves to chronic wounds, so stem cell-based treatments are a rational approach to chronic wound care [16]. cascade stops bleeding, vasodilation, neutrophils increased to stop infection tissue forms a loose network of collagen, fibronectin, and hyaluronic acid, angiogenesis, re-epithelization scar formation and degradation, fading of inflammatory reaction, wound maturation Table 1: Names and compares the three phases of wound healing [5,17]. Descriptions of early excision of burn wounds began in 1510 AD with [18]. However, limitations of medical technology made excision of large burns impossible. More recently, Advancement of burn wound treatments has been significant in the last century. The late 1950s advanced the early excision technique with enhanced shock monitoring, however the technique was not widely accepted because of expected outcomes such as mortality, infection, excess blood loss, and extended healing times 18]. Treatment of burn wounds has remained a difficult medical problem to be solved. Today, burn wound treatment begins with the removal of all necrotic tissue and debris [12]. Early excision coupled with autografting has improved burn patient outcomes dramatically over the past several decades [19]. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and limitations of healing from burn injuries, emphasizing that healing is influenced by factors like burn size, depth, and patient characteristics. It explains that while stem cells play a role in the healing process, stem cell functioning can be impaired, leading to chronic wounds. This indicates that stem cells do not regenerate tissue instantly or cure all injuries, but rather are part of a complex healing process influenced by various factors.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Download elife-80594-fig3-data2-v2. pptx Figure 3—source data 3 Examples of the adult anatomies of larval neurons MBON-d1, MBON-e2, and MBON-f2 obtained by flip-switch-mediated immortalization of expression of stable spilt lines late in larval life. The anatomy of the adult form of the three neurons was revealed using lines SS01705, SS04172, and SS04328, respectively. Download elife-80594-fig3-data3-v2. pptx Figure 3—source data 4 Examples of the adult anatomies of larval neurons MBON-g1 and -g2 obtained by flip-switch-mediated immortalization of expression of lines SS02130 and SS02121 late in larval life. Download elife-80594-fig3-data4-v2. pptx Figure 3—source data 5 Examples of the adult anatomies of larval neurons MBON-h1 and -h2 obtained by flip-switch-mediated immortalization of expression of line SS01725 late in larval life. Download elife-80594-fig3-data5-v2. pptx Figure 3—source data 6 Examples of the adult anatomies of larval neurons MBON-j1 and MBON-j2 obtained by flip-switch-mediated immortalization of expression of lines SS01973 and SS00860 late in larval life. Download elife-80594-fig3-data6-v2. pptx Figure 3—source data 7 Examples of the adult anatomies of larval neurons MBON-i1 and MBON-k1 obtained by flip-switch-mediated immortalization of expression of lines SS01962 and SS04236 late in larval life. Download elife-80594-fig3-data7-v2. pptx Table 1 Metamorphic fates of larval mushroom body extrinsic neurons. Larval nameCompartmentLineage *Adult identityRef for adult identity-a1,a2CXVUM†OA-VUM2aBusch et al. [SEP] Justify:

Output: The text does not directly address the claim regarding complete metamorphosis in insects. Instead, it focuses on the anatomies of adult neurons obtained from larval forms and does not provide information that supports or contrasts the concept of metamorphosis.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: It has been reported that chronic inflammatory responses are associated with the adverse prognosis of various cancer types, including breast cancer. Above all, neutrophil-to-lymphocyte ratio (NLR) correlates with poor prognosis in breast cancer patients [27, 28]. Therefore, we also investigated the effect of light/dark shifts on NLR. We also investigated the preventive effect of quercetin on breast cancer metastasis promoted by circadian disruption in mice implanted with mouse mammary cancer BJMC3879Luc2 cells. Flavonoids are widely distributed in the plant kingdom and their intake has been reported to be inversely correlated with breast cancer risk [29, 30]. Quercetin, a representative flavonoid compound, is found in many plant foods such as onions in the O-glycoside form, and its anticarcinogenic effects are receiving attention due to its strong antioxidant activity [31, 32]. We have previously shown that Quercetin-3-O-glucuronide (Q3G), a quercetin metabolite, acts as β2-AR antagonist and suppresses invasion of human breast cancer cells in vitro [20]. However, there is no report on the suppressive effect of quercetin on metastasis resulting from disruption of the circadian rhythm in mice. Therefore, we investigated the preventive effect of quercetin on light disruption-induced breast cancer metastasis by feeding quercetin mixed diet to breast cancer transplanted model mice. 2. Materials and Methods 2. 1. A highly metastatic murine BJMC3879Luc2 mammary adenocarcinoma cell line, which is estrogen receptor-positive and expresses luc2 gene, was a kind gift from Dr. Masa-(College, Osaka, Japan) [33]. The cells were maintained in RPMI-1640 medium (Wako, Osaka, Japan) containing 10% heat-inactivated fetal bovine serum (FBS; ) with 50 U/mL penicillin and 50 U/mL streptomycin () at 37 °C in 5% CO2 in a humidified cell incubator. 2. 2. Animals and Experimental Light//c mice (7 weeks of age) were purchased from Japan SLC (Shizuoka, Japan). Five mice were kept in each plastic cage (W × D × H = 25. 5 × 38. 8 × 14. [SEP] Justify:

Output: The text supports the claim by discussing the effect of light/dark shifts on the neutrophil-to-lymphocyte ratio (NLR) and investigating the preventive effect of quercetin on breast cancer metastasis promoted by circadian disruption. This indicates a direct relationship between circadian rhythm disruption and potential health issues, specifically cancer metastasis.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Coverage of the burn wound helps to prevent fluid and protein loss, hypothermia, and the risk of infection [19]. Dressings that are biosynthetic, biological, dermal analogues, or derived from the patient have provided options beyond a simple meshed graft in recent years and allow for optimized healing (Table 2) [19]. EpiKeratinocyte-based Human origin, origin, Tissue scaffold Bovine/shark origin, Bilayer matrix Biocomposite dressing, nylon fibers in silicone with collagen Bioabsorbable polyglactin mesh scaffold with human fibroblasts (neonatal origin) Keratinocyte- based cultured epidermal autograft Autologous cell suspension of keratinocytes, fibroblasts, Langerhans cells and melanocytes, Sprayable after culture Table 2: Skin substitutes currently for sale on the commercial market [17]. Patients with severe burns often receive skin grafts, however donor skin and deficiency of eligible skin substitutions in severely burned patients hinders accuracy of treatment and prolongs hospital stays [18]. Patients are also often left with excess scarring and much less elasticity that normal skin [19]. Another new method involves application of antimicrobials to prevent wound infection [20]. Biofilms are a collection of microorganisms that delay wound healing by initiating a constant inflammatory response [20]. Finally, tissue engineering and regenerative medicine therapy have developed in an effort to overcome limitations of previously used treatment methods [20]. isolation techniques have enabled stem cells to be applied directly to injured areas in order to enhance wound closure [19]. Furthermore, stem cells included in multi-layer skin substitutes allow for complete repair and replacement of damaged tissue because they resemble normal skin more closely [19]. More specifically, dermal analogs and cultured epidermal autografts have been modified using stem cells to develop multipurpose products that replace both dermal and epidermal skin [21]. skin equivalents do not replace lost structures such as sebaceous and sweat glands, as well as hair follicles [22]. New techniques are also being used to further improve such engineered skin replacements. An example of these techniques is the addition of melanocytes to decrease hypopigmentation and achieve closer color matching [23]. [SEP] Justify:

Output: The text contrasts the claim by explaining that while stem cells have capabilities to enhance wound closure and are incorporated into skin substitutes, they do not achieve instant regeneration of all tissue types or cure all injuries. The text specifically mentions limitations, stating that engineered skin replacements do not replace structures like sebaceous and sweat glands or hair follicles. This illustrates that the ability of stem cells for tissue repair is not instantaneous and is subject to various developmental and biological constraints.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: , 2009MBIN-b1,b2-OLMao and Davis, 2009; this studyDAN-c1LPCPd2/3PPL1 01 (γ1pedc)Aso et al. , 2014; Li et al. , 2020MBIN-c1LPCPd2/3PPL1 01 (γ1pedc)Aso et al. , 2014; Li et al. , 2020DAN-d1LACPd2/3PPL1 03 (γ2α'1)Aso et al. , 2014; Li et al. , 2020MBIN-l1LABLV a3/4LAL>bi-CRPThis studyOAN-e1UVLCPd2/3PPL1-SMPMao and Davis, 2009; this studyMBIN-e2UVLCPd2/3UnknownDAN-f1IVLCPd2/3PPL1-bi-SMPMao and Davis, 2009; this studyDAN-g1LVLCPd2/3PPL1 02 (γ1)Aso et al. , 2014; Li et al. , 2020OAN-g1-VPM3Busch et al. , 2009DAN-h1-1/2DeadThis studyDAN-i1-1/2DeadThis studyDAN-j1-1/2DeadThis studyDAN-k1-1/2DeadThis studyMBONs:MBON-a1CXCPv2/3MBON 29 (γ4γ5)This studyMBON-a2CXCPv2/3MBON 22 (calyx)Aso et al. , 2014; Li et al. , 2020MBON-b1,-b2IPBLVa3/4LH-LNDolan et al. , 2019MBON-b3IPCPv2/3UnknownMBON-c1-CAThis studyMBON-d1-1/2MBON 11 (γ1pedc>α/β)Aso et al. , 2014; Li et al. [SEP] Justify:

Output: The text does not provide any information related to the claim regarding insects and complete metamorphosis. It appears to be a collection of references and studies without a clear connection to the specifics of metamorphosis in insects.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: 3% Q-Sh were calculated by following formula using the frequency of metastasis occurrence in the Control or Shift groups as the baseline data: Inhibition (%) = 1–[(rate of lymph node with metastasis/mouse in 0. 3% Q-Ctrl or Q-Sh group)/(rate of lymph node with metastasis/mouse in Control or Shift group)] × 100. 2. 9. Quantitative RT-was extracted from primary tumor, liver, cardiac atrium and cardiac ventricle using TR(), and then cDNA was synthesized using a RT reagent kit (. , Shiga, Japan). RT-PCR was performed using (Applied Biosystems, Warrington, UK) with specific primers on a StepOne Real-Time PCR System (Applied Biosystems). All specific primer pairs were modeled using web-based software Primer 3 and synthesized at STAR Oligo (Rikaken Co. Ltd. , Nagoya, Japan). For PCR primers for Per2 were 5’--3’ (forward) and 5’--3’ (reverse), the primers for Pai-1 were 5’--3’ (forward) and 5’--3’ (reverse), and the primers for Actb were 5’--3’ (forward) and 5’--3’ (reverse). The relative gene expression levels were calculated using the 2-∆∆Ct method, and normalized against Actb mRNA levels. 2. 10. All data are indicated as mean ± standard error (S. E. M. ). Statistical analyses were performed using Student’s T-tests with Statistics (Japan Co. , Ltd. , Tokyo, Japan). Differences were taken to be significant at P < 0. 05. 3. Results 3. 1. Disturbances in of To investigate whether circadian rhythm was impacted by light/dark shifts, a behavior analysis was performed using nano tag® devices. Under regular lighting conditions, active behavior was confirmed from several hours before the lights-out to during the dark period. Moreover, inactive behavior was observed in the light period. In contrast, mice activity during the dark period decreased due to irregular turn-on and/or -off the lights. [SEP] Justify:

Output: The text corroborates the claim by indicating that disturbances in circadian rhythm were investigated in relation to behavior analysis performed using devices, emphasizing that irregular light/dark shifts affected mouse activity during the dark period. This suggests a clear link between disrupted circadian rhythms and possible implications for health.


Input: Task: contrast the claim using the given text. Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Another example is the introduction of vascular endothelial growth factors and angiogenic cytokines to shorten healing time and prevent graft loss by counteracting the absence of a vascular plexus [24,25]. Stem cells allow for new opportunities in burn treatment as they have shown to improve the wound repair process both locally and systemically [19]. As a tool for healing burn wounds, stem cells show promise as they can be used to regenerate as well as accelerate re-epithelization [26]. These pluripotent cells can be clonally amplified in order to expedite epithelization and can also be transplanted without worries of rejection [19]. Stem cells lack immunogenic surface markers which gives them the privilege of avoiding rejection [27]. Stem cells are a valuable tool, but each type of stem cell must be evaluated for effectiveness in order to determine the best method of burn wound treatment (Table 3). Mesenchymal stem cells Bone marrow, stroma, blood Pluripotent Pluripotent, clonogenic Umbilical cord Umbilical cord blood Pluripotent Pluripotent, non-immunogenic, clonogenic Resident progenitor cells Numerous tissues/organs potential for trans-differentiation Adipose-derived stem cells Adipose tissue Multipotent Non-immunogenic, abundant supply, accessible, clonogenic Table 3: Depicts a review of stem cell nomenclature [28]. Chunmeng et al. , did not support the use of adult mesenchymal stem cells (MSCs), they found that systemic transplantation of dermis derived multipotent cells (DMC) promoted the healing of wounds [29]. However, DMC cultivation is widely unsuccessful and has a very low yield, so little further research has been performed to evaluate the effectiveness of DMCs in burn wound healing [22]. Another option would be to pursue treatment using hair follicle stem cells; however, these hair follicle stem cells are less common and have proved extremely difficult to populate ex-vivo [30]. Likewise, epidermal stem cells lack detailed research regarding their effectiveness in burn wound treatment (EPSCs). Llames et. al. , Used a culture of EPSCs on a bed of fibroblasts embedded with a plasma matrix to enable restoration of both epidermal and dermal component [31]. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexity and limitations of stem cell treatments, particularly in burn healing. It mentions that stem cells can enhance the wound repair process, but it does not support the idea that they can regenerate any type of tissue instantly or cure all injuries. Instead, it highlights the need to evaluate each type of stem cell for effectiveness and notes challenges in the use of specific cells such as adult mesenchymal stem cells (MSCs) and dermis-derived multipotent cells (DMC) which have low yields.


Input: Task: pass the claim using the given text. Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: , 2020MBON-d2LABAmd2SMP>IBThis studyMBON-e1UVLCPd2/3UnknownMBON-e2-d1MBON 03 (β'2mp)Aso et al. , 2014; Li et al. , 2020MBON-f2cl2MBON 30 (γ1,γ2,γ3)Li et al. , 2020MBON-f1-g1,g2-V2/3LAL. s-NO2i. bWolff and Rubin, 2018MBON-h1-V2/3MBON 09 (γ3β'1)Aso et al. , 2014; Li et al. , 2020MBON-h2-V2/3MBON 08 (g3)Aso et al. , 2014; Li et al. , 2020MBON-i1UTDAM-d1MBON 04 (β'2-bilat)Aso et al. , 2014; Li et al. , 2020MBON-j1ITDAM-d1MBON 02 (β2β'2a)Aso et al. , 2014; Li et al. , 2020MBON-j2-1/2MBON 05 (γ4>γ1,γ2)Aso et al. , 2014; Li et al. , 2020MBON-k1LTDAM-d1MBON 01 (γ5β'2a)Aso et al. , 2014; Li et al. , 2020a3/4APLAso et al. , 2014; Li et al. , 2020 CX, calyx; IP: intermediate peduncle; LP: lower peduncle; UVL: upper vertical lobe; IB: inferior bridge; IVL: intermediate vertical lobe; LVL: lower vertical love; LA: lateral 2018. † Lineage assumed to be from the ventral unpaired neuroblast because of position and nature of neurons. Four other members of the PPL1 cluster (DAN-c1, -d1, and -g1, and MBIN-c2) innervate compartments at the base of the lobes and the peduncle (LVL, LP, and LA compartments). [SEP] Justify:

Output: The text is irrelevant to the claim as it does not provide any information regarding insect metamorphosis or the life stages of insects. Instead, it appears to contain abstract or metadata about a study without discussing insect biology specifically.


Input: Task: corroborate the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: The peak behavioral time was no longer clear, and some animals seemed to free-run under the shift condition (Figure 1A and S1). Furthermore, the repeated light/dark shift caused dysregulation of expression of the representative circadian clock gene, Per2 gene in cardiac atrium (Figure 1B), cardiac ventricle (Figure 1C) and liver (Figure 1D), and Pai-1 gene in cardiac atrium (Figure 1E), cardiac ventricle (Figure 1F) and liver (Figure 1G). Figure 1 Circadian locomotor activity profiles, and Per2 and Pai-1 mRNA expression pattern in peripheral tissues. Circadian activities were measured for approximately 4 weeks using a nano tag. Actograms in the left and right panels represent the Control and Shift groups, respectively (n = 4, A). Locomotor activity levels were measured at 5-min intervals and are indicated by black bars. Per2 and Pai-1 expression levels in atria (B and E), ventricle (C and F) and liver (D and G) were analyzed at ZT2, 6, 11, 18, and 23. Values were normalized using Actb mRNA levels. Control gene expression levels at ZT2 were defined at as 1. Data represent mean ± S. E. M. (n = 4). *, P < 0. 05; **, P < 0. 01. Figure 2 Disturbance of the light/dark cycle does not affect tumor growth and decrease survival. Schematic representation of the experimental plan and light/dark conditions (A). Female BALB/c mice were implanted with BJMC3879Luc2 cells in the right fourth mammary fat pad and then maintained under each light/dark cycle condition for 3 to 8 weeks. The lighting conditions of each group were set as follows: Control group, 12:12 h light/dark cycle (lights on at 8:00; ZT0); Shift group, light on ZT0 for 2 days and then conversely on the following 2 days. The star mark (★) indicates the timing of body weight and tumor volume measurement (between ZT7 and ZT8). Mice were killed between ZT7 and ZT8 at 3, 5, or 8 weeks after tumor cell inoculation. Effect of light/dark shifts on body weight (B), tumor volume (C), tumor mass (D), and survival (E). [SEP] Justify:

Output: The text corroborates the claim by demonstrating that the repeated light/dark shift caused dysregulation of the circadian clock gene, Per2, in various organs such as the cardiac atrium, cardiac ventricle, and liver. This dysregulation indicates that disturbances in circadian rhythms can have biological consequences, which supports the assertion that such disruptions can lead to health issues.