Input: 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.

Output: pass


Input: 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.

Output: corroborate


Input: 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.

Output: contrast


Input: 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.

Output: pass


Input: 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.

Output: corroborate


Input: 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.

Output: contrast


Input: 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.

Output: pass


Input: 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).

Output: corroborate


Input: 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).

Output: pass


Input: 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).

Output: corroborate


Input: 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.

Output: contrast


Input: 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.

Output: pass


Input: 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].

Output: corroborate


Input: 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).

Output: contrast


Input: 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).

Output: pass


Input: 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].

Output: corroborate


Input: 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].

Output: contrast


Input: 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.

Output: pass


Input: 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.

Output: corroborate


Input: 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].

Output: contrast


Input: 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.

Output: pass


Input: 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.

Output: corroborate


Input: 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].

Output: contrast


Input: 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).

Output: pass


Input: 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).

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Mice with third-degree burns were treated with EPSCs that were activated by human a-defensin-5 and it was found to both promote hair regeneration as well as accelerate wound healing [32]. The transplantation of LGR6-positive EPSCs isolated by fluorescence-activated cell sorting and administered by injection into the wound significantly promoted re-epithelization, hair growth, and angiogenesis [32]. Carrier substrates could create an optimized physiological environment that may improve the regenerative performance of EPSCs [33]. Adult mesenchymal stem cells (MSCs) Most regenerative medicine research is focused on mesenchymal stem cells (MSCs) because they are derived mainly from bone marrow and adipose tissue [9]. CD34+ hematopoietic stem cells are the most widely studied and represent the only clinically approved stem cell [3]. MSCs can be derived from various tissues and have high differentiation potential [34]. MSCs are able to migrate to injured tissues, differentiate, and regulate tissue regeneration by the production of growth factors, cytokines, and chemokines [35]. Shumakov et al. , performed experiments on 40 Wistar rats where MSCs were applied to wounds showing decreased cell infiltration of the wound [36]. Accelerated formation of new vessels and granulation tissue was noted in comparison with embryonic fibroblasts and controls, burn wounds with no transplanted cells [36]. Likewise, Abbas et al. found in their experimentation with Wistar rats that the vital tissue percentage within the zone of stasis was significantly higher in the stem cell group of rats [15]. Huo et al. , found that MSCs have great potentials in the burn field [37]. However, the cell survival and outcome are also facing challenges from poor microenvironment of the burn wound – their struggle to survive in a burn wound environment is a potential draw-back of the use of MSCs [37]. Bone marrow stem cells (BMSCs) Bone marrow derived stem cells (BMSC) were analyzed against embryonic fibroblasts by Shumakov et al. in the first use of BMSCs for burn wound healing research [14]. In 2004, Rasulov et al. , were the first to report using BMSCs in humans [38]. They confirmed high tempo of wound regeneration in the presence of active neoangiogenesis [38].

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: They undergo moderate remodeling and continue innervating compartments at the base of the mature MB peduncle and lobes (the PED, γ1, γ2, and α'1 compartments) (Figure 3). The octopaminergic -g1, exclusively targets the LVL compartment in the larva, but in its adult form, named OA-VPM3 (Busch et al. , 2009), it extends extensive arbors into the fan-shaped body and the medial and lateral superior protocerebrum (Figure 3—figure supplement 2) with some arbor extending into adult γ1 compartment. This neuron shows profound metamorphic changes, but we still classify it as remodeling because it has some contact with the adult MB. The four larval dopaminergic neurons of the PAM cluster innervate the four medial lobe compartments (and MT). Using our flip-switch method, we could not find an adult counterpart for any of them despite using nine different split-GAL4 lines. We therefore assumed that they died during metamorphosis (Figure 3A) and this is confirmed in the next section. We established the fates of 14 of the 17 types of larval MBONs (Figure 4, Table 1). None died. They either remodeled or trans-differentiated, although as described for OAN-g1 above, such a distinction is not clear-cut for some neurons. We categorized the two calyx neurons, MBON-a1 and -a2, as remodeling because they also innervate the mature MB. This is clearly the case for MBON-a2 since its larval and adult morphologies (as MBON 22) are extremely similar. MBON-a1, by contrast, completely withdraws from the calyx and directs its adult growth into the adult γ4 and γ5 compartments as MBON 29. Three larval MBONs from the lobe system show similar dramatic morphological changes but also remain within the MB circuit. MBON-c1 retracts from the larval lower peduncle compartment and grows into the adult calyx (as MBE-calyx). MBON-e2 and MBON-f2 retract from the vertical lobes and regrow into medial lobe compartments, becoming the adult MBON 03 and MBON 30, respectively.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Data represent mean ± S. E. M. (n = 10–30). 3. 2. Light/investigate the effect of irregular light/dark cycles on breast cancer metastasis, BJMC3879Luc2-bearing mice were kept for 3, 5, or 8 weeks under the conditions shown in Figure 2A, and metastases to tissues were evaluated. No difference in body weight (Figure 2B), tumor volume (Figure 2C), or tumor weight (Figure 2D) was observed between normal light conditions and shift conditions. However, in the shift group, the survival rate began to decrease after about 5 weeks of tumor-bearing (Figure 2E). In addition, 8 weeks after inoculation, several mice in the shift group had symptoms of crouching, irregular respiration, and piloerection (data not shown). At the terminal sacrifice, cancer cell migration was captured using luciferase activity as a reporter and revealed that luminescence intensity tended to increase in the lung tissue and axillary lymph nodes of the shift group (Figure 3). Figure 3 Bioluminescent imaging of metastatic lesion areas of mice housed under normal or light/dark cycle shift conditions. Representative bioluminescent images of metastatic lesions obtained at 8 weeks after inoculation (A). Bioluminescent images were obtained 7 min after intraperitoneal administration of luciferin to mice. Quantification of bioluminescent intensities in each tissue taken from mice (B). Regions of interest (ROI) from displayed images were identified in the primary tumor, lung, kidney lymph node, and axillary lymph node, and quantified as photons per second. Data represent mean ± S. E. M. (n = 13–15). Necropsy of the major lymph nodes (i. e. , axillary, brachial, mediastinal, renal, iliac, inguinal, and popliteal) revealed markedly increased lymph node metastasis per mouse in the shift group (Figure 4A). In addition, metastasis in the right inguinal lymph node was observed in all mice (Figure 4B). However, the incidence of cancer metastasis in the right brachial lymph node was significantly higher in the shift group (Figure 4B).

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Rasulov et al. , on rats also showed the superiority of stem cells in burn wound healing [39]. Xue et al. , explored BMSCs to improve burn wound healing in the skin of mouse models [29,40]. Wound surface healing was significantly accelerated as well as the number and density of new blood vessels increased [40]. These mice showed no corresponding tumor growth and they gained weight faster [29,40]. Ha et al. transfected BMSCs with adenovirus as a vector with hepatocyte growth factor (HGF) [29,40,41]. The group treated with the MSCs had more significant re-epidermal growth at a shorter interval, less type 1 collagen and a thicker epidermis [41]. Although BMSCs have been successful in recent trials, a search for effective stem cell therapies continues because of invasive methods of retrieval for BMSCs as well as their low cell yields [40,41]. into skin of scalded fore limbs of male mice 0. 7 x 106 viable cells in 60 μL of PBS (1 million cells) Daily until wound was healed (covered by newly formed epithelium) Wound surface healing significantly accelerated Partial thickness skin burns on female rats BMSCs in adenovirus vector with HGF Days 3, 5, 7, 14, and 21 postburn BMSCs have positive effects on healing of burn wounds Umbilical cord mesenchymal stem cells (UCMSCs) Umbilical cord stem cells (UCMSCs) are used as a source of mesenchymal stem cells [42]. They have endothelial progenitor cells, in addition to hematopoietic and non-haemopoietic stem cells. can be transformed into skin, endothelium or bone [43]. Liu et al. , used UCMSC on burns in rats and found expedited wound healing. Higher neo-angiogenesis, the formation of new blood vessels, was recorded [44]. Similarly, Li et al. , used exosome from human UCMSCs to attenuate burn-induced excessive inflammation with 30% total body surface area (TBSA) burn wound on the dorsal side of rats [45]. A 30% TBSA full-thickness burn injury typically causes an excessive inflammatory response [45].

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: s-NO2i. b neurons that innervate the nodulus (Wolff and Rubin, 2018). The time course of MBIN and MBON metamorphic changes The fates of most of the larval MBINs and MBONs, as determined by the flip-switch method, were confirmed by following the expression of the parental lines through early metamorphosis. Although most enhancer-based lines change their expression patterns during metamorphosis, we found that GFP expression typically persists through enough of the remodeling period to confirm a neuron’s adult identity. As expected from our failure to find the adult versions of the medial lobe MBINs (DAN-h1 to -k1) using the flip-switch method, we found that they degenerate early in metamorphosis (Figure 5—figure supplement 1). Their dendritic arbors collapsed by 8 hr after puparium formation (APF), the cell bodies were disrupted by 16 hr APF, and the neurons were reduced to scattered GFP-labeled debris by 24 hr APF. The MBINs and MBONs that either remodel or trans-differentiate (Figures 5 and 6) showed a time course of pruning and outgrowth like that reported for the γ Kenyon cells (Watts et al. , 2003). Pruning of γ neuron axons is evident by 4 hr APF and is completed by 16–18 hr APF. Adult outgrowth commences by 24 hr and is finished by 48 hr APF (Yaniv et al. , 2012; Mayseless et al. , 2018). The larval MBINs (Figure 5, Figure 5—figure supplement 2) and MBONs (Figure 6) also showed arbor loss by 8 hr APF and were maximally pruned by 16 hr APF. Growth cones were evident between 16 and 24 hr APF. MBIN-b1 and -b2 showed the most exuberant outgrowth, having formed growth cones that were halfway to the optic lobes by 16 hr APF and had reached them by 24 hr (Figure 5). Most neurons achieved their adult form by 48 hr APF. The GABAergic anterior paired lateral (APL) neuron and MBON-j2 neurons were exceptional in that they continue arbor extension beyond 48 hr (Figure 6—figure supplements 1 and 2).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Furthermore, metastasis in the left brachial and inguinal lymph nodes, lymph nodes located distal to the implantation site, were significantly increased by light/dark shifts (Figure 4B). These results suggested that disturbances in the light/dark cycle may promote distant metastasis of breast cancer. Figure 4 Frequency of metastasis in lymph nodes. Number of lymph node metastasis in each group (A) and frequency of metastasis in distant lymph nodes (B). Data represent mean ± S. E. M. (n = 18). *, P < 0. 05; **, P < 0. 01; ***, P < 0. 001. 3. 3. Light/influence of light/dark shifts on the immune system, especially total WBC count and NLR, were analyzed. There was no effect of light/dark shifts on total WBC counts in both groups (Figure 5A). However, a decrease in the lymphocyte ratio and an increase in the neutrophil ratio at 5 weeks after cancer cell transplantation were confirmed in the Shift group, and the NLR was significantly higher in the Shift group than in the Control group (1. 64-fold, Figure 5B). Figure 5 Total white blood cells (WBCs) and neutrophil-to-lymphocyte ratio (NLR). Total WBCs were measured at 5- or 8-weeks post-inoculation (A). NLR was calculated from the neutrophil and lymphocyte percentage of WBCs at 5- or 8-weeks post-inoculation (B). Data represent mean ± S. E. M. (n = 6). *, P < 0. 05. 3. 4. NA Content in Intratumoral NA concentration tended to increase in the Shift group after 5 weeks of inoculation, but the NA concentrations in both groups were not significantly different after 8 weeks of inoculation (Figure 6). Figure 6 Change in tumor NA levels. Intratumoral NA concentration was measured at 5- or 8-weeks post-inoculation. Data represent mean ± S. E. M. (n = 5–10). 3. 5. Effect of Quercetin on in investigate the anti-metastatic effect of quercetin on breast cancer cells, a 0.

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: However, the administration of their hUCMSC-exosome reduced the number of white blood cells [45]. This reduction became especially clear after 24 hours, and Li et al. , concluded that hUCMSC-exosome, in general, mildly suppressed inflammation after burn injury [45]. Zhou et al. , created a human umbilical cord mesenchymal stem cell-conditioned medium in the form of a hydrogel, which could be topically applied to burn wounds [46]. Injured mice were treated with either conditioned or unconditioned hydrogel and compared with a control group [46]. Application of the UCMSC conditioned hydrogel shortened healing time, reduced area of inflammation, and enhanced reepithelization effectively in third-degree burned mice; however, effects were not found to be statistically significant 46]. Although topical application of the UCMSC allowed for ease of treatment, effects were not optimal and alternative treatments should be developed and evaluated [46]. Finally, Abo-Elkheir et al. , compared BMSCs and UCMSCs with standard grafting and early excision of recent thermal full-thickness burned human patients 22]. Patients’ burn percentages ranged from 10% to 25% TBSA, and following treatment, the percentage of burn extent was significantly reduced in both UCMSC and BMSC groups compared to standard grafting and early excision groups [22]. Ultimately, however, no significant difference between UCMSC and BMSC groups was found and further research is required to determine if one is more effective than the other [22]. ASCs (adipose-derived stem cells) Adipose-derived stem cells (ASCs) are pluripotent and capable of differentiating into all three germ layers [47]. These stem cells can be cultured to up to 1000 times their yield making them distinctly more attractive than MSCs [48]. Adipose tissue can be harvested by a minimally invasive procedure, which makes it a promising source of adult stem cells [49]. Fujiwara et al. , used an ovine burn model and topical application of ASCs from non-injured healthy sheep 47]. They assessed wound healing at one- and two-weeks following application and treatment with ASCs was found to accelerate the patch graft growth compared to the control [47].

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: *Expression due to nontarget neurons in some driver lines; filled arrowheads: axonal growth cones; open arrowheads: dendritic growth cones; P+#: # hours after pupariation. Magenta: Fasciclin II; blue: Bruchpilot (nc82). Lines used for developmental timelines: MBON-a1: JRC-SS00867, MBON-a2: JRC-SS02006, MBON-g: JRC-SS02130, MBON-h: JRC-SS01725, MBON-j1: JRC-SS01973. MBON-a1 and -a2 provide an interesting contrast of divergent remodeling of two similar larval cells (Figure 6). Both cells show retraction of dendritic and axonal arbors by 8 hr APF. MBON-a1 removes its larval dendritic arbor by 16 hr, and its distal axonal region then extends new growth cones to innervate the adult γ4 and γ5 compartments and surrounding neuropils. In contrast, the dendritic arbor of MBON-a2 only partially regresses. It organizes into a dendritic growth cone by 16 hr APF, which then reinvades the calyx. Its adult form, MBON-20 (MBON-calyx; Aso et al. , 2014; Li et al. , 2020), is very similar to its larval form. The most stable extrinsic neuron is DAN-d1 (Figure 5). Its dendritic arbor remains intact through metamorphosis. Its axonal tuft shows moderate thinning from 8 to 18 hr APF and then extends fine processes into the forming γ2 and α'1 compartments between 24 and 48 hr APF. A more extreme remodeling is evident in the larval MBON-d1, which becomes the adult cell MBON 11 (Figure 6—figure supplement 1). Its larval dendritic tuft retracts and reorganizes into a growth cone by about 18 hr APF. The latter extends into the γ1 and peduncle compartments by 24 hr and achieves its adult dendritic configuration by 48 hr APF.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: 3% quercetin diet was given to tumor-bearing mice for 8 weeks under the same conditions as described previously (Figure 2A). There were no differences in food intake or body weight changes in each group (Figure 7A and 7B). There was also no effect of quercetin intake on tumor volume and tumor weight (Figure 7C and 7D). Regarding lymph node metastasis, metastasis to various lymph nodes was suppressed in the 0. 3%Q-Ctrl and 0. 3%Q-Sh groups. In particular, it was observed that metastasis to the kidney lymph nodes and iliac lymph nodes was strongly suppressed (Figure 7E). Figure 7 Effect of 0. 3% quercetin diet on the lymph node metastasis. All animals were given normal MF diet or 0. 3% quercetin-containing MF diet over the experimental period. Food intake (A), body weight (B), and tumor volume (C) were measured once a week (n = 6–10). Tumor weight was measured at the final necropsy (D, n = 6–10). Data represent mean ± S. E. M. The lymph node metastasis inhibition rates in 0. 3% Q-Ctrl and 0. 3% Q-Sh were calculated using the frequency of metastasis occurrence in the Control or Shift groups as the baseline data (E, n = 6–10). *, P < 0. 05 vs. control; †, P < 0. 05 vs. shift. 4. cancer is the most frequent cancer type in women worldwide. Many previous epidemiological studies reported that shift and night workers are at a higher risk of breast cancer than day shift workers [16, 36]. These reports suggest that circadian disruption of biological functions due to deviations from the natural day/night cycle may affect breast cancer development. In this study, the effect of circadian rhythm disruption by light/dark shifts on metastasis of breast cancer was investigated using BALB/c mice transplanted with BJMC3879Luc2 mouse breast cancer cells. A radical shift pattern (12:12 light:dark cycle with inverting every two days) that imitated the rotating two-shift work was chosen to disrupt the circadian rhythms of the mice. The 12-hour rotating shift cycle caused clear circadian disruption and a free-running behavioral rhythm was observed (Figure 1A and Figure S1).

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Topical application of ASCs significantly increased wound blood flow [47]. Expression of Vascular endothelial growth factor (VEGF) was significantly higher in the wounds treated with ASCs compared to those treated with placebo [47]. Foubert et al. , compared local injection and topical application of ASCs [50]. They created full-thickness thermal burns on 10 Gottingen minipigs and either sprayed ADSCs onto the wound surface (0. 25 × 106 viable cells/cm2) or performed multiple injections into or surrounding the wound bed [50]. No significant difference between delivery approaches was found, and they concluded that the spray system did not cause loss of cell number or viability and is recommended because less invasive [50]. Necrosis is a common complication in skin graft therapy [51]. Subsequently, Zografou et. al. measured the effectiveness of ASCs in the mitigation of necrosis after skin graft procedures on rats [51]. ASCs were isolated, cultured, and labelled with fluorescent dye and injected beneath a full-thickness skin graft on the dorsal side of ten rats [51]. The grafts were analyzed by assessing the Collagen’s framework, and the mean area of graft necrosis was significantly less in the injected group than control group [52]. They concluded that the autologous transplantation increased full-thickness skin graft survival via two pathways: in situ differentiation of ASCs into endothelial cells as well as increase secretion by ASCs of growth factors such as VEGF and TGFb3 which enhance angiogenesis and wound healing [51]. Finally, Zhou et al. isolated ASCs of Sprague-Dawley rats and labeled them with green fluorescent protein 53]. Previous success with ASCs in other research allowed Zhou et al. to compare different injection patterns of ASC therapy [53]. They concluded that multiple injections of the ASCs significantly accelerated the wound healing process and also efficiently participated in angiogenesis [53] (Table 4). application of ASCs to ovine burn model 3. 5 x 106 viable cells/cm2 One- and two-weeks post injury ASCs significantly increased growth & blood flow Injection and topical application (spray on) of ASCs on porcine model 0.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Its axonal arbor changes from a compact projection in the larva to a sparse arbor innervating the adult α and β lobes (Aso et al. , 2014; Li et al. , 2020). Amongst the cells undergoing trans-differentiation, the most extreme changes are seen in MBON-g1 and g2, which shift from the larval MB to the adult central complex (Figure 6). Their larval axonal arbors are retracting by 8 hr APF and organize into axonal growth cones by 18 hr APF. The growth cones then navigate medially to innervate the intermediate zone of the nodulus. The dendritic tufts of MBON-g1 and -g2 thin by 8 hr APF and then fragment as new dendritic growth cones sprout from the base of the old arbor (18 hr APF). The dendrites innervate the ipsilateral lateral accessory lobe of the adult. MBON-c1 was refractory to the flip-switch approach, but its early metamorphic changes gave us insight into its mature function. As seen in Figure 6—figure supplement 3, by 24 hr APF, its larval dendritic arbor is essentially gone, and new growth cones are invading the calyx neuropil. This split-GAL4 line lost its GFP expression after 24 hr, but the extensive invasion of the calyx neuropil by this time indicates that the calyx is its adult target. Its anatomy at 24 hr APF, though, is too immature to allow it to be matched to any described adult cell, so we have called its adult form MBE-CA (mushroom body extrinsic neuron to calyx). The larval form is a derived state for the neurons that show trans-differentiation The γ Kenyon cells first assume a larval form, with vertical and medial axon branches, and then remodel into their adult form. The latter form, with its single medially directed axon, is the same as seen in the γ neurons of nymphs and adults of the more basal, direct-developing insects, such as the cricket (Malaterre et al. , 2002).

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Also, the peak times of Per2 and Pai-1 were phase advanced about for 7 h (Figure 1B and 1C) and 12 h (Figure 1E and 1F) in shift group mice, respectively. Furthermore, the expression levels of Per2 and Pai-1 showed noticeable downregulation. The association of Per2 or Pai-1 in many types of cancer, including breast, is well-documented [37, 38]. Per2 is known to have tumor suppressive activity against mammary tumors, and its down-regulation is advantageous for cancer progression [39]. These outcomes support the hypothesis that light/dark shift accelerate breast cancer progression. Incidentally, the relationship between breast cancer malignancy and Pai-1 has been discussed in several papers and it is presumed that Pai-1 promotes cell migration [40, 41]. We demonstrated that disruption of biological rhythms by light/dark shifts promoted tissue metastasis, especially distal lymph node metastasis and further caused a decrease in survival (Figures 2E, 3 and 4). But it did not affect the tumor volume or weight of transplanted breast tumors (Figure 2C and 2D). The effect of biorhythm disturbance on tumor growth and metastasis has been reported in previous study [42], along with downregulation of per2 by jet lag condition. And, it presents interesting data on the acquisition of the stemness and growth potential of tumor cells and antitumor immunity. In contrast, as mentioned above, our model did not show the effect of light-disturbance on tumor growth. It is difficult to make a general comparison with previous study [42], because of the different tumor model (spontaneous or orthotopic transplant), subtypes of breast cancer cells (estrogen receptor and progesterone receptor sensitivity and HER2 protein expression) and light/dark conditions. Therefore, we think that it will be necessary to consider the systems that more closely resemble human rotating shift work, e. g. , comparison with a 3-shift work system (shifted by 8 hours for 3 groups), of different light-dark compositions (6:18 light:dark cycle, and/or 18:6 light:dark cycle) in future studies. In mammals, various physiological functions including temperature regulation, sleep/arousal, and hormone secretion are known to change periodically over approximately a 24-hour period over a day/night cycle, which is an environmental time signal [1].

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: 25 x 106 viable cells/cm2 days 7, 12, 16, 21, and 28 posttreatment No significant difference between treatment methods was found ASCs injected under full-thickness skin grafts in rats 1 x 106 viable cells/cm2 One-week post injection Mean area of graft necrosis was significantly less in injected group than control group ASCs injected beneath 2-cm2 burn wound on dorsal skin of rat 2 x 106 viable cells/cm2 injected either 1 or 3 times Digital images of wound area taken pre- and posttreatment and throughout healing Multiple injections increased healing and promoted angiogenesis Table 4: Compares animal studies using ASCs in a burn wound model. comparing each type of stem cell for potential success in burn wound treatment, adipose-derived stem cells (ASCs) seem to possess the least limitations for clinical applications [54]. These ASC’s stem cells are considered the “holy-grail” in regenerative medicine as they are widely available, easily obtainable and propagated, have pluripotent potential and promote wound healing [55]. As compared with are easier to access, and they yield higher amounts of stem cells when isolated [52]. BMSCs carry several disadvantages such as a painful isolation procedure, low cell yields, and the need for general anesthesia [52]. As far as properties of self-renewal and multipotential differentiation, both BMSCs and ASCs were shown to be similar, therefore making ASCs an attractive substitute for BMSCs [52]. When compared to were not significantly different, although both improved healing compared to traditional treatment methods [22]. As important as it is to identify the most effective stem cell therapy for burn wound treatment, the work will not stop there. Once successful stem cells are identified, work must be done to determine the best method of application and if additional treatments should be performed on the cells prior to application. For example, Imam and Rizk found success when using erythropoietin pre-treated stem cells [56]. Ramhormozi et al. also found success through the use of combination therapy utilizing BMSCs and simvastatin with increased wound closure and decreased overall healing times [57]. Thus, co-cultures with other cell types as well as other various pretreatments using chemicals or cell media should be explored in greater detail [58].

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Thus, the adult version of Drosophila γ neurons is like that of a direct developing ancestor, while its larval form is derived to accommodate the lack of αβ class neurons in the larva. Is this a general rule for cells that have different larval and adult phenotypes? Do the adult phenotypes approximate the ancestral phenotype while the larval phenotypes are derived? It is difficult to directly deal with these designations for the trans-differentiating MBONs and MBINs because we do not know the corresponding neurons in direct developing species. We can, however, make this comparison for some VNC neurons such as the thoracic midline spiking interneurons (Figure 7). These neurons are found in a large cluster in each thoracic hemineuropil, and each cluster is the progeny of a single, identified neuroblast (Shepherd and Laurent, 1992). Each cluster includes two sets of GABAergic neurons that are based on the asymmetrical division of the ganglion mother cells. The 'A' group (hemilineage) remains ipsilateral, while the 'B' hemilineage projects to the contralateral leg neuropil where, as the midline spiking interneurons, they shape the response of leg motoneurons to input from leg mechanoreceptors (Siegler and Burrows, 1984). They were first described in grasshoppers (Siegler and Burrows, 1984) but they are found in both direct developing and metamorphic insects (Witten and Truman, 1998), indicating their involvement in leg function through insect evolution. Figure 7 with 1 supplement see all Download asset Open asset The phenotypes of neurons made by thoracic neuroblast (NB) 4–2 during its embryonic and postembryonic phases of neurogenesis. Neurons are generated pairwise during both phases to produce the 13A and 13B hemilineages. (A) Four examples of embryonic born, 13B interneurons that function in the larva. All are commissural interneurons having ipsilateral dendrites and contralateral output sites. Boxed image shows the neurons overlapping in segment T1. (B) Example of a postembryonic clone of NB4-2 showing the neurons of the two hemilineages at the end of larval life.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Our previous studies revealed that nocturnal light exposure increases secretion of adrenaline and NA through the function of the sympathetic-adrenal-medullary axis (SAM) system and the sympathetic nervous system, the stress response systems, showing evidence that a departure from the natural light/dark cycle is a stress factor [5, 22]. A recent investigation demonstrated that chronic stress load activated the sympathetic nervous system accompanied by secretion of NA, and promoted remodeling of tumor lymphatic vessels and cancer metastasis in mice transplanted with MDA-MB-231 cells [43]. We previously reported that NA elevated breast cancer cell infiltration via adrenergic receptors and upregulated MMP9 expression, which contributes to extracellular matrix degradation in MDA-MB-231 cells [20]. These findings suggest that disruption of light/dark cycles causes a stress response accompanied by NA secretion, which may affect breast cancer development. As shown in Figure 6, the concentration of NA in breast tumors tended to increase due to light/dark shifts. However, no increase in Mmp9 expression in tumors due to light/dark shift was observed (data not shown). As mentioned above, some biological functions including enzyme activity and gene expression show circadian rhythms. It is known that the activity and expression levels of these factors are continuously changing [44, 45]. All final sampling in this study was conducted at the same time (ZT 7–8). Therefore, to resolve the relationship between NA and MMP9, further experiments at multiple time points are required in future studies. We here shown that the NLR is significantly increased by light/dark shifts (Figure 5B). At the same time, shortening of survival was observed (Figure 2E). 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. Various internal and external factors affect the metastasis of many cancers including breast cancer through the complex mechanisms, and in recent years there have been many reports that neutrophils have an active role in tumor progression [46, 47]. It has been reported that frequent changes in the light/dark environment can induce chronic inflammation and increase the early mortality rate [48]. It has been also reported that the risk of developing liver and lung cancer increases with long-term light/dark shifts [49, 50].

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: Economic barriers must also be overcome in order to adopt stem cell therapies for skin regeneration [16]. Costs of cell-based therapies are frontloaded, which delays return on investment [16]. Additionally, the technology to standardize and mass-produce such treatments is not yet available, so considerable funding must also be directed into the development of this large-scale infrastructure [16]. Currently, a search of clinical trials. gov including keywords “burn” and “stem cell” yielded 25 active clinical trials in the that are focused on these treatments [59]. Of these trials, seven are currently examining the success of Adipose-derived stem cells (ASCs) in burn wound treatment: NCT03686449, NCT03113747, NCT02779205, NCT03183648, NCT03183622, NCT02619851, NCT02394873 [59]. A summary of these trials can be found in Table 5. Each trial represents progress in the research of stem cell therapies for burn wounds. In particular, trial NCT03183648 is a phase 2 trial measuring the safety and tolerability of ALLO-ASC-DFU, a hydrogel sheet containing allogenic ASCs [59]. The ease of application of a hydrogel sheet as a wound dressing makes this method of delivery a favorable approach for both patients and practitioners [59] (Table 5).

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: Neuron#1_04 (α'3)1PostembryonicDL2Ren et al. , 2016PPL1-05 (α'2α2)1PostembryonicDL2Ren et al. , 2016PPL1-06 (α3)1PostembryonicDL2Ren et al. , 2016PAM 01 (γ5)19PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 02 (β'2a)8PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 03 (β2β'2a)4PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 04 (β2)16PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 05 (β'2p)10PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 06 (β'2m)15PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 07 (γ4<γ1γ2)5PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 08 (γ4)26PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 09 (β1ped)6PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 10 (β1)6PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 11 (α1)7PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 12 (γ3)11PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 13 (β'1ap)7PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 14 (β'1)8PostembryonicCREa1A, CREa2ALee et al. , 2020PAM 15 (γ5β'2a)3PostembryonicCREa1A, CREa2ALee et al.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: In addition, it has been demonstrated that a chronic inflammatory response is associated with cancer malignancy and poor prognosis in various types of cancer [49, 51, 52]. From these findings, the inflammatory response is an important factor in cancer progression. Peripheral blood NLR is a parameter that reflects systemic inflammation, and it has been shown that a high NLR is associated with poor prognosis in various cancers such as breast, lung, and prostate cancer [28, 53]. These outcomes suggest that 12-hour rotating shift cycle is an environmental factor that affects the survival of breast tumor-bearing mice. To prevent metastasis, treatment with anticancer drugs and/or radiation is performed. On the other hand, adverse effects associated these treatment cause complications and add to increased morbidity and mortality among patients [54]. Therefore, chemoprevention by food is important. We here focused on quercetin contained in plants as a tool to prevent cancer progression (i. e. , development, proliferation, and metastasis). Our laboratory previously reported that a quercetin metabolite, Q3G inhibited MDA-MB-231 human breast cancer cell invasion induced by NA via β2-adrenoreceptor [20]. It has also been shown that quercetin inhibited the proliferation of MCF-7 human breast cancer cells [55]. In addition, quercetin has an inhibitory effect on cancer cell migration, and it has been reported that cancer metastasis is suppressed by quercetin therapy [56, 57, 58]. Thus, evidence on the antitumor effect of quercetin is accumulating. However, the suppressive effect of quercetin on metastasis progression as a result of disturbances to the circadian rhythm has not been verified. Therefore, we investigated whether breast cancer metastasis suppression by feeding a 0. 3 % quercetin diet is observed or not in breast cancer-transplanted mice under a light/dark shift environment. The effects of quercetin on food consumption and tumor size and weight were not observed in all groups (Figure 7A, 7C and 7D). Whereas, metastasis to kidney lymph nodes and iliac lymph nodes was strongly suppressed in mice fed a 0. 3 % quercetin diet in a light/dark shift environment (Figure 7E).

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: 03686449 Adipose-Cell-for Post-with Full-Loss Procedure: Non-cultured Suspension Procedure: Adipose-Cell-Procedure: Split skin graft N/A NCT03113747 Allogenic ADSCs and Platelet-to Treat the Patients with (ADSCs-BWs) Second- or Third-degree Burns Biological: ALLO-AS1 Phase 2 NCT02779205 Child’s Adipose Cells: Capacity of Burns Procedure: adipose tissue sample N/A NCT03183648 A Follow-to Evaluate the Safety of ALLO-ASC-DFU in ALLO-ASC-BI-201 Burn Biological: ALLO-ASC-03183622 A Follow-to Evaluate the Safety of ALLO-ASC-DFU in ALLO-ASC-BI-101 Burn Biological: ALLO-ASC-02619851 A clinical Trial to Evaluate the Safety and Efficacy of ALLO-ASC-DFU for : ALLO-ASC-DFU Device: Phase 2 NCT02394873 A Study to Evaluate the Safety of ALLO-ASC-DFY in the Subjects with Deep Second-degree Burn Biological: ALLO-ASC-DFU Phase 1 Table 5: Summary of current clinical trials involving the use of ASCs [59]. Although the outlook of these ASC trials is promising, many therapies are still in early stages of development and remain in small animal models [60]. A devastating morbidity is associated with burn wound healing as poor outcomes may lead to lifelong disability and severe scarring [60]. There is a profound potential impact of stem cell therapy to facilitate wound healing and dramatically improve the lives of trauma and burn victims. 1. Lin G, Xu RH. (2010) Progresses and challenges in optimization of human pluripotent stem cell culture. Ther. 5(3):207-14. 2. M Witkowska-Zimny M, Wrobel E. (2011) Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion. Biol Lett. 16(3):493-514. 3. . (2009) A review of gene and stem cell therapy in cutaneous wound healing, Burns. 35(2):171-180. 4. . (2014) Immunology and Skin in Health and Disease. Med.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: , 2020PAM γ4/5? PostembryonicCREa1A, CREa2ALee et al. , 2020 06 (β1>α]1UnknownMBON 07 (α1)2UnknownMBON 10 (β'1)8UnknownMBON 12 (γ2α'1)2PostembryonicFLAa2This studyMBON 13 (α'2)2PostembryonicFLAa2This studyMBON 14 (α3)2PostembryonicFLAa2This studyMBON 15 (α'1)2PostembryonicDL1This studyMBON 16 (α'3ap)1PostembryonicDL1This studyMBON 17 (α'3m)2PostembryonicDL1This studyMBON 18 (α2sc)1postembryonicDL1This studyMBON 19 (α2p3p)2PostembryonicDL1This studyMBON 21 (γ4,γ5)1UnknownMBON 23 (α2sp)1PostembryonicDL1This studyMB-DPM1PostembryonicUnknownMayseless et al. , 2018 Adult names according to Aso et al. , 2014 and Li et al. , 2020, except PAM γ4/5, which is based on Lee et al. , 2020. The origins of the remaining adult MBINs have already been determined (Figure 8A). About 150 PAM neurons divided into at least 15 different types are found in the adult MB (Aso et al. , 2014; see also Lee et al. , 2020; Li et al. , 2020). These neurons are born during the postembryonic phase of neurogenesis and come from the CREa1A and CREa2A neuroblasts (Lee et al. , 2020; Table 2). For the PPL1 cluster MBINs, the number is about the same in the larva and the adult, but the cell population partially changes. We find that three of the larval PPL1 MBINs retract from the MB and join other circuits in the adult (Figure 3), and Ren et al. , 2016 found that three adult-specific neurons are added from the postembryonic DL2 lineage.

Output: pass


Input: Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: In previous reports of the pharmacokinetics of quercetin and quercetin metabolites, high levels of quercetin and its metabolites were observed in lung, kidney, and liver after quercetin ingestion [59]. Another report showed that Quercetin glucosides administered to the duodenum is partly transported to the iliac lymph vessels [60]. From these studies, it is assumed that the tissue-specific kinetics of quercetin cause local accumulation of quercetin in the iliac lymph nodes and kidney lymph nodes, leading to suppression of cancer cell migration. In examining the preventive effect of the ingestion of quercetin-containing foods on breast cancer, further investigation is required to clarify the detailed mechanism of metastasis inhibition by quercetin. In conclusion, our study has shown that an irregular light environment that reverses the light and dark phases every two days induced shorter lifespan and high level NLR that is a poor prognostic factor of breast cancer. Circadian rhythm disruption contributes to distal lymph node metastasis even though it did not affect the tumor growth in breast cancer transplanted in mice. These results with breast cancer transplant model and the modified light environment suggest that night-shift work may also affect distant metastasis and prognosis. In addition, in order to investigate the preventive effect of plant components on breast cancer, we fed quercetin mixed diet to breast cancer transplanted model mice and examined the anticancer effect against photodisturbation-induced breast cancer metastasis. We have demonstrated that distant lymph node metastasis due to disruption of the light/dark cycle is suppressed in certain lymph nodes by quercetin. This suggests that quercetin may be useful as a novel tool for the food prevention of light environment-induced breast cancer migration. To the best of we knowledge, this is the first report to the effect of quercetin on distal lymph node metastasis promoted by the disruption of circadian rhythm by the light environment modeled shift worker. The additional file for this 10. 5334/jcr. 203.

Output: corroborate


Input: Claim: Stem cells can regenerate any type of tissue instantly, curing all injuries. [SEP] Text: 4(12):a015339. 5. . (1982) Biomedicine & pharmacotherapy, Biomedicine & Pharmacotherapy. 117 (1982) 109191. 6. . (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 102(4):451-61. 7. (2005) Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 11(12):1351-4. 8. (2019) Stem cells in burn wound healing: A systematic review of the literature. Burns. 45(5):1014-23. 9. (2011) Stem cell therapy: a new treatment for burns? J Pharm. 4(10):1355-80. 10. . (2019) The effects of stem cells on burn wounds: a review. IJBT. 9(1):1. 11. Hettiaratchy S, Dziewulski P. (2004) Pathophysiology and types of burns. Bmj. 328(7453):1427-9. 12. . Acute burns. (2000) Surg. 105(7):2482-92. 13. . (2006) Burn wound infections. Rev. 19(2):403-34. 14. (2015) of in Healing: A Review. BioInt. 84. 15. (2018) Prevention of Progression by Cell Transplantation: Mechanisms. Surg. 81(6):715-24. 16. (2019) Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside. Genes & diseases. 6(4):342-58. 17. (2015) Burn wound healing and treatment: review and advancements. Crit care. 19(1):243. 18. . (2017) History and Advancement of Burn Treatments. Surg. 78(2):S2-8. 19. . (2013) ABA Organization and Delivery of Committee. Wound coverage technologies in burn care: novel techniques. J Res. 34(6):612-20. 20. . (2017) Burn wound healing: present concepts, treatment strategies and future directions. J Wound Care. 26(1):5-19. 21. Boyce ST.

Output: contrast


Input: Claim: Some insects can undergo complete metamorphosis, transitioning through larval stages. [SEP] Text: The MBONs of the larval distal ‘toes’ (the UT, IT, and LT compartments) distribute their dendrites amongst the adult distal medial lobe compartments (γ4, γ5, β2, and β'2). The basal larval compartments, LP, LA, and LVL, correspond to adult compartments PED, γ1, and γ2, respectively. Most of their MBINs and MBONs stay within this set of compartments but there is some shuffling amongst them. The general pattern is that larval MBINs and MBONs that supply the seven larval compartments that are incorporated into the adult MB continue to function in the adult MB, while those that innervate the three larval-specific compartments retract from the MB and join non-MB circuits of the adult brain. From the perspective of the mature, adult MB, 10 of its 16 compartments have axon cores from the postembryonic born α'β' or αβ Kenyon cells. The α and α' compartments are supplied almost exclusively by postembryonic-born MBINs and MBONs (Figure 8, Table 2). By contrast, the β and β' compartments show a mixed picture: their input is provided exclusively by postembryonic-born PAM neurons (Figure 8A; Lee et al. , 2020), while their known outputs are through embryonic-born neurons from the larval MB (Figure 4A). Transmitter stability and shifts in compartments through metamorphosis The input and output transmitters associated with MB compartments of the larval and adult systems are similar but not identical (Figure 9B). For the MBINs, the calyx receives octopaminergic input from the same neurons in the two stages. The adult calyx also receives a sparse serotonin input from a remodeled CSD neuron that projects from the contralateral antennal lobe (Roy et al. , 2007). The compartments of the larval lobe system are primarily supplied by dopaminergic neurons, but the UVL and LVL compartments also have octopaminergic input (Saumweber et al. , 2018).

Output: pass