Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: In terms of the functional impact of NO in the working of the SCN, blocking of NO production disrupts light transmission to the SCN [63], thus indicating the possibility of the role of NO in the light-input pathway. NO synthesis is required for phase changes of electrical activity [64]. Intracerebroventricular application of L-NAME (a drug that blocks NOS in hamsters) produces attenuation of light-induced phase-advances of activity rhythms [65]. Reports also indicate interruption in the light-triggered cascade of glutamate release from retinal terminals in the SCN by blockade of NO action in intact animals, which leads to subsequent interruption of NMDA receptor activation [66,67]. Interruption of intracellular increase of calcium, activation of nNOS, augmented production of cyclic guanosine monophosphate (cGMP), activation of protein kinase C, and phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), as well as interruption of the expression of immediate early genes, are other effects of blockade of NO action. Starkey and co-workers [68] provided evidence for the presence of functional type II NOS within the SCN of guinea pig. All isotypes of NO synthase have also been identified in the normal adult mammalian SCN. Contribution by more than one NOS isotype to the regulation of circadian rhythms cannot be ruled out. In this context, it is interesting to note the demonstration by Kriegfeld and co-workers [69] that mice lacking the gene for type I NOS experience no change in the ability to phase-shift or entrain circadian rhythm of locomotor activity. Yet another study, also by Kreigfeld and co-workers [70], has suggested that endothelial isoform of NOS among the three known isoforms may not be necessary for photic entrainment in mice. However, considering the three different forms of NOS identified, until the isoforms of NOS involved in regulating the clock phase by modulating inputs are completely established it is difficult to speculate the exact role of NO. There has been much speculation as to the photopigment mediating light information to the SCN. However, this is not yet known with certainty [71]. [SEP] Justify:

Output: The text discusses the role of nitric oxide (NO) in the functioning of the suprachiasmatic nucleus (SCN) and its impact on circadian rhythms, but does not specifically state that the SCN is the master regulator of these rhythms. It presents complex biochemical pathways and effects of NO without directly supporting or contradicting the claim that the SCN is the master regulator. Therefore, the text is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Flora imbalance in cirrhotics might be caused by decreased gut motility, diminished excretion of sectretory IgA, lysozyme, mucus, acids, increased pH, shortage of bile acids, and excessive alcohol intake. Elevated blood ammonia is a crucial factor in hepatic encephalopathy aetiology. Loguercio et al[21] conducted a pilot study in patients suffering from hepatitis of various causes (HCV, alcoholism, and NASH). The patients received a probiotic mix (Lactobacillus acidophilus, L. bifidus, L. rhamnosus, L. plantarum, L. salivarius, L. bulgaricus, L. lactis, L. casei, L. breve + fructo-oligosaccharides + vitamins). Interestingly, the authors reported no effect of probiotics in HCV patients. In NASH patients some liver function parameters (ALT and γ-glutamyltransferase) improved, TNF-α decreased and plasma malondialdehyde decreased in some patients with probiotic treatment. The strongest effect of protiotics was seen in patients with alcoholic liver cirrhosis, where all parameters of liver function improved, as did TNF-α and malondialdehyde. From these studies in humans, it appears that the microflora is an important cofactor in the aetiology of chronic liver disease, and that probiotics might have a therapeutic role. Probiotics to bind toxins and carcinogensSome experimental evidence suggests that probiotics could be used to bind and immobilise toxic compounds within the gut lumen. Through this process, the negative effects of dietary toxins could be reduced and gut and liver health improved. In vitro, L. rhamnosus GG is able to bind mycotoxins known to interfere with intestinal mucosal barrier. In Caco-2 cells, the negative effects of mycotoxins on cell differentiation and intestinal integrity can be attenuated with L. rhamnosus GG[41,42]. In rats, genotoxic effects of food carcinogens, such as heterocyclic amines, on the colonocytes and hepatocytes were counteracted by the use of different probiotics[43,44]. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential therapeutic role of probiotics in improving gut and liver health. It mentions that probiotics might help in the aetiology of chronic liver disease and could bind toxins to reduce negative effects, which aligns with the idea that probiotics can support gut health by improving the balance of bacteria and function within the gut.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: This could lead to less successful weight loss. In addition, after exclusion and drop-out of some participants, in the remaining evaluable 100 participants, there was a significant difference in baseline body weight and BMI between CG and EG. However, even if CG participants had been heavier from the start, it cannot be assumed that the applied sham treatment with an eating window of 18 hours during wake time would have had a stronger effect. Second, those subjects in the EG group whose baseline BMI was similar to those of the CG subjects lost significant weight during the intervention, while CG participants did not. Taking these two arguments into account, it cannot be assumed that a floor effect, in which the CG participants cannot lose any more weight due to a lower baseline weight, is the reason for the lack of weight loss in the CG. Lasty, studies show that even much larger baseline BMI differences do hardly affect the success of weight loss programs [45, 46], so we assume that this also applies to our study. During the course of the study, there were some drop-outs in both groups. Importantly, these did not differ in baseline weight from the completers, which is why it can be ruled out that the intervention was not effective in a particular BMI group. Rather, the subjects who dropped out were those who either could not continue due to illness or did not adhere to the meal plan. However, the inclusion of drop-outs in the analysis of weight progression does not fundamentally change the results. 3. 2. ConclusionThe present study can be regarded as a pilot study, the results of which we believe justify a continuation with adjustment of the above-mentioned limitations. In summary, our data show that the increase of regularity of meals to a period of 90 min for each meal promotes a significant reduction of body weight and a significant increase of well-being within short time. Importantly, the successes achieved do not seem to be related to a reduction in calories, a change in food composition, or other eating behaviors. Additionally, we believe that this intervention poses hardly any health risks since it is most likely solely based on the optimization of metabolic processes. On the contrary, the strong increase in general well-being during the study rather indicates an improvement in health on many different levels. 4. Methods4. 1. Experimental approachThe study was a randomized controlled intervention trial with repeated measures investigating the effect of regularity of mealtimes on body weight and parameters related to overall well-being. [SEP] Justify:

Output: The text contrasts the claim by presenting evidence from a study indicating that the regularity of meals rather than carbohydrate intake is responsible for significant weight loss. It emphasizes that the intervention promoting a structured eating schedule led to weight loss, and that the success was not associated with a reduction in calories or food composition changes. This counters the absolute claim that eating carbohydrates results in weight gain.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: A novel opsin, melanopsin, was identified [72] and found to be exclusively expressed in the ganglion cells of RHT [20,73,74]. Melanopsin-containing RHT ganglion cells also use PACAP, another well known neurotransmitter of the RHT [20]. Melanopsin, however may not be the only circadian photoreceptor since melanopsin knock-out mice showed typical, although reduced, light responses such as entrainment and phase shifting. Possibilities of other neuroactive substances serving as neurotransmitters in the RHT in addition to glutamate and PACAP, which are the most important candidates, have been indicated. Projections of substance P (SP)-containing ganglion cells to the ventrolateral part of the SCN have been demonstrated in lesion experiments in the rat [75]. Electrophysiological investigations also further support the role of substance P as an excitatory neuromodulator [76] responsible for the expression of both NMDA and non-NMDA receptor-mediated components of RHT transmission. Moreover, it is also reported that SP and glutamate work as agonists upstream of glutamate [77]. substantial evidence [17,78,79] suggesting a role for histamine as a neurotransmitter in circadian entrainment [17,78,79], its role has been underplayed. With more information available and even a suggestion that histamine may be acting as a final neurotransmitter on which photic and non-photic entrainment converge [80], there has been more attention in this direction. Histamine can induce phase shifts in circadian rhythms in a manner similar to that of light pulses. Intracerebroventricular injection of histamine is also found to alter circadian function [81]. Direct effects of histamine on SCN neurons have been shown in vitro either as inhibitory or excitatory depending on experimental conditions [82,83]. It is also reported that at the level of the SCN the direct excitatory effects of histamine on neuronal firing is mediated via H1 receptors and the inhibitory effects via H2 receptors [82,83]. However, in vivo studies, it has been shown that the effects of histamine on circadian rhythms may be mediated through receptors other than histamine receptors [84,85]. The foregoing discussion supports the view that histamine may exert modifying effects on circadian rhythmicity as well as neuronal excitability. [SEP] Justify:

Output: The text is irrelevant to the claim because it discusses various neurotransmitters and their roles in circadian rhythms without explicitly mentioning the suprachiasmatic nucleus (SCN) as the master regulator. The discussion focuses on substances like melanopsin and histamine and their effects on circadian processes, but does not support or contradict the specific claim regarding the SCN.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Salminen et al[51] investigated the severity and outcome of lactobacillus bacteraemia in 89 patients, and report mortality of 26% 1 mo after illness onset, but only in patients with severe underlying comorbidities. Future of probiotic researchMost recent developments in probiotic and prebiotic research use a new systems biology approach to assess the complex relationship between the microflora, probiotic modulations, and the impact on host metabolism in multiple compartments. A major finding is the impact of microflora modulation on host energy metabolism, especially lipid metabolism in the liver where marked decreases in plasma lipoproteins and hepatic glutamine and glycogen levels are observed[52]. This group uses a germ free mouse model colonized with human baby flora, to study the effects of a probiotic intervention (L. paracasei or L. rhamnosus) on gut flora composition, SCFA in caecal content, plasma, urine, faecal and liver metabolomics, and bile acids in ileal flushes. The integration of multicompartment metabolic data using hierarchical principal component analysis showed that probiotic lactobacilli induce changes in hepatic influx and efflux of fatty acids, increased enterohepatic recycling of bile acids and dietary fats, lowered plasma LP, and stimulated glycolysis. Probiotic intervention also changed the proteolytic activity and bacterial metabolism of AA and SCFA in the gut[53]. In a mouse model of high-fat feeding and NAFLD, an association was shown between the metabolism of choline by microbiota and the host. The author suggested a contribution of microflora to the development of the NAFLD phenotype[54]. This complex analytical and statistical methodology allows investigation of the impact of microflora and probiotics on various body compartments simultaneously and might, in the future, lead to a better understanding of the influence of probiotics on the host. Similarly, the complex metabolic relationships between the microflora and the host have also been studied in human cohorts and this approach might be used to gain further understanding of the relation between changes in the microflora (dysbiosis) and disease[55]. appears that specific clinical applications of probiotics are safe, effective, and can clearly be recommended. [SEP] Justify:

Output: The text corroborates the claim by discussing the effects of probiotics such as L. paracasei or L. rhamnosus on gut flora composition and metabolic processes within the host. It highlights the complex relationship between probiotics and the microflora, noting that 'probiotic lactobacilli induce changes in hepatic influx and efflux of fatty acids' which suggests a supportive role in gut health and an improved balance of bacteria. Furthermore, it mentions that specific applications of probiotics are 'safe, effective, and can clearly be recommended,' aligning directly with the assertion made in the claim.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: 2-way repeated-measure ANOVA with Bonferroni post-hoc test, CG: n=30; EG: n=67, * p ≤ 0. 05, (detailed statistics in Tab. S3). (L) Correlation between reported ingested energy during the exploration phase vs. the intervention phase. Linear regression, CG: n=30; EG: n=67 (some participants were excluded from this analysis because of several erroneous diary entries about unrealistic amounts of food), (detailed statistics in Tab. S6). (M) Determined and estimated cumulative intake of fat, carbohydrates, and proteins during the study. Mixed-effects model with Bonferroni post hoc test comparing determined and estimated cumulative energy intake. The estimated macronutrient intake is formed as an assumed continuation of the average daily intake during the exploration phase. post hoc test showed no significant differences on any study day. (N) No significant correlation between body weight/BMI and changes of cumulative macronutrient intake. Linear regression, CG: n=30; EG: n=67, (detailed statistics in Tab. S6). (K, L, M, N) Some participants were excluded from this analysis because of several erroneous diary entries about unrealistic amounts of food. (O) The absolute deviation between the times of weekend meals and the times of food intake calculated for the EG intervention did not affect the subjects’ BMI change. Linear regression, n=67 (detailed statistics in Tab. S6). Table S1:Baseline characteristics of final 100 participants. Table S2:Statistical data on the difference between two groups. Missing n-numbers in 3I are due to incomplete diary entries on weekends during the exploratory phase or because participants usually did not have a particular meal. The data in the table refers to the data shown in Fig. S2A, S2G, and 3I. Table S3:Statistical data from all Two-way-analyzing time, group, as well as interaction effects between time x group. In data for Figure 1, missing p-values in the and EG are due to the different number of meals for each participant. In the data for Figure 2, some participants were excluded from this analysis because of several probably erroneous diary entries about unrealistic amounts of food. In data for Figure 3, varying n-numbers result from incomplete entries in the diaries. [SEP] Justify:

Output: The text contrasts the claim by detailing statistical analyses that show no significant correlation between body weight/BMI and changes in cumulative macronutrient intake, including carbohydrates. It specifically states that 'no significant correlation between body weight/BMI and changes of cumulative macronutrient intake' was found, indicating that carbohydrate consumption does not necessarily lead to weight gain.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: There is a clear circadian rhythm in the histaminergic activity, with high levels during the active period and low levels during the sleep period. Maintenance of circadian rhythmicity of sleep-wakefulness cycles, food intake, motility and adrenocortical hormone release seems to depend on histaminergic activity. Thus, although evidence is accumulating for a role of histamine in circadian function, it is difficult to assign it a specific role in circadian activity at this time. Neurotensin (NT) Cell bodies of the rat SCN contain the neuropeptide neurotensin (NT) and two NT receptor types, namely NTS1 and NTS 2 [86 - 88]. In humans there is a larger population of NT neurons as compared to monkeys and other animals. Although involved in many physiological processes, the role of NT in circadian rhythm is not completely known at present. Meyer-Spasche and co-workers [89] reported that NT can phase shift the firing rate rhythm of SCN neurons. They also provided evidence that NT may play a role in regulating the circadian pacemaker through NTS1 and NTS2 receptors. NT-binding sites found in the ventral region of the SCN, which receives photic and non-photic information, is indicative of the involvement of NT in the synchronization of clock to these environmental stimuli [90]. Studies using NTS1 and NTS2 agonists, neurotransmitter receptor antagonists, as well as the exogenous application of NT, have yielded some valuable results. An increase in discharge rate of SCN neurons was observed on NT application [90]. NT-mediated effects on SCN neurons seem to result from activation of NTS1 and NTS2 receptors rather than involve glutamate or GABA receptors or modulation of the synaptic release of glutamate or GABA [90]. NPY, which is an established neurotransmitter of the geniculohypothalamic tract (GHT), was found to regulate SCN neuronal activity [91 - 93] and to produce long lasting suppression of firing rate of SCN neurons. When co-applied with NPY, NT was found to damp the profound inhibitory effect of NPY [90,92,93]. This is interesting since there are studies showing that NPY immunoreactive terminals overlap with NT-binding sites in the ventral part of the SCN. This was considered as evidence of an interaction of NPY and NT to regulate neural activity. [SEP] Justify:

Output: The text is largely irrelevant to the claim because it discusses the role of histaminergic activity and neurotensin (NT) in circadian rhythms but does not specifically address the function of the suprachiasmatic nucleus (SCN) as the master regulator of circadian rhythms. While it mentions the SCN and its neuronal activity, it does not substantiate or refute the claim directly.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect Immun. 2008;76:1340-1348. [PubMed] [DOI] [Cited in This 8. Isolauri E, Salminen S. Probiotics, gut inflammation and barrier function. North Am. 2005;34:437-450, viii. [PubMed] [DOI] [Cited in This 9. Corthésy. Cross-talk between probiotic bacteria and the host immune system. J Nutr. 2007;137:781S-790S. [PubMed] [DOI] [Cited in This 10. Macpherson AJ, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1662-1665. [PubMed] [DOI] [Cited in This 11. Wang M, Molin G, Ahrné S, Adawi D, Jeppsson B. High proportions of proinflammatory bacteria on the colonic mucosa in a young patient with ulcerative colitis as revealed by cloning and sequencing of 16S rRNA genes. Sci. 2007;52:620-627. [PubMed] [DOI] [Cited in This 12. . Intestinal bacteria and ulcerative colitis. Intest Microbiol. 2003;4:9-20. [PubMed] [DOI] [Cited in This 13. . Probiotics and their derivatives as treatments for inflammatory bowel disease. Dis. 2009;15:1906-1914. [PubMed] [DOI] [Cited in This 14. . Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology. 2001;121:580-591. [PubMed] [DOI] [Cited in This 15. . Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology. 1999;116:1107-1114. [PubMed] [DOI] [Cited in This 16. . [SEP] Justify:

Output: The text corroborates the claim by mentioning various studies that support the role of probiotics, including specific strains like Lactobacillus rhamnosus, in maintaining gut barrier function and potentially influencing gut health. The citations throughout the text relate to how probiotics, through their interaction with the gut and immune system, can positively affect gut health and the equilibrium of intestinal bacteria.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: AbstractObjectiveMany weight loss strategies are based on the restriction of calories or certain foods. Here, we tested a weight loss intervention based solely on increasing the regularity of meals to allow the circadian system to optimally prepare food metabolism for these times. Participants & MethodsIn a two-group, single center randomized-controlled single-blind study (pre-registration DRKS00021419) with participants aged 18-65 years and BMI ≥ 22 kg/m², we used a smartphone application to identify the times at which each participant eats particularly frequently and asked participants of the experimental group to restrict their meals to only these times for six weeks. Control participants received sham treatment. Primary outcome was self-reported body weight/BMI and secondary outcome the well-being of participants. ResultsOf 148 participants entering the study, 121 were randomized and of these 100 (control: 33, experimental: 67) finished the study. Our results show that the more regular the meals of participants of the experimental group became, the more weight/BMI they lost, averaging 2. 62 kg (0. 87 kg/m²); p < 0. 0001 (BMI: p < 0. 0001) compared to an insignificant weight loss of 0. 56 kg (0. 20 kg/m²) in the control group; p = 0. 0918 (BMI: p = 0. 0658). Strikingly, weight loss was not related to changes in self-reported calories, food composition, and other food-related factors. Additionally, physical and mental well-being improved significantly. ConclusionIn summary, increasing the regularity of meals causes participants to lose excess body weight and improves overall well-being. HighlightsIndividual optimal times for meals are determined via an app-based meal diary. Generation of a structure plan for mealtimes are adjusted to individual circadian clocks. Following this plan, participants lost an average body weight of 2. 6 kg over six weeks. Weight loss is achieved without changes in self-reported food quantity or composition. Regular mealtimes contribute to the improvement of the general well-being. 1. IntroductionCircadian clocks induce endogenous 24-hour rhythms in the expression of more than half of all genes across all tissues [1, 2], allowing the body to anticipate daily changes between day and night and to prepare and harmonize physiological processes accordingly. [SEP] Justify:

Output: The text contrasts the claim by indicating that a study on meal regularity demonstrated participants losing weight without altering caloric intake or food composition. This suggests that weight gain is not solely determined by carbohydrate consumption or total food intake but instead is more complexly influenced by meal timing and regularity.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: From a developmental point of view, NT-expressing neurons developed earlier than the other 3 types of peptidergic neurons, and AVP [94]. It remains to be seen whether NT-expressing neurons contribute significantly to the generation of circadian rhythms in early human life. (NMS) A recent addition to the ever increasing list of neurotransmitters of the SCN is neuromedin S (NMS), a 36 amino acid neuropeptide. It is a potent brain-gut neuropeptide whose presence in the SCN was reported by Nakahara and co-workers [95] as a neurotransmitter of the circadian oscillator system. NMS expression is found to be restricted to the core part of the SCN and has a diurnal peak under light-dark cycle [96]. Intracerebroventricular administration of neuromedin S in rats activates SCN neurons and has the capability to induce non-photic type of phase shifts in the circadian rhythm of locomotor activity. It is also possible that NMS along with VIP may have a role in maintenance of circadian rhythmicity. Recently, it has been shown that neuromedin M (NMU) is regulated in a circadian manner with peak expression in the light phase of LD cycle [97]. Further studies are required to understand the specific role of NMS in the SCN. At present, it is implicated in the regulation of circadian rhythms through autocrine andor paracrine actions through its receptors [96]. Gastrin releasing peptide (GRP) Gastrin releasing peptide (GRP) has also been identified as a neurotransmitter in the SCN. Although GRP and its receptor BB2 are found to be synthesized by rodent SCN neurons [98 - 100], the role of GRP in circadian rhythm regulation is not well known. Evidence points towards a role for GRP in photic entrainment [101,102], in spite of a number of studies favouring glutamate as the main neurotransmitter [36,37,103]. McArthur and co-workers [104] studied the role of GRP in photic entrainment by using the resetting actions of GRP application on electrical activity rhythms during subjective day, early subjective night, and late subjective night in vitro in rats and hamsters. [SEP] Justify:

Output: The text does not directly address the claim regarding the suprachiasmatic nucleus (SCN) as the master regulator of circadian rhythms. Instead, it discusses specific neurotransmitters like neuromedin S (NMS) and gastrin releasing peptide (GRP) and their roles within the SCN, mentioning their implications in the regulation of circadian rhythms but not conclusively supporting the claim that the SCN is the primary regulator. Therefore, the text is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Bacteria-free solution derived from Lactobacillus plantarum inhibits multiple NF-kappaB pathways and inhibits proteasome function. Dis. 2009;15:1537-1547. [PubMed] [DOI] [Cited in This 17. . Meta-analysis of probiotics for the treatment of irritable bowel syndrome. Gastroenterol. 2008;14:2650-2661. [PubMed] [DOI] [Cited in This 18. . The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gastroenterol. 2009;104:1033-1049; quiz 1050. [PubMed] [DOI] [Cited in This 19. -Boussard T, Morton JM. Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg. 2009;13:1198-1204. [PubMed] [DOI] [Cited in This 20. . Does the use of probiotics/synbiotics prevent postoperative infections in patients undergoing abdominal surgery? A meta-analysis of randomized controlled trials. Clin Pharmacol. 2009;65:561-570. [PubMed] [DOI] [Cited in This 21. ì M. Gut-liver axis: a new point of attack to treat chronic liver damage? Gastroenterol. 2002;97:2144-2146. [PubMed] [DOI] [Cited in This 22. Sheth AA, Garcia-Tsao G. Probiotics and liver disease. J Clin Gastroenterol. 2008;42 Suppl 2:S80-S84. [PubMed] [DOI] [Cited in This 23. . Non-alcoholic fatty liver disease: lumen-liver interactions and possible role for probiotics. J Hepatol. 2003;38:681-687. [PubMed] [DOI] [Cited in This 24. Medina J, Fernández-Salazar LI, García-Buey L, Moreno-Otero R. Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care. 2004;27:2057-2066. [SEP] Justify:

Output: The text corroborates the claim by discussing the utility of probiotics in various gastrointestinal settings, including their effects on irritable bowel syndrome and liver disease. References to meta-analyses and systematic reviews suggest a positive contribution of probiotics to gut health, which aligns with the claim that they improve the balance of bacteria.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: (H) Significant correlation between change in BMI, baseline BMI, and improvement in MTVS. Individuals with higher BMI benefit more from similar improvements in MTVS (shades of data points) than individuals with lower BMI in EG participants. Multiple regression, n=67, * p ≤ 0. 05, ** p ≤ 0. 01. Detailed statistics in Tab. S9. 2. 3. Weight changeDuring the exploration phase, when no instructions on eating times were given, CG and EG participants had a statistically non-significant average loss of 0. 17 kg (0. 06 kg/m²) and 0. 21 kg (0. 06 kg/m²), respectively (Figs. 1E, S2B-F, Tabs. S4, 5). However, during the intervention phase, when EG participants took their meals more regularly, they lost an average of about 2. 6 kg (95% CI [-2. 906, -1. 915]) and 0. 81 kg/m² (95% CI [-0. 9729, -0. 6420]) (Figs. 1E, S2B-E, Tabs. S4, 5), which translates to an average weight loss of 0. 40 kg (0. 145 kg/m²) per week during the intervention. In contrast, weight and BMI changes of -0. 39 kg (95% CI [-0. 9125, 0. 1307]) and -0. 14 kg/m² (95% CI [-0-3152, 0. 0304]), respectively, were not significant in the CG (Figs. 1E, S2B, C, F, Tabs. S4, 5), resulting in a significant difference in weight loss between groups at the end of the intervention (Figs. 1F, S2C, Tab. S5). The inclusion of the last available weight and BMI data of the drop-outs in an end-point analysis did not lead to any notable change in this result (Fig. S2G, Tab. S5). Four weeks after the intervention ended, all participants were contacted again for a follow-up assessment. 34 of the 67 EG participants reported to have maintained the regularity of their meals and continued to lose body weight significantly, on average another 1. 12 kg (95% CI [-1. 479, -0. 7626]) and 0. [SEP] Justify:

Output: The text contrasts the claim by presenting data indicating that during an intervention phase, participants who took their meals more regularly (which likely included carbohydrates) achieved an average weight loss of about 2.6 kg. This suggests that rather than leading to weight gain, the consumption of carbohydrates in conjunction with regular meal timing can actually contribute to weight loss, contradicting the claim.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: This belief is further strengthened by the observation that dysfunction of serotonergic pathways play a role in affective disorders and that these disorders are frequently treated with agents that alter serotonergic neurotransmission. Further studies about this pathway are likely to give more information about the link between disruptions of circadian function and affective disorders. GABA It is now widely accepted that gamma amino butyric acid (GABA) is an important neurotransmitter of the SCN for regulating SCN function. Most SCN neurons express the neurotransmitter GABA and are thus GABAergic [12]. GABA receptors and receptor subunits have been described by Castel and Morris [139], Naun and co-workers [140], van den Pol [141], Gao and co-workers [142], and O'Hara and co-workers [143]. In most of the brain regions, GABA primarily acts through interaction with GABAA and GABAB receptors and produces neuronal inhibition through membrane hyperpolarization and increased membrane conductance. Glutamic acid decarboxylase (GAD) is the enzyme required for synthesizing GABA and is found in nearly all neurons of the SCN [116]. Additional support for an inhibitory role of GABA in the rat SCN has come from the studies of Gribkoff and co-workers [144,145]. However, recent investigations have shown that GABA has dual effects on the SCN neurons, excitatory during day and inhibitory at night [146], and this has been attributed to changes in [Cl-]I during the circadian cycle. This dual inhibitory [147] and excitatory [148] action of GABA has been thought of as the probable reason for the synchronization of spiking in the SCN neurons. Under some circumstances, such as in early development, GABA can also be depolarizing and potentially excitatory [126,149 - 151]. The excitatory effect of GABA on SCN neurons in the night seems to be complex. While the action of GABA in the day on SCN neurons is uniformly inhibitory, the effects of GABA during the night are heterogeneous due to both depolarizing and hyperpolarizing effects. The GABA-mediated depolarizing effect seen at night is restricted to a subset of SCN neurons. [SEP] Justify:

Output: The text discusses various aspects of GABA's role in the function of the suprachiasmatic nucleus (SCN), including its inhibitory and excitatory effects on SCN neurons and the implications for circadian rhythms. However, it does not directly address or support the claim that the SCN is the master regulator of circadian rhythms. Therefore, the text is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: [PubMed] [DOI] [Cited in This 25. à. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49:1877-1887. [PubMed] [DOI] [Cited in This 26. -Arenzana JM, Aldazabal P. Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome. J Pediatr Surg. 2002;37:699-702. [PubMed] [DOI] [Cited in This 27. . The role of the gut microbiota in energy metabolism and metabolic disease. Des. 2009;15:1546-1558. [PubMed] [DOI] [Cited in This 28. . Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37:343-350. [PubMed] [DOI] [Cited in This 29. . Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009;139:905-911. [PubMed] [DOI] [Cited in This 30. . Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. Syst Rev. 2007;CD005165. [PubMed] [DOI] [Cited in This 31. . Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol. 2008;49:821-830. [PubMed] [DOI] [Cited in This 32. . Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol. 2008;42:675-682. [PubMed] [DOI] [Cited in This 33. . Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis. Alcohol. 2009;43:163-172. [PubMed] [DOI] [Cited in This 34. . Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. [SEP] Justify:

Output: The text supports the claim by indicating several studies that suggest probiotics have beneficial effects on health, particularly in relation to gut flora and liver health. For instance, it mentions that probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury, which implies a positive role of probiotics in maintaining or enhancing gut health.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: 36 kg/m² (95% CI [-0. 4907, -0. 2457]), respectively (Figs. 1E, S2B, D, E, Tabs. S4, 5). In contrast, participants who reported to have resumed irregular eating gained a significant average of 0. 48 kg (95% CI [0. 1984, 0. 7616]) and 0. 17 kg/m² (95% CI [0. 07434, 0. 2603]), respectively (Fig. 1E, S2B, D, E, Tab. S4). 2. 4. Relation between weight change and improvement in the regularity of mealsTo examine the extent to which EG participants’ weight loss was effectively related to improvements in meal regularity, we correlated changes in body weight and BMI with individual MTVS changes. Consistent with our hypothesis, a significant relationship exists between weight loss and improvement in regularity in the EG (Fig. 1G, Tab. S6). A breakdown of meals shows that increasing the regularity of lunch and dinner has the greatest effects, with no significant relationship between increasing the regularity of breakfast and weight loss (Fig. S2H, Tab. S6). In contrast, in the CG, there were no or little improvements in regularity and, accordingly, no correlation with weight/BMI changes. Further analyses revealed that all MTVS up to 3, which corresponds to a time window for meals of up to ±45 min, resulted in comparably effective weight loss, whereas the efficiency of weight loss decreases significantly with an MTVS greater than 3 (Tab. S7). 2. 5. Relation between weight change and baseline BMIA weight loss intervention which is particularly based on metabolic optimization is likely to be most effective for individuals with exceeded body weight. In fact, the higher the baseline BMI of EG participants at T1, the greater the weight loss (Fig. S2I, Tab. S6). Stratifying the subjects by baseline BMI, including the control group, confirms this result, but also shows that in all strata the BMI of EG subjects decreased more than that of CG subjects, even if they had the same initial BMI (Fig. S2J, Tab. S8). Multiple regression shows that the reduction in MTVS and baseline BMI together predict the weight loss of the participants (Fig. 1H, Tab. S9). [SEP] Justify:

Output: The text contrasts the claim by discussing the relationship between meal regularity and weight change, indicating that irregular eating can lead to weight gain as evidenced by participants gaining an average of 0.48 kg. It emphasizes that improvements in meal regularity were associated with weight loss, suggesting that factors beyond carbohydrate intake contribute to weight management.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: SCN transplants lacking CalB cells failed to restore rhythmicity [247]. CalB cells are found to co-localize with other peptides such as GRP, SP, and VIP. Interconnections of CalB cells with and VIP have been reported [246], and the pattern of interconnection of CalB cells appear specialized in the sense that some are bilateral, while others are not [248]. The strength of linkage between interconnections also varies. Intra-SCN connections are influenced to a great extent by the projections of CalB cells. The connections are direct in some cases and indirect in others. However, indirect communication as is the case with CalB to AVP is equally effective. In addition to intra SCN communication, CalB cells may also project to extra SCN regions [248]. CalB cells appear to be non rhythmic. They, however, receive photic input from the RHT and GHT, and rapid transmission of light information to CalB neurons may facilitate circadian output [226]. Light exposure always increases firing rates of SCN neurons. However, cells in the core of the SCN oscillate in their responsiveness to photic input [5]. Light also induces clock gene expression in the SCN but only during the night [8,249]. This gene expression pattern seems to be mirrored by changes in subcellular localization of CalB, the cellular nucleus being devoid of CalB during the night [249]. Behavioural and molecular responses to nocturnal light pulses also disappeared on decreasing CalB levels [249]. Thus, CalB cells in the SCN function as gates to relay photic signals when open and to block the signals when closed, which suggests a central role for CalB neurons in gating photic input. Further investigation seems essential to elucidate the relation between functional connectivity and a single coherent output from the SCN. Calretinin (CALR) Calretinin (CALR) is another variety of neurons found in the SCN (in the core ventral part) that appears to be co-localized with VIP neurons. CALR cells are small to medium sized. Optic tracts also show heavy immunoreactivity for CALR. Like calbindin (CalB), CALR is a calcium binding protein. [SEP] Justify:

Output: The text provides detailed information about various cellular components within the suprachiasmatic nucleus (SCN) and their roles, such as CalB and CALR cells, as well as the interconnections among them. However, it does not explicitly support or contradict the claim regarding the SCN being the master regulator of circadian rhythms. Instead, it focuses on intricate cellular dynamics and signaling mechanisms which may indirectly relate to circadian functions but does not definitively address the claim itself.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Exp Res. 2009;33:1836-1846. [PubMed] [DOI] [Cited in This 35. . Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374-2383. [PubMed] [DOI] [Cited in This 36. Lata J, Novotný I, Príbramská V, Juránková ůrek O. The effect of probiotics on gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study. Gastroenterol Hepatol. 2007;19:1111-1113. [PubMed] [DOI] [Cited in This 37. Guerrero Hernández. Intestinal flora, probiotics, and cirrhosis. Ann Hepatol. 2008;7:120-124. [PubMed] [DOI] [Cited in This 38. . Intestinal microflora in patients with liver cirrhosis. Dig Dis. 2004;5:64-67. [PubMed] [DOI] [Cited in This 39. Adawi D, Ahrné S, Molin G. Effects of different probiotic strains of Lactobacillus and Bifidobacterium on bacterial translocation and liver injury in an acute liver injury model. Food Microbiol. 2001;70:213-220. [PubMed] [DOI] [Cited in This 40. Osman N, Adawi D, Ahrné S, Jeppsson B, Molin G. Endotoxin- and D-galactosamine-induced liver injury improved by the administration of Lactobacillus, Bifidobacterium and blueberry. Dis. 2007;39:849-856. [PubMed] [DOI] [Cited in This 41. -änen H, Turner PC. Lactobacillus rhamnosus strain GG reduces aflatoxin B1 transport, metabolism, and toxicity in Caco-2 Cells. Microbiol. 2007;73:3958-3964. [SEP] Justify:

Output: The text corroborates the claim by referencing multiple studies that examine the effects of probiotics on gut flora. For instance, the mention of selective increases of bifidobacteria and their role in improving high-fat-diet-induced diabetes suggests that probiotics can positively influence gut health by enhancing the balance of beneficial bacteria.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: These data show that regularity in meal intake can lead to a significant loss of body weight and suggest that this effect is especially pronounced in individuals with a higher BMI. 2. 6. Relation between weight change and self-reported food quantity and compositionBy restricting meals to specific times and shortening the time window in which food is eaten, it is feasible that EG participants ate less or changed food composition during the intervention phase and therefore lost weight. However, on average, the reported food energy ingested by CG and EG participants did not substantially change during the study (Fig. 2A, S2K, L, Tab. S3, 6), apart from a minor average reduction of ∼350 kJ (95% CI [-627. 6, - 67. 67]) per day in the EG (Fig. S2K, Tab. S3, 6), and did not differ between CG and the EG. As they are rather small, these differences do not add up to a significant reduction in the total average energy consumed over the course of the study. Accordingly, the determined cumulative average energy intake during the intervention phase did not differ on any day from the estimated energy intake based on an extrapolation of the cumulative food consumption during the exploration phase, neither in the CG nor in the EC group (Fig. 2B). Nevertheless, there were some participants who reported having consumed fewer calories during the intervention phase, while some also reported having ingested more calories. However, consistent with our hypothesis that high regularity of mealtimes optimizes metabolism of similar amounts of food, there is no relationship between reported changes in average daily and cumulative energy intake and change in body weight/BMI of either CG or EG participants (Fig. 2C, D, Tab. S6). Likewise, the composition of the ingested foods did not change considerably in either group, and participants reported a normal distribution of the macronutrients of fat, carbohydrate, and protein in both phases of the study (Fig. 2E, S2M). Also, there was no correlation between weight change and change in reported average daily and cumulative macronutrient intake (Fig. 2D, S2N, Tab. S6). Fig. 2:Changes in body weight/BMI are not related to changes in reported caloric intake and composition of macronutrients. [SEP] Justify:

Output: The text contrasts the claim by explaining that changes in body weight and BMI are not related to changes in reported caloric intake and macronutrient composition, stating that 'there was no correlation between weight change and change in reported average daily and cumulative macronutrient intake.' This suggests that consuming carbohydrates does not inherently result in weight gain, contrary to the claim.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: Apparently, there is a developmental reduction in Calbindin-D28k expression parallel to RHT formation and a developmental increase in calretinin expression which is independent of RHT connections to SCN neurons [250]. Galanin (Gal) Galanin is yet another peptide associated with the SCN. It is a 29/30 amino acid neuropeptide seen in many parts of the nervous system [251], including the SCN [9,252,253]. In fact, neurons containing both galanin and AVP have been reported in human SCN [253]. In rat SCN, galanin receptor subtype R2 (Gal-R2) expression has been identified [254]. Angiotensin II (ANG II) Angiotensin II (ANG II) is an octapeptide found in the SCN [15,255] and is likely to be involved in circadian function. The presence of ANG II in the SCN has been demonstrated both at light microscopic [15] and electron microscopic level [256] in normotensive rats. Of late there has been much interest in the physiological, pharmacological, and immunohistological studies of angiotensins of the SCN. At present the available information on the role of angiotensin II at the level of the SCN is much less than that on the role of known transmitters of the SCN. It has been proposed that SCN-derived angiotensin II acts as a neuromodulator as well as neurotransmitter with the effects being mediated through angiotensin1(AT1) receptors located on the endothelial plasma membrane of SCN parenchyma [257]. Met-Enkephalin (mENK) These neurons are located primarily dorsomedially in the shell of the SCN and overlap with the distribution of AVP neurons. mENK cells are large to medium sized. Enkephalin has been found in the neurons of the IGL [116,117,122,258] projecting to the ventrolateral aspect of the SCN. The role of enkephalin as a putative neurotransmitter has been demonstrated in hamster SCN. Injection of retrograde tracer fluoro-gold into the SCN showed the existence of a population of labelled neurons in the intergeniculate leaflet which are immunoreactive for enkephalin [117]. [SEP] Justify:

Output: The text passes regarding the claim as it provides detailed information about the various neuropeptides and signaling molecules associated with the suprachiasmatic nucleus (SCN), but it does not explicitly support or reject the idea that the SCN is the master regulator of circadian rhythms.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: [PubMed] [DOI] [Cited in This 42. änen H, El-Nezami H. Lactobacillus rhamnosus strain GG restores alkaline phosphatase activity in differentiating Caco-2 cells dosed with the potent mycotoxin deoxynivalenol. Toxicol. 2008;46:2118-2123. [PubMed] [DOI] [Cited in This 43. üller S. Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains. Carcinogenesis. 2003;24:1913-1918. [PubMed] [DOI] [Cited in This 44. . Effects of lactic acid bacteria on binding and absorption of mutagenic heterocyclic amines. Biochem. 1998;62:197-200. [PubMed] [DOI] [Cited in This 45. Gratz S, Täubel änen H, El-Nezami H. Lactobacillus rhamnosus strain GG modulates intestinal absorption, fecal excretion, and toxicity of aflatoxin B(1) in rats. Microbiol. 2006;72:7398-7400. [PubMed] [DOI] [Cited in This 46. El-änen HM. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. Clin Nutr. 2006;83:1199-1203. [PubMed] [DOI] [Cited in This 47. Liong MT. Safety of probiotics: translocation and infection. Nutr Rev. 2008;66:192-202. [PubMed] [DOI] [Cited in This 48. ärvinen A. Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland. Dis. 2002;35:1155-1160. [PubMed] [DOI] [Cited in This 49. . Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. J Can. [SEP] Justify:

Output: The text includes references to various studies involving Lactobacillus strains and their effects on health, which supports the claim that probiotics can positively impact gut health. For instance, it mentions that Lactobacillus rhamnosus strain GG plays a role in modulating intestinal absorption and has beneficial effects on gut bacteria.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: CG: 21:31 (95% CI [21:05, 21:57])) (Fig. 3C, D, Tab. S3). However, weight changes of participants were not related to one of these changes in eating characteristics (Fig. 3B-D, Tab. S6). Fig. 3:Influence of other changes in eating times and of personalization of meal schedules on weight loss. (A) 95th percentile of the time period during which food was ingested by 15 example participants during the exploration phase (yellow) and the intervention phase (purple). (B) Change in length of this period and its relation to weight/BMI changes. (C, D) Change in time of first (C) and last (D) caloric intake and their association with weight/BMI changes. (B-D) 2-way repeated-measures ANOVA with Bonferroni post hoc test comparing CG and EG during the exploration or intervention phase and T0-T1 and T1-T2 within groups, *** p ≤ 0. 001, **** p ≤ 0. 0001. Linear regression. EG: n=67, varying n-numbers result from incomplete entries in the diaries. Detailed statistics in Tables S3 and S6. (E) The relation between mid-Sleep phase and mid-Eat phase (brown) on the weekends of the exploration phase. The goodness of fit of this association improves during through EG intervention and affects both workdays and weekend days (purple). Linear regression, n=65, **** p ≤ 0. 0001. Detailed statistics in Table S6. (F) Relation of the mid-Sleep phase (mSP) and mid-Eat phase (mEP) during exploration and intervention phase. The circles represent 24 h, the gray area represents the estimated sleep time, and the black arrow represents the mid-sleep phase, which is normalized for all subjects. The colored triangles represent the mid-Eat phase of each subject in relation to their mid-Sleep phase. The red arrow shows the average mid-Eat phase across all subjects. n=65. Detailed statistics in Table S10. (G) The smaller the residuals, i. e. , the vertical distances of observation points from the regression line, became, the more BMI the EG subjects lost. Linear regression, n=65, ** p ≤ 0. 01. Detailed statistics in Table S6. [SEP] Justify:

Output: The text contrasts the claim by discussing various factors affecting weight changes that are not related to specific eating characteristics, as indicated by the statement 'However, weight changes of participants were not related to one of these changes in eating characteristics.' This suggests that carbohydrates alone do not determine weight gain and implies other factors are influential in weight management.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: Among the three main classes of opioid receptors, little δ or μ opioid receptor expression has been identified through autoradiographic techniques in hamster SCN in vitro [259,260]. No direct effect on basal or N-methyl-D-aspartate (NMDA)-evoked firing rates of SCN neurons in hamster has been observed on short -term application of opioid receptor agonists [261]. However, the observation of SCN neurons exhibiting withdrawal responses after the influence of enkephalins had been removed indicates that endogenous opioids may play a role in modulation of SCN function. On the other hand, naloxone injection into the SCN is reported to produce disruption of the circadian pattern of food [262] and water [263] intake. Prokineticin 2 (PK2) Prokineticin 2 (PK2) has been identified as an output molecule from the SCN circadian clock [236]. PK2 is a cystein-rich secreted protein. It is reported to be involved in the transmission of behavioural circadian rhythm as well as in local function within the SCN to synchronize the out put [236]. PK2, named for its ability to stimulate intestinal smooth muscle contractility, is proposed to have a major role in inhibiting locomotor activity during the day in nocturnal species [236]. Receptors for PK2, PKR2, are found abundantly in the target nuclei of the SCN output pathway, indicating again that it is an output molecule. A recent study [264] demonstrated that the molecular rhythm of PK2 in the SCN is regulated by both circadian clock and light, with the clock having a predominant role and light having a modulatory role. PK2 expression induced by light independent of the circadian oscillator may also indicate participation of PK2 in the photic entrainment of circadian rhythms. Evidence suggesting diurnality in behavioural patterns based on alterations in PK2 receptors in regions receiving SCN efferents does not seems to provide a complete answer at least in rodents[265]. The action may be downstream of the SCN or may be in parallel to the PK2/PKR2 receptor systems[265]. Relationship between the biological clock of humans and those of other mammals The majority of studies of SCN function has been conducted on laboratory animals, particularly the rat. [SEP] Justify:

Output: The text is largely irrelevant to the claim regarding the suprachiasmatic nucleus (SCN) being the master regulator of circadian rhythms. It discusses opioid receptor expression, the involvement of endogenous opioids in SCN function, and the role of Prokineticin 2 (PK2) in behavioral circadian rhythms. While it touches on aspects concerning the SCN and its potential functions, there is no direct support or contradiction to the specific claim about the SCN as the master regulator of circadian rhythms.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Remarkably, these effects were largely reversed following fecal transplantation and treatment with SCFA (Lahiri et al. , 2019). Studies in animal models consistently reveal that alterations in gut microbiome composition can regulate the metabolic functions of skeletal muscle. Thus, understanding the intricate relationship between the gut microbiome and host physiology is crucial for developing lifestyle, nutritional, and pharmaceutical interventions to preserve and enhance skeletal muscle health. Studies in humans have also identified a link between the composition of the gut microbiome in the elderly and skeletal muscle function. Alterations in the gut microbiome, often observed when older adults move to long-term care facilities, can impact bone and body composition. This transition seems largely attributable to dietary modifications, shifting from a fiber-rich, predominantly plant-based diet at home to one with lower fiber, increased fat, and greater sucrose levels in the facilities. Furthermore, elderly adults in these institutions frequently undergo prolonged antibiotic therapy and have coexisting medical conditions. They also live alongside other seniors, factors which collectively impact gut microbiota. Such changes can potentially contribute to conditions such as sarcopenia, osteoporosis, and obesity, consequently heightening fracture risks (Inglis and Ilich, 2015). Correlation between gut microbiota and age-related sarcopenia via gut-muscle axis Currently, the role of the gut-muscle axis in maintaining muscle health during aging is supported by evidence from animal studies and human research. Nonetheless, the precise mechanisms at play are not fully elucidated. This study intends to thoroughly investigate the possible underlying mechanisms. These encompass factors such as protein metabolism, systemic chronic inflammation, metabolic resistance, mitochondrial dysfunction, and their impact on the expression of host genes. In older adults, the gut microbiota may impact their health by affecting aging-related sarcopenia. The reduction in muscle mass and strength observed in the elderly could be linked to changes in their gut microbiota. Studies have shown that individuals with sarcopenia, or those at risk of sarcopenia, exhibit notably lower microbial diversity compared to healthy controls. These individuals tend to have higher levels of Lactobacillus and lower levels of Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium (Kang et al. , 2021). [SEP] Justify:

Output: The text corroborates the claim by discussing the relationship between gut microbiota and health, particularly focusing on the aging population. It mentions that alterations in gut microbiome composition can impact metabolic functions and the overall health of skeletal muscle, indirectly supporting the implication that a balanced gut microbiome, which probiotics aim to achieve, is crucial for health. Additionally, it highlights studies indicating that individuals with sarcopenia have reduced microbial diversity compared to healthier individuals, emphasizing the importance of gut bacteria balance.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: (H) Representative example of a meal diary showing a shift from meals on weekends. The purple arrows represent the calculated times, based on the events of the more frequent workdays, for the meal schedule of the intervention phase. (I) Shifts from weekend meals caused by the EG intervention. Paired t-test, n=65, *** p ≤ 0. 001, **** p ≤ 0. 0001. Data are normalized so that all baseline data at T0-T1 equal 0 to represent the change in hours. Detailed statistics in Table S11. (J) Large phase shifts of breakfast and dinner, equivalent to a correction of the social jetlag of meals on weekends, are related to greater weight loss. Linear regression, breakfast: n=55, lunch: n=64, dinner: n=63, ** p ≤ 0. 01. Missing n-numbers are due to incomplete diary entries on weekends during the exploratory phase or because participants usually did not have a particular meal. Detailed statistics in Table S6. (K) Results of a multiple regression to investigate the influence of individual variables while holding the others constant on the BMI of EG participants. The Quantile-Quantile (QQ) plot shows the data are normally distributed (left). The multiple regression plot and R2 value shows that the multiple regression model explains the data well (middle). Additionally, the assignment of each regression beta coefficient to the independent variables is shown along with the p-values showing the influence on BMI. The data used are the same as those used in the individual regressions shown previously. Detailed statistics in Tab. S9. (L) Covariance matrix with normalized covariances for each pair of parameters. Values close to 1 (blue) or -1 (red) indicate high intertwining of the data, values close to 0 (white) indicate independence or orthogonality of the data. The assignment of the coefficients to the independent variables is the same as in (K). 2. 8. Effect of meal schedule personalization on weight lossA key part of our hypothesis involves the personalization of meal schedules. Consistent with the concept of social jet lag, our data show that during the exploration phase, eating times on workdays differ from those on work-free days, and we expect eating times on non-workdays to correspond more closely to individual circadian characteristics. [SEP] Justify:

Output: The text contrasts the claim by discussing how meal scheduling and timing, rather than just carbohydrate consumption, play significant roles in weight loss and body mass index (BMI). It emphasizes that 'large phase shifts of breakfast and dinner... are related to greater weight loss' indicating that when meals are properly timed, they can lead to weight loss despite the carbohydrate intake.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: Pituitary adenylate cyclase-activating polypeptide produces a phase shift associated with induction of mPer expression in the mouse suprachiasmatic nucleus Neuroscience 113: 37–45. [PubMed] Bos, NP and Mirmiran, M (1993). Effects of excitatory and inhibitory amino acids on neuronal discharges in the cultured suprachiasmatic nucleus Bull 31: 67–72. [PubMed] Scott, G and Rusak, B (1996). Activation of hamster suprachiasmatic neurons in vitro via metabotropic glutamate receptors Neuroscience 71: 533–541. [PubMed] Abe, H, Rusak, B and Robertson, HA (1992). NMDA and non-NMDA antagonists inhibit photic induction of Fos protein in the hamster suprachiasmatic nucleus Bull 28: 831–835. [PubMed] Colwell, CS and Menaker, M (1992). NMDA as well as non-NMDA receptor antagonists can prevent the phase shifting effects of light on the circadian system of the golden hamster J 7: 125–136. [PubMed] Decker, K and Reuss, S (1994). Nitric oxide -synthesizing neurons in the hamster suprachiasmatic nucleus: a combined NOS -and NADPH-staining and retinohypothalamic tract tracing study 666: 284–288. [PubMed] -mayer, A and Sppessert, R (1995). Nitric oxide synthase in the hypothalamic suprachiasmatic nucleus of rat: evidence from histochemistry, immunochemistry and western blot and colocalization with VIP 695: 257–262. [PubMed] le, Mayer, B and Gillette, MU (1997). Localization and characterization of nitric oxide synthase in the rat suprachiasmatic nucleus: evidence for a nitergic plexus in the biological clock J Neurochem 68: 855–861. [PubMed] and Schirar, A (2000). Endothelial and neuronal nitric oxide synthases are present in the suprachiasmatic nuclei of Syrian hamsters and rats Neurosci 12: 649–661. [PubMed] and Gillette, MU (1989). [SEP] Justify:

Output: The text provides various studies and references related to the suprachiasmatic nucleus, but it does not clearly support or refute the claim that it is the master regulator of circadian rhythms. Instead, it lists different aspects and factors influencing neuronal functions within the suprachiasmatic nucleus without directly addressing the claim itself.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Additionally, recent investigations have shown that metabolites produced by the commensal gut microbiota, such as SCFAs and secondary bile acids, can impact mitochondrial activities related to energy generation, mitochondrial formation, redox equilibrium, and inflammatory pathways, suggesting their potential role in enhancing endurance (Circu and Aw, 2012; et al. , 2013; Mottawea et al. , 2016). For instance, gut commensal microbiota reduce ROS production via SCFA such as N-butyrate (Mottawea et al. , 2016). Therefore, a disruption of the relationship leads to dysfunctional mitochondria. It is worth noting that mitochondrial dysfunction may play a vital role to link the relation between chronic inflammation and age-related sarcopenia, and the gut microbiota dysbiosis may be a key role in the gut–muscle crosstalk (Picca et al. , 2018). Consequently, any disruption of this intricate relationship can precipitate mitochondrial dysfunction. (et al. , 2018). Systemic chronic inflammation and metabolic resistance Sarcopenia’s progression is intimately linked to age-related systemic chronic inflammation (Grosicki et al. , 2018; et al. , 2018). Disruptions in gut microbiota can compromise the integrity of the host’s intestinal barrier and disturb the balance between pro-inflammatory and anti-inflammatory cytokines, which in turn can lead to the development of sarcopenia (et al. , 2018; Picca et al. , 2018). Beyond changes in microbial composition, microbial by-products like LPS can also contribute to sarcopenia by inducing systemic chronic inflammation and insulin resistance. Therefore, inflammaging – the chronic, low-grade inflammation associated with aging – plays a crucial role in both the development and persistence of sarcopenia (Livshits and Kalinkovich, 2019). SCFA production SCFAs, key by-products of the gut microbiota, play a significant role in altering muscle biology (Lahiri et al. , 2019). SCFAs are known to aid in increasing muscle mass and enhancing physical function by boosting muscle glycogen levels (Fushimi and Sato, 2005; Lahiri et al. , 2019). [SEP] Justify:

Output: The text corroborates the claim by discussing the role of gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs), in maintaining gut health and impacting systemic inflammation. It highlights that disturbances in gut microbiota can lead to issues like sarcopenia and inflammation, suggesting that a balanced gut microbiome is crucial for overall health. The mention of SCFA production and its beneficial effects on muscle biology implies that probiotics, which help maintain healthy gut bacteria, can indeed support gut health.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: Indeed, our data show that the later the chronotype of participants (measured by the MCTQ mid-sleep phase, mSP [24]), the later their mid-eat phase (mEP) on weekends (Fig. 3E, Tab. S6), with the mSP and mEP being almost antiphasic on average (Fig. 3F, Tab. S10). The EG intervention maintains most of this relationship. However, the residuals of the regression become smaller, resulting in a model fitting the data better (Fig. 3E, Tab. S6). Interestingly, the closer the intervention brought participants’ observed values to their individual fitted values, i. e. , the smaller the residuals became, the more weight they lost (Fig. 3G, Tab. S6). From a clinical point of view, this indicates that a personalized adjustment of eating times to the individual chronotype, i. e. , the establishment of a highly accurate phase relation between mEP and mSP, leads to a particularly effective reduction of excess weight. The calculation of individual eating times was based on the frequency of hours at which meals were eaten during the exploration phase, which typically included more workdays than non-workdays (Fig. 3H). Consequently, for some subjects, the EG intervention created a discrepancy between what may have been physiologically optimal eating times, reflected by weekend data, and the calculated eating times (Fig. 3I, Tab. S11). However, the magnitude of this discrepancy has no effect on weight changes (Fig. S2O, Tab. S6). On the contrary, if the calculated eating times resulted in large shifts of the weekend meals, this also means that previously particularly large “meal jet lags” between working and non-working days were eliminated. Indeed, the more the calculated eating times led to an advance of the first meal and a delay of the last meal, thus the greater the effect of the “meal jet lag” elimination was, the more the participants lost weight (Fig. 3J, Tab. S6). Interestingly, this also includes the elimination of too early dinners on work days. Our data show that a later dinner on all days of the week can lead to weight loss if this time corresponds to the calculated individual optimal time. The independent variables used above for simple regressions may influence each other and therefore their influence on BMI may be confounded. [SEP] Justify:

Output: The text contrasts the claim by indicating that personalized adjustments in eating times can lead to weight loss, which implies that carbohydrates do not inherently lead to weight gain. The text emphasizes that a later dinner and adjustment of meal timings can facilitate weight loss, suggesting that factors beyond just carbohydrate intake influence weight management.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: cGMP induces phase shifts of mammalian circadian pacemaker at night in antiphase to cAMP effect 86: 6812–6815. [PubMed] Amir, S (1992). Blocking NMDA receptors or nitric oxide production disrupts light transmission to the suprachiasmatic nucleus 586: 336–339. [PubMed] and Watanabe, S (1994). Effects of nitric oxide synthase inhibitors on N-methyl-D-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro 646: 161–164. [PubMed] and Rea, MA (1995). Nitric oxide synthase inhibitor blocks light-induced phase shifts of the circadian activity rhythm, but not c-fos expression in the suprachiasmatic nucleus of the Syrian hamster 692: 137–142. [PubMed] and Gillette, MU (1997). Resetting the biological clock: mediation of nocturnal CREB phosphorylation via light, glutamate and nitric oxide J Neurosci 17: 667–675. [PubMed] and Yannielli, PC (2000). Neurochemistry of mammalian entrainment: Signal transduction pathways in the suprachiasmatic nuclei Res 31: 56–70. and Hagan, RM (2001). A rapid and transient synthesis of nitric oxide (NO) by a constitutively expressed type II NO synthase in the guinea -pig suprachiasmatic nucleus Pharmacol 34: 1084–1092. [PubMed] and Nelson, RJ (1999). Circadian locomotor analysis of male mice lacking the gene for neuronal nitric oxide synthase (nNOS-/-) J 14: 20–27. [PubMed] and Nelson, RJ (2001). Circadian organization in male mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-) J 16: 142–148. [PubMed] Bellingham, J and Foster, RG (2002). Opsins and mammalian photoentrainment Res 309: 57–71. [PubMed] and Rollag, MD (2000). A novel human opsin in the inner retina J Neurosci 20: 600–605. [PubMed] and Yau, KW (2002). [SEP] Justify:

Output: The text does not directly support, refute, or relate to the claim about the suprachiasmatic nucleus being the master regulator of circadian rhythms. Instead, it discusses various studies and effects related to circadian rhythms and the suprachiasmatic nucleus without establishing a clear stance on its regulatory status.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: These interactions, whether direct or indirect, establish a connection with sarcopenia via the gut-muscle axis, thereby significantly impacting the physiological functions of the host. Therapeutic interventions targeting gut-muscle axis for sarcopenia Based on the understanding of the gut-muscle axis, numerous studies have proposed that modifying gut microbiota could be a potential therapeutic approach for managing age-related sarcopenia. There is a growing body of preclinical and human research that either directly or indirectly establishes a connection between gut microbiota and muscle mass/function. Several interventions targeting gut microbiota have been suggested, including the use of probiotics and/or prebiotics, SCFAs, dietary supplementation, and exercise, all of which have shown effectiveness in improving muscle mass and overall host function. The composition of the gut microbiota is influenced by dietary habits, which can lead to microbiota changes critical for organism function (Singh et al. , 2017). Supplementing with prebiotics and/or probiotics has shown to be beneficial in improving intestinal homeostasis and enhancing skeletal muscle metabolism and synthesis (Salazar et al. , 2017). Furthermore, exercise or physical activity also contributes to regulating the gut microbiota, showcasing its role in gut health and overall physiological function (Franko et al. , 2016). High-protein diets Protein supplementation is a commonly utilized approach for preventing and managing sarcopenia. It is well-established that increasing dietary protein intake can have a positive impact on both skeletal muscle mass and function. Furthermore, there is empirical evidence to suggest that adhering to a high-protein diet in accordance with recommended macronutrient distribution guidelines can be effective in alleviating the consequences of sarcopenia. (Ford et al. , 2018). A study has demonstrated a positive correlation between protein intake and the diversity of gut microbiota (Singh et al. , 2017). It appears that the source of protein may also play a role in this relationship. Additionally, research indicates that the supplementation of whey protein and leucine has the potential to enhance muscle mass and function (Bechshøft et al. , 2016; Kobayashi, 2018). However, further investigation is required to establish a connection between the improvement in muscle mass and function achieved through high-protein diets and the modulation of gut microbiota. Prebiotics and probiotics An increasing number of both animal and human studies suggest that the use of prebiotics and/or probiotics can have beneficial effects on skeletal muscle. [SEP] Justify:

Output: The text corroborates the claim by stating that numerous studies have shown that probiotics can improve intestinal homeostasis, which is crucial for gut health. It highlights that using probiotics and/or prebiotics can have beneficial effects on skeletal muscle, indicating a link between gut health and overall physiological function, thereby supporting the idea that probiotics positively impact gut health through the balance of bacteria.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: (A) Significant improvements are observed in various aspects of physical and mental health (SF-36), sleep quality (PSQI), depressed mood (IDS-SR), and self-efficacy (SWE) in participants of the EG (colored columns), but hardly among CG participants (gray columns). Scales are either upward or downward, depending on whether low or high scores on the questionnaires mean subjectively good or poor well-being. (B) The chronotype of EG and CG participants did not change during the study. 2-way repeated-measures ANOVA with Bonferroni post hoc test comparing CG and EG during the exploration or intervention phase and T0-T1 and T1-T2 within groups, * p ≤ 0. 05, ** p ≤ 0. 01, *** p ≤ 0. 001, **** p ≤ 0. 0001. CG: n=33; EG: n=67. Detailed statistics in Tab. S3. 3. DiscussionIn our study, we show that increased regularity of the Zeitgeber food can lead to a significant reduction in body weight. Although the diary entries of some participants show that they changed their energy intake and also the food composition of fat, carbohydrates and proteins during the study, the observed weight loss is not related to these changes. Related results have already been shown in mice, although here with a restriction to the entire active phase rather than specific eating times. Not surprisingly, mice gain weight and develop diabetes-like states under a high-fat diet [17]. It is surprising, however, that the negative physiological consequences of the high-fat diet can be almost completely prevented if the mice consume the equivalent amounts of high-fat food exclusively during their activity phase and do not receive any food during their sleep phase [17, 25]. In our study, an increase in the regularity of lunch, and somewhat more strongly that of dinner, is related to weight loss, which to some extent contrasts with previously published data in which increased regularity of breakfast in particular, and not so much that of dinner, was identified as a predictor of weight loss [26]. Besides increased regularity, our intervention has additional effects on eating behavior, such as shortening the hours in which food is eaten, which in our study is not related to weight loss. [SEP] Justify:

Output: The text contrasts the claim by stating that 'the observed weight loss is not related to these changes' in diet composition, which includes carbohydrates. Additionally, it mentions that increased regularity of meals can contribute to weight loss, implying that it is not solely the intake of carbohydrates that leads to weight gain. This suggests that carbohydrates do not inherently cause weight gain under varying conditions.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity Science 295: 1065–70. [PubMed] and Saper, CB (2001). Melanopsin in cells of origin of the retinohypothalamic tract 4: 1165. [PubMed] Takatsuji, K, Miguel-Hidalgo, JJ and Tohyama, M (1991). Substance P-immunoreactive innervation from the retina to the suprachiasmatic nucleus in the rat 568: 223–229. [PubMed] and Hong, SK (1999). Electrophysiological evidence for the role of substance P in retinohypothalamic transmission in the rat 274: 99–102. [PubMed] and Kim, YI (2001). Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus J Neurosci 21: 4026–4031. [PubMed] Tuomisto, L (1991). Watanabe T, ed. Involvement of histamine in circadian and other rhythms Histaminergic neurons: Mophology and function. 295. and Moss, RL (1981). Efferent connections of the rat suprachiasmatic nucleus Neuroscience 6: 2625–2641. [PubMed] Jacobs, EH, Yamatodani, A and Timmerman, H (2000). Is histamine the final neurotransmitter in the entrainment of circadian rhythms in mammals? Sci 21: 293–298. [PubMed] and Wada, H (1991). Effects of intracerebroventricular histamine injection on circadian activity phase entrainment during rapid illumination changes 123: 53–56. [PubMed] and Ueki, S (1983). Inhibitory and excitatory effects of histamine on suprachiasmatic neurons in rat hypothalamic slice preparation 41: 109–113. [PubMed] Stehle, J (1991). Effects of histamine on spontaneous electrical activity of neurons in rat suprachiasmatic nucleus 130: 217–220. [PubMed] and Harrington, ME (1995). Histamine synthesis inhibition reduces light-induced phase shifts of circadian rhythms 695: 227–230. [PubMed] and Harrington, ME (1996). [SEP] Justify:

Output: The text does not provide a direct correlation to the claim regarding the suprachiasmatic nucleus as the master regulator of circadian rhythms. Instead, it lists a series of studies about various aspects of neuronal connections and neurotransmitters related to the suprachiasmatic nucleus without establishing it as the definitive regulator of circadian rhythms.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: Prebiotics, which are non-digestible carbohydrates fermented in the lower part of the gut and selectively stimulate the growth and/or activity of specific bacteria, have been shown to have positive effects on the host (Delzenne and Cani, 2011). Some studies have explored the impact of prebiotics on skeletal muscle mass and strength by altering gut microbiota (Bindels and Delzenne, 2013). In one study involving elderly human subjects, a prebiotic supplement containing inulin and fructooligosaccharide, expected to promote a healthy microbiome, was administered. The subjects who consumed the prebiotic supplement exhibited greater hand strength and endurance compared to control subjects, although the effects on the microbiome were not reported (Y. Liu et al. , 2016; et al. , 2021). Additionally, research by Cani et al. demonstrated the beneficial effects of prebiotic supplementation on the skeletal muscle of mice (Cani et al. , 2009). Prebiotic intake modulated bacteria that produce SCFAs, which in turn altered skeletal muscle mass and function. SCFAs promoted the release of insulin-like growth factor-1 from the host, acting as an anabolic hormone to enhance skeletal muscle and reduce inflammation (Schroeder and Bäckhed, 2016; Ticinesi et al. , 2017). Probiotics are live microorganisms that provide health benefits to the host when administered in adequate amounts (Delzenne and Cani, 2011). In a mouse model of acute leukemia, sarcopenia was attenuated through oral supplementation with specific Lactobacillus species as one of representative probiotics (Bindels et al. , 2012). Furthermore, supplementation with Lactobacillusplantarum resulted in increased muscle mass and function In young adults, the consumption of TWK10 for a duration of six weeks resulted in improved endurance performance in a maximal treadmill running test (Huang et al. , 2018). Furthermore, the intake of heat-killed Bifidobacterium breve B-3 had a significant positive impact on skeletal muscle mass and function. This effect was accompanied by enhanced mitochondrial biogenesis, indicated by increased phosphorylation of AMP-activated protein kinase, activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and elevated cytochrome c oxidase activity in the rat soleus muscle (Toda et al. , 2020). [SEP] Justify:

Output: The text corroborates the claim by discussing the role of probiotics, defined as live microorganisms providing health benefits when administered in adequate amounts. Specific examples include the supplementation of Lactobacillus species to attenuate sarcopenia and improve endurance performance in subjects. This supports the idea that probiotics can positively affect gut health and overall well-being.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: This is similar to the principle of 16:8 intermitted fasting or time-restricted eating (TRE), in which meals are taken only specific time window, yet at unspecified times during that period. The effects of these protocols is mixed and often less pronounced, as less [21, 23, 27] weight loss or a longer period is required to achieve similar results [22] than in our study - with the caveat that more overweight and older participants participated in these studies than in ours. However, other studies have also explored the effect of restricting individual meals to specific times. In mice, restricting the same amount of high-fat chow to two times per day reduces the development of obesity [28]. And in humans, restricting meals to three fixed, uniform times leads to similar weight loss like we observed in our study - but in combination with calorie reduction and standardized food [29]. The fact that our participants lost weight to a similar extent despite free choice of meals could be due to the individual tailoring of meal schedules. It is true that our data show that scheduling single meals to supposedly circadian optimal eating times of the participants is not essential for successful weight loss. Circadian clocks can flexibly adjust to Zeitgebers and it is apparently more important to choose a time when individuals (have to) eat particularly frequently than the exact genetically determined eating time. However, our data still show that personalization of meal schedules is nevertheless useful. First, depending on the individual chronotype of the participants, their mealtime windows were earlier or later in the day. And those for whom the intervention optimized this relationship were particularly effective at losing excess weight. Second, if the schedule is designed to prevent large jumps between meals, especially dinner, on workdays and work-free days, weight loss is more successful. Since food serves as a Zeitgeber for a large number of tissues, including several brain regions, it can be hypothesized that regular eating not only has a positive effect on body weight, but also on other aspects of well-being. A previous study by Panda et al. [18] has already shown that shortening the eating interval to 10-12 hours per day has a positive effect on the general well-being of the participants. Similarly, in our study, we also found significant improvements in different aspects of subjective well-being over the course of the study, specifically in physical and mental health, sleep quality, and self-efficacy. [SEP] Justify:

Output: The text contrasts the claim by discussing various dietary strategies, including intermittent fasting and meal scheduling, that do not inherently suggest that consuming carbohydrates leads to weight gain. It highlights that effective weight loss can occur without strict adherence to carbohydrate restriction, and individual meal timing can influence weight management positively. Additionally, it emphasizes that regular eating patterns may benefit overall well-being, which contradicts the notion that carbohydrate consumption solely contributes to weight gain.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: Circadian rhythm photic phase shifts are not altered by histamine receptor antagonists. Bull 41: 227–229. [PubMed] Alexander, MJ and Leeman, SE (1998). Widespread expression in adult rat forebrain of mRNA encoding high-affinity neurotensin receptor J 402: 475–500. [PubMed] and Beaudet, A (1996). Cellular distribution of neurotensin receptors in rat brain: immunohistochemical study using an antipeptide antibody against the cloned high affinity receptor J 373: 76–89. [PubMed] Francois-and Beaudet, A (1992). Association of neurotensin receptors with VIP-containing neurons and serotonin-containing axons in the suprachiasmatic nucleus of the rat Synapse 10: 282–290. [PubMed] Meyer-Spasche, A, Reed, HE and Piggins, HD (2002). Neurotensin phase-shifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro Neurosci 16: 339–44. [PubMed] and Piggins, HD (2001). Effects of neurotensin on discharge rates of rat suprachiasmatic nucleus neurons in vitro Neuroscience 103: 663–672. [PubMed] Schmahl, C and Bohmer, G (1997). Effects of excitatory amino acids and neuropeptide Y on the discharge activity of suprachiasmatic neurons in rat brain slices 746: 151–163. [PubMed] and Mason, R (1998). Responses to neuropeptide Y in adult hamster suprachiasmatic nucleus neurones in vitro Pharmacol 345: 155–162. [PubMed] van den Pol, AN and Yocca, FD (1998). Phase shifting of circadian rhythms and depression of neuronal activity in the rat suprachiasmatic nucleus by neuropeptide Y: mediation by different receptor subtypes J Neurosci 18: 3014–3022. [PubMed] and Zhou, JN (2003). Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus 335: 175–178. [PubMed] and Kojima, M (2004). [SEP] Justify:

Output: The text does not directly address the claim regarding the suprachiasmatic nucleus acting as the master regulator of circadian rhythms. Instead, it provides information about various studies mentioning neurotensin receptors, their effects on neuronal activity in the suprachiasmatic nucleus, and phase shifts in circadian rhythms, but does not confirm or deny the specific claim.


Input: Task: corroborate the claim using the given text. Claim: Probiotics can support gut health by improving the balance of bacteria. [SEP] Text: and (2017) Epidemiology of sarcopenia: Determinants throughout the lifecourse. Calcif. Tissue Int. 101(3), 229–247. 71. -and Parkinson SJ (2017) Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats. Aging (Albany NY), 9(7), 1698. 72. Singh RK, Chang H-and Zhu TH (2017) Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 15(1), 1–17. 73. ‐Saberi B, (2020) Dysbacteriosis‐induced LPS elevation disturbs the development of muscle progenitor cells by interfering with retinoic acid signaling. . 34(5), 6837–6853. 74. St‐Jean‐‐Gaudet J, Sgarioto N, Zovilé I, Barbat‐and (2017) The impact of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men. J. Cachexia. Sarcopenia Muscle, 8(2), 213–228. 75. and (2017) Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: is there a gut–muscle axis? Nutrients, 9(12), 1303. 76. and (2019) Exercise and immune system as modulators of intestinal microbiome: Implications for the gut-muscle axis hypothesis. Exerc. Immunol. Rev. 25. 77. and (2020) The gut-muscle axis in older subjects with low muscle mass and performance: A proof of concept study exploring fecal microbiota composition and function with shotgun metagenomics sequencing. Int. J. Mol. Sci. 21(23), 8946. 78. and (2019) Gut microbiota, muscle mass and function in aging: A focus on physical frailty and sarcopenia. Nutrients, 11(7), 1633. 79. and (2020) Heat-killed Bifidobacterium breve B-3 enhances muscle functions: Possible involvement of increases in muscle mass and mitochondrial biogenesis. Nutrients, 12(1), 219. 80. [SEP] Justify:

Output: The text supports the claim by discussing various studies that explore the connection between gut microbiota, diet, and health outcomes, suggesting that specific interactions between gut microbes and health can influence well-being. For example, the mention of 'The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype' suggests that the composition of gut bacteria is important for health across different aspects, including muscle function.


Input: Task: contrast the claim using the given text. Claim: Eating carbohydrates always leads to weight gain. [SEP] Text: This shows that adhering to daily structured mealtimes can improve not only metabolic but also other physical and also psychological levels of health. There are several explanatory approaches for why increased meal regularity can lead to weight loss despite equal caloric intake. For example, circadian clocks influence the composition of the microbiome, which regulates metabolic balance and body weight [30–34]. Additionally, circadian clocks help to anticipate mealtimes and provide the necessary digestive components in advance of food intake in advance [35–38]. Accordingly, the number of rhythmic genes in the liver of mice increases from ∼350 to ∼3,000 when the animals can follow their natural feeding rhythm and even to ∼5,000 when the feeding time is restricted to a certain period of time [39]. 3. 1. LimitationsHowever, in our study, we did not collect metabolic parameters that could provide mechanistic explanations for the observed weight loss. Therefore, the assumption of an optimized metabolism remains speculation. Another limitation of the study is the self-assessment of key data on body weight, eating times, and food composition. Body weight could not be collected in our clinic under supervision because of the Covid-19 pandemic. Regarding food intake, some participants underreported during the study, as indicated by unrealistically low kJ intakes. However, the individual reporting behavior of each participant remained largely the same during the exploration and intervention phases, so underreporting is not indicative of a change in eating behavior and, conversely, the observed kJ differences are likely due to actual changes in eating behavior. In addition, in the remaining evaluable 100 study participants, there was a significant difference in baseline body weight and BMI between CG and EG. However, even if CG participants had been heavier from the start, it cannot be assumed that the applied sham treatment with an eating window of 18 hours during wake time would have had a stronger effect. Second, those subjects in the EG group whose baseline BMI was similar to those of the CG subjects lost significant weight during the intervention, while CG participants did not. Taking these two arguments into account, it cannot be assumed that a floor effect, in which the CG participants cannot lose any more weight due to a lower baseline weight, is the reason for the lack of weight loss in the CG. Lasty, studies show that even much larger baseline BMI differences do hardly affect the success of weight loss programs [40, 41], so we assume that this also applies to our study. [SEP] Justify:

Output: The text contrasts the claim by discussing how adherence to structured mealtimes can improve not only metabolic health but can also lead to weight loss despite equal caloric intake. It suggests that factors like circadian clocks and eating behavior play significant roles in weight management, providing evidence that contradicts the idea that all carbohydrate consumption results in weight gain.


Input: Task: pass the claim using the given text. Claim: The suprachiasmatic nucleus is the master regulator of circadian rhythms. [SEP] Text: he gut-brain peptide neuromedin U is involved in the mammalian circadian oscillator system 318: 156–161. [PubMed] and Kangawa, K (2005). Identification of neuromedin S and its possible role in the mammalian circadian oscillator system EMBO J 24: 325–335. [PubMed] and Barrett, P (2005). Neuromedin -U is regulated by circadian clock in the SCN of the mouse Neurosci 21: 814–819. [PubMed] Battey, J and Wada, E (1991). Two distinct receptor subtypes for mammalian bombesin-like peptides 14: 524–528. [PubMed] and Moran, TH (1990). Receptor heterogeneity for bombesin-like peptides in the rat central nervous system 537: 233–240. [PubMed] and Moran, TH (1992). Distinct distributions of two bombesin receptor subtypes in the rat central nervous system 593: 168–178. [PubMed] and Ibata, Y (1997). Direct retinal projections to GRP neurons in the suprachiasmatic nucleus of the rat NeuroReport 8: 2187–2191. [PubMed] Aïoun, J, Chambille, I, Peytevin, J and Martinet, L (1988). Neurons containing gastrin-releasing peptide and vasoactive intestinal polypeptide are involved in the reception of the photic signal in the suprachiasmatic nucleus of the Syrian hamster: an immunocytochemical ultrastructural study Res 291: 239–253. Piggins, HD and Rusak, B (1999). Lydic R, Baghdoyan HA ed. Intercellular interactions and the physiology of circadian rhythms in mammals Handbook of behavioral state control: cellular and molecular mechanisms. 44. and Piggins, HD (2000). Gastrin-releasing peptide phase-shifts suprachiasmatic nuclei neuronal rhythms in vitro J Neurosci 20: 5496–5502. [PubMed] and Silver, R (2005). Signaling within the master clock of the brain: localized activation of mitogen-activated protein kinase by gastrin-releasing peptide J Neurosci 25: 2447–2454. [SEP] Justify:

Output: The text does not provide explicit information supporting or contradicting the claim about the suprachiasmatic nucleus (SCN) being the master regulator of circadian rhythms. Instead, it primarily discusses various studies related to peptides and their roles within the circadian oscillator system, mentioning the SCN without directly addressing its regulatory status. Thus, the text is considered irrelevant to the claim.