Input: Task: contrast the claim using the given text. Claim: Gene therapy is being researched to treat diseases like cystic fibrosis and sickle cell anemia. [SEP] Text: We found no trials to provide reliable evidence about the risks or benefits of gene therapy for this condition. There is a need for trials that assess the benefits or risks of gene therapy for sickle cell disease. Visual summary Authors' conclusions Implications for practice No randomised controlled trials of gene therapy for sickle cell disease (SCD) were found for inclusion in this review. Thus, no objective conclusions or recommendations for practice can be made on gene therapy for SCD. Implications for research This systematic review has identified the need for well‐designed and possibly multicentred randomised controlled trials to assess the benefits and risks of gene therapy for SCD. The primary outcome for these trials should be a cure for SCD, where individuals survive and are free of SCD symptoms. Also, because of the potential side effects of using viruses as vectors in gene therapy, further progress in new non‐viral vector development is necessary. The current viral vectors should be used with caution in humans. of the condition Sickle cell disease (SCD) is a group of genetic conditions that result from the inheritance of abnormal haemoglobin genes, thereby resulting in the production of abnormal haemoglobin in red blood cells (Akinyanju 1989). Haemoglobin is responsible for transporting oxygen around the body packaged in red blood cells. In people with SCD, the red blood cells contain abnormal haemoglobin and change from their normal round disk shape to narrow sickle forms. The sickle shape is the end result of a series of complex biochemical and biophysical events within the red cell after deoxygenation of Hb S. The sickle‐shaped cells do not flow smoothly through small blood vessels the way disk‐shaped red blood cells do; they block the vessels, causing pain and organ damage. About 5% of the world's population carry genes responsible for haemoglobinopathies with most of the people living in, or originating from sub‐(WHO 2006). Each year about 300,000 infants are born with major haemoglobin disorders, including more than 200,000 cases of sickle cell anaemia in Africa (WHO 2006). Some parts of Africa have up to 10% to 30% of the population with the sickle cell trait and approximately 8% of people of African descent carry one sickle gene in the USA and the Caribbean (Ohene‐Frempong 1994; Serjeant 1992). [SEP] Justify:

Output: The text contrasts the claim by indicating that there is currently no reliable evidence from randomized controlled trials assessing the risks or benefits of gene therapy for sickle cell disease (SCD). It emphasizes the lack of objective conclusions or recommendations on the use of gene therapy for this condition, thereby suggesting that although gene therapy may be a focus of research, there is insufficient evidence to support its effectiveness or safety at this time.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: Moreover, the investigators further reported that the lipid-modulating effect of canola oil was greater when ∼15 % of total energetic intake from other oils was replaced with canola oil. Despite evidence suggesting that coconut oil (a rich source of saturated fat) raises TC, LDL-cholesterol and HDL-cholesterol compared with unsaturated plant oils(Reference Eyres, Eyres and Chisholm29), when compared against butter, coconut oil has been shown to be beneficial for cardiovascular health by raising HDL-cholesterol and lowering HDL-cholesterol(Reference Teng, Zhao and Khoo30). Despite their potential impact on cardiometabolic risk indices, use of dietary oils and fats in Western countries remains largely unknown and has likely changed in recent decades due to multicultural societies and population-based health promotion messaging specifically targeting reductions in saturated fat intake. It is also unclear whether the use of dietary oils and fats for different cooking methods has altered in response to supplier messaging; in recent years, some vegetable oils have been promoted as having a high smoke point for the purpose of certain cooking methods including frying(Reference Eyres31). Nevertheless, there is recent evidence from the of America (USA) showing that olive oil is now the most commonly used dietary fat source for cooking and food preparation, followed by vegetable oil and canola oil(and Hopkin32). However, p2021. As the research involved the completion of a self-administered online survey, participants were informed that all information collected would remain confidential. Participants acknowledged an informed consent statement to participate in the study. Data collection Dietary oil and fat use amongst Australian adults was assessed using a nineteen-item self-administered online questionnaire, designed to be completed in approximately 10 minutes. Given the lack of a previously validated and reliable survey instrument, the authors developed a prototype questionnaire that was initially piloted against a separate representative sample for face validity. For the assessment of face validity, a convenience sample of volunteers across a range of ages (18–75 years) was invited to complete the prototype questionnaire that was administered online. A total of n 12 participants completed the prototype questionnaire (75 % female; 25 % male). Nil changes to the readability of the questions were required following administration of the prototype questionnaire. The online questionnaire was divided into two parts (see online 1). consisted of open- and closed-ended questions related to participant demographic characteristics. [SEP] Justify:

Output: The text does not relate to the claim regarding charred plant remains and their indication of cooking methods or food preferences. Instead, it discusses dietary oils and fats, their usage trends, and health implications, which is irrelevant to the claim about charred plant remains.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: (e) Identification of effectively neutral selective conditions (when |⟨N⟩·⟨S⟩|<1, region shaded) in terms of gene expression (y) and genome size (G), which determines the effective population size (⟨N⟩). In this context, no benefit was considered (a = 0), with moderate noise levels. However, the preceding argument only focuses on a static picture, ignoring the dynamics of the genetic process. In bacteria (lacZ gene), the time to reach the equilibrium point is about 68 generations (three times the inverse of the deletion rate), which is a relatively short transient period. By contrast, in flies (Drosophila melanogaster), the formation rate is of 10−7 dup. /gene/gen. and the deletion rate of 10−6 -/gene/gen. (Schrider et al. , 2013). Although this would yield equilibrium frequencies up to 10%, the transient periods would be longer than 106 generations (0. 2 Ma in natural conditions; Pool, 2015). Fixation could then happen by drift, as their effective population sizes are of 106 flies (Lynch et al. , 2016), although not persistently. Note that the inverse of this number indeed specifies an upper limit for the deletion rate. In addition, the formation-deletion balance could be shifted if further genome rearrangements affecting duplicated genes were considered, such as gene relocation (about 10−11 fixed rearr. /gene/gen. for D. melanogaster; Ranz et al. , 2001). In effective terms, gene relocation would reduce the deletion rate, and, consequently, fixation would be more likely (Wong and Wolfe, 2005). Such a relocation would also shift the intrinsic-extrinsic noise balance toward more uncoupled responses (Becskei et al. , 2005), which could enhance the benefit by intrinsic noise reduction. Most of the new-born duplicates lead to increased expression and are costly for the cell So far, we have demonstrated that a duplicated gene offers a selective advantage provided the total gene expression level is maintained, with one or two copies (gene dosage sharing). However, this condition is not usually met during the critical very initial phase, when the duplicate has just born. [SEP] Justify:

Output: The text corroborates the claim by discussing different conditions under which genetic mutations can offer selective advantages or be neutral. It refers to gene duplication as presenting a selective advantage when gene expression levels are maintained, highlighting that the effects of these mutations depend significantly on circumstances such as effective population size and the dynamics of gene processes. The mention of gene relocation and its potential to alter deletion rates further indicates that the impact of genetic mutations can vary, supporting the claim that mutations can be beneficial, neutral, or harmful depending on specific contexts.


Input: Task: pass the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Real-time quantitative RT-PCR for various genes and the control 18S rRNA was performed with master mix (Stratagene) with the following conditions: 1 denaturation cycle for 10 min at 95°C followed by 30-40 cycles (15-25 cycles for 18S rRNA) of 30 seconds denaturation, 1 minute annealing at 55-60°C and 1 minute extension at 72°C. The number of cycles, annealing temperature and extension time were optimized for the abundance of the transcripts, the T m of the primers and the size of the amplicons. All reactions were performed in a Mx3000p PCR system (Stratagene). The dissociation curves were generated for all samples and the relative gene expression was normalized with the control 18S rRNA. The threshold cycle Ct value was determined as described [34]. Real-time quantitative RT-PCR reactions were performed multiple times to validate our results using the PCR primers listed in Table 1. The representative results of the real-time quantitative RT-PCR following ES cell differentiation using protocol D are presented in Figure 1c since the IPCs generated using the protocol D consistently expressed the highest levels of insulin. Table 1 Nucleotide sequence of the PCR primers Full size tableImmunostaining and immunohistochemistryThe ES cells grown on chambered glass slides were differentiated using the highly efficient protocol D and were fixed at different stages of differentiation with 2% paraformaldehyde, quenched in PBS containing 30 mM glycine and permeabilized with 0. 1% Triton X-100 for 30 minutes at RT and blocked for 2 hours in PBS containing 2% Albumin fraction V. The cells were stained with primary antibodies (1:250 dilution) against Ngn3 (SC-13794, goat polyclonal ), Foxa2 (SC-6554, goat polyclonal IgG, Biotechnology), Sox17 (SC-17356, goat polyclonal IgG, Biotechnology), glucagon (SC-13091, rabbit polyclonal IgG, Biotechnology), somatostatin (SC-20999, rabbit polyclonal IgG, Biotechnology) insulin (SC-7838, goat polyclonal IgG, Biotechnology) and C-peptide (4593, rabbit polyclonal. , ), respectively. [SEP] Justify:

Output: The text does not reference genetic engineering or its application in producing insulin. It discusses technical protocols related to RT-PCR and immunostaining in stem cell research without providing information that supports or contrasts the claim about insulin production.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: of the online questionnaire consisted of open- and closed-ended questions related to type and household quantity of daily oil used, main fat and oil use for different cookery methods (e. g. shallow frying, deep frying, stir frying, stewing, etc. ) as well as perceived attitudes and beliefs related to oil use within the household (Table 1). There were no time restrictions applied to complete the questionnaire and participants were not required to answer all questions before proceeding to subsequent questions. The link to the survey was recognisable once only to the server it was sent thus preventing duplication when responding to the survey. The investigators also screened all of the participant responses (IP address and postcode viewed to ensure participants were from Australia) to ensure all responses were consistent with the eligibility criteria. Table 1. Summary of questions from part B of the online survey evaluating the types of oils used in cooking and food preparation in analysis Qualitative data were analysed using conventional content analysis(and Shannon33). Data were read for familiarisation and to determine initial codes. A recursive process was undertaken independently by two authors (NW and EM) during content analysis to maintain the rich detail of the data(Reference Anzul, Downing and Ely34,and Clarke35) and descriptions and rationale for codes were documented to confirm the reliability of the data(and Swift36). This iterative process was continued by the same two authors (NW and EM) until the research team was in agreement, with the addition of a third researcher (AV) to resolve any discrepancies. Related codes were grouped into representative themes. Representative quotations that illustrate the themes are presented alongside each theme and referenced with the participant number (in brackets). Furthermore, quantitative content analysis of response data was undertaken(Reference Bryman37). Identified themes were expressed as frequencies and percentages of responses using software. for the (SPSS) for Windows 27. 0 software(38) was also used to perform analysis of descriptive data and expressed as means ± standard deviations for continuous data and frequencies and percentages for categorical data. A one-way ANOVA was used to explore differences in oil use according to age categories. Additionally, χ 2 analysis using Fisher’s exact test was conducted to explore potential differences in the frequency of reported oil use type and the presence of self-reported medical conditions (e. g. medical condition v. no medical condition). characteristics A total of n 1248 participants completed the survey and were included in the final analyses. [SEP] Justify:

Output: The text does not provide any information or evidence related to charred plant remains or their significance in indicating past cooking methods and food preferences. Instead, it focuses on a survey related to oil use in cooking and participant responses, which is unrelated to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: In general, we can assume that the expression level is doubled upon duplication, although this may vary due to the particular position in the chromosome of the duplicated gene and the type of cell (Stranger et al. , 2007). Certainly, an increase of expression due to gene duplication is detrimental in most environments (Figure 5c,d; Price and Arkin, 2016), thus positive or neutral selective conditions are difficult to invoke to explain the fixation of these type of genotypic changes, mainly in prokaryotes and lower eukaryotes (Lynch and Marinov, 2015). For instance, at constant 0. 13 mM lactose, we obtained mean selection coefficients between −28% (at very high noise levels) and −1% (at no noise) upon duplication of the lacZ gene (assuming double expression), which yield negligible fixation probabilities (almost 0) for a sufficiently large bacterial population. It can be argued, nevertheless, that the cost of over-expression decreases as long as the genome size increases (Lynch and Marinov, 2015). This assumption, together with the negative correlation between complexity and population size (Lynch and Conery, 2003), makes effectively neutral selective conditions plausible to rationalize the fixation of duplicates that are expressed (e. g. , essential genes) in higher eukaryotes (Figure 5e; Makino et al. , 2009). Only in absence of lactose, when the enzyme is not needed, the duplication is strictly neutral (no benefit, no cost due to regulation). But neutral selective conditions can be reached de facto if the absolute value of the selection coefficient is lower than the inverse of the effective population size (Kimura, 1983). This condition is challenging for prokaryotes, as their population sizes are very large (Lynch and Conery, 2003). In our particular case, we obtained mean selection coefficients in the order of −10−10 (at moderate noise levels) when the nutrient amount is scarce (1 μM lactose), which could favor the fixation of a lacZ duplicate by genetic drift. Gene dosage sharing upon duplication, fitness increase on average, and estimation of the fixation probability Can a cell carrying a new-born duplicate that is expressed (in principle, in an operation point close to a local optimum) overcome the cost of an additional copy and then invade the population without invoking the need for more expression (to face an extreme environment)? [SEP] Justify:

Output: The text supports the claim by discussing how gene duplication can lead to different outcomes depending on environmental conditions. It states that 'an increase of expression due to gene duplication is detrimental in most environments,' indicating a harmful context. It also mentions that 'the duplication is strictly neutral (no benefit, no cost due to regulation)' in the absence of lactose, implying neutral conditions. Additionally, it talks about conditions under which a genetic alteration could be favorable, namely under 'positive or neutral selective conditions.' This illustrates the claim that genetic mutations may not have a uniform effect but are instead context-dependent.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Full size imageES cell-derived IPCs significantly reduce hyperglycemiaTo determine whether R1Pdx1AcGFP/RIP-Luc ES cell-derived IPCs correct hyperglycemia in diabetic mice, 1 × 106 IPCs were transplanted under the kidney capsule in STZ-induced diabetic syngeneic 129/SvJ mice. Healthy mice have a fasting serum glucose level of about 105 ± 10 mg/dl. In contrast, our diabetic mice had elevated glucose levels in the range of 500 to 650 mg/dl. The IPC treatment group comprised of 12 mice while normal non-diabetic as well as STZ treated control group comprised of 5 mice each. Blood glucose levels were measured prior to IPCs transplantation and every three to five days post-IPCs transplantation. The STZ-treated diabetic control mice exhibited elevated blood glucose levels (>600 mg/dl), polyuria, weight loss, muscle wasting, hunched back posture, poor mobility, soiled body coat color, shivering and died within 14 days. The IPCs transplanted mice showed remarkable correction of the hyperglycemia as early as Day 15 post-transplantation. Further, these mice continued to exhibit near normoglycemic blood glucose levels beyond 40 days post-transplantation (Figure 3a). 40 blood glucose values for the IPCs-treated mice reached the lower threshold of 250 mg/dl (mean 243. 8 (95% CI 216. 2 to 271. 4)) remaining higher than that of control mice. Although complete correction of blood glucose levels was not observed, the IPC transplanted mice survived for >150 days post IPC transplantation. This finding suggests that our IPCs were not capable of fully reducing the blood glucose levels. With a significant improvement in the blood glucose levels, the IPC transplanted mice displayed improved feed consumption, improved posture, increase in body weights, reduced urination frequency, lack of shivering, improved mobility, shiny body coat color and survival throughout the duration of the study. To confirm that the IPCs transplanted under the kidney capsule were indeed responsible for the correction of hyperglycemia, the kidney sections from the nephrectomized mice were subjected to immunostaining using anti-insulin antibody. Our immunostaining results (Figure 3b) confirm the presence of insulin expressing cells in the transplanted kidney. [SEP] Justify:

Output: The text contrasts the claim as it discusses a study on the transplantation of insulin-producing cells (IPCs) derived from embryonic stem (ES) cells to treat hyperglycemia in diabetic mice. While the study shows that insulin-expressing cells may improve blood glucose levels in diabetic mice, it does not provide evidence that genetic engineering is specifically used for producing insulin in diabetic patients. Instead, it highlights the effects of IPC transplantation, suggesting alternative methods for diabetes management rather than direct genetic engineering applications in insulin production.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: More than 90 % of the survey questions were completed by all participants. Participant characteristics are outlined in Table 2. Participants were predominantly female (females n 1143, males n 99) with more than half of participants (56·7 %) aged between 25 and 44 years. The majority of participants were born in Australia (n 1046; 83·8 %); however, participants reported a diverse range of cultural backgrounds including 72·8 % who identified as Australian, 8·0 % identified as English, 3·1 % identified as Greek, 2·4 % identified as Italian and 1·2 % identified as Chinese. More than half of participants (59·0 %) reported a total annual household income of between $75 000 and $199 999 AUD. Less than half of the participants (43·3 %) reported no medical conditions, 25·4 % reported one medical condition and 14·6 % reported two medical conditions. Anxiety, depression, hypertension, arthritis and high cholesterol were the most reported medical conditions amongst participants. Table 2. Demographic characteristics of participants (n 1248) Quantity and type of oil use in cooking and food preparation Quantity and reported use of all oil types is presented in Table 3. Approximately half of all participants (n 629; 50·4 %) reported using less than one tablespoon per day in cooking and food preparation. In contrast, more than one-third of participants (n 459; 36·8 %) reported using 1–2 tablespoons of oil per day. More than three-quarters of participants (n 1055; 84·5 %) reported using some form of olive oil as their main source of oil for cooking and food preparation, with almost two-thirds of the sample (n 816; 65·4 %) using EVOO (Table 3). Of those who reported using some form of olive oil, almost half (n 514; 48·7 %) reported using less than one tablespoon per day. The next commonly used oils were rice bran (n 57; 4·6 %) and canola (n 54; 4·3 %) (Table 3). Rice bran oil (n 39; 68·4 %) and canola oil (n 32; 59·3 %) were also reported to be consumed in amounts of less than one tablespoon per day. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on demographic characteristics of participants in a survey and their reported use of various cooking oils. It does not mention charred plant remains, cooking methods, or food preferences in a historical context, thus failing to address the claim directly.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: We here predicted that the genetic variability existing in a population would allow reaching adaptive gene duplications (Figure 6a). Mutations in the cis-regulatory region of the lacZ gene may change its wild-type expression level. According to previous results (Otwinowski and Nemenman, 2013), the distribution of mutations in terms of maximal promoter activity is peaked at 1, but skewed to the left (Figure 6b). This indicates that about 10% of them yield cells with nearby 50% lower expression. Thus, if a gene duplication event occurred in one of these cells, the genotypic change would be selectively advantageous (Figure 6c). The frequency of such cells in the population depends, of course, on the mutation rate; the greater the ability to generate genetic diversity, the higher the chances to reach adaptive duplications. For E. coli, where the per base mutation rate is of 10−10 mut. /bp/gen. (Lee et al. , 2012), this frequency can be estimated in 10−9 (i. e. 0. 2 mutants with nearby 50% lower expression per generation in a natural population of 2·108 cells). Hence, the probability that a duplication and such a mutation concur in the same cell in a generation (duplication after promoter mutation) is of 10−4 (=0. 2·10−3/2; i. e. , 1 suitable concurrence each 104 generations). Figure 6 Download asset Open asset Gene duplication leading to maintained expression. (a) Schematics of fitness as a function of expression showing a path to reach adaptive gene duplications without the need for more expression. Two steps are considered: first a base-pair mutation that reduces in half the expression level, and then a duplication that recovers the ancestral level. (b) Distribution of the activity of lac promoter mutants based on experimental data, as the maximal LacZ expression (ymax, irrespective of lactose dose). The mean activity is shown (dashed line). Skewness coefficient of −0. 68. (c) ⟨S⟩ of the promoter mutants versus the wild-type system (solid line), with fluctuating lactose dose and high noise levels. The dashed line corresponds to the comparative between promoter mutants that duplicated the lacZ gene and the wild-type system. [SEP] Justify:

Output: The text corroborates the claim by discussing how mutations can have different impacts based on context. It explains that certain mutations, specifically in the cis-regulatory region of the lacZ gene, can lead to either advantageous or disadvantageous genotypic changes in the population. The mention of adaptive gene duplications illustrates that some mutations may result in beneficial outcomes (selectively advantageous), while the skewed distribution of mutations indicates that others may lead to harmful effects (about 10% yielding cells with 50% lower expression). Thus, the text supports the idea that the effects of genetic mutations are context-dependent.


Input: Task: contrast the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Collectively, these results indicated that transplantation of IPCs led to superior glucose control and tolerance as compared to controls. cell regeneration is a promising therapy for patients with insulin dependent DM after TP. Since multipotent mesenchymal stromal cells are free of ethical and immunological complications, they could provide unprecedented opportunity as starting material to derive insulin secreting cells. Many studies have demonstrated the low immunogenicity and pluripotency of UCMSCs[10,11]. Thus, these cells are expected to be an ideal source for transplantation. The phenotypic characteristic of the UCMSCs isolated in our study was in accordance with previous studies[16]. Indeed, the UCMSCs were positive for surface antigens CD13, CD90, and CD105 and negative for surface antigens CD34, CD45 and HLA-DR. Our results illustrate that UCMSCs could be differentiated into IPCs under specific conditions. The pancreatic inductive protocol for UCMSCs was performed according to a previous study[6]. The adherent spindle-like cells acquired a round shape and assembled together after 1 wk of induction. Some new islet-like clusters began to appear after 2 wk of induction. DTZ staining is a method to identify IPCs, as reported previously[17,18]. DTZ is a substance that can bind to zinc. Compared with other cells, pancreatic islets have higher zinc contents. They become crimson red after DTZ staining[19]. As control cells were negative for DTZ staining, our results demonstrated that insulin has been produced by differentiated cells. We used human C-peptide to represent insulin secretion by differentiated cells due to the controversy surrounding insulin uptake by cells from medium supplements[20,21]. As the precursor of insulin, proinsulin is comprised of three segments: A-chain, B-chain, and C-peptide. However, unlike the A- and B-chains, cells cannot take up C-peptide, so C-peptide levels can be regarded as a marker of insulin production. In our studies, differentiated cells secreted more C-peptide than control cells after 2, 3 and 4 wk of induction. The islet-like clusters were found to be responsive to glucose challenge as evidenced by an around 1. 5-fold increase in C-peptide secretion over basal stimulation. [SEP] Justify:

Output: The text contrasts the claim because it discusses the use of multipotent mesenchymal stromal cells (UCMSCs) for producing insulin-secreting cells but does not explicitly mention genetic engineering as the method employed for insulin production. Instead, the focus is on cell regeneration and differentiation of UCMSCs into insulin-producing cells (IPCs). While the results illustrate insulin production from differentiated cells, they do not provide evidence or mention the role of genetic engineering in this process.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: No significant differences in oil use were observed according to age category (F(16, 1231) = 1·25, P = 0·22). No significant differences were observed according to the presence of a medical condition in those that used EVOO, olive oil, light olive oil, rice bran or canola oil as the main household oil (medical condition: n 626; no medical condition: n 540; not reported n 82; all P values = >0·05). Walnut oil, safflower oil and animal fat/lard were not reported as the main household oils used by participants; however, they were used for specific food preparation and cooking methods. Table 3. Frequency and percentage of main household oil use differentiated by daily serve size (n 1248) Abbreviations: EVOO, extra virgin olive oil. *Quantity of EVOO used was not reported by n 6 participants. Participants reported using a range of different oils for various cooking and food preparation methods (Table 4). Oil use was reported across all food preparation and cooking techniques. However, over three-quarters of participants (n 1036; 83·0 %) reported nil use of oil for boiling. EVOO was the most frequently reported oil used for raw food preparation methods (e. g. salad/vegetable dressings) (n 882; 71·5 %), followed by savoury baking or roasting (n 724; 58·0 %) and sauteing (n 679; 54·4 %). In contrast, butter was most frequently used by participants for sweet baking (n 471; 37·7 %). Canola oil and rice bran oil were both most frequently used for shallow frying (canola oil: n 140, 11·2 %; rice bran oil: n 117, 9·4 %), while sesame oil was most frequently used for stir frying (n 123; 9·9 %). However, EVOO was still the main oil used by most participants for shallow and/or stir frying (Table 4). Table 4. Frequency n (%) of oil use for different cooking methods (n 1248) EVOO, extra virgin olive oil. Perceived motivators for main household oil consumption Survey responses on the perceived motivators for main oil use were analysed for themes and presented in combination with representative quotes, frequency and percentage of responses (Table 5). [SEP] Justify:

Output: The text does not provide information about charred plant remains or their significance in indicating past cooking methods and food preferences. Instead, it discusses the types of oils used in cooking and food preparation methods without addressing the claim directly.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: (d) Fixation probability (Pfix) of gene duplication as a function of the mutation rate of the cell (μ), with ⟨S⟩ = 0. 19% and ⟨N⟩ = 2·108. (e) ⟨S⟩ as a function of the expression imbalance between the two lacZ copies (ymax,1 ymax,2), when the system recovers its ancestral expression levels (ymax,1 = ymax,2 = 0. 5), with constant x = 0. 13 mM and high noise levels. Arrows illustrate the corresponding promoter strengths. In particular, at constant 0. 13 mM lactose, we obtained a relatively high mean selection coefficient of 0. 19% when the wild-type expression is recovered upon duplication (in a highly noisy scenario). However, the selection coefficient has to be greater than the duplication deletion rate to ensure fixation (Figure 5b); a condition that is not met here. Certainly, the high deletion rates observed in bacteria (Reams et al. , 2010) protect them from acquiring genetic redundancy (perhaps, this is why lacZ is not duplicated in E. coli despite this may be beneficial). In other local genetic contexts, also in bacteria, the deletion rate of a lacZ duplicate can be as low as 4. 1·10−4 -/gene/gen. (Reams et al. , 2012). In this scenario, a selection coefficient of 0. 19% would lead to fixation. We then estimated a global fixation probability of 3·10−7 (= 2·15·10−4·10−4; Figure 6d; see Materials and methods). Remarkably, our estimation is much higher than 5·10−9, the fixation probability under hypothetical neutrality (Kimura, 1983). A fitness increase on average due to expression noise reduction could also lead to the fixation of duplicates in eukaryotes, as nothing prevents assuming the same positive selective conditions (Raser et al. , 2004; Hansen et al. , 2015), which now largely outperform the duplication deletion processes. For D. melanogaster, for instance, where the per base mutation rate is of 5·10−9 mut. /bp/gen. (Schrider et al. , 2013), and complete gene duplications have little impact on fitness (Emerson et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the conditions under which genetic mutations, such as gene duplications, can have varying effects on fitness depending on the context. It illustrates that the fixation of gene duplications can be beneficial under specific conditions, such as a high selection coefficient of 0.19% when expression levels are recovered. Conversely, it highlights that high deletion rates in bacteria might prevent beneficial mutations from fixing, thus establishing that mutations can indeed have different consequences depending on genetic and environmental contexts.


Input: Task: pass the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest. 1983;71:1544-1553. [PubMed] [DOI] [Cited in This 15. øland A. Sensitivity and reproducibility of urinary C-peptide as estimate of islet B-cell function in insulin-treated diabetes. Diabet Med. 1989;6:329-333. [PubMed] [DOI] [Cited in This 16. -. Minimal criteria for defining multipotent mesenchymal stromal cells. Society for position statement. Cytotherapy. 2006;8:315-317. [PubMed] [DOI] [Cited in This 714. 8] [Analysis (1)] 17. Bonner-’Neil JJ. In vitro cultivation of human islets from expanded ductal tissue. . 2000;97:7999-8004. [PubMed] [DOI] [Cited in This 18. . Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone. Stem Cells. 2002;20:284-292. [PubMed] [DOI] [Cited in This 7. 4] [Analysis (0)] 19. . A simple method of staining fresh and cultured islets. Transplantation. 1988;45:827-830. [PubMed] [DOI] [Cited in This 20. åkansson J, Fleckner J, Sköld HN. Artifactual insulin release from differentiated embryonic stem cells. Diabetes. 2004;53:2603-2609. [PubMed] [DOI] [Cited in This 21. . Insulin staining of ES cell progeny from insulin uptake. Science. 2003;299:363. [PubMed] [DOI] [Cited in This 14. 0] [Analysis (0)] 22. Lopez-Talavera JC, Garcia-Ocaña -Castellano I, Stewart AF. Hepatocyte growth factor gene therapy for pancreatic islets in diabetes: reducing the minimal islet transplant mass required in a glucocorticoid-free rat model of allogeneic portal vein islet transplantation. Endocrinology. 2004;145:467-474. [SEP] Justify:

Output: The text does not address the claim regarding the use of genetic engineering in producing insulin for diabetic patients. Instead, it references various scientific studies and methodologies related to insulin release and islet cells, but does not provide information supporting or contrasting the claim about genetic engineering specifically.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: A total of seventeen themes were identified as perceived motivators. Almost half of all participants (n 619; 49·6 %) identified perceived health benefits as the primary motivating factor for the main choice of oil in cooking and food preparation methods. Sensory preference including flavour, taste and smell was also frequently reported as an influential factor determining choice of oil (n 583; 46·7 %). Versatility (n 127; 10·2 %) and convenience (n 110; 8·8 %) were also frequently reported. Table 5. Perceived motivators of the main oil used by participants in their household (n 1248) Given that some form of olive oil (e. g. EVOO, olive and light) was identified as the predominant oil used in Australian households (n 1055; 84·5 %), the perceived motivators for its use were akin to those outlined in Table 5. As such, the most frequently reported motivator for olive oil use included the perceived health benefits of olive oil (n 561; 53·2 %), followed by flavour and taste, including the flavour of infused olive oils (n 503; 47·7 %), and its versatility for use across different cooking methods (n 112; 10·6 %). Convenience was also frequently reported as a perceived motivator for using olive oil (n 98; 9·3 %). Of the n 193 participants who reported not using any form of olive oil as their main dietary oil source, sensory preference, in particular taste and flavour, was the most frequently reported reason for not using this type of oil (n 58; 30·1 %). Limiting cooking problems (e. g. EVOO having a lower smoke point and potential damage to cooking utensils) was also frequently reported (n 49; 25·4 %). Moreover, expense (n 32; 16·6 %) was also identified as an important barrier for not using a form of olive oil. from this large cross-sectional analysis demonstrated that olive oil, in particular EVOO, was the main choice of oil for use in cooking and food preparation in this sample of Australian households. The perceived motivators for the use of the main cooking oil in the household included its potential for health benefits, sensory preference and its versatility. Our findings are indeed novel as this, to the best of our knowledge, is the first Australian study to investigate oils used in cooking and food preparation in Australian households. [SEP] Justify:

Output: The text does not address the claim regarding charred plant remains and their indication of past cooking methods and food preferences. Instead, it focuses on the perceived motivators for choosing olive oil in cooking and food preparation among participants, which is not directly related to archaeological indicators or historical cooking practices.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: , 2008; note that other genome rearrangements not affecting entire genes are significantly deleterious), we estimated that 0. 05 mutants with nearby 50% lower expression and up to 105 duplicants of the gene of interest would be found in the natural population. Hence, the probability of concurrence in the same organism (duplication after promoter mutation) would be of 2. 5·10−3. Consequently, the global fixation probability would be of 10−5; again, higher than the one under hypothetical neutrality (Kimura, 1983). Maintenance of a duplicate upon fixation in the population A forthcoming change in lactose dose would be highly detrimental if a second lacZ copy were fixed in the population either under neutrality due to insignificant expression or under strong selection due to expression demand. In the former case, an increase of lactose would be detrimental; in the latter, a decrease would. Consequently, either the elimination of the duplicate by purifying selection (Lynch and Conery, 2000) or the accumulation of mutations that lower the LacZ expression to recover the ancestral phenotype (Force et al. , 1999; Qian et al. , 2010) would be promoted; with clonal interference in the case of asexual populations (Rozen et al. , 2002; Desai et al. , 2007). In the latter case, the two gene copies could be maintained in the genome for long time by buffering of costly stochastic fluctuations of intrinsic nature if they held similar expression levels (Figure 6e; Gout and Lynch, 2015); otherwise the gain in accuracy decreased. Conversely, if a second lacZ copy were fixed according to the path shown in Figure 6a under weak selection, it would be safe from changes in lactose dose. The genomic inspection of organisms in which genetic drift is not, in principle, a suitable force to drive the fixation of duplicates (e. g. bacteria or yeast; Lynch and Marinov, 2015) gave us some empirical insight, despite the masking produced by subsequent evolutionary trajectories. In many cases of duplication, there is no a significant increase in total expression (e. g. duplicates in Saccharomyces cerevisiae vs. singletons in Schizosaccharomyces pombe; Qian et al. , 2010). [SEP] Justify:

Output: The text corroborates the claim by discussing various contexts in which genetic mutations can have different effects. It explains how duplications of genes can be either detrimental in changing environments or beneficial under weak selection conditions. The mention of purifying selection and the balance of expression levels highlights that the mutations' impact varies based on environmental pressures and genetic context, aligning directly with the claim that mutations can be beneficial, neutral, or harmful.


Input: Task: pass the claim using the given text. Claim: The majority of genetic therapies are still in experimental stages but show promising results. [SEP] Text: , 2011) of histones can have profound consequences on the cell. In most cells, histone availability is tightly regulated at multiple levels, including transcriptionally, post-transcriptionally, and post-translationally (Marzluff et al. , 2008; Bannister and Kouzarides, 2011). For example, in mammalian cultured cells, transcription of canonical histones is highly upregulated during S-phase, when replication occurs, and afterwards throttling of transcription and mRNA turnover bring messages back to very low levels. And in yeast, excess histone proteins are degraded via the ubiquitin-proteasome system (Singh et al. , 2009). For early Drosophila embryos, regulation of histones is particularly challenging. On the one hand, these embryos develop incredibly rapidly: during the first ~90 min after fertilization, nuclei divide near simultaneously every ~8 min, deep within the embryo (cleavage stages); a subset of these nuclei migrates to the surface and divides four more times over the next hour (syncytial blastoderm stages). All these divisions occur near simultaneously and in the absence of cytokinesis. As a result, histone demand goes up exponentially during this period, in a fluctuating manner, as S-phases and mitoses alternate on minute time scales (the entire interphase is dedicated to DNA replication during these cycles). On the other hand, zygotic transcription is minimal during these stages, being upregulated only in late syncytial blastoderm as part of the midblastula transition (MBT). Thus, early embryos cannot control histone expression transcriptionally. Instead, they draw on abundant histone proteins and mRNAs, produced by the mother during oogenesis. Newly fertilized embryos already contain sufficient histone proteins for thousands of nuclei, and they increase histone levels further by translation of the maternal mRNAs. Thus, histone proteins are consistently overabundant. How is chromatin assembly regulated under those conditions? Previous work revealed that for three histones, the canonical histones H2A and H2B as well as H2Av, the single H2A variant in Drosophila, LDs play an important role in regulating histone availability (Li et al. , 2012). [SEP] Justify:

Output: The text is irrelevant to the claim regarding genetic therapies. It discusses the regulation of histones in cellular biology, specifically in Drosophila embryos, without mentioning genetic therapies or their experimental status. Therefore, it does not provide any information that corroborates or contrasts with the claim.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: Nevertheless, our data are representative of previous apparent consumption from international data on the use of olive oil for cooking and food preparation in Western countries(Reference Uylaşer and Yildiz39,40). Specifically, current available data on trends related to olive oil consumption indicate that over the past 30 years, there has been a 75 % increase in the consumption of olive oil in Australia(40). In comparison, olive oil consumption in the USA has also seen a 78 % increase from 1991 to 2021. In contrast, olive oil consumption in some Mediterranean countries, including Italy and Greece, has seen between a 13 and 45 % decline in olive oil consumption over this timeframe(40). The rise in EVOO use in Australian households has the potential to contribute to healthier dietary patterns and positively impact population health due to the myriad of health benefits associated with its high nutritional quality and its unique composition. In particular, oleic acid in addition with bioactive polyphenolic molecules (such as oleuropein, hydroxytyrosol and tyrosol) are important constituents of EVOO which may help to explain its cardioprotective role including reductions in TC and LDL-cholesterol, blood pressure, pro-inflammatory markers, improved insulin sensitivity and endothelial function and reductions in oxidative stress(Reference George, Marshall and Mayr41–Santis, Cariello and Piccinin45). Regular consumption of EVOO has also been associated with reductions in diabetes mellitus, inflammatory bowel disease, obesity and some cancers(Reference Jiménez-Sánchez, Martínez-Ortega and Remón-Ruiz46). As such, it is not surprising that perceived health benefits were identified as the primary motivator for olive oil use in Australian households. Our findings are in agreement with a smaller study involving n 35 men and women in the USA who also identified the perceived health benefits of olive oil as an important factor influencing consumer choice(Reference Santosa, Clow and Sturzenberger47). Importantly, however, results from the present study as well as the aforementioned study conducted by Santosa et al. (Reference Santosa, Clow and Sturzenberger47) did not further articulate the specific details related to perceived health benefits such as cardiovascular benefits and/or reductions in disease risk. [SEP] Justify:

Output: The text does not address the claim about charred plant remains indicating past cooking methods and food preferences. Instead, it discusses trends in olive oil consumption and its health benefits, which are unrelated to the investigation of cooking methods or food preferences from charred remains.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Thus, either duplicates were fixed by dosage in a definite environment to then return to ancestral expression levels, or duplicates were fixed by other means. In any case, the preservation of the ancestral function in the second copy is expected (DeLuna et al. , 2008). Whether noise reduction was actually relevant for some fixations or not is hard to say without conducting an experimental approach to measure variability and selection (revealing the fitness landscape; Figure 2); notwithstanding, it seems a plausible mechanism according to our results, already put forward with the computational analysis of gene expression patterns (Lehner, 2010) and metabolic flux balances (Wang and Zhang, 2011) in yeast. If dosage mattered at some point, the function encoded by the duplicated gene would be more important at the time of duplication than today. In E. coli, for example, genes fsaA and fsaB are paralogs, with high sequence (69%) and functional similarity, coding for a genuine fructose-6-phosphate aldolase (Sánchez-Moreno et al. , 2012). The relevance of this enzyme for today E. coli is unclear, suggesting that fsaB might have been fixed by dosage in past habitats in which rare sugars were frequent. However, if noise were the critical aspect, the system would present some regulation to link environment with phenotype and the function would be of routine for the cell. In particular, E. coli expresses two redundant gluconokinases, encoded in genes gntK and idnK (51% of sequence identity), to face environments in which gluconate is the carbon source due to glucose oxidation (Vivas et al. , 1994). Similar to the regulation of lacZ by lactose (Jacob and Monod, 1961), gluconate activates the expression of gntK and idnK by inhibiting the transcriptional repressor GntR (Afroz et al. , 2014). Again, there would be a trade-off between metabolic benefit and expression cost (Figure 1c; read gluconate instead of lactose and GntK/IdnK instead of LacZ). Arguably, duplication might have been fixed in this case to cope with gene expression inaccuracies, especially when GntR produces bimodal responses (captured in single-cell experiments; Afroz et al. , 2014). [SEP] Justify:

Output: The text discusses how gene duplicates can be fixed based on the context of their environment, indicating that genetic factors are influenced by environmental conditions (e.g., ‘the function encoded by the duplicated gene would be more important at the time of duplication than today’). This supports the claim that genetic mutations can have varying consequences—beneficial if they enhance fitness in a particular environment, neutral if they do not impact fitness significantly, or harmful if they detract from the organism's functionality. The mention of metabolic benefits and expression costs provides a direct connection to how mutations are context-dependent.


Input: Task: pass the claim using the given text. Claim: The majority of genetic therapies are still in experimental stages but show promising results. [SEP] Text: GSK1120212 is another potent and selective inhibitor of the MEK1/2 enzymes with promising anti-tumor activity in a phase I clinical trial, resulting in response rate > 70% in advanced melanoma patients with known BRAF mutations, including one patient who was previously treated with PLX4032 (Infante 2010). This drug is currently investigated in phase II and III clinical trials for advanced BRAF mutant melanoma patients who were either previously treated with a BRAF inhibitor or not. (NCT01245062, NCT01037127). Although targeting the MAPK pathway is a promising new therapeutic approach for the treatment of melanoma, and treatment with selective BRAF and MEK inhibitors can induce high response rates, the limited duration of these responses in most patients, most likely because of emerging resistance to these inhibitors represents a significant clinical challenge. Molecular redundancy, in part due to the existence of RAF isoforms and signaling through alternative oncogenic pathways, such as PI3K/AKT/mTOR pathway (Jiang et al. 2011; Paraiso et al. 2010), receptor tyrosine kinase (PDGFRβ)-dependent pathway (Nazarian et al. 2010) and COT (MAP3K8) (Johannessen et al. 2010), may provide the melanoma cells’ escape mechanisms to specific pathway inhibitors and underscore their ability to adapt to pharmacological challenges (Jiang et al. 2011; Paraiso et al. 2010). In preclinical models, it has been reported that acquired resistance of melanoma cells to the BRAF inhibitors was associated with rebound activation of the RAF/MEK/ERK pathway (Paraiso et al. 2010). In line with this finding, activating signals to downstream MEK/ERK has been shown to switch to ARAF (Villanueva et al. 2010) or CRAF (Montagut et al. 2008; Villanueva et al. 2010) via N-RAS upregulation (Nazarian et al. 2010) to overcome the effect of BRAF inhibition. [SEP] Justify:

Output: The text discusses GSK1120212 and its performance as a MEK1/2 inhibitor in clinical trials for melanoma but does not mention genetic therapies specifically. While it describes promising results concerning response rates and challenges with resistance in cancer treatment, it does not support or contrast the claim regarding genetic therapies, which makes it irrelevant.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: Nevertheless, despite the perceived health benefits reported by participants in the present study, the majority reported using less than one tablespoon of olive oil per day, which is markedly less than reported in previously published clinical trials investigating cardiovascular benefits from the use of EVOO(Reference Estruch, Ros and Salas-Salvadó13,Reference George, Marshall and Mayr41,Reference Davis, Hodgson and Woodman48). Whether lower quantities of EVOO incorporated into an otherwise healthy dietary pattern will exert the same cardiovascular benefits remains largely unknown and is subject to ongoing research. Nevertheless, given the potential cardioprotective health benefits associated with EVOO consumption, it would be prudent for health care clinicians to advocate the use of EVOO, particularly in high-risk patients, at quantities that are acceptable to individual, social and health-related needs. Sensory preference was also a determining factor in the main choice of oil used. In particular, participants favoured a ‘neutral’ oil including EVOO or olive oil. Nevertheless, some participants reported olive oil as having ‘too strong’ a flavour and favoured alternative oils depending on cuisine type. Previous evidence suggests that the fatty acid composition of oils may be responsible for taste perception and can play a role in determining taste intensity and perceived retention of taste(Reference Koriyama, Wongso and Watanabe49). Furthermore, some studies have indicated that the phenolic compounds present in EVOO, namely oleuropein, may influence the bitterness and thus perceived taste of the oil(Reference Campestre, Angelini and Gasbarri50). In a sample of n 60 Italian adults, Barbieri et al. (Reference Barbieri, Bendini and Valli51) reported that participants did indeed appreciate the fruity flavour when sampling EVOO; however, this was superseded by the perceived bitterness of the oil. Furthermore, sensory perception has been reported to be influenced by more than taste and smell alone, with brand, price, country of origin, and label information and presentation playing a key role in sensory perception(Reference Fernandes, Ellis and Gámbaro52). In the present study, data on the sensory perception of olive oil beyond comments related to the perceived neutrality of the oil were not collected, and as such, we have limited information regarding respondents’ motivations on choosing olive oils based on perceptions of specific flavours, pungency or other sensory characteristics. Limiting cooking problems (e. g. [SEP] Justify:

Output: The text does not address the claim regarding charred plant remains and cooking methods. Instead, it discusses the use of olive oil in dietary patterns and sensory perceptions related to its flavor, which is unrelated to the indication of past cooking methods or food preferences based on charred plant remains.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: A comprehensive model compatible with population genetics to explain the early fate of gene duplications Taking all our results together, we formulated a comprehensive model to explain the early fate (viz. , fixation or elimination) of gene duplications (Figure 7). Notably, this model is compatible with population genetics, involving positive and neutral selective conditions (Lynch, 2007). On the one hand, a significant number of duplicates could be fixed by genetic drift only in complex organisms (i. e. higher eukaryotes; sector A in Figure 7). This would be due to their increased ability to allocate additional resources for expression (Lynch and Marinov, 2015), and their apparently reduced duplication deletion rate with respect to the inverse of the population size (Schrider et al. , 2013). However, these fixed duplications would not be stable, due to the formation-deletion balance (Reams et al. , 2010), and then, for a long-term preservation, they would require the accumulation of beneficial mutations (Han et al. , 2009), or the relocation of the second copy in the genome to prevent its deletion (Ranz et al. , 2001). This would lead to late fates of sub- or neo-functionalization (Force et al. , 1999; Conant and Wolfe, 2008). Figure 7 Download asset Open asset General model to explain the fixation of duplicated genes as a function of the degree of selection in the population and preservation in the genome for long time. Representative silhouettes correspond to bacteria (prokaryotes), yeasts (lower eukaryotes), insects, plants, and mammals (higher eukaryotes). On the other hand, positive selection could drive the fixation of duplicates in both complex and simple organisms. When the environmental changes were relatively rapid, only organisms with short generation times (i. e. , prokaryotes and lower eukaryotes) could fix duplications (sector C in Figure 7; Riehle et al. , 2001). However, such duplications would be quickly eliminated from the population afterwards (once the environment changed again), as the genome rearrangement rates are orders of magnitude higher than the per base mutation rates (Reams et al. , 2010). By contrast, when a given environmental change were prolonged, any organism, irrespective of its generation time, could fix duplications (sector D in Figure 7; Emerson et al. , 2008). [SEP] Justify:

Output: The text corroborates the claim by discussing how different selection pressures can influence the fate of gene duplications in various organisms. It notes that genetic drift, environmental changes, and the requirement for beneficial mutations all factor into whether genetic changes can be fixed or eliminated in populations, aligning with the idea that mutations can be beneficial, neutral, or harmful depending on context. For instance, it mentions that 'positive and neutral selective conditions' impact fixation and suggests that duplications would require 'the accumulation of beneficial mutations' for long-term preservation.


Input: Task: pass the claim using the given text. Claim: The majority of genetic therapies are still in experimental stages but show promising results. [SEP] Text: Such moves could reduce compliance burdens for businesses engaged in cross-border trade, especially smaller businesses. Our study shows that reductions in the costs of complying with different VAT rules in different countries could boost cross-border trade, GDP and household consumption so such efforts should be welcomed. Plans to encourage the sharing of information and best practise between national revenue authorities and to investigate the potential of a trans-national anti-fraud team also seem sensible. Another promising proposal is to abandon the long-standing objective of moving towards a VAT based upon taxing cross-border trade at the rate of VAT applicable in the exporting country (the origin principle). Doing this will allow the Commission to focus on improving the operation of the existing EU VAT system largely based on the destination principle: taxation in the importing country at the importing country's VAT rate. Such a system has real benefits. For instance, cross-country differences in rates of VAT should not distort where firms choose to source their inputs from: they pay the domestic rate of VAT whether they buy things from a domestic supplier or a supplier based in another EU country. Perhaps more controversially, the Commission envisages broadening the VAT base with efforts to reduce the extent of exemptions in the public interest (including in the public sector), and in the provision of passenger transport services. This will initially focus on areas where the distortions to the Market and competition with non-exempt firms are greatest. The report also recognises that the plethora of reduced rates of VAT increases the complexity of the system for relatively little gain. A review of the current rate structure of VAT is proposed, with the aim of abolishing reduced rates that are harmful to the Internal Market, or that apply to goods for which consumption is discouraged by other EU policies, whilst ensuring similar goods and services face the same VAT rate. This represents a step in the right direction, but will leave many exemptions and reduced rates in place. However, as stated by the Commission "the are primarily responsible for limiting as far as possible the scope of such [reduced] rates", and they also have some discretion about when to apply exemptions. Implementing a reduction in the use of exemptions and reduced rates is likely to be political difficult: those sectors benefiting from them will lobby against their abolition, and it is unlikely to be popular with national electorates either. But doing so would bring real economic gains. Exemptions, in particular, are anathema to the whole principle of VAT. [SEP] Justify:

Output: The text is irrelevant to the claim about genetic therapies, as it discusses VAT systems, trade compliance, and economic policies without any mention of genetic therapies or experimental stages. Therefore, it does not support or contrast the claim in any way.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: burning food, damage to cookware) was frequently reported as a perceived motivator for choosing the main household cooking oil. Specifically, respondents reported selecting an oil with a high smoke point for the style of cooking (e. g. frying) that would not damage cookware or utensils. As such, this was more frequently reported amongst participants who did not use a form of olive oil as the main oil in the household. Indeed there is a perceived perception that olive oils do not have a high smoke point and are not suitable for certain cooking methods, such as frying; however, evidence continues to mount suggesting that EVOO in particular can be heated to temperatures of 180 degrees Celsius for deep frying and up to 240 degrees Celsius for shallow frying while maintaining stability and producing less polar by-products than its polyunsaturated counterparts and in turn protecting cookware(Alzaa, Guillaume and Ravetti53–Reference Ramírez-Anaya, Castañeda-Saucedo and Olalla-Herrera56). Furthermore, there is also a common perception that heating olive oil to high temperatures may damage the properties of the oil. However, previous evidence suggests that the phenolic compounds within EVOO play a protective role in minimising oxidation during frying(Reference Servili, Sordini and Esposto57,Reference Santos, Cruz and Cunha58) and EVOO with a high oleic acid composition demonstrates a lower formation of toxic compounds during frying(Reference Procida, Cichelli and Compagnone59). Nevertheless, in the present study, EVOO continued to be the most frequently used oil for sautéing, shallow frying and stir frying which is a finding consistent with a previous cross-sectional survey of n 2234 participants in the USA which reported that 86 % of participants sautéed with olive oil despite suggestions of the proposed low smoke point associated with the oil(Reference Wang, Moscatello and Flynn60). Despite the high use of EVOO across these cooking techniques, we did observe differences between sauteing, stir frying and shallow frying. For example, we observed that a greater proportion of participants (74·3 %) used a form of olive oil for sauteing rather than for stir frying (46·3 %), which is considered a similar cooking technique albeit at a lower temperature. However, this may also reflect the interpretive differences in oil use for different cooking methods across different ethnicities. [SEP] Justify:

Output: The text does not directly address the claim regarding charred plant remains as indicators of past cooking methods or food preferences. Instead, it focuses on the selection of cooking oils based on their properties and the cooking techniques utilized by participants. The discussion revolves around olive oil's smoke point and its usage in various cooking methods, which is not relevant to the claim about charred plant remains.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: In this case, they would be under strong positive selection, and, consequently, they would be preserved for long time. Furthermore, all organisms could fix duplications by producing more accurate responses (sector B in Figure 7), without the need of significant environmental changes; provided the gene of interest were noisily expressed (Elowitz et al. , 2002; Raser et al. , 2004), and the duplication deletion rate were lower than the weak selective advantage. In the very long term, these weak selective conditions could also allow the exploration of novel functions, as they ensure the preservation of duplicates, without invoking fortuitous exploration in the ancestral state (Bergthorsson et al. , 2007), and with amplification when the advantage provided by the narrowed novel function were higher than the advantage by noise reduction. inherently stochastic nature of gene expression is certainly an evolutionary driver when it is linked to cell fitness to dictate the selection of particular genetic architectures (Batada and Hurst, 2007; Maamar et al. , 2007). Our results demonstrate that gene duplication can be positively selected as an architecture that allows enhancing information transfer in genetic networks (i. e. mitigation of expression errors; Rodrigo and Poyatos, 2016). Accordingly, the genetic robustness indeed observed upon the accumulation of genetic redundancy (Keane et al. , 2014) would be more a consequence than a selective trait (Kafri et al. , 2006). Certainly, by aggregating the responses of two genes, intrinsic fluctuations can be mitigated, but not fluctuations of extrinsic nature. This way, duplication would be more favorable in scenarios in which intrinsic noise is preponderant. The balance between intrinsic and extrinsic noise depends on the particular environmental conditions and the regulatory structures in which the gene in embedded. Intrinsic noise can be significant when the medium is rich in nutrients, the expression levels are low, and no further regulations affect the gene (Swain et al. , 2002). For example, competence in Bacillus is mainly governed by intrinsic noise (Maamar et al. , 2007). To follow our model, noise has to mainly impinge the regulation of the system, that is, disturb the link between the signal molecule and gene expression (Blake et al. , 2006). Moreover, our results highlight that a population genetic model with the mean selection coefficient is enough to explain the complex, stochastic evolutionary dynamics of duplication fixation. [SEP] Justify:

Output: The text corroborates the claim by discussing how genetic duplications can be under strong positive selection, which indicates that some genetic mutations can provide a beneficial effect in certain contexts. It also explains that the genetic robustness observed from the accumulation of genetic redundancy may provide advantages depending on environmental conditions, indicating that the impact of genetic mutations is context-dependent.


Input: Task: pass the claim using the given text. Claim: The majority of genetic therapies are still in experimental stages but show promising results. [SEP] Text: Taken together, these results suggest that the topical application of new treatments targeting the proteins associated with cancer cell formation have the potential to treat cutaneous squamous cell carcinomas and other related skin conditions, and raise the possibility that topical treatments containing multiple cancer-associated protein (enzyme) inhibitors together could be more effective than utilising a single compound. ‘These innovations represent a promising and much-needed alternative to today’s topical therapies, one that directly targets the biological mechanisms driving the tumour’s growth,’ explains Dr Seykora, ‘with the number of cases of cutaneous squamous cell carcinoma steadily rising, it’s important we work to identify safer, more precise therapies to treat these cancers before they progress and spread. We believe topical kinase inhibitors are potential candidates that warrant further study. ’ E-book the researcher T. Seykoraof MedicineUniversity of. Seykora is a tenured Professor of Dermatology in the of Medicine at the University of Pennsylvania. He received his undergraduate degree in Biology with Honors and concurrently was awarded a Masters in Biochemistry from the University of Chicago. received his PhD from Rockefeller University, and then an MD qualification from Medical College. After undertaking residency and fellowship at the University of Pennsylvania, began teaching and performing research in the School of Medicine at the University of Pennsylvania, and later went on to become a tenured Professor of Dermatology, a position he still holds today. From being a Scholar at the University of Chicago in 1982 to receiving the Dean’s Award for Excellence in Teaching from the of Medicine in 2019, has received an abundance of awards and honours throughout his career. : seykora@pennmedicine. upenn. edu W: 01AR051380, RO1-CA165836, RO1-ES02811, and P30-AR069589 of Health grant P30-AR069589 Whole exome and transcriptome analysis of UV-exposed epidermis and carcinoma in situ reveals early drivers of carcinogenesis, Journal of Investigative Dermatology, 2020, 141(2), 295–307. , Voriconazole enhances UV-induced DNA damage by inhibiting catalase and promoting oxidative stress, Experimental Dermatology, 2020, 29(1), 29–38. [SEP] Justify:

Output: The text does not address genetic therapies or their experimental status. Instead, it discusses new topical treatments for skin cancers, particularly focusing on their potential effectiveness against cutaneous squamous cell carcinoma. While it mentions promising alternatives to current therapies, it does not affirm or contrast the specific claim regarding genetic therapies.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: Additionally, the theme of minimising damage to cookware was more frequently reported as a perceived motivator for oil choice than cost. This is indeed a novel finding given that some form of olive oil was the most commonly reported oil used in Australian households, despite its high costs relative to other common cooking oils(Reference D’Adamo, Falcone and Gastaldi61,Reference Martínez, Aragonés and Poole62). Our findings are in contrast to those previously reported by Erraach et al. (Reference Erraach, Sayadi and Gomez63) and Santosa et al. (Reference Santosa, Clow and Sturzenberger47) who identified that cost was one of the main determining factors in participants’ decisions to purchase olive oil in n 439 adult consumers of olive oil (52·5 % female; 47·5 % male) in Spain and n 35 adults (82·9 % female; 17·1 % male) in the USA, respectively. However, more recent findings suggest that when choosing a household oil, factors, including sustainability, are more considered than the cost of olive oil (Reference Erraach, Jaafer and Radić64). In contrast to these findings, supporting local production of oils and environmental sustainability were not as frequently reported in the present study. Cultural background and family p10. 1017/S0007114522003798 1070. CrossRef1737. 3978. CrossRef406. CrossRef546. CrossRef605. CrossRef8. CrossRef63. CrossRef0252. CrossRef2345. 1080. CrossRef34. CrossRef11. CrossRef1130. CrossRef29. 10. 3390/foods7030029CrossRef10. 1093/advances/nmz069CrossRef2124. 10. 1080/10408398. 2018. 1438349CrossRef7675. CrossRef262. CrossRef1258. CrossRef559. CrossRef1273. CrossRef1459. CrossRef56. CrossRef1512. CrossRef122. 10. 1093/ajcn/63. 1. 116CrossRef2145. CrossRef280. CrossRef259. CrossRef31. 284. CrossRef1288. CrossRef240. 101. CrossRef114. CrossRef27. 0. Armonk, NY: IBM Corp. 1101. CrossRef2795. [SEP] Justify:

Output: The text does not address the claim about charred plant remains indicating past cooking methods and food preferences. Instead, it discusses factors influencing oil choice in cooking, such as damage to cookware and sustainability. This information is not related to the claim regarding charred plant remains.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Of note, the reported intrinsic adaptive value, which cannot be captured by sequence analyses, was derived from basic mathematical models of gene regulation and cell fitness (Dekel and Alon, 2005). Notably, we anticipated a series of testable results by following our theory of error buffering upon duplication. First, the gene expression level is indicative of the fixation path. The theory requires that gene expression is roughly maintained (i. e. gene dosage sharing, duplicates vs. . singletons), with the aim of minimizing deleterious fitness effects. This would hold for several fixed duplicates in different organisms (Qian et al. , 2010; Gout and Lynch, 2015; Cardoso-Moreira et al. , 2016; Lan and Pritchard, 2016), although most of the formed duplicates would be under strong purifying selection due to the cost of over-expression, as already proposed (Lynch and Conery, 2000). By contrast, those fixed duplicates showing increased gene expression levels would reflect the effect of genetic drift (Lynch and Conery, 2003) or positive selection for dosage after prolonged environmental changes (e. g. the case of flies; Emerson et al. , 2008; Cardoso-Moreira et al. , 2016). Second, noisy genes are expected to be more duplicable (e. g. as it seems to happen in yeast; Lehner (2010); Dong et al. , 2011) when noise has deleterious fitness effects. Indeed, the gain experimented by the system upon duplication is greater when gene expression inaccuracies are significant (Rodrigo and Poyatos, 2016). This would explain the TATA box enrichment in the cis-regulatory regions of duplicated genes, as these genetic motifs are associated to high plasticity (i. e. high sensitivity to multiple environmental changes) and high gene expression noise by inducing transcriptional bursts (Blake et al. , 2006; Lehner, 2010). Note that if noise were beneficial (e. g. as a survival strategy in fluctuating environments; Acar et al. , 2008), duplication would not be favored. Moreover, we might argue that essential genes would be less duplicable (He and Zhang, 2006) as a consequence of their reduced gene expression noise (Batada and Hurst, 2007). Genes under the control of regulatory structures that buffer noise (e. g. [SEP] Justify:

Output: The text corroborates the claim by discussing how gene expression levels and their regulation can influence the adaptive value of genetic variations in different contexts. It highlights that genetic mutations can lead to both positive and negative effects, with the expression levels influenced by environmental changes and fitness costs. For instance, it mentions that increased gene expression levels can result from positive selection under certain conditions, indicating that some mutations can be beneficial. Conversely, it also notes the presence of strong purifying selection due to the potential harmful effects of over-expression. This aligns with the claim's assertion that genetic mutations can have varying impacts based on the context.


Input: Task: contrast the claim using the given text. Claim: The majority of genetic therapies are still in experimental stages but show promising results. [SEP] Text: The minimum level of dystrophin that might be reasonably likely to predict clinical benefit in patients with BMD remains unknown, but experts in DMD have stated that levels less than 3 percent of that of normal healthy muscle are generally associated with the typical DMD phenotype. ”The FDA also questioned whether the 13 historical controls had received the same intensity of physical therapy and steroid treatment. It stated that “performance on the 6-minute walk test could be influenced by motivation and coaching. ” The agency also expressed concern that “open-label trials are susceptible to bias on the part of investigators, patients, and parents. ”Perhaps of greatest concern, the FDA stated in its briefing document that the clinical course of the 12 patients treated with eteplirsen “appears to be within the expected natural history of DMD. ” Treated children, it stated, “experienced a sequential worsening of functional abilities and muscle weakness, as demonstrated by changes in rise times from the floor and the evolution of (NSAA) scores. ”The principal investigator of the trial, Jerry R. chair of pediatric research and professor of pediatrics and neurology at Nationwide Children's Hospital and University in Columbus, declined via email to speak with due to concerns about how such an interview might be viewed by the FDA. But the four-year data presented at AAN were seen by many as the best answer to the FDA's doubts. Still, some expressed concerns about how the challenges in seeking approval might affect enrollment for future trials seeking more definitive (and needed) blinded data. . Nelson, MD, professor of human genetics, and Carrie Miceli, PhD, professor of microbiology immunology and molecular genetics — co-directors of the Center for Dystrophy at the School of Medicine at the University of California, (UCLA) — coauthored a letter of support to the FDA to underscore the importance with which the DMD scientific community regards the drug. “We felt perplexed that the data looks good, yet has not been met with a clear path forward for approval,” Dr. Nelson said. “The data are highly supportive of the drug having a positive effect with good safety. I think the effect is substantive but not curative. [SEP] Justify:

Output: The text contrasts the claim by highlighting uncertainties and concerns expressed by the FDA regarding the effectiveness of certain treatments for Duchenne muscular dystrophy (DMD). It mentions that the expected clinical benefits and the minimum level of dystrophin necessary to predict such benefits remain unknown, thus suggesting a lack of conclusive support for genetic therapies. Additionally, the text notes that treated children experienced worsening functional abilities, which counters the idea that experimental therapies show promising results.


Input: Task: pass the claim using the given text. Claim: Charred plant remains can indicate past cooking methods and food preferences. [SEP] Text: CrossRef35. CrossRef28. CrossRef13. CrossRef2085. CrossRef1440. CrossRef2111. CrossRef1313. CrossRef873. CrossRef1833. CrossRef195. CrossRef71. CrossRef11. 9. CrossRef12. 246. CrossRef23. CrossRef2024. CrossRef229. CrossRef1911. CrossRef180. CrossRef19. 2310. CrossRef387. CrossRef7630. CrossRef12. CrossRef2840. CrossRef186. CrossRef1. Summary of questions from part B of the online survey evaluating the types of oils used in cooking and food preparation in in content Table 2. Demographic characteristics of participants (n 1248) View in content Table 3. Frequency and percentage of main household oil use differentiated by daily serve size (n 1248) View in content Table 4. Frequency n (%) of oil use for different cooking methods (n 1248) View in content Table 5. Perceived motivators of the main oil used by participants in their household (n 1248) Wilson et al. supplementary material Wilson et al. supplementary material File 33. 8 KB You have Access 1 Cited by Cited by Loading. . . [SEP] Justify:

Output: The text is irrelevant to the claim as it primarily consists of references and survey data without directly addressing the role of charred plant remains in indicating past cooking methods or food preferences. It does not provide evidence or examples related to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: negative feedbacks) would not be duplicable either (Warnecke et al. , 2009). However, this consideration should be taken with caution, as genes not essential a priori could be duplicated and then, upon fixation, accumulate beneficial mutations (Han et al. , 2009) to ensure preservation for long time, resulting a posteriori in essential genes due to functional diversification (as it seems in the case of mammals; Makino et al. , 2009). Third, the local genetic context would be highly determinant of the fixation of a duplicate (Reams et al. , 2012), explaining why some genes are more duplicable than others in scenarios of apparent neutrality (hot spots; Perry et al. , 2006). Moreover, duplicates would be much shorter lived in prokaryotes than in eukaryotes (Lynch and Conery, 2003), due to the differences of orders of magnitude in the duplication deletion rates. After all, the precise experimental determination of the molecular rates of gene copy number variation would unveil to what extent natural selection has actually rivaled random genetic drift to shape complexity along the course of life history (Rodrigo, 2017). These predictions involve, nevertheless, some limitations. On the one hand, due to a simplified mathematical model not considering the many molecular/genetic attributes that impinge implicitly on gene expression, such as promoter sequence-dependent noise levels (Metzger et al. , 2015), response coupling due to genetic proximity (Becskei et al. , 2005), or recursive fitness-expression dependence (Klumpp et al. , 2009). On the other hand, due to the difficulty to provide direct empirical evidence supporting the fixation of duplicates by reducing intrinsic noise. In this regard, we expect to carry out in the future an experimental approach (Dekel and Alon, 2005; Keane et al. , 2014) complementary to this theoretical study. Despite these edges, our results complete a mechanistic model in which duplicates are fixed either by genetic drift (no selection) or by gene dosage (strong selection) with the addition of a new principle, viz. , reduction of gene expression inaccuracies upon duplication can result in a weak selective advantage. Materials and methods Fitness function Request a detailed protocol The lac operon of E. [SEP] Justify:

Output: The text discusses the concept of genetic duplication and how it can lead to beneficial mutations under certain circumstances. It mentions that genes, when duplicated, can accumulate beneficial mutations that may become essential due to functional diversification. This indicates that mutations can indeed have beneficial effects based on the genetic context, thus corroborating the claim that genetic mutations can be beneficial, neutral, or harmful depending on the context.


Input: Task: contrast the claim using the given text. Claim: Personalized medicine uses genetic data to tailor treatments to individual patients. [SEP] Text: AbstractObjective:Response to specific depression treatments varies widely among individuals. Understanding and predicting that variation could have great benefits for people living with depression. Method:The authors describe a conceptual model for identifying and evaluating evidence relevant to personalizing treatment for depression. They review evidence related to three specific treatment decisions: choice between antidepressant medication and psychotherapy, selection of a specific antidepressant medication, and selection of a specific psychotherapy. They then discuss potential explanations for negative findings as well as implications for research and clinical practice. Results:Many previous studies have examined general predictors of outcome, but few have examined true moderators (predictors of differential response to alternative treatments). The limited evidence indicates that some specific clinical characteristics may inform the choice between antidepressant medication and psychotherapy and the choice of specific antidepressant medication. Research to date does not identify any biologic or genetic predictors of sufficient clinical utility to inform the choice between medication and psychotherapy, the selection of specific medication, or the selection of a specific psychotherapy. Conclusions:While individuals vary widely in response to specific depression treatments, the variability remains largely unpredictable. Future research should focus on identifying true moderator effects and should consider how response to treatments varies across episodes. At this time, our inability to match patients with treatments implies that systematic follow-up assessment and adjustment of treatment are more important than initial treatment selection. On average, antidepressant medication and specific psychotherapies have similar success in the first-line treatment of moderate depression (1–3). And on average, different antidepressants show equal or similar efficacy (4, 5). But the fact that treatments have similar efficacy on average does not imply that treatment selection is unimportant (6, 7). Individuals vary widely in response to specific treatments, and poor response to one treatment does not necessarily imply poor response to others. For example, among patients who do not benefit from initial treatment with one antidepressant, up to one-half experience significant improvement after switching to an alternative medication (8), adding a second medication (9), or adding psychotherapy (10). Unfortunately, many patients treated in community practice, especially in primary care, have no chance to benefit from second-line treatments. After starting antidepressant treatment, nearly one-half make no follow-up visits, and only one-quarter return often enough to pursue additional treatment options (11, 12). Accurate selection of the best initial treatment could have tremendous benefits for people living with depression. [SEP] Justify:

Output: The text contrasts the claim by stating that current research does not identify any biologic or genetic predictors that can inform treatment choices in depression. While the claim suggests that personalized medicine utilizes genetic data for tailoring treatments, the text indicates that, despite variability in patient responses, there is an absence of genetically based predictors that can aid in treatment selection.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Full text Figures and data Peer review Side by side Peer review process Decision letter Author response Peer review process This 10. 7554/eLife. 02743. 017 Author response Reviewer #1: I suggest saying up front when the # of units is given that males and females were grouped together (until they're not) and how many there were of each. Good point. The legend for Figure 3 now reads: “(C) Selectivity of sensory responses for units recorded in the adult AOB (197 units from male and female animals). (D) Selectivity of sensory responses for units recorded in the adult MeA (274 units from male and female animals). ” The legend for Figure 4 now reads: “(A) Responses of AOB neurons to vomeronasal stimuli in adult male (210 units) and female (64 units) mice. (B) Responses of MeA neurons to vomeronasal stimuli in adult male (106 units) and female (91 units) mice. (C) Responses of MeA neurons to vomeronasal stimuli in juvenile male (37 units) and female (50 units) mice. Units shown in panels A-C are the same data shown in Figure 3C,D but classified according to the sex of the animal recorded. ” I think that the response selectivity description in the Results is understated and suggest it needs defining in the Results. The results now include the following statement: “To further compare the stimulus selectivity of individual neurons, we calculated a selectivity index that ranges linearly from 0 (all stimuli elicit equal responses: center of triangles in panels C,D) to 1 (only one stimulus elicits a response: vertices of triangles in panels C,D) for units recorded from the AOB (mean 0. 38; 95% CI: 0. 36 to 0. 41; see supplementary information) and from the MeA (mean 0. 54; 95% CI: 0. 50 to 0. 58). ” Single-and multi-units were classified by spike shape, separation of principal component projections, and the presence or absence of a refractory period between successive spikes – I don't understand this for multi units. Our wording was poor; this was the process to identify single units. [SEP] Justify:

Output: The text is irrelevant to the claim regarding neural circuits processing social cues. It discusses experimental details related to sensory responses in the accessory olfactory bulb (AOB) and the medial amygdala (MeA), focusing on the methodology and results without addressing social cues or dedicated neural circuits for them.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: The dynamics of a punctual beneficial mutant appeared in an evolutionary experiment of serial dilution passages, with maximal population size N and dilution factor D, is given by r = 2S·t ⟨N⟩, where ⟨N⟩ = N D1/2 is the geometric mean population size (also considered the effective population size; Lewontin and Cohen, 1969). The fixation probability is Pfix = 2S, and the characteristic fixation time tfix = log2(⟨N⟩2)/S. Note that the time for 50% invasion of the population is thalf-fix = log2(⟨N⟩)/S = tfix/2. However, we have Pfix = 1/⟨N⟩ and tfix = 2⟨N⟩ for a neutral mutant (Kimura, 1983). By contrast, if multiple beneficial mutants are recurrently produced at rate μb, the dynamics is given by r = μb·N·2S·t [S·log(D)·⟨N⟩] ≈ μb·2S·t S, as in each passage μb·N different mutants are generated (valid for μb·N > 1; Desai et al. , 2007). Because mutants are now recurrent, Pfix = 1, and the characteristic fixation time reads tfix = log2[⟨N⟩·S μb]/S. When m different mutations accumulate successively, tfix ≈ tfix(m) + thalf-fix(m-1) + … + thalf-fix(1), that is, a subsequent mutation can start its fixation when the preceding mutation has invaded the 50% of the population (Lang et al. , 2013). If μb·N << 1, the system can be treated as in the case of a punctual beneficial mutation, and the dynamics can be written as r = 2S·(t - T) ⟨N⟩, with a delay of T = log2(D) (μb·N), the mean number of generations required to produce a mutant, and Pfix = 2S. [SEP] Justify:

Output: The text corroborates the claim by detailing the dynamics of beneficial and neutral mutations within an evolutionary context. It discusses how the fixation probabilities and times differ for beneficial mutants compared to neutral mutants, indicating that the impact of mutations is context-dependent. For instance, it mentions a beneficial mutant having a characteristic fixation time and the fixing probability varies for neutral mutations, thereby aligning with the claim that genetic mutations can have different effects based on their circumstances.


Input: Task: contrast the claim using the given text. Claim: Personalized medicine uses genetic data to tailor treatments to individual patients. [SEP] Text: This group includes numerous cohort studies examining the associations between specific genetic variations and favorable treatment outcomes in patients treated with a single antidepressant (45–52) or class of antidepressants (53, 54). Cohort studies of this type cannot distinguish between general predictors of prognosis and true moderators that predict differential response to alternative drugs. Similarly, studies identifying genetic variations associated with better response to one active antidepressant than to placebo (55) cannot distinguish general predictors of benefit with antidepressant treatment from specific predictors of differential response to alternative medications. Because none of the aforementioned reports compare alternative active treatments, none can provide evidence to personalize antidepressant selection. Relatively few studies have examined the association between genetic variations and outcomes in patients treated with alternative antidepressants. These include both randomized comparisons of alternative antidepressants (56–59) and nonrandomized comparisons (60, 61). In some cases, the pattern of associations is consistent with presumed mechanisms of drug action. For example, Kim et al. (60) found that response to an SSRI (either fluoxetine or sertraline) was significantly associated with variation in serotonin transporter genes but not with variation in norepinephrine transporter genes. Using data from a randomized comparison of the two drugs, Szegedi et al. (56) and Tadic et al. (57) found that variations in both monoamine oxidase and catechol-O-methyltransferase genes were associated with response to mirtazapine but not with response to paroxetine. Wakeno et al. (59) found that variation in alpha 2A-adrenergic receptor genes was associated with response to milnacipran but not to paroxetine. Primary analyses in each of these studies addressed the following question: Does a specific genetic variation predict better outcome in patients treated with a specific medication? These analyses are appropriate for testing hypotheses regarding mechanisms of drug action, but they do not directly address our question regarding differential efficacy: Does a specific genetic variation identify a group of patients with significantly more favorable response to one antidepressant than to another? This question regarding differential efficacy is formally addressed by a test for interaction or moderation. Kim et al. (60) did report a post hoc subgroup analysis in which patients with a specific variation of the norepinephrine transporter gene experienced significantly higher response rates during treatment with nortriptyline than with either fluoxetine or sertraline. [SEP] Justify:

Output: The text contrasts the claim by explaining that while there are studies examining genetic variations and treatment outcomes, none of the reports provide evidence to effectively personalize antidepressant selection. It emphasizes that cohort studies cannot distinguish between general predictors of prognosis and specific predictors for differential response to drugs. This highlights a limitation in the application of genetic data for tailoring treatments, which is fundamental to the concept of personalized medicine.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: The text now reads: “Single units were classified from multi-unit activity based on spike shape, separation of principal component projections, and the presence or absence of a refractory period between successive spikes (Figure 1–figure supplement 1; Harris et al. , 2000; Hazan et al. , 2006). ” In most experiments, ∼2-6 recording sites were located dorsal to the MeA and were easily distinguished from the quiet baseline activity of the MeA. Do you mean to say that “units located dorsal to the MeA were easily distinguished from the quiet units of the MeA”? The text has been amended as follows: “In most experiments, ∼2-6 recording sites were located dorsal to the MeA and were easily distinguished from the quiet units of the MeA in the absence of vomeronasal stimulation. ” PLCO is not defined at first use and is not actually defined anywhere except in a figure legend. What does PLCO stand for? PLCO is now defined properly: “MOE stimulation elicited clear olfactory-evoked neuronal activity in the MOB and the posterolateral cortical amygdala (PLCO) in response to volatile urinary cues and odorants (Figure 1–figure supplement 3). ” In Figure 1, average histograms of the mean response (left panels) are shown with standard error (shaded region). Is this a typo and should be right panels? If not, I do not understand. Also, any SEM shading is way too small; even at 125% to see. Either increase the size of the figure or delete this. I don't see what Figure 1–figure supplement 2B adds? Our wording was unclear. The legend for Figure 2 now reads: “(Left) Each row shows the responses elicited in a single MeA unit by four different VNO stimuli, with each stimulus presented 5 times. The order of stimulus presentation was randomized during the experiment, but is shown grouped by stimulus for clarity. (Right) Histograms showing the mean response and standard error (shaded region) for each unit. Responses were aligned to the onset of stimulus presentation. All significant responses (p<0. 01; ) are indicated by an asterisk in the top right corner of the average histogram plots. Response magnitudes for each unit were normalized to the maximum response for all stimuli. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses technical aspects of neural activity recording and analysis, but does not provide evidence or context regarding neural circuits dedicated to processing social cues.