Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: Additional notes *The chronic diseases are diabetes, heart failure, ischemic heart disease, asthma, chronic obstructive pulmonary disease (COPD) and cancer (all cancers, prostate, breast, colorectal and lung cancer). All rates presented are crude except for trends where rates are age-standardized to the 1991 Canadian Population. A low rate for this indicator can be interpreted as a positive result. 31. Multimorbidity is the co-occurrence of more than 1 chronic disease simultaneously, where one condition isn't necessarily more central than the other. Multimorbidity is increasingly recognized as an independent predictor of disability, poor quality of life, complications of treatment, high health care costs and increased mortality. Endnote 117Endnote 118 Measure(s) Percentage of the population with multiple chronic diseases (2 or more of 10 chronic diseases), population aged 20 years and older. Percentage of the population with multiple chronic diseases (3 or more of 10 chronic diseases), population aged 20 years and older. of people aged 20 years and older living with more than 1 chronic condition (2 or more or 3 or more correspondingly) within the population. Data source. aged 20 years and older. Method of calculation Numerator: Number of people aged 20 years and older who report 2 or more (or 3 or more) of 10 chronic diseases. * Denominator: Total population, aged 20 years and older. Additional notes *The chronic conditions included are: heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease (COPD), diabetes, arthritis, Alzheimer's or other dementia, mood disorder (depression), and anxiety. A low rate for this indicator can be interpreted as a positive result. 32. Chronic diseases may result in functional limitations that affect people's ability to perform their usual activities of daily living at home, school or work. Endnote 119Endnote 120 Short- or long-term disability has negative social impacts on a person's quality of life and ability to care of themselves or their family. Endnote 121Disability can also have direct negative economic impacts as a result of loss of income due to time lost at work. Endnote 122 of population who report being limited in their activities "sometimes" or "often" due to disease/illness, population aged 12 years and older. [SEP] Justify:

Output: The text contrasts the claim by discussing the prevalence of multimorbidity and chronic diseases, indicating that chronic diseases often co-occur and can lead to functional limitations and decreased quality of life. It implies that the existence of multiple chronic conditions, along with their economic and social impacts, suggests that biohacking techniques cannot likely eliminate the risk of chronic diseases entirely.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Wildtype HIPK2 leads to an increase of p53 expression or stabilitySince HIPK2 activated p53-mediated transcription, we looked whether HIPK2 leads to an increase in the level of p53 protein after transient transfection of HeLa cells. Wildtype HIPK2 enhanced protein expression or stability of p53 compared to the vector transfected controls (Fig. 2A). The kinase-defective mutant K221A and the amino-terminal deletion AN which lacks the kinase domain led to a decrease of p53 protein. The carboxy-terminal HIPK2 deletion mutant AC which contains the kinase part did not influence p53 protein levels (Fig. 2A). This is a hint that the increase of p53 protein induced by wildtype HIPK2 could be responsible for the enhanced transcriptional activity mediated by p53 binding promoter elements (Fig. 1). Figure 2Enhancement of p53 protein levels by wildtype HIPK2. HeLa cells were transiently transfected with the indicated HIPK2 expression constructs. Cellular extracts were analyzed for p53 expression by Western blotting. The signals corresponding to p53 or phosphorylated p53 (Phospho-p53) are indicated by an arrow. Equal loading was confirmed by reprobing the blots with an anti-β-actin antibody as shown below. (A) Cells were left untreated after transfection. (B) 24 h after transfection, doxorubicin was added to a final concentration of 0. 1 μg/ml for 3 and 6 h as indicated. (C) 24 h after transfection doxorubicin was added to a final concentration of 0. 1 μg/ml for 6 h and anti-phospho-p53 (Ser 15)-antibody was used for detection of phosphorylated serine 15 in p53. wt, wildtype; vec, vector. Full size image Doxorubicin enhances the HIPK2-mediated increase of p53 expression or stabilitySince p53 is stabilized in response to DNA damage, we tested whether HIPK2 has an effect on stabilization of p53 mediated by the DNA damaging drug doxorubicin in HeLa cells. Doxorubicin induced a significant increase of the p53 protein level after 6 h in the vector-transfected controls (Fig. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of wildtype HIPK2 on p53 expression in HeLa cells and the impact of doxorubicin on p53 stability, which has no connection to urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Gene therapy is being researched to treat diseases like cystic fibrosis and sickle cell anemia. [SEP] Text: objectives of this review are: ‐ to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; ‐ to examine the risks of gene therapy against the potential long‐term gain for people with sickle cell disease. Search methods We searched the Fibrosis and which comprises of 2020. Selection criteria All randomised or quasi‐randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. Data collection and analysis No trials of gene therapy for sickle cell disease were found. Main results No trials of gene therapy for sickle cell disease were reported. Authors' conclusions No randomised or quasi‐randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well‐designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease. model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome. See more on using PICO in the Cochrane Handbook. Plain language summary available in English Español فارسی Français 한국어 Русский ภาษาไทย 简体中文 Gene therapy for sickle cell disease Review question We reviewed the evidence about the effect and safety of gene therapy on survival and on preventing symptoms and complications associated with sickle cell disease. cell disease results when a child inherits faulty genes for producing haemoglobin from both parents. It is a disease that is linked with frequent illness from early life and often results in death earlier than in the general population. Gene therapy replaces these faulty genes with normal ones. Search date The evidence is current to: 21 September 2020. Key results We looked for trials that used this approach of replacing faulty genes for producing haemoglobin with normal ones in the treatment of sickle cell disease. [SEP] Justify:

Output: The text corroborates the claim by discussing the objectives of a review focused on gene therapy for sickle cell disease, indicating that research is being conducted to assess the effects and safety of gene therapy as a potential treatment. It highlights the goal of replacing faulty genes in patients with sickle cell disease, which aligns with the broader context of utilizing gene therapy for treating genetic disorders like cystic fibrosis and sickle cell anemia.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: All-(Diabetes) analysis of mortality statistics based exclusively on immediate cause of death can significantly underestimate mortality attributable to other diseases that a person may have (i. e. underlying causes). Endnote 126 Diabetes mellitus is rarely recorded as the immediate cause of death on the death certificate because the people affected die of the complications of diabetes and not of the disease itself. For example, in 2007, diabetes was recorded as the main cause of death on the death certificate of only 3. 1% of all deaths in Canada, even though more than one-quarter (29. 9%) of all individuals who died in 2008/09 had been diagnosed with the condition. Endnote 127 All-cause mortality (the mortality rate due to any cause of death) can instead be used to estimate the all-cause mortality among people with and without diabetes independently of the immediate cause of death registered by the physician in the death certificate. Measure All-cause mortality rate ratio among people with and without diabetes. all-cause mortality rate ratio among people with and without diabetes is a measure of excess mortality associated with diabetes. Data source of Canada. aged 20 years and older. Method of calculation The "mortality rate due to any cause of death among individuals who have met the criteria for diagnosed diabetes" is divided by the "mortality rate due to any cause of death among individuals who have not met the criteria for diagnosed diabetes. " Numerator: Death rate among prevalent cases in the fiscal year (death rate [with diabetes]). Denominator: Death rate among individuals without diabetes in the fiscal year (death rate [without diabetes]). Additional notes All rates presented are crude except for trends where rates are age-standardized to the 1991 Canadian Census. A rate ratio close to one can generally be interpreted as a positive result. 35. (of Life Lost) Years of (PYLL) is a widely used measure of premature mortality (early death) and is an important indicator of the general health of the population. Endnote 128 PYLL represents the total number of years not lived by people who die prematurely before reaching a given age. Endnote 124 Deaths among younger people contribute more to the PYLL measure than deaths among older people. Multiple studies suggest that premature mortality rate is a sensitive indicator of the effectiveness of measures preventing chronic diseases such as cancer and cardiovascular disease, etc. Endnote 129Endnote 130 Measure PYLL by cause(s) of death. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexity of mortality related to chronic diseases like diabetes. It highlights that diabetes is often not listed as the immediate cause of death, indicating that simply identifying and addressing one condition does not eliminate risk associated with underlying health issues. Furthermore, it mentions that measures aimed at preventing chronic diseases yield varying effectiveness, suggesting that biohacking techniques are unlikely to completely remove the risk of such diseases.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: 2B). When cells were transiently transfected with wildtype HIPK2, the increase of p53 protein was similar to that observed after 6 h doxorubicin treatment. The combination of overexpression of HIPK2 and treatment with doxorubicin for 6 h resulted in an increase in p53 protein levels compared to either treatment alone, i. e. the HIPK2-mediated increase of the p53 protein level was further enhanced by the addition of doxorubicin (Fig. 2B). In summary, these results show that wildtype HIPK2 but not kinase deficient or severely truncated mutants led to an increase of p53 protein. Treatment with doxorubicin for at least 6 h further increased the amount of p53 protein. HIPK2 is not sufficient for phosphorylation of serine 15, serine 20 and serine 392 of p53Since HIPK2 contains a serine/threonine kinase domain and since multiple serine/threonine phosphorylation sites are present in p53 protein, we used antibodies that specifically detect single phosphorylated serine residues of p53 to look for a putative HIPK2-mediated phosphorylation of p53. Upon treatment with doxorubicin, serine 15 is phosphorylated in HeLa cells (Fig. 2C). However, no serine 15 phosphorylation was detected after transient transfection of HIPK2 in the absence of doxorubicin treatment. The amount of phosphorylated protein after doxorubicin treatment reflects the total amount of p53 protein (Fig. 2A, B and 2C), which suggests that almost all p53 protein present became phosphorylated on serine 15. Since the kinase defective HIPK2 mutant K221A probably acts in a dominant negative way, the amount of p53 which was induced by endogenous HIPK2 in the vector-transfected controls decreased. Similar to the decrease in the amount of p53 protein in the presence of the K221A mutant (Fig. 2A) there was a decrease in phosphorylated p53 after treatment with doxorubicin (Fig. 2C). [SEP] Justify:

Output: The text provided discusses scientific observations related to HIPK2 and p53 protein levels in the context of doxorubicin treatment. There is no mention or relevant discussion regarding urban living or its impact on stress levels, making the text irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Gene therapy is being researched to treat diseases like cystic fibrosis and sickle cell anemia. [SEP] Text: Therefore, development of a gene therapy approach has been sought for many years (Nathan 2001; Persons 2003). Description of the intervention Gene therapy holds a great deal of promise for the future of medical treatment. It involves the introduction of genetic material into a cell to treat disease. The momentum was generated in 2000 when it was demonstrated that lentivirus vectors containing normal human globin genes and regulatory regions from the beta‐globin locus control region could be faithfully transduced into mouse hematopoietic stem cells and expressed in erythroid cells (Bodine 2003; May 2000). How the intervention might work Gene therapy is the introduction of genes into an individual's cells and tissues in order to treat a disease. Most of the conditions treated in this way are genetic disorders that result from gene mutation malfunctions (Postnote 2005). Viruses are the most widely used vectors in gene therapy. Some of the different types of viruses used as vectors in gene therapy include: retroviruses; adenoviruses; adeno‐associated virus; parvovirus; herpes simplex virus; hepatitis virus; and vaccinia virus (Postnote 2005). The viral vectors are made harmless by removing the viral gene and replacing them with the therapeutic gene. This approach is known as gene addition (the transfer of normal beta globin gene into hematopoietic cells via retroviral vectors or adeno‐associated viruses that have been modified or crippled so they do not become infective). In theory, the viral vectors used in gene therapy are made harmless to prevent them from replicating and causing unwanted effects. However, these viruses could trigger unwanted immune responses and cause unwanted side effects. Other approaches of gene therapy that have been developed include gene replacement (targeted insertion of the transferred gene into the endogenous globin locus by homologous recombination) and gene repair or chimeroplasty (introduction of chimeric oligonucleotides composed of DNA and modified RNA residues into stem cells to direct correction of the mutation in the sickle gene). Good candidates for gene therapy include autosomal recessive disorders (such as SCD) because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene (Goncz 2002). Gene therapy, if successful, will provide a viable alternative for permanent correction of the abnormal gene in SCD. [SEP] Justify:

Output: The text corroborates the claim by discussing the promising potential of gene therapy for treating genetic disorders, specifically mentioning sickle cell disease (SCD). The text states that gene therapy has been sought for many years and describes different approaches, such as gene addition and gene repair, which aim to correct genetic mutations. It confirms that SCD is deemed a good candidate for gene therapy, aligning with the claim that research into gene therapy is focused on diseases like cystic fibrosis and sickle cell anemia.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: Definition PYLL rates measure the number of years of potential life not lived when a person dies prematurely (i. e. before the age of 75 years) due to specific cause(s)* per 100 000 population, in a given year. Data source Vital Statistics, Statistics Canada. population. Methods of calculation PYLL due to death is calculated for each age group (< 1, 1–4, 5–9, …, and 70–74) by multiplying the number of deaths by the difference between age 75 years and the mean age at death in each age group. PYLL correspond to the sum of the products obtained for each age group. The PYLL rate is obtained by dividing total PYLL by the total population aged 75 years or less. Endnote 131 Additional notes *Specific cause(s) of death: mortality rates are calculated using primary causes of death due to cardiovascular diseases, cancer and chronic respiratory diseases disease groups and suicide. PYLL is a measure of premature mortality in the population. All rates presented are crude except for trends where rates are age-standardized to the 1991 Canadian Census. A low rate for this indicator can be interpreted as a positive result. 36. (Probability of Dying) May 2012, the Assembly adopted the global target of a 25% reduction in premature mortality from non-communicable diseases (NCDs) by 2025. This is intended to reflect the impact of prevention efforts as well as improvements in access to resources that manage and treat NCDs. According to the Organization, of the 57 million global deaths that occurred in 2008, about 36 million (63%) were due to NCDs, including 14. 2 million premature deaths between the ages of 30 and 69 years. Endnote 132 Evidence shows that most premature deaths due to chronic disease are avoidable. Endnote 133Endnote 134 of dying (%) between the ages of 30 and 69 years from chronic disease(s). * mortality from major chronic diseases measures the unconditional probability of dying early (between the ages of 30 and 70 years) from any of 4 major chronic diseases,* expressed as a percentage. Data source Vital Statistics, Statistics Canada. population. Methods of calculation This indicator is calculated from age-specific death rates for each disease group as well as for the combined chronic disease categories. [SEP] Justify:

Output: The text contrasts the claim by providing evidence that premature deaths due to chronic diseases are largely avoidable, indicating that while some prevention efforts exist, the complete elimination of risk from chronic diseases through biohacking techniques is not supported. It mentions that of the 57 million global deaths in 2008, about 63% resulted from non-communicable diseases (NCDs), highlighting the significant impact of these diseases despite potential prevention methods.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: As expected from these findings, overexpression of the HIPK2 mutants AN and AC yielded less phosphorylated p53 compared to overexpression of wildtype HIPK2 in the presence of doxorubicin (Fig. 2C). Similar results were obtained using an antibody against serine residue 20 (data not shown). Using an antibody that specifically detects phosphorylation of serine 392 in p53 we could not detect phosphorylated p53 either in the presence of doxorubicin or during overexpression of HIPK2 (data not shown). Taken together, HIPK2 is not sufficient for phosphorylation of p53 at serine residues 15 and 20, where doxorubicin seems to be required, and for phosphorylation of serine 392. HIPK2 leads to a decrease of p53-induced Mdm2 expressionTo further characterize the interaction of HIPK2 and p53, Saos2 cells were transiently cotransfected with constructs coding for p53, p53 and wildtype HIPK2 or p53 and the kinase defective HIPK2 mutant K221A together with pEGFP-Nl coding for a green fluorescence protein (Fig. 3A). Mdm2 and p53 proteins were not detectable in Saos2 cells (lane 1). In agreement with previous observations [16, 17], wildtype p53 led to an induction of endogenous Mdm2 expression (lane 2). Interestingly, a p53-mediated induction of Mdm2 expression was not observed in the presence of wildtype HIPK2 (lane 3). Therefore, HIPK2 overexpression led to a decrease of p53-induced Mdm2 protein levels. This decrease in Mdm2 protein was not observed by coexpression of the kinase defective HIPK2 mutant K221A (lane 4), which suggests that the kinase domain is necessary for Mdm2 downregulation. Equal protein loading was shown by reprobing the filters with an antibody detecting β-actin. pAGFP-Nl was cotransfected in all cases to normalize overexpression. GFP fluorescence was not significantly different (Fig. 3B), indicating similar transfection efficiencies. Figure 3Downregulation of p53-induced Mdm2 by overexpressed HIPK2. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses findings related to the HIPK2 gene and its effects on p53 phosphorylation and Mdm2 expression, none of which relate to urban living or stress levels. It focuses solely on molecular biology research without addressing any aspects of living conditions or psychological stress.


Input: Task: corroborate the claim using the given text. Claim: Gene therapy is being researched to treat diseases like cystic fibrosis and sickle cell anemia. [SEP] Text: It will circumvent the problem of donor shortage and avoid complications related to graft versus host rejection that are involved with bone marrow or other forms of stem cell transplant. Gene therapy has been used to correct SCD in mice (Nathan 2001). Despite the technical problems faced, major progress in the globin gene therapy field has been achieved. This progress has advanced the possibility of gene therapy for haemoglobin disorders in the near future (Persons 2003; Chang 2006). The first successful use of gene therapy in humans for SCD has been reported; the investigators used a lentivirus to achieve integration of a normal beta globin gene into the participants hematopoetic cells (Ribeil 2017). A further clinical trial using the lentivirus is ongoing by other researchers (Kohn 2014). Review is an update of previously published versions (Olowoyeye 2010; Olowoyeye 2012; Olowoyeye 2014; Olowoyeye 2016; Olowoyeye 2018). Why it is important to do this review SCD causes significant morbidity and mortality. Identifying therapies that can be potentially curative, with a clear description of the evidence around these interventions, is vital to the care of individuals with SCD. objectives of this review are to: determine whether gene therapy can improve survival and prevent symptoms and complications associated with SCD; examine the risks of gene therapy against the potential long‐term gain for people with SCD. for considering studies for this review Types of studies Randomised control trials or quasi‐randomised trials. We plan to include any relevant phase I, II and III trials. Types of participants People of any age and sex with SCD of all phenotypes and regardless of geographic or healthcare setting. Types of interventions Gene therapy (any approach) plus standard treatment versus standard treatment or other 'curative' type treatment such as bone marrow transplantation, stem cell transplantation or cord blood transplantation. Types of outcome measures We will assess the following outcome measures. Primary outcomes Event‐free survival (individuals alive and free of SCD symptoms) Change in mean life expectancy of individuals with SCD attributable to gene therapy Secondary outcomes Changes in haematocrit (as measured by the primary trial) Severity as assessed by changes in complications associated with SCD (e. g. acute chest syndrome, strokes, chronic renal failure, liver and gallbladder diseases, leg ulcers, sequestration crises, etc. [SEP] Justify:

Output: The text corroborates the claim by discussing the use of gene therapy to correct sickle cell disease (SCD) in mice and mentioning progress in the globin gene therapy field, which is relevant to the potential treatment of hemoglobin disorders like SCD. Additionally, it mentions the first successful gene therapy in humans for SCD, indicating ongoing research and clinical trials in this area. The emphasis on the importance of identifying curative therapies for SCD also supports the claim.


Input: Task: pass the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: Return to endnote 79 referrer Footnote 80 Association of total cholesterol/high-density lipo-protein cholesterol ratio with proximal coronary atherosclerosis detected by multislice computed tomography. Prev Cardiol. 2009;12(1):19-26. Return to endnote 80 referrer Footnote 81. Usefulness of the triglyceride-high-density lipoprotein versus the cholesterol-high-density lipoprotein ratio for predicting insulin resistance and cardiometabolic risk (from the Cohort). Cardiol. 2008;101(4):497-501. DOI: 10. 1016/j. amjcard. 2007. 09. 109. Return to endnote 81 referrer Footnote 82 The 2003 Canadian recommendations for dyslipidemia management. CMAJ. 2005;172(8): 1027-31. Return to endnote 82 referrer Footnote 83 Society/ Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Cardiol. 2009;25(10): 567-79. Return to endnote 83 referrer Footnote 84 The 2003 Canadian recommendations for dyslipidemia management: revisions are needed. CMAJ. 2005;172(8):1027-31. Return to endnote 84 referrer Footnote 85 Describing and analysing primary health care system support for chronic illness care in Indigenous communities in Australia's - use of the Model. . 2008;8:112. DOI: 10. 1186/1472-6963-8-112. Return to endnote 85 referrer Footnote 86 Towards a national primary health care strategy: a discussion paper from the Australian government. Canberra (AU): Australian Government, Department of Health and Ageing; 2008. Return to endnote 86 referrer Footnote 87 Association. Position paper on access to oral health care for Canadians. Ottawa (ON): Association; 2010 May. Return to endnote 87 referrer Footnote 88 Agency of Canada. Organized breast cancer screening programs in Canada: report on program performance in 2005 and 2006. Ottawa (ON): Agency of Canada; 2011. Cat. : HP32-1/2006E-PDF Return to endnote 88 referrer Footnote 89 A review of screening mammography participation and utilization in Canada. Inj Can. 2011;31(4):152-6. [SEP] Justify:

Output: The text is irrelevant to the claim as it does not discuss biohacking techniques or chronic diseases at all. Instead, it consists mainly of references and citations related to various studies on cardiovascular health and screening programs. Therefore, it does not provide any information that corroborates or contrasts with the claim.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (A) Saos2 cells were transiently cotransfected with pEGFP-N and expression constructs coding for wildtype 53, wildtype HIPK2 or the kinase defective HIPK2 mutant K221A as indicated. After 24 h cells were lysed and analysed by Western blotting with the indicated antibodies. (B) GFP fluorescence was measured by quantitative fluorometry to show equal transfection efficiencies. Background fluorescence was set to 1 (lane 0). Fluorescence fold is increased above background (lanes 1 to 4). Bars, SD. Full size image HIPK2 overexpression does not change Mdm2 mRNA expressionNext we asked the question whether HIPK2 downregulates Mdm2 by decreasing Mdm2 transcription. We transiently transfected Saos2 cells either with vector alone or with expression plasmids coding for p53 or HIPK2. In addition, the plasmid coding for p53 was transiently transfected in the presence of either wildtype HIPK2 or the kinase defective HIPK2 K221A mutant (Fig. 4). Relative Mdm2 mRNA levels were detected by quantitative TaqMan RT-PCR with sequence specific primers for human Mdm2 (GenBank accession AF201370). As expected, p53 led to an approximately 4 fold increase of Mdm2 mRNA levels [16, 17]. In contrast, overexpression of HIPK2 did not lead to a change of Mdm2 mRNA compared to vector transfected controls (Fig. 4). Overexpression of p53 together with either wildtype HIPK2 or the kinase defective HIPK2 mutant K221A showed no significant decrease in p53-induced Mdm2 mRNA levels. Similar data were obtained with HeLa cells (data not shown). Therefore, HIPK2 does not downregulate Mdm2 at the transcriptional level. It seems that HIPK2 destabilizes Mdm2 by modifying the Mdm2 protein. Figure 4Quantitative mRNA Expression levels of Mdm2. Saos2 cells were transiently transfected with the indicated expression constructs. Mdm2 mRNA expression levels were determined by TaqMan RT-PCR as described in Materials and Methods. As internal reference, mRNA expression of GAPDH mRNA was used. [SEP] Justify:

Output: The text discusses cellular and molecular biology related to HIPK2 and Mdm2 mRNA levels and does not address urban living or stress levels. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Gene therapy is being researched to treat diseases like cystic fibrosis and sickle cell anemia. [SEP] Text: Data synthesis If the trials are found to be clinically homogenous, meta‐analysis will be conducted. For comparable trials, we will summarize their findings using a fixed‐effect model. We shall consider the appropriateness and value of a meta‐analysis if there is significant clinical heterogeneity among the included trials. Subgroup analysis and investigation of heterogeneity In the event of significant heterogeneity, we plan to explore the possible causes by undertaking the following subgroup analyses: gene therapy technique; age; sex; and type of SCD. Sensitivity analysis We plan to perform a sensitivity analysis based on the generation of the allocation sequence within the trials (including and excluding quasi‐randomised trials). Summary of findings and assessment of the certainty of the evidence In a post hoc change, we aim, in future updates when trials are included, to present summary of findings tables for each comparison included. We aim to report on all seven outcomes as pre‐defined in 'Types of outcome measures'. We will determine the quality of the evidence using the GRADE approach; and downgrade evidence in the presence of a high risk of bias in at least one trial, indirectness of the evidence, unexplained heterogeneity or inconsistency, imprecision of results, high probability of publication bias. We will downgrade evidence by one level if we consider the limitation to be serious and by two levels if very serious. of studies We did not identify any trials that were eligible for inclusion in this review. Results of the search We did identify 26 studies by searching trial registries, however, none of these required further investigation. Included studies We did not identify any trials that were eligible for inclusion in this review. Excluded studies We did not identify any trials that were eligible for inclusion in this section of the review. Risk of bias in included studies No trials were eligible for inclusion in the review. trials were eligible for inclusion in the review. trials were eligible for inclusion in the review. Incomplete outcome data No trials were eligible for inclusion in the review. Selective reporting No trials were eligible for inclusion in the review. Other potential sources of bias No trials were eligible for inclusion in the review. Effects of interventions No trials were eligible for inclusion in the review. therapy aims to replace a defective gene with a normal one. Though no trials were found that are eligible for inclusion in this review, the fact that gene therapy is an evolving field assures us that trials will be available in the future. [SEP] Justify:

Output: The text corroborates the claim by indicating that gene therapy aims to replace defective genes, which aligns with the ongoing research in the field. Although it mentions the absence of currently eligible trials, it notes that gene therapy is an evolving field and implies future research will include trials that could potentially apply to diseases like cystic fibrosis and sickle cell anemia.


Input: Task: pass the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: (CA): Google; 2010 [cited 2012 Aug 3]. Available from: support. google. com/trends/bin/answer. py? hl=en&answer=96693 Return to footnote15 referrer Footnote 16 [Internet]. Boston (MA): iProspect; 2006 Apr[cited 2011 Jul 20]. Available from: district4. extension. ifas. ufl. edu/Tech/TechPubs/WhitePaper_2006_ SearchEngineUserBehavior. pdf Return to footnote16 referrer Footnote 17 Is the data normalized? [Internet]. (CA): Google; [cited 2011 Jun 8]. Available from: www. google. com/support/insights/bin/bin/answer. py? answer=87284&&hl=en Return to footnote17 referrer Footnote 18. Auld lang Syne: success predictors, change processes, and self-reported outcomes of New Year's resolvers and nonresolvers. J Clin Psychol. 2002;58(4):397–405. Return to footnote18 referrer Footnote 19 LA Fitness times email marketing campaign to perfection [Internet]. Brighton (UK): Pure360; [cited 2011 Aug 3]. Available from: www. pure360. com/customer-success/case-studies Return to footnote19 referrer Footnote 20 Calendar of health promotion days - 2010 [Internet]. Ottawa (ON): Health Canada; [cited 2011 Aug 3]. Available from: www. hc-sc. gc. ca/ahc-asc/calend/index-eng. php#may Return to footnote20 referrer Footnote 21 May 2010: portal: current events [Internet]. (CA): Wikipedia; [cited 2011 Aug 3]. Available from: en. wikipedia. org/wiki/May_2010 Return to footnote21 referrer Footnote 22 Loser (U. S. TV series) [Internet]. (CA): Wikipedia; [cited 2011 Aug 3]. Available from: Return to footnote22 referrer Footnote 23 Ybarra ML, Suman M. Help seeking behavior and the Internet: a national survey. Med Inform. 2006 Jan;75(1):29-41. Return to footnote23 referrer Footnote 24. An investigation of smoking cessation video content on YouTube. Misuse 2011;46(7): 893-7. [SEP] Justify:

Output: The text provided is irrelevant to the claim, as it contains citations and references to various sources without discussing biohacking techniques or chronic diseases. It does not address the claim nor provide any supportive or contrasting information regarding the effectiveness of biohacking in eliminating the risk of chronic diseases.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Relative Mdm2 mRNA expression is shown and Mdm2 mRNA expression of vector transfected cells was set to 1. Bars, SD. Full size image HIPK2 induces Elk1- but not NFκB-mediated transcriptionTo test the expected influence of HIPK2 on other transcription factors we used a chimeric protein consisting of the GAL4 DNA binding domain fused to the activation domain of the transcription factor Elk1. The transcription activator Elk1 becomes phosphorylated and activated by the MAP (mitogen-activated protein) kinase. Direct or indirect phosphorylation of this transactivator by HIPK2 would activate transcription of the luciferase gene from a reporter plasmid with the GAL4-binding element. Cotransfection of the trans-activator plasmid pFA-Elk1, the luciferase reporter plasmid pFR-Luc and the positive control MEK1 encoding plasmid pFC-MEK1 resulted in an 115 fold increase in luciferase activity in 293 cells compared to pFA2-Elk1 and pFR-Luc transfected control cells (data not shown). In comparison, cotransfection of pFA2-Elk1 and the wildtype HIPK2 expression construct gave only a 6 fold increase (Fig. 5A). This increase was reduced to 3 fold when the kinase defective HIPK2 mutant K221A was used. However, using the carboxy-terminal deletion AC with an intact kinase domain, the increase of luciferase activity was about 17 fold. A possible direct effect of HIPK2 on the luciferase construct has been tested by cotransfection of wildtype HIPK2 and pFR-Luc into 293 cells. In this control, the luciferase activity was similar to the pFR-Luc and pFA2-Elk1 transfected control cells (data not shown). These results suggest that HIPK2 may weakly activate the transactivator Elk1-GAL4 and that the kinase function of HIPK2 is necessary for this activation. The carboxy-terminus of HIPK2 may contain inhibitory sequences for Elk1-phosphorylation. The conclusion is, that HIPK2 seems to activate components of the MAP kinase pathway. The exact role remains to be elucidated. [SEP] Justify:

Output: The text is irrelevant to the claim because it discusses the influence of HIPK2 on transcription factors and luciferase activity rather than addressing any aspects of urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: C, Programmed cell death ligand-1 expression was strongly expressed in IPCs generated from commercially obtained ADSCs. D, PDL-1 expression was also strongly expressed in IPCs generated from ADSCs isolated from the adipose tissue of the type 1 diabetes mellitus patient. E, Immunostained placenta is shown as a positive control stained with PDL-1. have focused on MSCs, especially ADSCs as a feasible cell source for β-cell replacement thrapy. 24,25 Adipose-derived stem cells are easy to procure, less invasive procedure compared with other MSCs, less ethical problems (often under local anesthesia) compared with ES cells and are reported that their multipotency is superior to other MSCs. 26 Indeed, we succeeded in the establishment of effective IPC generation in vitro and demonstrated their in vivo functions. 8–10 These IPCs are monoclonal (insulin positive, glucagon negative, and pancreatic peptide negative). 7 Moreover, these generated IPCs had a DNA quantity of 88. 4% and same level of cell viability by ATP assay compared with original ADSCs. 9 If the stable generation of own effective IPCs can be realized by an easy, safe and low cost procedure, IPCs autotransplantation would be extremely beneficial for T1DM patients. However, there are some major issues to be resolved before clinical application. 8–10 The first issue is whether functional IPCs can be generated from a T1DM patient’s own fat tissue. The present study demonstrated not only that functional IPCs could be generated from ADSCs freshly isolated from human adipose tissue but also that these IPCs, including those obtained from the T1DM patient, were capable of secreting enough insulin to normalize the blood glucose concentrations of diabetic nude mice. Freshly isolated ADSCs from the T1DM patient and commercially provided ADSCs had similar cell surface marker expression, reflecting both stromal and stem cell characteristics. Moreover, the generated IPCs demonstrated the ability to secrete insulin autonomously in vitro, even when derived from T1DM patient adipose tissue. Indeed, these IPCs performed similarly to those derived from nondiabetic patients. However, the insulin responsiveness was significantly lower when the IPCs were derived from visceral fat tissue. The number of T1DM patients was small. [SEP] Justify:

Output: The text corroborates the claim by discussing the generation of insulin-producing cells (IPCs) from adipose-derived stem cells (ADSCs) and their ability to secrete insulin to normalize blood glucose concentrations in diabetic mice. This indicates that cellular engineering techniques are being employed to produce insulin, which directly supports the claim regarding genetic engineering in insulin production for diabetic patients.


Input: Task: pass the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: To be consistent, we classified 2007 to 2010 respondents as and Métis only if they had also reported being born in one of these four countries. Footnote 20 We used mutually exclusive ethnocultural categories despite that respondents could report multiple Aboriginal identities. For example, any respondent who replied that they were only or and Inuit was classified as First Nations. Any respondent who replied that they were Métis only or Métis and any other Aboriginal identity was classified as Métis. Due to small sample sizes, we did not generate Inuit-specific estimates in this report. Our definitions of and Métis are further illustrated in Table 1. TABLE 1 Definitions of (off-reserve), Métis and non-Aboriginal identity based on responses Aboriginal identityTable 1 - Footnote a Subgroup identityTable 1 - Footnote b aRespondents were asked: ''Are you an Aboriginal person, that is, Indian, Métis or Inuit? '' bRespondents were asked: ''Are you Indian (First Nations)? …Métis? …Inuit (Inuk)? '' and were permitted to provide multiple affirmative responses. Dark grey boxes are used because single and multiple identity responses are mutually exclusive. (off-reserve) étis Yes Métis Nations Métis Yes Métis Métis Inuit Non-Born in any country outside of analysis The CCHS has a multi-stage, complex sampling design. Sampling weights assigned by are used to account for selection probability, nonresponse and non-coverage. For this report, weights were also adjusted to take into account the amalgamation of several survey cycles. Footnote 14 We used bootstrapping techniques to calculate the coefficient of variation (CV) and 95% confidence intervals (CIs). In accordance with regulation, estimates with a CV ranging from 16. 6% to 33. 3% are flagged to be interpreted with caution. Those with a CV greater than 33. 3% are suppressed because of extreme sampling variability. Estimates were age-standardized to the age structure of the identity population in the 2006 Census using the age groups 20 to 24, 25 to 44, 45 to 64, and 65 years and over. For those indicators whose cut-off points for age did not line up with those provided by the census, age-standardization was to the nearest age group (e. g. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses survey categorization of respondents' identities and provides methodological details regarding data collection. It does not mention biohacking techniques or chronic diseases, thus failing to corroborate or contrast the claim.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Figure 5Activation of Elk 1-mediated transcription but no activation of NFκB by HIPK2 overexpression. (A) 293 cells were cotransfected with a GAL4-luciferase reporter construct, an Elk1-GAL4 transactivator expression construct and the indicated HIPK2 constructs or vector. (B) 293 cells were cotransfected with an NFκB-luciferase reporter construct and the indicated HIPK2 constructs or vector. Results represent the mean of three independent experiments. Bars, SD. Full size image In a similar assay, which we have used to study HIPK2-mediated activation of p53 specific promoter elements, we looked for a role of HIPK2 in activation of NFκB-mediated transcription. 293 cells were cotransfected with a luciferase reporter plasmid containing five tandem NFκB binding sites and different HIPK2 expression constructs (Fig. 5B). Only wildtype HIPK2 activated NFκB-mediated transcription slightly but not significantly. No effect was seen with the HIPK2 mutants (Fig. 5B). NFκB-mediated luciferase activation was 100 fold with a MEK kinase positive control plasmid (data not shown). The luciferase values of vector and pNF-κB-luc transfected cells were set as 1. Taken together, we conclude that HIPK2 does not activate NFκB. DiscussionHIPK2 enhances p53 activity and p53 expression or stabilityHIPK2 acts as a co-repressor for homeodomain containing transcription factors. We show here that HIPK2 has additional functions, namely the activation of transcription mediated by p53 specific promoter elements. Thereby, overexpression of HIPK2 leads to an increase of the p53 protein level. Neither the transcriptional activation nor the enhancement of p53 protein amounts is detected with overexpressed HIPK2 mutants. The p53 responsive enhancer element becomes activated by HIPK2 in cell lines with p53 but not in a cell line devoid of p53 (Fig. 1). We conclude, that the activation of the enhancer element is indeed mediated by p53 and not by another transcription factor of the p53 family. [SEP] Justify:

Output: The text is irrelevant to the claim regarding urban living and stress levels, as it discusses scientific experiments involving HIPK2 and its effect on transcription, specifically focusing on p53 and NFκB activations without addressing urban living or stress.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: PDX1-engineered embryonic stem cell-derived insulin producing cells regulate hyperglycemia in diabetic mice Download PDF Download eeOpen access Published: 18 October 2012 PDX1-engineered embryonic stem cell-derived insulin producing cells regulate hyperglycemia in diabetic mice Raikwar1 & Nicholas Zavazava1 3. Transplantation of the IPCs under the kidney capsule led to sustained long-term correction of hyperglycemia in diabetic mice. Although these newly generated IPCs effectively rescued hyperglycemic mice, an unexpected result was teratoma formation in 1 out of 12 mice. We attribute the development of the teratoma to the presence of either non-differentiated or partially differentiated stem cells. ConclusionsOur data show the potential of Pdx1-engineered ES cells to enhance pancreatic lineage commitment and to robustly drive the differentiation of ES cells into glucose responsive IPCs. However, there is an unmet need for eliminating the partially differentiated stem cells. BackgroundType 1 diabetes is an autoimmune disease that can be surgically corrected by the transplantation of either the whole pancreas or that of pancreatic islets [1–4]. However, chronic shortage of organ donors, lifelong immunosuppressive therapy and chronic graft rejection currently limit the therapeutic potential of both options. Ultimately, chronic graft rejection leads to insulin dependence and the development of serious diabetic complications [5–10]. With the incidence of diabetes increasing at an alarming rate worldwide, there is an urgent and compelling need to develop novel treatment approaches. In this regard, embryonic stem (ES) cells and the recently developed induced pluripotent stem (iPS) cells potentially offer a novel alternative for the development of stem cell-based therapies [11–13]. However, the generation of functional insulin producing cells (IPCs) from ES or iPS cells has been rather inefficient; thus there is a need to improve on the protocols for the differentiation process. Published work by others appeared to suggest that it is feasible to directly differentiate ES cells into IPCs [14]. Unfortunately, this work has remained irreproducible in many laboratories around the world. During embryonic development, a wide variety of transcription factors, including Pdx1, Ngn3, 4, Gata6, Ptf1a and Pax4 are involved in pancreatic β cell development and function. [SEP] Justify:

Output: The text corroborates the claim by discussing the use of PDX1-engineered embryonic stem cell-derived insulin-producing cells (IPCs) to regulate hyperglycemia in diabetic mice. It highlights that these genetically engineered cells have the potential to differentiate into glucose-responsive IPCs, thus supporting the notion of genetic engineering in insulin production for diabetic treatment.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: To monitor trends and identify targets for intervention, analyses such as this should be repeated over time. The increased prevalence of chronic disease risk factors among and Métis reported here supports provincial recommendations that culturally appropriate and specific actions be taken to address these factors to reduce the burden of cancer in particular and chronic disease more generally in this and future generations. Footnote 41 2006. Return to footnote4 referrer Footnote 5 Survey, 2011: Aboriginal peoples in Canada: People, Métis and Inuit [Internet]. Ottawa (ON): Statistics Canada; 2013 [Statistics Canada, Catalogue No. : 99-011-X2011001]. Return to footnote5 referrer Footnote 6 Gionet L, Roshanafshar S. Select health indicators of people living off-reserve, Métis and Inuit. Health at a Glance. 2013 Jan [Statistics Canada, Catalogue No. : 82-624-X]. Return to footnote6 referrer Footnote 7 Institute (NCI). Tobacco facts [Internet]. Bethesda (MD): Institute; 2013 [cited 2013 Jul 13]. Return to footnote7 referrer Footnote 8 Institute (NCI). Obesity and cancer risk [Internet]. Bethesda (MD): of Health; 2012 [updated 2012 Jan 3; cited 2013 Jul 13]. Return to footnote8 referrer Footnote 9 Institute (NCI). Physical activity and cancer [Internet]. Bethesda (MD): Institute; 2009 [updated 2009 Jul 22; cited 2013 Jul 13]. Return to footnote9 referrer Footnote 10 UK. Diet and cancer: the evidence [Internet]. London (UK): UK; 2009 Sep 25 [cited 2013 Jul 13]. Return to footnote10 referrer Footnote 11 Institute (NCI). Alcohol and cancer risk [Internet]. Bethesda (MD): Institute; 2013 [updated 2013 Jun 24; cited 2013 Jul 13]. Return to footnote11 referrer Footnote 12 Lynch BM. Sedentary behavior and cancer: a systematic review of the literature and proposed biological mechanisms. Biomarkers Prev. 2010;19(11): 2691-709. Return to footnote12 referrer Footnote 13 Statistics Canada. Other reference periods – – [Internet]. Ottawa (ON): Statistics Canada; [cited 2013 Nov 3]. Return to footnote13 referrer Footnote 14 Thomas S, Wannell B. Combining cycles of the Health Survey. Health Rep. [SEP] Justify:

Output: The text contrasts the claim by discussing the importance of addressing chronic disease risk factors rather than suggesting that biohacking techniques can completely eliminate such risks. It mentions 'provincial recommendations that culturally appropriate and specific actions be taken to address these factors to reduce the burden of cancer and chronic disease', indicating that chronic diseases require ongoing intervention and cannot be fully eliminated through biohacking alone.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: The kinase defective mutant of HIPK2, K221A, leads to a decrease of p53 protein amounts (Fig 2A). However, this decrease does not correspond with a further decrease on p53-mediated transcription compared to HIPK2 mutants AC and AN (Fig. 1A and 1B). HIPK2 is not sufficient for phosphorylation of crucial serine residues of p53The nuclear phosphoprotein p53 is regulated and stabilized by different modifications [3, 18], e. g. serine 15 phosphorylation has been detected as prerequisite for phosphorylation of tyrosine residue 18 [19]. HIPK2 could not activate or stabilize p53 either directly or indirectly by phosphorylation. DNA damaging agents such as doxorubicin induce increased p53 phosphorylation by as yet undefined mechanisms. In the presence of wildtype HIPK2 and doxorubicin, serine residue 15 and 20 of p53 become phosphorylated, which could be either due to transfected or endogenous HIPK2 of HeLa cells. In the presence of doxorubicin alone or together with mutants of HIPK2 serines 15 and 20 could be phosphorylated by endogenous HIPK2 (Fig. 2C). Thus, we conclude that HIPK2 is not sufficient for serine 15 and 20 phosphorylation, for which doxorubicin may be required. HIPK2 is also not sufficient for phosphorylation of residue 392, but doxorubicin requirement is excluded. Additional phosphorylation sites have not been tested since the absolute requirement of phosphorylation for DNA-damage induced stabilization of p53 remains controversial [20]. Other proteins, which regulate p53, like e. g. Mdm2, could be the targets for phosphorylation by HIPK2. Doxorubicin treatment and HIPK2 overexpression show an additive effect on p53 protein expression or stability (Fig. 2B). The relative amounts of the increase of the p53 protein levels and the increase in doxorubicin induced phosphorylation of serine residue 15 are comparable and give rise to the assumption that the total amount of p53 protein present becomes phosphorylated under doxorubicin treatment. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the role of HIPK2 in the phosphorylation and regulation of the p53 protein in response to doxorubicin treatment, with no relation or mention of urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Pdx1 is the master regulator of pancreatic development [15–18] during embryogenesis, β cell differentiation [16, 19–21] and is essential for the maintenance of β-cell function in the adults [15, 16, 22, 23]. Mutations in the Pdx1 coding sequence in humans and mice lead to failure of the pancreatic organ to develop [25]. Here, we hypothesized that pancreatic lineage commitment of ES cells by pancreatic β cell-specific transcription factor Pdx1 enhances the generation of IPCs, thereby providing an unlimited source of cells for the treatment of diabetes. The rationale underlying this approach is that expression of pancreatic β cell-specific transcription factor Pdx1 will maximize the pancreatic lineage commitment and differentiation of ES and iPS cells into IPCs [15, 17, 26–31]. To facilitate greater efficiency of the generation of IPCs from ES cells, we have generated a double transgenic ES cell line R1Pdx1AcGFP/RIP-Luc to stably express an in-frame Pdx1AcGFP fusion protein [32]. Here, we describe the generation of IPCs in vitro using ES cells ectopically expressing Pdx1. For the real-time non-invasive in vivo bioluminescence imaging (BLI), we engineered a rat insulin promoter (RIP) driven luciferase reporter to monitor the fate and function of the IPCs post transplantation. Further, we show that transplantation of ES cell-derived IPCs efficiently corrects hyperglycemia in diabetic mice. However, the lack of cell surface markers specific for IPCs raises the potential for teratoma formation by residual non-differentiated ES cells. These studies justify the need to develop novel strategies for ES cell differentiation and purification of IPCs prior to transplantation. Materials and methodsCell linesWe have recently described the generation and characterization of the double transgenic mouse ES cell line R1Pdx1AcGFP/RIP-Luc stably expressing an in-frame Pdx1AcGFP fusion protein and RIP driven luciferase reporter in detail elsewhere [32]. The R1Pdx1AcGFP/RIP-Luc mouse ES cell line was maintained in DMEM containing 1,000 IU/ml leukemia inhibitory factor (1107, Inc. [SEP] Justify:

Output: The text corroborates the claim by discussing the use of genetic engineering in the context of pancreatic β cell-specific transcription factor Pdx1, which is pivotal in differentiating embryonic stem (ES) cells into insulin-producing cells (IPCs). It details the generation of a double transgenic ES cell line that expresses Pdx1, suggesting that this engineered approach contributes to developing an unlimited source of cells for treating diabetes, thereby linking genetic engineering directly to insulin production for diabetic patients.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: · Number 2-3 · July 2014 and Injuries in feedback to editors Modelling preventive effectiveness to estimate the equity tipping point: at what coverage can individual preventive interventions reduce socioeconomic disparities in diabetes risk? Download this 0. 2 Mb - 9 pages) Submit a manuscript the This 10. 24095/hpcdp. 34. 2/3. 04 This 1. 76%. Assuming complete coverage across all income groups, the difference was reduced to 0. 90% (144 000 cases prevented) with lifestyle interventions and 1. 24% (88 100 cases prevented) with pharmacotherapy. The equity tipping point was estimated to be a coverage difference of 30% for preventive interventions (100% and 70% coverage among the highest and lowest income earners, respectively). Conclusion: Disparities in diabetes risk could be measurably reduced if existing interventions were equally adopted across SEP. However, disparities in coverage could lead to increased inequity in risk. Simple modelling approaches can be used to examine the community effectiveness of individual preventive interventions and their potential to reduce (or increase) disparities. The equity tipping point can be used as a critical threshold for disparities analyses. Keywords: inequalities, public health, health impact assessment, diabetes role of individual preventive therapy in reducing health disparities is the subject of current debate. One the one hand, health disparities may be reduced when relative treatment effects are constant across the spectrum of underlying risk. Footnote 1, Footnote 2, Footnote 3 If this assumption held true, the absolute community effectiveness from health interventions would be greater for disadvantaged groups compared to others because disadvantaged groups tend to have a higher baseline risk. Greater gains in absolute benefit for those in the lowest socioeconomic position (SEP) compared to those in higher SEP would therefore lead to a decrease in disparities between them. Footnote 1 On the other hand, constant intervention efficacy should not be assumed and intervention coverage is often inequitable. Intervention coverage, defined as the proportion of the target population that is adherent to the intervention, encompasses the range of factors that affect the uptake of interventions, such as accuracy in identifying the target population, level of participation in the intervention and consumers' adherence. Footnote 4 Groups at a lower socioeconomic level tend to experience greater barriers in access to care, for example through income effects, or they may be less adherent to preventive therapies, for example, education effects. Footnote 5 Together, differences in efficacy and coverage undermine efforts to reduce disparities or else they can, perversely, increase disparities. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and inequalities in the effectiveness of preventive interventions for chronic diseases. It emphasizes that health disparities could be reduced if existing interventions were equally adopted, but it does not support the idea that biohacking techniques can completely eliminate the risk of chronic diseases. The text highlights that disparities in coverage can lead to increased inequity in risk and that intervention efficacy should not be assumed to be constant across different socioeconomic groups, indicating that there are significant barriers to achieving complete risk elimination.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Since p53 has a high turnover rate [4], the increase of p53 protein levels seems to be due to stabilization of p53 rather than induction of enhancement of transcription of p53. An increase of p53 mRNA stability or translation efficiency could play additional roles. HIPK2 downregulates Mdm2 proteinHIPK2 may exert all its effects on p53 via Mdm2, since it leads to a decrease of the p53-induced Mdm2 protein level (Fig. 3). HIPK2 has no influence on Mdm2 transcription (Fig. 4). Therefore, HIPK2 regulates Mdm2 stability at the protein level. The most likely mechanism is serine/threonine phosphorylation of Mdm2 either directly or indirectly by HIPK2. At present, we did not get convincing data showing a direct serine/threonine phosphorylation of Mdm2 by HIPK2. Mdm2 shuttles between the nucleus and the cytoplasm and this nucleo-cytoplasmic shuttling of Mdm2 is essential for its ability to promote p53 degradation by the cytoplasmic proteasome [21]. Mdm2 seems to have a role in exporting p53 from the nucleus [22, 23]. HIPK2 did not directly interact with either p53 or Mdm2 in yeast and 293T cells (data not shown). Whether HIPK2 can influence the shuttling of Mdm2 remains to be clarified. Effect of HIPK2 on target genes of p53We have addressed the issue to check expression of described downstream targets of p53 at the protein level in HeLa cells. The best characterized target gene that becomes transactivated by p53 is the cyclin/Cdk inhibitor p21 (Waf1/Cip1) [3]. But we did not detect a significant increase of expression of p21 (Waf1/Cip1) mediated by overexpression of HIPK2 or treatment with doxorubicin in Western blotting analysis. As a positive control 2 μg of the wildtype p53 expression construct pFC-p53 was transiently transfected and transient overexpression of wildtype p53 led to a weak increase of p21 (Waf1/Cip1) expression (data not shown). [SEP] Justify:

Output: The text does not address the claim about urban living and stress levels. Instead, it provides detailed information about the regulation of p53 protein levels and its interaction with HIPK2 and Mdm2, which is unrelated to the effects of urban living on stress.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: In all cases, *P < 0. 05 was considered significant. ResultsES cell-derived IPCs secrete insulinThe results from multiple earlier studies have indicated low insulin secretion by ES cell-derived IPCs [27, 35–39]. Since Pdx1 is a major transcription factor for the development of the pancreas as well as pancreatic β cells, we reasoned that generating a stable Pdx1-expressing ES cell line R1Pdx1AcGFP/RIP-Luc and directing its differentiation towards IPCs could increase the yield of IPCs. To investigate which approach was more effective at generating IPCs, four different differentiation protocols as described in the methods section and depicted in Figure 1a were studied. The progressive differentiation of the R1Pdx1AcGFP/RIP-Luc ES cell line into IPCs was monitored by immunostaining for various pancreatic markers (Figure 1b). As expected the differentiation process led to the expression of insulin producing cell clusters. Our immunostaining results using the differentiation protocol D indicate that the cells express Foxa2, Sox17, Ngn3 and NeuroD markers during the early steps of differentiation (Figure 1b). In addition to C-peptide and insulin expressing cells, we found that a significant cell population expressed glucagon. The newly generated IPCs were organized into small islet-like clusters (Figure 1b). Based on immunostaining results, we estimated that approximately 25 to 30% of the cells were expressing insulin. To further confirm that the cells had differentiated into pancreatic lineage, the expression of various pancreatic genes was studied. We used real-time quantitative RT-PCR analysis on RNA isolated from the cells at the completion of various stages to monitor the in vitro differentiation of ES cells into IPCs (Figure 1c). The RT-PCR results from a representative differentiation using protocol D indicate a progressive up-regulation of pancreatic β-cell-specific genes commensurate with the differentiation status of the ES cells. A significant up-regulation of Foxa2, Pax4, insulin 1, insulin 2, PC2/3 and glucagon gene expression in the IPCs was observed. The insulin production by ES cell-derived IPCs was determined by an ultrasensitive ELISA. results indicate that the ES cell-derived IPCs robustly secrete insulin (Figure 2a). [SEP] Justify:

Output: The text corroborates the claim by detailing a study that involves generating insulin-producing cells (IPCs) from embryonic stem (ES) cells through genetic manipulation, indicating that these engineered cells express and secrete insulin. The passage mentions the use of ectopic Pdx1 expression in ES cells to enhance insulin production, demonstrating the role of genetic engineering in the production of insulin for diabetic patients.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: Footnote 6 In this study, we show how a simple modelling approach can be used to estimate the potential effectiveness of prevention interventions at reducing disparities (see Formula 1). We demonstrate this using diabetes prevention in Canada. 1 Community effectiveness = target population X baseline risk X intervention efficacy X intervention coverageFootnote * Community effectiveness: the benefit, or absolute risk reduction, of preventive interventions in the real-world community setting. Target population: the proportion of the population, or each sociodemographic strata, that is eligible for the preventive intervention. Baseline risk: the risk or probability of developing a disease prior to intervention implementation. Intervention efficacy: the relative benefit of an intervention as determined from intervention trials or other studies, i. e. ideal or controlled settings. Intervention coverage: the proportion of the target population that is adherent to the intervention. Footnote 1 Derived from the ''evidence equity loop. '' Return to footnote1 referrer The potential for interventions to reduce inequalities can be estimated when we calculate and compare community effectiveness for each socioeconomic stratum. Disease disparities will narrow if community effectiveness is larger for low socioeconomic groups compared to their higher SEP counterparts. A common challenge when estimating community effectiveness for individual socioeconomic strata is the lack of information that is specific to the different strata, including variation in the target population size, baseline risk, intervention efficacy and coverage. For such situations, we introduce the concept of the ''equity tipping point,'' defined as the point at which the disparity between highest and lowest socioeconomic strata becomes larger as a result of differences in intervention efficacy, coverage or target population. The objective when calculating the equity tipping point is to gauge whether potential differences realistically exist. In the example of diabetes prevention, we sought to identify the point at which intervention coverage gaps resulted in a widened disparity in diabetes risk. To show this better, we did not vary intervention efficacy or target population criteria. We examined 2 types of diabetes prevention interventions that have well-established efficacy: lifestyle interventions and pharmacotherapy. Footnote 7 Lifestyle interventions reduce obesity through diet and exercise programs. Pharmacotherapy uses medications such as metformin to reduce weight and insulin resistance so as to reduce new cases of diabetes among those at risk. While these therapies appear to be efficacious across socioeconomic groups,Footnote 7, Footnote 8 achieving high coverage for diabetes in particular and chronic diseases in general is a challengeFootnote 9, Footnote 10 and the level of coverage likely varies across socioeconomic groups. [SEP] Justify:

Output: The text contrasts the claim by discussing the challenges of achieving high coverage for diabetes prevention interventions and chronic disease management. It highlights that lifestyle interventions and pharmacotherapy have established efficacy but emphasizes that achieving high coverage—where interventions effectively reach the target population—is a significant challenge. This suggests that biohacking techniques alone cannot eliminate risk, as effective implementation and coverage play critical roles.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Western blotting does not seem to be sensitive enough to detect a significant difference in p21 expression between vector and wildtype HIPK2 transfected cells. In the same experimental setting an increase of expression of the pro-apoptotic Bcl2 family member Bax, whose gene has been described as a p53 target [3], was not detectable (data not shown). Therefore, induction of p53 target genes seems to be cell type specific. The recently described p53-dependent pro-apoptotic Bcl-2 family member Noxa [24] is a further candidate that could be regulated via HIPK2. In this respect, a further difficulty is that HIPK2 downregulates the p53-induced Mdm2 protein level. This may also be the case for other p53-induced proteins. Other functions of HIPK2HIPK2 is also termed PKM (for Mx-interacting protein kinase) since it has been cloned in a yeast two-hybrid screen as an interaction partner for the interferon type I-induced protein MxA, that displays antiviral activity against a variety of RNA viruses [10]. The nuclear distribution of murine Mx1 is similar to HIPK2/PKM, but a direct interaction of the Mx protein with HIPK2/PKM and phosphorylation of Mx by HIPK2/PKM could not be demonstrated so far [10]. HIPK2/PKM phosphorylates several phosphoproteins expressed in E. coli. This reaction is inhibited by a kinase defective mutant K221W of HIPK2/PKM. Thereby it was also shown that HIPK2/PKM is a true serine/threonine kinase, rather then a dual specificity protein kinase which is able to phosphorylate both, serine/threonine and tyrosine residues [10]. HIPK2 interacts with the death factor receptor CD95 in the yeast two-hybrid system [25]. When overexpressed in mammalian cells it associates with TRADD [26]. TRADD has been described to bind to the tumor necrosis factor type I and thereby executing essential functions in signaling [27, 28]. Whether HIPK2 plays an important role in death receptor mediated apoptosis is not clear at present. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses topics related to molecular biology and cellular mechanisms regarding HIPK2 and p53, without any mention of urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Finally, to rule out the possibility of endogenous pancreatic β cell regeneration, we performed hematoxylin-eosin staining of the pancreas on Day 150 from the STZ treated mice that were transplanted with IPCs. Our histopathology data (Figure 3c) demonstrates that the normal pancreas has extremely large pancreatic islets. However, the pancreas from the mice transplanted with IPCs revealed near complete loss of pancreatic islets and no evidence of endogenous pancreatic β-cell regeneration. Taken together, our data suggest that ES cell-derived IPCs were indeed responsible for the long-term survival and correction of the diabetic phenotype post-transplantation in the diabetic mice. Figure 3R1Pdx1cell-derived IPCs correct hyperglycemia in diabetic mice. (a) The therapeutic efficacy of R1Pdx1AcGFP/RIP-Luc ES cell-derived IPCs was evaluated following transplantation under the kidney capsule of syngeneic 129/SvJ mice (n = 12) rendered diabetic by streptozotocin (STZ) treatment. The blood glucose levels continued to decline beyond Day 15 post-transplantation and stabilized thereafter. Normal nondiabetic mice (n = 5) and STZ-treated 129/SvJ mice (n = 5) were used as appropriate controls for comparing the blood glucose levels. As early as Day 15 and throughout the duration of the study, the blood glucose levels of mice transplanted with IPCs were significantly lower compared to the STZ-treated mice. The data were analyzed by one-way ANOVA and are presented as mean ± SD, ***P < 0. 0001, using Tukey’s pairwise multiple comparison for Day 15. (b) The kidney bearing the transplanted IPCs was evaluated for insulin expression by immunostaining using an anti-insulin antibody. The results indicate the localized presence of ES cell-derived insulin expressing cells. (c) Control mouse pancreas and the pancreas from IPCs transplanted mice 150 days post transplantation were examined by hematoxylin-eosin staining. Unlike control pancreas from non-diabetic mouse, the IPCs transplanted streptozotocin-treated diabetic mouse pancreas did not show any evidence of pancreatic beta cell regeneration. [SEP] Justify:

Output: The text corroborates the claim by explaining that IPCs derived from ES cells express insulin and have therapeutic efficacy in correcting the diabetic phenotype in mice. It mentions that after transplantation, the insulin expression was evaluated, and the results indicated the presence of insulin-expressing cells. This highlights the role of genetic engineering in producing insulin through ES cell-derived IPCs, providing support for the claim.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: 33 Cases preventedTable 3 - Footnote d, n 27 100 30 500 10 800 90 100 159 000 Pharmacological intervention Absolute risk reduction,Table 3 - Footnote c % 2. 05 1. 68 1. 36 1. 23 1. 43 1. 90 0. 82 Cases preventedTable 3 - Footnote d, n 16 600 18 700 6610 55 200 97 000 Figure 2 shows how the complete coverage of health interventions affects diabetes risk disparities across different levels of income and education. As expected, the disparity widens when the intervention coverage drops in the lowest SEP groups, but is maintained at 100% for the highest SEP groups. The equity tipping point is reached at 70% coverage for lowest income earners and 60% for lowest education groups. Below these coverage levels, there is progressive widening of diabetes risk between SEP groups. 2 Estimating the impact of intervention coverage on the disparity in diabetes risk and identifying the equity tipping point for lifestyle and pharmacological interventions 2 [2, Text Equivalent] and Injuries in Canada - Number 2-3, July 2014 2 Estimating the impact of intervention coverage on the disparity in diabetes risk and identifying the equity tipping point for lifestyle and pharmacological interventions Figure 2 shows how the complete coverage of health interventions affects diabetes risk disparities across different levels of income and education. As expected, the disparity widens when the intervention coverage drops in the lowest SEP groups, but is maintained at 100% for the highest SEP groups. The equity tipping point is reached at 70% coverage for lowest income earners and 60% for lowest education groups. Below these coverage levels, there is progressive widening of diabetes risk between SEP groups. Note: These scenarios assume 100% coverage in the highest socioeconomic group and varying coverage among the lowest socioeconomic group. study presents a straightforward modelling approach to estimate the potential reduction in socioeconomic disparities in disease risk using individual preventive interventions. In the considerable debate about whether individual interventions can or should have a role for reducing health disparities, the discussion is typically buttressed with either theoretical arguments or examples from specific studies or populations. Footnote 13, Footnote 14 In practice, most preventive interventions—whether they are individual-based or community-wide—have the potential to narrow or widen health disparities depending on the extent of disparities in baseline risk, intervention efficacy and intervention coverage. The ability to analytically examine the settings in which preventive interventions will likely narrow or widen health disparities is helpful for practical health planning and for more general discussions about disease prevention. [SEP] Justify:

Output: The text contrasts the claim by discussing the potential impacts of health interventions on diabetes risk disparities rather than suggesting that biohacking techniques can entirely eliminate chronic disease risk. It highlights that preventive interventions can have varying effects on health disparities depending on socioeconomic factors. The discussion implies that while interventions can help reduce risks, they don't guarantee complete elimination of chronic diseases.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Recently, it has been described that HIPK3, a member of the HIPK family, binds to CD95 and thereby inhibits c-Jun N-terminal kinase activation [29]. An additional function of HIPK2 may be the activation of the mitogen-activated protein kinase pathways since we detected a weak activation of Elk1 mediated transcription. The carboxy-terminal deletion of HIPK2 ΔC augments the activation of Elk1-mediated transcription in comparison to wildtype HIPK2. The carboxy-terminal deletion of HIPK2 ΔC is equally distributed in the nucleus. In contrast, wildtype HIPK2 and the kinase defective K221A mutant localize to nuclear speckles [25]. This suggests that the equal nuclear distribution of the HIPK2 mutant ΔC is responsible for the increase in Elk1 mediated transcription. It has been shown that DNA damage in addition to stabilization of p53 leads to an activation of a MAP kinase homolog, the c-Jun N-terminal kinase or stress activated protein kinase [30]. ConclusionsHIPK2 is a nuclear kinase that activates transcription mediated by tumor suppressor p53 responsive promoter elements upon overexpression. Furthermore, it plays a role in the induction of expression or stability of p53 protein. Overexpression of HIPK2 does not lead to a change of Mdm2 mRNA levels, but it leads to a downregulation of p53-induced Mdm2 protein. Most likely, this HIPK2-induced decrease of Mdm2 is responsible for the stabilization of p53. The involvement of HIPK2 kinase activity remains to be identified. Materials and methodsCell lines and cell cultureHeLa cells were maintained in RPMI 1640 containing 10% heat-inactivated fetal bovine serum, L-glutamine, and penicillin/streptomycin (all from Technologies, Karlsruhe, Germany). The stock solution of doxorubicin (Amersham-Pharmacia, Freiburg, Germany) was 2 mg/ml in H20. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses scientific details related to HIPK2 and protein kinases, with no mention of urban living or stress levels. Therefore, it does not provide any support or contradiction to the claim that urban living leads to increased stress.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Our ES cells were engineered using rat insulin promoter (RIP) driven luciferase reporter. Following differentiation of the ES cells, the transcriptional activation of the RIP leads to a selective robust expression of luciferase in the IPCs. In one of the IPC transplanted mouse, the BLI signal showed a progressive increase, especially beyond Day 40 post-transplantation with maximum BLI signal intensity at Day 50 post-transplantation. (b) The mouse transplanted with ES cell-derived IPCs was sacrificed and the internal organs were examined. The kidney bearing the transplanted IPCs revealed the presence of teratoma formation covering the dorsal and ventral sides of the kidney. (c) Histopathology following hematoxylin-eosin staining revealed the presence of epidermal, mucous secreting, ciliated epithelial as well as the neuronal tissues. However, there was no evidence of any metastatic lesions in any other organs. (d) Immunostaining using anti-GFP and anti-C-peptide antibodies revealed the presence of both AcGFP and insulin-positive transplanted cells. Full size imageHistopathological examination of the teratoma revealed the presence of epidermoid, mucous secreting, ciliated epithelial as well as neuronal cells (Figure 4c). Finally, to confirm the presence of IPCs in the kidney bearing teratoma, immunostaining was performed. Insulin staining cells were detectable (Figure 4d) in the kidney containing IPCs but not in control kidneys from the contra-lateral side, suggesting that the transplanted cells were producing insulin under the renal capsule. Taken together, our results highlight the potential of ES cells to generate IPCs that can be used therapeutically. However, the differentiation process is not yet optimal since one of the IPC-transplanted mouse developed a teratoma. DiscussionES and iPS cells could potentially overcome the chronic shortage of cadaveric organs if we are able to establish efficient differentiation protocols. Derivation of specific cell types and tissues from ES and iPS cells could end the need for donated cadaveric tissue. However, the current protocols for the in vitro differentiation of ES and iPS cells into IPCs are still very inefficient, time consuming and very expensive. [SEP] Justify:

Output: The text corroborates the claim by demonstrating that genetically engineered embryonic stem (ES) cells can differentiate into insulin-producing cells (IPCs) which produce insulin. It states, 'Immunostaining using anti-GFP and anti-C-peptide antibodies revealed the presence of both AcGFP and insulin-positive transplanted cells,' indicating that these genetically engineered cells are indeed capable of producing insulin, which is directly relevant to the production of insulin for diabetic patients.


Input: Task: contrast the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: RoseFootnote 15 rightly indicated that an understanding of absolute measures of risk is a cornerstone of population health planning. However, the limitations of Rose's approach for evaluation of equity issues have been much debated. Footnote 6, Footnote 13, Footnote 16 Tugwell et al. Footnote 4 outlined a framework for considering equity issues when evaluating health policies. The modelling approach used here is similar to the ''effectiveness equity loop'' described by Tugwell et al. ,Footnote 4 except that our calculations were specific to preventive interventions and used a multivariate risk tool to estimate baseline risk. As a measure the equity tipping point is also analogous to threshold or sensitivity analyses in economic studies where there is uncertainty or variation in costing of components and estimates of effectiveness. Footnote 17, Footnote 18 We varied only one component of community effectiveness—coverage—to examine its effect on the equity tipping point. We chose this variable because of concerns that coverage varies considerably across socioeconomic groups and because lower coverage of diabetes preventive therapies has been observed in low-income communities. Footnote 19 Intervention uptake is influenced by a complex array of individual, provider and health system factors—attitudes, language and cultural barriers, trust in the health care system, quality of the communication relationship and continuity of careFootnote 9, Footnote 10, Footnote 20, Footnote 21, Footnote 22—all of which can have varied effects on intervention coverage. As expected, we found that when intervention coverage decreased among those in the lowest SEP group, so did the ARR. We further demonstrated the potential for poor coverage to exacerbate baseline disparity in diabetes risk when the intervention coverage surpasses the equity tipping point. At this threshold, the difference in intervention coverage voided any equity benefit of the health intervention and led to an increased disparity in diabetes risk. In an attempt to explain this predicted effect, others have theorized that health interventions may increase disparities if advantaged groups are more likely than their poorer, less educated and unemployed counterparts to have the financial and knowledge resources to capitalize on available opportunities to improve health. Footnote 13, Footnote 23 However, Anderson et al. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of health interventions and how varying coverage among socioeconomically disadvantaged groups can lead to greater disparities in diabetes risk. It emphasizes that when intervention coverage is low, it exacerbates health disparities, suggesting that biohacking techniques may not fully eliminate chronic disease risk as the claim suggests.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Human osteosarcoma Saos2 cells and human embryonic kidney 293 cells were cultured in Dulbecco's modified Eagle's medium containing 10% heat-inactivated fetal bovine serum, L-glutamine, and penicillin/streptomycin (all from Technologies, Karlsruhe, Germany). Plasmids, construction of expression plasmids, mutagenesis and transient transfectionThe full length human HIPK2 cDNA [25] was subcloned into the EcoR1 and XhoI sites of pcDNA3. 1-zeo(+) (Invitrogen, Groningen, The Netherlands). The DNA fragments for the deletion constructs were generated by PCR using polymerase (Biolabs, Frankfurt, Germany) and primers with appropriate restriction sites and epitope tags. Details about the used primers can be obtained upon request. The carboxy-terminal HIPK2 deletion AC contains amino acids until position 527, the amino-terminal deletion AN from amino acid position 559. The PCR fragments were subcloned in pBSIIsk(-) (Stratagene, Offenbach, Germany), sequenced using an automated sequencer (Applied Biosystem, Langen, Germany) and inserted into pcDNA3 (Invitrogen, Groningen, The Netherlands). The point mutant HIPK2 K221A was generated using the QuickChangeTM kit (Stratagene, Offenbach, Germany) according to the manufacturer's instructions. The plasmid pEGFP-Nl coding for a green fluorescent protein was obtained from Clontech (Heidelberg, Germany). The plasmid coding for wildtype p53 was a kind gift from M. Oren (Institute of Science, Israel). HeLa and Saos2 cells were transiently transfected by using the () according to the protocol of the manufacturer. Transient transfections of 293 cells were performed by the calcium phosphate method. Prior to transfection approximately 5 × 105 cells were plated onto a 60 mm dishes to a confluency of 20%. Cells were harvested at 20–30 h following transfection and lysed in 500 μl of lysis buffer (20 mpH 7. 4, 150 mM NaCl, 5 mM EDTA, 10 % glycerol, 0. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses a scientific process related to cell culture and molecular biology without any mention of urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: Our results are not entirely surprising because in an earlier study, inducible biphasic expression of Pdx1 led to the differentiation of mouse ES cells into both insulin and glucagon expressing cells [26]. It is possible that sustained Pdx1 expression in our ES cells leads to the development of a bihormonal progenitor cell population during differentiation, which in turn gives rise to both insulin- and glucagon-expressing cells. These findings suggest that ectopic Pdx1 expression alone may not be sufficient to allow for the complete maturation of the IPCs in vitro. We, however, anticipate that these cells eventually mature in vivo post-transplantation and become mono-hormonal. In a recent study, adenoviral-mediated coexpression of Pdx1 and MafA with either Ngn3 or NeuroD has been shown to improve the generation of IPCs [56]. However, the critical transplantation experiments to demonstrate the therapeutic efficacy of the ES cell-derived IPCs were not performed. The insulin secretion, as well as glucose responsiveness, of the R1Pdx1AcGFP/RIP-Luc ES cell-derived IPCs was confirmed by an ultrasensitive ELISA. data suggest that constitutive Pdx1 expression in our R1Pdx1AcGFP/RIP-Luc ES cell-derived IPCs leads to a robust glucose responsive insulin secretion as compared to the biphasic Pdx1 expression or combined inducible Pdx1 and Ngn3 expression as reported earlier [26, 57]. It is possible that constitutive Pdx1 expression maintains the insulin processing and secretion mechanism in ES cell-derived IPCs in a dynamic state, thereby facilitating glucose responsive insulin secretion. Moreover, in these earlier studies, the much needed transplantation experiments to evaluate the therapeutic efficacy of ES cell-derived IPCs to correct hyperglycemia in diabetic mice were not performed. The therapeutic efficacy of the IPCs derived using our new differentiation protocol was tested in streptozotocin-treated 129/SvJ syngeneic diabetic mice by transplanting the cells under the kidney capsule. The 129/SvJ mice administered STZ for five consecutive days become progressively diabetic, do not recover from severe hyperglycemia and die between Days 10 and 15 due to failure of endogenous β-cell regeneration as reported earlier [32]. [SEP] Justify:

Output: The text corroborates the claim by discussing the differentiation of embryonic stem (ES) cells into insulin-expressing cells, which aligns with the idea of using genetic engineering techniques (such as Pdx1 and other factors) to produce insulin for diabetic patients. It highlights advancements in the generation of insulin-producing cells (IPCs) and mentions the therapeutic efficacy of these cells in correcting hyperglycemia in diabetic models, suggesting that such genetically engineered cells are intended for use in managing diabetes.


Input: Task: pass the claim using the given text. Claim: Most biohacking techniques can entirely eliminate the risk of chronic diseases. [SEP] Text: 85) Compared with the adjusted estimates from the original data, the imputed ORs for facial injury risk tended to be further from 1. 00. The odds of facial injury increased significantly if the helmet tilted back (OR = 4. 81, 95% CI: 2. 74–8. 46), shifted to the side (OR = 1. 83, 95% CI: 1. 04–3. 19) or came off (OR = 3. 31, 95% CI: 1. 24–8. 85). Data quality and reliability For helmet fit, overall observed agreement was 87. 5% and expected agreement was 81. 0% (Table 4). Weighted kappa was calculated since the responses were ordered, and kappa was 0. 34 (95% CI: 0. 16–0. 64), which represents fair agreement. Endnote 14 For head and face injury cases (n = 24), observed agreement was 91. 7% and expected agreement was 79. 8%, resulting in a kappa of 0. 59 (95% CI: 0. 28–1. 00), representing moderate agreement. For controls, kappa was 0. 22 (95% CI: 0. 00–0. 44). TABLE 4 Agreement and kappa for helmet fit and position by cases and controls for cyclists injured in Calgary and Edmonton, agreement, % Expected agreement, % k 95% CI Abbreviations: CI, confidence interval; k, kappa. Cases (n = 24) Helmet fit 91. 7 79. 8 0. 59 (0. 28–1. 00) Helmet position 62. 5 49. 3 0. 26 (0. 00–0. 54) Controls (n = 53) Helmet fit 85. 5 81. 6 0. 22 (0. 00–0. 44) Helmet position 90. 6 85. 6 0. 35 (0. 19–0. 71) Overall (n = 77) Helmet fit 87. 5 81. 0 0. 34 (0. 16–0. 64) Helmet position 81. 8 72. 0 0. 35 (0. 20–0. 74) An un-weighted kappa score was calculated for helmet position. For head and face injury cases, observed agreement was 62. 5%, expected agreement was 49. 3% and kappa was 0. 26 (95% CI: 0. 00–0. 54) or fair agreement. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses helmet fit and position in relation to facial injury risk, without mentioning biohacking techniques or chronic diseases. Therefore, it does not corroborate or contrast the claim.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: 5% Triton X-100, 20 μl/ml protease inhibitor cocktail (Sigma, Taufkirchen, Germany). Elk1 activation assay293 cells have been transiently cotransfected with 1 μg pFR-Luc (Stratagene, Offenbach, Germany) and 50 ng pFA2-Elk1 (PathDetect in vivo signal transduction pathway trans-reporting systems, Stratagene, Offenbach, Germany) with or without 1 μg of the indicated plasmids coding for HIPK2. 50 ng of pFC-MEK1 (Stratagene, Offenbach, Germany) served as positive control. After 24 h cells were starved for 8 h. Then lysophosphatidic acid (Sigma, Taufkirchen, Germany) was added to a final concentration of 10 μM for 30 min. Cells lysis and measurement of luciferase activity were done according to the instructions for the luciferase assay system (Promega, Mannheim, Germany). p53 and NFκB activation assay293 or HeLa cells have been transiently cotransfected with 1 μg pNF-κB-Luc (PathDetect in vivo signal transduction pathway cis-reporting systems, Stratagene, Offenbach, Germany) with or without 1 μg of the indicated plasmids coding for HIPK2. 50 ng of pFC-MEKK (Stratagene, Offenbach, Germany) served as positive control for activation of NFκB-mediated transcription. For measuring activation of p53, 1 μg pf p53-Luc (PathDetect in vivo signal transduction pathway cis-reporting systems, Stratagene, Offenbach, Germany) has been used for cotransfection instead of pNF-κB-Luc. The positive control for activation of p53-mediated transcription was 50 ng pFC-p53 (Stratagen, Offenbach, Germany), which contains the p53 cDNA under the control of a cytomegalovirus promoter. Cells were collected after 24 h. Cell lysis and measurement of luciferase activity were done according to the instructions for the luciferase assay system (Promega, Mannheim, Germany). Western blottingHeLa or Saos2 cells were transiently transfected with either the vector pcDNA3. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses cell transfection techniques and assays related to biological research, with no mention of urban living or stress levels.


Input: Task: pass the claim using the given text. Claim: Genetic engineering is used in producing insulin for diabetic patients. [SEP] Text: : Our results show that UCMSCs can differentiate into islet-like cells in vitro under certain conditions, which can function as IPCs both in vivo and in vitro. Key Words: Human umbilical cord mesenchymal stem cells; 90% pancreatectomy; Diabetic mellitus Core tip: It is well known that islet transplantation can decrease the morbidity related to diabetes mellitus (DM) after total pancreatectomy (TP); however, islet shortage limits its application. To solve the islet shortage problem, we tried to induce mesenchymal stem cells isolated from human Wharton’s jelly to differentiate into insulin-producing cells (IPCs) in this study. To imitate the pathophysiological status of diabetic patients after TP, we used Sprague-Dawley rats after 90% pancreatectomy as a model of type 1 DM. We for the first time tested the possible curative effects of transplanting IPCs differentiated from umbilical cord mesenchymal stem cells into the model rats. Citation:. Transplantation of insulin-producing cells to treat diabetic rats after 90% pancreatectomy. Gastroenterol 2015; 21(21): 6582-6590 URL: DOI: adenocarcinoma is a highly malignant and invasive disease. It has the worst prognosis of all gastrointestinal malignancies[1]. Pancreatic resection plays an essential role in the treatment of pancreatic adenocarcinoma and is the only treatment with the potential to achieve long-term survival[2]. The most common operation for pancreatic neoplasia is pancreaticoduodenectomy. heel of this operation is the pancreatic anastomosis, with an incidence of pancreatic leak ranging from 2%-29%[3]. The prognosis remains poor even in patients undergoing radical resection, and there is a median overall survival period of about 20 mo due to the high rate of relapse[4]. Theoretically, elimination of high risk pancreatic anastomosis by performing total pancreatectomy (TP) could reduce perioperative morbidity. Thus, TP has attracted more attention. TP for pancreatic adenocarcinoma was first reported in 1943 and the patient died in the perioperative period because of a bile duct leak[5]. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the differentiation of umbilical cord mesenchymal stem cells into insulin-producing cells and their potential application in treating diabetes after pancreatectomy. While it mentions insulin-producing cells, it does not explicitly address the use of genetic engineering in their production, leaving the claim uncorroborated.