Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: Identifying vulnerable targets is challenging because some essential genes are non-vulnerable, including targets for which specific inhibitors with antimalarial activity are available, such as deoxyhypusine synthase (Aroonsri et al. , 2019), Niemann-C1-Related protein (Istvan et al. , 2019), and plasmepsin V (Sleebs et al. , 2014; Polino et al. , 2020). Partial loss-of-function (LOF) mutants of these genes have latent proliferation defects, and in the case of plasmepsin V, a defect was observed after 96 h only in LOF mutants with greater than 90% knockdown of the wild-type level of expression (Polino et al. , 2020). Antimalarial discovery efforts might be better focused on directly identifying vulnerable targets with alternative assays rather than proving essentiality, which may require laborious monitoring of proliferation in LOF mutants with varying degrees of knockdown and/or conditional knockout mutants over extended periods for non-vulnerable targets. We propose to define vulnerable targets for the purpose of assay development as genes for which a partial LOF mutant (with significant knockdown of about 50 to 90% reduction of the wild-type expression level) has an acute proliferation defect observable at 96 h or sooner. In this study, we developed a target vulnerability assay for LOF mutants created with the glmS ribozyme tool (Prommana et al. , 2013). To apply the tool, the gene of interest must be modified by DNA transfection. Proof of concept for the tool was previously demonstrated for the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene modified by single-crossover integration of transfected circular DNA (Prommana et al. , 2013; Aroonsri et al. , 2016). This transfection method has been superseded by the more efficient -Cas9 gene editing system (Ghorbal et al. , 2014). We edited the DHFR-TS gene to assess whether the glmS ribozyme was functional in the context of an edited gene, particularly one with the 3′ coding region replaced with artificial recodonized sequence as a consequence of gene editing. In addition, the LOF mutant obtained with an edited DHFR-TS gene was used to validate the target vulnerability assay. [SEP] Justify:

Output: The text contrasts the claim by discussing the challenges and risks associated with gene editing techniques. It highlights that partial loss-of-function mutants can exhibit 'latent proliferation defects,' indicating potential adverse effects. Additionally, it explains that gene editing may require substantial monitoring for various outcomes, suggesting inherent risks in the process.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: The simplest example is a Markov process: (3) Xt=aXt−1+Zt. Where t is time, a is a coefficient derived from the data and Zt is white noise [5]. This simplest process may be extended by going backwards in time to earlier and earlier values, with each weighted by a coefficient derived from the known observed values [5]: (4) Xt=aXt−1+bXt−2+…+cXt−p+Zt. and, again, a, b, c,… are the model’s coefficients and p is the order of the filter. These coefficients form the prediction error filter (PEF) [21]. Crucially, it is possible to use the model to predict future values based on what is known of all the past values. In the case at hand, the analysis is functionally extending the autocorrelation function out to the needed number of values by prediction from those that can be reliably estimated [16]. Entropy, in information theory, is equivalent to ignorance. If one can formally calculate estimates that maximize ignorance, this means these values are the most honest based on what is known from data in hand and this is demonstrated through the calculus of variations [16 - 18]. A pile of zeros certainly does not fit this criterion. The spectrum is constructed from the coefficients as follows [17,18]: (5) Sω=P/1−∑k=1pake−iωk2 Where: S(ω) is spectral power as a function of angular velocity (see above), P is the power passed by the PEF, p is the order of the PEF and ak is the set of PEF coefficients. The algorithm commonly used by us and others calculates the filter in an iterative fashion and is based on the work of Anderson [22]. Each iteration extends the AR model by one. The number of coefficients in the prediction error filter employed to construct the spectrum is hence not fixed and requires some care in its choice. If a number that is too low is chosen, resolution and important detail can be lost. On the other side of the coin, if the number of coefficients is run up too high, there may be spurious peaks [21]. An objective method has been developed using the methods of Akaike [21], based on information theory. [SEP] Justify:

Output: The text does not address the claim directly and instead focuses on a Markov process and various mathematical and statistical concepts. There is no mention of circadian rhythms or their disruption, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Machine learning is transforming fields like healthcare and finance. [SEP] Text: 10. 55124/jaim. v1i1. 234 Submitted: 2023-10-18 Published: 2023-10-18 Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States. ISSN 2995-2336 : and Future of in Dr. Suryakiran Navath, Ph. D. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States. integration of (AI) in healthcare has ushered in a new era, transforming the industry in unprecedented ways. This manuscript delves into the profound impact of AI on healthcare systems and envisions its future trajectory. Through a comprehensive analysis of current applications, challenges, and emerging trends, this study illuminates the revolutionary changes brought about by AI technologies. From advanced diagnostics to personalized treatment plans, AI is reshaping patient care, improving operational efficiency, and fostering innovative solutions. Furthermore, the manuscript explores ethical considerations, regulatory frameworks, and the societal implications of widespread AI adoption in healthcare. By examining the intersection of technology and human well-being, this manuscript provides a holistic view of how AI is revolutionizing healthcare and offers valuable insights into the future of medicine. introduction section provides an overview of the rapid advancements in AI and its integration into the healthcare sector. It outlines the motivation for the study, emphasizing the need to explore the transformative impact of AI technologies on healthcare delivery, patient outcomes, and overall industry dynamics. 1 The integration of (AI) into the healthcare sector has set in motion a paradigm shift in the way we approach medical diagnosis, treatment, and patient care. The fusion of advanced machine learning algorithms, big data analytics, and cutting-edge technology has given rise to a new era in healthcare, one that holds the promise of improved patient outcomes, more efficient healthcare delivery, and better resource allocation. 2 In this manuscript, we embark on a journey to explore the profound impact of AI in healthcare. We delve into the current state of affairs, where AI is already playing a pivotal role, and then we peer into the future, envisioning a healthcare landscape where AI technologies will become even more integral. This exploration is not merely a technical one but a holistic examination of the socio-economic, ethical, and regulatory dimensions. We dissect the multifaceted ways in which AI is reshaping medical imaging, disease diagnosis,3 drug discovery, treatment personalization, and patient management. [SEP] Justify:

Output: The text corroborates the claim by discussing how AI, which includes machine learning techniques, is leading to transformative changes in healthcare. It highlights various applications of AI like advanced diagnostics and personalized treatment plans that illustrate the broader impact of AI technologies on the healthcare industry and its operations, thus supporting the assertion that machine learning is transforming these fields.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: DHFR-TS is a known vulnerable target that is inhibited by antifolate drugs such as pyrimethamine and P218 (Yuthavong et al. , 2012), and LOF mutants of DHFR-TS show significant proliferation defects at 72 h or earlier (Prommana et al. , 2013; Aroonsri et al. , 2019). To search for new antimalarial targets, we propose testing LOF mutants of unexplored genes in target vulnerability assay. Methionine metabolic pathways contain several unexplored antimalarial targets. Methionine is an essential amino acid in P. falciparum that must be obtained from salvage because proliferation is markedly reduced in culture media lacking methionine (Divo et al. , 1985; Marreiros et al. , 2023). P. falciparum salvages methionine via the new permeation pathway and a neutral amino acid transporter (Cobbold, Martin & Kirk, 2011). In addition to protein synthesis, methionine is used as a cofactor to produce the essential metabolite S-adenosyl-l-methionine (SAM) by the SAM synthase (SAMS) enzyme. The methyl group from SAM is transferred to various acceptors by methyltransferases to form S-adenosyl-l-homocysteine (SAH). SAH is hydrolyzed to adenosine and l-homocysteine (Hcy) by the highly conserved enzyme S-adenosyl-l-homocysteine hydrolase (Tanaka et al. , 2004). P. falciparum lacks key enzymes in the reverse transsulfuration pathway for the conversion of Hcy to cysteine. Consequently, Hcy accumulates and is effluxed from the parasite during intra-erythrocytic growth (Beri et al. , 2017). However, excess Hcy is deleterious and can trigger gametocytogenesis in P. falciparum (Beri et al. , 2017). In addition to efflux for the control of Hcy, Hcy can be converted to methionine by the action of the methionine synthase enzyme (MS, 5-methyl tetrahydrofolate homocysteine methyltransferase, EC. 2. 1. 1. 13). [SEP] Justify:

Output: The text contrasts the claim by discussing the vulnerabilities and potential deleterious effects associated with specific biochemical processes in P. falciparum, such as the accumulation of homocysteine (Hcy), which is noted to be 'deleterious' and can 'trigger gametocytogenesis' in the organism. Such adverse effects indicate that gene editing may not be risk-free and could result in unintended consequences.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: The filter length chosen is consistent with the most amount useful information that is being extracted as each iteration extends the length of the filter. This is used in the MESA software employed in our work, but we also commonly set a minimum filter length of about N/4 for biological rhythm analyses to ensure adequate representation of any long period cycles in the presence of noise, which can be considerable. N/3 is a good safe maximum [5,21]. MESA has proven itself superior to ordinary Fourier analysis as it does not produce artifacts from the various manipulations needed absent a model for the function and both resolution and sidelobe suppression are superior to standard Fourier analysis [16,23]. To show the difference between Fourier analysis and MESA in one critical area, it was noted above that the possible estimates that can be computed for period in Fourier analysis is constrained by the fact that these estimates can only be calculated for fixed values that are harmonics based on the length of the time series at hand. Longer series mean more tightly spaced estimates and this can be “faked” by adding zeros. MESA does not need to do this. Since the spectrum is extracted from an AR model, the spacing can be narrowed to any needed level. As an example, for the time series we have been working with, we have one week’s worth of data, sampled at half hour intervals. Note that shortening the bin size will have no effect on the spacing of the samples. Figure 5 shows the MESA for the test data set with the number of estimates increased by a factor of 32. Unlike the DFT, which had only 2 estimates in the interval between 22 and 25 h, MESA produced 60. Increasing MESA coefficients could go as high as needed, with the downside being a growing number of values that need plotting. Here 32X is more than sufficient to tease out a good estimate. Figure 5 This is the MESA spectrum with the coefficients upped to 32X. The period reported is 22. 88, compared to the known input of 23. 0. The tiny discrepancy is likely a result of the 20% added noise in the signal. Data conditioning Biological signals can be notoriously non-stationary and noisy. This variation can take the form of linear or nonlinear trends in amplitude, variations in period and the waveform. As with any signal analysis system, MESA output can be improved by conditioning the signal. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses technical aspects of the MESA software and its analysis capabilities for biological signals, without mentioning circadian rhythms or their association with health issues.


Input: Task: corroborate the claim using the given text. Claim: Machine learning is transforming fields like healthcare and finance. [SEP] Text: Simultaneously, we examine the ethical quandaries posed by AI, as well as the steps being taken to ensure responsible and equitable use. Furthermore, we will analyze the challenges faced by healthcare providers and stakeholders in adopting AI, from data privacy concerns to the need for medical practitioners to adapt to this technological revolution. We scrutinize the ongoing regulatory efforts and the international consensus on AI in healthcare standards. The journey we embark upon in this manuscript aims to not only provide an in-depth understanding of the AI revolution in healthcare but also to empower stakeholders with the knowledge needed to make informed decisions in this dynamic landscape. 4 As we move forward, we shall encounter fascinating breakthroughs, inspiring success stories, and complex dilemmas. The journey is one of discovery, reflection, and anticipation, and it is one that promises to illuminate the path to a healthcare system that is not just efficient but truly patient-centric. 5 This section explores the diverse range of applications of AI in healthcare. It covers AI-driven diagnostics, predictive analytics, robotic surgery, virtual health assistants, and smart healthcare management systems. Real-world examples and case studies illustrate how these applications are revolutionizing patient care, enhancing accuracy, and reducing healthcare costs. Examining the challenges associated with AI implementation in healthcare,6 this section discusses issues related to data privacy, security, and the ethical implications of AI algorithms in decision-making processes. It delves into the importance of bias mitigation and transparency in AI systems, emphasizing the need for responsible AI practices. This section explores the future of AI in healthcare. 7 It discusses cutting-edge technologies such as quantum computing, AI-driven drug discovery, and genomics. The section also delves into the role of AI in addressing global health challenges, such as pandemics and rare diseases, highlighting the potential for AI to revolutionize public health strategies. 8 Examining the regulatory landscape, this section analyzes existing frameworks governing AI in healthcare and proposes recommendations for creating standardized guidelines. Additionally, it discusses the societal impact of AI adoption, including workforce implications, patient-doctor relationships, and accessibility to advanced healthcare services. 9 Methods 1. Our research journey began with an extensive and systematic literature review. We conducted searches across a range of academic databases and healthcare industry publications, encompassing 2. further bolster our exploration, we gathered and analyzed data from various sources. [SEP] Justify:

Output: The text corroborates the claim by detailing how AI applications, including machine learning, are revolutionizing healthcare through various means such as diagnostics, predictive analytics, robotic surgery, and more. It emphasizes the impact of these technologies on patient care and healthcare efficiency, which aligns with the idea that machine learning is transforming industries.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: MS uses 5-methyltetrahydrofolate (5-mTHF) as a cofactor to generate tetrahydrofolate (THF) as a by-product (Banerjee & Matthews, 1990). P. falciparum can obtain 5-mTHF from salvage or by synthesis from 5,10 methylenetetrahydrofolate via a methylenetetrahydrofolate reductase enzyme (Asawamahasakda & Yuthavong, 1993). Cobalamin-dependent MS enzymatic activity was reported previously in P. falciparum intra-erythrocytic stage protein extract. Nitrous oxide inhibits the activity of this enzyme and parasite proliferation, suggesting that parasite cobalamin-dependent MS may be a potential antimalarial target (Krungkrai, Webster & Yuthavong, 1989). However, the gene encoding the parasite MS enzyme has not yet been identified in the P. falciparum 3D7 genome (Müller & Hyde, 2013). We identified a candidate P. falciparum MS gene and created a LOF mutant for assessing the vulnerability of this target. Materials & approval Blood for parasite culture was obtained by a protocol approved by the Ethics Committee, Agency (NSTDA), Thailand, approval document #0021/2560. Written consent was obtained from all volunteers. Bioinformatic analyses The InterPro database (Paysan-Lafosse et al. , 2023) was searched using the InterPro entry IPR003726 (homocysteine-binding domain) via the InterPro web interface ( Protein sequences were obtained from UniProt (The Uniet al. , 2023) of the cobalamin-dependent methionine synthase (MS) enzymes from human (MTR, Q99707-1) and Escherichia coli K12 (metH, P13009), together with Plasmodium spp. candidate MS from orthologous group 1324at5820 encoded by P. falciparum PF3D7_1233700 (Pf, Q8I585), P. knowlesi PKH_145080 (Pk, A0A384KWI2), P. [SEP] Justify:

Output: The text contrasts the claim because it discusses various complexities and challenges in gene editing, particularly in the context of malaria research and methionine synthase enzymes, without presenting any claims that gene editing is without risks or side effects. It highlights the need for ethical approvals and biological complexities that imply potential risks associated with genetic modifications.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: It should be noted, however, that MESA is robust in the face of such problems from the start. Incorporated into our MESA program is a detrending step which fits a line by regression and subtracts it. This eliminates linear trend and removes the mean. Mean removal is highly recommended, as this DC component can obscure the rhythmic one if it is excessive [12]. Removal of nonlinear trend can be accomplished by high-pass filtering by numerous methods and will not be discussed here as it is beyond the scope of this work. Low pass filtering to remove high frequency noise, however, is of considerable interest and is commonly done in preparation for spectral analysis (Review: [12,24]). We have had excellent success with Butterworth recursive filters [9,12,24]. They are considered recursive because in addition to incorporating the original time series data into the moving filtering process, previously filtered values are used as well. Butterworth filters are highly accurate and reliable, and the cutoff frequency is sharp [9]. 6, the artificial test signal depicted in Figure 1 is shown after filtering with a two-pole low-pass Butterworth filter with a ~3 dB amplitude rolloff at the specified period of 4 h. The number of poles reflects the depth of the recursion [9]. The filter equation showing the recursion is: (6) Yt=Xt+2Xt−1+Xt−2+AYt−1+BYt−2/C Figure 6 This is the original data set after being filtered twice with a Butterworth recursive digital filter. The second pass reverses the filter’s introduction of a four-hour phase delay owing to its recursive nature. is the original data series and Yt is the output series. A and B are the filter coefficients: A = 9. 656 and B = −3. 4142. C is the “gain” or amplitude change of the filter and equals 10. 2426. See [9,12,24] for a more detailed description of this filter. Owing to the recursion there is a 4-h phase delay in this example and this needs either to be made clear when the data are plotted or actually reversed. Reversal can easily be accomplished by running the filter in reverse. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the technical aspects of the MESA program and the filtering techniques used in data analysis, without mentioning circadian rhythms or health issues. Therefore, it does not support or refute the claim in any way.


Input: Task: corroborate the claim using the given text. Claim: Machine learning is transforming fields like healthcare and finance. [SEP] Text: This data encompassed healthcare utilization statistics, patient outcomes, AI implementation in medical institutions, and the economic implications of AI adoption in healthcare. We applied statistical and data analysis tools to identify correlations and trends that highlight the impact of AI on healthcare quality, efficiency, and costs. 3. In our quest for comprehensive insights, we conducted interviews with experts and thought leaders in the field of healthcare and artificial intelligence. These interviews provided valuable qualitative data and personal perspectives on the challenges, opportunities, and ethical considerations related to AI in healthcare. We engaged experts from diverse backgrounds, including clinicians, data scientists, healthcare administrators, and regulatory authorities. 4. To substantiate our findings, we examined a series of real-world case studies from healthcare institutions that have successfully integrated AI into their operations. These case studies were selected to illustrate different applications of AI, such as medical image analysis, predictive analytics, and personalized medicine. Through these case studies, we aimed to highlight the practical impact of AI on healthcare providers and patients alike. 5. Ethical and The ethical and regulatory aspects of AI in healthcare were a focal point of our study. We analyzed existing ethical frameworks, guidelines, and regulations governing AI implementation in healthcare. In addition, we explored ongoing discussions within the international community on the responsible use of AI, as well as emerging regulatory developments. This analysis aimed to shed light on the measures being taken to ensure patient privacy, data security, and equity in AI-enabled healthcare. 6. The manuscript also incorporates a future-oriented analysis, which involved forecasting the trajectory of AI in healthcare. This forward-looking segment was informed by expert opinions, historical trends, and ongoing research and development efforts in the field. Our aim was to provide readers with a glimpse of what to expect in the coming years, including potential breakthroughs, challenges, and transformative changes. Trends 1. AI Adoption in The adoption of AI in healthcare institutions has shown a consistent upward trajectory. In 2019, approximately 40% of hospitals and medical facilities had integrated some form of AI into their clinical and administrative workflows. By 2020, this figure increased to around 60%, and in 2021, it further rose to approximately 80%. This three-year trend illustrates a steady and significant increase in AI adoption within healthcare. 2. application of AI in medical imaging has witnessed continuous improvements over this period. In 2019, AI-assisted diagnosis led to a 10% increase in diagnostic precision. [SEP] Justify:

Output: The text corroborates the claim by providing evidence of the integration and impact of AI (a subset of machine learning) in healthcare. It discusses the increasing adoption of AI in healthcare institutions, highlighting a significant upward trajectory—40% in 2019, 60% in 2020, and 80% in 2021. This trend demonstrates how machine learning technologies are indeed transforming the healthcare sector. Furthermore, the text references various applications of AI, including medical image analysis and predictive analytics, which underscores the transformation within healthcare brought about by machine learning.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: Repair vectors (Dataset S2 & Dataset S3) were constructed by simultaneous Gibson assembly cloning (NEB) of three synthetic fragments for each target (recodonized partial open reading frame, 5′ and 3′ HR) into the p3HA_glmS plasmid, linearized by digestion with KpnI (NEB). Recodonized coding region fragments were obtained as gBlocks synthetic DNA (IDT, Singapore). 5′ and 3′ HR fragments were obtained by PCR using PrimeSTAR® (Inc. Shiga, Japan) and P. falciparum 3D7 genomic DNA template. Gene editing by DNA transfection P. falciparum 3D7 reference (NCBI txid: 36329) wild-type parasite was cultured in vitro as previously described (Aroonsri et al. , 2016; Aroonsri et al. , 2019). Cas9 (20 µg) and PstI-linearized repair (50 µg) vectors were co-transfected into late schizont parasites by AMAXA nucleofection, as previously described (Knuepfer et al. , 2017). WR99210 (2 nM, a gift from Prof. Tirayut Vilaivan) was applied 48 h post-transfection to select transfected parasites. WR99210-resistant parasites emerged within 30 days post-transfection, and gene editing events were detected by PCR with integration-specific primers (Table S1). Transfected parasites with detectable gene edits were treated for 7 days with 1 µM 5-fluorocytosine (Sigma-) and 2. 5 µg/mL blasticidin S HCl (Gibco™, ) to remove Cas9 plasmid retained as episome and eliminate wild-type parasites. Clonal lines of gene-edited parasites were obtained by limiting dilution in 96-well microtiter plates. Western blotting Clonal lines of transgenic parasites DHFR-TS_glmS and MS_glmS with edited PF3D7_0417200 and PF3D7_1233700 genes, respectively were synchronized by sorbitol treatment and cultured for 24 h in the presence or absence of 5 mM glucosamine (GlcN, Sigma-). [SEP] Justify:

Output: The text contrasts the claim by detailing a complex process of gene editing in P. falciparum that involves several steps, including the use of Cas9, selection of transfected parasites, and treatment to remove the Cas9 plasmid. It indicates that gene editing events were detected and that specific treatments were required to eliminate wild-type parasites and plasmids, suggesting that there are significant procedural steps and potential consequences involved, thereby implying there are risks and possible side effects associated with gene editing.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Since it is highly inadvisable to run a filter more than once to achieve additional smoothing before spectral analysis, as this will result in artifact [9], this reversal must only be done for display of simple plots for visualizing data. A single pass with the phase change is not an issue for MESA, since the attendant phase shift is of no consequence in this context. A second reversing pass with this filter actually resulted in a widening of the MESA peak (data not shown). After filtering, the RI (see above) is improved from 0. 697 to 0. 715. MESA at work MESA has seen notable success since first being implemented for use in biological rhythms in the 1980s. MESA is useful for an extremely wide range of living oscillatory processes. It was instrumental in discovering the presence of ultradian rhythms in Drosophila locomotor activity rhythms early on, most remarkably in flies bearing the per0 and per- mutations, which have no overt circadian periodicity [25,26]. These ultradian rhythms have been central in a competing hypothesis describing the mechanism of the circadian clock [26,27]. It has been used extensively in circadian rhythm work since that time. Given its superior resolving power, it settled an old dispute about the presence of lunar rhythmicity in physiological activity in marine organisms [9]. When applied in conjunction with powerful trend removal techniques, it was instrumental in teasing out the role of the gene cryptochrome (cry) in the fly clock system. Luciferase activity was monitored in antennae bearing either tim-luc or per-luc constructs and a central role for CRY protein in the peripheral antennal clock was established [28,29]. Ultradian and circadian rhythms were examined in premature infants (24–29 weeks) prior to their developing robust circadian periodicity enabling inferences on prenatal periodicity in normal pregnancies [30]. A cryptic human core body temperature of about one hour was elucidated [31]. Electroencephalography has yielded considerable information on ultradian periodicity in rats with MESA analysis combined with aggressive filtering enabling an incorporation of these high-frequency rhythms into models of sleep-wake dynamics [32]. A genetic component in strain differences among normal mice was discerned when locomotor activity was investigated with MESA, revealing robust ultradian components [33]. The presence of an endogenous vertical migration rhythm in Antarctic krill was verified [34]. [SEP] Justify:

Output: The text is irrelevant to the claim, as it primarily discusses the use of MESA in biological rhythms and various experiments related to ultradian and circadian rhythms without addressing the potential health issues arising from the disruption of circadian rhythms.


Input: Task: corroborate the claim using the given text. Claim: Machine learning is transforming fields like healthcare and finance. [SEP] Text: By 2020, this increase had grown to 15%, and in 2021, it accelerated further to 25%. These findings demonstrate a notable evolution in the impact of AI on medical imaging in just three years. 3. for The use of AI-driven predictive analytics for disease prevention has also seen notable progress. In 2019, hospitals and healthcare providers that utilized AI for patient data analysis and risk prediction achieved a 15% reduction in hospital readmissions. By 2020, this reduction had increased to 20%, and in 2021, it reached 30%. This trend highlights the growing effectiveness of AI algorithms in identifying patients at higher risk of complications and enabling timely interventions. 4. Plans AI's role in developing personalized treatment plans for patients has advanced over this period. In 2019, AI-driven recommendations led to a 5% increase in treatment plan efficacy. By 2020, this increase had reached 10%, and in 2021, it further improved to 15%. This data indicates a continuous refinement of AI algorithms in tailoring treatment strategies based on individual patient data. Table 1. Use of AI in Healthcare category by 2021 2020 2019 AI Adoption in 80% 60% 40% Enhancement 25% 15% 10% for 30% 20% 15% Plans 15% 10% 5% 20% 15% 10% and Engagement 25% 20% 15% 15% 10% 5% 5. The economic implications of AI integration in healthcare have shown promise. In 2019, the implementation of AI in administrative tasks led to a 10% reduction in operational costs for healthcare institutions. By 2020, this reduction increased to 15%, and in 2021, it reached 20%. These trends indicate a growing impact of AI on cost reduction within healthcare. 6. related to patient satisfaction and engagement have consistently shown positive trends. In 2019, healthcare facilities that employed AI-powered virtual health assistants and chatbots reported a 15% increase in patient satisfaction rates. By 2020, this increase grew to 20%, and in 2021, it reached 25%. These findings highlight the ongoing enhancement of patient satisfaction and engagement through AI-driven tools. 7. While the statistics showcased the potential benefits of AI in healthcare, they also highlighted the ethical concerns. Data breaches and privacy violations related to AI were identified in approximately 15%, 10%, 5% of healthcare AI projects. This underscored the importance of robust data security and privacy measures in AI adoption. [SEP] Justify:

Output: The text corroborates the claim by providing extensive data on the transformative impact of AI in the healthcare field. It details how AI-driven predictive analytics and personalized treatment plans have led to significant improvements in patient outcomes, with reductions in hospital readmissions and increases in treatment efficacy. Additionally, it mentions the economic implications of AI on reducing operational costs within healthcare institutions, evidencing the technology's influence. The statistics provided reflect the growing effectiveness and extensive implementation of AI in healthcare, reinforcing the idea of transformation in this field.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: PF3D7_1233700 is annotated in OrthoDB (Kuznetsov et al. , 2023) as a member of the syntenic Plasmodium orthologous group 1324at5820 (Hcy-binding domain). PF3D7_1233700 and orthologous (single-copy) proteins from other human-infective Plasmodium spp. showed low (≈20%) identity with human and Escherichia coli cobalamin-dependent MS (Figs. S1 & S2). We searched for candidate MS using a three-dimensional structural superposition-based approach (Foldseek), which is more sensitive for identifying homologous proteins (et al. , 2023). Full-length cobalamin-dependent MS comprises four modules (N-terminal Hcy-binding, 5-mTHF-binding, cobalamin-binding, and C-terminal adenosylmethionine-binding/reactivation; Matthews, Sheppard & Goulding, 1998). The X-ray structures of cobalamin-dependent MS protein fragments from different species have been determined, although the structure of the N-terminal fragment containing Hcy- and 5-mTHF substrate binding domains is available only for Thermotoga maritima (Evans et al. , 2004). We selected the structure of the T. maritima cobalamin-dependent MS fragment co-complexed with Hcy and 5-mTHF as a query for Foldseek. The top-ranked Foldseek hit to P. falciparum 3D7 proteins was PF3D7_1233700. Lower-ranked hits had well-defined annotations unrelated to methionine metabolism, suggesting incidental structural similarity of protein folds with functions unrelated to MS (Table S2). Notwithstanding the possibility of even more diverged proteins not detectable by sequence- or structure-based homology, PF3D7_1233700 is putatively assigned as P. falciparum MS. However, definitive annotation requires direct functional data, e. g. , biochemical assay of the purified PF3D7_1233700 protein for MS activity. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and uncertainties involved in annotating the PF3D7_1233700 protein and the need for definitive functional data. It highlights that while candidates may be structurally similar, without direct functional assays, one cannot assert complete safety or absence of side effects in gene editing processes, thereby suggesting potential risks.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Work on the cardiac pacemaker of the fly heart has benefitted from the use of MESA for measuring heart rate [35,36]. When combined with a novel preliminary Fourier treatment to alter the sampling structure, the presence of rhythmicity in the spacing of pulses in the Drosophila mating song was confirmed and it was shown to be under the control of the period gene [37]. In summary, has proven itself to be a highly useful and versatile tool for the investigation of periodic biological phenomena. Technical note A full explanation of the mathematics underlying MESA and the ways in which algorithms have been implemented is beyond the scope of this paper. For those wishing to explore these topics in detail, the author recommends the following: For a good general introduction to the basic logic of MESA see Able’s review [16]; Burg’s original papers are the next step in seeing how the technique developed [17,18]; the very thorough paper by Ulrych and Bishop [21] should be sufficient to answer almost any mathematical question on the procedure and the algorithm used in our version of the technique, which we implemented in is found in Andersen’s contribution [22]. Some of these papers, notably those of Burg himself, are difficult to locate. The compendium edited by D. G. Childers entitled “Analysis” (1978, Wiley) has all these recommended papers and many more that are on point. All software used in this lab, including the source code, is available free of charge from the author: dowse@maine. edu. A step by step annotated guide in its use has been published by this author [38]. Competing interests The author declares that he has no competing interests. 55. Lloyd, D; Rossi, EUltradian rhythms in life processes: An inquiry into fundamental principles of chronobiology and psychobiology. Springer-Verlag. Winfree, ATof biological Time. Springer-Verlag. Bünning, EClock. Springer-Verlag. Chatfield, Cof Time Series: An Introduction. Chapman and Hall. Lanczos, CApplied Analysis. Prentice Hall. Lanczos, CDiscourse on Fourier Series. Oliver and Boyd. Beauchamp, K; Yuen, CKfor Signal Analysis. George, Allen, Unwin. Hamming, RWDigital Filters. Prentice-Hall. [SEP] Justify:

Output: The text is irrelevant to the claim as it primarily discusses the technical aspects of measuring heart rate in Drosophila and does not mention anything about circadian rhythms or their implications for health issues.


Input: Task: corroborate the claim using the given text. Claim: Machine learning is transforming fields like healthcare and finance. [SEP] Text: In the following sections, we delve deeper into these statistics, providing detailed analyses and discussions that paint a comprehensive picture of the transformative impact of AI on the healthcare sector. conclusion synthesizes key findings from the manuscript, emphasizing the transformative potential of AI in healthcare. It underscores the importance of ethical considerations, collaborative efforts between the industry and regulators, and ongoing research to fully harness the benefits of AI technologies. The conclusion also provides a forward-looking perspective, envisioning a future where AI-driven healthcare becomes not just a possibility but a global reality, transforming the lives of millions. Acknowledgement. The authors thank to Dr. Mir Mahammad, Baylor and for his constant encouragement and valuable discussions. aThe reaction was conducted in anoxic conditions. bThis is the format for table footnotes. 10. 1186/2047-2501-2-3 D. W. Bates, S. Saria, L. Ohno-Machado, A. Shah, G. EscobarBig data in health care: using analytics to identify and manage high-risk and high-cost patientsHealth Aff. , 33 (2014), 10. 1377/hlthaff. 2014. 0041 E. A. Mohammed, B. H. Far, C. NauglerApplications of the MapReduce programming framework to clinical big data analysis: current landscape and future trendsBioData Min. , 7 (2014), p. 22, 10. 1186/1756-0381-7-22 Y. Wang, N. HajliExploring the path to big data analytics success in healthcareJ. Bus. Res. , 70 (2017), 10. 1016/j. jbusres. 2016. 08. 002 B. Kayyali, D. Knott, S. Van KuikenThe big-data revolution in US health care: accelerating value and innovationMcKinsey Co. (2013), 10. 1145/2537052. 2537073. Orjuela-Canon, Andres L. undefined, 2021 43rd Conference of the IEEE Engineering in Medicine & (EMBC), 10. 1109/EMBC46164. 2021. 9631006, (2468-2471), (2021). promise of artificial intelligence: a review of the opportunities and challenges of artificial intelligence in healthcare, Bulletin, 10. [SEP] Justify:

Output: The text corroborates the claim by emphasizing the transformative impact of AI on the healthcare sector. It discusses the comprehensive picture of AI's potential to change healthcare significantly, underscoring that AI-driven healthcare is envisioned to become a global reality, which aligns with the assertion that machine learning is transformative in this field.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: We edited the PF3D7_1233700 and PF3D7_0412700 (DHFR-TS) genes, placing them under the control of the glmS ribozyme (Prommana et al. , 2013). The edited DHFR-TS and MS genes were confirmed by PCR genotypic assays in clonal lines of transgenic parasites (Figs. 1 & 2). One clonal line of each edited gene (designated as DHFR-TS_glmS and MS_glmS, respectively) was selected for phenotypic analysis. The expressions of target proteins in transgenic parasites were assessed by western blotting of synchronized transgenic parasites cultured for 24 h in the presence or absence of GlcN. Protein species of sizes expected for modified MS (72. 7 kDa) and DHFR-TS (75. 5 kDa) were detected in transgenic parasites (Fig. S3). GlcN treatment caused significant reductions in MS and DHFR-TS protein expression (DHFR-TS mean = 40%, P-adjusted = 0. 004; MS mean = 51%, P-adjusted = 0. 03; Fig. 3A). There was no significant difference in the mean % target protein (GlcN treated relative to untreated control) level between DHFR-TS and MS (P = 0. 34). Figure 1: PF3D7_0417200 (DHFR-TS) gene editing. (A) Schematic of PF3D7_0417200 gene editing (drawn to scale). The location of the guide RNA target for mediating double-strand DNA break is indicated by the lightning bolt symbol. Repair vector (Dataset S2) elements are indicated by the colored boxes, including homologous regions in blue, recodonized protein coding region (Rec. ) in magenta, triple hemagglutinin epitope tag (HA) in cyan, glmS ribozyme (glmS) in red, blasticidin S deaminase selectable marker gene (BSD) in orange, and Plasmodium transcriptional regulatory elements in teal. The locations and sizes of amplicons expected from PCR using primers DHFR_37 F (P1), _1558R (P2), and glmS_3R (P3) are indicated by black arrows. [SEP] Justify:

Output: The text contrasts the claim by detailing the results of gene editing where significant reductions in protein expression were observed when GlcN was administered to the transgenic parasites. This implies that there are responses and potential side effects associated with the gene editing process, contradicting the assertion that gene editing is risk-free and without side effects.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Chui, CKto Wavelets. Academic Press. Dowse, HB; Ringo, JMSumming locomotor activity into “bins”: How to avoid artifact in spectral analysis Research 11: 2–14, DOI: (2009). Analyses for physiological and behavioral rhythmic Methods in Enzymology, Computer Methods, Part A,. 2009: Elsevier, 174. Schuster, AOn the investigation of hidden periodicities with application to a supposed 26-day period of meterological phenomena 11: 13–41, DOI: Whitaker, E; Robinson, Gof Observations. Blackie and Son. Kendall, MGContributions to the study of oscillatory time series. Press. Ables, JGMaximum entropy spectral analysis 11: 383–393. (1978). . Wiley, 41. (1978). A new analysis technique for time series data Analysis. Wiley, 48. Dowse, HB; Ringo, JMThe search for hidden periodicities in biological time series revisited J 11: 487–515, DOI: Dowse, HB; Ringo, JMComparisons between “periodograms” and spectral analysis: Apples are apples after all J 11(148): 139–144. Ulrych, T; Bishop, TMaximum entropy spectral analysis and autoregressive decomposition Rev. Geophysics and 11: 183–300, DOI: Andersen, NOn the calculation of filter coefficients for maximum entropy spectral analysis Geophys 11: 69–72, DOI: Kay, SM; Marple, SGSpectrum analysis, a modern perspective IEEE Proc 11: 1380–1419. Levine, J; Funes, P; Dowse, H; Hall, JSignal analysis of behavioral and molecular cycles Neurosci 11: 1–25. Dowse, HB; Hall, JC; Ringo, JMCircadian and ultradian rhythms in period mutants of Drosophila melanogaster 11: 19–35, DOI: [PubMed] (2008). Mid-range ultradian rhythms in Drosophila and the circadian clock problem from Molecules to Mind: A of Life. Springer Verlag, 199. [SEP] Justify:

Output: The text provided does not address the claim directly. It consists of a list of citations and titles related to various research topics, primarily focusing on methodologies in spectral analysis and the study of oscillatory time series. Therefore, it fails to provide any relevant information about circadian rhythms or their health implications, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: Glass additive manufacturing is an emerging research topic showing an increase in publications in recent years. 20–28 Recent studies demonstrated MLA fabrication in fused silica using two-photon polymerization through a direct laser writing technique,29,30 an approach that combined hot embossing with custom glass 3D printing,31 stereolithography,32 and microscale computed axial lithography. 33 These studies were realized by utilizing a new type of silica nanocomposite resin. After printing, thermal postprocessing is required to create fully dense glass microlenses. This includes removing the binder (polymer), followed by a high-temperature sintering step. This postprocessing can be time consuming, requiring several hours of heating. The debinding and sintering steps also result in significant volume shrinkage, which can deform the structure and influence the resulting surface roughness of the print. Despite this challenge, the state-of-the-art techniques demonstrate up to 6 nm roughness for the printed surface after sintering. 29,30,32,33In this study, we report on 3D printing fused silica glass MLA through CO2 laser heating of glass filaments. This technique enables highly customizable MLA design having sub-mm lens diameters, without the need for any thermal postprocessing. Through laser heating, lenses with sub-nm surface roughness can be achieved. The demonstrated technique is well suited for rapid prototyping of MLAs, as well as for small- to medium-size production in glass. Material and FabricationThe feedstock material used for MLA fabrication was fused silica glass filaments, having a diameter of 200 μm. The filaments were made using a conventional draw tower designed for optical fiber fabrication. Fused silica is a synthetic silicon dioxide glass of high purity, providing enhanced optical transmission in the wavelength range from ∼180 nm to 2. 5 μm, enabling MLAs to be designed for a large range of wavelengths. The MLA was fabricated directly onto a 25 × 25 mm2 fused quartz plate having a thickness of 300 μm. A glass 3D printer (Nobula™ Zero; Nobula3D AB) was used for printing the MLA as well as for postprocessing. The printer used multiple beams from a CO2 laser to locally heat and soften/melt the substrate and glass filament. The CO2 laser operated at a wavelength of 10. 6 μm. [SEP] Justify:

Output: The text corroborates the claim by detailing how a new glass 3D printing technique enables highly customizable microlens array (MLA) designs with sub-mm lens diameters, thus supporting the notion of customized manufacturing. It emphasizes that the process allows for rapid prototyping and production, aligning well with the concept of on-demand manufacturing.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: The structures of the PF3D7_0417200 gene before editing in parental reference strain 3D7 wild-type (3D7 WT) and after editing in transgenic (DHFR-TS_glmS) parasites are shown. (B) PCR products from genotypic assay separated in 0. 8% agarose gel. Three clonal lines of transgenic parasites were isolated; DHFR-TS_glmS clone #1 was selected for phenotypic analysis. Lane M: 1kb+ DNA ladder (Invitrogen, sizes indicated on the left). Download full-size image DOI: 10. 7717/peerj. 16595/fig-1 Figure 2: PF3D7_1233700 (MS) gene editing. (A) Schematic of PF3D7_1233700 gene editing (drawn to scale). The location of the guide RNA target for mediating double-strand DNA break is indicated by the lightning bolt symbol. Repair vector (Dataset S3) elements are indicated by the colored boxes, including homologous regions in blue, recodonized protein coding region (Rec. ) in magenta, triple hemagglutinin epitope tag (HA) in cyan, glmS ribozyme (glmS) in red, blasticidin S deaminase selectable marker gene (BSD) in orange, and Plasmodium transcriptional regulatory elements in teal. The locations and sizes of amplicons expected from PCR using primers MS_5IntF (P1), MS_HR2_rev (P2), glmS_3R (P3), and MS_5recodonR (P4) are indicated by black arrows. The structures of the PF3D7_1233700 gene before editing in parental reference strain 3D7 wild-type (3D7 WT) and after editing in transgenic (MS_glmS) parasites are shown. (B) PCR products from genotypic assay separated in 0. 8% agarose gel. Two clonal lines of transgenic parasites were isolated; MS_glmS parasite clone #1 was selected for phenotypic analysis. Lane M: 1kb+ DNA ladder (Invitrogen, sizes indicated on the left). Download full-size image DOI: 10. 7717/peerj. [SEP] Justify:

Output: The text contrasts the claim by detailing the processes and experiments involved in gene editing. It highlights the selection of clonal lines of transgenic parasites for phenotypic analysis following gene editing of the PF3D7_1233700 and PF3D7_0417200 genes. The mention of 'transgenic parasites' and 'clonal lines' implies that gene editing is being rigorously analyzed, suggesting a level of risk and the consideration of effects that inherently contradict the idea that gene editing is completely risk-free.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Dowse, H; Ringo, JFurther evidence that the circadian clock in Drosophila is a population of coupled ultradian oscillators J 11: 65–76, DOI: [PubMed] Krishnan, B; Levine, J; Sisson, K; Dowse, H; Funes, P; Hall, J; Hardin, P; Dryer, SA new role for cryptochrome in a Drosophila circadian oscillator Nature 11: 313–317, DOI: [PubMed] Plautz, J; Straume, M; Stanewsky, R; Jamison, C; Brandes, C; Dowse, H; Hall, J; Kay, SQuantitative analysis of Drosophila period gene transcription in living animals J 11: 204–217, DOI: [PubMed] Tenriero, S; Dowse, H; D’Souza, S; Minors, DS; Chiswick, M; Simms, D; Waterhouse, JMRhythms of temperature and heart rate in premature babies in intesive care Dev 11: 33–52, DOI: [PubMed] Lindsley, G; Dowse, H; Burgoon, P; Kilka, M; Stephenson, LA persistent circhoral ultradian rhythm is identified in human core temperature 11: 69–78, DOI: [PubMed] Stephenson, R; Joonbum, L; Famina, S; Caron, A; Dowse, HSlep-wake behavior in the rat: ultradian rhythms in a light–dark cycle and continuous bright light J 11: 490–501, DOI: [PubMed] Dowse, H; Umemori, J; Koide, TUltradian components in the locomotor activity rhythms of the genetically normal mouse, Mus musculus J 11: 1788–1795, DOI: [PubMed] Gaten, E; Tarling, G; Dowse, H; Kyriacou, C; Rosato, EIs vertical migration in Antarctic krill (Euphausia superba) influenced by an underlying circadian rhythm? [SEP] Justify:

Output: The text does not address the claim directly as it focuses on various studies related to circadian rhythms in different organisms such as Drosophila and mice but does not mention health issues related to the disruption of those rhythms. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: For producing size- and shape-specific microlens designs parameter mapping is required, for which the matrix printing ability of the glass 3D printer is highly suitable for. The high laser power used during printing caused a small amount of glass to be evaporated from the hot zone, with a subsequent partial redeposit of fumed silica surrounding the microlens and, in some instances, onto nearby microlenses. To remove this unwanted redeposited material, each lens was irradiated using the CO2 laser for a duration of ∼10 s, using the four laser beams with a total power of 5 W. Figure 2a shows the printed and postprocessed MLA. The redeposited fumed silica can be seen here as darker regions between the microlenses. Figure 2b shows a close-up of a single lens from the same MLA, corresponding to the sliced model in Figure 1c. FIG. 2. Top view (a) of the 5 × 5 MLA, and side view (b) of a single microlens. Fabrication of microlenses with different heights was possible simply by varying the number of print layers. Figure 3 shows images of three different microlenses, having a similar convex radius but different thickness, printed with a single layer (shown in Fig. 3a), double layer (Fig. 3b), and five layers (shown in Fig. 3c). Note that within the five-layer microlens, some small voids are visible that likely are formed during layer shifting. Further improvement of the process parameters is needed for printing multilayer MLA (≥5 layers). FIG. 3. Microlenses in different thickness: (a) 1-layer microlens, (b) 2-layer microlens, (c) 5-layer microlens. CharacterizationTo evaluate the reproducibility of the 3D printing technique, the MLA was characterized using optical microscopy (LV100) in combination with image processing (ImageJ). The surface roughness was measured for several microlenses using atomic force microscopy (). The optical properties of the lenses were measured and compared with the lens maker's formula as well as the ray optics model using simulations. Optical microscopyThe plano-convex shape of the printed microlenses, shown in Figure 2, was characterized using an optical microscope in combination with image processing. [SEP] Justify:

Output: The text corroborates the claim by demonstrating the ability of 3D printing to create customized microlens designs with specific sizes and shapes. It describes the parameter mapping required for these designs, indicating how different fabrication techniques (like varying the number of print layers) enable customization. The discussion on the printing of microlenses with different heights and thicknesses illustrates the on-demand manufacturing capability of 3D printing.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: 16595/fig-2 Figure 3: Phenotypic analysis of gene-edited parasites. In vitro cultures were established for Plasmodium falciparum reference 3D7 parental strain and transgenic parasite strains MS_glmS and DHFR-TS_glmS with edited PF3D7_1233700 (MS) and PF3D7_0417200 (DHFR-TS) genes, respectively. (A) Knockdown of target proteins in transgenic parasites. MS and DHFR-TS % target protein signals were obtained by western blotting (Fig. S3). Boxplots show the data from triplicate experiments. (B) Target vulnerability assay. Parasites were cultured for 96 h at different glucosamine (GlcN) concentrations. The left panel shows all data and model fits (curves). The right panel shows EC_50 values for each transgenic line compared with that of the 3D7 parental strain. The points show the estimated EC_50 ratio (3D7: transgenic parasite) and error bars represent S. E. M. The dashed line indicates the line of no effect. Estimated EC_50 ratios:- 3D7: DHFR-TS_glmS = 11. 25, adjusted P = 7. 9E-6; 3D7: MS_glmS = 0. 89, adjusted P = 0. 84. Download full-size image DOI: 10. 7717/peerj. 16595/fig-3 Next, we assessed the consequences of target protein knockdown in transgenic parasites with respect to proliferation in target vulnerability assay. In previous studies of the acute effect of glmS-ribozyme mediated target knockdown on parasite proliferation, treatment was performed for up to 72 h in which GlcN has a minor inhibitory effect on wild-type strains (Prommana et al. , 2013). By extending the GlcN treatment to 96 h, greater than 50% inhibition of the 3D7 wild-type strain was observed at the highest concentrations such that we could determine the EC50 (8. 0 mM; 95% confidence intervals 5. 9 to 10. 0 mM). [SEP] Justify:

Output: The text contrasts the claim by discussing the outcomes of gene editing on transgenic parasites. It highlights that the edited strains have varying degrees of efficacy and effects when subjected to glucosamine treatment, showing that gene editing does not produce risk-free or uniform results. Specifically, the mention of inhibitory effects on wild-type strains indicates potential side effects related to gene editing.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: 0 cm) on soft wood chip bedding in a controlled environment of 23 ± 1ºC, 60% humidity, and 12:12 h light/dark cycles (light on at 8:00) in the Multi-chamber System (& Co. , Osaka, Japan). The bedding in each cage was changed and the food and water were refreshed twice a week. For the lighting in each chamber, a high color-rendering cold cathode lamps having a wavelength near-natural light was installed. The light intensity was measured by installing an illuminometer (T-10, Konica Minolta, Tokyo, Japan) on the floor in the cage and set to 250 lux intensity. All animals were provided with MF diet, Co. , Tokyo, Japan) and water ad libitum. Mice were held for 1-week acclimatization period before test initiation and then subjected to experiments at 8 weeks-old. After acclimatization, the light/dark cycle in each experimental group was set as follows: Control, 12:12 h light/dark cycle; Shift, 12:12 light:dark cycle with inverting every two days, which imitated the rotating two-shift work [34] (Figure 2A). Lighting time is denoted as Zeitgeber time (ZT), where ZT0 represents the start of the light period (the light period was from ZT0 to ZT12 and the dark period was from ZT12 to ZT24). During the test period, the general condition and body weight of the animals were observed once a week. All procedures were carried out under protocols approved by of the University of Shizuoka (Approval number: 165149, 175172). 2. 3. anesthesia with isoflurane, a momentum measuring device (nano tag®, Co. , Ltd. Nagano, Japan) was subcutaneously implanted into the necks of mice. During operation, the animals were cared for with a thermal pad to prevent decrease body temperature. After an acclimatization period of one week, animals were randomly assigned to either of the two types of light/dark cycles and kept for 4 weeks. Locomotor activity was measured by 3-axis accelerometer inside the device. The recording of the momentum data was aggregated every 5 minutes, and the threshold was set to 170. [SEP] Justify:

Output: The text is irrelevant to the claim as it provides a detailed description of an experimental setup involving light/dark cycles for mice, but does not mention any health issues or consequences related to circadian rhythm disruption.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: The focal length (fmeasured = 483 ± 40 μm) was obtained by subtracting the average lens height (475 ± 5 μm) from the measured distance ΔL between the two microscope positions (958 ± 40 μm). The homogeneity of the spots was then analyzed by comparing the intensity of the spots along a selected array of spots. The light intensity of the selected array with five spots (indicated by the red box in Fig. 7a) was measured with the results presented in Figure 7b. The intensities were measured across the center of each spot and quantified using image processing software ImageJ. The result from the five selected microlenses shows uniform light intensities for the different lenses with a variation of ±3. 4%, indicating similar focusing performance for each microlens in the glass MLA. FIG. 7. (a) Spot-matrix image captured from the focal plane of the MLA, (b) light intensities of five spots taken from the red box area. Imaging performanceThe imaging performance of the microlens was also evaluated as shown in Figure 8. Here a parallel white light source was projected through a filter (black horse on a white paper), through the MLA with the image captured using the CCD camera of the optical microscope. Each lens provides a clear image with little distortion (see Fig. 8b) indicating reproducible fabrication and homogeneous refractive index of the different lenses with overall good imaging performance of the MLA. FIG. 8. (a) The setup for the MLA imaging performance test, (b) the top view of the 5 × 5 MLA imaging of a horse and the comparison of a lens imaging with the original image outline (red dashed outline). ConclusionsWe present results on a simple and rapid method of 3D printing silica glass MLA using a filament-based laser deposition technology. The microlenses had a hemispherical plano-convex shape. An ultrasmooth lens surface was achieved with a measured roughness of 0. 12 nm. The 5 × 5 MLA displays uniform focusing performance with an average EFL of 483 ± 40 μm across the whole array, in agreement with theoretical values and simulation results. The MLA provides good imaging quality. The capability of creating microlenses in different thickness enables versatile customizations of microlenses and multifocal MLA fabrications for 3D imaging applications. 1. [SEP] Justify:

Output: The text corroborates the claim by discussing the capability of 3D printing to create microlenses with versatile customizations. It states that 'the capability of creating microlenses in different thickness enables versatile customizations of microlenses and multifocal MLA fabrications for 3D imaging applications,' supporting the idea of customized manufacturing that is central to the claim.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: We posited that knockdown of vulnerable target gene expression by the action of the glmS ribozyme enhances the proliferation defect caused by GlcN treatment itself over 96 h manifested as a significantly lower EC50 compared with 3D7 wild-type. The EC50 of the DHFR-TS_glmS parasite, but not that of the MS_glmS parasite, was significantly different from that of the 3D7 wild-type strain (Fig. 3B). Hence, reduction in DHFR-TS, but not MS expression affected parasite sensitivity to GlcN. Based on these results, DHFR-TS is defined as a vulnerable antimalarial target as expected. In contrast, MS is a non-vulnerable target. Discussion PF3D7_1233700 was identified as the only candidate gene encoding MS from a bioinformatic search of the P. falciparum 3D7 genome, suggesting that the parasite possesses a single MS gene. However, P. falciparum MS is not a vulnerable antimalarial target, in contrast to the vulnerability of the downstream SAMS enzyme in the P. falciparum methionine pathway (Musabyimana et al. , 2022). Salvage is the major source of methionine substrate for P. falciparum SAMS because reducing exogenous methionine leads to a concomitant decrease of SAM (Harris et al. , 2023). Hence, methionine synthesized by MS is of minor importance for intra-erythrocytic proliferation under standard in vitro culture conditions. However, methionine synthesis may be more important for P. falciparum proliferation in natural infections, since the methionine concentration in human serum (Barić et al. , 2004) is approximately two to seven times lower than that of parasite culture medium. The other roles of P. falciparum MS besides methionine synthesis should be considered to explain the conservation of MS in Plasmodium and its tentative annotation of essentiality in P. falciparum based on the absence of transposon insertions in the encoding gene (Zhang et al. , 2018). It should be noted that definitive proof of essentiality requires demonstration of a proliferation defect from more complete knockdown using a different tool (e. g. [SEP] Justify:

Output: The text contrasts the claim by discussing the intricacies of gene expression and the potential vulnerabilities related to the knockdown of genes, specifically mentioning that the reduction in expression of the DHFR-TS target affects parasite sensitivity. This implies that gene editing can have significant effects and highlights potential risks, thus casting doubt on the assertion that gene editing is completely risk-free.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: The recorded locomotor activity data was captured by FeliCa communication, and changes in behavioral rhythms were analyzed with the nanotag/Viewer (Co. , Ltd. Nagano, Japan). 2. 4. acclimatization, mice were randomly divided into Control group and Shift group. BJMC3879Luc2 tumor cells were implanted into the right fourth mammary fat pad of female BALB/c mice by injection of 0. 1 mL PBS containing 5 × 106 cells. Mice were kept for 3, 5, or 8 weeks, either under normal or irregular light/dark cycle conditions. Transplanted tumor size was measured with a caliper once a week, and volume was calculated using the following formula: tumor volume = maximum diameter (mm) × (minimum diameter (mm))2 × 0. 4 [35]. The endpoint for tumor size defined a maximum diameter of 20 mm. Rate of metastasis to lymph node that located distal to the implantation site was calculated as follows: Rate of metastasis (%) = (Number of metastasis to individual lymph node/Total number of mice in each group) × 100. 2. 5. Imaging of Prior examination has shown that the development of peak luciferase activity is strongly influenced by depth of anesthesia and body temperature. The general condition of mice varied in distribution from mild to severe. Therefore, ex vivo imaging was performed to avoid the effects of anesthesia depth and body temperature to luciferase activity. For imaging of tumors and metastatic sites, mice received an intraperitoneal (i. p. ) injection of 120 mg/kg D-luciferin (Wako) dissolved in PBS. 7 minutes post-injection, tissue-specific metastasis in lung, kidney lymph nodes, and axillary lymph nodes were tracked with bioluminescence using the imaging system () by measuring luciferase activity for 50 seconds exposure time. Images were analyzed with software version 3. 0. 2. 6. Determination of NA in To detect intratumoral NA, breast tumors developed in the mammary fat pad were collected. Tumor tissues were homogenized in 0. 01 N HCl (containing: 1% sodium disulfite and 1 mM EDTA) and supernatant was collected. NA was measured using the kit (ImmuSmol, Talence, France) in accordance with the manufacturer’s protocol. 2. 7. [SEP] Justify:

Output: The text does not directly address the claim regarding the disruption of circadian rhythms and health issues. It primarily describes a method of conducting experiments on mice involving tumor implantation and measurement of various parameters without mentioning circadian rhythms or any related health implications.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: For all specimens, the following design principles are considered:•Continuous toolpath, no start and stop, and no individual printing islands•Blend between individual layers, no straight z movement upwards•No self-intersecting toolpaths•Blend radius for corners/minimal feature sizeVariable cross-sectionThe footprint of the printed samples is 500 × 75 mm and the height of the elements varies; at least seven layers are printed. The single outline toolpath is chosen, as it allows a stable printing process and a fast cooldown (fast fabrication time). Furthermore, the single outline print eliminates interface interactions between different beads within the same layer. The distance between the layers (resolution in Z direction) varies for every print. The experiments start with a layer height of 16 mm and increase in 2 mm steps until a layer height of 32 mm is reached. Although the layer height is not limited to 32 mm, it is beyond the scope of the 3. Close-up of a section, layer height 24mm and diagram of measurement points. c: center point, determined by ImageJ. h(c): height at point c; w(c): width at point c; w(max): maximum width, determined by ImageJ bounding box; r(x): wall thickness at point x. Different nozzles: Internal geometryThe increased dimension of the 3D printable bead offers the opportunity to create subdivided die geometries. Those internal substructures can potentially improve the properties of the printed component in regard to structural, optical, or thermal performance (Fig. 4). FIG. 4. Different nozzles types, prototyped using 3DP of aluminum. a) o24w. b) o24w1Quad. c) o24w1Crosshair. d) o24tubeInTube. Please see Table 1 for more detail regarding the different types. As a first attempt, four different die typologies are designed and fabricated. All nozzles have an outer diameter of 24 mm, (a) is a nozzle with no internal geometry, (b) contains a cross to reinforce the bead, (c) contains a crosshair pattern, and (d) consists of five individual tubes. Table 1 provides a detailed overview of the shape, pocket size, and plastic cross-section for each design. Similar to the experiments described in and Fabrication section, basic rectangular elements are 3D printed and sections of the printed object are analyzed. [SEP] Justify:

Output: The text supports the claim by detailing various aspects of 3D printing techniques and design principles that enable customized manufacturing. It mentions the ability to create 'subdivided die geometries' and internal structures that enhance the properties of the printed components, indicating a level of customization. Additionally, it discusses the adjustment of layer heights and the design of various nozzle types, which contribute to the on-demand aspect of 3D printing, allowing for rapid, tailored fabrication processes.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: , the TetR-DOZI system with 5′ and 3′ aptamers installed at the target gene (Polino et al. , 2020)) or from conditional gene knockout mutagenesis. Essential genes are expressed through the life cycle, and P. falciparum MS is detectably expressed by data-independent proteomics throughout the intraerythrocytic stages at a level approximately 40–1000-fold lower than that of DHFR-TS (Siddiqui et al. , 2022). Moreover, single-cell RNA sequencing data indicate that P. falciparum MS is expressed during mosquito stages (Real et al. , 2021), and the P. vivax MS ortholog PVP01_1451800 is expressed in liver stages (Mancio-Silva et al. , 2022). Although malaria parasites possess a mechanism for the efflux of Hcy (Beri et al. , 2017), lack of MS function may lead to increased levels of Hcy and redox stress, which may be important for sporogonic development in the mosquito vector when Plasmodium is more dependent on glutathione (Vega-Rodríguez et al. , 2009) and α-lipoic acid (Biddau et al. , 2021) to mitigate oxidative stress. The conversion of 5-mTHF to THF by MS may be important for recycling folate required for other enzymatic reactions, particularly during the developmental stages with the greatest folate demand. Plasmodium can salvage folates and the folate precursor para-aminobenzoic acid (p ABA), but the levels of folates are too low, or are not in a form capable of being efficiently transported to support intra-erythrocytic development in the absence of de novo synthesis (Salcedo-Sora & Ward, 2013). P. berghei lacking the p ABA synthetic enzyme aminodeoxychorismate synthase cannot develop in p ABA-deficient medium during intraerythrocytic stages; however, the growth of these mutant parasites is unaffected in p ABA-deficient medium during liver stages (Matz et al. , 2019). [SEP] Justify:

Output: The text contrasts the claim by discussing the potential risks associated with gene editing, specifically highlighting the lack of methionine synthase (MS) function which may lead to increased levels of homocysteine (Hcy) and redox stress in malaria parasites. It suggests that these biochemical alterations could be important for mosquito vector development, indicating that gene editing might not be risk-free and could have significant biological consequences.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Counting and Classification of For counting of peripheral white blood cells (WBCs), blood samples were treated with 10-fold the amount of Tuerk’s solution (Sigma-Aldrich, St. ), and the number of WBCs per 1 mm3 were calculated by hemocytometer. To perform WBC classification, heparinized blood was smeared onto a slide glass and quickly dried with cool air using a blow-dryer. Slides were fixed and stained with May-Gruenwald stain solution (Sigma-Aldrich) for 3 min, and then stained using 1:20 May-Gruenwald stain solution diluted with phosphate buffer (pH 6. 4, M/15, Sigma-Aldrich) for 3 min. Slides were then stained with Giemsa stain solution (Merck, Darmstadt, Germany) diluted 20 times with phosphate buffer for 15 min. Blood smear specimens were inspected (magnification, × 1,000) using immersion oil. One hundred WBCs were counted and classified into five types (i. e. , lymphocyte, monocyte, neutrophil, eosinophil, and basophil). Each WBC count per 1 mm3 was calculated using the following formula: presence ratio of each type of WBCs × total WBC count. 2. 8. Feeding a Quercetin-in the 3879Luc2 cells were transplanted into female BALB/c mice as described above. The mice were provided MF diet or 0. 3% quercetin-containing MF diet. All food was changed three times a week to reduce the effects of deterioration of quercetin in the MF diet. Mice were maintained for 8 weeks in normal light conditions (Control) or light/dark shift environment (Shift). All mice were divided into the following four groups: MF diet (Control) or 0. 3% quercetin-containing MF diet (0. 3%Q-Ctrl) in a normal light/dark environment; MF diet (Shift) or 0. 3% quercetin-containing MF diet (0. 3%Q-Sh) in an irregular light/dark shift environment. The lymph node metastasis inhibition rates in 0. 3% Q-Ctrl and 0. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on laboratory processes for counting and classifying peripheral white blood cells, along with details on experimental setups involving diet for mice, without any mention of circadian rhythms or health issues related to their disruption.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: HC3DP at large dimensions provides the opportunity to create bespoke, noncircular, and such cross-sections that increase the range of possible applications. Adaptive extrusion section control allows the creation of unseen designs, material efficient structures, and significant improvements on fabrication speed. With this 1. . Large-format fused deposition additive manufacturing: A review. J 2020;26(5):793–799;Crossref2. Large-format additive manufacturing of polymer extrusion-based deposition systems: Review and applications. Manuf 2023;8:1257–1280;Crossref3. Designing for big area additive manufacturing. 2019;25:275–285;Crossref4. . Large-scale hollow-core 3D printing (HC3DP): A polymer 3D printing technology for large-scale ultralightweight components. 2023;78:103874;Crossref5. Scott CS. for Three-Dimensional Objects. US5340433A, 8, 1992, and 23, 1994. 6. Barnatt C. 3D Printing: Industrial Revolution. Third edition. United States: ExplainingTheFuture. com, 2013. ISBN: 978-1-5396-5546-6. 7. . A review of melt extrusion additive manufacturing processes: I. Process design and modeling. J 2014;20(3):192–204;Crossref8. Leapfrog XceL. Industrial 3D Printer. 2019. Available from: [Last accessed: October 23, 2023]. 9. Prusa. . 2020. Available from: E3D. SuperVolcano. 2018. Available from: Structure and mechanical behavior of (BAAM) materials. J 2017;23(1):181–189;Crossref12. van der Kooij D. Endless Chair—Kooij; 2011. Available from: [Last accessed: February 1, 2023]. 13. Infrared preheating to improve interlayer strength of big area additive manufacturing (BAAM) components. 2017;14:7–12;Crossref14. Extrusion control for high quality printing on (BAAM) systems. 2019;28:445–455;Crossref15. Determination of the Distance in Additive Manufacturing. In: 4th on 3D Printing (Additive Manufacturing) Technologies and Digital Industry. [SEP] Justify:

Output: The text corroborates the claim by highlighting that HC3DP allows for creating bespoke designs and noncircular cross-sections, which enhances the range of possible applications, thereby supporting the concept of customized manufacturing. The mention of adaptive extrusion section control further suggests improvements in efficiency and fabrication speed, aligning with the notion of on-demand manufacturing.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: Despite an inefficient folate transport system for the uptake of 5-mTHF (Salcedo-Sora & Ward, 2013), elevated levels of 5-mTHF in the liver may drive its accumulation and conversion to THF by Plasmodium MS, such that the parasite is less reliant on de novo folate synthesis during this stage of the life cycle. A knockout mutant of the P. berghei orthologous MS gene (_1448300) shows no growth defect during intraerythrocytic stages (Bushell et al. , 2017), but growth of the mutant is reduced during the transition from the sporozoite (through the liver) to the blood stage (Stanway et al. , 2019). Although these data suggest a non-essential role of Plasmodium MS, dispensability in P. falciparum cannot be extrapolated from knockout data in P. berghei because of species-specific differences in Plasmodium host cell tropism. P. berghei preferentially invades reticulocytes, whereas P. falciparum invades mature erythrocytes. The reticulocyte milieu has a greater metabolic complexity than that of erythrocytes, which can support the growth of P. berghei parasites with knockouts of genes functioning in the intermediary carbon metabolic pathway, pyrimidine metabolism, and glutathione biosynthesis that are essential in P. falciparum (Srivastava et al. , 2015). finding that MS is a non-vulnerable antimalarial target raises the question of what other enzymes in the Plasmodium parasite methionine pathway and other pathways related to folate metabolism (Müller & Hyde, 2013) are also non-vulnerable targets. This could be tested by target vulnerability assay of LOF mutants for other genes annotated as essential. Although the role of MS as an antimalarial target is deprioritized, it would be interesting to test whether the roles of P. falciparum MS in Hcy metabolism and folate recycling are more important in mosquito and liver stages. [SEP] Justify:

Output: The text contrasts the claim by discussing species-specific differences in Plasmodium metabolism and targeting vulnerabilities, which implies that interventions like gene editing can have varying effects and may not be completely risk-free or without side effects. The mention of non-essential roles and the exploration of target vulnerabilities suggest that outcomes may vary, indicating that the assertion of being completely risk-free is overly simplistic.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: s1 Abbreviations DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; for Research on Cancer; MMP, matrix metalloproteinase; NA, noradrenaline; NLR, neutrophil-to-lymphocyte ratio; PBS, phosphate buffered saline; Q3G, quercetin-3-o-glucuronide; SAM, sympathetic-adrenal-medullary axis; WBC, white blood cell; ZT, Zeitgeber time. authors thank Dr. Taka-aki Suzuki (Institute of Shizuoka Prefecture, Japan), Mr. Tadakazu Takahashi, Ms. Chika Tokuyama, and Mr. (University of Shizuoka, Japan) for their technical support, and Dr. (of Science, Japan) for helpful advice for leukocytes differentiation on this study. We also thank H. Nikki March, PhD, from (www. edanzediting. com/ac) for editing a draft of this manuscript. This work was supported by grant number 15H02899 and 18H03194(KS). The authors have no competing interests to declare. M. Y. and K. S. designed and directed the project. M. N, A. H. and Y. Y. performed experiment and statistical analyses. N. M. designed light-dark cycle conditions. K. S. and M. S. provided the breast cancer cell line, BJMC3879luc2 cells and instructed implantation experiment. T. A. and N. O. provided bioimaging instruction and analytical equipment, N. M. provided instruction and analytical equipment for the quantitative analysis of quercetin. M. N. and K. S. wrote the manuscript and all authors reviewed and commented on the manuscript. 437. DOI: Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res. 1983; 53: 96–104. DOI: Circadian rhythm of leucocytes and lymphocytes subsets and its possible correlation with the function of the autonomic nervous system. Immunol. 1997; 110(3): 500–508. DOI: Okamura H. Clock genes in cell clocks: roles, actions, and mysteries. J Biol Rhythms. [SEP] Justify:

Output: The text provided is largely a list of acknowledgments and author contributions, along with various abbreviations and references, without any direct mention or discussion of circadian rhythms or health issues. Therefore, it is irrelevant to the claim regarding the connection between circadian rhythm disruption and health problems.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: 3D Printing of medicines: Engineering novel oral devices with unique design and drug release characteristics. 2015;12:4077–4084. CrossrefPubMed71. Verstraete G, Samaro A, Grymonpré W, et al. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes. Pharm 2018;536:318–325. CrossrefPubMed72. 3D printed tablets with internal scaffold structure using ethyl cellulose to achieve sustained ibuprofen release. 2018;115:11–18. CrossrefPubMed73. Immediate release 3D-printed tablets produced via fused deposition modeling of a thermo-sensitive drug. 2018;35:124. CrossrefPubMed74. 3D printing of metformin HCl PVA tablets by fused deposition modeling: Drug loading, tablet design, and dissolution studies. 2019;20:1–11. Crossref75. 3D printed polyvinyl alcohol tablets with multiple release profiles. 2019;9:1–8. PubMed76. Matijašić G, Gretić M, Kezerić K, et al. Preparation of filaments and the 3D printing of dronedarone HCl tablets for treating cardiac arrhythmias. 2019;20:1–13. Crossref77. Customized novel design of 3D printed pregabalin tablets for intra-gastric floating and controlled release using fused deposition modeling. Pharmaceutics 2019;11:1–14. Crossref78. Development of 3D printed tablets by fused deposition modeling using polyvinyl alcohol as polymeric matrix for rapid drug release. J 2020;109:1558–1572. CrossrefPubMed79. Fabrication of taste-masked donut-shaped tablets via fused filament fabrication 3D printing paired with hot-melt extrusion techniques. 2020;21:1–11. Crossref80. Three-dimensional (3D)-printed devices composed of hydrophilic cap and hydrophobic body for improving buoyancy and gastric retention of domperidone tablets. 2020;155:105555. CrossrefPubMed81. . A flexible-dose dispenser for immediate and extended release 3D printed tablets. 2015;96:380–387. CrossrefPubMed82. [SEP] Justify:

Output: The text corroborates the claim by providing multiple examples of how 3D printing is applied in the production of customized oral dosage forms, such as the 'customized novel design of 3D printed pregabalin tablets for intra-gastric floating and controlled release.' This indicates the ability of 3D printing to create unique designs specific to individual needs, which supports the idea of on-demand manufacturing.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: Sequence alignment of methionine synthases Protein sequences were obtained from UniProt of the cobalamin-dependent methionine synthase (MS) enzymes from human (MTR, Q99707-1) and Escherichia coli K12 (metH, P13009), together with Plasmodium candidate MS from orthologous group 1324at5820 encoded by P. falciparum PF3D7_1233700 (Pf, Q8I585), P. knowlesi PKH_145080 (Pk, A0A384KWI2), P. malariae PmUG01_14067900 (Pm, A0A1A8X239), P. ovale wallikeri PowCR01_140053700 (Pow, A0A1C3L5P3), P. ovale curtisi PocGH01_14059300 (Poc, A0A1D3UAH7), and P. vivax PVX_100640 (Pv, A0A1G4H5F2) genes. Sequences were aligned using the T-Coffee tool with default options in the Expresso web interface (Armougom et al. , 2006). DOI: 10. 7717/peerj. 16595/supp-1 matrix of methionine synthases Percent identity matrix of the protein alignment (Fig. S1) was created using the bio3d R package version 2. 4-4. Cells are shaded according to the percent identity as indicated by the scale bar on the right. DOI: 10. 7717/peerj. 16595/supp-2 blotting of target proteins Clonal lines of transgenic parasites DHFR-TS_glmS and MS_glmS with edited PF3D7_0417200 (DHFR-TS) and PF3D7_1233700 (MS) genes, respectively were cultured for 24 h in the presence or absence of 5 mM glucosamine (GlcN). A sample of parasite protein extract (50, 50, and 2. [SEP] Justify:

Output: The text contrasts the claim by discussing gene editing in the context of transgenic parasites and detailing experimental conditions that imply there may be effects from gene editing, such as the presence or absence of glucosamine in the culture. This suggests that gene editing practices may lead to variable outcomes and thus are not risk-free.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: Lymphangiogenesis and axillary lymph node metastases correlated with VEGF-C expression in two immunocompetent mouse mammary carcinoma models. Breast Cancer. 2011; 2011: 867152. DOI:. Systemic Immune-inflammation Index, Based on and Neutrophil-Lymphocyte Ratio, for in Lung Cancer. Exp Med. 2015; 236: 297–304. DOI: Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer. SpringerPlus. 2015; 4: 255. DOI: Grosso G, Godos J, Lamuela- A comprehensive meta-analysis on dietary flavonoid and lignan intake and cancer risk: Level of evidence and limitations. Food Res. 2017; 61(4): DOI: ás-Barberán Flavonoids in food and their health benefits. Hum Nutr. 2004; 59(3): 113–122. DOI:. Dietary antioxidant flavonoids and risk of coronary heart disease: the Study. Lancet. 1993; 342(8878): 1007–1011. DOI: Dihal AA, de Boer VC, van der Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats. J Nutr. 2006; 136(11): 2862–2867. DOI: An immunocompetent murine model of metastatic mammary cancer accessible to bioluminescence imaging. Anticancer Res. 2009; 29(11): 4389–4395. Combined effect of circadian dysfunction and cadmium on immune suppression. Sci. 2016; 3(5): 237–242. DOI: Synthetic a-mangostin dilaurate strongly suppresses wide-spectrum organ metastasis in a mouse model of mammary cancer. Cancer Sci. 2018; 109(5): 1660–1671. DOI:. the Risks of Cancers in Women: A and Meta-analysis of 61 423. DOI: Morales--Gallego A, Jimenez-Lopez JC, Morell M. of the Polymorphisms of Associated with Endocrine Cancer. [SEP] Justify:

Output: The text does not address the claim about circadian rhythms and their relation to health issues. Instead, it presents various studies related to cancer, immune response, and other health risk factors without making any reference to circadian rhythms.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: Goyanes A, Kobayashi M, Martínez-Pacheco R, et al. Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets. Pharm 2016;514:290–295. CrossrefPubMed83. . Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. 2015;68:11–17. CrossrefPubMed84. Fused deposition modeling (FDM) 3D printed tablets for intragastric floating delivery of domperidone. 2017;7:1–9. CrossrefPubMed85. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. Pharm 2017;527:21–30. CrossrefPubMed86. . Formulation of 3D printed tablet for rapid drug release by fused deposition modeling: Screening polymers for drug release, drug-polymer miscibility and printability. J 2018;107:390–401. CrossrefPubMed87. . 3D printing of vaginal rings with personalized shapes for controlled release of progesterone. Pharm. 2018;539:75–82. CrossrefPubMed88. Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler. Pharm 2018;543:361–367. CrossrefPubMed89. Development of customised 3D printed biodegradable projectile for administrating extended-release contraceptive to wildlife. Pharm 2018;548:349–356. CrossrefPubMed90. Development of immediate release (IR) 3D-printed oral dosage forms with focus on industrial relevance. 2020;155:105558. CrossrefPubMed91. . Novel gastroretentive floating pulsatile drug delivery system produced via hot-melt extrusion and fused deposition modeling 3D printing. Pharmaceutics 2020;12:52. CrossrefPubMed92. Investigations of process parameters during dissolution studies of drug loaded 3D printed tablets. J 2021;235:523–529. Crossref93. Development of controlled porosity polymer-ceramic composite scaffolds via fused deposition modeling. 2003;23:611–620. [SEP] Justify:

Output: The text corroborates the claim by illustrating various applications of 3D printing technology, particularly in the pharmaceutical field, where customized and tailored drug delivery systems are developed. For example, it mentions the 'development of customised 3D printed biodegradable projectile for administrating extended-release contraceptive to wildlife' which clearly demonstrates the ability to create tailor-made solutions using 3D printing. Additionally, the mention of 'patient-tailored prednisolone tablets' further supports the notion of customization and on-demand manufacturing in the text.


Input: Task: contrast the claim using the given text. Claim: Gene editing is completely risk-free with no side effects. [SEP] Text: 16595/supp-6 vector sequence for PF3D7_0417200 (DHFR-TS) gene editing Color key:- Yellow: unique 6 bp restriction sites; Cyan: 3x haemagglutinin (HA) epitopes; Gray: RNA spacer; Red: glmS riboswitch (Bacillus subtilis); Dark blue: Plasmodium berghei DHFR-TS terminator; Blue: Plasmodium falciparum histidine-rich protein 2 terminator; Green: Blasticidin-S-deaminase open reading frame; Brown: Plasmodium falciparum calmodulin promoter; Magenta: DHFR-TS 3′homology region; Purple: DHFR-TS 5′homology region; Black: recodonized DHFR-TS. DOI: 10. 7717/peerj. 16595/supp-7 vector sequence for PF3D7_1233700 (MS) gene editing Color key:- Yellow: unique 6 bp restriction sites; Cyan: 3x haemagglutinin (HA) epitopes; Gray: RNA spacer; Red: glmS ribozyme (Bacillus subtilis); Dark blue: Plasmodium berghei DHFR-TS terminator; Blue: Plasmodium falciparum histidine-rich protein 2 terminator; Green: Blasticidin-S-deaminase open reading frame; Brown: Plasmodium falciparum calmodulin promoter; Magenta: MS 3′homology region; Purple: MS 5′homology region; Black: recodonized MS. DOI: 10. 7717/peerj. 16595/supp-8 blot raw data Raw data from western blotting shown in Fig. 3A. DOI: 10. 7717/peerj. 16595/supp-9 assay raw data Raw data from proliferation assay shown in Fig. 3B. DOI: 10. 7717/peerj. 16595/supp-10 We thank Prof. (Chulalongkorn University, Bangkok, Thailand) for the gift of WR99210 and Dr. (Crick Institute, London, UK) for transfection plasmids and protocols. authors declare there are no competing interests. [SEP] Justify:

Output: The text contrasts the claim because it provides specific information about complex gene editing vector sequences and the methodologies involved in gene editing which imply that this process involves sophisticated techniques and potentially intricate risks. However, the text does not provide any explicit claims or evidence that gene editing is risk-free, suggesting that there may be inherent risks involved.


Input: Task: pass the claim using the given text. Claim: Disruption of circadian rhythms can lead to health issues. [SEP] Text: also measures head movements with solid-state accelerometers to characterize behavioral activity. Detailed information about the Daysimeter is available elsewhere [20]. Figure 1 Daysimeter and functional block diagram. Figure 2 Spectral response graph. Spectral response functions generated from the model of human circadian phototransduction by Rea et al. [22]. The dashed line represents the predicted spectral response function for an equal energy spectrum light source. The continuous line represents the predicted spectral responses to individual, narrow-band light sources. The two sets of symbols represent empirical spectral response data from two independent laboratories [34, 35]. Figure 3 Logistic transfer function graph. Logistic transfer function relating nocturnal melatonin suppression to the rectified circadian light stimulus (CS) from the model of human circadian phototransduction by Rea et al. [22]. Data from several studies using both narrow-band [34, 35] and polychromatic light sources [36–38] to induce nocturnal melatonin suppression were plotted as a function of CS. A logistic function from Zeitzer et al. [23] was used to fit the data yielding a regression coefficient (r2) for the transfer function equal to 0. 82. Figure was adapted from Rea et al. [22]. It should be emphasized that activity as measured by the Daysimeter is not a direct measure of the endogenous clock in the SCN. Like every downstream measure of circadian function, behavior can only yield partial insight into circadian entrainment. It is presently impossible to directly measure SCN activity in vivo, and thus it is impossible to measure entrainment in the purest sense in living and active humans; the term "behavioral entrainment" is used in this paper to describe the observed levels of synchrony between light-dark exposures and activity-rest responses as measured by the Daysimeter. Data collection was sent to nurses throughout the to measure their actual CS exposures and activity for seven consecutive days. Forty-three pre-menopausal female nurses, both day-shift (n = 32) and rotating-shift nurses (n = 11), participated in the study. They wore the Daysimeter for seven consecutive days and were scheduled to work at least two and no more than three consecutive days during that period. was worn while nurses were awake. The nurses were instructed to place the Daysimeter next to them when they slept or bathed. [SEP] Justify:

Output: The text is irrelevant to the claim as it does not discuss the effects of disrupted circadian rhythms on health. Instead, it focuses on the use of a device called the Daysimeter and the methodology of a study involving nurses without mentioning any health outcomes related to circadian disruptions.


Input: Task: corroborate the claim using the given text. Claim: 3D printing allows for customized, on-demand manufacturing. [SEP] Text: 3D-printed poly lactic acid scaffolds with tetrapod-interlocked structure containing dipyridamole. 2020;28:5–8. Crossref107. Fused deposition modeling of poly (lactic acid)/macadamia composites-thermal, mechanical properties and scaffolds. Materials (Basel) 2020;13:258. CrossrefPubMed108. . Fabrication and characterization of poly lactic acid scaffolds by fused deposition modeling for bone tissue engineering. 2020;35:248–251. Crossref109. Calcium phosphate-PLA scaffolds fabricated by fused deposition modeling technique for bone tissue applications: Fabrication, characterization and simulation. 2020;46:2447–2456. Crossref110. 3D printed scaffolds with random microarchitecture for bone tissue engineering applications: Manufacturing and characterization. J 2020;103:103583. CrossrefPubMed111. Rapid development of dual porous poly(lactic acid) foam using fused deposition modeling (FDM) 3D printing for medical scaffold application. 2020;110:110693. CrossrefPubMed112. 3D printed Sr-containing composite scaffolds: Effect of structural design and material formulation towards new strategies for bone tissue engineering. Technol 2020;191:108069. Crossref113. Sanz- Fabrication of 3d-printed biodegradable porous scaffolds combining multi-material fused deposition modeling and supercritical CO2 techniques. Nanomaterials 2020;10:1080. CrossrefPubMed114. Preparation and in vitro evaluation of PLA/biphasic calcium phosphate filaments used for fused deposition modelling of scaffolds. 2020;114:111013. CrossrefPubMed115. Fused deposition modeling of patient specific polymethylmethacrylate implants. J 2010;16:164–173. Crossref116. 3D printing of PEEK–cHAp scaffold for medical bone implant. Bio-Design Manuf. Published online 2020. Crossref117. Effect of processing conditions on the bonding quality of FDM polymer filaments. J 2008;14:72–80. Crossref118. Direct ink writing of three-dimensional ceramic structures. J Soc 2006;89:3599–3609. Crossref119. . Fused deposition modeling with polypropylene. 2015;83:768–776. Crossref120. [SEP] Justify:

Output: The text corroborates the claim by detailing various applications of 3D printing relevant to the manufacturing of customized scaffolds for medical purposes. It mentions fabrication methods, such as fused deposition modeling and highlights the customization potential in the wording ‘patient specific polymethylmethacrylate implants,’ which supports the idea of on-demand and tailored manufacturing through 3D printing technologies.