Input: Task: contrast the claim using the given text. Claim: All healthcare treatments can be effectively delivered using virtual reality headsets. [SEP] Text: Simulations of clinical scenarios are necessary to evaluate AR surgical guidance systems (Pérez-Pachón et al. 2020), but limit the number and type of measurements and number of participants that can be included in the analyses due to the complexity of the experimental design (Herzog et al. 2019). In addition, measuring localisation errors during a surgical task includes variations in the participants’ expertise and dexterity as additional sources of error (Bann et al. 2003; Sondak and Zager 2010). Moreover, X-ray vision (i. e. the perception that virtual models of internal anatomical structures lie on the surface of the patient) is a common problem in AR applications for surgery and may lead to localisation errors (Avery et al. 2009). 1. 3 AimsThis study measured the error with which users of an AR headset localise virtual models aligned with real world features. A simple setup was used to reduce perception issues typically associated with X-ray vision and to facilitate a large sample size and thus the collection of a sufficiently large number of measurements for statistical testing. The research questions were:(RQ1) What is the error in the users’ localisation of virtual models and to what extent does it result in errors in the perceived position and dimensions of the virtual models? (RQ2) Is there a relationship between these errors and the position and distance of the virtual models from the user’s eyes? 2 Methods2. 1 ParticipantsWe recruited 54 adults aged 20–59 years from staff and students at the University of Aberdeen for this study. All those selected were in good health and without vision problems except those corrected by glasses or contact lenses. The sample size was determined following the results of a power analysis for an ANOVA using G*Power (Faul et al. 2007). 2. 2 Experimental setupThe first generation of the AR headset HoloLens () was used in the experiment as the equipment was purchased at the beginning of our project prior to the release of HoloLens 2. An AR app (App-1) was created using (Kress and Cummings 2017a). App-1 allowed for the detection of a 12 × 12 cm digital image marker (referred to as “marker” henceforth) by the headset’s camera. This triggered the rendering of a virtual model (a 5-cm-radius virtual hexagon) on the headset’s lenses in a set position (Fig. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and complexities associated with using augmented reality (AR) systems, specifically in the context of surgical guidance. It highlights the necessity of simulations to evaluate AR applications while pointing out that they can restrict the number and type of measurements and participants due to the experiment's complexity. Additionally, it mentions issues like ‘X-ray vision’ problems, which can further lead to localization errors during surgical tasks.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: Notably, genes targeted by strong purifying selection are likely to fulfil functions that are essential. By contrast, genes evolving under more relaxed constraints (such as weaker purifying selection or neutrality) may have variably redundant functions in immune signalling. Finally, genes targeted by positive or balancing selection are possibly involved in mechanisms in which genetic variation has conferred a selective advantage to the population. Membrane-bound receptors: the case of TLRs. Population genetics studies have provided important insights in terms of the evolution and function of TLRs45,46,47,48,49,50,51,52,53. In humans, TLRs are broadly subdivided into two groups: those primarily expressed at the cell surface (TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10), which detect predominantly pathogen-associated molecular patterns from bacteria, fungi and protozoa, and those expressed within endosomes (TLR3, TLR7, TLR8 and TLR9), which primarily recognize nucleic acids from viruses and bacteria14,38,39. Comparative interspecies studies have shown that species-wide positive selection has accelerated the divergence of some TLRs among primates, with the strongest evidence obtained for TLR1 and TLR4 (Refs 48, 51, 53). These two TLRs contain the highest number of positively selected codons, several of which are involved in ligand binding or in interaction with the TLR4 co-receptor MD2 (also known as LY96)51. This high interspecies divergence suggests that the presence or absence of pathogens that are sensed by TLR1 and TLR4 may be one of the most important variants in the ecological niches of the different primate species. Within species, and in humans in particular, balancing selection was initially proposed to be pervasive among innate immunity genes52, including some TLRs. However, most intraspecific studies thus far converge towards the opposite conclusion: TLRs, taken as a set, have mainly evolved under the action of purifying selection46,47,49,51, which highlights their indispensability. More precisely, intracellular TLRs evolve under the strongest purifying selection (Fig. 2), and neither nonsense nor damaging missense mutations are tolerated at these genes46. [SEP] Justify:

Output: The text does not address the claim regarding biophilia or the innate connection humans have to nature. Instead, it discusses genetic evolution, TLRs (Toll-like receptors), and their roles in immune signaling, which are unrelated topics. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Attention can be selectively focused, altering cognitive processing. [SEP] Text: In contrast, the conflict adaptation effect was not influenced by the anxious mood. These findings suggest that an anxious mood can accelerate target processing through enhancing focused attention but not inhibitory control. The practical implications for human directional choice in an evacuation situation are discussed. 본 연구는 불안한 정서상태가 방향선택 수행에 미치는 영향을 확인하고자, 불안상태를 유발한 후 공간 스트룹 과제에서 측정한 스트룹 촉진효과와 간섭효과에 미치는 영향을 확인하고자 하였다. 이를 위해, 한 집단에게는 불안수준이 높은 그림 및 소리 세트를 제시하고, 다른 집단에게는 중성적인 그림 및 소리 세트를 제시하여 기분상태를 조작하였다. [SEP] Justify:

Output: The text corroborates the claim by discussing how an anxious mood can enhance focused attention, which indicates that attention can be selectively directed, thus affecting cognitive processing. It mentions the influence of mood on processing speed and decision-making in specific contexts, supporting the idea that attention can be adjusted based on emotional states.


Input: Task: contrast the claim using the given text. Claim: All healthcare treatments can be effectively delivered using virtual reality headsets. [SEP] Text: In contrast, area errors were significantly smaller (p < 0. 05) for virtual hexagon positions 1, 2, 3, 8 and 9, i. e. generally, on the viewers’ eye level and above this level (Fig. 3c). Fig. 3Virtual hexagon positions with smallest errors for vertex localisation, centroid position and absolute area (highlighted in green) and their mean errors (a) and vertex localisation (b) and absolute area (c) errors for virtual hexagon positions 1–9 (n = 4146). Whiskers indicate ± 1. 5 IQR. Weak outliers (i. e. values > 1. 5 IQR and < 3 IQR) are indicated with circles and virtual hexagon positions with significantly smaller errors (p < 0. 05) with asterisks (H test). Strong outliers (i. e. values > 3 IQR) were excludedFull size image3. 3 Effect of the distance between the virtual models and the users’ eyesErrors in vertex localisation and centroid position decreased as the distance between the headset’s camera and the monitor increased (Fig. 4a and 8). These errors were significantly different (p < 0. 001) between distances 1–3 (i. e. 65, 85, and 105 cm, respectively). Distances 2 and 3 produced smaller absolute area errors than distance 1 (Fig. 4b). Fig. 4Vertex localisation (a) and absolute area (b) errors for distances 1–3 (n = 4146). Whiskers indicate ± 1. 5 IQR. Weak outliers (i. e. values > 1. 5 IQR and < 3 IQR) are indicated with circles and distance associated with the smallest errors (p < 0. 05) with asterisks (H test). Strong outliers (i. e. values > 3 IQR) were excludedFull size image4 DiscussionThis study measured the errors in the perceived position and dimensions of virtual models by users of the HoloLens 1 headset and investigated the relationship between these errors and the virtual models’ position and distance from the users’ eyes. An increased localisation accuracy for virtual hexagons on the right side of the field of view was found (Fig. 3). This may be partially due to ocular dominance, i. e. [SEP] Justify:

Output: The text contrasts the claim by discussing the errors in the perceived position and dimensions of virtual models during a study using the HoloLens 1 headset, indicating that there are limitations in the effectiveness of virtual reality in certain settings. It highlights that inaccuracies in vertex localisation and absolute area errors persist despite the use of VR headsets, which suggests that not all healthcare treatments can be effectively delivered using such technology.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: By contrast, the selective constraints on cell-surface TLRs are much more relaxed, and these TLRs present high levels of genetic and functional diversity across populations46,54. In the human population, up to 23% of individuals have damaging missense mutations and up to 16% present a nonsense mutation in at least one cell-surface TLR46,50, suggesting higher redundancy. The case of TLR5 — the receptor of flagellin — is particularly extreme, as the R392X nonsense variant, which has a dominant-negative effect55, is present at high frequencies (up to 23%) in Europeans and South Asians46,50. This suggests that TLR5 is not crucial for immunity to infection against at least some flagellated bacteria, and that accessory mechanisms of flagellin recognition, such as those involving the cytosolic receptor Ice protease-activating factor (IPAF; also known as NLRC4)56, may provide sufficient protection. Figure 2: Evolutionary dynamics and biological relevance of innate immunity genes. Genes that have undergone purifying selection are shown in red, and those that have evolved under weaker selective constraints are shown in blue. Genes for which no significant evidence of a selective constraint was observed are shown in grey. Colours reflect the intensity of the selective constraints on amino acid-altering variation, as obtained by the McDonald–random field method McDonald-random field method (omega and gamma)31 (Box 2). Genes presenting robust signatures of positive selection in all humans are outlined with a thick black line, whereas genes presenting robust signatures of positive selection that are restricted to specific human populations are outlined with a dashed black line. Endosomal Toll-like receptors (TLRs) show signs of stronger purifying selection than do cell-surface TLRs. Myeloid differentiation primary response protein 88 (MYD88) is the TLR adaptor molecule that has evolved under the strongest purifying selection, which indicates its central role as a pan-adaptor molecule. [SEP] Justify:

Output: The text is irrelevant to the claim since it discusses the genetic and functional diversity of Toll-like receptors (TLRs) in humans, their evolutionary dynamics, and the mechanisms of immune response, without addressing the concept of biophilia or any innate connection humans may have to nature.


Input: Task: corroborate the claim using the given text. Claim: Attention can be selectively focused, altering cognitive processing. [SEP] Text: 이러한 결과는 불안한 정서상태가 초점주의를 향상시켜 목표자극에 대한 처리를 가속시키지만, 억제적 통제에 대해서는 그러한 효과가 없음을 시사한다. 또한 피난 상황에서 방향선택과 관련하여 본 연구의 함의를 논의하였다. 키워드 the spatial Stroop task, the facilitation effect, the interference effect, an anxious mood, evacuation behavior 공간 스트룹 과제, 촉진효과, 간섭효과, 불안, 피난행동 참고문헌(34) 1. [학술지] Baumgartner, T. / 2006 From emotion perception to emotion experience : Emotions evoked by pictures and classical music of Psychophysiology 60 (1) : 34 ~ 1 2. [학술지] Birk, J. L. / 2011 Threat facilitates subsequent executive control during anxious mood Emotion 11 (6) : 1291 ~ 6 3. [학술지] Bolte, A. [SEP] Justify:

Output: The text corroborates the claim by indicating that an anxious emotional state enhances selective attention toward target stimuli, which alters cognitive processing outcomes. It suggests a facilitation effect in processing relevant stimuli when focused, supporting the idea of selective attention influencing cognitive processes.


Input: Task: contrast the claim using the given text. Claim: All healthcare treatments can be effectively delivered using virtual reality headsets. [SEP] Text: the tendency of individuals to favour visual input from one eye, typically the eye with which visual information is perceived more clearly (Lopes-Ferreira et al. 2013). Ocular dominance occurs in 97% of individuals of which 65% show a dominant right eye (Reiss 1997). Vertex localisation and area errors were larger for the shortest distance of the virtual hexagons from the participants’ eyes (65 cm) than for larger distances, i. e. 85 and 105 cm (Fig. 4). A reason for this may be that a 65 cm distance lies outside the optimal zone for the visualisation of virtual content with HoloLens 1, which was determined as 125–200 cm from the eyes by Condino et al. (2018), and lies further from this zone than 85 and 105 cm distances. Another reason may be a reduced viewing quality of the virtual models if users observe them from short distances (Bach et al. 2018). Centroid position errors over 5 mm represent a risk of incorrect localisation of perforator vessels during soft tissue flap surgery, which may lead to accidental injury to these vessels, thus compromising flap viability (Corbitt et al. 2014). In addition, the observed margins error, with strong outliers in 4. 3% of cases (6), are larger than in surgeons’ drawings of skin tumour resection margins using traditional tools (surgical markers, rulers and loupes), which have been reported to be around 1 mm (Lalla et al. 2003). The observed centroid position errors and margin shrinkage combined may compromise the complete excision of skin tumours or cause the inaccurate mapping of subcutaneous tumours (Table 2). Organization for Research and Treatment of Cancer (EORTC) reports a 17. 5% cumulative incidence of tumour recurrence associated with incomplete tumour excision (Poortmans et al. 2009). Therefore, the risk for potential errors over 1 mm must be carefully considered before implementing the use of AR headsets in clinical practice. It should be noted as a study limitation that a 12 × 12 cm marker was used as opposed to previous studies that used smaller markers (Luzon et al. 2020). Small markers are preferable for surgery, because they have a lower risk of occluding the surgical working area and thus interfering with surgical workflows. [SEP] Justify:

Output: The text contrasts the claim by highlighting the potential risks and errors associated with using augmented reality (AR) headsets in clinical practice, notably in surgical settings. It explains that centroid position errors and margin shrinkage could compromise the excision of skin tumors and emphasizes careful consideration of risks before implementing AR technology. This indicates that not all healthcare treatments can be effectively delivered via such technology, directly opposing the claim.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: Furthermore, all adaptors have been targeted by positive selection, either in the entire human lineage (MYD88 and sterile alpha and TIR motif-containing protein (SARM)) or in specific human populations (TIR domain-containing adapter molecule 1 (TRIF), TIR domain-containing adapter molecule 2 (TRAM) and Toll/interleukin-1 receptor domain-containing adapter protein (MAL)), suggesting advantages in terms of immunity that are shared by all humans or that are due to geographically restricted microbial exposure, respectively. Purifying selection has driven the evolution of most and pyrin domain-containing proteins (NALPs), whereas other cytosolic microbial sensors, such as the NOD-like receptors (NLRs), Ice protease-activating factor (IPAF) and MHC class II transactivator (CIITA) and most NOD subfamily members, as well as the RIG-I-like receptors (RLRs), have evolved under weaker constraints. NLR family, apoptosis inhibitory protein (NAIP) is not represented in the figure as no population genetic data are available. DAMPs, damage-associated molecular pattern molecules; HA, haemagglutinin; IFNs, interferons; -regulatory factors; LAM, lipoarabinomannan; LPS, lipopolysaccharide; LTA, lipoteichoic acid; MAPK, mitogen-activated protein kinase; MDA5, melanoma differentiation-associated protein 5; NF-κB, nuclear factor-κB; family CARD domain containing; NLRX1, NLR family member X1; NOD, nucleotide-binding oligomerization domain-containing; PG, peptidoglycan; PLM, phospholipomannan; RIG-I, retinoic acid-inducible gene I protein; tGPI, Trypanosoma cruzi-derived glycosylphosphatidylinositol. Full size imageThe evolutionary relaxation characterizing some TLRs appears to be specific to humans when compared with other primates51. This observation has been associated with reductions in the size of human populations (during the out-of-Africa migration), which compromised the efficiency of purifying selection and resulted in an increased frequency of deleterious alleles57. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses evolutionary biology and immune system adaptations of humans without mentioning biophilia or a connection to nature. It focuses instead on the evolution of various proteins and the effects of selection pressures in human populations.


Input: Task: corroborate the claim using the given text. Claim: Attention can be selectively focused, altering cognitive processing. [SEP] Text: [학술지] Phillips, L. H. / 2002 : Stroop and Emotion 2 (1) : 12 ~ 1 28. [학술지] Rowe, G. / 2007 Positive affect increases the breadth of attentional selection Proceedings of the of Sciences 104 (1) : 383 ~ 1 29. [학술지] Schuch, S. / 2015 Mood states influence cognitive control : the case of conflict adaptation Psychological Research-/ 79 (5) : 759 ~ 5 30. [학술지] Stroop, J. R. / 1935 Studies of interference in serial verbal reactions Journal of 18 (6) : 643 31. [학술지] van Steenbergen, H. / 2009 : Evidence for a Role of Affect in 20 (12) : 1473 ~ 12 32. [학술지] van Steenbergen, H. / 2010 In the Mood for Adaptation : Regulates Conflict-/ 21 (11) : 1629 ~ 11 33. [학술지] Yik, M. S. M. / 1999 Structure of self-reported current affect : Integration and beyond Journal of Personality and 77 (3) : 600 ~ 3 34. [학술지] Zwosta, K. / 2013 Mood states determine the degree of task shielding in dual-task performance Cognition and Emotion 27 (6) : 1142 ~ 6 TOP 초록 키워드 참고문헌 toggle menu 타입을 선택하세요 of an on Choice by Attention @10. 22172/cogbio. 2019. 31. 2. [SEP] Justify:

Output: The text includes references to several studies that point towards the influence of mood states and affect on cognitive control and attention. For instance, it mentions that mood states influence cognitive control and that positive affect increases the breadth of attentional selection. These studies support the claim that attention can be selectively focused, thereby affecting cognitive processing.


Input: Task: contrast the claim using the given text. Claim: All healthcare treatments can be effectively delivered using virtual reality headsets. [SEP] Text: However, small markers may also lead to errors that are not acceptable for surgery (Pérez-Pachón et al. 2021). In addition, our study did not include surgeon participants. Surgeons usually have increased dexterity compared to non-surgeons, due to their surgical training, and thus they are expected to show smaller errors (Sadideen et al. 2013). Moreover, this study did not measure changes in the hexagon shape, although this information would help to prevent complications derived from mismatches between flaps and defects (Kimura 2009). Finally, our results are limited to HoloLens 1 and cannot be generalised to other headsets. Experiments analysing user accuracy with AR headsets inform the research community and healthcare professionals on the readiness of AR technologies for their use in the operating theatre. Additional key aspects to be considered include usability, reliability, and workflow. These aspects, with accuracy likely being the next key barrier for implementation in the surgical arena, are especially relevant within the context of high-precision surgical tasks. Extensive research has explored this topic for a wide variety of surgical fields such as neurosurgery, cranio-maxillofacial surgery, or cardiovascular medicine (Gsaxner et al. 2023). With the advent of AR technologies tailored to surgical practice, HoloLens-like technology are expected to become an integral part of high-precision surgical setups within the next decade (Zhang et al. 2023). Due to the abstract nature of our experiment, our results can also be applied to other fields that involve high-precision tasks. Research on the application of HoloLens-like technologies to high-precision tasks outside of healthcare is currently limited, however, the authors expect that there will be applications within the fields of engineering, manufacturing, and repair in the near future. 5 ConclusionIn this study, we found that some model positions and the shortest distance (65 cm) led to larger localisation errors than other positions and larger distances. Localisation errors tended to be smaller for virtual models rendered on the right side of the user's field of view. Adjusting the location of virtual models according to this may help to maximise localisation accuracy. Developers and manufacturers should also aim for minimising localisation errors for distances of 65 cm or less between the user’s eyes and the virtual models, especially considering open surgery applications, where surgeons operate at an arm range distance from the surgical working area. [SEP] Justify:

Output: The text contrasts the claim by discussing limitations associated with the use of HoloLens and augmented reality (AR) in surgical settings. It emphasizes the importance of accuracy and reliability of AR technologies in high-precision surgical tasks, highlighting that the study's results cannot be generalized beyond the specific headset tested. The mention of errors that may occur during surgery and the need for improved usability, reliability, and workflows indicates that not all healthcare treatments can necessarily be effectively delivered using virtual reality headsets.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: However, it is tempting to speculate that such an evolutionary relaxation might also indicate that pathogens recognized by cell-surface TLRs have imposed a milder burden on humans than on other primates. In some cases, genetic variation at cell-surface TLRs may be advantageous for the host, as attested by the signature of positive selection detected in the TLR6–TLR1–TLR10 cluster (Box 4). Together, the major differences in the intensity of selection between intracellular and cell-surface TLRs indicate that the two groups differ in their biological relevance, with intracellular TLRs being essential and cell-surface TLRs being more redundant. This evolutionary dichotomy is likely to reflect the differences of the two TLR groups in terms of their subcellular localization, the type of microorganisms and ligands that they target, and their self-reactive potential14,38,39. Cell-surface TLRs detect microbial molecules, such as bacterial cell-surface lipopolysaccharides or flagellin, which are usually very distinct from host molecules. By contrast, intracellular TLRs principally sense nucleic acids, such as double-stranded RNA of viruses or the unmethylated CpG islands of bacterial and viral DNA. Although these microbial nucleic acids can be distinguished from host nucleic acids on the basis of specific chemical modifications58, there is still the risk that intracellular TLRs could be stimulated 'inappropriately' by self-derived nucleic acids, which may lead to autoimmunity59,60,61,62. Thus, the extreme conservation of intracellular TLRs might reflect the very narrow window they have to ensure effective pathogen sensing while preventing dangerous recognition of host nucleic acids and thereby minimizing the risk of autoimmunity. Cytosolic receptors: the RLRs and NLRs. Recent population genetics data have increased our understanding of the relative importance of the different members of the RLR and NLR families63,64,65. Similarly to intracellular and NLRs detect signs of infection or danger within the cell14,40,41,42. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the evolutionary aspects of TLRs and pathogen recognition without mentioning anything related to biophilia or the human connection to nature.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: -Cas and -based screening system for precise gene editing and targeted cancer therapy access Published: 30 May 2024 -Cas and -based screening system for precise gene editing and targeted cancer therapy Mingming Qin1,2 na1, Chunhao Deng3 na1, Liewei Wen4, Guoqun Luo1 & …Ya Meng4 Show authors Journal of 1. Fig. 1Schematic representative ofCas loci in Class 1 and Class 2 system. Class 1 system show multi-component effectors, while the Class 2 system have one effector. Three subgroups of Class 2 systems are presented. II-protein contains: Streptococcus pyogenes Cas9 (SpCas9), Staphylococcus aureus Cas9 (SaCas9) and Streptococcus thermophilus Cas9 (StrCas9), all of which have the tracrRNA sequences. which comprises Cas12a, Cas12b and Cas12c, exhibits distinct genome structures. Cas12b has the tracrRNA structure, while Cas12c only has one assistant protein cas1 for genome editing. Cas14 subgroup is not depicted in this figure. systems show few assistant proteins to identify RNA virus, however, type VI-B has csx27 and csx28 proteins to regulate nuclease activity. Illustrated according to Ref [14, 16, 20, 21]. Full size image/Cas system has been utilized for cellular genetic modification [22, 23] and the generation of animal models for cancer research [24, 25]. Furthermore, theCas-based genetic screening system was developed for cellular investigation [26,27,28], as well as in tumor studies [25, 29]. In addition, high throughput gRNA libraries have been established to enable efficient genetic screening, specially facilitating personalized treatment strategies for cancer patients individually [30]. In this review, we provide a comprehensive overview of theCas system and essential elements for successful screening system, including gRNA libraries, gRNA validation, and clinical application for cancer research. Furthermore, we explored the application of the screening system in cancer therapy from both ex vivo and in vivo investigation, aiming to elucidate the inherent advantages and potential obstacles for clinical precision medicine. [SEP] Justify:

Output: The text corroborates the claim by discussing a Cas-based screening system utilized for precise gene editing and genetic modification, indicating that CRISPR technology is indeed enabling targeted applications in cancer therapy and genetic research.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Intended for healthcare professionals email alerts BMA member login * Password * Forgot your log in details? Need to activate in via Openin via your institution Edition: company Toggle navigation The BMJ logo Site map form Searchsearch Search responses Search blogs Toggle top menu covid-19 ResearchAt a glance Research papers Research methods and reporting news EducationAt a glance Clinical reviews of the art What your patient is thinking Rapid recommendations & ViewsAt a glance to head Editor's choice Views and reviews responses CampaignsAt a glance Better evidence Climate change Divestment from fossil fuels Patient and public partnership Too much medicine authors Effect of patient. . . Effect of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial BMJ 2006; 332 doi: (Published 25 May 2006) Cite this as: BMJ 2006;332:1238 0. 2 (95% confidence interval 0. 1 to 0. 4) with the agenda form, by 0. 3 (0. 1 to 0. 6) with education, and by 0. 5 (0. 3 to 0. 7) with both interventions. The time required to manage each problem was not affected. The duration of consultations with the agenda form was increased by 0. 9 minutes (0. 3 to1. 5 minutes) and with the combined intervention by 1. 9 minutes (1. 0 to 2. 8 minutes). Patient satisfaction with the depth of the doctor-patient relationship was increased with the agenda form. The occurrence of “by the way” presentations did not change. patient completed agenda form before the consultation or general practitioner education about the agenda form, or both, enabled the identification of more problems in consultations even though consultations were longer. consultation between a doctor and patient is the core activity of clinical practice. 1 Anything that improves the quality of the consultation therefore has the potential to improve all aspects of health care. Although identification of why the patient has attended is a key objective of the consultation,2 doctors commonly fail to achieve this. 3 4 Consequently, patients report that they have been unable to discuss their concerns with their doctors5 or have received unwanted prescriptions6 or referrals. 7 Communication in the consultation can be improved by enhancing doctors' ability to facilitate communication or by assisting patients to communicate. Doctors' skills can be enhanced through education. [SEP] Justify:

Output: The text contrasts the claim by emphasizing the importance of in-person doctor-patient consultations, stating that 'consultation between a doctor and patient is the core activity of clinical practice.' It highlights that improving consultation quality is crucial for healthcare and notes that common issues in consultations include communication failures and unaddressed patient concerns, which VR technology is unlikely to fully resolve.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: The three RLR members, retinoic acid-inducible gene I protein (RIG-I; also known as DDX58), melanoma differentiation-associated protein 5 (MDA5; also known as IFIH1) and LGP2 (also known as DHX58), detect viral RNA and induce inflammatory cytokines and type I and type 41. RIG-I and MDA5 sense directly viral molecules, whereas LGP2 acts as a regulator of RIG-I and MDA5 signalling. The NLR proteins, which have a structure that closely resembles that of the resistance proteins (also known as R proteins) in plants16, are encoded by a family of 22 genes, which include the 14 members of the large and pyrin domain-containing protein (NALP) subfamily (NALP1–NALP14), the five nucleotide-binding oligomerization domain-containing (NOD) proteins (NOD1, NOD2, NLR family CARD domain containing 3 (NLRC3), NLRC5 and NLR family member X1 (NLRX1)) and other proteins, such as MHC class II transactivator (CIITA), IPAF and NLR family, apoptosis inhibitory protein (NAIP)40,42. NLRs either activate nuclear factor-κB and mitogen-activated protein kinases to induce inflammatory responses or participate in large cytoplasmic protein complexes called inflammasomes40,42. RLRs evolve under weaker constraints (weak purifying selection or neutrality) compared with other families of innate receptors, and this suggests that there is some degree of redundancy in their roles (Fig. 2). Within the RLR family, RIG-I displays the most constrained amino acid-altering variation, particularly in the carboxy-terminal and helicase domains (which are involved in RNA recognition)65. This may reflect the fact that RIG-I senses a broader range of RNA viruses than MDA5, which only recognizes picornaviruses. Moreover, the particular structure of RIG-I viral substrates (short double-stranded RNAs and 5′-triphosphate single-stranded RNAs)41 may have stricter binding requirements than MDA5 substrates (long double-stranded RNAs). [SEP] Justify:

Output: The text is irrelevant to the claim about biophilia. It discusses the roles of RLR and NLR proteins involved in immune responses and does not mention or support the concept of an innate connection between humans and nature.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: The application of Class 2 -Cas effectors and genome modification in cancer therapyType II effector Cas9 in cancer researchpyogenes Cas9 (SpCas9) and Staphylococcus aureus Cas9 (SaCas9), classified as the type II-A effectors, showed comparable genome editing efficiency for in vitro and in vivo study [21, 31,32,33]. These effectors enable rapid modification of cellular or animal models for transcriptional modulation via knockout/knockin or high throughput genomic screening [23, 34]. The compact size of SaCas9 renders it an optimal enzyme for in vivo AAV application. However, SpCas9, one of the pioneering Cas9 proteins, has been extensively investigated and utilized in gene editing. Three variants of SpCas9 have been developed, the wild-type Cas9, nickase Cas9 (nCas9), and dead Cas9 (dCas9). Cas9 mediated DNA cleavage with the two distinct active sites RuvC and HNH, under the assistance of (crRNA) and trans-activating crRNA (tracrRNA) ribonucleoprotein complex [8]. The dual-tracrRNA: crRNA chimera single guide RNA (sgRNA) was created and directed Cas9 nuclease to the potential target loci for site-specific DNA cleavage, initiating the genome editing system in vitro [35]. The binding of Cas9 to the adjacent sequence of three nucleotides, known as protospacer adjacent motif (PAM), triggers DNA cleavage by inducing double-strand breaks with its scissor-like activity [36]. The recently used Cas9-gRNA ribonucleoprotein (RNP) complexes remarkably increase fidelity and efficacy for double-strand DNA breaks with minimized cell mortality [37]. It also combined with repair donor to achieve site-specific correction of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in epithelial organoids [38]. Cre-dependent Cas9 knockin mouse was generated, and KRAS, p53, and LKB1 depletion resulted in carcinoma formation in these transgenic mice, providing a robust cancer model for research [24]. One mutation in D10A of Cas9 protein makes a nCas9, which improves genome editing specificity [39]. [SEP] Justify:

Output: The text corroborates the claim by detailing the mechanisms of CRISPR technology, specifically the Cas9 proteins which facilitate precise gene editing through site-specific DNA cleavage. It highlights the efficiency of Cas9 in editing genes for research purposes and applications, especially in cancer therapy, demonstrating that CRISPR indeed allows for accurate genome modification.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Nevertheless, although educational interventions have been shown to have beneficial effects on the observed behaviours of doctors8–11 few have been shown to improve the outcome of consultations with real patients. 12 Enhancement of patients' ability to participate in the consultation improves communication between the doctor and patient13 14 and patient outcomes. 13–17 These studies have used information packages and workshops to develop patient skills that are either condition specific or difficult to disseminate widely. One study, however, showed that simply encouraging obstetrics and gynaecology patients to write down three questions they wished to ask in their consultation reduced their anxiety more than giving them information. 18 This type of approach has the advantage of being relatively easy to disseminate. One of us previously developed a patient agenda form, to be completed by patients before they consulted with their doctor. 19 Before giving the form to their doctor, patients write down why they have requested a consultation and what they expect from it. Pilot studies in one practice indicated that the agenda form increased the number of problems identified in consultations but that the consultations were longer. McCann piloted a similar intervention, which also prolonged consultations, but despite patients asking more questions outcomes from the consultation were unchanged. 20 A second pilot study suggested that educating doctors about patients' agendas reduced the time required to manage each problem. 21 We examined the effect of the patients' agenda form and educating general practitioners on identifying the patients' agenda on the outcome of consultations. We hypothesised that patient satisfaction, the number of problems identified in the consultation, and the duration of the consultation would be increased by the interventions when used separately but when combined would reduce the time required to manage each problem. Both interventions would reduce the occurrence of “by the way” presentations, when patients raise extra problems after the doctor considers the consultation finished. Participants and methods We invited all general practice principals in Leicestershire and Nottinghamshire to take part in our study. Potential patient participants were those who requested an appointment in one of the study consultations of participating practitioners. Patient participants were told about the study by the receptionist and that they could consult with another doctor or at another time if they wished. Those who accepted an appointment in a study consultation were asked to think of a list of their concerns, to arrive five minutes earlier for the consultation, and to bring spectacles and an interpreter if required. No exclusion criteria were applied. [SEP] Justify:

Output: The text contrasts the claim by discussing various methods of enhancing doctor-patient consultations without mentioning VR technology. It highlights educational interventions and a patient agenda form that aim to improve consultation outcomes, demonstrating that traditional methods are still in focus. The text implies that rather than replacing consultations, enhancements to communication and interaction methods are being explored.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: Among NLRs, most NALPs have evolved under strong purifying selection (10 of the 14 NALPs)64 (Fig. 2), reflecting the rapid elimination from the population of mutations at these genes as a result of their highly deleterious effects. These observations are consistent with the idea that NALPs have acquired a function that is essential and non-redundant in host survival. By contrast, the weaker selective constraints characterizing and most NOD subfamily members64 testify to their higher degree of redundancy. In some cases, certain genetic variants at some RLRs or NLRs (for example MDA5, LGP2, NALP1, NALP14 or CIITA) have been targeted by positive selection in specific human populations, suggesting that functional variation at these genes and the resulting changes in the downstream immunological mechanisms have allowed for increased host survival under specific environmental pressures63,64,65. Taken together, population genetics studies have shown that the NALPs have evolved under much stronger selective constraints than other NLR members and RLRs, and the extreme NALP conservation may reflect the type of the ligands that are likely to be sensed by these molecules and/or the important nature of the responses triggered by them. These hypotheses need now to be experimentally validated. Soluble receptors: the humoral arm. In contrast to the cellular receptors described above, there are only scarce population genetics studies on secreted receptors, such as complement receptors, collectins, ficolins and pentraxins, which are all involved in highly diverse functions (for example, phagocytosis, opsonization and apoptosis)44,66,67. However, the case of the mannose-binding lectin (MBL) — an extensively-studied collectin that binds a broad range of microorganisms and activates the lectin–complement pathway66,68 — neatly illustrates the value of the population genetics approach for determining the ecological relevance of genes and mechanisms in immunity to infection. Conflicting results have been obtained by clinical and epidemiological genetic studies as to the detrimental or beneficial effects of MBL deficiency69,70. MBL deficiency has been associated, although not conclusively, with increased susceptibility to several infectious diseases, such as meningococcal infection or HIV infection71. [SEP] Justify:

Output: The text is irrelevant to the claim about biophilia and the innate human connection to nature. It discusses genetic evolution and immune responses, focusing on NLRs and NALPs, without mentioning any aspects related to biophilia or human-nature relationships.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: The combination of sgRNA pairs with nCas9 significantly enhances cutting specificity by 50-1000 folds in cell lines and mouse zygotes [40]. -Cas base editing using nCas9 enables precise incorporation of point mutations in genomic DNA without inducing double-strand breaks, demonstrating its potential in treating genetic diseases caused by base-pair alterations through adenine base editors (ABEs) or cytosine base editors (CBEs) [41]. In addition, DNA base editors combining with the leading platform adeno-associated virus (AAV) vector for viral delivery expanded the -base-edit toolkit for Prime-editing (PE) [42]. Meanwhile, the recently developed genome editing technique known as NICER utilizes Cas9D10A nickase to correct heterozygous mutations. It generates multiple DNA nicks and triggers gene correction via interhomolog homologous recombination (IH-HR) which rarely induces genomic alterations, making it a precise strategy to restore genetic diseases or single nucleotide mutations [43]. Except the precise single nucleotide restoration, cancer translocations were generated by double strand breaks and paired nicks with either Cas9 or nCas9, creating endogenous chromosomal translocations cell model for investigating tumor driving genes [44]. Catalytically inactive Cas9, a ‘dead’ protein (dCas9) with both mutations in D10A and H840A of RuvC and HNH domains, showed its popularity in gene regulation with inhibition, activation, and cell imaging and labeling [45]. Genome-scale screenings utilizing inhibition () and activation () have been employed to identify both known and novel genes involved in controlling cell growth and sensitivity to toxins [46]. Precise inducible gene knockdown or overexpression can be supported using dCas9-KRAB (Krüppel-associated box) or Cas9 combined with Expression promoter (TetO) [47]. Firstly, the fusion of dCas9 with transcriptional repressor produces the genetic tool [48]. The dCas9-BFP-KRAB repressor domain enables the suppression of gene expression [49]. Second, fusing dCas9 with RNA polymerase (RNAP) omega subunit upregulates gene expression [50], and dCas9-VP64 was used for transcriptional activation [51]. [SEP] Justify:

Output: The text corroborates the claim by detailing various CRISPR-related techniques such as the use of nCas9 for precise gene editing without inducing double-strand breaks. It highlights the capability of base editing and the NICER technique as 'precise strategies' for correcting genetic mutations and restoring genetic diseases, thus supporting the assertion that CRISPR technology enables precise gene editing.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Finally, our study gives no information on whether the identification of additional problems in a consultation results in fewer future consultations. If patients are encouraged to make their agenda more explicit by writing it down before the consultation, then general practitioners will identify an average of four additional new problems for each consultation session of 18 patients, although the consultation session will take 19 minutes longer. Educating general practitioners about the patient's agenda will result in the identification of six more problems and the session will last an additional 13 minutes. The combined intervention will enable the identification of an additional nine problems but sessions will be 34 minutes longer. Although this represents an increased workload for doctors, it may also represent a potential pool of unrecognised need among patients which, with the introduction of a simple intervention, can be addressed. What is already known on this topic Answering the question “Why have you come to see me today? ” is a key step in consultations, which is often not achieved Asking patients to prepare for the consultation by writing down questions they want to ask improves some patient outcomes What this study adds Training doctors to elicit the patient's agenda or asking patients to write down what they want from the consultation increases the number of problems identified and may increase patient satisfaction even though consultations are longer These interventions are not additive These interventions may reduce the pool of unidentified problems during the consultation patient's agenda form and doctor's encounter form are on bmj. comWe thank the patients and doctors who participated in this study. Contributors JFM devised and designed the interventions. JFM and RKM designed the study, JFM recruited all practitioners, delivered the educational intervention, processed and checked the integrity of all data, carried out the preliminary analysis, and contributed to writing the paper. RKM supervised the research, devised the strategy for presentation of the results, and wrote the first draft of the paper. CLG advised on, and carried out, the statistical analysis and contributed to writing the paper, in particular, the statistical and results sections. JFM and RKM are guarantors. of the of General Practitioners. Competing interests None declared. Ethical approval This study was approved by Leicestershire local research ethics committee. 1. ↵Spence J. The need for understanding the individual as part of the training and function of doctors and nurses. In: for Mental Health, ed. The purpose and practice of medicine. Oxford: Press, 1960; 271–80. 2. [SEP] Justify:

Output: The text contrasts the claim by emphasizing the importance of doctor-patient consultations and the identification of problems during these interactions. It discusses how consultations can lead to the identification of additional medical issues and enhance patient outcomes, highlighting that longer consultations are beneficial even as they increase the workload for doctors. This indicates that traditional consultations are still vital, thereby implying that VR technology is unlikely to completely replace the need for in-person consultations.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: However, MBL-deficiency alleles are common worldwide (they occur in up to 30% of individuals)69,72,73, suggesting that they may also have a protective effect, as reported for infections with intracellular pathogens such as Mycobacterium tuberculosis and Leishmania s75. Some population genetics studies have proposed that balancing selection has driven MBL2 diversity47,72, but others have failed to detect any evidence of selection favouring the increased frequency of deficiency alleles73,76. Indeed, when analysing larger population data sets, the pattern of MBL2 variation appears to be consistent with neutral evolution73. These population genetics observations provide novel insights that inform the long-standing and highly controversial debate as to whether MBL is protective, deleterious or both, and they suggest instead that the immunological mechanisms triggered by this lectin are largely redundant. So, other molecules or pathways, such as the ficolins or the C1q-dependent classical pathway, may compensate for MBL deficiency. Future studies exploring whether the genes involved in these pathways have compensatory mutations in MBL-deficient individuals should help to substantiate this hypothesis. Adaptor molecules: the TIR domain-containing adaptors. Linking the evolutionary fate of innate immune receptors with their corresponding adaptors, which associate with receptor proteins and initiate downstream signalling14, can further increase our knowledge of the biological relevance of specific immune pathways. This is best exemplified by population genetics data on the five Toll/IL-1R (TIR) domain-containing adaptors: myeloid differentiation primary response protein 88 (MYD88), Toll/interleukin-1 receptor domain-containing adapter protein (MAL; also known as TIRAP), TIR domain-containing adapter molecule 1 (TRIF; also known as TICAM1), TIR domain-containing adapter molecule 2 (TRAM; also known as TICAM2) and sterile alpha and TIR motif-containing protein (SARM), which are involved in the initiation of signalling downstream of TLRs and IL-1R-like receptors14,77. Across primates, the five adaptors have evolved under strong selective constraints48. In humans, MYD88 and TRIF display the highest degree of purifying selection (Fig. 2), indicating that the signals mediated by these two molecules are essential and non-redundant78. [SEP] Justify:

Output: The text is irrelevant to the claim regarding biophilia and the innate connection to nature. It discusses the population genetics of MBL-deficiency alleles, their effects on immunity, and the role of various adaptors in the immune system. There is no mention or implication of the concept of biophilia or any innate human connection to nature within the provided text.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: In addition, dCas9 protein serves as a valuable tool for labeling of endogenous genomic loci in living cells. By employing an optimized sgRNA fused with EGFP-tagged dCas9, repetitive elements in telomeres and various other regions can be robustly labeled [52]. A double-color labeling method was established by incorporating MS2 or PP7 RNA aptamers into the sgRNA, fused with the catalytically inactive Cas9 (dCas9) for direct visualization [53]. Finally, dCas9 can be employed for in vivo imaging of chromosomal dynamics and genome organization dimensions [47], allowing systematic fluorescent labeling of up to 10 proteins [48]. Summary of the type II Cas9 enzymes was depicted in Fig. 2. Fig. 2Summary of Cas9 proteins and modified nCas9 and dCas9 genome editing tools. (A) PAM for SpCas9 is NGG, while PAM for SaCas9 is with the ability to cut DNA double helix. (B) Mutation of D10A leads to the formation of nCas9 while both mutations generate dCas9 protein. (C) nCas9 can be applied for base editing such as CBE and ABE, also for Base editor and developed as NICER to repair heterogenous mutation. (D) dCas9 was modified to generate and labeling tools. dCas9: dead Cas9. nCas9: nickase Cas9. CBE: : Editor. RT: reverse transcriptase. pegRNA: prime editing guide RNA. Full size imageand type VI effectors in cancer researchMainly three subtypes of type V effectors were investigated for gene editing, named as type V-A, V-B and V-C. The type V-A effector Cpf1 (from Prevotella and Francisella 1), exhibits enhanced genome editing specificity attributed to a T-rich PAM (-5′TTTV) [54], resulting in a staggered DNA double stranded break [55]. Two candidate Cpf1 (Cas12a) enzymes, AsCpf1 from Acidominococcus sp. BV3L6 and LbCpf1 from Lachnospiraceae bacterium ND2006, show a robust genome editing ability in human cells compared to that of Cas9 [56]. [SEP] Justify:

Output: The text supports the claim by discussing various applications and mechanisms of CRISPR technology, particularly focusing on dCas9 protein and its role in gene editing. It describes how dCas9 can be utilized for in vivo imaging and labeling of genomic loci, highlighting the precision involved when combining sgRNA with dCas9 for specific targeting and visualization of genomic regions.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Nevertheless, most related to their patients as more than mere objects, but the doctors interacted with their patients as human beings in a trivial manner. We have used the term courteousness to describe how the doctors often displayed a friendly attitude, kept a good tone and emphasised the social relationship with patients. By courteousness we refer to a display of general respect for the patient as a fellow human being, but it is not to be taken as any deeper concern for the life of the patient. On the contrary, the doctors showed little curiosity about the individual and neglected more personal aspects of the patients' conditions, showing little or no existential care. The patients frequently spoke of their personal feelings—for example, describing how they had experienced the current event and how it had affected their lives, but this was rarely addressed or pursued by the doctors, who instead directed the focus away from personal meanings onto medical facts. These three dimensions of doctors' involvement emerged as a result of the analysis of the entire material; the cases presented below are observed encounters that are selected simply as illustrations of these dimensions. Case I: visiting the pulmonary specialistThe doctor greets the patient, a middle-aged man, inviting him to sit. He says he now has recovered from what was probably just an infection. The doctor turns to the computer, nodding occasionally while attending to the screen. The patient suddenly speaks up: “I have really been physically healthy all my life, right until my wife died three… three years ago. Three years ago. ” The doctor looks at her computer, showing no reaction: “Yes. ” Patient: “And… and then a great deal seemed to happen… and so the last three years there has been a lot concerning my heart and so, but… otherwise… I guess I am… relatively…” The doctor: “…But otherwise you have been healthy, yes? ” Patient: “Yes…” The doctor pulls her chair over to the patient and smiles: “Then there is the big question that is asked of everyone who comes here: Do you smoke? ”The doctor says she has some extra time and enthusiastically draws a curve explaining the effects of smoking on lung function. The patient tells her that he was healthy until his wife's death, and the doctor commends his healthy look. Suddenly she asks if he has any symptoms, which is denied. She says this makes him difficult to diagnose and they both laugh. [SEP] Justify:

Output: The text contrasts the claim by illustrating how doctors often fail to deeply engage with their patients on a personal level. It emphasizes that while doctors may interact with patients in a courteous manner, they tend to overlook the personal aspects and experiences of the patients, focusing instead on medical facts. This suggests that the human aspect of patient consultations is currently lacking, which indicates that replacing human interaction with VR technology could further diminish the depth of patient-doctor relationships rather than enhance them.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: and SARM are subject to more relaxed constraints, which indicates that their functions are more dispensable. The selective regime that has constrained the evolution of adaptor proteins to different extents has not prevented these genes from undergoing some episodes of positive selection78,79. Collectively, the integration of population genetics data from the TLRs and TIR-containing adaptors has shed light on the mechanisms and pathways triggered by these molecules78 (Fig. 2). MYD88 has a pan-adaptor role77, so a strong constraint is expected, but TRIF has also evolved under strong purifying selection despite not functioning as a pan-adaptor. TRIF is involved in signalling downstream of TLR3 and TLR4 (Ref. 77), and of these two only TLR3 evolves under purifying selection46. Indeed, clinical genetic studies have revealed that rare mutations affecting the TLR3–TRIF pathway underlie herpes simplex virus 1 (HSV-1) encephalitis in childhood45,80,81. This suggests that the entire pathway activated by TLR3 in a TRIF-dependent manner is non-redundant in host defence, at least against HSV-1 (Refs 45, 78). Together with immunological, clinical and epidemiological approaches, future population genetics studies aiming to dissect the selective signatures at the level of entire signalling pathways will allow us to further delineate the most critical mechanisms involved in innate immunity to infection. Effector molecules: interferons and AMPs. The signalling pathways initiated by adaptor proteins culminate in the expression of cytokines, including interleukins and IFNs, chemokines, members of the tumour necrosis factor (TNF) family and growth factors. Among these effector molecules, IFNs have been extensively studied82, but the biological relevance of the different IFN subtypes for host survival remains largely unknown. Like other families of innate immunity genes, IFNs belong to a multigene family of highly paralogous loci, so gene conversion can markedly alter their genetic diversity, making population genetics data more difficult to interpret83. Recent analyses have shown that the three IFN families and their individual members have followed very different evolutionary trajectories, ranging from highly constrained to redundant and expendable84,85. [SEP] Justify:

Output: The text is irrelevant to the claim concerning the concept of biophilia and the innate connection of humans to nature. It discusses various aspects of innate immunity, adaptor proteins, and cytokine expression without any mention of biophilia or human connections to nature.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: Furthermore, successful generation of gene knockout transgenic mice was achieved using both AsCpf1 (40. 7%) and LbCpf1 (28. 6%), providing a wonderful animal model for research [57, 58]. Multiplex genome editing was conducted using Cpf1 from Aspergillus aculeatus strain TBRC277 [59] and AsCpf1 was engineered with adeno-associated viral vectors (AAVs) for multiplex genome editing of mouse brain in vivo [60]. One-step generation of homology-directed repair (HDR) and checkpoint knockout CAR-T (-T) was achieved with the adeno-associated virus andCpf1 system, establishing an efficient AAV-Cpf1 double knockin system and opening new possibilities for cancer research [61]. The type V-effector Cas12b (C2c1) discovered in Bacillus hisashii (BhCas12b) showed a nickase effect at 37 °C for human gene editing, while BhCas12b v4, containing K846R/S893R/E837G mutants, demonstrated strong genome editing ability in human cells comparable to SpCas9 [62]. While the type V-effector Cas12c (C2c3) is a site-specific ribonuclease generating mature crRNAs for DNA targeting, crRNAs direct DNA binding by Cas12c without DNA cutting, providing a DNase-free pathway for transient antiviral immunity [63]. While both type II and type V are effective for DNA targeting in the genome level, the type VI effector Cas13 exhibits efficacy in treating genetic diseases and rescuing diseased sequences at the RNA level. They provide valuable genetic tools for diagnosis and degradation of viruses such as HIV and HPV [64, 65]. Several Cas13 proteins were characterized, such as Cas13a, Cas13b, Cas13bt and Cas13d, showed the efficiency to cleave single stranded RNAs [66,67,68]. Of which Cas13a based (Specific High-) system can detect Zika or as well as somatic mutations in cell free DNA (cfDNA) samples such as serine/threonine kinase (BRAF) V600E cancer mutation [69]. Shortened detection time and high sensitivity were applied for virus detection via 2 system [70, 71]. [SEP] Justify:

Output: The text corroborates the claim by detailing various applications of CRISPR technology, specifically mentioning successful gene editing capabilities through the use of type V-effectors such as Cas12b and Cas12c. It states that these systems are effective for gene editing at both the DNA and RNA levels, highlighting the creation of gene knockout transgenic mice and mentioning their effectiveness in human gene editing. This illustrates the precision and versatility of CRISPR technology in gene editing as asserted in the claim.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Referring to the computer system requiring a diagnosis she enters ‘COPD’. The patient says another doctor suggested asthma: “…my son has asthma, but it…was also what my wife died from, and… And asthma runs in the family. ” The doctor stares at the screen, nods and states that further follow-ups are unnecessary. The patient says that he agrees, but goes on to raise additional concerns. The doctor quickly raises her head: “Is there anything else you would like to ask? ” “No! ” he vigorously declares and rises to leave. The doctor leads him out and wishes him well. The doctor's first concern is to define the medical problem, and she focuses more on the computer than on the patient. She relies on medical facts from the records, which are read out loud. The doctor overlooks the patient's own accounts of his life and he is declared healthy on the basis of a test result. When the patient plucks up the courage to mention that his wife has died, the doctor ignores it. Instead of addressing this existential aspect, she quickly changes the subject with a medically focused question about smoking. The next time the subject is brought up, the doctor comments on the patient's physical condition instead. The patient mentions his deceased wife three times, finally revealing that she died of asthma, but any potential anxieties related to his own lung condition are not touched upon. The doctor explicitly states that she has plenty of time, but even so the clearly existential dimensions of the patient's suffering are avoided. Nevertheless, they speak in a jovial manner. The doctor politely stands up to greet the patient and invites him to sit. She does not rush the consultation, answers the patient's questions about lung function and exercise and takes time to explain matters in detail. Smiling and laughing, she appears to value the social contact. An ambiguous element to the expressed courteousness is revealed, however, when the doctor's otherwise polite request for questions actually serves to interrupt the patient and bring an end to the consultation; a sign the patient seems to sense. Case II: the anaesthesiologist's roundAn elderly woman sits in bed, glancing regularly at the door. “Mrs Peterson, is that you? ” The doctor smiles, introduces himself as an anaesthesiologist and gets a chair. [SEP] Justify:

Output: The text contrasts the claim by illustrating a traditional doctor-patient consultation where the doctor relies heavily on a computer for diagnosis rather than engaging deeply with the patient's personal experiences and concerns. This example suggests that human interaction and personal connection between doctors and patients still play critical roles in consultations, which implies that VR technology may not entirely replace the nuances of these interactions anytime soon.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: Some type I IFNs, such as IFNα6, IFNα8, IFNα13 and IFNα14 and the type II IFNγ, have evolved under strong purifying selection, displaying very low levels or even a complete absence, as in the case of IFNγ, of amino acid-altering genetic variation (Fig. 3a). Clinical genetic studies have shown that immunodeficiencies due to defects in the type I IFN pathway strongly affect antiviral immunity, and disorders of the IFNγ circuit are associated with Mendelian susceptibility to mycobacterial disease (MSMD)82. The integration of population and clinical genetic data thus indicates that at least IFNγ and a subgroup of type I IFNs have a crucial, non-redundant role in antiviral and anti-mycobacterial immunity, respectively82,84,85. Figure 3: Major differences in selective pressures characterize the evolution of the human interferon families. a | Type I, type II and type III interferons (IFNs) display different levels of functional diversity. The circles represent the proportion of chromosomes for each IFN subtype carrying different types of functional variants in the general population. For each circle, the proportion of chromosomes carrying at least one non-synonymous polymorphism is shown in red, and the proportion carrying at least one nonsense polymorphism is shown in black. The blue segment corresponds to the proportion of chromosomes carrying neither non-synonymous nor nonsense polymorphisms. The IFN subtypes in boxes are those for which statistical significance of strong purifying selection was obtained84,85. A schematic representation of the signalling pathways activated by the interaction of type I, type II and type with their corresponding receptors is also presented. b | are the only group of IFNs that have evolved under the action of positive selection, specifically in European and Asian populations. The scheme shows the distribution of the genetic variants under positive selection across the genomic region in which the three type genes are located. Note that one of the positively selected single-nucleotide polymorphisms (SNPs) in the interleukin-28B (IL28B) region (SNP −3180A>G, rs12979860) has been recently found to lay within the newly discovered IFNL4 gene, which is located upstream of IL28B123. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses immune system genetics and interferons rather than addressing the concept of biophilia or any innate connection humans may have to nature.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: enables to identify EGFR-T790M mutation in patient DNA with high efficiency by detecting 0. 6% mutant ratio samples [72], this system was also used for DNA and RNA detection with single-base specificity and attomolar sensitivity in cancer patients samples [73]. Cas13b was used to fight RNA viruses such as porcine reproductive and respiratory syndrome virus (PRRSV) [74], chikungunya (CHIKV) and dengue in mosquito cells [75] as well as SARS-CoV-2 resistance [76, 77]. Since Cas13b targets RNA without interfering genome sequence of the targeted gene, it provides a potential safer alternative to Cas9 enzymes. Catalytically inactive Cas13b (dCas13b) was engineered to direct adenosine-to-inosine deaminase for precise base editing, enabling the to I Replacement () RNA editing platform. This platform can be utilized in transcriptome engineering of advanced leukemias, as well as head, liver, and breast cancers, thereby demonstrating a feasible strategy for investigating gene function in cancer at the RNA level [78, 79]. The RNA-targeting -Cas13 system showed promising roles in cancer diagnosis, therapy, and research; with the ability for early detection of cancer markers in liquid biopsy samples, degradation and manipulation of cancer-related mutant transcripts, as well as identification of novel therapeutic drug targets described in the recent review [80]. Altogether, the class 2 effectors expanded the currentCas toolkit. Cas9 possesses recognition ability of specific target sequences, and has the genomic editing ability for precision cancer treatment and mutation detection [2]. Meanwhile, the recently discovered Cas12 and Cas13 expand RNA editing tool, providing novel genetic methods for cancer diagnosis and molecular examination of cancer research [3]. The application of screening system in cancerThe development ofCas system and high-throughput sequencing makes genetic screening easily accessible in basic biology, drug discovery, and personalized medicine for cancer therapy [3]. Cas9 nuclease is a preferred choice for genetic screening, and has been used for genomic modification in multiple researches [26, 28, 81, 82]. One-step generation of multiplex genome mutations viaCas9 system was successfully achieved in mice, facilitating in vivo functional analysis of redundant genes [83]. screening system was developed based onCas combined with thousands of gRNAs integrated into viral vectors [81, 84]. [SEP] Justify:

Output: The text corroborates the claim by discussing the capabilities of CRISPR technology, specifically highlighting how the Cas9 enzyme has genomic editing ability for precision in cancer treatment and mutation detection. It explains that the system facilitates in vivo functional analysis of genes and emphasizes the ability of Cas9 to generate multiplex genome mutations, thus reliably contributing to precise gene editing.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: But this we can… We can manage to radiate this one, I'm sure. ”Left alone for a moment, the patient and his wife express anxiety at the rapid progress of the disease. In a timid voice, the wife questions the treatment when the doctor re-enters the room, and he briefly explains why radiation is the preferred treatment, going into details about the radiation procedure while the patient listens and nods. He sums up the plan, but the patient makes no move to leave. The wife brings up the liver metastasis, but the doctor dismisses her. The patient nods: “Right, right. Yes, yes. ”, but he does not move. After a moment of silence, the patient finally rises: “Well, well… But then… I guess it sounds okay then. ” The doctor smiles, says “see you later” and shakes their hands. Again, the doctor's strong medical concerns guided the conversation, overshadowing other important matters. Even though all the treatment is palliative, the patient's underlying existential agony is never addressed, and is even actively disregarded. The doctor focuses on the medical data and only allows the patient to comment on this. The computer, rather than the patient, is asked about the reason for the consultation, which is defined as ‘growth of one of the metastases’. The doctor avoids obvious existential concerns; when the patient talks about the tumour, the doctor does not address the underlying fear but asks about symptoms. Likewise, when the patient's increasing tiredness is brought up, he is made to quantify his activity levels. Explicit worries are met with medical answers, and the patient's dying process is even described as ‘a catabolic condition’. The tacit existential dimension appears uncomfortably present at the end, when the fears that are unaddressed seem to prevent the patient from leaving. But the doctor also shows courteousness, and is attentive to both the patient and his wife, maintaining a good atmosphere and often smiling. He is polite, listens patiently, takes time to answer questions and does not hurry the patient out. Still, the light tone and the almost cheerful doctor make a stark contrast to the patient's grave situation. These contrasts are highlighted at the end of the consultation when the doctor says he will see them later, when they are probably all aware that there might be no “later” for this patient. [SEP] Justify:

Output: The text contrasts the claim by depicting a traditional doctor-patient interaction that emphasizes the importance of personal communication and emotional support in medical consultations. It illustrates how the doctor focuses on medical data while neglecting existential concerns of the patient, suggesting that human elements in consultations cannot be easily replaced by technology, such as VR.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: Highlighted mutations result in amino acid changes, whereas the rest are non-coding SNPs. Signatures of positive selection were detected in Asia for the variants in IL28A and IL28B, and in both Asia and Europe for that in IL29. Figure is modified from Ref. 84. γ-activated site; α/β receptor; IFNγR, IFNγ receptor; IFNλR1, IFNλ receptor 1 (also known as IL-28Rα); IL-10Rβ, IL-10 receptor-β; IRF9, IFN regulatory factor 9; ISRE, interferon-stimulated response element; JAK, Janus kinase; STAT, signal transducer and activator of transcription; TYK, tyrosine kinase. Full size imageBy contrast, other type I IFN subtypes (mainly IFNα10 and IFNɛ, but also IFNα1, IFNα4, IFNα7, IFNα16 and IFNα17) have accumulated missense or nonsense mutations at high population frequencies (Fig. 3a), suggesting that their functions largely overlap with those of other IFN subtypes84. The varying degrees of genetic diversity and redundancy displayed by type I IFNs suggest that there may be variability in the antiviral potencies and/or expression pattern of the different IFN subtypes. Finally, genetic variants at type have been targeted by positive selection, conferring a selective advantage to Eurasian populations84 (Fig. 3b). Another set of effector molecules that have been thoroughly studied with population genetics approaches are the AMPs. In particular, the defensins are an AMP family with broad antimicrobial activities and non-immune functions, such as in reproduction or cell signalling86. In humans, the α- and β-defensin multigene families contain multiple paralogous genes, with some genes displaying copy-number variability87,88. Comparative analyses of α- and β-defensins in human and non-human primates have revealed that episodes of purifying, positive and balancing selection have driven the evolution of these gene families88,89,90,91. These complex patterns may reflect the need to preserve the functional integrity of these molecules while favouring, in several cases, functional diversity to provide responses to a wide range of pathogens. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses genetic mutations, positive selection in populations, and antimicrobial peptides, without any reference to the concept of biophilia or the human connection to nature.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: These libraries harbor gRNAs targeting various genes, and have received up to 1000 annual requests globally, enabling unbiased, phenotypic forward genetic screening [17]. The first whole genomic gRNA libraries for both mouse and human were generated with mouse lentiviral gRNA library containing 87,897 gRNAs for 19,150 coding genes, naming as (GeCKOv1), and was established to screen out unknown genes for Clostridium septicum alpha-toxin or 6-thioguanine (6TG) drug resistance [81]. However, low viral titer of the lentiviral delivery systems in GeCKOv1 limited the usage for biological screening, and genome-scale knockout v2 (GeCKOv2), contained 123,411 unique sgRNAs targeting 19,050 annotated protein-coding genes and 1000 control sgRNAs (sg-NTCs), resulting in a 10-fold increase for viral generation [84]. Optimized mouse gRNA libraries targeting 20,611 genes with 130,209 gRNAs were also established with 100-fold increase of functional viral titer [84]. Innovative strategies of -Cas9 system have been developed for large-scale genome knockout and transcriptional activation [85], as well as combinatorial genetic screening [27]. Processes for gRNA library generation and amplification were illustrated as depicted in the following Fig. 3. Fig. 3Schematic representation of gRNA library construction and virus production. (A) Oligoes synthesis and vector construction for gRNA library. (B) Amplification of gRNA library by bacterial culture, collection, and plasmid extraction. (C) PCR examination and sequence confirmation for library coverage. (D) Plasmids transfection and virus production with a certain gRNA library. Full size imagegRNA libraries for cancer researchVarious of genome-scale gRNA libraries were established for screening, and some gRNA libraries for specific selected genes were also established with small capacity. Established gRNA libraries of genome wide and specific selected targets for cancer research were summarized in the Table 1. Human lentiviral GeCKOv1 library (lenti1) was established for high throughput gene targeting of 18,080 genes, with 64,751 unique gRNAs total, and was used for cell viability-related gene screening in cancer. [SEP] Justify:

Output: The text corroborates the claim by detailing the establishment of gRNA libraries used for gene targeting and genetic screening, which are fundamental components of CRISPR technology. Specifically, it mentions the creation of gRNA libraries that can target thousands of coding genes, thereby supporting the idea that CRISPR enables precise genetic modifications. The mention of optimization and innovative strategies for the -Cas9 system further reinforces the ability of CRISPR technology to allow targeted gene editing.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: DiscussionThe study confirms our earlier findings: the doctors' main focus was on medical problems, which overshadowed other aspects of the consultations, most notably the existential dimensions. 17 Personal meanings of the patients' conditions were systematically omitted or overlooked. Others have described doctors' lack of empathetic responses and failure to respond to patients' clues. 21–23 The regularity of this conduct suggests that it should not be taken as an example of bad medical practice, but as part of the ordinary interactions between doctors and patients—that is, a function of ‘medical processing’. 24 Bioethicists, as well as a major humanist movement in medicine, have called attention to the suffering of the patient, requested personal involvement of the doctor and emphasised the need to address patients as whole human beings with unique lifeworlds. 25–27 Yet, in order to perform their clinical tasks, doctors must apply their scientific medical knowledge to their patients, which involves some objectification and a certain disregard for personal narratives; a suggestion advanced by medical sociologists decades ago. 28 If it is inevitable that patients are treated as objects in order to help them medically, this might illuminate why the humanistic medical ideal has been so hard to achieve. When doctors disregard patients' personal accounts, they risk missing information that is clinically important, making the consultations less medically effective. In the second case, probing the elderly woman's fear of surgery might have lessened her anxiety more than tranquillisers. But what is at stake here is more than optimising patients' medical treatment. By ignoring expressed existential matters, doctors disregard their patients' humanity, which is a moral offence that is often perceived negatively. 29 At the core of the conception of morality and human dignity is the idea that individuals are not reducible to objects, but intrinsically valuable. 30 While most patients probably allow for this objectification, those with conditions that fundamentally affect their personal lives may be particularly vulnerable. Although the study confirms doctors' lack of personal curiosity and existential care, it also reveals that they are not insensitive to their patients as individuals. Indeed, the doctors in our study demonstrated a respect for their patients as fellow humans through social contact, polite behaviour and friendliness. Their strong medical focus often led the doctors to neglect personal accounts, but patients were also clearly treated with courteousness. While this ambiguity of professional care was exposed in many of the cases observed, there is little to suggest that the doctors were aware of it. [SEP] Justify:

Output: The text contrasts the claim by highlighting the limitations of current medical consultations and the necessity of personal engagement, which implies that replacing human interactions with VR technology may not effectively address the human dimensions of healthcare. It discusses how doctors often overlook existential aspects of patient interactions and the moral implications of treating patients as objects. This suggests that while technology can aid medical processes, it cannot replace the essential human contact that recognizes patients' individuality and humanity.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: An interesting example of increased functional diversity is provided by the human β-defensin gene DEFB1, which has evolved under the action of long-term balancing selection91, a process that is thought to be extremely rare outside the MHC genes. The balancing selective event has been localized to the promoter region of DEFB1, where increased functional variation (through heterozygosity) appears to have conferred a selective advantage, possibly against severe sepsis91,92. Overall, population genetics studies of effector molecules such as IFNs or AMPs emphasize the complex events of selection characterizing these molecules. Although the nature of such variable pressures is not totally clear, the identification of individual genes, such as specific IFN subtypes, subject to strong constraints or to positive evolution paves the way for additional studies to evaluate the potential of these molecules for use in vaccination, diagnosis and treatment. Selection patterns and immunological relevance The examples discussed above illustrate how the delineation of the selection mode that has driven the diversity of innate immunity genes can complement immunological and clinical and epidemiological genetic studies. Receptors such as endosomal TLRs and most NALPs, adaptors such as MYD88 and TRIF or effector molecules such as a subset of type I IFNs and IFNγ have been targeted by strong purifying selection46,48,51,64,78,84,85, highlighting the essential and non-redundant nature of the immunological mechanisms involved. Moreover, the fact that selective constraints acting on RLRs are weaker than those acting on endosomal TLRs46,51,65, even though both types of receptors detect nucleic acids, might reflect some degree of redundancy for RLR-mediated antiviral immunity. Similarly, the weaker constraints acting on most and CIITA subfamily members and cell-surface TLRs with respect to NALPs46,64 suggest greater redundancy in the pathways triggered by the former molecules in response to microbial products and stress signals (Fig. 2). Extreme cases of redundancy are provided by molecules such as MBL or TLR5, for which the frequency of loss-of-function alleles can increase in the population by genetic drift46,50,73,76. This contrasts with other situations in which gene loss has conferred an advantage to the host. [SEP] Justify:

Output: The text does not address the concept of biophilia or the innate connection between humans and nature. Instead, it discusses genetic diversity, immunological mechanisms, and evolutionary pressures on specific genes and receptors in the context of immunity. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: Total 5920 candidate enhancers were perturbed by the dCas9-KRAB enzyme, establishing the multiplex, expression quantitative trait locus (eQTL) framework, and total 664 cis enhancer-gene pairs were identified and enriched based on 254,974 single-cell transcriptomes in K562 derived from a chronic myologenous leukemia patient [49]. Undescribed immunotherapy targets for transplantable melanoma tumors in mice were explored with the 9992 sgRNAs targeting 2368 genes selected from transduced cells, establishing the in vivo genetic screen tumor models [88]. Recurrently mutated genes derived from pan-cancer datasets were recognized as well-known tumor suppressors genes (TSGs) or oncogenes. Total 49 orthologs of human TSGs were found in mouse genome, and the mouse TSG library containing 280 sgRNAs targeting 56 different genes (7 housekeeping genes) were used for tumor metastasis analysis [89]. Table 1 gRNA libraries for cancer researchFull size tableThe improvements of specificity and validation methods for gRNA LibraryThe procedure to perform pooled genome-editing experiments was clearly described, and successfulCas9 screening needs the specific and efficient gRNA sequence with proper quality and low off-target effect [91]. Off-target predictions calculated by algorithms indicating false positives and quantified error rates were developed by Bowtie and BWA sequencing methods, or considered by MIT-Broad score and the CFD score as summarized in previous reviews [92]. Computational tools for sgRNA designing with low off-target and high on-target efficacy and specificity have been developed and summarized in 2018 [93]. Several methods have been built for eliminating off-target results such as the utilization of high-efficiency delivery RNP tool, modification of the gRNA sequence, and improvement the specificity of Cas9 Enzymes [94]. The computational tool established high-quality gRNA libraries by selection according to off-target and on-target predictions, it also helps with vector cloning, gRNA validation and expression with primer designing and restriction enzymes depiction [95]. Optimized on-target efficiency prediction model was generated to illustrate the cleavage ability of gRNA sequence ( [96]. provides a robust and user-friendly computational pipeline to evaluate effects of coding and noncoding sequences and select off-target sites [97]. [SEP] Justify:

Output: The text corroborates the claim by detailing the use of the dCas9-KRAB enzyme and sgRNAs for gene editing in various experimental contexts, emphasizing the focus on improving specificity and reducing off-target effects, which are critical aspects of precise gene editing. It discusses the development of computational tools and methods that enhance the efficiency and accuracy of CRISPR applications, explicitly supporting the notion that CRISPR technology can enable precise modifications of the genome.


Input: Task: contrast the claim using the given text. Claim: VR technology will soon replace all forms of patient consultations with doctors. [SEP] Text: Often, patients were handled in an almost mechanical manner, suggesting that the doctors conceived the circumstances as straightforward and uncomplicated. They shifted readily from talking cheerfully to patients, to reducing them to medical objects by letting the dialogue drift into a physical examination, or looking at the computer while making conversation. The doctors' overt expressions of courteousness might actually conceal the ongoing objectification for both doctor and patient, leading the former to perceive the consultation as straightforward and satisfactory. When personal concerns were overlooked, the doctors' friendliness often seemed to make their patients puzzled and unable to voice any protest. When it comes to professional caring, the study reveals the importance of distinguishing between doctors' existential care, which they mostly lack, and their courteousness, which they clearly display. Various attempts to foster professionalism among medical students and doctors have demanded empathy, altruism and integrity. 31 However it is uncertain whether it is possible for doctors to care for patients existentially while also attending to their clinical responsibilities which requires them to apply a depersonalised medical science. Courteousness may improve the doctor–patient relationship, but the moral offence of being handled like a medical object cannot simply be undone by a friendly and polite doctor. Doctors should be familiar with the negative effects of their professional care even if they are unavoidable. When doctors are unable to follow-up on a patient's personal perspective, they should be aware of the moral harm caused by this rejection. They should seek to minimise it by attending to his/her humanity as far as possible within the medical setting, and apologise when unable to address personal issues. Courteousness can thus have moral significance if expressed, not to conceal an ongoing medical objectification, but to recognise the patients' humanity, which is always threatened in a professional doctor–patient relationship. Our qualitative findings cannot be generalised in the same way as quantitative results. 32 The consultations were taped at one Norwegian hospital, and care should be taken in applying our findings to other fields. Medical practice in Norway is not fundamentally different from that in other Western countries, suggesting that the results are transferable to similar settings elsewhere. Our findings are also in accordance with similar studies from other countries, as highlighted in this discussion. We had a large sample size and the participant doctors varied in specialty, age and experience. However, only hospital doctors were included, and it is possible that general practitioners attend more to the patients as people. [SEP] Justify:

Output: The text contrasts the claim by discussing the inherent limitations of current doctor-patient interactions, emphasizing that medical consultations often reduce patients to objects. It highlights the moral implications of such objectification, suggesting that the personal aspects of patient care are neglected. This implies that while technology might aid consultations, it cannot fully replace the essential human elements of care that are currently lacking in practice.


Input: Task: pass the claim using the given text. Claim: The concept of biophilia suggests humans have an innate connection to nature. [SEP] Text: For example, the increased frequencies of loss-of-function alleles of DARC (which encodes Duffy antigen/chemokine receptor) or CASP12 (which encodes inactive caspase 12) is a result of positive selection that is likely to be due to their protective effects against Plasmodium vivax infection and sepsis, respectively93,94. The occurrence of positive selection attests to more dynamic immunological mechanisms, variation in which has been beneficial for the host8,9,10,45. These positive selection events can be ancient and shared by all humans. Such is the case for the adaptor MYD88 (Ref. 78): a functional change in this protein may have favoured the survival of the entire human species. The human MYD88 differs from its primate orthologue by a single amino acid substitution (H80Q), which might represent the target of selection48,78. This variant is located within the DEATH domain, which is crucial for downstream protein–protein interactions, and mutations in this domain have been associated with defective immunity to infection95,96. Conversely, other events of positive selection seem to be more recent and restricted to specific populations, such as those detected at some -containing adaptors and type 63,64,65,78,79,84. So, the advantage conferred by such events is more dependent on environmental variables, possibly related to exposure to pathogens. For example, a variant in MDA5 (R460H) has been targeted by positive selection in Europeans and Asians63,65, suggesting an advantage to host defence that could be related to the sensing of particular RNA viruses by this sensor. Population genetics thus helps us to differentiate between genes with a high degree of redundancy and genes that are essential and non-redundant. The identification of essential genes is particularly important for molecules with poorly described functions, such as most NALPs, as this helps to prioritize which genes should be studied from an immunological standpoint. Does the evolution of innate immunity genes and their signatures of selection reflect a quest for improved host defence against pathogenic microorganisms? The answer is yes, but not exclusively. It is obvious that pathogens are likely to be a major force exerting pressure on host genes26,97. However, we coexist with millions of symbiotic, generally non-pathogenic microorganisms, and these can also be recognized by innate immunity receptors98,99,100,101,102. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses evolutionary genetics and the immune system without addressing the concept of biophilia or any innate connection humans have with nature. The focus on genes, positive selection in human populations, and immune responses does not relate to the emotional or psychological connection implied by biophilia.


Input: Task: corroborate the claim using the given text. Claim: CRISPR technology enables precise gene editing. [SEP] Text: For precise gene selection analysis, the Model-based Analysis of Genome-wideCas9 Knockout (MAGeCK) is the optimized method for both positive and negative selection, which offers high sensitivity and low FDR regardless of sequencing depth or sgRNA numbers for a single gene [98]. Besides that, intergration deficient lentiviral (IDLV) capture [99], and high-throughput genome-wide translocation sequencing (HTGTS) [100] are other methods for off-target detection. Analysis of gRNAs abundance in pooled libraries plays an important role in targeting efficiency and screening accuracy and specificity. PCR products of gRNA library vectors can be sequenced on Hiseq 2500 and aligned to sgRNAs by Bowtie, an ultrafast, efficient program for aligning short DNA sequence to large genomes [101]. Rigorous analytical methods mitigate the false discovery rates generated by screens via a Bayesian classifier of gene essentiality [102]. Sequence quality control can also be carried out under the guide of ( and statistical enrichment and gene depletion were calculated by hit calling algorithm STARS ( based on normalized fold changes [103]. High-content downstream gRNA library sequence validation in tumor immunology were summarized in the recent review [29]. Generally speaking, breaks labeling, enrichment on streptavidin and next-generation sequencing (BLESS) [104], genome-wide unbiased identification of DSBs enabled by sequencing (GUIDE-seq) [105, 106] and discovery of in situ Cas off-targets and verification by sequencing (-seq) [107,108,109] were used as cell based methods with direct sequencing. More sensitive biochemical methods such as digested genome sequencing (Digenome-seq) [110,111,112], selective enrichment and identification of adapter-tagged DNA ends by sequencing (SITE-Seq) [113], circularization for in vitro reporting of cleavage effects by sequencing (-seq) [114, 115] and circularization for high-throughput analysis of nuclease genome-wide effects by sequencing (-seq) [116] were developed for accurate sequence confirmation. screening application in cancer therapyThe application of theCas system for cancer therapy has been investigated using viral vectors including lentivirus, adenovirus, and AAV vectors, as well as non-viral vectors such as polymer nanop4. Fig. [SEP] Justify:

Output: The text supports the claim by discussing various methods of analyzing precise gene selection, including the Model-based Analysis of Genome-wide Cas9 Knockout (MAGeCK), which is described as an optimized method for gene selection offering high sensitivity and low false discovery rates. This indicates an emphasis on the precision of gene editing techniques.