Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: I examine two mechanisms through which regulated translocation can generate ultrasensitivity, and consider two specific contexts where such mechanisms are likely to be important. 1 Graded, switch-like and bistable responsesA phosphorylation–dephosphorylation reaction can be used as an example of a simple signaling pathway (Fig. 1a). The concentration or activity of the kinase represents the stimulus; the steady-state concentration of phosphorylated substrate is the response. This simple signaling pathway can exhibit one of three types of response: graded, switch-like and bistable. I shall begin by discussing how these responses differ. Fig. 1 Three types of response for the steady-state level of phosphorylated substrate as a function of kinase activity for a phosphorylation–dephosphorylation reaction. (a) Reaction scheme for phosphorylation and dephosphorylation. (b) A graded response. The red curve depicts a Michaelian response. The green curve depicts a subsensitive response, defined by a Hill-equation response in which the Hill coefficient, n, is 0. 33. The blue curve depicts a response that approaches its maximum more abruptly than does a Michaelian response. This type of response occurs when the kinase reaction is close to saturation and the phosphatase reaction is far from saturation[35]. (c) A switch-like response. The blue curve is defined by a Hill equation in which n=3. The red curve depicts the response of a system in which the kinase and phosphatase reactions are close to saturation[35]. (d) A bistable response—a true switch[28]. P, phosphate. 1. 1 Graded responsesWhen the kinase and phosphatase are far from saturation, and no `extras' are present, the system exhibits a graded response (Fig. 1b, red curve), which can be defined by the following mathematical expression:(1)response=stimulusEC50+stimulusEC50 denotes the stimulus concentration/activity at which the response is half maximal. The equation is identical in form to the familiar Michaelis–Menten equation; this type of graded response is therefore termed Michaelian[7, 8]. A Michaelian response is linear at low stimulus concentrations, and then levels off as the stimulus increases and the amount of unphosphorylated substrate decreases.

Output: pass


Input: Claim: Antibiotics are effective against bacterial infections, not viral ones. [SEP] Text: , McHugh K. J. et al. Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice. 2015; 309: L158–167. 42. Robinson K. M. , McHugh K. J. , Mandalapu S. et al. virus exacerbates Staphylococcus aureus pneumonia in mice by attenuating antimicrobial peptide production. J 2014; 209: 865–875. 43. Kudva A. , Scheller E. V. , Robinson K. M. et al. inhibits Th17- mediated host defense against bacterial pneumonia in mice. J Immunol 2011; 186: 1666–1674. 44. Robinson K. M. , Choi S. M. , McHugh K. J. et al. exacerbates Staphylococcus aureus pneumonia by attenuating IL-1beta production in mice. J Immunol 2013; 191: 5153–5159. 45. Warnking K. , Klemm C. , Loffler B. et al. Super-infection with Staphylococcus aureus inhibits influenza virus-in- duced type I IFN signalling through impaired STAT1-STAT2 dimerization. 2015; 17: 303–317. 46. Warshauer D. , Goldstein E. , Akers T. et al. Effect of influenza viral infection on the ingestion and killing of bacteria by alveolar macrophages. 1977; 115: 269–277. 47. Lamikanra A. , Paul B. D. , Akinwole O. B. , Paul M. O. Nasal carriage of Staphylococcus aureus in a population of healthy Nigerian students. J 1985; 19: 211–216. 48. Dancer S. J. , Noble W. C. Nasal, axillary, and perineal carriage of Staphylococcus aureus among women: identification of strains producing epidermolytic toxin. J 1991; 44: 681–614. 49. Hamdan-Partida A. , Sainz-Espunes T. , Bustos-Martinez J. Characterization and persistence of Staphylococcus aureus strains isolated from the anterior nares and throats of healthy carriers in a Mexican community.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: Similar to our findings, patients chose tele-pharmacy primarily to “reduce costs,” “save time,” and “lower disease transmission risk,” while in-person visits were driven by factors like “direct pharmacist communication,” “limited internet access,” and “addressing patient anxiety and enhancing peace of mind”. Non-acceptance of the use of telemedicine by patients was observed while the use of this technology has expanded significantly in the last decade. Kichloo et al. [35] noted that the scope of telemedicine has rapidly expanded worldwide, connecting global providers and patients to address physician shortages, distribute medical resources more equitably, and enable distinct pathways for specialized care. [35]. Other studies [36,37,38] highlight that telemedicine offers convenient access to care providers globally, reducing travel expenses and inconvenience, particularly when used as an alternative for costly services or over long distances from medical centers. But it’s important for us to understand that widespread acceptance and high satisfaction among patients and healthcare providers are crucial for successful telemedicine. This necessitates involvement in system design, administrative support, ensuring reliability, user-friendliness, and fair reimbursement [36]. Physician satisfaction drives adoption; education, patient training, and online support improve acceptance [39]. Ultimately, telemedicine must provide value, convenience, and satisfaction akin to in-person visits [36]. In our study, patients also favored telemedicine to overcome distance barriers, decrease extra trips, enhance treatment adherence, and minimize waiting times. Other studies have also shown that telemedicine can reduce the time away from work or school, reduce the waiting time of patients, increase the number of visits made by specialists [40] and easy access of patients living in deprived areas and rural and urban communities to therapists by reducing and remove the geographical distance [41]. A study by Nguyen et al. [36] also indicated that reduced travel time and costs elevate patient willingness to use telemedicine. Consequently, patient and therapist contentment with telemedicine involves diverse aspects beyond health, encompassing home comfort, care continuity, accessibility, cost savings, and convenience. [36]. So, when designing a telemedicine system, not only the dimensions of treatment or health should be considered, but also the other dimensions introduced should be included.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: Thus, the first increment of stimulus produces a substantial response, but each subsequent increment produces a smaller increment of response. Certain modifications of the basic phosphorylation–dephosphorylation mechanism preserve the essential law-of-diminishing-returns character of the Michaelian response but change the rate at which the system approaches its maximal response. The system will approach its maximal response more gradually if there is negative cooperativity (Fig. 1b, green curve)—for example, if phosphorylation of one site in the substrate makes the phosphorylation of a second site more difficult. Conversely, the system will approach its maximal response more abruptly if the kinase is close to saturation (Fig. 1b, blue curve). 1. 2 Switch-like responsesUltrasensitive systems behave as if they have a built-in threshold: they respond very little to the first increments of stimulus but, as the stimulus is increased, begin to respond better and better[7, 8]. The result is a sigmoidal stimulus–response curve (Fig. 1c) that resembles that of a cooperative enzyme. In the extreme, steep sigmoidal curves approach a step function or digital on/off switch; these responses are therefore sometimes referred to as switch-like responses. A variety of mechanisms can produce an ultrasensitive or switch-like response: stoichiometric inhibitors that soak up the first increments of stimulus; co-operative interactions between subunits of a multisubunit enzyme; saturation of the back reaction (in this case, dephosphorylation), or of the forward and back reactions; a requirement for multiple phosphorylations; and other mechanisms[9]. The shapes of the resulting stimulus–response curves vary from mechanism to mechanism (Fig. 1c). Often, the responses are well approximated by the Hill equation:(2)response=stimulusnEC50n+stimulusncoefficient (n) can be taken as a quantitative measure of how switch-like the response is. Irrespective of the exact mechanism underpinning the response or the exact shape of the stimulus–response curve, a switch-like system filters out small stimuli and then once it responds does so decisively. 1. 3 Bistable responsesBistable responses occur in systems that involve positive feedback (e. g. where the phosphorylated substrate brings about activation of the kinase) and under certain other circumstances[10].

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: Environmental noise exposure, early biological risk and mental health in nine to ten year old children: a cross-sectional field study Download PDF Download eeOpen access Published: 14 May 2011 Environmental noise exposure, early biological risk and mental health in nine to ten year old children: a cross-sectional field study Rosanna Crombie1, Charlotte Clark1 & Stansfeld1 11. 5% of the sample were in the 'biological risk' category (no biological risk = 1704, biological risk = 196). Of those with biological risk 23. 5% (n = 46) were premature, 39. 8% (n = 78) were born with a low birth weight and the remaining 36. 7% (n = 72) were both premature and of a low birth weight. Table 1 illustrates the characteristics of the sample by early biological risk. From this we can see that there is a higher percentage of British and a lower percentage of Dutch among those with early biological risk. Further there are a higher percentage of females, and children with unemployed and non-home owning parents with early biological risk compared to the no early biological risk category. Classroom glazing also varied by early biological risk. Table 1 Sample characteristics by early biological riskFull size table In terms of mental health, 15. 5% of the participants were cases on the emotional symptoms subscale (scoring 5+), 14. 5% on the conduct problems subscale (scoring 4+) and 16. 5% on the hyperactivity subscale (scoring 7+). 10. 6% of the sample had a total SDQ score that was abnormal (scoring 18+). The main analyses used the continuous SDQ measures of mental health. Sociodemographic variablesThe pattern of sociodemographic status predictors was largely similar across models, thus only model 3 with total SDQ score as the outcome variable is presented in Table 2. Country was significantly associated with all the SDQ outcome measures, indicating that children in the UK and the Netherlands were reported to have better mental health than those in Spain. Males were reported to have significantly poorer mental health than females on the total SDQ measure, conduct problems and hyperactivity, but this finding was reversed for the emotional symptoms measure. Non-home ownership, longstanding illness, lower educational achievement of the child's mother, and lower parental support for school work were all significantly associated with all SDQ measures indicating poorer mental health for these children.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: In our study, patients leaned towards telemedicine for treatment to reducing the possibility of contracting infectious diseases, employ effective contact-free evaluations, protect service providers, and prevent disease spread. Alexander et al. [42] asserted that the unexpected outbreak of COVID-19 has reshaped people’s perceptions of telemedicine. In this context, telemedicine can play a vital role in conserving healthcare resources, such as personal protective equipment, while ensuring the delivery of safe and high-quality patient care. Furthermore, it facilitates the maintenance of social distancing measures, thus aiding in the minimization of virus transmission. The findings from the study conducted by Ben-Ar et al. [43] demonstrated a noteworthy surge in the utilization of telemedicine visits for managing upper extremity musculoskeletal complaints within outpatient settings during the COVID-19 pandemic. The study reported a staggering 76-fold increase in telemedicine visits within a specific institution. It is important to emphasize that, prior to the COVID-19 pandemic, the adoption of telemedicine services remained limited across various medical disciplines, despite the documented advantages for patients. These advantages encompassed reduced time spent in the office, alleviated travel burdens and associated costs, heightened patient comfort, and the opportunity for family members to participate in medical consultations[11, 44]. Therefore, it can be said that the significant increase in the use of telemedicine services during the COVID-19 epidemic could be due to the limited access to in-person visits (most physicians’ offices were closed during the epidemic) and the fear of contracting COVID-19 through in-person visits [43]. It is noteworthy to highlight the significance of endorsing telemedicine during a pandemic. This endorsement serves as a mechanism to avert direct exposure of individuals to infectious diseases while surmounting the many barriers that obstruct access to care within clinical settings [45]. Moreover, our study’s findings indicate that in-person visits offer advantages like improved clinical history, direct and comfortable patient-physician communication, focused physician attention, strong patient-physician rapport, and effective treatment guidance. Research by Gordon et al. [46] highlighted issues with clinical video telehealth (CVT) encounters, including provider inattentiveness due to computer monitor and note-related distractions, leading patients to feel overlooked and unheard.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: Bistable responses are sigmoidal, as are switch-like responses, but the two types of response differ in two important respects. First, in bistable systems, an intermediate response is not only unlikely, it is impossible; there is a true discontinuity in the stimulus–response curve (Fig. 1d). Second, bistable systems exhibit hysteresis: once a stimulus has reached a sufficient level to switch the system to the on state (Fig. 1d, red curve), the system will remain on even if the stimulus is lowered back below the threshold (Fig. 1d, blue curve and arrows). Thus, a bistable system has the potential to remember a stimulus long after the stimulus has been removed. A bistable system behaves like a light switch—once you have flipped the switch, you can let go of it and it will stay on—whereas a switch-like system is more like a doorbell that rings only while it is being pushed. 2 Regulated translocation and switch-like responsesThere are at least three mechanisms through which regulated translocation could generate a switch-like response: (1) translocation of multiple components of a signaling cascade; (2) translocation-induced enzyme saturation; and (3) translocation to a compartment that contains a stoichiometric inhibitor. Here, I discuss the first two mechanisms in detail in the context of two important signaling processes: the activation of CDC2–cyclin-B1 at the onset of mitosis; and the activation of MAP kinase (MAPK) by strong or sustained stimuli. A discussion of the third mechanism can be found elsewhere[9]. 3 Example I: the pre-mitotic nuclear translocation of CDC25C and CDC2–cyclin-B1Underlying principle: if a stimulus causes both a signaling protein and its activator to translocate to the same subcellular compartment, then the steady-state response of the signaling protein can be switch-like. During G2 phase, cyclin B1 is synthesized and forms complexes with CDC2 that are held in an inactive state through the phosphorylation of Thr14 and Tyr15 in CDC2. In animal cells, the kinases that carry out the inactivating phosphorylation are WEE1 and MYT1; the phosphatase that reverses the phosphorylation and activates CDC2 is CDC25C.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: 20, df = 1, p <. 05) which remained after further adjustment for early biological risk (Table 3: model 3) (χ2 = 4. 74, df = 1, p <. 05) (Table 3). Referring to model 3, this revealed a 0. 01 point decrease in conduct disorder for every one dB (A) increase in road traffic noise at school. There were no significant associations between road traffic noise at school and overall SDQ, emotional symptoms and hyperactivity, either before or after the addition of early biological risk (Table 3: models 2 and 3). Effects of early biological risk on mental healthFor early biological risk, the pattern of results was the same in the unadjusted and adjusted models, thus parameters quoted are from the adjusted model (model 3) (Table 3). A significant effect of biological risk was found for the total SDQ score (χ2 = 15. 97, df = 1, p <. 001) where those at risk score on average 1. 641 more points than those not at risk. Similarly there was a significant association between early biological risk and emotional symptoms (χ2 = 10. 88, df = 1, p <. 001) with those at risk scoring on average 0. 520 points more than those not at risk. There was also a significant association between early biological risk and conduct problems (χ2 = 11. 63, df = 1, p <. 001) with those at risk scoring on average 0. 402 points more than those not at risk. Finally there was no significant association between early biological risk and hyperactivity. Interaction between early biological risk and noise exposureModel 4 included an interaction term between early biological risk and either aircraft or road traffic noise exposure at school. There were no significant interactions between early biological risk and aircraft noise at school for any of the outcomes: total SDQ (χ2 = 0. 82, df = 1, p =. 37), emotional symptoms (χ2 = 0. 57, df = 1, p =. 45), conduct problems (χ2 = 0. 33, df = 1, p =. 56), hyperactivity (χ2 = 0. 74, df = 1, p =. 39). Further there were also no significant interactions between early biological risk and road traffic noise at school for any of the outcomes: total SDQ (χ2 = 0.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: Studies emphasize that in-person visits’ success is tied to factors such as friendly interactions, information exchange, body language, and face-to-face engagement, positively impacting patient satisfaction [9, 36]. Non-verbal cues like eye contact are vital in communication, but telemedicine’s camera view limits these cues, creating a challenge [47]. Overcoming this entails training patients to engage actively and teaching providers to eliminate distracting behaviors and use literal cues when addressing the camera [46, 48]. Study implicationsThe study’s findings have significant implications for integrating and adopting telemedicine in healthcare. Despite telemedicine’s potential to overcome barriers and provide efficient medical services, patients still prefer in-person consultations. Factors affecting this preference, like education, health conditions, and experience, highlight the need for tailored approaches to promote telemedicine. Addressing these factors could make telemedicine more appealing to a broader patient group. Additionally, the study highlights perceived advantages of telemedicine over in-person visits, such as cost savings, disease prevention, distance elimination, and time-saving. Leveraging these benefits could form the basis for targeted marketing and awareness efforts, emphasizing telemedicine’s tangible benefits. The study’s main conclusion is that despite telemedicine’s advantages, patients still favor in-person visits, underlining the importance of effective change management in healthcare. To encourage wider telemedicine acceptance, healthcare institutions must align with patient p95. 43. 40. 5. 22. 61. 8528. PubMed Pub10. Duffy S, Lee TH. In-person health care as option B. N Med. 2018;378(2):104–6. 5105. 42. 9. 9. 4250. 13. . Telemedicine practice: review of the current ethical and legal challenges. E Health. 2020;26(12):1427–37. 2019. . strategies to improve hypertension: the experience. Cardiol. 2014;30(5):544–52. 9. . Patient perspectives with telehealth visits in cardiology during COVID-19: online patient survey study. JMIR Cardio. 2021;5(1):e25074. 4. 6. ôté.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: Immediately prior to nuclear envelope breakdown, in late G2 phase or mitotic prophase, both CDC25C and its substrate, CDC2–cyclin-B1, are induced to translocate to the nucleus[11–13]. This translocation appears to be essential for initiation of nuclear and cytoplasmic manifestations of mitosis[13–15]. Accumulation of CDC2–cyclin-B1 in the nucleus depends upon the phosphorylation of cyclin B1 at multiple sites, four of which are situated within the nuclear-export sequence of cyclin B1[15–19]. These phosphorylations inhibit nuclear export of CDC2–cyclin-B1, leading to nuclear accumulation of the complex. The kinase or kinases responsible for cyclin-B1 phosphorylation are unknown, as is the trigger for nuclear translocation of CDC25C. The fact that both CDC2–cyclin-B1 and CDC25C are induced to translocate to the nucleus is a potential source of ultrasensitivity, provided that nuclear CDC2–cyclin-B1 is not permanently locked into its active, Thr14- and Tyr15-dephosphorylated, form. I shall illustrate this point by building up the pathways that lead to accumulation of activated CDC2–cyclin-B1 one pathway at a time. Assume that CDC25C is constitutively active and constitutively cytoplasmic, and that the accumulation of nuclear CDC2–cyclin-B1 depends upon a factor, X, that inhibits nuclear export of CDC2–cyclin-B1 (Fig. 2a). Initially, the amount or concentration of active nuclear CDC2–cyclin-B1 increases linearly with [X] and then levels off as the nuclear export of CDC2–cyclin-B1 becomes maximally inhibited. The result would be a Michaelian response (Fig. 2a). Fig. 2 A switch-like response arising from nuclear translocation of CDC25C and CDC2–cyclin-B1 just prior to mitosis. (a) Michaelian response, in which a factor, X, stimulates CDC2–cyclin-B translocation alone. (b) Modestly switch-like response, in which X stimulates translocation of both CDC2–cyclin-B and CDC25C.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: 01, df = 1, p =. 92), emotional symptoms (χ2 = 0. 75, df = 1, p =. 39), conduct problems (χ2 = 1. 22, df = 1, p =. 27), hyperactivity (χ2 = 0. 33, df = 1, p =. 57). DiscussionThe present study explored the effect of early biological risk as a moderator of the association of noise exposure at school and mental health using data from the RANCH study. Contrary to our hypotheses, no interaction was found between either road traffic or aircraft noise at school and early biological risk for mental health outcomes. Nevertheless a main effect of early biological risk on mental health was found. Further, results regarding noise exposure at school and mental health were similar to Stansfeld et al. [12] after adjustment for early biological risk as expected. The finding of no interaction between early biological risk and either aircraft or road traffic noise at school was unexpected as it does not support Lercher et al. [13] who found an interaction between early biological risk and ambient neighbourhood noise in children. Methodological variations between the two studies could account for the difference in findings, such as the noise source measured (aircraft noise and road traffic noise at school versus ambient neighbourhood noise which was predominantly rail and road noise); whether noise was estimated for the school or home environment; the quality of the road exposure assessments, the measurement of mental health (parental report versus self report) and the measurement of early biological risk (parental report versus doctors' entry). Further, the finding of no interaction between aircraft noise at school and early biological risk could be explained by the transient nature of aircraft noise compared to the steady state sound levels emitted by ambient neighbourhood noise. The finding of a main effect of early biological risk with mental health was of interest. Specifically, participants at risk were rated by their parents as scoring higher on the total SDQ scale and the emotional symptoms and conduct problems subscales, than participants not at risk. These findings support previous studies that have found increased rates of behavioural problems in low birth weight children and higher externalising and internalising symptoms in children who were born prematurely [17–19].

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: full text icon contents icon Contents figure icon Figures Tables multimedia icon Multimedia attach icon 1. of by rates of primary care visits with any medication prescribing during the index visit based on results from multivariable logistic regression models adjusting for patient demographics, potential barriers to in-person visits, chronic conditions, Classification of Diseases and Problems, grouping of primary diagnoses, and medical center, with SEs adjusted for repeated visits by patients. Analyses were repeated for subgroups of visits for upper respiratory tract infections (URIs) and skin conditions, 2 commonly reported categories of telemedicine chief complaints and diagnoses. Whiskers indicate 95% CIs. Figure 2. of by rates of primary care visits with any order (eg, laboratory tests or imaging) during the index visit based on results from multivariable logistic regression models adjusting for patient demographics, potential barriers to in-person visits, chronic conditions, Classification of Diseases and Problems, grouping of primary diagnoses, and medical center, with SEs adjusted for repeated visits by patients. Analyses were repeated in subsets of visits for upper respiratory tract infections (URIs) and skin conditions, 2 commonly reported categories of telemedicine chief complaints and diagnoses. Whiskers indicate 95% CIs. Figure 3. of Follow-up by rates of primary care visits with any in-person office visit within 7 days after the index visit based on results from multivariable logistic regression models adjusting for patient demographics, potential barriers to in-person visits, chronic conditions, Classification of Diseases and Problems, grouping of primary diagnoses, and medical center, with SEs adjusted for repeated visits by patients. Analyses were repeated in subsets of visits for upper respiratory tract infections (URIs) and skin conditions, 2 commonly reported categories of telemedicine chief complaints and diagnoses. Whiskers indicate 95% CIs. Figure 4. of Follow-up (ED) Visits and Hospitalizations by rates of primary care visits with any ED visit or hospitalization within 7 days after the index visit based on results from multivariable logistic regression models adjusting for patient demographics, potential barriers to in-person visits, chronic conditions, Classification of Diseases and Problems, grouping of primary diagnoses, and medical center, with SEs adjusted for the repeated visits by patients. Analyses were repeated in subsets of visits for upper respiratory tract infections (URIs) and skin conditions, 2 commonly reported categories of telemedicine chief complaints and diagnoses.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: (c) More-markedly switch-like response, in which X stimulates CDC25C activation (in the nucleus and/or cytoplasm) as well as translocation of CDC2–cyclin-B1 and CDC25C. The constants a–e represent combinations of rate constants and component concentrations. B1, cyclin B1. The situation changes, however, if we assume that X stimulates nuclear uptake of both CDC2–cyclin-B1 and CDC25C. Now, X impinges upon the accumulation of active CDC2–cyclin-B1 in the nucleus in two ways (Fig. 2b): (1) it increases the concentration of nuclear CDC2–cyclin-B1 directly; and (2) it increases the concentration of the enzyme that keeps nuclear CDC2–cyclin-B1 active. Consequently, the amount of active nuclear CDC2–cyclin-B1 initially increases as the square of [X] (Fig. 2b). The translocation of multiple components has produced a switch-like response with an overall apparent Hill coefficient of 1–2 (Fig. 2b). In addition, the timing of CDC2–cyclin-B1 activation becomes more abrupt. If the nuclear concentrations of both CDC2–cyclin-B1 and CDC25C initially increase linearly with time (t) then, for small values of t, the nuclear concentration of active CDC2–cyclin-B1 will be proportional to t[2]. Finally, if we assume that X stimulates the nuclear uptake of CDC25C and CDC2–cyclin-B1, and also stimulates the activation of CDC25C (Fig. 2c), then X would affect the production of active nuclear CDC2–cyclin-B1 in three ways. Consequently, the amount of nuclear CDC2–cyclin-B1 initially increases as [X][3](Fig. 2c). The overall apparent Hill coefficient could be as much as three, and the amount of active nuclear CDC2–cyclin-B1 will initially be proportional to t[3]. There are several caveats to this analysis. The prediction of an ultrasensitive response depends upon the assumption that nuclear CDC2–cyclin-B1 equilibrates between active and inactive forms (Fig. 2b and c), and this assumption is untested.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: Environmental and genetic influences on early attachment Download PDF Download eeOpen access Published: 04 September 2009 Environmental and genetic influences on early attachment Judit Gervai1 Child and 0. 24-0. 32). Over the last three decades, it has been shown that different demographic risk factors, especially if accumulated may effect the development of attachment, presumably through their proximal or distal influence on parenting [12]. Income and family size, parental age and education, major stressful events, such as loss of a parent, birth of a sibling, severe illness, marital relationships and breakdown affect the quality of attachment relationships [13–19]. It has been expected that secure attachment is promoted by the psychological health of parents, especially mothers. Empirical studies have provided contradictory results, but the majority found that mothers depressed postnatally were more likely to develop insecure attachment relationships with their infants [20–23]. Studies in general have not been able to find direct associations of mother-infant attachment with child care arrangements and with mothers' social support systems [12], but in high social risk groups, lack of support correlated with higher rates of insecure attachment relationships [24–26], while extensive support was found to promote security [27, 28]. Security of mother-infant attachment has been found to be related to mother's mental state with respect to close (attachment) relationships. In several studies, the security of maternal attachment representations, as assessed by the Interview (AAI) [29], has been found to be significantly related to mother-infant attachment security [30]. It has also been shown that while isolated individual risk factors may not have a significant effect on parent-child attachment, the accumulation of adversity may result in sub-optimal relationship development and insecurity of infant attachment [12]. Raikes and Thompson [31] have tested the effect of multiple social and economical factors on attachment and confirmed that their effects were mediated by mothers' care-giving behaviour. In several longitudinal studies, cumulative risk indices and life stress were used to explain discontinuities in attachment security through the life course [32–34]. Friedman and Boyle [35] have recently reviewed attachment-related findings from the longitudinal of Care (SECC) aiming to identify effects of timing, extent, quality, and type of child care experiences on children's development in a large sample, using well-controlled methodology.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: Whiskers indicate 95% CIs. Table. Patient-by. e1. Temesgen ZM, DeSimone DC, Mahmood M, Libertin CR, BR, Berbari EF. Health care after the COVID-19 pandemic and the influence of telemedicine.  Proc. 2020;95(9S):S66-S68. doi:10. 1016/j. mayocp. 2020. 06. 052PubMed2. Uscher-Pines L, Mulcahy A, Cowling D, Hunter G, Burns R, Mehrotra A. Access and quality of care in direct-to-consumer telemedicine.  E Health. 2016;22(4):282-287. doi:10. 1089/tmj. 2015. 0079PubMed3. Li KY, Zhu Z, Ng S, Ellimoottil C. Direct-to-consumer telemedicine visits for acute respiratory infections linked to more downstream visits.  (Millwood). 2021;40(4):596-602. doi:10. 1377/hlthaff. 2020. 01741PubMed4. Shi Z, Mehrotra A, Gidengil CA, Poon SJ, Uscher-Pines L, Ray KN. Quality of care for acute respiratory infections during direct-to-consumer telemedicine visits for adults.  (Millwood). 2018;37(12):2014-2023. doi:10. 1377/hlthaff. 2018. 05091PubMed5. Daniel H, Sulmasy LS; Health and Committee of the of Physicians. Policy recommendations to guide the use of telemedicine in primary care settings: an of Physicians position paper.  Med. 2015;163(10):787-789. doi:10. 7326/M15-0498PubMed6.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: Also, the details of CDC25C and CDC2–cyclin-B1 translocation have not been established—for example, X might be multiple proteins. Alternatively, CDC25C might induce CDC2–cyclin-B1 translocation, or CDC2–cyclin-B1 might induce CDC25C translocation. Irrespective of the exact mechanism, however, the underlying idea—that induced translocation of multiple components of a cascade can cause a switch-like response—remains valid. A Hill coefficient of two or three might not seem too dramatic, but for a multistep process the overall Hill coefficient can be as high as the product of the Hill coefficients for the individual steps[20, 21]. coefficients ⩾2 might well contribute to the overall response of nuclear CDC2–cyclin-B1 to CDC25C. For example, the timing of CDC2 dephosphorylation in starfish oocytes suggests a two-step, nonprocessive mechanism for the activating dephosphorylation of CDC2–cyclin-B1 by CDC25C (Ref. [22]), which could provide another Hill coefficient of ∼2. In addition, the prolyl isomerase PIN1 appears to act as a stoichiometric inhibitor of CDC25C[23, 24], which, as mentioned above, should contribute an additional measure of ultrasensitivity. So far, I have not taken into account the positive feedback loops through which active CDC2–cyclin-B1 brings about activation of CDC25C and inactivation of WEE1[25–27]. As mentioned above, positive feedback loops can produce a bistable response—which in this case might ensure that entry into mitosis is an all-or-none process—but they produce a bistable response only if some additional mechanism prevents the loop being triggered by tiny perturbations[10, 28]. The intrinsic ultrasensitivity of the response of CDC2–cyclin-B1 to CDC25C could be one mechanism for filtering out small stimuli. Moreover, the greater the magnitude of the intrinsic ultrasensitivity, the tighter and more complete the bistable switch can be (further discussions of bistability in CDC2 activation[10], and the interplay between ultrasensitivity and positive feedback[28]can be found elsewhere).

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: The study followed the development of more than one thousand children, of varied backgrounds, from birth and periodically assessed attachment to their mothers. Family SES and maternal sensitivity, especially in responding to the child's distress, predicted the quality of attachment at 15 months [36, 37] and at 36 months of age [38] confirming the previously found moderate strength of the relationship. Recurring symptoms of maternal depression across the first three years predicted higher prevalence of insecure attachment at age 36 months [39]. Analysis of effects of non-maternal care, a special focus of the NICHD study, confirmed the lack of main effects of children's age of entry, quality of care and length of time children spent in non-maternal care, but also revealed interaction effects. The study found higher rates of insecurity if a low quality of non-maternal care was combined with low maternal sensitivity and more time spent in child care. Altogether, the conclusion of the study was that, under some circumstances, early non-maternal child care can be an environmental risk factor for attachment security and compromised later development. Environmental effects on disorganized attachmentAttachment disorganisation became a focus of developmental research when rarely occurring incoherent and contradictory infant behaviours, not fitting the Ainsworth categories, appeared to be predominant among maltreated or otherwise deprived groups of infants and young children [6, 40]. Infants whose attachment strategy collapses even under the mild stress of brief separation experienced in the and who show high degree of incoherence and disorganisation upon reunion with their caregivers comprise on average 15% of typical populations and as high as 50-80% of high social risk groups [8]. Early disorganised attachment also proved to be one of the rare early predictors of subsequent childhood behaviour problems [41–44] and adolescent psychopathology, such as dissociative symptoms and borderline personality disorder [45, 46]. Regarding the parenting background, Main and Hesse [47] proposed that caregivers of infants displaying disorganized attachment showed bouts of "frightened, threatening, and dissociative" behaviour in interactions with their infants, and this was confirmed by later studies [48–50]. In addition, Lyons-Ruth and colleagues [51] identified a broader spectrum of anomalous parental behaviour contributing to attachment disorganisation, including also communication errors, role confusion and extreme withdrawal. To some extent, these behaviours were also found in low-social-risk groups of mothers [43, 52–55].

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: Reed ME, Huang J, Graetz I, et al. Patient characteristics associated with choosing a telemedicine visit vs office visit with the same primary care clinicians. . 2020;3(6):e205873. doi:10. 1001/jamanetworkopen. 2020. 5873PubMed7. Reed ME, Parikh R, Huang J, Ballard DW, Barr I, Wargon C. Real-time patient-provider video telemedicine integrated with clinical care.  N Med. 2018;379(15):1478-1479. doi:10. 1056/NEJMc1805746PubMed8. Reed ME, Huang J, Parikh R, et al. Patient-provider video telemedicine integrated with clinical care: patient experiences.  Med. 2019;171(3):222-224. doi:10. 7326/M18-3081PubMed9. Uscher-Pines L, Mehrotra A. Analysis of Teladoc use seems to indicate expanded access to care for patients without prior connection to a provider.  (Millwood). 2014;33(2):258-264. doi:10. 1377/hlthaff. 2013. 0989PubMed10. Alexander GC, Tajanlangit M, Heyward J, Mansour O, Qato DM, Stafford RS. Use and content of primary care office-based vs telemedicine care visits during the COVID-19 pandemic in the US. . 2020;3(10):e2021476. doi:10. 1001/jamanetworkopen. 2020. 21476PubMed2793. doi:10. 1001/jamanetworkopen. 2021. 32793 Manage 2793. doi:10. 1001/jamanetworkopen. 2021. 32793 visual abstract icon editorial comment icon related 2018.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: Thus, by generating extra ultrasensitivity, the nuclear translocation of CDC25C and CDC2–cyclin-B1 could make activation of CDC2–cyclin-B more of an abrupt, all-or-none process than it would be if all components were constitutively cytoplasmic. 4 Example II: nuclear translocation of MAP kinase in response to strong stimuliUnderlying principle: translocation can raise the concentration of a signaling protein to a level that is high enough to partially saturate the enzyme that inactivates it (or, better still, to saturate partially its activator and its inactivator). The result is a switch-like response. The Raf–MEK–-kinase cascade is activated in response to growth factors and a variety of other intra- and extracellular stimuli. Even if all of the components were constitutively cytoplasmic, the cascade would be expected to generate a switch-like response[9, 28, 29]. However, both the MAP-kinase kinase MEK and the MAP kinases ERK1 and ERK2 shuttle from the cytoplasm to the nucleus when they are activated by strong upstream stimuli; MEK remains predominantly cytoplasmic, and the ERKs concentrate in the nucleus[30–34]. The translocation of multiple components could result in a modest n≈1–2 response through the mechanism described above for CDC2–cyclin-B1 activation. In addition, a second mechanism—translocation-dependent saturation or zero-order effects—should make the response substantially more switch-like. The key here is a phenomenon termed zero-order ultrasensitivity, which is defined as ultrasensitivity that occurs because converting enzymes [MEK and an unidentified MAP-kinase phosphatase in this pathway] operate near saturation[8, 35]. The expected degree of zero-order ultrasensitivity for the response of MAP kinase to MEK, in the face of a constant level of MAP-kinase-phosphatase activity, can be calculated if the relevant Michaelis constants (Km) and concentrations are known. for tyrosine phosphorylation of mammalian ERK2 by MEK (generally the tyrosine residue is phosphorylated before the threonine) is ∼300nm (Ref.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: data, Campbell and colleagues [39] have shown that chronic depression combined with low maternal sensitivity is associated with a higher prevalence of disorganised attachment in 3-year-old children. Mothers' unresolved trauma or loss has been considered as a potential source of disruptions in maternal care-giving behaviour [43, 47, 50, 56]. According to a recent meta-analysis, however, anomalies of caregiver's mental state and behaviour had only low explanatory power in accounting for attachment disorganization [49]. Including 12 studies examining relations between maternal unresolved loss and trauma, anomalous parenting and disorganised attachment, moderate effect sizes were found for both links between maternal unresolved mental state and anomalous behaviour and infant disorganized attachment (r =. 26 and. 21, respectively), as well as for the link between mother's anomalous behaviour and infant disorganization (r =. 34). Biological contribution to individual variations in infant attachmentNewborns' biologically based capabilities of self-regulation of arousal and distress states have an immediate impact on parents. The great individual variation in these capabilities can be described by dimensions such as the infant's disposition for distress or negative emotionality, irritability and soothability [57, 58]. There is a long tradition of two different interpretations of the role of infant temperament in the formation of attachment relationships. Attachment theorists have suggested that temperament has no direct effect on the quality of attachment, since infant characteristics such as difficult temperament can be accommodated by sensitive caregivers, who can still foster secure attachment relationships [59]. Temperament researchers, on the other hand, have kept emphasizing that infant-caregiver interactions in the reflect the infant's temperament rather than the quality of the relationship [60]. In their extensive review, Vaughn and Bost [61] argue that temperament and attachment are separate constructs, and studies showing inter-relationships on the one hand, and independence on the other result from different conceptualisations and assessments of both. There is a body of empirical research results, which has demonstrated relations between attachment quality and infant irritability, proneness to distress or stress regulation [26, 58, 62–64]. Based on their review of literature, Mangelsdorf and Frosch [65] have suggested that effects of infant temperament on attachment may be indirect and moderated by other maternal and social variables. Several studies have found that newborn behavioural measures are related to later secure and insecure attachment classifications [66–70].

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: rates of any medication prescribed or laboratory tests or imaging ordered and rates of follow-up health care utilization (in-person visits, emergency department visits, and hospitalizations) within 7 days after the index visit, stratified by index primary care visit type, were generated using multivariable adjustment for patient, access, and clinical characteristics. study included 1 131 722 patients (611 821 [54%] female; mean [SD] age, 43 [22] years) with 2 178 440 total appointments (307 888 [14%] telemedicine), of which 13. 5% were for patients younger than 18 years, 22. 2% were for patients 65 years or older, and 54. 9% were for female patients. After adjustment, 38. 6% (95% CI, 38. 0%-39. 3%) of video visits, 34. 7% (95% CI, 34. 5%-34. 9%) of telephone visits, and 51. 9% (95% CI, 51. 8%-52. 0%) of office visits had any medication prescribed; laboratory tests or imaging were ordered for 29. 2% (95% CI, 28. 5%-29. 8%) of video visits, 27. 3% (95% CI, 27. 1%-27. 5%) of telephone visits, and 59. 3% (95% CI, 59. 3%-59. 4%) of clinic visits. After adjustment, follow-up visits within 7 days occurred after 25. 4% (95% CI, 24. 7%-26. 0%) of video visits, 26. 0% (95% CI, 25. 9%-26. 2%) of telephone visits, and 24. 5% (95% CI, 24. 5%-24. 6%) of office visits. Adjusted emergency department visits and rates of hospitalizations were not statistically significantly different by primary care index visit type. Conclusions and this cohort study of patient self-scheduled primary care telemedicine visits within ongoing patient-physician relationships, prescribing and orders were significantly lower for telemedicine visits than for clinic visits, with slightly higher follow-up office visits for telemedicine but no difference in health events (emergency department visits or hospitalizations). Video or telephone visits may be a convenient and efficient way to access primary care and address patient needs.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: [36]), and the apparent Km for ERK1/2 dephosphorylation in one system, crude Xenopus laevis oocyte extracts, is also ∼300nm (C-Y. F. Huang and J. E. Ferrell, unpublished). The total ERK1 and ERK2 concentration in a variety of cell types is typically 300–1000nm (Ref. [9]). From these concentration and Km estimates, it follows that, if ERK1/2 protein were distributed uniformly throughout the cytoplasm, the zero-order ultrasensitivity generated by partial saturation of MEK and MAPK phosphatase would be small (Fig. 3a). Fig. 3 A switch-like response arising from saturation of the MAP-kinase kinase MEK and the MAP-kinase phosphatase by high concentrations of nuclear ERK (a)[35]. The degree of phosphorylation of cytoplasmic (b) and nuclear (c) MAP kinase is shown. The situation changes markedly, however, if the MAP kinase translocates to the nucleus and is maintained there by active nuclear MEK. Roughly 30–50% of a cell's ERK1/2 accumulates in the nucleus in response to strong ERK-activating stimuli[30]. If 50% of the 300-nm MAP kinase present in the cytoplasm translocates to the nucleus, then the nuclear concentration of ERK1/2 will be about 3000nm (given that the nucleus constitutes ∼5% of the cell's volume[37]). MEK and possibly MAP-kinase phosphatase will therefore be operating close to saturation, and the steady-state response of nuclear MAP kinase to increasing concentrations of active nuclear MEK should be strikingly switch-like (Fig. 3b). Again, several caveats arise from our incomplete understanding of the details of the system. We do not know whether the relatively low levels of nuclear MEK that accumulate in stimulated cells are responsible for keeping nuclear ERK1/2 activated, or whether any inactivated nuclear ERK1/2 must exit the nucleus to become reactivated. Active ERK1/2 can dimerize with both active and inactive ERK1/2 (Ref. [34]), and the Km for the interaction between the active/inactive dimer and MEK is not known.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: These studies are particularly interesting because neonatal measures reflect minimal social experience. Results from the Regensburg longitudinal studies have shown that poor neonatal behavioural organisation was related to disorganised behaviour in the at 18 months of age [71, 72]. This, together with findings that some of the behaviours characteristic of attachment disorganisation have also been found in children with developmental disorders [73, 74] imply that biological factors such as the infant's capability to organise environmental stimuli, communicate and regulate internal states and behaviour may also contribute to the development of disorganised attachment. Summarizing the empirical evidence, Barnett and colleagues [75] suggested a two-dimensional model in which both biological vulnerability as well as adverse environment might contribute to the development of atypical (disorganised) attachment behaviour. Twin studies of attachment security and disorganisationSince the study of parent-child attachment was so strongly driven by the environmental theory, a quantitative behaviour-genetic approach has only recently been used to investigate heritable and environmental variance components of attachment security. Most of the existing twin studies of attachment overviewed here have not been designed to focus on attachment, therefore they are quite heterogeneous regarding children's age and the method of assessment. In the Study (LTS), Finkel and Matheny [76] found a significant difference between concordances of attachment classifications of 99 monozygotic (MZ) and 108 dizygotic (DZ) two-year-old twins. Model-fitting resulted in estimates of 25% genetic and 75% non-shared environmental effects. In another study of 57 MZ and 53 same-sex DZ twins aged 3. 5 years, O'Connor and Croft [77] reported results of genetic model-fitting: variance estimates due to genetic, shared and non-shared environmental factors were 14%, 32% and 53%, respectively, but the genetic effect on secure vs. insecure attachment was not significant. Comparing 57 MZ and 81 DZ twin pairs, Bokhorst and colleagues [78] found only unique environmental factors accounting for the variance in disorganised vs. organised attachment, while both shared and non-shared environmental effects accounted for the variance in secure vs. insecure attachment.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: -19 pandemic unexpectedly shifted the US health care system toward a large volume of telemedicine care. Longer-term telemedicine use in primary care, however, may not be driven primarily by social distancing efforts but instead may focus on ways that telemedicine can offer a convenient option for expanding access to health care. 1 Many patients and health care practitioners now recognize that video or telephone telemedicine can offer patients access to a clinician without transportation arrangements, time off from work, or time spent in a waiting-room. Still, it is unclear whether telemedicine visits adequately address the patient’s clinical concern, are more likely to require subsequent follow-up outpatient care, or are more likely to be followed by a serious health event that requires an emergency department visit or hospital stay. In addition, prior evidence from direct-to-consumer telemedicine, which is often not integrated with the patient’s regular physician or full electronic health record, suggests potential over-prescribing and differences in physician orders and follow-up visits when primary care is delivered through telemedicine compared with through a typical office visit. 2-4 In contrast, little evidence exists about these care processes in telemedicine visits between patients and their own primary care physicians. 5 In a setting with prepandemic patient-scheduled video and telephone telemedicine with patients’ own primary care physicians, we compared telemedicine visits and in-person office visits with regard to care processes and postvisit health care utilization. We hypothesized that serious outcomes would be rare after telemedicine visits but that some patients would require additional follow-up visits. In this cohort study, we examined primary care visits in a large integrated health care delivery system with more than 4 million members, Northern California, which uses a comprehensive outpatient-inpatient electronic health record (EHR; including outpatient, emergency, inpatient, laboratory, imaging, and pharmacy history) and patient portal. The institutional review board of the approved the study protocol and materials and waived the requirement for written informed consent for participants because the study used deidentified data. This study followed Strengthening the Reporting of in Epidemiology () reporting guideline.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: In addition, because the relevant nuclear MAP-kinase phosphatase has not yet been identified, it is unclear whether MAP-kinase phosphatase would be saturated by nuclear MAP kinase. Finally, scaffold proteins might alter the mechanism of MAP kinase phosphorylation in ways that could either increase or decrease the resulting ultrasensitivity. Nevertheless, translocation-induced saturation remains an attractive concept; surely nature has made use of it somewhere. 5 ConclusionStraightforward kinetic arguments show that regulated protein translocation can result in switch-like, ultrasensitive responses, provided that multiple components of a signaling cascade are induced to translocate, that translocation results in saturation of one or more of the inactivation reactions in the signaling cascade, or that translocation gives one of the activating components access to a stoichiometric inhibitor. Thus, translocation can, in principle, make the response of a signaling system nonlinear, suppressing initial responses—that is, building a noise gate into the system—and potentiating subsequent responses. We should now be able to test these ideas experimentally. AcknowledgementsI thank for sharing unpublished information and the NIH (grant number GM46383) for support. 1. Hubbard, M. J. ∙ Cohen, P. Trends Biochem. Sci. 1993; 18:172-177Abstract(PDF)Scopus (822)PubMed2. Inagaki, N. ∙ Ito, M. ∙ Nakano, T. . . . Trends Biochem. Sci. 1994; 19:448-452Abstract(PDF)Scopus (88)PubMed3. Mochly-Rosen, D. Science. 1995; 268:247-251CrossrefScopus (835)PubMed4. Faux, M. C. ∙ Scott, J. D. Trends Biochem. Sci. 1996; 21:312-315Abstract(PDF)PubMed5. Newton, A. C. Curr. Biol. 1996; 6:806-809Full Text(PDF)Scopus (59)PubMed6. Lester, L. B. ∙ Scott, J. D. Recent Prog. Horm. Res. 1997; 52:409-429PubMed7. Koshland, Jr, D. E. Science.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: In a model-fitting analysis using data from 485 twin pairs, Roisman and Fraley [79] have also emphasized the role of environment (parenting quality) in accounting for the variability in toddlers' observed secure-base behaviour. Using staff/parent-rated zygosity, a model containing only shared (C) and non-shared (E) environmental variances "was able to explain the data just as well as the full [ACE] model" (p. 835) providing a heritability estimate of 0. 17. Finally, using questionnaire data of attachment disorder behaviours in a very large community sample of 13,472 twins, both twin correlations and model-fitting results suggested a strong genetic influence on attachment disorder behaviour, especially in boys [80]. It is important to recognize the power constraints of quantitative genetic studies such as those using twin comparisons. These analyses aim at assessing heritability; that is, estimating how much of the population variance is due to genetic effects (the rest is environmental variance and measurement error). The twin method is based on comparison of twin correlations or concordances. If genetic effects are important for the trait in question, then correlation or concordance between monozygotic twins should be significantly greater than that between dizygotic twins. Limited sensitivity is inherent in the methodology based on detecting significant differences between twin correlations. This is not such a great limitation for many psychological and psychiatric phenotypes with substantial heritabilities of around 0. 5, but may cause problems in detecting smaller, yet potentially important genetic effects. (It is estimated that any specific gene effect accounts for less than 1% of the variance of complex traits [81]. ) The power limitations of relatively small twin studies are not trivial. Statistical power analysis by Visscher [82] has addressed the questions of rejecting CE models within the classical twin design when the true model is ACE, i. e. there is a significant genetic variance. The simulation results have shown that necessary sample sizes become fairly large at 0. 2 heritability except when shared environmental variance exceeds 0. 5-0. 6. Visscher and colleagues [83] have provided a web-based power calculation tool for determining the minimum number of twin pairs required to detect A and C in an ACE model of given parameters. Unfortunately, all published twin studies of attachment seem to be underpowered for detecting heritability (A), but most are powerful enough for detecting large environmental contributions.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: All clinicians in the setting have had access to video visit technology since 2014, and since 2016, patients scheduling a primary care appointment through the patient portal have been required choose their visit type: office, video, or telephone visit. The only exception was for visits designated as a “routine physical,” which were offered only as office visits. Available clinicians included patients’ own personal primary care clinician (primarily MDs, including nurse practitioners) or other primary care clinicians the patient had visited recently. The scheduling availability and clinicians available were comparable across visit types, with appointment availability generally within 3 days (often available the same day). Further details about video visits used in this setting, patient characteristics associated with use, and patient experiences have been described in prior publications. 6-8 As in an office visit, clinicians conducting telemedicine visits had full access to the patient’s EHR history and documented telemedicine visits directly within the EHR. Patients could receive a call for a telephone visit at any phone number and could access video visits from home or elsewhere in their daily lives directly through any internet-connected and video-enabled computer or mobile device. We studied all completed primary care appointments booked via the patient portal from January 2016 to May 2018. We included only index visits without any other clinical visits within the previous 7 days to define a relatively distinct patient-initiated care-seeking episode. We also excluded visits for routine physical, which were not eligible for telemedicine. 6 We also identified subsets of visits with diagnoses of upper respiratory tract infection (URI) and skin conditions, 2 commonly reported categories of telemedicine chief complaints and diagnoses. For each visit, we identified any prescribing or other orders (eg, for laboratory testing or imaging) associated with the visit, including the subset of prescriptions specifically for antibiotics. To characterize short-term follow-up health care utilization, we extracted all office-visits, emergency department visits, and hospitalizations within 7 days after the index primary care visit. We examined each outcome in the full sample of all patient visits, and in the subset of visits with diagnoses of URI and skin conditions because these were common visit reasons with prior telemedicine evidence.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: 1998; 280:852-853CrossrefScopus (89)PubMed8. Koshland, Jr, D. E. ∙ Goldbeter, A. ∙ Stock, J. B. Science. 1982; 217:220-225CrossrefScopus (367)PubMed9. Ferrell, Jr, J. E. Trends Biochem. Sci. 1996; 21:460-466Abstract(PDF)Scopus (497)PubMed10. Thron, C. D. Oncogene. 1997; 15:317-325CrossrefScopus (56)PubMed11. Pines, J. ∙ Hunter, T. J. Cell Biol. 1991; 115:1-17CrossrefScopus (761)PubMed12. Ookata, K. . . . EMBO J. 1992; 11:1763-1772CrossrefScopus (218)PubMed13. Heald, R. ∙ McLoughlin, M. ∙ McKeon, F. Cell. 1993; 74:463-474Abstract(PDF)Scopus (404)PubMed14. Jin, P. ∙ Gu, Y. ∙ Morgan, D. O. J. Cell Biol. 1996; 134:963-970CrossrefScopus (254)PubMed15. Jin, P. ∙ Hardy, S. ∙ Morgan, D. O. J. Cell Biol. 1998; 141:875-885CrossrefScopus (269)PubMed16. Pines, J. ∙ Hunter, T. EMBO J. 1994; 13:3772-3781CrossrefScopus (229)PubMed17. Li, J. ∙ Meyer, A. N. ∙ Donoghue, D. J. Proc. Natl. Acad. Sci. U. S. A. 1997; 94:502-507CrossrefScopus (184)PubMed18. Toyoshima, F. . . . EMBO J. 1998; 17:2728-2735CrossrefScopus (284)PubMed19. Yang, J. . . . Genes Dev. 1998; 12:2131-2143CrossrefScopus (285)PubMed20. Brown, G. C. ∙ Hoek, J. B.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: In addition, behaviour-genetic analyses usually employ main effects models dividing up the total phenotypic variance into additive (or dominant) genetic, shared and non-shared environmental components. They normally do not separate gene-environment interactions (genetic sensitivity to environments) and gene-environment correlations (arising from experiences correlated with genetic propensities). Finally, quantitative genetic modelling does not go beyond the extent to which genetic factors influence behavioural traits, that is they are not informative about specific genes or specific environmental factors affecting the behaviours in question. Molecular genetic studies of attachmentThe development of molecular genetic methodology started to shift the focus of study towards locating and identifying specific genes underlying genetic effects evident in twin and adoptive studies, even before sequencing the human genome was completed. The widely used strategy of allele association investigates correlations of gene variants with phenotypes, i. e. , it probes if individuals with a trait of interest carry a specific gene variant more frequently than individuals in a control group (case-control studies). The method of allele association has been quickly and productively applied in the area of multi-factorial mental illnesses for which genetic components have long been demonstrated by large heritability estimates. Genes regulating the cerebral levels of important neurotransmitters (dopamine, serotonin, GABA, etc. ) or signal transmission efficiency (neurotransmitter receptors and genes) have been targeted in association studies of major psychiatric disorders such as schizophrenia, bipolar disorders, attention deficit/hyperactivity disorder (ADHD), and autism [84], as well as of personality traits [85]. The first investigation of the specific genetic background of attachment behaviour showed an association between D4 dopamine receptor (DRD4) gene polymorphism and infants' attachment behaviour [86]. The level of dopamine and the density of dopamine receptors in the PFC increase between 6-12 months of infant life, when many of these functions go through intensive development [87] and when the development of first attachment relationships typically takes place. The highly polymorphic DRD4 gene has a number of frequent functional variants in the populations [88]. One of these is a variable number 48 base pair tandem repeat (48 bp VNTR) in the coding region of the gene [89].

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: 9 comparing outcomes associated with index visit type, we accounted for a broad set of visit covariates using several types of patient characteristics previously shown to be associated with visit-type choice, including patient sociodemographic characteristics, and other measures of accessibility and affordability grouped into technology access, in-person visit barriers, and patient-clinician affiliation. 6 We used the EHR to identify patient sociodemographic characteristics (age, sex, race and ethnicity, and language preference), patient’s residential address to define patient neighborhood socioeconomic status (2010 US census measures at the census block group level), and neighborhood residential high-speed internet access level (Commission census tract level data). We included patients’ mobile portal use in the prior 365 days as a measure of mobile device access and video visit use in the prior 365 days as a measure of video visit experience. We extracted the patient’s insurance benefit cost-sharing for office visits. We also extracted the estimated drive time from the patient’s residence to the nearest health system medical facility and the type of parking offered at that facility (free parking lot or structure vs paid parking structure). We used automated data to identify whether the index visit was scheduled by a family care partner with permissions to act for the patient through the patient portal and whether the appointment was scheduled with the patient’s own personal primary care clinician. We used a multivariable logistic regression model to examine the association between index visit type (in-person visit, video visit, or telephone visit) and outcomes, including any prescribing, antibiotic prescribing, and orders during the visit; any in-person visit, emergency department visit. and hospitalization within 7 days after the index visit. The model was adjusted for patient age, sex, and race and ethnicity; neighborhood socioeconomic status; preferred language for health care; out-of-pocket cost-sharing for office visits; drive time to clinic; facility parking garage and fee; neighborhood internet access level; mobile portal use in prior 365 days; video visits in prior 365 days; whether the appointment was booked by a care partner on behalf of the patient; whether the clinician was the patient’s own personal primary care clinician; patient medical problem (Classification of Diseases and Problems, code grouping of primary diagnosis); whether the patient had preexisting chronic conditions (in clinical registry of asthma, heart failure, diabetes, and hypertension in quarter prior to index visit); and medical center.

Output: contrast


Input: Claim: Bacteria can be engineered to produce pharmaceuticals like insulin. [SEP] Text: ∙ Kholodenko, B. N. Trends Biochem. Sci. 1997; 22:288(PDF)Scopus (72)PubMed21. Ferrell, Jr, J. E. Trends Biochem. Sci. 1997; 22:288-289(PDF)Scopus (120)PubMed22. Borgne, A. ∙ Meijer, L. J. Biol. Chem. 1996; 271:27847-27854CrossrefScopus (125)PubMed23. Crenshaw, D. G. ∙ Yang, J. ∙ Means, A. R. . . . EMBO J. 1998; 17:1315-1327CrossrefScopus (170)PubMed24. Shen, M. ∙ Stukenberg, P. T. ∙ Kirschner, M. W. . . . Genes Dev. 1998; 12:706-720CrossrefScopus (311)PubMed25. Solomon, M. J. . . . Cell. 1990; 63:1013-1024Abstract(PDF)Scopus (623)PubMed26. Izumi, T. ∙ Maller, J. L. Mol. Biol. Cell. 1993; 4:1337-1350CrossrefScopus (255)PubMed27. Hoffmann, I. . . . EMBO J. 1993; 12:53-63CrossrefScopus (569)PubMed28. Ferrell, Jr, J. E. ∙ Machleder, E. M. Science. 1998; 280:895-898CrossrefScopus (885)PubMed29. Huang, C-Y. F. ∙ Ferrell, Jr, J. E. Proc. Natl. Acad. Sci. U. S. A. 1996; 93:10078-10083CrossrefScopus (973)PubMed30. Chen, R. H. ∙ Sarnecki, C. ∙ Blenis, J. Mol. Cell. Biol. 1992; 12:915-927CrossrefPubMed31. Fukuda, M. ∙ Gotoh, I. ∙ Gotoh, Y. . . . J. Biol. Chem.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: Receptor molecules coded by the 7-repeat allele have been found to have a lower potency for dopamine-mediated coupling to adenylate cyclase than receptors encoded by the other frequent, 2- or 4-repeat forms [90], and more recent results suggest an additional effect of the 48 bp VNTR on gene expression [91, 92]. Allele association studies have linked the 48 bp repeat polymorphism of the DRD4 gene with normal variations of neonatal, infant, and adult temperament [85], but also with clinical hyperactivity (ADHD) [93, 94]. In the longitudinal Budapest Infant-(BIPS), a relative over-representation of the 7-repeat variant of the 48 bp VNTR polymorphism was found in the group of infants displaying insecure-disorganised attachment behaviour with their mothers in the [86]. The estimated relative risk for disorganised attachment among children carrying the 7-repeat allele was four-fold, with the frequency of the 7-repeat allele being 67% in disorganised infants as opposed to 20% in securely attached infants [95], and with 50% frequencies in the insecure-avoidant and resistant groups. Subsequently, we also reported an interaction between the structural 48 bp repeat polymorphism and the -521 C/T promoter polymorphism in the same group of infants: the association between disorganised attachment and the 7-repeat allele was enhanced by the presence of the -521T allele [96]. researchers have failed to replicate this association [97, 98], parental genetic data and family-based analyses in the Hungarian sample showed a highly significant non-transmission of the 7-repeat allele (and the -521T~7-repeat haplotype) to securely attached infants, as well as a trend for preferential transmission to disorganised infants [95]. The preferential non-transmission of the 7-repeat allele to securely attached infants suggested that not carrying this allele might, in fact, have a protective effect, favouring the development of secure early attachment in this sample. Gene-environment interaction effects on infant attachmentSpecific genetic effects on phenotypes may be conditional on specific environments and thus be undetected in other environments. Similarly, exposure to specific environments are often influenced by choices that depend on the individuals' genetic make-up.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: We examined each outcome using a separate logistic regression model because standard composite measures of study outcomes were not readily available and each outcome represents a clinically distinct action and outcome. Standard errors were adjusted for repeated visits by patients. For easier interpretation, we calculated an adjusted rate for each outcome from the multivariable logistic regression model as if every visit in the entire cohort was an in-person visit, as if every visit in the entire cohort was a video visit, and as if every visit in the entire cohort was a telephone visit. We repeated the analyses for the 2 subsets of visits with diagnoses of URI and skin conditions (e14. 2 (StataCorp LLC). all 2 178 440 patient-scheduled primary care visits scheduled by 1 131 722 patients (611 821 [54%] female; mean [SD] age, 43 [22] years), 1 870 552 (86%) were scheduled as office visits and 307 888 (14%) as telemedicine visits, with 20 115 (7%) of the telemedicine visits by video. Overall, 13. 5% of visits were for patients younger than 18 years and 22. 2% were among patients 65 years or older; 54. 9% were for female patients, 59. 8% were for White patients, and 95. 1% were for English-speaking individuals (Table). 6 Prescribing and adjustment (Figure 1 and the eTable in the Supplement), the rate of visits with any medication prescribing was 51. 9% (95% CI, 51. 8%-52. 0%) for office visits, 38. 6% (95% CI, 38. 0%-39. 3%) for video visits, and 34. 7% (95% CI, 34. 5%-34. 9%) for telephone visits; the rate of any antibiotics prescribing was 13. 5% (95% CI, 13. 4%-13. 5%) for office visits, 10. 6% (95% CI, 10. 2%-11. 0%) for video visits, and 9. 7% (95% CI, 9. 5%-9. 8%) for telephone visits. As shown in Figure 2, the adjusted rate of ordering any laboratory test or imaging was 59. 3% (95% CI, 59. 3%-59. 4%) for office visits, 29. 2% (95% CI, 28. 5%-29.

Output: contrast


Input: Claim: CRISPR technology allows for targeted gene editing in various organisms. [SEP] Text: is Open Access? is an initiative that aims to make scientific research freely available to all. To date our community has made over 100 million downloads. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. As PhD students, we found it difficult to access the research we needed, so we decided to create a new publisher that levels the playing field for scientists across the world. How? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers. are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including winners and some of the world’s most-cited researchers. Publishing on IntechOpen allows authors to earn 10. 5772/intechopen. 1003940 this 1. Choose citation style Select style to clipboard Get citation 2. Choose citation style Select format Bibtex RIS Download citation by From the and purchase hard copies of this book, please contact the representative in India: CBS Publishers & Distributors Pvt. Ltd. www. cbspd. com | customercare@cbspd. com 1. Choose citation style Select style to clipboard Get citation 2. Choose citation style Select format Bibtex RIS Download citation Impact of this 1. IntroductionPotato (Solanum tuberosum), a member of the Solanaceae family, is at fourth position among the most important staple food crops in the globe succeeded by rice and wheat in terms of human consumption [1]. By 2050, the estimated world population will be 9. 7 billion and potato will have a vital role in the future in securing food resources for the human beings [2]. From breeding point of view, potato has both morphological and genetical advantages and disadvantages. As potato is asexually propagated, it is exempted from the need to be bred from true seeds to produce homogenous plants. Being tetraploid makes it extremely difficult for desired features to be passed on to offspring in the future [3]. Moreover, potato research is complicated and time-taking process as it is highly heterozygous and polyploid crop, which cause significant hinderance while utilizing standard breeding approaches, ultimately making use of genome editing indispensable [4, 5]. At present, research is being conducted for improvement of specific desirable traits in several crops through genome editing (GE) technologies.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: Such interplay between genes and environment may channel individual development into different trajectories early in life and affect the long-term development of mental health and disorder. A shift from association studies targeting genetic main effects towards investigating the interaction of genetic and environmental influences is reflected by the accumulating evidence for such processes being reported in recent literature [99]. Important reports are emerging, describing the moderation of behavioural responses to early rearing conditions by specific genotypes. For example, in the Dunedin study, Caspi and colleagues found that links between childhood maltreatment and later psychological maladjustment were moderated by genetic factors [100]. The functional polymorphism of the monoamine oxidase A (MAOA) gene affecting enzyme activity moderated the relation between early maltreatment and later antisocial behaviour in males. In the same population, the 5-regulatory polymorphism of the serotonin transporter gene was shown to moderate the effect of early maltreatment on adult depression in both sexes [101]. Both findings have since been replicated [102–104]. Importantly, in these studies, the genetic factors had no main effects on the outcome and the genetic influence was detected only when the environmental measure of maltreatment was included in the analyses. Our own study of the genetic effects on disorganised attachment has been extended by investigating the interplay between DRD4 gene polymorphism and maternal behaviour [54]. In order to increase the range of environmental and behavioural measures, we have done this in collaboration with the Boston-based US research group led by Dr. Karlen Lyons-Ruth, an expert on disorganised attachment in infants and atypical behaviour of mothers. Demographic risk, DRD4 7-repeat genotype, levels of atypical maternal behaviour and infant disorganised attachment were combined across the middle income, low risk Hungarian and the low income, high social risk US samples (N = 96 and 42, respectively). We found that, in the combined sample, disorganised attachment was related to both cumulative demographic risk and maternal atypical behaviour, but the main effect of infant 7-repeat genotype on disorganised attachment was no longer significant. However, the relation between maternal atypical behaviour and infant disorganisation was moderated by infant DRD4 genotype.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: 8%) for video visits, and 27. 3% (95% CI, 27. 1%-27. 5%) for telephone visits. This pattern in care processes between office visits and telemedicine visits was consistent among the subset of visits with diagnoses of URI and skin conditions. Postvisit Follow-up adjustment, 24. 5% (95% CI, 24. 5%-24. 6%) of office visits, 25. 4% (95% CI, 24. 7%-26. 0%) of video visits, and 26. 0% (95% CI, 25. 9%-26. 2%) of telephone visits were followed by an in-person office visit in the subsequent 7 days (Figure 3). Adjusted rates of emergency department visits within 7 days were not statistically significantly different between office visits (1. 30%, 95%CI, 1. 29%-1. 32%) and video visits (1. 23%; 95% CI, 1. 06%-1. 40%) but slightly higher among telephone visits (1. 37%; 95% CI, 1. 33%-1. 41%) (Figure 4). Adjusted rates of hospitalizations were not statistically significantly different by primary care index visit type; 0. 23% (95% CI, 0. 22%-0. 24%) of in-person office visits, 0. 23% (95% CI, 0. 14%-0. 32%) of video visits, and 0. 22% (95% CI, 0. 21%-0. 24%) of telephone visits were followed by hospitalization within 7 days. a large, integrated health care setting newly offering patient-scheduled primary care telemedicine visits, adjusted rates of prescribing and ordering were statistically significantly lower for telemedicine visits compared with in-person office visits. This was consistent for all visits and for the subset of visits with diagnoses of URI or skin conditions. Return office visit utilization was slightly higher after video and telephone visits than after an in-person primary care visit. Rates of emergency visits and hospitalizations were low and comparable between in-person and video or telephone primary care visits. We examined the integration of patient-initiated telemedicine visits with ongoing clinical care and patient-clinician relationships in a nonpandemic study period.

Output: contrast


Input: Claim: CRISPR technology allows for targeted gene editing in various organisms. [SEP] Text: The binding domain consists of eukaryotic transcription factors and 3–6 zinc finger repeats which recognize between 9 and 18 base pairs [22], whereas the DNA-cleavage domain has a FokI restriction enzyme DNA cleavage. To cleave the DNA, the zinc finger domain fused at its C-termini via a peptide linker to the FokI of the cleavage domain. This cleavage domain must dimerize in order to cut DNA. For two cleavage domains to dimerize, the two different ZFNs with their C-termini must bind to opposing DNA strands. If zinc finger, domains are unable to target their specific site within the genome, then off-target cleavage occurs. This off-target cleavage may result in significant double-strand breaks that stop the repair process, which results in cell death or chromosome rearrangements. Further, this leads to the random integration of donor DNA [23]. These domains can be customized to target desired DNA sequences within the complex genomes. By utilizing endogenous DNA repair mechanisms, ZFNs can be used for the precise genome alteration of higher organisms. The efficiency of a given ZFN pair depends on its binding affinity and sequence specificity, both of which impact long-term stability and on-target modification [24]. It is a time taking process to design successful ZFNs. Moreover, ZFNs have poor targeting density which leads to off-targets. 2. 2 activator-like effector nucleases (TALENs) are synthetic restriction enzymes that merge the FokI nucleases with the DNA-binding domain of TALEs. TALEs are the natural lethal proteins derived from the Xanthomonas bacteria that bind with specifically targeted DNA sites via a DNA-binding domain in the centre to activate host gene expression. This central domain uses a unique DNA-binding mechanism that involves one-to-one correspondence between an individual repeat and a single nucleotide. Each TALE array has fifteen to nineteen individual tandem repeats and is highly conserved that varies only at amino acid positions twelve and thirteen, known as repeat variable di-residue (RVD) [25]. The RVDs determine the binding specificity of DNA with the TALE array base on one-to-one correspondence along with the base as specified RVD.

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: The relationship was strong in the group of infants lacking the 7-repeat variant; as expected, mothers showing a low level of anomalous behaviour had infants displaying a low level of disorganisation, and conversely, infants of highly atypical mothers showed a high level of disorganised attachment behaviour. In contrast, the level of disorganisation in infants who carried the 7-repeat allele was at an intermediate level and unrelated to the degree of maternal atypical behaviour. Infants carrying the 7-repeat allele thus seemed to be less sensitive to maternal behaviour. At the same time, the previously reported main effect of the 7-repeat genotype on attachment disorganisation was restricted to the group with mothers low on atypical behaviour. This pattern of results was also present in the separate US and the Hungarian samples. We hypothesised that functional variations in the DRD4 gene expressed preferentially in brain regions of the reward circuit might modulate sensitivity to maternal stimuli, which in turn might result in infants' differential sensitivity to aspects of care-giving behaviour. Results of this first molecular genetic study of infant attachment [86, 96] seem to have transformed the attachment field by increasing interest in studying genetic and gene-environment interaction effects. A number of research groups have genotyped participants of previous and ongoing attachment studies, or have begun including genetic markers in the design of new studies. A further investigation of the DRD4 48 bp VNTR showed that infant genotype moderated the previously reported intergenerational transmission of mothers' unresolved trauma to disorganised attachment: the link was significant for infants carrying the 7-repeat allele only [105]. Studies have been extended by investigating associations with other candidate genes. The polymorphic serotonin transporter gene, coding for one of the important regulator of the synaptic level of the neurotransmitter serotonin, has been linked previously to anxiety-related traits [106] and affective disorders [107]. The 5-repeat polymorphism in the promoter region of the gene affects gene expression, that is the number of available serotonin transporter molecules. The 'short' 5-allele has been associated with low serotonin metabolism and behavioural problems in infant and juvenile Rhesus monkeys reared with peers only, but not in monkeys who were reared with their mothers and peers during infancy. In contrast, monkeys carrying only the 'long' allele showed normal metabolism and behavioural functioning, regardless of their early rearing history [108].

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: Although the landscape of telemedicine payment barriers has improved particularly during the COVID-19 pandemic, this study offers an opportunity to examine a study setting with patient-scheduled telemedicine fully integrated into clinical care delivery and into the EHR, with consistent clinicians and availability between visit types. This type of integration between physicians conducting in-person and telemedicine visits and settings is increasingly common under pandemic telemedicine expansions. 10 In contrast to prior findings from direct-to-consumer telehealth physicians that may not be linked with a patient’s history or ongoing clinician relationships, we found lower rates of antibiotic prescribing via clinically integrated telemedicine visits compared with in-person clinic visits. 2,3 Our findings of low but differentially higher in-person follow-up visits after telemedicine are consistent with prior findings in direct-to-consumer telemedicine settings. 4 Still, even in cases in which a telemedicine visit does not serve as a stand-alone visit, there may be additional potential visits in telemedicine in offering initial clinical and site-of-care guidance. Even as pandemic concerns subside over time and telemedicine use rates continue to evolve, our findings suggest that telemedicine can be used to safely address some concerns when offered in the context of integrated in-person health care services. Aside from social-distancing aspects of telemedicine, patients will likely continue to choose virtual care for convenient health care access, potentially when facing barriers to in-person health care services, such as travel, mobility, taking time off from work, or caregiving responsibilities. 8 We have previously published associations between patient sociodemographic and technology access characteristics and visit type choice. 6 In addition, patients may also choose telemedicine if they do not expect that their condition will require in-person examination or services. Despite increasing use and availability of video technology, telephone-based virtual care is often still the dominant type of telemedicine used by patients and physicians, including during the COVID-19 pandemic. 3 Furthermore, given the potential digital divide in technology access to support video telemedicine visits, our findings of general comparability in adverse health events between telephone and video-based telemedicine visits in primary care suggest that phone visits may continue to offer a simple health care access option without raising safety concerns.

Output: contrast


Input: Claim: CRISPR technology allows for targeted gene editing in various organisms. [SEP] Text: Accretion of reducing sugars through cold induced sweetening is swayed by several metabolic processes viz starch synthesis, degradation, glycolysis, hexogenesis and mitochondrial respiration. A family of ubiquitous enzymes termed invertases degrades starch into sucrose and fructose [51]. These invertases have been sub-localized to cell wall, vacuole and cytoplasm. Vacuole localized invertases (VInv) play a significant role in cold induced sugar production. Therefore, these have been targeted most to prevent cold induced sweetening. Silencing VInv gene has been accomplished mostly by RNAi [52], TALEN [23] andCas technologies [53]. Significant reduction in sugar levels were observed in the transgenics developed via these technologies. 4. 5 StarchPotato is a valuable source of starch. Potato starch is used for both culinary and industrial purposes. It is often made up of amylose (20–30%) and amylopectin (70–80%) [54]. The amylose/amylopectin ratio influences the characteristics of both dietary and industrial starch [55]. Amylose-free starch has better freeze-thaw stability and is thus a key component in the manufacturing of frozen foods. Amylopectin has good binding properties and is therefore employed in the paper and glue industries [56]. Therefore, to increase amylopectin content; earlier the genetic engineering efforts primarily aim to produce amylose-free (waxy) potatoes. This might be accomplished by targeting specific genes involved in starch production [57]. Potatoes that produce amylopectin starch may be created by knocking out or silencing the GBSS gene. Various methods have been used to accomplish development of amylopectin rich cultivars viz. , radiation-induced mutagenesis, antisense technologies like and, more recently,Cas [58]. Amylose-free or amylose-reduced lines of sweet potato cultivars have also been developed utilizingCAS genome editing system [59]. Nowadays main focus of researchers has been on altering starch properties to reduce its harmful effects on humans prone to obesity and diabetes. Potatoes with less digestible starch i. e. , resistant starch has been engineered by RNAi mediated silencing of genes encoding for starch binding enzymes (SBE).

Output: pass


Input: Claim: Mental health conditions can have genetic, biological, and environmental causes. [SEP] Text: A similar protective effect of the homozygous 'long/long' (l/l) genotype or else a buffering effect of maternal behaviour was found in human studies of infant attachment. For infants with a 'short' allele, variation in mothers' responsiveness was significantly associated with attachment security [109] or attachment disorganisation [110, 111]. For infants homozygous for the 'long' allele (l/l), there was no association between maternal responsiveness and attachment security or disorganisation. The gene-environment interaction effects on attachment reported in the above-cited publications are consistent with Belsky's differential susceptibility hypothesis [112], i. e. , children's susceptibility to care-giving experience seems to be moderated by genetic factors. Unfortunately, all these attachment studies, as usual, involved relatively small sample sizes. In the light of the latest meta-analyses questioning the 5-main effects [113] and 5-by stressful environment interaction effects [114], these initial investigations of genetic and gene-environment interaction effects on attachment need to be confirmed by larger studies, possibly including multiple polymorphisms of multiple candidate genes. Genetic moderation of effects of early mother-child relationship on children's problem behaviourFollowing up their above mentioned study [109], Kochanska and colleagues [115] found that the 5-promoter genotype moderated not only the relationship between maternal responsiveness and attachment security to the mother, but also the relationship of attachment security with children's later ability for self-regulation at 2, 3 and 4 years of age. Insecurely attached children with a 'short' 5-allele (s/s and s/l) developed poor regulatory capacities, but those who were securely attached did not show a deficit compared to children who were homozygous for the 'long' allele (l/l). For children homozygous for the 'long' 5-allele, attachment security was not related to self-regulation. The authors' interpretation that secure attachment relationship can serve as a protective factor in the presence of risk conferred by a genotype might however be confounded by their previously reported finding [109] that infants with l/l genotype were predominantly securely attached. It seems that in this case, consistent with other primate and human studies, the 5-l/l genotype has a protective effect in the face of parenting risk.

Output: corroborate


Input: Claim: Telemedicine eliminates the need for in-person visits entirely. [SEP] Text: 6 study has limitations. In this observational study, although our analyses adjusted for a wide range of patient and clinical covariates, we could not rule out unmeasured confounding, especially because the visit type in our study was self-selected by patients. Also, in examining patients self-scheduled visits via the portal, these findings may not represent visits booked by clinic staff at the request of a physician. More research is needed to fully characterize the full range of telemedicine visits used by patients and physicians. Our study outcomes were constructed such that the orders we identified in a given visit (eg, the ordering of future preventive tests) or visits in a given follow-up period (eg, new health problems may arise) may not have been directly related to the index visit. Because the subgroup analyses were limited to 2 specific common clinical subsets (skin and URI concerns), further research is also needed to characterize the use and outcomes associated with the wide range of specific clinical concerns and pathways addressed in primary care. In using a relatively short number of days to define a distinct care-seeking episode, we were not able account for patients’ longer-term history with a condition or the condition’s severity or its effect on the current visit type or outcome. This study did not aim to directly assess clinical appropriateness of a given visit type or health care utilization choice; further research is needed to closely examine this question. Also, the generalizability of our study is limited to the care delivery and nonpandemic setting of the data. Further research in the use of telemedicine during the COVID-19 pandemic is needed, particularly as the balance between telemedicine and in-person services and between telephone and video visits continues to evolve. Similarly visit types may vary between health care systems and geographic areas and may also vary over time. contrast to direct-to-consumer telemedicine, in this cohort study of patients using telemedicine to visit their own primary care physicians, we did not find evidence of overordering or overprescribing. Future study is needed to further examine the quality and safety of telemedicine within ongoing patient-physician relationships. Patient-scheduled video or telephone visits with their own primary care physicians were associated with a modestly higher rate of follow-up outpatient office visits than were initial in-person visits.

Output: contrast


Input: Claim: CRISPR technology allows for targeted gene editing in various organisms. [SEP] Text: Enzymatic browning (EB) causes nutritional quality loss and alters the flavor and texture of tubers. Mechanical injury caused when tubers are cut, sliced or peeled disrupts subcellular compartmentation, resulting in the release of amyloplast-localized PPOs and vacuole-localized phenolic compounds [68]. PPOs catalyze the oxidation of monophenols and/or o-diphenols to o-quinones in the presence of oxygen, which then polymerize and form complexes with proteins, resulting in brown pigment build-up [69]. This enzyme is coded by a multi-gene family, and five PPO genes in potato have been recognized thus far, with numerous allele variants for each gene [68]. Though enzymatic browning is a quantitative characteristic, PPOs are frequently used as target genes to minimize browning in tubers because the PPO loci have a strong correlation with the QTL associated with browning of tubers [70]. Because PPOs are involved in numerous physiological functions as well as defense against diseases and pests, knocking out all PPO genes would almost certainly be fatal to plants. As a result, specific gene targeting or allele silencing is necessary [68]. Substantial progress has been made in this direction. StPPO2 gene was effectively modified in the cv. Desiree viaCas9 [13]. Two different types of edited lines were created by the four-allele StPPO2 edition: those with 111-bp non-frameshift alterations and those with frameshift mutations in the coding region that may have affected the activity of the enzyme after translation. No matter the mutation type, all lines had lower PPO expression levels and were less susceptible to EB than the wild type [13]. GM potato varieties (Innate® potato) with decreased enzymatic browning (EB) and minimal acrylamide generation have been successfully developed and are under cultivation [71]. Advertisement 5. Challenges in potato gene editingPotato is an asexually propagated, heterozygous and polyploid crop, which causes multiple obstacles in utilization of genome editing approaches. Major obstacles are: complications in target designing for gene editing and acquiring homozygous mutants with mutation of all targeted gene(s), which make it essential to screen a vast number of transformed plants to identify and propagate mutated lines carrying multiple alleles.

Output: pass