โจทย์ ปรนัย
Which of the following best describes the concept of "beat perception" as it relates to the auditory capabilities of newborn infants?

Research has shown that newborn infants can extract temporal regularities from sound sequences

A B S T R A C T Newborn infants have been shown to extract temporal regularities from sound sequences, both in the form of learning regular sequential properties, and extracting periodicity in the input, commonly referred to as a regular pulse or the ‘beat’. However, these two types of regularities are often indistinguishable in isochronous sequences, as both statistical learning and beat perception can be elicited by the regular alternation of accented and un­ accented sounds. Here, we manipulated the isochrony of sound sequences in order to disentangle statistical learning from beat perception in sleeping newborn infants in an EEG experiment, as previously done in adults and macaque monkeys. We used a binary accented sequence that induces a beat when presented with isochronous timing, but not when presented with randomly jittered timing. We compared mismatch responses to infrequent deviants falling on either accented or unaccented (i.e., odd and even) positions. Results showed a clear difference between metrical positions in the isochronous sequence, but not in the equivalent jittered sequence. This suggests that beat processing is present in newborns. Despite previous evidence for statistical learning in newborns the effects of this ability were not detected in the jittered condition. These results show that statistical learning by itself does not fully explain beat processing in newborn infants.

โจทย์ ปรนัย
According to the research, what experimental method is used to differentiate beat perception from statistical learning in newborns?

There are deviant and standard stimuli at the Beat and Offbeat positions in the Isochronous and Jittered conditions which are used to differentiate beat perception from statistical learning in newborns

3. Results Fig. 3 shows an overview of the central (average of C3, Cz, and C4) responses elicited by deviant and standard stimuli at the Beat and Offbeat positions in the Isochronous and Jittered conditions

โจทย์ ปรนัย
What does the mismatch response (MMR) in EEG studies indicate about newborns' auditory processing?

Due to the current experiment, statistic is not the accurate way to detect beat in infants

4. Discussion The results show that whereas in the isochronous condition there was a significant difference between the MMR amplitudes obtained for de­ viants presented at beat and offbeat positions, this difference was absent

โจทย์ ปรนัย
What does the term "statistical learning" refer to in the context of auditory processing in newborns?

statistical learning is the intregation of raw data and analyzation in order to make up an avaliable information

Statistical learning is a rapid and robust mechanism that enables adults and infants to extract patterns of stimulation embedded in both language and visual domains. Importantly, statistical learning operates implicitly, without instruction, through mere exposure to a set of input stimuli. From acquiring specific items to forming general rules - PMC

โจทย์ ปรนัย
Which condition in the EEG study did NOT result in a differentiation between beat and offbeat responses in newborns?

according to the result of experiment offbeat and beat can only be sensed in isochronous condition.

Fig. 3. Left: Grand average (N = 27) ERP responses averaged over the three central electrodes (C3, Cz, C4) to deviant (D1, D2), standard (S1, S2) stimuli and the deviant minus standard difference waveforms (D1-S1, D2-S2) for the isochronous and the jittered condition. The panel on the bottom overplots all four difference waveforms. Right: Scalp distributions the average deviant-minus-standard difference amplitudes from the 200–300 ms time window (marked by grey rectangles on the signals on the left). 0 ms denotes the start of the sound at the Beat position for D1 and S1 and the start of the sound at the Offbeat position for D2 and S2. Note that the labels Beat and Offbeat are used to refer to the position of the deviants in the rhythmic sequence. But a Beat (or Offbeat) can, of course, only be sensed in the isochronous condition, and not in the jittered condition.

โจทย์ ปรนัย
Which neural mechanism is thought to underlie the synchronization of movement to a beat?

โจทย์ ปรนัย
How does beat perception in newborns relate to their later musical abilities?

This experiment is about the ability in each infant showing the different of their cognitive in beat and offbeat in jittered or isochronous condition.

3. Results Fig. 3 shows an overview of the central (average of C3, Cz, and C4) responses elicited by deviant and standard stimuli at the Beat and Offbeat positions in the Isochronous and Jittered conditions, together with the corresponding difference waveforms. The difference wave­ forms for the beat deviants appear as a broad negative wave, which is consistent with the morphology of mismatch response (MMR) in newborn infants (Kushnerenko et al., 2002). Figures including all channels included in the analyses for all grand averages (Supplementary Figs. 1–3) as well as individual averages and 95% confidence intervals (CI) for all grand averages (Supplementary Figs. 4–15) are given in the Supplementary Materials. Descriptive statistics are given in Supple­ mentary Table 2. Fig. 4 shows the distributions of the MMR amplitudes obtained for the Beat and Offbeat positions, separately for the Isochro­ nous and the Jittered conditions

โจทย์ ปรนัย
What is the primary purpose of using EEG in studies of auditory processing in newborns?

It was settled nearby infants' brain

Fig. 2. Rhythmic sequence generation visualized as a transition network, showing the transition probabilities between the individual sound elements A, U and T. Note that this representation is a simplification as it does not include certain constraints on the way concatenated patterns can follow each other (see main text). (Adapted from Honing et al., 2018). G.P. Haden ´ et al.Cognition 243 (2024) 105670 5 the ground electrode on the forehead. Data was recorded using a directcoupled amplifier (V-Amp, Brain Products, Munich, Germany) at 24-bit resolution with a sampling rate of 1000 Hz. Signals were off-line filtered between 1.5 and 30 Hz and epochs of − 100–500 ms with respect to sound onset were extracted for each of the D1, D2, S1 (only after S2 to control for acoustic context; for brevity referred to simply as S1 from this point on), and S2 stimuli. The 100-ms pre-stimulus interval served as the baseline for amplitude measurements and illustrations. Due to low signal-to-noise ratio on other electrodes only data from electrodes F3,

โจทย์ ปรนัย
What does an isochronous condition in an auditory study typically involve?

It was mentioned in this article as a consistent temporal interval between sounds.

Here, we presented a variant of Bouwer et al. (2016) stimulus paradigm (same stimuli, but no active condition, no silent movie pre­ sented, fewer but longer stimulus blocks, cf. Procedure sections) to sleeping newborn infants to separate the effects of beat perception from those of statistical learning (Fig. 1) in order to provide converging evi­ dence to the notion that newborns brains can process the beat in rhythm, as suggested in our previous study (Winkler et al., 2009), while con­ trolling for the effects of statistical learning. Response differences (MMR) between rare deviant and corresponding standard sounds were calculated at beat (odd) and offbeat (even) positions, separately for the isochronous and the jittered sequences (note that we refer to odd and even positions as “beat” and “offbeat” even for the jittered sequences, to make the terminology more consistent). In line with the effects in adults, firstly we expected newborns to learn the statistically predictable alternation between louder and softer sounds. Since beat perception does not occur in the jittered condition and the MMR is calculated by comparing the responses to sounds with identical acoustic properties and context (i.e., no acoustic difference between the tones in the compared nor in the preceding position), differences in the MMR re­ sponses between beat and offbeat positions should result from learning the sequential statistical regularities of the sound sequence (i.e., the alternation). Secondly, we expected to find evidence for beat perception, to corroborate our previous results (c.f. Bouwer et al., 2016 as well as Winkler et al., 2009). Based on Bouwer et al. (2016) results, beat perception should make the MMR difference between beat and offbeat position larger in the isochronous than in the jittered condition, as it would additionally contribute to the beat-offbeat difference.

โจทย์ ปรนัย
Which auditory feature is NOT directly studied in the newborn auditory processing research?

This experiment only look for beat perception, statistical learning, rhythmic entrainment and melody recognition

A B S T R A C T Newborn infants have been shown to extract temporal regularities from sound sequences, both in the form of learning regular sequential properties, and extracting periodicity in the input, commonly referred to as a regular pulse or the ‘beat’. However, these two types of regularities are often indistinguishable in isochronous sequences, as both statistical learning and beat perception can be elicited by the regular alternation of accented and un­ accented sounds. Here, we manipulated the isochrony of sound sequences in order to disentangle statistical learning from beat perception in sleeping newborn infants in an EEG experiment, as previously done in adults and macaque monkeys. We used a binary accented sequence that induces a beat when presented with isochronous timing, but not when presented with randomly jittered timing. We compared mismatch responses to infrequent deviants falling on either accented or unaccented (i.e., odd and even) positions. Results showed a clear difference between metrical positions in the isochronous sequence, but not in the equivalent jittered sequence. This suggests that beat processing is present in newborns. Despite previous evidence for statistical learning in newborns the effects of this ability were not detected in the jittered condition. These results show that statistical learning by itself does not fully explain beat processing in newborn infants.

โจทย์ ปรนัย
What term is used to describe the appearance of scientific credibility used in the marketing of unproven cell-based therapies?

This research offers products commercialized cell and cell-based products with unknown safety

A B S T R A C T The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-toconsumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and genebased interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven

โจทย์ ปรนัย
According to the article, which of the following is NOT a recognized reporting mechanism for adverse effects from cell and gene therapies?

From the overall of this article, I suppose there is no safety or any adequate about this product

 unclear scientific rationale to suggest potential efficacy;  lack of understanding on the mechanism of action and/or the biological function to support clinical use;  insufficient data from in vitro assays, animal models and/or clinical studies regarding the safety profile to support the use in patients;  lack of a standardized approach to confirm product quality and ensure consistency in cell manufacturing based on adherence to mandatory guidelines;  inadequate information disclosed to patients to enable proper informed consent;  use within non-standardized or non-validated administration methods;

โจทย์ ปรนัย
What ethical consideration is primarily challenged by direct-to-consumer marketing of unproven cell and gene therapies?

This product is not approved as a safety product to general people yet

The primary ethical consideration challenged by direct-to-consumer (DTC) marketing of unproven cell and gene therapies is informed consent and the potential for patient harm, due to the misleading advertising and lack of regulation that often accompanies these products.

โจทย์ ปรนัย
What key feature differentiates proven CGT products from unproven ones according to regulatory standards?

CGT-based interventions are often promoted through patient testimonials, celebrity endorsements and other tools of persuasion due to the unproven in widespread

In the absence of clinical trial data to establish safety and efficacy, unproven CGT-based interventions are often marketed through patient testimonials, celebrity endorsements and other tools of persuasion. Clinic websites may include positive statements purportedly obtained from patients or contain videos featuring patients discussing improvements that they claim resulted from the marketed intervention. While these testimonials often seem compelling, they are, even if believed to be accurate by the patient, problematic for use in medical decision-making. In addition, their veracity is often in question, for a variety of reasons, further limiting their utility. First, it is impossible to know whether the purported benefits, either transient or long-term, result from CGT administration. This includes placebo effects, which may play a role in any given patient’s sense of improvement. Second, patients may have been paid or offered discounts on procedures in exchange for providing positive statements. In any case, evidence-based medical treatments cannot rely on anecdotal cases but are developed on the consistency of results following a standardized procedure that has to be authorized, supervised and evaluated by regulatory bodies.

โจทย์ ปรนัย
Which of the following is a risk associated with unproven CGT products highlighted in the article?

It is not approved yet because of the high risk effect on patient

 unclear scientific rationale to suggest potential efficacy;  lack of understanding on the mechanism of action and/or the biological function to support clinical use;  insufficient data from in vitro assays, animal models and/or clinical studies regarding the safety profile to support the use in patients;  lack of a standardized approach to confirm product quality and ensure consistency in cell manufacturing based on adherence to mandatory guidelines;  inadequate information disclosed to patients to enable proper informed consent;  use within non-standardized or non-validated administration methods;  uncontrolled experimental procedures in humans;  supervision, review and approval by competent government organizations is lacking; and  payment, often of exorbitant fees, for experimental treatments or for participation in so-called clinical studies (“pay-to-participate”).

โจทย์ ปรนัย
Which of the following is NOT a typical characteristic of unproven CGT products as discussed in the article?

High treatment costs for patients is not mentioned in the article

In the absence of clinical trial data to establish safety and efficacy, unproven CGT-based interventions are often marketed through patient testimonials, celebrity endorsements and other tools of persuasion. Clinic websites may include positive statements purportedly obtained from patients or contain videos featuring patients discussing improvements that they claim resulted from the marketed intervention. While these testimonials often seem compelling, they are, even if believed to be accurate by the patient, problematic for use in medical decision-making. In addition, their veracity is often in question, for a variety of reasons, further limiting their utility. First, it is impossible to know whether the purported benefits, either transient or long-term, result from CGT administration. This includes placebo effects, which may play a role in any given patient’s sense of improvement. Second, patients may have been paid or offered discounts on procedures in exchange for providing positive statements. In any case, evidence-based medical treatments cannot rely on anecdotal cases but are developed on the consistency of results following a standardized procedure that has to be authorized, supervised and evaluated by regulatory bodies. Another common characteristic of unproven CGT-based interventions is the supposed ability of the same treatment approach to help patients with many different and unrelated conditions. Cells, particularly purported “stem cells,” are sometimes claimed to have special abilities to seek out and repair damaged tissues in such a manner that the same unproven intervention could potentially help patients with conditions ranging from neurological disorders to male-pattern baldness. These broad claims of efficacy across unrelated conditions do not align with established CGTs nor with those under legitimate clinical investigation and may be a useful indicator of clinics offering interventions not supported by appropriate evidence. These unproven interventions are often marketed in a manner that appears to suggest they are supported by stronger scientific evidence than exists. These marketing strategies are collectively referred to as “tokens of scientific legitimacy” (Table 1), and they have been discussed in the literature [8
10]. Although each of these might be a characteristic of legitimate clinical research, none on its own provides sufficient evidence to establish a novel therapy as safe and effective. Their widespread use in direct-to-consumer advertising makes it more difficult for patients, families or caregivers considering their treatment options to assess if these interventions are appropriate. As a result, these tokens may mislead some patients into choosing unproven interventions without fully understanding the extent to which they are unproven rather than supported by appropriate scientific evidence. Patients considering their medical options, as well as clinicians and others involved in the development of CGTs that may be called on to offer advice to patients, should be aware of the various marketing tactics and tokens of legitimacy commonly used by providers of unproven cell and gene therapies.

โจทย์ ปรนัย
How do regulatory bodies like the FDA and EMA ensure the safety of CGT products?

Clinical trial progression is an indispensable evidence to improve safety for patient

There are considerable risks involved if proper evidence of clinical benefit and safety are not proven by a structured and phased approach to clinical trial progression. If a medical product receives accelerated approval without evidence of effectiveness, then the likelihood of ever generating scientific evidence is greatly reduced. Sponsors and product developers would not be motivated to demonstrate effectiveness because they are already in the market and often have no direct competition. Patients and their family members do not wish to miss any chance that a therapy might offer a benefit, especially if the risks or harm are perceived as low. Subsequent efforts to conduct randomized controlled trials are therefore likely to experience significant difficulties recruiting study participants. Social media and internet-based communications often exacerbate the ambiguity perceived between “proven” and “unproven” therapies in patient communities. Regulators may be unable to challenge political lobbying, advocacy and market forces.

โจทย์ ปรนัย
What is the primary goal of the ISCT's position on cell and gene therapies as mentioned in the article?

The primary goal is to ensure the safety in the translation of cell and gene therapies

Introduction Two decades ago, businesses began advertising purported stem cell treatments on a direct-to-consumer basis for myriad indications. More recently, similar advertisements for purported gene therapy or extracellular vesicle treatments have also arisen. This phenomenon persists today, with a global marketplace of clinics selling putative advanced medicinal therapies without substantive evidence of safety and/or efficacy. This occurs under a number of different guises. Some clinics claim that the supposed advanced products they are selling are indeed safe and effective. Other businesses acknowledge the investigational nature of what they are selling but charge patients to access advanced products in pay-to-participate studies. These purported studies are generally poorly designed, unblinded, unrandomized and uncontrolled; typically, they have not been reviewed and authorized by national regulators. The International Society for Cell & Gene Therapy (ISCT), along with peer scientific organizations and patient advocacy groups, has played an important role in opposing the premature commercialization of unproven cell- and gene-based interventions and supporting the development of evidence-based, safe, and efficacious advanced medicinal products. The ISCT and other groups have also worked toward better regulation of cell and gene therapy investigations to assist the US Food & Drug Administration (FDA) and other regulatory bodies crack down on businesses offering unproven cell and gene therapies. The goal of ISCT and peer scientific organizations is to advocate for patient safety and access to new therapies by supporting clinical translational processes and corresponding regulatory paths developed to generate robust safety and efficacy data before products are commercialized. In particular, rigorous evaluation by national regulators of the benefit-to-risk balance for each individual product increases the likelihood that only safe and effective cell- and gene-based products enter the commercial marketplace. In this guide for ISCT members, the ISCT Committee on the Ethics of Cell and Gene Therapy provides background and suggested strategies to counteract the direct-to-consumer marketing of unproven and unapproved cell-based, cell-derived and gene-based interventions. For the purposes of the Members Guide, cell-based, cellderived and gene-based therapies/interventions will herein be consolidated under the term “CGT.” The purpose of this document is to address in an accessible manner the problematic scientific, ethical and legal concerns inherent in direct-to-consumer promotion of prematurely commercialized CGTs. The Guide also identifies additional resources that ISCT members might wish to consult to explore this subject in greater detail, including the 2015 ISCT comprehensive reference guide “Talking about Unproven Cell-Based Interventions” [1]. The Guide begins by identifying common and recognizable features of unproven CGTs. Although there are variations in how such products reach the marketplace and are commercialized, it is common for them to be advertised and administered without a clear scientific rationale, sufficient pre-clinical data to support their use in patients, convincing safety and efficacy data generated in properly controlled clinical trials and/or standardized and reliable methods to confirm product quality and consistency. The Guide further identifies other common characteristics of unproven CGTs. These include various strategies that businesses use to make unproven CGTs appear scientific and evidence-based. One prominent strategy is the use of “tokens of legitimacy” to make unproven products seem science-based, subject to appropriate oversight and ready for clinical deployment (Table 1) [2
4]. ISCT members, patients, families, caregivers, research participants and other relevant parties must be educated on how to identify such tokens of legitimacy and how they are often used to convince patients that CGT products are safe and effective in the absence of sufficient safety and efficacy data [5]. Next, the Guide provides insight into what constitutes evidencebased CGT products. There are cell- or gene-therapy based products that have been carefully tested in rigorously designed and conducted clinical trials and that subsequently have received pre-marketing authorization by national regulatory bodies. It is thus critically important to distinguish such evidence-based and approved therapies from products lacking evidence and regulatory approval. The Guide helps readers differentiate such products from one another and better understand why some products have obtained pre-marketing authorization. In brief, convincing, or substantial, evidence of safety and efficacy is typically required by regulatory bodies responsible for reviewing CGT products submitted for pre-marketing authorization. The Guide reviews what levels of evidence typically are required to obtain marketing approval and addresses how to determine when such evidence is absent or deficient. Many patients and their caregivers, as well as clinicians and scientists, do not have framework for what to do if a business is advertising potentially risky unproven CGTs or when there is reason to think that a recipient of an unproven CGT product has been harmed as a result of being administered such an intervention. The Guide identifies reporting mechanisms for ISCT members, patients and other parties to report possible adverse events associated with such products or what may be problematic marketing practices or clinical activities. Although reporting mechanisms differ across jurisdictions, many national regulatory bodies offer online tools that patients and clinicians can use to report adverse events or concerning marketing activities associated with the sale and administration of unproven CGT products. Resources that enable such reporting may be provided from various regulatory and professional bodies. Regulatory bodies responsible for enforcing laws requiring honest advertising practices and consumer protection agencies may provide recourse for deceptive advertising claims. Medical boards and colleges are responsible for regulating the practice of physicians and other licensed health care professionals and may provide tools for reporting physician practices related to unproven CGTs. Drug regulatory agencies also provide mechanisms to report provision of unlicensed cell- or genebased interventions and/or resulting adverse effects. The Guide provides insight into how to find and use a variety of such reporting tools. Finally, the Guide describes additional steps ISCT members and other concerned parties can take to contest direct-to-consumer

โจทย์ ปรนัย
What is a potential consequence for patients using unproven CGT products?

It is not approved by any organization or even general people which shows such a stable risk for patient

Conclusions Businesses selling unlicensed and unproven stem cell interventions and related “regenerative medicine” products have now operated in the global marketplace for approximately two decades. ISCT has played an important role in drawing attention to problematic commercial and clinical activities that put patients at risk and expose them to unnecessary and foreseeable risks. ISCT has also been an engaged participant in broader public conversations about the importance of ensuring that safety and efficacy of CGTs are evaluated in well-designed and carefully conducted clinical trials that comply with all applicable ethical, legal, scientific, and clinical standards. This document reflects ISCT’s commitment to promoting patient safety and public understanding by helping ISCT members, patients and other parties identify “red flags” associated with concerning practices and also understand the importance of conducting robust pre-clinical and clinical research to determine whether CGTs are backed by substantial safety and efficacy data and can justifiably be marketed for particular indications.

โจทย์ ปรนัย
What role does the ISCT play in the context of cell and gene therapies?

ISCT plublicized their support into safety therapies for general people

The International Society for Cell & Gene Therapy (ISCT) plays a key role in driving the translation of cell and gene therapies from research to clinical use by fostering collaboration, setting standards, and advocating for responsible development. It brings together researchers, clinicians, regulators, and industry partners to address challenges in areas like safety, manufacturing, and access to capital, while also working to combat unethical practices and protect patients from unproven and risky treatments.