You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


INTRODUCTION {#sec1-1}
============

Medicinal plants in India have been screened for contraceptive potential and anti-fertility effects, since the country has always been concerned about population explosion. The probable male/female antifertility effects arising from short or long term exposure of certain common and valuable Indian medicinal plants are published in scientific literature; but unfortunately, the outcomes of research investigations are more often complicated by scientists' compulsions to report positive results.

As Rob Verpoorte (Editor-in-Chief, *Journal of Ethnopharmacology*) emphasizes, "We must be objective in reporting our results, if one measures an activity in the mM range for a pure compound or mg/ml range for an extract, that is a finding, a number, but it does not mean that we can say that a compound or extract is active, or has an activity. That can only be discussed by comparing the results with proper controls and also taking into account the assays used."\[[@ref1]\] A cursory look at the published reproductive toxicity studies on a few medicinal herbs not only draws attention to the contradictory findings by various investigators, but also the startling differences in terms of test substances used, their standardization, and adopted test methodologies etc.\[[@ref2]--[@ref7]\]

Detailed description of herbal extract/formulation in scientific papers now seems to be essential, and no longer "add-on information," since peer-reviewed journals of international repute consider them mandatory requirements. The journal *Phytomedicine* (*International Journal of Phytotherapy and Phytopharmacology*), in its "instructions to authors," explains that "the extract being reported with pharmacological activity must have some type of standardization. The standardization can be carried out by means of a High Performance Liquid Chromatography (HPLC) fingerprint or quantitative assessment of known bioactive compounds. A qualitative HPLC-fingerprint analysis for extracts whose bioactive constituents are unknown may be used". Without standardization of an extract, the journal further states that results cannot be accepted for publication.\[[@ref8]\] *Planta Medica*, another leading journal in the field of medicinal plants, considers papers for publication only if preparation of the extracts is clearly described and supported with adequate analytical studies. \[[@ref9]\] Researchers should ensure that herbal extracts and formulations are prepared properly and well standardized for contents of pesticides, heavy metals, mycotoxin, solvent, and microbial residues, since these may create doubts as to whether adverse reproductive effects are induced by herbal constituents or by contaminants. Significantly, a good number of published articles that have "declared" certain herbs to be antifertility agents sorely lack this vital information. Such seemingly well-intended research papers have done more harm than good to ethnopharmacology and traditional medicine.

Fransworth and Waller (1982) reviewed the status of a number of plant products reported to inhibit sperm and observed contradictions that existed between findings of different researchers, "*in-vitro*" vs. "*in-vivo*" data, and also between scientific studies and traditional knowledge. They also summarized insufficient numbers of vehicle controls, poor experimental design, difficulties encountered in dissolving crude herbal extracts, different routes of administration, and variations in reproductive function among different experimental animals, as important aspects complicating the accurate assessment of effects of herbs on male fertility.\[[@ref7]\] Since several reproductive toxicity studies of the recent past were conducted according to a custom-made approach, and many times not in conformity with internationally accepted guidelines for reproductive/fertility studies, the aforementioned factors could potentially have influenced study outcomes either way.

In addition, such misleading information often attracts the attention of regulators since, in the regulatory framework, toxicity evaluation can have direct impact on restriction or removal of the herbal ingredients. Alternatively, they may lead to demands for additional safety data. Due to the lack of adequate toxicity data or existence of contrary reports on the substance under consideration, international regulatory agencies generally adopt a cautious approach, until enough scientific information is generated which can mitigate the uncertainty associated with the safety of consumption of such herbal preparations.\[[@ref10]\]

In Australia, the Complementary Medicine Evaluation Committee (CMEC) of Therapeutic Goods Administration (TGA), once objected to registration of Triphala, a polyherbal Ayurvedic formulation, based on a study which reported male reproductive toxicity on oral use of *Terminalia bellirica* extract (one of the three ingredients of the traditional formulation).\[[@ref11]\] Although the findings of the study were "successful demonstration" of contraceptive efficacy, the practical outcome turned out to be quite contrary. Consistent efforts towards generation of scientific data in subsequent years finally saw the TGA permitting inclusion of *T. bellirica* in the Australian Register of Therapeutic Goods (ARTG), thereby enabling export of such Ayurvedic products to Australia.

Another classical example is Brahmi (*Bacopa monnieri*), a popular herb with a cognition enhancing effect. Evaluation of antifertility potential of an aqueous extract of Brahmi in male mouse revealed *reversible* male infertility; but, as stated elsewhere, the phytochemcial and analytical specifications were not mentioned. Also, the study observed that the percentage of affected seminiferous tubules in the testis was 96.27% after 28 days of Brahmi treatment vs. 54.13% after 56 days of treatment and this observation, as a result, leads to contention.\[[@ref12]\]

Effects of *Ocimum sanctum* on reproductive systems of laboratory animals have attracted scientists globally, and extensive toxicological studies have been carried out, particularly on rats of both sexes. The early abortifacient effect of *O. sanctum* supplementation recorded by researchers during 1950s was later shown to be non-reproducible.\[[@ref13]\] As discussed earlier, some studies on *O. sanctum* or isolated compounds of *O. sanctum* were conducted using test material not properly standardized for purity, adopted the route of administration that is not commonly intended for the test material, or lack the rationale for appropriateness of the doses and duration of treatment used.\[[@ref14]--[@ref17]\] From established guidelines for reproductive toxicity studies, it can be observed that confirmation of the toxic potential of a test substance on fertility requires treatment of sufficient duration, a fact that seems to be "conveniently forgotten" by some investigators. Also, adverse effects in terms of transient, reversible or irreversible nature, need to be given due consideration before declaring unsafe herbs, which are otherwise relatively safe.

The observations on published literature on *Andrographis paniculata* may provide noteworthy insights in this regard. Even though *A. paniculata* is used in many hepatoprotective formulations in India, global acceptance warranted published scientific evidence in reputed journals. For quite some time, preclinical studies on *A. paniculata* have reported probable male and female antifertility effects following oral administration. However, previous investigations of rats/mice were based on oral administration of crude leaf powder of *A. paniculata* for 60 days. The phytochemical and analytical specifications of the test materials were found to be lacking in most of the published articles. Furthermore, the data on critical endpoints like sperm concentration, sperm motility, and testosterone levels were not available for possible comparison with such similar works.\[[@ref2]\] Burgos *et al*. (1998), with the aid of electron microscopic observations, disproved the earlier, conventional microscopic findings of disruption of testicular histology by treating male rats with *A. paniculata* extract (containing 6.1% andrographolide) up to 1000 mg/kg for 60 days,\[[@ref3]\] while a phase I clinical study by Mkrtchyan *et al*. (2005) found the semen quality of healthy male subjects remained unaffected upon treatment with three times the therapeutic dose level of *A. paniculata* fixed combination (180 mg of andrographolide daily for 10 days) and validated the safety of the herb. \[[@ref4]\] In another study, female mice were administered with feed mixed-sundried powder of *A. paniculata* and the dose employed was 2 g/kg per day for 6 weeks\[[@ref6]\] -- a dose level that OECD recommends for testing of substances in acute oral toxicity studies!\[[@ref18]\] Similar observations indicated that several authors of reproductive toxicity studies often do not correlate doses that can produce reproductive toxicity from dose levels normally administered in Ayurveda, Siddha and Unani (ASU) medicine. The famous dictum of Paracelsus (1493--1541) that "the dose makes the poison" should always be remembered before declaring any substance as unsafe.

Considering the importance of *A. paniculata* as a precious herbal remedy, Allan *et al*. (2009) reported in *International Journal of Toxicology* the findings of a study conducted taking into consideration internationally accepted guidelines. The authors reported that male rats orally administered with an extract of *A. paniculata* (≥10% andrographolide) up to the dose level of 1000 mg/kg daily for 86 days did not show any adverse effects in sperm parameters such as sperm concentration and sperm motility. The serum testosterone levels of treated rats were comparable to that of control rats and there were no gross and histopathological changes in testes and epididymides. The male rats, after 65 days of treatment with *A. paniculata* extract, were mated with females and produced healthy offspring.\[[@ref5]\] It appears that similar corrective studies are essential for other important medicinal plants as well.

In summary, publishing dubious antifertility effects of beneficial herbs not only leads to huge economic impact on industry for disproving the same, but also adversely affects traditional medicine\'s credibility. If so many plants were found to have antifertility effects, then where are the drugs made from them? Dose--response relationship is indeed crucial; however, convincing regulatory authorities after someone publishes conflicting reports, may be a phenomenal task. Hence, sufficient efforts should be directed to draw attention to this perplexing problem. Steps should be taken to prevent its recurrence. Adequate awareness has to be created among researchers toward developing the concept, designing, executing, interpreting, and reporting the findings of reproductive/antifertility studies in accordance with internationally accepted guidelines. This critical issue needs attention of all the funding agencies supporting research on natural products with an ethnomedical basis. Overall there is a need to promote genuine, reproducible findings based on sound scientific principles, and, at the same time, discourage publication of outcomes of studies falling short of basic and reliable research requirements. In addition to researchers and funding agencies, this point needs attention from custodians of published scientific research viz. editors, reviewers, and editorial board members of scientific journals. If such precautions are exercised at the level of researchers, funding agencies, and the publishing community, we shall together ensure that research declaring herbs to be "safe" or "toxic" is responsible and reliable.

**Source of Support:** Nil

**Conflict of Interest:** None declared.