update vignette

docs/vignette-rag.md

@@ -3,12 +3,14 @@
 This vignette demonstrates the RAG module of BioChatter as used by the
 BioChatter Next application. This basic use case involves an LLM manuscript
 reading assistant and a vector database with embedded scientific manuscripts.
-The manuscripts are recent reviews on the topic of ABC transporters and drug
-resistance phenomena, which we currently investigate in our DECIDER cohort.
-Manuscripts such as these can be absent from the knowledge base of LLMs for
-various reasons, such as their recency or the fact that they are not open
-access. RAG opens up the possibility to retrieve relevant information from
-these manuscripts, and to inject it into the LLM's generation process.
+The manuscripts are recent reviews on the topic of ABC transporters (active
+transport proteins that often serve as efflux pumps in many tissues, with a
+major function of clearing exogenous substances) in drug resistance phenomena,
+which we currently investigate in our [DECIDER](https://deciderproject.eu)
+cohort.  Manuscripts such as these can be absent from the knowledge base of LLMs
+for various reasons, such as their recency or the fact that they are not open
+access. RAG opens up the possibility to retrieve relevant information from these
+manuscripts, and to inject it into the LLM's generation process.
 
 ## Usage
 
@@ -58,7 +60,8 @@ Asking the naive ChatGPT 3.5 (free access), the same question yields a very
 different answer. The free version of ChatGPT cannot search the internet, and
 does not provide any citations for the general answer it provides. You can read
 the full answer
-[here](https://chat.openai.com/share/810075aa-69fe-4c06-859d-229e250f4c41). 
+[here](https://chat.openai.com/share/810075aa-69fe-4c06-859d-229e250f4c41). For
+convenience, all three conversations are copied below. 
 
 ## Conclusion
 
@@ -69,6 +72,85 @@ we provide an instance of BioChatter Next, including GPT access and a vector
 database instance, free of charge at
 [https://next.biochatter.org](https://next.biochatter.org).
 
+## Conversations
+
+### BioChatter RAG
+
+#### Contextual Prompt:
+You are an assistant to a biomedical researcher.
+
+#### Contextual Prompt:
+You have access to text fragments from one or multiple scientific manuscripts, which were retrieved by their semantic similarity to the user's question.
+
+#### Contextual Prompt:
+Your task is to help the user understand the manuscripts and their relevance to their questions. Be concise in your explanations, provide quotes from the manuscripts where appropriate, and be open about limitations in cases where the text does not contain pertinent information.
+
+#### Message From You:
+What is known about the CFTR protein in resistance to ovarian cancer?
+
+#### Message From BioChatter:
+Based on the provided information, there are several studies that suggest a potential role of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein in resistance to ovarian cancer. Here are some key findings from the referenced manuscripts:
+
+1. Gene expression profiling of ovarian tumors before and after chemotherapy revealed molecular signatures of chemoresistant tumors (M, et al., 2006). This study did not specifically mention CFTR, but it provides insights into the molecular changes associated with chemoresistance.
+
+2. ABCF2 expression, which is related to CFTR, was investigated in clear cell adenocarcinoma of the ovary. The study found a relationship between ABCF2 expression and response to chemotherapy or prognosis (Tsuda H, et al., 2010).
+
+3. Alterations in gene copy numbers, including CFTR, were identified as a mechanism for acquired drug resistance in cancer (Yasui K, et al., 2004).
+
+4. ABCF2, an Nrf2 target gene related to CFTR, was found to contribute to cisplatin resistance in ovarian cancer cells (Bao L, et al., 2017).
+
+5. CFTR was not specifically mentioned in the context of ovarian cancer, but a study on hepatocellular carcinoma found that silencing circ-TCF4.85 inhibited cancer progression through microRNA-486-5p-targeted inhibition of ABCF2 (Gao J, et al., 2020).
+
+6. Constitutive activation of nuclear factor κB (NF-κB) was associated with CFTR expression and promoted cancer progression and poor prognosis in cervical cancer (Wu Z, et al., 2013).
+
+7. High levels of CFTR expression were associated with tumor aggression in ovarian cancer, and knockdown of CFTR suppressed ovarian cancer cell proliferation (Xu J, et al., 2015).
+
+It is important to note that while these studies suggest a potential association between CFTR and resistance to ovarian cancer, the exact mechanisms and clinical implications are still being investigated. Further research is needed to fully understand the role of CFTR in ovarian cancer resistance.
+
+#### Message From You:
+Tell me more about the studies of aggression and knockdown of CFTR in vivo.
+
+#### Message From BioChatter:
+Based on the provided information, there are two relevant studies regarding the aggression and knockdown of CFTR in ovarian cancer:
+
+1. The study by Wu et al. (2013) investigated the constitutive activation of nuclear factor κB (NF-κB) and its contribution to CFTR expression, cancer progression, and poor prognosis in cervical cancer. Although this study is not specific to ovarian cancer, it provides insights into the role of CFTR and NF-κB in promoting cancer progression.
+
+2. The study by Xu et al. (2015) focused specifically on ovarian cancer and found that high levels of CFTR expression were associated with tumor aggression. They also demonstrated that knockdown of CFTR suppressed the proliferation of ovarian cancer cells in vitro and in vivo. This study suggests that CFTR may play a role in promoting ovarian cancer growth.
+
+These studies provide evidence for the involvement of CFTR in cancer aggression and suggest that targeting CFTR could be a potential therapeutic strategy. However, it is important to note that these studies focus on different types of cancer (cervical and ovarian), and the specific mechanisms underlying CFTR's role in ovarian cancer aggression and its knockdown effects are not fully elucidated.
+
+It is worth mentioning that the other references provided in the text fragments are not directly related to the aggression and knockdown of CFTR in ovarian cancer. They discuss topics such as the structure and function of ABC transporters, drug resistance, and inflammation in different contexts.
+
+### ChatGPT 4
+
+#### Anonymous
+What is known about the CFTR protein in resistance to ovarian cancer?
+
+#### ChatGPT
+The CFTR protein, known as the cystic fibrosis transmembrane conductance regulator, plays a significant role in ovarian cancer. Research has shown that CFTR is expressed more in ovarian cancer tissues compared to benign ovarian tumors and normal ovaries. This overexpression of CFTR is associated with more advanced stages of ovarian cancer, poor histopathological grade, and higher serum Ca-125 levels, which are all markers of more aggressive disease. Interestingly, the serous type of ovarian cancer shows stronger CFTR staining compared to other types.
+
+Moreover, the role of CFTR extends beyond its traditional function as an ion channel. It interacts with various intracellular signaling pathways that are crucial in cancer progression. For example, in ovarian cancer, CFTR overexpression is linked to interactions with the c-Src signaling pathway, which is involved in cellular growth.
+
+The implications of CFTR expression in ovarian cancer are significant. In studies where CFTR was downregulated, there was a decrease in cell invasion, migration, proliferation, adhesion, and colony formation in vitro. In vivo experiments also showed that the tumorigenic abilities of ovarian cancer cells were significantly repressed when CFTR expression was reduced.
+
+These findings highlight the complex role of CFTR in ovarian cancer and suggest that it could be a potential target for therapeutic intervention. However, it is important to note that the role of CFTR in cancer is multifaceted and varies among different types of cancers. Therefore, a detailed understanding of its function in specific cancer types, like ovarian cancer, is crucial for developing targeted treatments​​​​ (https://pubmed.ncbi.nlm.nih.gov/25738998/, https://jmhg.springeropen.com/articles/10.1186/s43042-022-00308-7).
+
+### ChatGPT 3.5
+
+#### Anonymous
+What is known about the CFTR protein in resistance to ovarian cancer?
+
+#### ChatGPT
+As of my last knowledge update in January 2022, there is limited direct information about the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein's role in resistance to ovarian cancer. CFTR is primarily associated with cystic fibrosis, a genetic disorder that affects the lungs and other organs. However, some research suggests potential links between CFTR and cancer, including ovarian cancer, although the mechanisms are not fully understood.
+
+Here are some key points to consider:
+
+CFTR Expression: Studies have shown that CFTR is expressed in various tissues, including the female reproductive system. Abnormal CFTR expression or function could potentially impact the development or progression of ovarian cancer. Research is ongoing to understand the role of CFTR in cancer biology.
+CFTR Mutations: Certain mutations in the CFTR gene have been associated with an increased risk of cancer, although the evidence for ovarian cancer specifically is limited. Mutations in CFTR are more commonly known for their role in cystic fibrosis. Individuals with cystic fibrosis have an increased risk of various cancers, including gastrointestinal cancers, but the link to ovarian cancer is not well-established.
+Ion Transport and Cancer: CFTR is involved in ion transport across cell membranes, and this function could potentially influence cellular processes relevant to cancer. Changes in ion transport can affect cell proliferation, apoptosis, and other cellular functions that are important in cancer development and progression.
+Potential Therapeutic Target: Some research suggests that modulating CFTR activity or expression could be a potential target for cancer therapy, including ovarian cancer. However, more research is needed to determine the feasibility and effectiveness of such approaches.
+It's important to note that the understanding of the role of CFTR in cancer, including ovarian cancer, is an evolving field, and new research findings may have emerged since my last update in January 2022. To get the most up-to-date information on this topic, I recommend consulting recent scientific literature and speaking with medical experts or researchers actively working in the field of ovarian cancer and CFTR biology.
+
 ## References
 
 - [1] [ABC transporters affects tumor immune microenvironment to regulate cancer