Dialogizer: Context-aware Conversational-QA Dataset Generation from Textual Sources

To address the data scarcity issue in Conversational question answering (ConvQA), a dialog inpainting method, which utilizes documents to generate ConvQA datasets, has been proposed. However, the original dialog inpainting model is trained solely on the dialog reconstruction task, resulting in the generation of questions with low contextual relevance due to insufficient learning of question-answer alignment. To overcome this limitation, we propose a novel framework called Dialogizer, which has the capability to automatically generate ConvQA datasets with high contextual relevance from textual sources. The framework incorporates two training tasks: question-answer matching (QAM) and topic-aware dialog generation (TDG). Moreover, re-ranking is conducted during the inference phase based on the contextual relevance of the generated questions. Using our framework, we produce four ConvQA datasets by utilizing documents from multiple domains as the primary source. Through automatic evaluation using diverse metrics, as well as human evaluation, we validate that our proposed framework exhibits the ability to generate datasets of higher quality compared to the baseline dialog inpainting model.Comment: Accepted to EMNLP 2023 main conferenc

Asking Clarification Questions to Handle Ambiguity in Open-Domain QA

Ambiguous questions persist in open-domain question answering, because formulating a precise question with a unique answer is often challenging. Previously, Min et al. (2020) have tackled this issue by generating disambiguated questions for all possible interpretations of the ambiguous question. This can be effective, but not ideal for providing an answer to the user. Instead, we propose to ask a clarification question, where the user's response will help identify the interpretation that best aligns with the user's intention. We first present CAMBIGNQ, a dataset consisting of 5,654 ambiguous questions, each with relevant passages, possible answers, and a clarification question. The clarification questions were efficiently created by generating them using InstructGPT and manually revising them as necessary. We then define a pipeline of tasks and design appropriate evaluation metrics. Lastly, we achieve 61.3 F1 on ambiguity detection and 40.5 F1 on clarification-based QA, providing strong baselines for future work.Comment: 15 pages, 4 figure

The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis

Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that function as key signal transducers of a wide spectrum of extracellular stimuli, including growth factors and pro-inflammatory cytokines. Dysregulation of the extracellular signal-regulated kinase (ERK) MAPK pathway is associated with human skeletal abnormalities including Noonan syndrome, neurofibromatosis type 1, and cardiofaciocutaneous syndrome. Here, we demonstrate that ERK activation in osteoprogenitors is required for bone formation during skeletal development and homeostasis. Deletion of Mek1 and Mek2, kinases upstream of ERK MAPK, in osteoprogenitors (Mek1(Osx)Mek2(-/-)), resulted in severe osteopenia and cleidocranial dysplasia (CCD), similar to that seen in humans and mice with impaired RUNX2 function. Additionally, tamoxifen-induced deletion of Mek1 and Mek2 in osteoprogenitors in adult mice (Mek1(Osx-ERT)Mek2(-/-)) significantly reduced bone mass. Mechanistically, this corresponded to decreased activation of osteoblast master regulators, including RUNX2, ATF4, and beta-catenin. Finally, we identified potential regulators of osteoblast differentiation in the ERK MAPK pathway using unbiased phospho-mass spectrometry. These observations demonstrate essential roles of ERK activation in osteogenesis and bone formation

Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling

Abstract Background Human mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine AD model by inhibiting the activation of mast cells and B cells. Also our phase I/IIa clinical trial showed clinical efficacy and safety of hMSCs in moderate-to-severe adult AD patients. However, hMSCs therapy against atopic dermatitis have had poor results in clinical field. Therefore, we investigated the reason behind this result. We hypothesized that drug–cell interaction could interfere with the therapeutic efficacy of stem cells, and investigated whether coadministration with pimecrolimus, one of the topical calcineurin inhibitors, could influence the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in AD. Methods hUCB-MSCs were subcutaneously injected to AD-induced mice with or without pimecrolimus topical application. To examine whether pimecrolimus influenced the immunomodulatory activity of hUCB-MSCs, hUCB-MSCs were treated with pimecrolimus. Results Pimecrolimus disturbed the therapeutic effect of hUCB-MSCs when they were co-administered in murine AD model. Moreover, the inhibitory functions of hUCB-MSCs against type 2 helper T (Th2) cell differentiation and mast cell activation were also deteriorated by pimecrolimus treatment. Interestingly, we found that pimecrolimus decreased the production of PGE2, one of the most critical immunomodulatory factors in hUCB-MSCs. And we demonstrated that pimecrolimus downregulated COX2-PGE2 axis by inhibiting nuclear translocation of NFAT3. Conclusions Coadministration of pimecrolimus with hMSCs could interfere with the therapeutic efficacy of hMSCs in atopic dermatitis, and this is the first study that figured out the interaction of hMSCs with other drugs in cell therapy of atopic dermatitis. Therefore, this study might give rise to improvement of the clinical application of hMSCs therapy and facilitate the widespread application of hMSCs in clinical field

FOXO protects against age‐progressive axonal degeneration

Summary Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself