Nano: Nested Human-in-the-Loop Reward Learning for Few-shot Language Model Control

Pretrained language models have demonstrated extraordinary capabilities in language generation. However, real-world tasks often require controlling the distribution of generated text in order to mitigate bias, promote fairness, and achieve personalization. Existing techniques for controlling the distribution of generated text only work with quantified distributions, which require pre-defined categories, proportions of the distribution, or an existing corpus following the desired distributions. However, many important distributions, such as personal preferences, are unquantified. In this work, we tackle the problem of generating text following arbitrary distributions (quantified and unquantified) by proposing Nano, a few-shot human-in-the-loop training algorithm that continuously learns from human feedback. Nano achieves state-of-the-art results on single topic/attribute as well as quantified distribution control compared to previous works. We also show that Nano is able to learn unquantified distributions, achieves personalization, and captures differences between different individuals' personal preferences with high sample efficiency.Comment: Accepted to ACL Findings 202

MultiZoo & MultiBench: A Standardized Toolkit for Multimodal Deep Learning

Learning multimodal representations involves integrating information from multiple heterogeneous sources of data. In order to accelerate progress towards understudied modalities and tasks while ensuring real-world robustness, we release MultiZoo, a public toolkit consisting of standardized implementations of > 20 core multimodal algorithms and MultiBench, a large-scale benchmark spanning 15 datasets, 10 modalities, 20 prediction tasks, and 6 research areas. Together, these provide an automated end-to-end machine learning pipeline that simplifies and standardizes data loading, experimental setup, and model evaluation. To enable holistic evaluation, we offer a comprehensive methodology to assess (1) generalization, (2) time and space complexity, and (3) modality robustness. MultiBench paves the way towards a better understanding of the capabilities and limitations of multimodal models, while ensuring ease of use, accessibility, and reproducibility. Our toolkits are publicly available, will be regularly updated, and welcome inputs from the community.Comment: JMLR Open Source Software 2023, Code available at https://github.com/pliang279/MultiBenc

Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss:Findings from the Shanghai Osteoarthritis Cohort

Objective: Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term. Methods: The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of &gt;40 000 adults with clinically diagnosed osteoarthritis aged &gt;45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure. Results: For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline-7.29 kg (95% CI-8.07 to-6.50 kg), p&lt;0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score-1.46 (95% CI-2.84 to-0.08), p=0.038; adjusted mean difference in WOMAC pain subscore-3.37 (95% CI-5.79 to-0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference-0.02 mm (95% CI-0.03 to-0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment:-0.03±0.05 vs-0.05±0.07 mm/year, p&lt;0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate). Conclusion: With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.</p

Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-Like Breast Cancer

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing the interaction of β-catenin with T-cell factor. Our study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC

MeWRKY IIas, subfamily genes of WRKY transcription factors from cassava, play an important role in disease resistance

Cassava (Manihot esculenta Crantz) is an important tropical crop for food, fodder, and energy. Cassava bacterial blight (CBB) caused by Xanthomonas axonopodis pv. manihotis (Xam) occurs in all cassava growing regions and threatens global cassava production. WRKY transcription factor family plays the essential roles during plant growth, development, and abiotic or biotic stress. Particularly, previous studies have revealed the important role of the group IIa WRKY genes in plant disease resistance. However, a comprehensive analysis of group IIa subfamily in cassava is still missing. Here, we identified 102 WRKY members, which were classified into three groups, I, II, and III. Transient expression showed that six MeWRKY IIas were localized in the nucleus. MeWRKY IIas transcripts accumulated significantly in response to SA, JA, and Xam. Overexpression of MeWRKY27 and MeWRKY33 in Arabidopsis enhanced its resistance to Pst DC3000. In contrast, silencing of MeWRKY27 and MeWRKY33 in cassava enhanced its susceptibility to Xam. Co-expression network analysis showed that different downstream genes are regulated by different MeWRKY IIa members. The functional analysis of downstream genes will provide clues for clarifying molecular mechanism of cassava disease resistance. Collectively, our results suggest that MeWRKY IIas are regulated by SA, JA signaling, and coordinate response to Xam infection

3D bioprinted hydrogel/polymer scaffold with factor delivery and mechanical support for growth plate injury repair

Introduction: Growth plate injury is a significant challenge in clinical practice, as it could severely affect the limb development of children, leading to limb deformity. Tissue engineering and 3D bioprinting technology have great potential in the repair and regeneration of injured growth plate, but there are still challenges associated with achieving successful repair outcomes.Methods: In this study, GelMA hydrogel containing PLGA microspheres loaded with chondrogenic factor PTH(1–34) was combined with BMSCs and Polycaprolactone (PCL) to develop the PTH(1–34)@PLGA/BMSCs/GelMA-PCL scaffold using bio-3D printing technology.Results: The scaffold exhibited a three-dimensional interconnected porous network structure, good mechanical properties, biocompatibility, and was suitable for cellchondrogenic differentiation. And a rabbit model of growth plate injury was appliedto validate the effect of scaffold on the repair of injured growth plate. The resultsshowed that the scaffold was more effective than injectable hydrogel in promotingcartilage regeneration and reducing bone bridge formation. Moreover, the addition ofPCL to the scaffold provided good mechanical support, significantly reducing limbdeformities after growth plate injury compared with directly injected hydrogel.Discussion: Accordingly, our study demonstrates the feasibility of using 3D printed scaffolds for treating growth plate injuries and could offer a new strategy for the development of growth plate tissue engineering therapy