Department of Computer Science

Generative Artificial Intelligence is set to revolutionize healthcare delivery by transforming traditional patient care into a more personalized, efficient, and proactive process. Chatbots, serving as interactive conversational models, will probably drive this patient-centered transformation in healthcare. Through the provision of various services, including diagnosis, personalized lifestyle recommendations, dynamic scheduling of follow-ups, and mental health support, the objective is to substantially augment patient health outcomes, all the while mitigating the workload burden on healthcare providers. The life-critical nature of healthcare applications necessitates establishing a unified and comprehensive set of evaluation metrics for conversational models. Existing evaluation metrics proposed for various generic large language models (LLMs) demonstrate a lack of comprehension regarding medical and health concepts and their significance in promoting patients’ well-being. Moreover, these metrics neglect pivotal user-centered aspects, including trust-building, ethics, personalization, empathy, user comprehension, and emotional support. The purpose of this paper is to explore state-of-the-art LLM-based evaluation metrics that are specifically applicable to the assessment of interactive conversational models in healthcare. Subsequently, we present a comprehensive set of evaluation metrics designed to thoroughly assess the performance of healthcare chatbots from an end-user perspective. These metrics encompass an evaluation of language processing abilities, impact on real-world clinical tasks, and effectiveness in user-interactive conversations. Finally, we engage in a discussion concerning the challenges associated with defining and implementing these metrics, with particular emphasis on confounding factors such as the target audience, evaluation methods, and prompt techniques involved in the evaluation process.

Facioscapulohumeral muscular dystrophy (FSHD) is linked to abnormal derepression of the transcription activator DUX4. This effect is localized to a low percentage of cells, requiring single-cell analysis. However, single-cell/nucleus RNA-seq cannot fully capture the transcriptome of multinucleated large myotubes. To circumvent these issues, we use multiplexed error-robust fluorescent in situ hybridization (MERFISH) spatial transcriptomics that allows profiling of RNA transcripts at a subcellular resolution. We simultaneously examined spatial distributions of 140 genes, including 24 direct DUX4 targets, in in vitro differentiated myotubes and unfused mononuclear cells (MNCs) of control, isogenic D4Z4 contraction mutant and FSHD patient samples, as well as the individual nuclei within them. We find myocyte nuclei segregate into two clusters defined by the expression of DUX4 target genes, which is exclusively found in patient/mutant nuclei, whereas MNCs cluster based on developmental states. Patient/mutant myotubes are found in FSHD-hi and FSHD-lo states with the former signified by high DUX4 target expression and decreased muscle gene expression. Pseudotime analyses reveal a clear bifurcation of myoblast differentiation into control and FSHD-hi myotube branches, with variable numbers of DUX4 target-expressing nuclei found in multinucleated FSHD-hi myotubes. Gene coexpression modules related to extracellular matrix and stress gene ontologies are significantly altered in patient/mutant myotubes compared with the control. We also identify distinct subpathways within the DUX4 gene network that may differentially contribute to the disease transcriptomic phenotype. Taken together, our MERFISH-based study provides effective gene network profiling of multinucleated cells and identifies FSHD-induced transcriptomic alterations during myoblast differentiation.

The profound impact of food on health necessitates advanced nutrition-oriented food recommendation services. Conventional methods often lack the crucial elements of personalization, explainability, and interactivity. While Large Language Models (LLMs) bring interpretability and explainability, their standalone use falls short of achieving true personalization. In this paper, we introduce ChatDiet, a novel LLM-powered framework designed specifically for personalized nutrition-oriented food recommendation chatbots. ChatDiet integrates personal and population models, complemented by an orchestrator, to seamlessly retrieve and process pertinent information. The personal model leverages causal discovery and inference techniques to assess personalized nutritional effects for a specific user, whereas the population model provides generalized information on food nutritional content. The orchestrator retrieves, synergizes and delivers the output of both models to the LLM, providing tailored food recommendations designed to support targeted health outcomes. The result is a dynamic delivery of personalized and explainable food recommendations, tailored to individual user preferences. Our evaluation of ChatDiet includes a compelling case study, where we establish a causal personal model to estimate individual nutrition effects. Our assessments, including a food recommendation test showcasing a 92% effectiveness rate, coupled with illustrative dialogue examples, underscore ChatDiet's strengths in explainability, personalization, and interactivity.

We prove that the stack-number of the strong product of three n-vertex paths is Θ(n1/3). The best previously known upper bound was O(n). No non-trivial lower bound was known. This is the first explicit example of a graph family with bounded maximum degree and unbounded stack-number. The main tool used in our proof of the lower bound is the topological overlap theorem of Gromov. We actually prove a stronger result in terms of so-called triangulations of Cartesian products. We conclude that triangulations of three-dimensional Cartesian products of any sufficiently large connected graphs have large stack-number. The upper bound is a special case of a more general construction based on families of permutations derived from Hadamard matrices. The strong product of three paths is also the first example of a bounded degree graph with bounded queue-number and unbounded stack-number. A natural question that follows from our result is to determine the smallest Δ0 such that there exists a graph family with unbounded stack-number, bounded queue-number and maximum degree Δ0. We show that Δ0∈{6,7}.

This dataset was collected from university students before, during, and after the COVID-19 lockdown in Southern California. Data collection happened continuously for the average of 7.8 months (SD=3.8, MIN=1.0, MAX=13.4) from a population of 21 students of which 12 have also completed an exit survey, and 7 started before the California COVID-19 lockdown order. This multimodal dataset included different means of data collection such as Samsung Galaxy Watch, Oura Ring, a Life-logger app named Personicle, a questionnaire mobile app named Personicle Questions, and periodical and personalised surveys. The dataset contains raw data from Photoplethysmogram (PPG), Inertial measurement unit (IMU), and pressure sensors in addition to processed data on heart rate, heart rate variability, sleep (bedtime, sleep stages, quality), and physical activity (step, active calories, type of activity). Ecological momentary assessments were collected from participants on daily and weekly bases containing their Positive and Negative Affect Schedule (PANAS) questionnaire and their emotional responses to COVID-19 and their health. Subjective data was also collected through monthly surveys containing standard mood and mental health surveys such as Beck Depression Inventory II (BDI-II), Brief Symptom Inventory (BSI), GAD-7, Inclusion of Other in the Self Scale (IOS-Partner), Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), Feasibility of Intervention Measure (FIM), Experiences in Close Relationships Scale Short Form (ECR-S), UCLA Three-Item Loneliness Scale (ULS), Multidimensional Scale of Perceived Social Support (MSPSS), Investment Model Scale (IMS), Conflict Management Scale (CMS), etc in addition to their response to important events and COVID-19. This dataset can be used to study emotions, mood, physical activity, and lifestyle of young adults through longitudinal subjective and objective measures. This dataset also contains valuable data regarding adjustment of lifestyle and emotions during the events of 2020 and 2021 including COVID-19 discovery and lockdown, Black Life Matter movement, 2020 US presidential elections, etc. On average, participants engaged in the EMA collection study at a rate of 86% (SD=10, MIN=65, MAX=99). Smartwatch usage saw an average participation rate of 51% (SD=20, MIN=16, MAX=88), while engagement with the Oura ring averaged at 85% (SD=12, MIN=60, MAX=99).

BACKGROUND: Alzheimers disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains. RESULTS: Specifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFβ, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons. CONCLUSIONS: In summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD.

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.

An important difference between brains and deep neural networks is the way they learn. Nervous systems learn online where a stream of noisy data points are presented in a non-independent, identically distributed way. Further, synaptic plasticity in the brain depends only on information local to synapses. Deep networks, on the other hand, typically use non-local learning algorithms and are trained in an offline, non-noisy, independent, identically distributed setting. Understanding how neural networks learn under the same constraints as the brain is an open problem for neuroscience and neuromorphic computing. A standard approach to this problem has yet to be established. In this paper, we propose that discrete graphical models that learn via an online maximum a posteriori learning algorithm could provide such an approach. We implement this kind of model in a neural network called the Sparse Quantized Hopfield Network. We show our model outperforms state-of-the-art neural networks on associative memory tasks, outperforms these networks in online, continual settings, learns efficiently with noisy inputs, and is better than baselines on an episodic memory task.

Despite numerous studies in the field of dementia and Alzheimer's disease (AD), a comprehensive understanding of this devastating disease remains elusive. Bulk transcriptomics have provided insights into the underlying genetic factors at a high level. Subsequent technological advancements have focused on single-cell omics, encompassing techniques such as single-cell RNA sequencing and epigenomics, enabling the capture of RNA transcripts and chromatin states at a single cell or nucleus resolution. Furthermore, the emergence of spatial omics has allowed the study of gene responses in the vicinity of amyloid beta plaques or across various brain regions. With the vast amount of data generated, utilizing gene regulatory networks to comprehensively study this disease has become essential. This review delves into some techniques employed in the field of AD, explores the discoveries made using these techniques, and provides insights into the future of the field.