Unlabelled: This paper studies the performance of open-source Large Language Models (LLMs) in text classification tasks typical for political science research. By examining tasks like stance, topic, and relevance classification, we aim to guide scholars in making informed decisions about their use of LLMs for text analysis and to establish a baseline performance benchmark that demonstrates the models' effectiveness. Specifically, we conduct an assessment of both zero-shot and fine-tuned LLMs across a range of text annotation tasks using news articles and tweets datasets.
View Article and Find Full Text PDFAs cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition.
View Article and Find Full Text PDFBackground: Secondary bacterial infection (SBI) occurs in a proportion of individuals with dengue and results in longer hospitalization, higher mortality, and increased health-related costs. However, the frequency, risk factors and predictive biomarkers of this comorbidity in pediatric dengue is partially known.
Methods: We conducted a retrospective multicenter study in a dengue hyperendemic region of Colombia, analyzing 1597 children from two pediatric cohorts.
Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival.
View Article and Find Full Text PDFAlthough p53 inactivation promotes genomic instability and presents a route to malignancy for more than half of all human cancers, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases-Trp53 (encoding mouse p53) loss of heterozygosity, accumulation of deletions, genome doubling, and the emergence of gains and amplifications-each associated with specific histological stages across the premalignant and malignant spectrum.
View Article and Find Full Text PDFThe degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifluorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases.
View Article and Find Full Text PDFUnlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity.
View Article and Find Full Text PDFA critical symptom of Parkinson's disease (PD) is the occurrence of Freezing of Gait (FOG), an episodic disorder that causes frequent falls and consequential injuries in PD patients. There are various auditory, visual, tactile, and other types of stimulation interventions that can be used to induce PD patients to escape FOG episodes. In this article, we describe a low cost wearable system for non-invasive gait monitoring and external delivery of superficial vibratory stimulation to the lower extremities triggered by FOG episodes.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2017
The current diagnosis of Parkinson's disease (PD) is based on a subjective assessment by the specialist. The monitoring of the tremor that presents in the hand index fingers in a patient with Parkinson's is one of the most important parameters to diagnose the evolution of the disease in an objective manner. This research analyze the tremor in the hand index fingers of patients with PD with medication and without medication.
View Article and Find Full Text PDFBackground: Although it is known that stress elevates the levels of pro-inflammatory cytokines and promotes hyper-excitable central conditions, a causal relationship between these two factors has not yet been identified. Recent studies suggest that increases in interleukin 6 (IL-6) levels are specifically associated with stress. We hypothesized that IL-6 acutely and directly induces cortical hyper-excitability by altering the balance between synaptic excitation and inhibition.
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