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BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.
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Adenocarcinoma Mucinoso , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Idoso , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Prognóstico , Receptores de Estrogênio/metabolismo , Adulto , Receptores de Progesterona/metabolismo , Estadiamento de Neoplasias , Carcinoma Ductal de Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Estudos de Coortes , Carcinoma Lobular/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologiaRESUMO
BACKGROUND: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. METHODS: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). RESULTS: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56). CONCLUSION: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.
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Neoplasias da Mama , Metilação de DNA , Humanos , Feminino , Condutos Olfatórios , Ilhas de CpGRESUMO
INTRODUCTION: Undiagnosed and untreated lung pathologies are among the leading causes of neonatal deaths in developing countries. Lung Ultrasound (LUS) has been widely accepted as a diagnostic tool for neonatal lung pathologies due to its affordability, portability, and safety. However, healthcare institutions in developing countries lack well-trained clinicians to interpret LUS images, which limits the use of LUS, especially in remote areas. An automated point-of-care tool that could screen and capture LUS morphologies associated with neonatal lung pathologies could aid in rapid and accurate diagnosis. METHODS: We propose a framework for classifying the six most common neonatal lung pathologies using spatially localized line and texture patterns extracted via 2D dual-tree complex wavelet transform (DTCWT). We acquired 1550 LUS images from 42 neonates with varying numbers of lung pathologies. Furthermore, we balanced our data set to avoid bias towards a pathology class. RESULTS: Using DTCWT and clinical features as inputs to a linear discriminant analysis (LDA), our approach achieved a per-image cross-validated classification accuracy of 74.39% for the imbalanced data set. Our classification accuracy improved to 92.78% after balancing our data set. Moreover, our proposed framework achieved a maximum per-subject cross-validated classification accuracy of 64.97% with an imbalanced data set while using a balanced data set improves its classification accuracy up to 81.53%. CONCLUSION: Our work could aid in automating the diagnosis of lung pathologies among neonates using LUS. Rapid and accurate diagnosis of lung pathologies could help to decrease neonatal deaths in healthcare institutions that lack well-trained clinicians, especially in developing countries.
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Morte Perinatal , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Feminino , Humanos , Análise de Ondaletas , Pulmão/diagnóstico por imagem , Tórax , UltrassonografiaRESUMO
BACKGROUND: Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumors, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumors' response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC. METHODS: The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on deep learning (DL). Clinical parameters were included to build a final prognostic model. RESULTS: The best performing models were based on space-resolved and DL approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855). CONCLUSIONS: Radiomics features extracted from diagnostic CT augment the predictive ability of pCR when combined with clinical features. The novel space-resolved radiomics and DL radiomics approaches outperformed conventional radiomics techniques.
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Neoplasias da Mama , Terapia Neoadjuvante , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). METHODS: Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH-) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH- status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS. RESULTS: ABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82-0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76-0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85-0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79-0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83-0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78-0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH- and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59-0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found. CONCLUSIONS: HER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC.
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Neoplasias da Mama , Variações do Número de Cópias de DNA , Neoplasias da Mama/patologia , Estudos de Coortes , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Recidiva Local de Neoplasia , PrognósticoRESUMO
Telehealth is a growing field, its pertinence magnified by COVID-19 causing the accelerated digitalization of the world. Given the significant global demand to provide telehealth services, it is important to explore patient receptiveness toward this alternative service model, particularly from regions where it has yet to be implemented. We conducted a cross-sectional study to understand the views and willingness of patients toward the use of telehealth for cancer genetic counseling. A survey was completed by 160 patients of the National Cancer Centre Singapore, and descriptive statistics were used to analyze the data. The study found that 95.6% (n = 153/160) of participants did not have prior telehealth experience. Most participants were willing or neutral toward having genetic counseling by phone (n = 114/160, 71.3%) and video (n = 106/160, 66.3%). However, majority prefer in-person appointments for first (n = 127/160, 79.4%) and follow-up (n = 97/160, 60.6%) visits over telehealth. Majority agreed that a phone/video consultation would meet most of their needs but voiced concerns regarding privacy and sharing of information (n = 79/160, 49.4% for phone; n = 74/160, 46.3% for video) and whether their emotional needs could be met (n = 61/160, 38.1%). Participants' age, employment status, income, mode of transportation to the appointment, and whether special arrangements were made to attend the in-person appointment were associated with receptivity to telehealth genetic counseling (p ≤ .05 for all). This study adds diversity to existing literature and demonstrates that patients from Asia are generally willing and accepting of the use of telehealth in a cancer genetics service. This will help meet increasing global demand of telehealth consultations in the post-pandemic new norm. Furthermore, it will also provide services for underserved populations and patients requiring urgent testing in a timely manner. Further studies are needed to explore the cost-effectiveness and fair billing methods, as well as willingness and acceptability of telehealth genetic counseling in post-COVID times.
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COVID-19 , Neoplasias , Telemedicina , Estudos Transversais , Humanos , Neoplasias/genética , Pandemias , SARS-CoV-2RESUMO
Family history taking is a fundamental part of genetic counseling, and however, it is also a time-consuming process. To cope with the increasing demands at the Cancer Genetics Service in Singapore, alternative methods to collect patients' family history were implemented to reduce the duration of the initial consultation and increase the clinic's capacity. Two interventions were performed in this study, where a family history questionnaire and telephone intakes (telephone calls to collect patient family history) were implemented prior to a cancer genetics consultation. The primary outcome of this study is the duration of the initial consultation in relation to both interventions while the secondary outcome is the clinic attendance rate before and after implementing the telephone intake. The impact of interventions was evaluated with a Plan-Do-Study-Act (PDSA) methodology. The use of a family history questionnaire could not be evaluated due to poor patient response while the telephone intake was found to be feasible among the local population. Two improvements were observed after the implementation of telephone intake: (a) a significant reduction in the duration of the initial consultation from 60 to 45 min (p = .001) and (b) a significant increase of 29.7% in clinic attendance (p = .01). This study demonstrates that collecting family history information ahead of genetic counseling via telephone intake is a useful measure in improving clinic capacity, which potentially resulting in optimization of clinical resources.
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Aconselhamento Genético/métodos , Neoplasias/genética , Telefone , Adulto , Feminino , Humanos , Masculino , Anamnese , Singapura , Inquéritos e QuestionáriosRESUMO
In XXZ chains with large enough interactions, spin transport can be significantly suppressed when the bias of the dissipative driving becomes large enough. This phenomenon of negative differential conductance is caused by the formation of two oppositely polarized ferromagnetic domains at the edges of the chain. Here, we show that this many-body effect, combined with a non-uniform magnetic field, can allow for a high degree of control of the spin current. In particular, by studying all of the possible shapes of local magnetic fields potentials, we find that a configuration in which the magnetic field points up for half of the chain and down for the other half, can result in giant spin-current rectification, for example, up to 108 for a system with only 8 spins. Our results show clear indications that the rectification can increase with the system size.
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Doença de Hirschsprung , Osteocondrodisplasias , Doenças da Imunodeficiência Primária , RNA Longo não Codificante , Humanos , Doenças da Imunodeficiência Primária/genética , Cabelo/anormalidades , Regiões Promotoras Genéticas , Doença de Hirschsprung/genética , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Cartilagem , MutaçãoRESUMO
We analyze the propagation of correlations after a sudden interaction change in a strongly interacting quantum system in contact with an environment. In particular, we consider an interaction quench in the Bose-Hubbard model, deep within the Mott-insulating phase, under the effect of dephasing. We observe that dissipation effectively speeds up the propagation of single-particle correlations while reducing their coherence. In contrast, for two-point density correlations, the initial ballistic propagation regime gives way to diffusion at intermediate times. Numerical simulations, based on a time-dependent matrix product state algorithm, are supplemented by a quantitatively accurate fermionic quasiparticle approach providing an intuitive description of the initial dynamics in terms of holon and doublon excitations.
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The angular gyrus (AG) and posterior cingulate cortex (PCC) demonstrate extensive structural and functional connectivity with the hippocampus and other core recollection network regions. Consequently, recent studies have explored neuromodulation targeting these and other regions as a potential strategy for restoring function in memory disorders such as Alzheimer's Disease. However, determining the optimal approach for neuromodulatory devices requires understanding how parameters like selected stimulation site, cognitive state during modulation, and stimulation duration influence the effects of deep brain stimulation (DBS) on electrophysiological features relevant to episodic memory. We report experimental data examining the effects of high-frequency stimulation delivered to the AG or PCC on hippocampal theta oscillations during the memory encoding (study) or retrieval (test) phases of an episodic memory task. Results showed selective enhancement of anterior hippocampal slow theta oscillations with stimulation of the AG preferentially during memory retrieval. Conversely, stimulation of the PCC attenuated slow theta oscillations. We did not observe significant behavioral effects in this (open-loop) stimulation experiment, suggesting that neuromodulation strategies targeting episodic memory performance may require more temporally precise stimulation approaches.
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Cognição , Estimulação Encefálica Profunda , Hipocampo , Lobo Parietal , Ritmo Teta , Estimulação Encefálica Profunda/métodos , Ritmo Teta/fisiologia , Hipocampo/fisiologia , Masculino , Humanos , Lobo Parietal/fisiologia , Cognição/fisiologia , Memória Episódica , Feminino , Giro do Cíngulo/fisiologia , AdultoRESUMO
PURPOSE: To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports. METHODS: A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports. RESULTS: The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P < .001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P < .001). CONCLUSION: We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions.
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Processamento de Linguagem Natural , Neoplasias , Tomografia Computadorizada por Raios X , Metástase Neoplásica/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Registros Eletrônicos de Saúde , Estudos Retrospectivos , Estudos ProspectivosRESUMO
The cholinergic system is essential for memory. While degradation of cholinergic pathways characterizes memory-related disorders such as Alzheimer's disease, the neurophysiological mechanisms linking the cholinergic system to human memory remain unknown. Here, combining intracranial brain recordings with pharmacological manipulation, we describe the neurophysiological effects of a cholinergic blocker, scopolamine, on the human hippocampal formation during episodic memory. We found that the memory impairment caused by scopolamine was coupled to disruptions of both the amplitude and phase alignment of theta oscillations (2-10 Hz) during encoding. Across individuals, the severity of theta phase disruption correlated with the magnitude of memory impairment. Further, cholinergic blockade disrupted connectivity within the hippocampal formation. Our results indicate that cholinergic circuits support memory by coordinating the temporal dynamics of theta oscillations across the hippocampal formation. These findings expand our mechanistic understanding of the neurophysiology of human memory and offer insights into potential treatments for memory-related disorders.
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Doença de Alzheimer , Gastrópodes , Humanos , Animais , Acetilcolina/farmacologia , Encéfalo , Transtornos da Memória , Escopolamina/farmacologia , ColinérgicosRESUMO
Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern. Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time. Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73â¯608 patients with cancer (23â¯217 active treatment, 50â¯391 cancer survivors) and 621â¯475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included. Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose. Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time. Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73â¯608 patients with cancer, 27â¯170 (36.9%) were men; 60â¯100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose. Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.
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COVID-19 , Neoplasias , Masculino , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Singapura/epidemiologia , Vacinas contra COVID-19 , Estudos de Coortes , Estudos Prospectivos , SARS-CoV-2 , Neoplasias/terapiaRESUMO
OBJECTIVE: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports. MATERIALS AND METHODS: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications. RESULTS: The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance. DISCUSSION: These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response. CONCLUSIONS: Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset.
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Neoplasias , Radiologia , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Neoplasias/diagnóstico por imagem , Relatório de Pesquisa , Processamento de Linguagem NaturalRESUMO
INTRODUCTION: Many multi-genic systemic diseases such as neurological disorders, inflammatory diseases, and the majority of cancers do not have effective treatments yet. Reinforcement learning powered systems pharmacology is a potentially effective approach to designing personalized therapies for untreatable complex diseases. AREAS COVERED: In this survey, state-of-the-art reinforcement learning methods and their latest applications to drug design are reviewed. The challenges on harnessing reinforcement learning for systems pharmacology and personalized medicine are discussed. Potential solutions to overcome the challenges are proposed. EXPERT OPINION: In spite of successful application of advanced reinforcement learning techniques to target-based drug discovery, new reinforcement learning strategies are needed to address systems pharmacology-oriented personalized de novo drug design.
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Desenho de Fármacos , Farmacologia em Rede , Descoberta de Drogas/métodos , Humanos , Medicina de Precisão/métodosRESUMO
Episodic memories, or consciously accessible memories of unique events, represent a key aspect of human cognition. Evidence from rodent models suggests that the neural representation of these complex memories requires cooperative firing of groups of neurons on short time scales, organized by gamma oscillations. These co-firing groups, termed "neuronal assemblies," represent a fundamental neurophysiological unit supporting memory. Using microelectrode data from neurosurgical patients, we identify neuronal assemblies in the human MTL and show that they exhibit consistent organization in their firing pattern based on gamma phase information. We connect these properties to memory performance across recording sessions. Finally, we describe how human neuronal assemblies flexibly adjust over longer time scales. Our findings provide key evidence linking assemblies to human episodic memory for the first time.
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Memória Episódica , Neurônios , Humanos , Neurônios/fisiologia , MicroeletrodosRESUMO
Background: Cemented Total Knee Arthroplasty (TKA) provides excellent long-term survival rates and functional results, however, radiolucent lines (RLLs) often appear during early post-operative follow-up and their incidence and clinical significance are unknown. The primary aim was to establish the incidence, location, frequency, and time taken for RLLs to appear within the first year after a primary cemented TKA with an anatomic tibial baseplate (Smith and Nephew, LEGION Total Knee System). Methods: This was a retrospective analysis of 135 primary cemented TKA in 131 patients over three years. We compared demographics, serial radiographs, and early clinical and functional outcomes. Results: There were 65 TKAs (48%) in 62 patients who had RLLs within the first year post-operatively. Most were females (58.8%). Mean age was 68.3 ± 7.9 years. There were 88 RLLs, with the most and second commonest location at the medial tibial baseplate (38%) and anterior femoral flange (23%). 89% were in the bone-cement interface. The largest average length of RLLs were at the anterior flange of the femoral component (1.98 ± 1.33 mm). The average time to development was 6.5 ± 4.1 months. None of these patients had infections nor required revision. Patients with RLLs did not do worse in functional and clinical scoring at 1-year. Conclusion: There was a 48% incidence of physiological RLLs after cemented TKA, with the highest occurrence at the medial tibial baseplate at 38%. These radiolucent lines did not affect early post-operative clinical and functional outcomes of patients.
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Dual γ/neutron radiation sensors are a critical component of the nuclear security mission to prevent the proliferation of a special nuclear material (SNM). While high-performing semiconductors such as high purity germanium (HPGe) and CdZnTe (CZT) already exist in the nuclear security enterprise, their high cost and/or logistical burdens make widespread deployment difficult to achieve. Metal lead halide perovskites (MHPs) have attracted interest in recent years to address this challenge. In particular, methylammonium lead tribromide (CH3NH3PbBr3, MAPbBr3, or MAPB) has been widely evaluated for its radiation sensing capabilities. While previous studies have demonstrated low-energy X-ray and α particle sensing of MAPB-based detectors and several studies discuss the potential for γ ray sensing, neutron sensing of this material has been rarely explored. Here, we explore the incorporation of lithium in the form of LiCl into the MAPB structure to add thermal neutron sensitivity. Characterizations of the lithium-doped MAPB crystals demonstrate that quality growths are achievable with single crystals that exhibit high crystallinity, no phase change, and high macroscopic bulk quality. Finally, we report on the first demonstrated γ ray and thermal neutron sensing based on lithium-doped MAPB single crystals, which is a significant milestone in the development of 3D dual γ/neutron MHP sensors.
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BACKGROUND: Video-sharing platforms are a common source for health information such as Coronavirus Disease 2019 (COVID-19) vaccines. It is important that they provide good quality, evidence-based information. However, to date, the quality of information surrounding COVID-19 vaccines on video-sharing platforms has not been established. OBJECTIVE: This study developed an assessment tool to evaluate the quality of Coronavirus Disease 2019 (COVID-19) vaccine videos on YouTube, Facebook Watch and TikTok. METHODS: Assessment of quality was based on understandability, actionability, accuracy, comprehensiveness and reliability. Videos were searched using the keywords "COVID-19 vaccine", "Coronavirus vaccine" and "SARS-CoV-2 vaccine". Seventy-two videos were evaluated. Descriptive statistics, Kruskal-Wallis and Wilcoxon-rank sum tests were used for analysis. RESULTS: YouTube had the highest median composite score compared to TikTok (36.8% versus 27.5%, p = 0.001). YouTube also had the highest median reliability score (37.5%), but those of Facebook Watch (35.0%) and TikTok (35.0%) were only marginally lower. Median accuracy scores of all platforms were 100%, but their median comprehensiveness scores were low (YouTube 12.5%; Facebook Watch 6.3%; TikTok 6.3%, p = 0.004). Median actionability scores (0%) were the lowest for all platforms. TikTok had the highest median understandability score compared to YouTube and Facebook Watch (96.9% versus 80.0 each, p < 0.001). CONCLUSION: The overall quality of videos on all video-sharing platforms were low. All platforms provided accurate COVID-19 vaccine information, but TikTok videos were the most understandable. Most videos did not provide full details about COVID-19 vaccines, thus viewers would need to watch several videos before making a better-informed decision.