Can cancer researchers accurately judge whether preclinical reports will reproduce?
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ABSTRACT:
SUBMITTER: Benjamin D
PROVIDER: S-EPMC5490935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The purpose of the present study was to explore what parents know about their Children's boredom in school; specifically, the frequency, intensity, and antecedents of their Children's boredom, as well as how they cope with boredom. A questionnaire was administered to 437 grade 9 students (54% female, M age = 14.82) and their parents (72% mothers, 14% fathers, 12% both parents, M age = 45.26) measuring variables related to students boredom in mathematics class. Three different measurements were used to evaluate the accuracy of parents' judgments: (1) the correlation between parents' and students' answers, (2) the mean differences between parents' and students' answers, and (3) the mean values of absolute differences of parents' and students' answers. The results suggest that parents generally have an informed knowledge about their child's boredom and related facets. This is reflected by a mean correlation of medium size ( = 0.34) and a small mean effect size of the difference between parents' and students' judgments over all items ( = 0.20). Parents are also substantially better in judging their Children's boredom compared to guessing for all variables (mean effect size of = 0.65). They had the most precise judgments for the frequency and intensity of boredom. The antecedents of boredom (e.g., characteristics of instruction) were also well estimated by parents; specifically, parents tend to have a bias in favor for their children evidenced by overestimating antecedents that cannot be influenced by the students and underestimating those that can be influenced by the students. The least concordance was found between parents' and Children's perception of boredom coping strategies (e.g., accepting boredom), implying that parents lack information about how their children intentionally cope with boredom. Implications for research on student boredom are discussed as well as practical applications involving parents in boredom prevention.
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Project description:Zebrafish patient-derived xenograft (zPDX) models have shown great potential in predicting the short-term treatment response in various types of tumor cases. However, few studies have used zPDX models for drug screening in non-small cell lung cancer (NSCLC). We aimed to compare the treatment responses of patients with NSCLC with those of the corresponding zPDX models. Tumor cells were obtained from pleural fluid or biopsy procedures from patients with NSCLC and injected into the perivitelline space of zebrafish larvae. Then, the same antineoplastic drugs administered to the corresponding patient were tested in the successfully constructed zPDX model, for 3 days. Responses to treatment were compared. A total of 21 patients with advanced NSCLC were enrolled in our study, and 13 corresponding zPDX models were successfully established. Based on the clinical medication of enrolled patients, we provided a corresponding drug treatment to these zebrafish embryos, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), pemetrexed/platinum (AP), or docetaxel/platinum (DP) administration. The chemosensitivity consistency rate between the clinical responses and those obtained from zPDXs was 76.9% (10/13). There was a high correlation between patient responses and the corresponding zPDX drug responses. Thus, zPDX can accurately and quickly reproduce patient responses to treatment with EGFR TKIs, AP, and DP and has a considerable potential to serve as a biological platform for predicting treatment effect on patients with NSCLC.
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Project description:We present what to our knowledge is a new method of optimized torsion-angle normal-mode analysis, in which the normal modes move along curved paths in Cartesian space. We show that optimized torsion-angle normal modes reproduce protein conformational changes more accurately than Cartesian normal modes. We also show that orthogonalizing the displacement vectors from torsion-angle normal-mode analysis and projecting them as straight lines in Cartesian space does not lead to better performance than Cartesian normal modes. Clearly, protein motion is more naturally described by curved paths in Cartesian space.
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Project description:Although animal vocalizations and human speech are known to communicate physical formidability, no previous study has examined whether human listeners can assess the strength or body size of vocalizers relative to their own, either from speech or from nonverbal vocalizations. Here, although men tended to underestimate women's formidability, and women to overestimate men's, listeners judged relative strength and height from aggressive roars and aggressive speech accurately. For example, when judging roars, male listeners accurately identified vocalizers who were substantially stronger than themselves in 88% of trials, and never as weaker. For male vocalizers only, roars functioned to exaggerate the expression of threat compared to aggressive speech, as men were rated as relatively stronger when producing roars. These results indicate that, like other mammals, the acoustic structure of human aggressive vocal signals (and in particular roars) may have been selected to communicate functional information relevant to listeners' survival.
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Project description:Alzheimer's disease biomarkers are widely accepted as surrogate markers of underlying neuropathological changes. However, few studies have evaluated whether preclinical Alzheimer's disease biomarkers predict Alzheimer's neuropathology at autopsy. We sought to determine whether amyloid PET imaging or CSF biomarkers accurately predict cognitive outcomes and Alzheimer's disease neuropathological findings. This study included 720 participants, 42-91 years of age, who were enrolled in longitudinal studies of memory and aging in the Washington University Knight Alzheimer Disease Research Center and were cognitively normal at baseline, underwent amyloid PET imaging and/or CSF collection within 1 year of baseline clinical assessment, and had subsequent clinical follow-up. Cognitive status was assessed longitudinally by Clinical Dementia Rating®. Biomarker status was assessed using predefined cut-offs for amyloid PET imaging or CSF p-tau181/amyloid-β42. Subsequently, 57 participants died and underwent neuropathologic examination. Alzheimer's disease neuropathological changes were assessed using standard criteria. We assessed the predictive value of Alzheimer's disease biomarker status on progression to cognitive impairment and for presence of Alzheimer's disease neuropathological changes. Among cognitively normal participants with positive biomarkers, 34.4% developed cognitive impairment (Clinical Dementia Rating > 0) as compared to 8.4% of those with negative biomarkers. Cox proportional hazards modelling indicated that preclinical Alzheimer's disease biomarker status, APOE ɛ4 carrier status, polygenic risk score and centred age influenced risk of developing cognitive impairment. Among autopsied participants, 90.9% of biomarker-positive participants and 8.6% of biomarker-negative participants had Alzheimer's disease neuropathological changes. Sensitivity was 87.0%, specificity 94.1%, positive predictive value 90.9% and negative predictive value 91.4% for detection of Alzheimer's disease neuropathological changes by preclinical biomarkers. Single CSF and amyloid PET baseline biomarkers were also predictive of Alzheimer's disease neuropathological changes, as well as Thal phase and Braak stage of pathology at autopsy. Biomarker-negative participants who developed cognitive impairment were more likely to exhibit non-Alzheimer's disease pathology at autopsy. The detection of preclinical Alzheimer's disease biomarkers is strongly predictive of future cognitive impairment and accurately predicts presence of Alzheimer's disease neuropathology at autopsy.
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Project description:IntroductionAccurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate - leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports.MethodsRadiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone.ResultsThe dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing.ConclusionClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.
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Project description:Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research.
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Project description:Introduction and objectiveScientific reporting on major incidents, mass-casualty incidents (MCIs), and disasters is challenging and made difficult by the nature of the medical response. Many obstacles might explain why there are few and primarily non-heterogenous published articles available. This study examines the process of scientific reporting through first-hand experiences from authors of published reports. It aims to identify learning points and challenges that are important to address to mitigate and improve scientific reporting after major incidents.MethodsThis was a qualitative study design using semi-structured interviews. Participants were selected based on a comprehensive literature search. Ten researchers, who had published reports on major incidents, MCIs, or disasters from 2013-2018 were included, of both genders, from eight countries on three continents. The researchers reported on large fires, terrorist attacks, shootings, complex road accidents, transportation accidents, and earthquakes.ResultsThe interview was themed around initiation, workload, data collection, guidelines/templates, and motivation factors for reporting. The most challenging aspects of the reporting process proved to be a lack of dedicated time, difficulties concerning data collection, and structuring the report. Most researchers had no prior experience in reporting on major incidents. Guidelines and templates were often chosen based on how easily accessible and user-friendly they were.Conclusion and relevanceThere are few articles presenting first-hand experience from the process of scientific reporting on major incidents, MCIs, and disasters. This study presents motivation factors, challenges during reporting, and factors that affected the researchers' choice of reporting tools such as guidelines and templates. This study shows that the structural tools available for gathering data and writing scientific reports need to be more widely promoted to improve systematic reporting in Emergency and Disaster Medicine. Through gathering, comparing, and analyzing data, knowledge can be acquired to strengthen and improve responses to future major incidents. This study indicates that transparency and willingness to share information are requisite for forming a successful scientific report.
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Project description:Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.
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