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Scientific Reports Apr 2024Given the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The...
Given the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The development of blood-based molecular biomarkers for pancreatic cancer screening and early detection which provide less-invasive, high-sensitivity, and cost-effective, is urgently needed. The goal of this study is to identify and validate the potential molecular biomarkers in white blood cells (WBCs) of pancreatic cancer patients. Gene expression profiles of pancreatic cancer patients from NCBI GEO database were analyzed by CU-DREAM. Then, mRNA expression levels of three candidate genes were determined by quantitative RT-PCR in WBCs of pancreatic cancer patients (N = 27) and healthy controls (N = 51). ROC analysis was performed to assess the performance of each candidate gene. A total of 29 upregulated genes were identified and three selected genes were performed gene expression analysis. Our results revealed high mRNA expression levels in WBCs of pancreatic cancer patients in all selected genes, including FKBP1A (p < 0.0001), PLD1 (p < 0.0001), and PSMA4 (p = 0.0002). Among candidate genes, FKBP1A mRNA expression level was remarkably increased in the pancreatic cancer samples and also in the early stage (p < 0.0001). Moreover, FKBP1A showed the greatest performance to discriminate patients with pancreatic cancer from healthy individuals than other genes with the 88.9% sensitivity, 84.3% specificity, and 90.1% accuracy. Our findings demonstrated that the alteration of FKBP1A gene in WBCs serves as a novel valuable biomarker for patients with pancreatic cancer. Detection of FKBP1A mRNA expression level in circulating WBCs, providing high-sensitive, less-invasive, and cost-effective, is simple and feasible for routine clinical setting that can be applied for pancreatic cancer screening and early detection.
Topics: Humans; Early Detection of Cancer; Biomarkers; Pancreatic Neoplasms; RNA, Messenger; Leukocytes; Biomarkers, Tumor; Tacrolimus Binding Proteins
PubMed: 38570626
DOI: 10.1038/s41598-024-58324-z -
Consciousness and Cognition Apr 2024Aphantasia is a condition that is often characterized as the impaired ability to create voluntary mental images. Aphantasia is assumed to selectively affect voluntary... (Review)
Review
Aphantasia is a condition that is often characterized as the impaired ability to create voluntary mental images. Aphantasia is assumed to selectively affect voluntary imagery mainly because even though aphantasics report being unable to visualize something at will, many report having visual dreams. We argue that this common characterization of aphantasia is incorrect. Studies on aphantasia are often not clear about whether they are assessing voluntary or involuntary imagery, but some studies show that several forms of involuntary imagery are also affected in aphantasia (including imagery in dreams). We also raise problems for two attempts to show that involuntary images are preserved in aphantasia. In addition, we report the results of a study about afterimages in aphantasia, which suggest that these tend to be less intense in aphantasics than in controls. Involuntary imagery is often treated as a unitary kind that is either present or absent in aphantasia. We suggest that this approach is mistaken and that we should look at different types of involuntary imagery case by case. Doing so reveals no evidence of preserved involuntary imagery in aphantasia. We suggest that a broader characterization of aphantasia, as a deficit in forming mental imagery, whether voluntary or not, is more appropriate. Characterizing aphantasia as a volitional deficit is likely to lead researchers to give incorrect explanations for aphantasia, and to look for the wrong mechanisms underlying it.
Topics: Humans; Imagination; Imagery, Psychotherapy; Volition
PubMed: 38564857
DOI: 10.1016/j.concog.2024.103679 -
Scientific Reports Mar 2024Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform...
Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform analysis (CFWA) and global fibrinolysis capacity (GFC) assay, were recently developed. These were compared with rotational thromboelastography (ROTEM). Healthy donor blood samples were divided into four groups based on tPA-spiked concentrations: 0, 100, 500, and 1000 ng/mL. CFWA and GFC fibrinolysis times, including 4.1 µg/mL and 100 ng/mL tPA in the assays, were determined, denoted as CFWA-Lys and GFC-Lys, respectively. Statistical differences were recognized between tPA concentrations of 0 and 500/1000 ng/mL for CFWA-Lys, and 0 and 100/500/1000 ng/mL for GFC-Lys. The correlation coefficients with lysis onset time (LOT) of extrinsic pathway evaluation and intrinsic pathway evaluation in ROTEM were statistically significant at 0.610 and 0.590 for CFWA-Lys, and 0.939 and 0.928 for GFC-Lys, respectively (p-values < 0.0001 for all correlations). Both assays showed significant correlations with ROTEM; however, the GFC assay proved to have better agreement with ROTEM compared with the CFWA assay. These assays have the potential to reflect a hyperfibrinolysis status with high tPA concentrations.
Topics: Humans; Fibrinolysis; Thrombelastography; Fibrin Clot Lysis Time; Thrombosis; Tissue Plasminogen Activator; Blood Coagulation Disorders
PubMed: 38556522
DOI: 10.1038/s41598-024-58436-6 -
NPJ Microgravity Mar 2024As the International Space Station comes to the end of a transformative era of in-space research, NASA's Commercial Low Earth Orbit (LEO) Destinations (CLD) Program aims... (Review)
Review
As the International Space Station comes to the end of a transformative era of in-space research, NASA's Commercial Low Earth Orbit (LEO) Destinations (CLD) Program aims to catalyze a new generation of platforms with co-investment from the private sector, preventing a potential gap in research performed in LEO, while building a robust LEO economy. In this paper, we provide insight into the CLD Program focusing on Orbital Reef, describing its operational and technical characteristics as well as new opportunities it may enable. Achieving about a third of the pressurized volume of the ISS with the launch of a single pressurized module and growing to support hundreds of Middeck Locker Equivalents (MLE) in passive and active payloads internally and externally, Orbital Reef will enable government, academic, and commercial institutions to continue and expand upon research and development (R&D) efforts currently performed on ISS. Additionally, it will enable nascent markets to establish their operations in space, by initiating new lines of research and technology development and the implementation of new ventures and visions. Using Blue Origin's New Glenn heavy launch system, Sierra Space's cargo and crew Dream Chaser® vehicles, and Boeing's Starliner crew vehicle, and expertise from Amazon/Amazon Supply Chain, Arizona State University, Genesis Engineering, and Redwire, Orbital Reef is being designed to address ISS-era transportation logistics challenges. Finally, this manuscript describes some of the expected challenges from the ISS-to-CLD transition, and provides guidance on how researchers in academia and industry can shape the future of commercial destinations and work performed in LEO.
PubMed: 38553503
DOI: 10.1038/s41526-024-00363-x -
Trends in Cognitive Sciences May 2024The vividness of imagery varies between individuals. However, the existence of people in whom conscious, wakeful imagery is markedly reduced, or absent entirely, was... (Review)
Review
The vividness of imagery varies between individuals. However, the existence of people in whom conscious, wakeful imagery is markedly reduced, or absent entirely, was neglected by psychology until the recent coinage of 'aphantasia' to describe this phenomenon. 'Hyperphantasia' denotes the converse - imagery whose vividness rivals perceptual experience. Around 1% and 3% of the population experience extreme aphantasia and hyperphantasia, respectively. Aphantasia runs in families, often affects imagery across several sense modalities, and is variably associated with reduced autobiographical memory, face recognition difficulty, and autism. Visual dreaming is often preserved. Subtypes of extreme imagery appear to be likely but are not yet well defined. Initial results suggest that alterations in connectivity between the frontoparietal and visual networks may provide the neural substrate for visual imagery extremes.
Topics: Humans; Imagination; Memory, Episodic; Dreams
PubMed: 38548492
DOI: 10.1016/j.tics.2024.02.007 -
BMJ Open Mar 2024With advancing age comes the increasing prevalence of frailty and increased risk of adverse outcomes (eg, hospitalisation). Evidence for comprehensive geriatric...
OBJECTIVE
With advancing age comes the increasing prevalence of frailty and increased risk of adverse outcomes (eg, hospitalisation). Evidence for comprehensive geriatric assessment (CGA), a multidimensional holistic model of care, is mixed in community settings. Uncertainties remain, such as the key components of CGA, who delivers it, and the use of technology. This study aimed to understand the perspectives, beliefs and experiences, of both older people and health professionals, to improve the current CGA and explore factors that may impact on CGA delivery in community settings.
DESIGN
A qualitative interview study was conducted with older people and healthcare professionals (HCPs) identified using a maximum variation strategy. Data were analysed using an abductive analysis approach. The non-adoption, abandonment, scale-up, spread and sustainability framework and the theoretical framework of acceptability guided the categorisation of the codes and identified categories were mapped to the two frameworks.
SETTING
England, UK.
RESULTS
27 people were interviewed, constituting 14 older people and 13 HCPs. We identified limitations in the current CGA: a lack of information sharing between different HCPs who deliver CGA; poor communication between older people and their HCPs and a lack of follow-up as part of CGA. When we discussed the potential for CGA to use technology, HCPs and older people varied in their readiness to engage with it.
CONCLUSIONS
Viable solutions to address gaps in the current delivery of CGA include the provision of training and support to use digital technology and a designated comprehensive care coordinator. The next stage of this research will use these findings, existing evidence and stakeholder engagement, to develop and refine a model of community-based CGA that can be assessed for feasibility and acceptability.
Topics: Humans; Aged; Frailty; Geriatric Assessment; Hospitalization; Primary Health Care; Qualitative Research
PubMed: 38548360
DOI: 10.1136/bmjopen-2023-081304 -
Targeted Oncology May 2024Recurrent or refractory solid and central nervous system (CNS) tumours in paediatric patients have limited treatment options and carry a poor prognosis. The EnGeneIC...
BACKGROUND
Recurrent or refractory solid and central nervous system (CNS) tumours in paediatric patients have limited treatment options and carry a poor prognosis. The EnGeneIC Dream Vector (EDV) is a novel nanocell designed to deliver cytotoxic medication directly to the tumour. The epidermal growth factor receptor is expressed in several CNS and solid tumours and is the target for bispecific antibodies attached to the EDV.
OBJECTIVE
To assess the safety and tolerability of EGFR-Erbitux receptor EnGeneIC Dream Vector with mitoxantrone (EDVs) in children with recurrent / refractory solid or CNS tumours expressing EGFR.
PATIENTS AND METHODS
Patients aged 2-21 years with relapsed or refractory CNS and solid tumours, or radiologically diagnosed diffuse intrinsic pontine glioma (DIPG), were treated in this phase I open-label study of single agent EDVs. Thirty-seven patients' tumours were screened for EGFR expression. EDVs was administered twice weekly in the first cycle and weekly thereafter. Standard dose escalation with a rolling 6 design was employed. Dosing commenced at 5 × 10EDVs per dose and escalated to 5 × 10EDVs per dose.
RESULTS
EGFR expression was detected in 12 (32%) of the paediatric tumours tested. Nine patients were enrolled and treated on the trial, including three patients with diffuse midline glioma. Overall, EDVs was well tolerated, with no dose-limiting toxicities observed. The most common drug-related adverse events were grade 1-2 fever, nausea and vomiting, rash, lymphopaenia, and mildly deranged liver function tests. All patients had disease progression, including one patient who achieved a mixed response as the best response.
CONCLUSIONS
EGFR-Erbitux receptor targeted EnGeneIC Dream Vector with mitoxantrone can be safely delivered in paediatric patients aged 2-21 years with solid or CNS tumours harbouring EGFR expression. The discovery of EGFR expression in a high proportion of paediatric gliomas means that EGFR may be useful as a target for other treatment strategies. Targeted therapeutic-loaded EDVs may be worth exploring further for their role in stimulating an anti-tumour immune response.
GOV IDENTIFIER
NCT02687386.
Topics: Humans; Child; ErbB Receptors; Adolescent; Male; Female; Child, Preschool; Central Nervous System Neoplasms; Young Adult
PubMed: 38546944
DOI: 10.1007/s11523-024-01051-2 -
Sleep Science (Sao Paulo, Brazil) Mar 2024
PubMed: 38545243
DOI: 10.1055/s-0044-1779688 -
Biomolecules Feb 2024Drug combination therapy shows promise in cancer treatment by addressing drug resistance, reducing toxicity, and enhancing therapeutic efficacy. However, the intricate...
Drug combination therapy shows promise in cancer treatment by addressing drug resistance, reducing toxicity, and enhancing therapeutic efficacy. However, the intricate and dynamic nature of biological systems makes identifying potential synergistic drugs a costly and time-consuming endeavor. To facilitate the development of combination therapy, techniques employing artificial intelligence have emerged as a transformative solution, providing a sophisticated avenue for advancing existing therapeutic approaches. In this study, we developed SynerGNet, a graph neural network model designed to accurately predict the synergistic effect of drug pairs against cancer cell lines. SynerGNet utilizes cancer-specific featured graphs created by integrating heterogeneous biological features into the human protein-protein interaction network, followed by a reduction process to enhance topological diversity. Leveraging synergy data provided by AZ-DREAM Challenges, the model yields a balanced accuracy of 0.68, significantly outperforming traditional machine learning. Encouragingly, augmenting the training data with carefully constructed synthetic instances improved the balanced accuracy of SynerGNet to 0.73. Finally, the results of an independent validation conducted against DrugCombDB demonstrated that it exhibits a strong performance when applied to unseen data. SynerGNet shows a great potential in detecting drug synergy, positioning itself as a valuable tool that could contribute to the advancement of combination therapy for cancer treatment.
Topics: Humans; Artificial Intelligence; Neural Networks, Computer; Combined Modality Therapy; Drug Therapy, Combination; Antineoplastic Agents
PubMed: 38540674
DOI: 10.3390/biom14030253 -
Frontiers in Bioscience (Landmark... Mar 2024As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current...
BACKGROUND
As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospective studies. The exploration for diagnostic and therapeutic markers in small cell NETs is of great significance.
METHODS
In this study, we conducted single-cell RNA sequencing on a specimen obtained from a patient diagnosed with small cell endometrial neuroendocrine carcinoma (SCNEC) based on pathology. We revealed the cell map and intratumoral heterogeneity of the cancer cells through data analysis. Further, we validated the function of ISL LIM Homeobox 1 () in an established neuroendocrine cell line. Finally, we examined the association between and tumor staging in small cell lung cancer (SCLC) patient samples.
RESULTS
We observed the significant upregulation of expression in tumor cells that showed high expression of the neuroepithelial markers. Additionally, cell function experiments demonstrated that the high expression group exhibited markedly higher cell proliferation and migration abilities compared to the low expression group. Finally, we showed that the expression level of was correlated with SCLC stages.
CONCLUSIONS
protein in NETs shows promise as a potential biomarker for diagnosis and treatment.
Topics: Female; Humans; Transcription Factors; Retrospective Studies; Single-Cell Gene Expression Analysis; LIM-Homeodomain Proteins; Neuroendocrine Tumors; Biomarkers, Tumor; Endometrium; Carcinoma, Neuroendocrine
PubMed: 38538277
DOI: 10.31083/j.fbl2903100