3714 research outputs found
Sort by
Pursuing the physician-scientist path to satisfy research curiosity and passion for patient care
No full textA proteomic approach to better understand the role of human neutrophil peptides in the NSCLC microenvironment
No full textAim: Although treatment of lung cancer, one of the deadliest diseases worldwide, with immune checkpoint inhibitors (ICIs) has shown promising outcomes, these survival outcomes are only observed in a relatively small subset of lung cancer patients. In a previous study, we elucidated that the presence of human neutrophil peptide (HNP) 1, 2 and 3 in non-small cell lung cancerous (NSCLC) biopsies is associated with a clinical response towards treatment with PD-1/PD-L1 immune checkpoint inhibitors. Furthermore, HNP1 has shown in vitro an immune-activated function towards lung cancer cells, but the specific role of HNP1 in (lung) cancer is still unknown. The aim of this study was to provide a better understanding of HNP1 in an NSCLC microenvironment.Methods: To gain better insights into the role of HNP1 on cancer growth and to unravel immune responses, in vitro (SILAC-labelled) A549/PBMC (from three healthy donors) cocultures were set up and treated/not treated with HNP1. After 5 days, both secretome and cellular analysis using mass spectrometry were performed on these cocultures. After protein identification in all different tested conditions, pathway analyses (MetaCoreTM) were performed to investigate the biological significance of HNP1 stimulation on the A549/PBMC cocultures. The proteomic outcomes were confirmed by multiplex ELISA for a proinflammatory cytokine panel (TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-12p70 and IL-18). Results: A number of biological pathways and process networks were observed to be upregulated after treatment of the coculture with HNP1. HNP1 stimulation leads to an increase in pathways and proteins stimulating chemotaxis (including plasmin signaling, leucocyte recruitment, CCL2 and CXCL8 expression), proinflammatory cytokine secretion (including IL-1β, IL-6 and TNF-α), dendritic cell (DC) maturation, phagocytosis and antigen presentation, leading to a more efficient adaptive anti-tumoral immunity.Conclusion: These results enhance our understanding of the role of HNP1 in the tumor microenvironment and suggest that HNP1 may be able to induce tumor necrosis by inducing prostimulatory immune responses
Novel techniques for the management of esophageal anastomotic leaks
No full textAnastomotic leaks (ALs) after esophageal resection remain a dreaded complication and are associated with high morbidity and mortality, along with an increased cost of care and prolonged hospitalization. Management strategies include confirming conduit viability, controlling sepsis with drainage/antibiotics, and maintaining nutrition. Traditional treatment of ALs has given way to nonoperative management including endoscopic and radiological techniques, which are associated with decreased morbidity. This article aims to review novel technologies and techniques for the management of esophageal ALs, including self-expandable metal stents, endoluminal vacuum therapy, leak content drainage, and radiology-guided drain placement
Cryoablation for the management of Small Renal Masses
No full textRenal cell carcinoma is identified most often in the sixth or seventh decade of life, coinciding with the rise in incidental diagnosis of small renal masses as imaging technology has advanced. However, not all patients in this older age group are surgical candidates owing to their comorbidities. Cryoablation is a well-established minimally invasive technique for the treatment of small renal masses. The advent of less invasive ablative treatment has alleviated the surgical dilemma for certain patients who are contraindicated for extirpative procedures. With the appropriate patient selection, cryoablation is safe and effective, resulting in comparable local tumor control, fewer complications, better preservation of renal function, a faster recovery, and a shorter hospital stay. The percutaneous procedure has increased in popularity due to the advantages of reduced pain, shorter hospitalization, the ability to be performed without general anesthesia, and decreased cost relative to surgery
Selenium nanomaterials enabled flexible and wearable electronics
No full textSelenium (Se), as an intriguing chalcogenide semiconductor, has traditionally been used for solar energy harvesting. The recent development of nanoscience and nanotechnology has enabled a myriad of Se nanomaterials with compelling structures and unique features. Compared with other chalcogens, Se nanomaterials possess anisotropic crystalline structure, intrinsic chirality, and high reactivity, as well as unique optical, electrical, photoconductive, and piezoelectrical properties. The integration of these Se nanomaterials with technologically important materials, such as conductors and semiconductors, over flexible, bendable, stretchable, and highly curved substrates offer a new generation of Se nanomaterial-based flexible and wearable electronics. In this mini review, we survey the recent scientific and technological breakthroughs in Se nanomaterials-enabled flexible and wearable electronics. We highlight the synthesis, fabrication, morphologies, structure, and properties (optical, electrical, optoelectrical, photovoltaic, and piezoelectric) of Se nanomaterials as well as their integration into innovative functional devices that deliver higher forms of applications across smart sensing, health care, and energy domains. We conclude with a critical analysis of existing challenges and opportunities that will trigger the continued progress of the field
Luminescent alkynylplatinum(II) terpyridine-containing conjugated polymers: synthesis, characterization and photophysical studies
No full textA series of alkynylplatinum(II) terpyridine complexes and alkynylplatinum(II) terpyridine-containing conjugated polymers with different polymer backbones has been synthesized, and their spectroscopic properties and Förster resonance energy transfer (FRET) processes has been investigated. The platinum(II)-containing polymers exhibit dual emissive features with emission maxima at ca. 416-465 nm and ca. 671-673 nm, which are assigned to be originated from singlet intraligand (1IL) excited states from the polymer backbone and triplet metal-metal-to-ligand charge transfer (3MMLCT) excited states from the platinum(II) pendants, respectively. The Förster radii (R0) of the platinum(II)-containing conjugated polymers have been determined, and their distinctive thermo-responsive luminescence changes have also been observed. The present work has demonstrated the utilization of “click” reaction for the preparation of platinum(II)-containing conjugated polymers, which show unique photophysical and spectroscopic properties. Through the judicious design, this type of platinum(II)-containing polymer is found to be sensitive to temperature, resulting in ratiometric emission changes. This study has provided valuable insights into the preparation of metal-containing polymeric systems for different applications
Potential of artificial intelligence in the risk stratification for and early detection of pancreatic cancer
No full textPancreatic ductal adenocarcinoma (PDAC) is the third most lethal cancer in the United States, with a 5-year life expectancy of 11%. Most symptoms manifest at an advanced stage of the disease when surgery is no longer appropriate. The dire prognosis of PDAC warrants new strategies to improve the outcomes of patients, and early detection has garnered significant attention. However, early detection of PDAC is most often incidental, emphasizing the importance of developing new early detection screening strategies. Due to the low incidence of the disease in the general population, much of the focus for screening has turned to individuals at high risk of PDAC. This enriches the screening population and balances the risks associated with pancreas interventions. The cancers that are found in these high-risk individuals by MRI and/or EUS screening show favorable 73% 5-year overall survival. Even with the emphasis on screening in enriched high-risk populations, only a minority of incident cancers are detected this way. One strategy to improve early detection outcomes is to integrate artificial intelligence (AI) into biomarker discovery and risk models. This expert review summarizes recent publications that have developed AI algorithms for the applications of risk stratification of PDAC using radiomics and electronic health records. Furthermore, this review illustrates the current uses of radiomics and biomarkers in AI for early detection of PDAC. Finally, various challenges and potential solutions are highlighted regarding the use of AI in medicine for early detection purposes
Minimally invasive transthoracic resection of a segment eight liver tumor
No full textDespite advances in technology and technique of minimally invasive liver surgery, resection of lesions in the posterosuperior segments such as segment 8 (S8) remains challenging. Compared to open surgery, there are specific differences that make minimally invasive access to S8 challenging. These include the caudal view along the axis of the hepatoduodenal ligament, increased distance between trocars and the operative field, and the liver fulcrum created by the anterolateral segments limiting the view. However, several advancements have helped to overcome these challenges, such as the use of intercostal trocars (combined lateral-abdominal approach) and a flexible tip camera. Consequently, a total thoracoscopic (transthoracic) approach was developed to resect subdiaphragmatic tumors, which may particularly benefit patients with a hostile abdomen. This article summarizes the anatomic, technical, and technological considerations for safe resection of lesions in S8
Establishing genetic manipulation for novel strains of human gut bacteria
No full textRecent years have seen the development of high-accuracy and high-throughput genetic manipulation techniques, which have greatly improved our understanding of genetically tractable microbes. However, challenges remain in establishing genetic manipulation techniques in novel organisms, owing largely to exogenous DNA defence mechanisms, lack of selectable markers, lack of efficient methods to introduce exogenous DNA and an inability of genetic vectors to replicate in their new host. In this review, we describe some of the techniques that are available for genetic manipulation of novel microorganisms. While many reviews exist that focus on the final step in genetic manipulation, the editing of recipient DNA, we particularly focus on the first step in this process, the transfer of exogenous DNA into a strain of interest. Examples illustrating the use of these techniques are provided for a selection of human gut bacteria in which genetic tractability has been established, such as Bifidobacterium, Bacteroides and Roseburia. Ultimately, this review aims to provide an information source for researchers interested in developing genetic manipulation techniques for novel bacterial strains, particularly those of the human gut microbiota
Multimodal 4-arylchromene derivatives with microtubule-destabilizing, anti-angiogenic, and MYB-inhibitory activities
No full textAim: Efficient and readily available anticancer drugs are sought as treatment options. For this reason, chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic properties.Methods: 2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds (2A-R) were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol, various aryl aldehydes, and malononitrile. We performed assays to study the inhibition of tumor cell growth [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromid (MTT) assay], effects on microtubules (immunofluorescence), cell cycle (flow-activated cell sorting analysis), angiogenesis (zebrafish model), and MYB activity (luciferase reporter assay). Fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug derivative.Results: Compounds 2A-C and 2F exhibited robust antiproliferative activities against several human cancer cell lines (50% inhibitory concentrations in the low nanomolar range) and showed potent MYB inhibition. The alkyne derivative 3 was localized in the cytoplasm after only 10 min of incubation. Substantial microtubule disruption and G2/M cell-cycle arrest were observed, where compound 2F stood out as a promising microtubule-disrupting agent. The study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in vivo.Conclusion: The close interplay of various mechanisms, including cell-cycle arrest, MYB inhibition, and anti-angiogenic activity, led to identifying promising multimodal anticancer drug candidates
Data sources:
Access Repository Dashboard
Do you manage OAE Publishing (via Crossref)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!