935 research outputs found
Peripheral cytokine levels as a prognostic indicator in gastric cancer : a review of existing literature
Although strong connections exist between the carcinogenesis of gastric cancer and chronic inflammation, gastric cancer is unique in that the chronic gastritis which frequently precedes carcinogenesis is strongly associated with H. pylori infection. The interplay between H. pylori virulence factors and host immune cells is complex but culminates in the activation of inflammatory pathways and transcription factors such as NF-κB, STAT3, and AP-1, all of which upregulate cytokine production. Due to the key role of cytokines in modulating the immune response against tumour cells as well as possibly stimulating tumour growth and proliferation, different patterns of cytokine secretion may be associated with varying patient outcomes. In relation to gastric cancer, interleukin-6, 8, 10, 17A, TNF, and IFN-γ may have pro-tumour properties, although interleukin-10, TNF, and IFN-γ may have anti-tumour effects. However, due to the lack of studies investigating patient outcomes, only a link between higher interleukin-6 levels and poorer prognosis has been demonstrated. Further investigations which link peripheral cytokine levels to patient prognosis may elucidate important pathological mechanisms in gastric cancer which adversely impact patient survival and allow treatments targeting these processes to be developed
Biomarkers for tyrosine kinase inhibitors in renal cell cancer
Renal cell carcinoma (RCC) is a common malignancy. In 2012, in the USA, there were 65,000 new cases and 13,500 disease-specific deaths. In the same year it was the 6th most common new cancer diagnosed. During the last 50 years, despite an increase in incidence, the mortality has fallen, a possible result of earlier detection and improvements in therapy
A hybrid systematic narrative review of instruments measuring home-based care nurses\u27 competency
Aim: The aim of the study was to identify and synthesize the contents and the psychometric properties of the existing instruments measuring home-based care (HBC) nurses\u27 competencies. Design: A hybrid systematic narrative review was performed. Review Methods: The eligible studies were reviewed to identify the competencies measured by the instruments for HBC nurses. The psychometric properties of instruments in development and psychometric testing design studies were also examined. The methodological quality of the studies was evaluated using the Medical Education Research Study Quality Instrument and COSMIN checklist accordingly. Data Sources: Relevant studies were searched on CINAHL, MEDLINE (via PubMed), EMBASE, PsychINFO and Scopus from 2000 to 2022. The search was limited to full-text items in the English language. Results: A total of 23 studies reporting 24 instruments were included. 12 instruments were adopted or modified by the studies while the other 12 were developed and psychometrically tested by the studies. None of the instruments encompassed all of the 10 home-based nursing care competencies identified in an earlier study. The two most frequently measured competencies were the management of health conditions, and critical thinking and problem-solving skills, while the two least measured competencies were quality and safety, and technological literacy. The content and structural validity of most instruments were inadequate since the adopted instruments were not initially designed or tested among HBC nurses. Conclusion: This review provides a consolidation of existing instruments that were used to assess HBC nurses\u27 competencies. The instruments were generally not comprehensive, and the content and structural validity were limited. Nonetheless, the domains, items and approaches to instrument development could be adopted to develop and test a comprehensive competency instrument for home-based nursing care practice in the future. Impact: This review consolidated instruments used to measure home-based care nurses\u27 competency. The instruments were often designed for ward-based care nurses hence a comprehensive and validated home-based nursing care competency instrument is needed. Nurses, researchers and nursing leaders could consider the competency instruments identified in this review to measure nurses\u27 competencies, while a home-based nursing care competency scale is being developed. Patient or Public Contribution: No patient or public contribution was required in this review
The multiple potential biomarkers for predicting immunotherapy response : finding the needle in the haystack
Immune checkpoint inhibitors (ICIs) are being increasingly utilised in a variety of advanced malignancies. Despite promising outcomes in certain patients, the majority will not derive benefit and are at risk of potentially serious immune-related adverse events (irAEs). The development of predictive biomarkers is therefore critical to personalise treatments and improve outcomes. A number of biomarkers have shown promising results, including from tumour (programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB), stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a CARD (ASC)), from blood (peripheral blood mononuclear cells (PBMCs), circulating tumour DNA (ctDNA), exosomes, cytokines and metal chelators) and finally the microbiome
Phenomenological Consequences of Right-handed Down Squark Mixings
The mixings of quarks, hidden from view in Standard Model (SM), are
naturally the largest if one has an Abelian flavor symmetry. With supersymmetry
(SUSY) their effects can surface via squark loops. Squark and
gluino masses are at TeV scale, but they can still induce effects comparable to
SM in (or ) mixings, while mixing could be close to recent
hints from data. In general, CP phases would be different from SM, as may be
indicated by recent B Factory data. Presence of non-standard soft SUSY
breakings with large could enhance (or )
transitions.Comment: Version to appear in Phys. Rev. Let
Evidence for Factorization in Three-body B --> D(*) K- K0 Decays
Motivated by recent experimental results, we use a factorization approach to
study the three-body B --> D(*) K- K0 decay modes. Two mechanisms are proposed
for kaon pair production: current-produced (from vacuum) and transition (from B
meson). The Bbar0 --> D(*)+ K- K0 decay is governed solely by the
current-produced mechanism. As the kaon pair can be produced only by the vector
current, the matrix element can be extracted from e+ e- --> K Kbar processes
via isospin relations. The decay rates obtained this way are in good agreement
with experiment. Both current-produced and transition processes contribute to
B- --> D(*)0 K- K0 decays. By using QCD counting rules and the measured B- -->
D(*)0 K- K0 decay rates, the measured decay spectra can be understood.Comment: 17 pages, 6 figure
Spawning rings of exceptional points out of Dirac cones
The Dirac cone underlies many unique electronic properties of graphene and
topological insulators, and its band structure--two conical bands touching at a
single point--has also been realized for photons in waveguide arrays, atoms in
optical lattices, and through accidental degeneracy. Deformations of the Dirac
cone often reveal intriguing properties; an example is the quantum Hall effect,
where a constant magnetic field breaks the Dirac cone into isolated Landau
levels. A seemingly unrelated phenomenon is the exceptional point, also known
as the parity-time symmetry breaking point, where two resonances coincide in
both their positions and widths. Exceptional points lead to counter-intuitive
phenomena such as loss-induced transparency, unidirectional transmission or
reflection, and lasers with reversed pump dependence or single-mode operation.
These two fields of research are in fact connected: here we discover the
ability of a Dirac cone to evolve into a ring of exceptional points, which we
call an "exceptional ring." We experimentally demonstrate this concept in a
photonic crystal slab. Angle-resolved reflection measurements of the photonic
crystal slab reveal that the peaks of reflectivity follow the conical band
structure of a Dirac cone from accidental degeneracy, whereas the complex
eigenvalues of the system are deformed into a two-dimensional flat band
enclosed by an exceptional ring. This deformation arises from the dissimilar
radiation rates of dipole and quadrupole resonances, which play a role
analogous to the loss and gain in parity-time symmetric systems. Our results
indicate that the radiation that exists in any open system can fundamentally
alter its physical properties in ways previously expected only in the presence
of material loss and gain
Integration of Engineered “Spark-Cell” Spheroids for Optical Pacing of Cardiac Tissue
Optogenetic methods for pacing of cardiac tissue can be realized by direct genetic modification of the cardiomyocytes to express light-sensitive actuators, such as channelrhodopsin-2, ChR2, or by introduction of light-sensitized non-myocytes that couple to the cardiac cells and yield responsiveness to optical pacing. In this study, we engineer three-dimensional “spark cells” spheroids, composed of ChR2-expressing human embryonic kidney cells (from 100 to 100,000 cells per spheroid), and characterize their morphology as function of cell density and time. These “spark-cell” spheroids are then deployed to demonstrate site-specific optical pacing of human stem-cell-derived cardiomyocytes (hiPSC-CMs) in 96-well format using non-localized light application and all-optical electrophysiology with voltage and calcium small-molecule dyes or genetically encoded sensors. We show that the spheroids can be handled using liquid pipetting and can confer optical responsiveness of cardiac tissue earlier than direct viral or liposomal genetic modification of the cardiomyocytes, with 24% providing reliable stimulation of the iPSC-CMs within 6 h and >80% within 24 h. Moreover, our data show that the spheroids can be frozen in liquid nitrogen for long-term storage and transportation, after which they can be deployed as a reagent on site for optical cardiac pacing. In all cases, optical stimulation was achieved at relatively low light levels (<0.15 mW/mm2) when 5 ms or longer pulses were used. Our results demonstrate a scalable, cost-effective method with a cryopreservable reagent to achieve contactless optical stimulation of cardiac cell constructs without genetically modifying the myocytes, that can be integrated in a robotics-amenable workflow for high-throughput drug testing
Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer
The role of the local tumour and stromal immune landscape is increasingly recognised to be important in cancer development, progression and response to
therapy. The composition, function, spatial orientation and gene expression profile of the infiltrate of the innate and adaptive immune system at the tumour
and surrounding tissue has an established prognostic role in colorectal cancer (CRC). Multiple studies have confirmed that a tumour immune microenvironment
(TIME) reflective of a type 1 adaptive immune response is associated with improved prognosis. There have been significant efforts to evolve these observations into validated, histopathology-based prognostic biomarkers, such as the Immunoscore. However, the clinical need lies much more in the development of predictive, not prognostic, biomarkers which have the potential to improve patient outcomes. This is particularly pertinent to help guide cytotoxic chemotherapy use in CRC, which remains the standard of care. Cytotoxic chemotherapy has recognised immunomodulatory activity distinct from its antimitotic effects, including mechanisms such as immunogenic cell death (ICD) and induction/inhibition of key immune players. Response to chemotherapy
may differ with regard to molecular subtype of CRC, which are strongly associated with immune phenotypes. Thus, immune markers are potentially useful, though under-reported, predictive biomarkers. In this review, we discuss the impact of the TIME on response to cytotoxic chemotherapy in CRC, with a focus on baseline immune markers, and associated genomic and transcriptomic signatures
Droplet digital PCR based detection of EGFR mutations in advanced lung cancer patient liquid biopsies : a comparison of circulating tumour DNA extraction kits
Background: Mutations in the epidermal growth factor receptor gene, EGFR, predict response or resistance to first generation tyrosine kinase inhibitors in non-small cell lung cancer. These biomarkers can now be conveniently detected from liquid biopsies, however technical details of these assays are still being refined. Objective: To compare detection of four different non-small cell lung cancer (NSCLC) associated EGFR mutations from patient ctDNA isolated with five different ctDNA isolation kit. Methods: Droplet digital PCR (ddPCR) assays detecting four EGFR mutations were developed. ctDNA was isolated with five kits from plasma samples, one pleural and one ascites fluid from nine NSCLC patients with known EGFR mutations. ctDNA fragment sizes and concentrations were also assessed. Results: Each kit isolated DNA from all samples which contained an expected dominant DNA fragment of ~ 170 base pairs. Normalised for plasma input, one kit produced ctDNA extracts which consistently enabled the highest
cop n umber detection for all EGFR variants, and importantly was able to validate mutations in all patient samples. Other kits stood out in regards to cost economy as well as ease and speed of processing but were less efficient and
one kit was found to be incompatible with ddPCR. Conclusion: This study demonstrated successful ctDNA isolation from plasma, pleural fluid and ascites by four of five ctDNA isolation kits. The QIAmp circulating nucleic acid kit produced consistently the most sensitive detection of EGFR variants. While other kits allow for lower volume plasma input down to 0.1 ml, are faster, more economical and simpler to use, they are challenged by very low ctDNA concentrations in plasma
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