We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis.
We ...collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups.
Median follow-up duration was 74 months (24-162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR.
We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent advances in medical technology and endo‐laparoscopic devices have enabled the treatment of gastrointestinal (GI) cancers to be minimally invasive through endo‐laparoscopic photodynamic therapy ...(PDT). To achieve an efficient regional or endo‐laparoscopic PDT, it is necessary to develop a highly target specific photosensitizer (PS) that can be easily treated to the lesion site with endo‐laparoscopic device. Here, an ideal polymeric PS is demonstrated for effective endo‐laparoscopic PDT. In the synthetic process, conventional PS (i.e., Chlorin e6, Ce6) is conjugated with an Aptamer (i.e., AS1411) targeting nucleolin (also called C23) overexpressed on the cancer cell membrane using a water‐soluble polymeric linker (i.e., polyethylene glycol, PEG). The synthesized Aptamer‐PEG‐Ce6 could target nucleolin‐overexpressing tumor cells efficiently and visualize the tumor tissues through optical and fluorescent imaging both in vitro and ex vivo, and effectively kills cancer cells under laser irradiation. Tumor staining with Aptamer‐PEG‐Ce6 is easily accomplished through endoscopic equipment within a few minutes. Furthermore, after laser irradiation, Aptamer‐PEG‐Ce6 is found to penetrate deeply into the tumor tissue and induce apoptosis of tumor cells. Taken together, the tumor‐specific Aptamer‐conjugated polymeric PS developed in this study has great potential as an ideal photomedicine for effective tumor treatment using endo‐laparoscopic PDT.
An ideal polymeric photosensitizer (PS) conjugated with an aptamer that specifically binds to nucleolin overexpressing tumor is developed for highly efficient endo‐laparoscopic photodynamic therapy. The polymeric PS is easily sprayed through the endoscopic device to distinguish tumors from healthy tissue via an optical and fluorescence imaging system. Finally, the tumor tissue labeled with Aptamer‐conjugated PSs is efficiently eliminated under laser irradiation.
Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding ...of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aimed to develop a computer-aided diagnostic system (CAD) for predicting colorectal polyp histology using deep-learning technology and to validate its performance. Near-focus narrow-band imaging ...(NBI) pictures of colorectal polyps were retrieved from the database of our institution. Of these, 12480 image patches of 624 polyps were used as a training set to develop the CAD. The CAD performance was validated with two test datasets of 545 polyps. Polyps were classified into three histological groups: serrated polyp (SP), benign adenoma (BA)/mucosal or superficial submucosal cancer (MSMC), and deep submucosal cancer (DSMC). The overall kappa value measuring the agreement between the true polyp histology and the expected histology by the CAD was 0.614-0.642, which was higher than that of trainees (n = 6, endoscopists with experience of 100 NBI colonoscopies in <6 months; 0.368-0.401) and almost comparable with that of the experts (n = 3, endoscopists with experience of 2,500 NBI colonoscopies in ≥5 years) (0.649-0.735). The areas under the receiver operating curves for CAD were 0.93-0.95, 0.86-0.89, and 0.89-0.91 for SP, BA/MSMC, and DSMC, respectively. The overall diagnostic accuracy of the CAD was 81.3-82.4%, which was significantly higher than that of the trainees (63.8-71.8%, P < 0.01) and comparable with that of experts (82.4-87.3%). The kappa value and diagnostic accuracies of the trainees improved with CAD assistance: that is, the kappa value increased from 0.368 to 0.655, and the overall diagnostic accuracy increased from 63.8-71.8% to 82.7-84.2%. CAD using a deep-learning model can accurately assess polyp histology and may facilitate the diagnosis of colorectal polyps by endoscopists.
This article presents a <inline-formula> <tex-math notation="LaTeX">400\ttimes 200</tex-math> </inline-formula> single-photon avalanche diode (SPAD) X-ray detector that supports seamless global ...shutter operation. The pixel consists of an SPAD with two time-encoded extrapolation counters. For use under low X-ray dose conditions, the pixels and readout circuitry operate in a fully digital manner, avoiding the noise penalty of the readout. Under high X-ray dose conditions, the proposed counter operates in the extrapolation mode and thus achieves a high dynamic range (HDR), while reducing the counter's power consumption. This is achieved by capturing the time of the counter overflow (<inline-formula> <tex-math notation="LaTeX">T_{\rm OF}</tex-math> </inline-formula>) and expanding the counter depth by the ratio between the integration time (<inline-formula> <tex-math notation="LaTeX">T_{\rm INT}</tex-math> </inline-formula>) and <inline-formula> <tex-math notation="LaTeX">T_{\rm OF}</tex-math> </inline-formula>. To reconstruct <inline-formula> <tex-math notation="LaTeX">T_{\rm OF}</tex-math> </inline-formula>, a <inline-formula> <tex-math notation="LaTeX">\phi_{\rm GCLK}</tex-math> </inline-formula> signal is distributed during <inline-formula> <tex-math notation="LaTeX">T_{\rm INT}</tex-math> </inline-formula> and accumulated from <inline-formula> <tex-math notation="LaTeX">T_{\rm OF}</tex-math> </inline-formula> to the end of <inline-formula> <tex-math notation="LaTeX">T_{\rm INT}</tex-math> </inline-formula> by reusing the counter. This only requires distribution of the <inline-formula> <tex-math notation="LaTeX">\phi_{\rm GCLK}</tex-math> </inline-formula> across the pixel array. Furthermore, seamless global shutter operation is realized through the use of two counters, which achieves a 100% temporal aperture for the X-ray photon. The proposed X-ray detector is implemented in a 1P5M 65-nm CMOS process. To be used for both medical diagnosis and industrial inspection, the pixel pitch is selected as 49.5 <inline-formula> <tex-math notation="LaTeX">\mu\text{m}</tex-math> </inline-formula>. The <inline-formula> <tex-math notation="LaTeX">400\ttimes 200</tex-math> </inline-formula> detector achieves a dynamic range (DR) of 113.3 dB, while consuming only 127.2 mW. Compared with previous X-ray detectors, the proposed detector exhibits a 24.9-dB improvement in DR.
Background The optimal technique for removal of diminutive or small colorectal polyps is debatable. Objective To compare the complete resection rates of cold snare polypectomy (CSP) and cold forceps ...polypectomy (CFP) for the removal of adenomatous polyps ≤7 mm. Design Prospective randomized controlled study. Setting A university hospital. Patients A total of 139 patients who were found to have ≥1 colorectal adenomatous polyps ≤7 mm. Interventions Polyps were randomized to be treated with either CSP or CFP. After the initial polypectomy, additional EMR was performed at the polypectomy site to assess the presence of residual polyp tissue. Main Outcome Measurements Absence of residual polyp tissue in the EMR specimen of the polypectomy site was defined as complete resection. Results Among a total of 145 polyps, 128 (88.3%) were adenomatous polyps. The overall complete resection rate for adenomatous polyps was significantly higher in the CSP group compared with the CFP group (57/59, 96.6% vs 57/69, 82.6%; P = .011). Although the complete resection rates for adenomatous polyps ≤4 mm were not different (27/27, 100% vs 31/32, 96.9%; P = 1.000), the complete resection rates for adenomatous polyps sized 5 to 7 mm was significantly higher in the CSP group compared with the CFP group (30/32, 93.8% vs 26/37, 70.3%; P = .013). Limitations Single-center study. Conclusion CSP is recommended for the complete resection of colorectal adenomatous polyps ≤7 mm. (Clinical trial registration number: NCT01665898.)
Oxide-based all solid state battery (ASSB) systems require highly enhanced cell assemblies technology in the light of the sintering issue, although various inorganic-based lithium ion conductors have ...been proposed and attempted to be adopted in battery systems. Here, the compatibility of Li-La-(Zr-Ta)-O garnet related lithium ion conductors with ASSB systems processed by spark plasma sintering (SPS) is reported. Further, the challenges with respect to the material and processing are also discussed. Li7-xLa3Zr1.5Ta0.5O12-d processed by SPS shows a high ionic conductivity of 1.35 10-3 S cm-1 and 1.23 10-2 S cm-1 at 25 degree C and 80 degree C, respectively. In addition, the material also shows good structural stability, which is a critical challenge encountered in garnet structured materials treated under severe SPS process conditions. An ASSB assembled by SPS using the Li4Ti5O12-Li7-xLa3Zr1.5Ta0.5O12-d composite electrode shows a surface capacity of 0.2 mAh cm-2 at 80 degree C. The battery shows a well-organized structure with a good lithium diffusion percolation path and the low solid contact resistance without any defects and undesirable reactions arising from the sintering method.
To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or ...coexisting CVD risk status of the participants.
Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease.
In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 confidence interval (CI) 1.14-1.54; RR for all-cause mortality = 1.20 CI 1.07-1.34). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 CI 1.28-3.77; RR for all-cause mortality = 1.66 CI 1.41-1.94), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 CI 1.08-1.85; I
= 0%).
SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.
The principle factors underlying gastric cancer (GC) development and outcomes are not well characterized resulting in a paucity of validated therapeutic targets. To identify potential molecular ...targets, we analyze gene expression data from GC patients and identify the nuclear receptor ESRRG as a candidate tumor suppressor. ESRRG expression is decreased in GC and is a predictor of a poor clinical outcome. Importantly, ESRRG suppresses GC cell growth and tumorigenesis. Gene expression profiling suggests that ESRRG antagonizes Wnt signaling via the suppression of TCF4/LEF1 binding to the CCND1 promoter. Indeed, ESRRG levels are found to be inversely correlated with Wnt signaling-associated genes in GC patients. Strikingly, the ESRRG agonist DY131 suppresses cancer growth and represses the expression of Wnt signaling genes. Our present findings thus demonstrate that ESRRG functions as a negative regulator of the Wnt signaling pathway in GC and is a potential therapeutic target for this cancer.
We reported the synthesis of a copolymer- and metal-organic framework-based electrochemical sensor, UiO-66-NH2@P(ANI-co-ANA) using the polymerization method for the highly sensitive and selective ...detection of hydrogen peroxide (H2O2) and dopamine (DA). The as-synthesized material was characterized via Fourier transform infrared spectroscopy, X-ray diffraction analysis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis. The electrochemical characteristics of the proposed sensor were evaluated via impedance spectroscopy and cyclic voltammetry (CV). The electrochemical oxidation of DA and the reduction of H2O2 were determined via CV, square-wave voltammetry, and chronoamperometric techniques. The fabricated sensor exhibited a wide linear range of 25–500 μM, with a sensitivity of 1396.1 μAμM−1cm−2 and a limit of detection of 0.6 μM, for the electrochemical reduction of H2O2. Additionally, it exhibited a wide linear range of 10–110 μM, with a sensitivity of 1110.2 μAμM−1cm−2 and a limit of detection of 0.3 μM, for the electrochemical detection of DA. The practical utility of the fabricated sensor was evaluated via the detection of H2O2 in milk samples and DA in human urine samples.
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•Fabrication of a copolymer-grafted metal organic framework-based electrochemical sensor in a facile way.•It exhibited a limit of detection of 0.6 μM and 0.3 μM for the electrochemical detection of H2O2 and DA.•The development of a cost-effective and eco-friendly technique.
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