Background
Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) ...after hepatectomy remains controversial. A systematic review and meta‐analysis was undertaken to evaluate its prognostic value.
Methods
References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease‐free survival after hepatic resection between patients with CRLM originating from right‐ or left‐sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random‐effects model. Meta‐regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this.
Results
The final analysis included 21 953 patients from 45 study cohorts. Compared with left‐sided primary tumour location, right‐sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease‐free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right‐sided primary tumour location on overall survival was more prominent in the non‐Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01).
Conclusion
This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.
Antecedentes
La ubicación del tumor primario (primary tumor location, PTL) ha surgido como un factor pronóstico importante en los cánceres colorrectales (colorectal cancers, CRCs) localizados y metastásicos. Sin embargo, todavía se discute su relevancia como factor pronóstico tras la resección de metástasis hepáticas de cáncer colorrectal (colorectal liver metastases, CRLM). Se realizó una revisión sistemática y un metaanálisis para determinar su valor pronóstico.
Métodos
En PubMed, EMBASE, Web of Science y la Biblioteca Cochrane se identificaron los trabajos que compararon la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease‐free survival, DFS) tras la resección hepática de CRLM cuyo CRCs estuviese situado en el lado derecho o izquierdo. Los datos se expresaron en forma del cociente de riesgos instantáneos (hazard ratio, HR) e intervalos de confianza del 95% (i.c. del 95%) de acuerdo con un modelo de efectos aleatorios. Se efectuaron análisis de metarregresión y de subgrupos para evaluar el efecto de los factors de confusión existentes en las estimaciones de HR, ajustando por los mismos.
Resultados
El análisis final incluyó 21.953 pacientes de cohortes de 45 estudios. La PTL en el lado derecho en comparación con el lado izquierdo se asoció con una peor supervivencia global (HR 1,39; i.c. del 95% 1,28‐1,51; P < 0,001; intervalo de predicción 1,00‐1,93) y una tendencia a un impacto negativo en la DFS (HR 1,18; i.c. del 95% 1,06‐1,32; P = 0,004; intervalo de predicción 0,79‐1,75). El análisis de subgrupos mostró que el efecto negativo de la PTL del lado derecho en la OS fue más prominente en la población no asiática (HR 1,47; i.c. del 95% 1,33‐1,62) que en la asiática (HR 1,18; i.c. del 95% 1,05‐1,32; Pinteracción < 0,01).
Conclusión
Este estudio demostró que la PTL tiene un papel pronóstico tras la hepatectomía de las CRLM, especialmente respecto a la OS. La adición de la PTL proporcionaría una optimización importante en los modelos actuales de predicción pronóstica de CRLM.
The prognostic role of primary tumour location in colorectal liver metastases (CRLM) after hepatectomy remains controversial. This meta‐analysis demonstrated a prognostic role of primary tumour location in CRLM receiving hepatectomy, especially regarding overall survival.
Primary tumor location has prognostic value
Summary
Tertiary lymphoid structure (TLS) provides a local and critical microenvironment for both cellular and humoral immunity and supports effective antigen presentation and lymphocyte activation. ...However, the gene expression profile and prognostic significance of TLS in oral cancer remain largely unrevealed. In this study, we found the presence of both intratumoral and peritumoral TLSs in a series of 65 patients with oral cancer treated by surgical resection, with positive detection rates of 33.8 and 75.4%, respectively. The presence of intratumoral TLSs, but not peritumoral TLSs, was significantly associated with decreased P53 and Ki67 scores (P = 0·027 and 0·047, respectively). The survival analyses revealed that oral cancer patients with higher grades of TLSs was associated with improved disease‐free survival (DFS) and overall survival (OS) (P = 0·037 and 0·031, respectively). Gene expression profiling analysis of the cytokines and chemokines responsible for lymph‐node neogenesis identified a three‐up‐regulated‐gene set, i.e. IL7, LTB and CXCL13, which was shown to be correlated with human oral cancer‐associated TLSs. This study provides a framework for better understanding of oral cancer‐associated TLSs and for delineating future innovative prognostic biomarkers and immune therapeutic strategies for oral cancer.
Tertiary lymphoid structure (TLS) provides a local and critical microenvironment for both cellular and humoral immunity and supports effective antigen presentation and lymphocyte activation. Here, we found that oral cancer patients with higher grade TLSs signified improved disease‐free survival (DFS) and overall survival (OS). Gene expression profiling analysis of the cytokines and chemokines responsible for lymph‐node neogenesis identified a 3‐upregulated‐gene set, i.e. IL7, LTB and CXCL13, which was indicated correlated with oral cancer‐associated TLSs.
Close white dwarf binaries consisting of a white dwarf and an A-, F-, G-, or K-type main-sequence star, henceforth close WD+AFGK binaries, are ideal systems to understand the nature of type Ia ...supernovae progenitors and to test binary evolution models. In this work we identify 775 WD+AFGK candidates from TGAS (The Tycho-Gaia Astrometric Solution) and Gaia Data Release 2 (DR2), a well-defined sample of stars with available parallaxes, and we measure radial velocities (RVs) for 275 of them with the aim of identifying close binaries. The RVs have been measured from high-resolution spectra obtained at the Xinglong 2.16 m Telescope and the San Pedro Mártir 2.12 m Telescope and/or from available LAMOST DR6 (low-resolution) and RAVE DR5 (medium-resolution) spectra. We identify 23 WD+AFGK systems displaying more than 3 RV variation among 151 systems for which the measured values are obtained from different nights. Our WD+AFGK binary sample contains both AFGK dwarfs and giants, with a giant fraction ∼43%. The close binary fractions we determine for the WD+AFGK dwarf and giant samples are 24% and 15%, respectively. We also determine the stellar parameters (i.e., effective temperature, surface gravity, metallicity, mass, and radius) of the AFGK companions with available high-resolution spectra. The stellar parameter distributions of the AFGK companions that are members of close and wide binary candidates do not show statistically significant differences.
Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin ...structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9
leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.
We present an amplitude analysis of the decay D 0 → K - π + π + π - based on a data sample of 2.93 fb −1 acquired by the BESIII detector at the ψ(3770) resonance. With a nearly background free ...sample of about 16000 events, we investigate the substructure of the decay and determine the relative fractions and the phases among the different intermediate processes. Our amplitude model includes the two-body decays D 0 → ¯K *0 ρ 0 , D 0 → K − a + 1 (1260) and D 0 → K − 1 (1270)π + , the three-body decays D 0 →¯K *0 π + π − and D 0 → K − π + ρ 0 , as well as the four-body nonresonant decay D 0 → K − π + π + π − . The dominant intermediate process is D 0 → K − a + 1 (1260), accounting for a fit fraction of 54.6%.
This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting ...the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. The 5-year overall survival was 68.3% for SND and 65.2% for RND/MRND patients (P = 0.590), while the 5-year disease-specific survival was 70.4% for SND and 75.7% for RND/MRND patients (P = 0.715). Histological grade and postoperative radiotherapy were independent predictors of the outcome for SND patients. For histological grade II/III cases, 5-year overall survival (P = 0.004) and disease-specific survival (P = 0.002) outcomes differed significantly between patients treated with and without postoperative radiotherapy, with worse survival for patients not treated with radiotherapy. Therefore, SND appears appropriate for cN1 OSCC patients, and postoperative radiotherapy is recommended for those with histological grade II or III tumours.
Spatio-temporal variation of aerosol optical properties and aerosol direct radiative effects (ADRE) are studied based on high quality aerosol data at 21 sunphotometer stations with at least 4-months ...worth of measurements in China mainland and Hong Kong. A parameterization is proposed to describe the relationship of ADREs to aerosol optical depth at 550 nm (AOD) and single scattering albedo at 550 nm (SSA). In the middle-east and south China, the maximum AOD is always observed in the burning season, indicating a significant contribution of biomass burning to AOD. Dust aerosols contribute to AOD significantly in spring and their influence decreases from the source regions to the downwind regions. The occurrence frequencies of background level AOD (AOD < 0.10) in the middle-east, south and northwest China are very limited (0.4%, 1.3% and 2.8%, respectively). However, it is 15.7% in north China. Atmosphere is pristine in the Tibetan Plateau where 92.0% of AODs are <0.10. Regional mean SSAs at 550 nm are 0.89–0.90, although SSAs show substantial site and season dependence. ADREs at the top and bottom of the atmosphere for solar zenith angle of 60 ± 5° are −16–−37 W m−2 and –66–−111 W m−2, respectively. ADRE efficiency shows slight regional dependence. AOD and SSA together account for more than 94 and 87% of ADRE variability at the bottom and top of the atmosphere. The overall picture of ADRE in China is that aerosols cool the climate system, reduce surface solar radiation and heat the atmosphere.
•A high-quality database of aerosol optical properties in China was established.•An empirical relationship of AOD and SSA to ADRE has been introduced.•Spatio-temporal variation of aerosol optical properties and ADRE was revealed.
The past decade has evinced a boom of computer-based approaches to aid movement assessment in early infancy. Increasing interests have been dedicated to develop AI driven approaches to complement the ...classic Prechtl general movements assessment (GMA). This study proposes a novel machine learning algorithm to detect an age-specific movement pattern, the fidgety movements (FMs), in a prospectively collected sample of typically developing infants. Participants were recorded using a passive, single camera RGB video stream. The dataset of 2800 five-second snippets was annotated by two well-trained and experienced GMA assessors, with excellent inter- and intra-rater reliabilities. Using OpenPose, the infant full pose was recovered from the video stream in the form of a 25-points skeleton. This skeleton was used as input vector for a shallow multilayer neural network (SMNN). An ablation study was performed to justify the network's architecture and hyperparameters. We show for the first time that the SMNN is sufficient to discriminate fidgety from non-fidgety movements in a sample of age-specific typical movements with a classification accuracy of 88%. The computer-based solutions will complement original GMA to consistently perform accurate and efficient screening and diagnosis that may become universally accessible in daily clinical practice in the future.
An early steep decay component following the prompt GRBs is commonly observed in Swift XRT light curves, which is regarded as the tail emission of the prompt gamma rays. Prompted by the observed ...strong spectral evolution in the tails of GRBs 060218 and 060614, we present a systematic time-resolved spectral analysis for the Swift GRB tails detected between 2005 February and 2007 January. We select a sample of 44 tails that are bright enough to perform time-resolved spectral analyses. Among them 11 tails are smooth and without superimposing significant flares, and their spectra have no significant temporal evolution. We suggest that these tails are dominated by the curvature effect of the prompt gamma rays due to delay of propagation of photons from large angles with respect to the line of sight. More interestingly, 33 tails show clear hard-to-soft spectral evolution, with 16 of them being smooth tails directly following the prompt GRBs, and the others being superimposed with large flares. We focus on the 16 clean, smooth tails and consider three toy models to interpret the spectral evolution. The curvature effect of a structured jet and a model invoking superposition of the curvature effect tail and a putative underlying soft emission component cannot explain all the data. The third model, which invokes an evolving exponential spectrum, seems to reproduce both the light curve and the spectral evolution of all the bursts, including GRBs 060218 and 060614. More detailed physical models are called for to understand the apparent evolution effect.
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