Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review

<p>Abstract</p> <p>Background</p> <p>To evaluate the objective clinical outcomes of active specific immunotherapy (ASI) in advanced colorectal cancer (advanced CRC) and suspected minimal residual colorectal cancer (suspected minimal residual CRC).</p> <p>Methods</p> <p>A search was conducted on Medline and Pub Med from January 1998 to January 2010 for original studies on ASI in colorectal cancer (CRC). All articles included in this study were assessed with the application of predetermined selection criteria and were divided into two groups: ASI in advanced CRC and ASI in suspected minimal residual CRC. For ASI in suspected minimal residual CRC, a meta-analysis was executed with results regarding the overall survival (OS) and disease-free survival (DFS). Regarding ASI in advanced colorectal cancer, a system review was performed with clinical outcomes.</p> <p>Results</p> <p>1375 colorectal carcinoma patients with minimal residual disease have been enrolled in Meta-analysis. A significantly improved OS and DFS was noted for suspected minimal residual CRC patients utilizing ASI (For OS: HR = 0.76, P = 0.007; For DFS: HR = 0.76, P = 0.03). For ASI in stage II suspected minimal residual CRC, OS approached significance when compared with control (HR = 0.71, P = 0.09); however, the difference in DFS of ASI for the stage II suspected minimal residual CRC reached statistical significance (HR = 0.66, P = 0.02). For ASI in stage III suspected minimal residual CRC compared with control, The difference in both OS and DFS achieved statistical significance (For OS: HR = 0.76, P = 0.02; For DFS: HR = 0.81, P = 0.03). 656 advanced colorectal patients have been evaluated on ASI in advanced CRC. Eleven for CRs and PRs was reported, corresponding to an overall response rate of 1.68%. No serious adverse events have been observed in 2031 patients.</p> <p>Conclusions</p> <p>It is unlikely that ASI will provide a standard complementary therapeutic approach for advanced CRC in the near future. However, the clinical responses to ASI in patients with suspected minimal residual CRC have been encouraging, and it has become clear that immunotherapy works best in situations of patients with suspected minimal residual CRC.</p

Automatic coronary artery segmentation of CCTA images using UNet with a local contextual transformer

Coronary artery segmentation is an essential procedure in the computer-aided diagnosis of coronary artery disease. It aims to identify and segment the regions of interest in the coronary circulation for further processing and diagnosis. Currently, automatic segmentation of coronary arteries is often unreliable because of their small size and poor distribution of contrast medium, as well as the problems that lead to over-segmentation or omission. To improve the performance of convolutional-neural-network (CNN) based coronary artery segmentation, we propose a novel automatic method, DR-LCT-UNet, with two innovative components: the Dense Residual (DR) module and the Local Contextual Transformer (LCT) module. The DR module aims to preserve unobtrusive features through dense residual connections, while the LCT module is an improved Transformer that focuses on local contextual information, so that coronary artery-related information can be better exploited. The LCT and DR modules are effectively integrated into the skip connections and encoder-decoder of the 3D segmentation network, respectively. Experiments on our CorArtTS2020 dataset show that the dice similarity coefficient (DSC), Recall, and Precision of the proposed method reached 85.8%, 86.3% and 85.8%, respectively, outperforming 3D-UNet (taken as the reference among the 6 other chosen comparison methods), by 2.1%, 1.9%, and 2.1%

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

Summary(#br)Resistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH

Prediction of dynamic liquid level in water-producing shale gas wells based on liquid film model

The accumulation of liquid in shale gas wells will lead to an increase in bottom-hole pressure, and a decrease in production, even the shutdown of gas wells. Accurately predicting the variation of liquid height in shale gas wellbore and the corresponding production is helpful to determine the liquid accumulation status and the development of reasonable drainage construction plans. It can provide theoretical support for the efficient and stable production of shale gas wells. A predictive analysis model of shale gas wellbore liquid accumulation was established based on a liquid film carrying model, which considers the coupling of flow in the reservoir and wellbore in shale gas production system. This model can accurately predict the liquid accumulation height, production rate, and the bottomhole pressure changes in liquid-accumulating gas wells. A comparative analysis was conducted on the effect of wellbore structure on liquid accumulation characteristics in the typical upward-type and downward-type horizontal wells in the W block. In upward-type horizontal wells, the liquid height increases slowly before the liquid accumulation fills the horizontal section, and the liquid height increases rapidly after the liquid accumulation fills the horizontal section. Compared to upward-type horizontal wells, the liquid height rises more quickly and the gas production rate is more sensitive to liquid accumulation in downward-type horizontal wells

Circuit Bootstrapping: Faster and Smaller

We present a novel circuit bootstrapping algorithm that outperforms the state-of-the-art TFHE method with 9.9× speedup and 15.6× key size reduction. These improvements can be attributed to two technical contributions. Firstly, we redesigned the circuit bootstrapping workflow to operate exclusively under the ring ciphertext type, which eliminates the need of conversion between LWE and RLWE ciphertexts. Secondly, we improve the LMKC+ blind rotation algorithm by reducing the number of automorphisms, then propose the first automorphism type multi-value functional bootstrapping. These automorphism-based techniques lead to further key size optimization, and are of independent interest besides circuit bootstrapping. Based our new circuit bootstrapping we can evaluate AES-128 in 26.2s (single thread), achieving 10.3× speedup compared with the state-of-the-art TFHE-based approach

Prognostic value of the ascites characteristics in pseudomyxoma peritonei originating from the appendix

BackgroundPseudomyxoma peritonei (PMP) is a rare disease, with the overall survival (OS) influenced by many factors. To date, no ascites characteristics have been reported to predict OS of patients with PMP. The present study therefore aims to describe the ascites characteristics for PMP and identify prognostic factors for survival.MethodsBetween June 2010 and June 2020, 473 PMP patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included in a retrospective study. Survival analysis was performed with the Kaplan–Meier method by the log-rank test and a Cox proportional hazards model. Associations between categorical variables were analyzed using the chi-squared test.ResultsAmong all included patients, 61% were women. The median OS was 47 months (range, 4–124 months) at the last follow-up in December 2020. Ascites characteristics can be divided into light blood ascites, “Jelly” mucus ascites, and faint yellow and clear ascites. Multivariate Cox analysis showed that the degree of radical surgery, ascites characteristics, and pathological grade were independently associated with OS in PMP patients. The chi-squared test documented that faint yellow “Jelly” ascites were related to low-grade PMP and light blood ascites were associated with high-grade PMP (P &lt; 0.01).ConclusionsLight blood ascites, incomplete cytoreduction surgery, and high-grade histopathology may predict poor OS in appendix-derived PMP

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance.

Resistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH

Nitrogen enrichment alters the resistance of a noninvasive alien plant species to Alternanthera philoxeroides invasion

Soil nitrogen can significantly affect the morphology, biomass, nutrient allocation, and photosynthesis of alien vs. native plants, thereby changing their coexistence patterns; however, the effect of soil nitrogen on the interspecific relationship between alien plants is currently unclear. We conducted a nitrogen addition experiment in a greenhouse to explore the effect of soil nitrogen on the interspecific relationship between invasive alien weed Alternanthera philoxeroides and the noninvasive alien horticultural plant Oxalis articulata. We set three experimental factors—nitrogen treatment, planting type, and species and measured the morphology, biomass, carbon (C) and nitrogen (N) content, physiological traits, and photosynthetic fluorescence of the studied plant species. We then used multi-way ANOVA and multiple comparisons to examine the differences in the above indicators among treatment combinations. We found that, in mixed cultures, nitrogen addition significantly increased the root area of O. articulata by 128.489% but decreased the root length by 56.974% compared with the control, while it significantly increased the root length of A. philoxeroides by 130.026%. Nitrogen addition did not affect the biomass accumulation of these two plant species; however, the biomass and root/shoot ratio of O. articulata were significant higher than those of A. philoxeroides. Nitrogen addition significantly increased the N content of A. philoxeroides by 278.767% and decreased the C:N ratio by 66.110% in mixed cultures. Nitrogen addition caused a significant trade-off between flavonoid and anthocyanin in O. articulata, and decreased the initial fluorescence (F0) and maximal fluorescence (Fm) of A. philoxeroides by 18.649 and 23.507%, respectively, in mixed cultures. These results indicate that nitrogen addition increased the N absorption and assimilation ability of A. philoxeroides in deep soil; furthermore, it significantly enhanced the advantages for O. articulata in terms of morphology, physiological plasticity, and photosynthetic efficiency. In addition, O. articulata had better individual and underground competitive advantages. Under intensified nitrogen deposition, the biotic replacement effect of O. articulata on A. philoxeroides in natural ecosystems could be further enhanced

Association of Hypertension With Both Occurrence and Outcome of Symptomatic Patients With Mild Intracranial Atherosclerotic Stenosis: A Prospective Higher Resolution Magnetic Resonance Imaging Study.

BACKGROUND: Intracranial atherosclerotic plaque causing mild luminal stenosis might lead to acute ischemic events. However, the difference between culprit and nonculprit lesions is unclear, as are the factors associated with favorable treatment outcomes. PURPOSE: To quantify characteristics of intracranial atherosclerosis with mild luminal stenosis and to identify factors associated with lesion type (culprit or nonculprit) and with clinical outcomes. STUDY TYPE: Prospective POPULATION: 293 patients who had acute stroke with mild luminal stenosis (<50%) in the middle cerebral or basilar artery. FIELD STRENGTH/SEQUENCE: 3.0 T higher resolution magnetic resonance imaging (hrMRI) of intracranial arteries and whole brain MR images. ASSESSMENT: Morphological and compositional analysis of plaques was performed. This included assessment of plaque volume, plaque burden, remodeling ratio, eccentricity, intraplaque hemorrhage, and enhancement ratio. Clinical outcomes were assessed according to the modified Rankin Scale (mRS) at day 90, with a favorable outcome being defined as a 90-day mRS ≤2. STATISTICAL TESTS: The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by a logistic regression model. RESULTS: Hypertension (OR 5.2; 95% CI 2.6-10.3; P < 0.05) and hrMRI enhancement ratio (OR 2.7; 95% CI 1.4-5.1; P < 0.05) were independently associated with lesion type. Patients without hypertension had significantly more (P < 0.05) favorable outcomes (124/144) than patients with hypertension (97/149). Most hypertensive patients without any previous blood pressure control (54/63) had a favorable outcome. However, these patients were significantly younger (P < 0.05) than those with adequate blood pressure control. After adjusting for all significant characteristics, hypertension duration (OR 1.19; 95% CI 1.09-1.29; P < 0.05), hypertension management (OR 2.49; 95% CI 1.18-5.26; P < 0.05), and enhancement ratio (OR 0.01; 95% CI 0.001-0.157; P < 0.05) were found to be independent high-risk factors for outcome prediction. DATA CONCLUSION: hrMRI provided incremental value over traditional risk factors in identifying higher risk intracranial atherosclerosis with mild luminal stenosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2

A ferritin nanoparticle vaccine based on the hemagglutinin extracellular domain of swine influenza A (H1N1) virus elicits protective immune responses in mice and pigs

IntroductionSwine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza.MethodsHere, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated.ResultsOur results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets.ConclusionTaken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection