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Finally, we found inter-species similarities in the microbiome stress response on a functional level. Our research highlights the effects of stress on the dynamic microbiome and underscores the informative value of volatility as a parameter that should be considered in all future analyses of the microbiome.
Liquid biopsy provides real-time data about prognosis and actionable mutations in metastatic breast cancer (MBC). The aim of this study was to explore the combination of circulating tumour DNA (ctDNA) analysis and circulating tumour cells (CTCs) enumeration in estimating target organs more susceptible to MBC involvement.
This retrospective study analysed 88 MBC patients characterised for both CTCs and ctDNA at baseline. CTCs were isolated through the CellSearch kit, while ctDNA was analysed using the Guardant360 NGS-based assay. Sites of disease were collected on the basis of imaging. Associations were explored both through uni- and multivariate logistic regression and Fisher's exact test and the random forest machine learning algorithm.
After multivariate logistic regression, ESR1 mutation was the only significant factor associated with liver metastases (OR 8.10), while PIK3CA was associated with lung localisations (OR 3.74). CTC enumeration was independently associated with bone metastases (OR 10.41) dynamically focus on high-risk organs defined by tumourbiology.
Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in about 35% of women with breast cancer. In such cases, breast surgery may be considered overtreatment. We evaluated multivariate algorithms using patient, tumor, and vacuum-assisted biopsy (VAB) variables to identify patients with breast pCR.
We developed and tested four multivariate algorithms a logistic regression with elastic net penalty, an Extreme Gradient Boosting (XGBoost) tree, Support Vector Machines (SVM), and neural network. We used data from 457 women, randomly partitioned into training and test set (21), enrolled in three trials with stage 1-3 breast cancer, undergoing VAB before surgery. False-negative rate (FNR) and specificity were the main outcome measures. The best performing algorithm was validated in an independent fourth trial.
In the test set (n=152), the logistic regression with elastic net penalty, XGboost tree, SVM, and neural network revealed an FNR of 1.2% (1 of 85 patients with missed residual cancer). Specificity of the logistic regression with elastic net penalty was 52.2% (35 of 67 women with surgically confirmed breast pCR identified), of the XGBoost tree 55.2% (37 of 67), of SVM 62.7% (42 of 67), and of the neural network 67.2% (45 of 67). External validation (n=50) of the neural network showed an FNR of 0% (0 of 27) and a specificity of 65.2% (15 of 23). BL-918 mw Area under the ROC curve for the neural network was 0.97 (95% CI, 0.94-1.00).
A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment.
A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment.Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.Most sturgeon and paddlefish are critically endangered; therefore, effective measures to conserve these genetic resources are required. Cryopreservation of gonad tissues containing germline stem cells could be an effective strategy for long term preservation and restoration of fish species using germ cell transplantation procedure. The aim of this study was to develop an optimal procedure for long-term cryopreservation of American paddlefish gonads using a slow-freezing method. Through optimization of permeating cryoprotectants, nonpermeating cryoprotectants, and supplementation of proteins, gonad tissues were frozen with a cryomedium containing 1.3 M dimethyl sulfoxide, 0.1 M trehalose, and 10 % fetal bovine serum at a cooling rate of -1 °C/min. This method was also successfully utilized for the cryopreservation of Yangtze sturgeon testes. Viability of gonadal cells isolated from frozen gonads was not different from cells isolated from fresh gonadal tissues, while the number of gonadal cells dissociated from frozen gonads was less. Germline stem cells dissociated from long-term (1 year) cryopreserved gonads were labeled with PKH26 fluorescent dye and intraperitoneally transplanted into larvae of Yangtze sturgeon. The colonization of transplanted germline stem cells was confirmed by the presence of PKH26-labeled donor germline stem cells and donor-derived mtDNA sequence in the recipient gonads, providing evidence that germline stem cells from sturgeon and paddlefish gonads that had been preserved for a long period maintained their functions. The results of present study indicate the procedures used are effective for long-term preservation of critically endangered species within the Acipenseriformes order which can later be regenerated using surrogate broodstock technology.The physiological and molecular responses of granulosa cells (GCs) from buffalo follicles were investigated when there were in vitro heat stress conditions imposed. The cultured GCs were heat-treated at 40.5 °C for 24, 48 or 72 h while GCs of the control group were not heat-treated (37 °C). There were no differences in viability between control and heat-treated groups. There was an upward trend in increase in E2 secretion as the duration of heat stress advanced, being greater (P ≤ 0.05) for the GCs on which heat stress was imposed for 72 as compared with 24 h. In contrast, P4 release was less (P ≤ 0.05) from GCs heat-treated for 48 h than those cultured for 24 h and GCs of the control group. The relative abundance of ATP5F1A and SOD2 mRNA transcripts was consistent throughout the period when there was imposing of heat stress to sustain mitochondrial function. The relative abundance of CPT2 transcript was less in heat-treated GCs than in GCs of the control group. There was a greater relative abundance of SREBP1 and TNF-α mRNA transcripts after 48 h of heat-treatment of GCs than GCs of the control group. In conclusion, the results from the current study indicate buffalo GCs cultured when there was imposing of heat stress maintained normal viability, steroidogenesis and transcriptional profile. The stability of antioxidant status and increased transcription of genes regulating cholesterol biosynthesis and stress resistance may be defense mechanisms of buffalo GCs against heat stress.Porous metallic scaffolds show promise in orthopedic applications due to favorable mechanical and biological properties. In vivo stress conditions on orthopedic implants are complex, often including multiaxial loading across off axis orientations. In this study, unit cell orientation was rotated in the XZ plane of a strut-based architecture, Diamond Crystal, and two sheet-based, triply periodic minimal surface (TPMS) architectures, Schwartz D and Gyroid. Sheet-based architectures exhibited higher peak compressive strength, yield strength and strain at peak stress than the strut-based architecture. All three topologies demonstrated an orientational dependence in mechanical properties. There was a greater degree of anisotropy (49%) in strut-based architecture than in either TPMS architectures (18-21%). These results support the superior strength and advantageous isotropic mechanical properties of sheet-based TPMS architectures relative to strut-based architectures, as well as highlighting the importance of considering anisotropic properties of lattice scaffolds for use in tissue engineering.Hydroxyapatite (HA, Ca10(PO4)6(OH)2) is the main constituent mineral of bone and teeth in mammals. Due to its outstanding biocompatibility and osteoconductive capabilities, it is preferred for bone repair and replacement. Owing to high potential to have excellent biological properties, ternary ions-doped HAs have just begun to be investigated in the biomedical field and preparing multi-doped HAs is a fairly new approach. Boron (B, BO33-), strontium (Sr, Sr2+) and magnesium (Mg, Mg2+) provide a beneficial effect on bone growth, bone strength, biocompatibility and positively affect bone microstructure. The motivation of this study is taking advantages of the potential of the combine effects of these bivalent ions. In this study, 8 different compositions of BO33-, Sr2+, Mg2+ multi-doped HAs were synthesized by microwave irradiation method to investigate the structural, mechanical and biological features of bone substitutes. This is the first time we report the effect of boron, strontium and magnesium ions multi-for bone implant applications samples sintered at 1100 °C were suggested to have potential as a biomaterial.This work exploits a one-pot method for directional depolymerizing organosolv lignin into high added-value phenolic monomers with synergistic reaction system consisted of methanol-dimethoxymethane binary solvents and acid catalyst. The influence of solvent composition and reaction parameters such as different catalyst, binary solvents ratio, time, and temperature on the conversion of lignin and yield of products were investigated carefully, the optimum yield of liquid products and phenolic monomers were achieved at 67.39% and 27.67% at 200 °C kept for 60 min with low amount of acid catalyst. The plausible mechanism on the depolymerization of lignin was proposed in view of product distributions. Moreover, the combination of co-solvents and acidic catalyst was also suitable for converting different types of lignin into phenolic monomers, and the recyclability of joint reaction system was satisfactory. These results can provide promising prospects on developing an effective method for achieving high added-value phenolic compounds from lignin.