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PurposeLung cancer is the leading cause of death from cancer and the number of operable elderly lung cancer patients is increasing, with advanced age being associated with a poorer prognosis. However, there is no easy and comprehensive prognostic assessment method for these patients.MethodsClinicopathological data of patients aged 65 years or older with TNM stage I-II lung cancer from 2004 to 2018 were downloaded from the SEER database. Patients from 2004 to 2015 were randomized into a training group (n = 16,457) and a validation group (n = 7,048). Data from 2016 to 2018 (n = 6,231) were used for external validation. Two nomogram prognostic models were created after independent prognostic factors connected to both overall survival (OS) and cancer-specific survival (CSS) in the training set by using univariate and multivariate Cox proportional hazards regression analysis. In turn, overall survival (OS) and cancer-specific survival (CSS) were predicted for patients at 1, 3, and 5 years. Based on the concordance index (C-index), calibration curves, area under the receiver operating characteristics (ROC) curve (AUC), the time-dependent area under the ROC curve, the validity, accuracy, discrimination, predictive ability, and clinical utility of the models were evaluated. Decision curve analysis (DCA) was used to assess the clinical value of the models.ResultsA total of 29,736 patients were included. Univariate and multivariate analyses suggested that age, race, gender, marriage, disease grade, AJCC stage, T-stage, surgery, radiotherapy, chemotherapy, and tumor size were independent risk factors for patient prognosis. These 11 variables were included in nomogram to predict OS and CSS of patients. C-indexes of OS for the training, validation and external validation sets were 0.730 (95% CI, 0.709–0.751), 0.734 (95% CI, 0.722–0.746), and 0.750 (95% CI, 0.734–0.766), respectively. The AUC results for the training and validation sets indicated good accuracy for this nomogram. The calibration curves demonstrated a high degree of concordance between actual and anticipated values, and the DCA demonstrated that the nomograms had better clinical application than the traditional TNM staging approach.ConclusionThis study identified risk factors for survival in operable elderly lung cancer patients and established a new column line graph for predicting OS and CSS in these patients. The model has good clinical application and can be a good clinical decision-making tool for physicians and patients.

Background:β-Catenin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here, we conduct a meta-analysis to better clarify the correlation between β-Catenin expression and survival outcomes in nasopharyngeal carcinoma (NPC) patients.Patients/methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for relevant studies to explore the prognostic significance of β-Catenin in NPC. Pooled hazards ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association of β-Catenin expression with survival outcomes in NPC patients. Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were also statistically analyzed.Results: Eight studies involving 1,179 patients with NPC were ultimately included in the meta-analysis. Pooled analysis indicated that elevated β-Catenin expression was significantly associated with poor OS (HR = 2.45, 95% CIs: 1.45–4.16, p = 0.001) and poor DFS/PFS (HR 1.79, 95% CIs: 1.29–2.49, p = 0.000). Furthermore, β-cadherin was signifcantly associated with higher TMN stages (OR = 5.10, 95% CIs 2.93–8.86, p = 0.000), clinical stages (OR = 5.10, 95% CIs 2.93–8.86, p = 0.000) and lymph node metastasis (LNM) (OR = 5.01, 95% CIs 2.40–10.44, p = 0.000).Conclusions: This study demonstrated that for NPC, patients with elevated β-Catenin expression are more likely to have poor survival.

BackgroundAlthough serum sodium concentration, particularly hyponatremia, has been shown to be a prognostic marker of survival in metastatic renal cell carcinoma (mRCC), the impact of normal sodium levels has not been investigated. Herein, we investigate the influence of normonatremia in mRCC patients treated with tyrosine kinase inhibitors (TKIs).Materials and methodsFor this retrospective study, the clinical and biochemical data of patients treated with first-line TKIs for mRCC were available from seven Italian cancer centers. We collected natremia levels at baseline and first evaluation after treatment excluding patients with sodium levels outside the normal range (145 mEq/L). The remaining patients were subdivided into two groups according to the median sodium value: natremia patients with

Background: Circular RNA (circRNA) is a newly-discovered endogenous transcript that has been reported to participate in osteosarcoma (OS) progression. However, the underlying mechanism of circ_0051079 modulating OS development remains unclear. Methods: RNA expressions of circ_0051079, miR-625-5p and tripartite motif containing 66 (TRIM66) were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis. The functional effects of circ_0051079 on OS cell malignancy were investigated by cell counting kit-8, clonogenicity, transwell, tube formation and flow cytometry assays. The interactions among circ_0051079, miR-625-5p and TRIM66 were identified by dual-luciferase reporter and RNA immunoprecipitation assays. Mouse xenograft model assay was performed to elucidate the effects of circ_0051079 knockdown on tumor formation in vivo. Results: Circ_0051079 and TRIM66 expressions were significantly upregulated, but miR-625-5p was downregulated in OS tissues and cells compared with control groups. Circ_0051079 expression was significantly associated with tumor-node-metastasis stage and tumor size of OS patients. Circ_0051079 knockdown inhibited OS cell proliferation, migration and invasion, repressed angiogenesis but induced cell apoptosis, accompanied by the decreases of PCNA and Bcl-2 production and an increase of Bax production. MiR-625-5p, a target miRNA of circ_0051079, participated in regulating circ_0051079-induced effects. Also, TRIM66 was identified as a target mRNA of miR-625-5p, and partially attenuated the inhibitory effects of miR-625-5p in OS cells. Circ_0051079 modulated the Wnt/β-catenin pathway through TRIM66 in vitro. Importantly, circ_0051079 silencing reduced TRIM66 expression by interacting with miR-625-5p. Further, circ_0051079 depletion inhibited tumor formation in vivo. Conclusion: Circ_0051079 regulated OS development by the miR-625-5p/TRIM66/Wnt/β-catenin pathway, providing a novel therapeutic target for OS.

BackgroundMultiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients.MethodsAmong a total of 357 participants in our institution’s MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan–Meier (K-M) curve analysis were applied to the research.ResultsA total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion < 0.0001, pfracture < 0.0001). The violin plot showed that MM patients with higher serum IL-17A levels had more severe bone lesions and higher fracture incidence than those with lower serum IL-17A levels. A total of 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A levels were independently related to the best inductive therapeutic efficacy (fully adjusted model, p = 0.037), and the relationship was especially obvious in the light chain group (fully adjusted model, p = 0.009) and IgA group (fully adjusted model, p = 0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (p = 0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (area under the curve (AUC) = 0.717, p = 0.0327). A total of 148 MM patients were observed in the longitudinal study of the relationship between serum IL-17A and progression-free survival/overall survival (PFS/OS). The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (p = 0.015) and OS (p = 0.0076) compared to those with low serum IL-17A. In the IgA type subgroup, the higher IL-17A level was related to worse OS (p = 0.0061).ConclusionThis retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.

Background: No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results: In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion: These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy. [ABSTRACT FROM AUTHOR]

Background: Treatments for patients with early-stage hepatocellular carcinoma (HCC) include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), and microwave ablation (MWA), are critical for their long-term survival. However, a computational model predicting treatment-independent prognosis of patients with HCC, such as overall survival (OS) and recurrence-free survival (RFS), is yet to be developed, to our best knowledge. The goal of this study is to identify prognostic factors associated with OS and RFS in patients with HCC and develop nomograms to predict them, respectively. Methods: We retrospectively retrieved 730 patients with HCC from three hospitals in China and followed them up for 3 and 5 years after invasive treatment. All enrolled patients were randomly divided into the training cohort and the validation cohort with a 7:3 ratio, respectively. Independent prognostic factors associated with OS and RFS were determined by the multivariate Cox regression analysis. Two nomogram prognostic models were built and evaluated by concordance index (C-index), calibration curves, area under the receiver operating characteristics (ROC) curve, time-dependent area under the ROC curve (AUC), the Kaplan-Meier survival curve, and decision curve analyses (DCAs), respectively. Results: Prognostic factors for OS and RFS were identified, and nomograms were successfully built. Calibration discrimination was good for both the OS and RFS nomogram prediction models (C-index: 0.750 and 0.746, respectively). For both nomograms, the AUC demonstrated outstanding predictive performance; the DCA shows that the model has good decision ability; and the calibration curve demonstrated strong predictive power. The nomograms successfully discriminated high-risk and low-risk patients with HCC associated with OS and RFS. Conclusions: We developed nomogram survival prediction models to predict the prognosis of HCC after invasive treatment with acceptable accuracies in both training and independent testing cohorts. The models may have clinical values in guiding the selection of clinical treatment strategies. [ABSTRACT FROM AUTHOR]

Forkhead box protein A1 (FOXA1) is pioneer factor has a dual role either as growth stimulator or a repressor and the significance role of this protein as a prognostic biomarker still controversial, so the aim of this study was to identify the precise role of FOXA1 protein expression in prediction of BC patients outcome and recurrence of BC by immunohistochemical (IHC) staning method. In this study, seventy three tissues samples embedded in wax block were taken from BC patients with (52.71+11.55) years who had surgery between 2014-2020 and thirty eight of normal (non tumoral) breast tissues samples with (54.17+10.84) years as a control group. Negative FOXA1 expression increased significantly in patients with recurrence BC (P=0.006), BC patients with good prognosis and moderate prognosis have a significant correlation with positive FOXA1 expression (P=0.018). Overall survival (OS) was 82.74% in patients with positive expression of FOXA1 which is longer than OS in BC patients with negative expression of FOXA1 (61.31%), (P=0.001). Disease free survival (DFS) was 81.36% in BC patients with positive expression of FOXA1 which also longer than in BC patients with negative expression of FOXA1 (59.8%) (p=0.0001). FOXA1 was a good prognostic marker for survival of BC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The Cancer Genome Atlas (TCGA) and more recent genome profiling recently revealed major intrinsic molecular subtypes in urothelial carcinoma (UC). Here we propose a fast and standardized immunophenotypical classification score (Piescore) that may discriminate between luminal, basal, or neu-like UC as a surrogate of molecular profile, and we describe, for the first time, an intratumoral phenotypical switch in tissue protein expression, from non-muscle to muscle-invasive progression. Our data show that a change from a luminal to a neu-like phenotype could worsen overall survival compared with a transition to a basal phenotype. In recent years, immunohistochemical protein expression was studied as a surrogate to the molecular classification of bladder cancer, although no tissue biomarkers are available for clinical use to predict survival or the response to neoadjuvant chemotherapy (CT) in UC, as the literature produced conflicting results. This retrospective study included TURB specimens harboring foci of HG pT2 muscle-invasive bladder carcinoma (MIBC) from 251 patients who subsequently underwent radical cystectomy. We performed immunohistochemical analysis on tumor samples, for relevant gene-expression-based markers for basal type (CD44, CK5/6) and luminal type (CK20 and pPARγ). Piescore, investigated in both non-muscle-invasive (NMI) and muscle-invasive (MI) components of the tumor, divided basal and luminal UC-types when at least three of the four markers were consistent with a specific phenotype, mixed types if one/two luminal and basal markers were present simultaneously, and neu-like types when all four markers investigated were negative. Eighteen selected cases were also investigated with RT-PCR to validate, and to increase the specificity of, the immunohistochemical results. We observe an immunophenotypical difference in the NMI and MI components in 96/251 UC patients (38.25%): half of tumors (44/96 cases) have a transition to basal, 36.46% (35/96 cases) to neu-like, 12.5% (12/96 cases) to mixed, and 5.2% (5/96 cases) to luminal phenotypes. Mixed tumors in the NMI component are more likely to change phenotype than other groups, particularly compared with basal tumors, which demonstrate greater stability (only 8/96 cases, p < 0.00001). The transition of luminal tumors to basal display a better OS compared with the transition toward neu-like tumors (p = 0.027). Overall, the phenotypical switch does not affect lymphovascular invasion, pT, DFS, or OS compared with non-switched cases. In the MI component, the presence of CD44 expression, irrespective of score-related phenotype, shows a protective effect in papillary-type UC (OS p = 0.008, HR 0.453, PFS p = 0.07, HR 0.599), and in UC naïve for CT (p = 0.0479). Piescore immunophenotyping reveals an intratumoral phenotypical transition between the NMI and MI components of the same tumor. The molecular change is a common event in the mixed and luminal categories, but not in basal tumors, which show better phenotypical stability. This phenomenon could partially explain the sensitivity of a subset of luminal UC to chemotherapy: good responders could be "non-real" luminal UC, which acquire nasal markers, such as CD44. [ABSTRACT FROM AUTHOR]

LncRNAs have been suggested to participate in the growth and metastasis of cancer through a variety of molecular mechanisms. Recently, SNHG10, a newly discovered lncRNA, is reported to play a role of an oncogene in osteosarcoma (OS) genesis. Nonetheless, the mechanism underlying OS remains unclear. The present work found that SNHG10 expression increased within OS cells and tissues, while suppressing its expression decreased OS cell proliferation, migration, invasion, but increased their apoptosis. As for the mechanism, we confirmed that SNHG10 could bind to miR‐141‐3p, while the latter could bind to WTAP. SNHG10 upregulated WTAP through decreasing miR‐141‐3p expression. More importantly, SNHG10 deletion remarkably reduced proliferation, migration, and invasion of cells, but accelerated their apoptosis. However, when cells were subjected to miR‐141‐3p inhibitor cotransfection or overexpressed WTAP, these effects were partially recovered. In summary, this study suggested that the expression of SNHG10 markedly elevated within OS, and the SNHG10/miR‐141‐3p/WTAP axis facilitated OS progression. [ABSTRACT FROM AUTHOR]

This study substantiates the usefulness of a systemic approach to investigate the multi-dimensional challenges regarding environmental, economic, and social impacts facing the sustainable development of unconventional energy resources, particularly oil sands (OS) in Canada. This research uses the system dynamics (SD) methodology to examine the impact of shocks in oil demand using real and theoretical scenarios. This was done by identifying leading indicators critical to OS resource development to capture sustainable development effects. The study identifies the contribution of OS resources in Canada to global sustainable development and has developed a model structure that captures the critical parameters associated with the economic-dynamics, socio-dynamics, and enviro-dynamics for the next 30 years. It also includes the impact of sudden oil supply and demand shocks and presents various recovery scenarios. The results from these scenarios indicate that it may take up to 25 years for the industry to return to its pre-shock trajectory, even assuming a rapid recovery. As such, the study proposes an adaptive model to assist sustainable energy development policies and decision-making. Accordingly, the approach can be helpful for academicians, policymakers, and practitioners for objective decision-making regarding sustainable development. Meanwhile, it provides cogent and valuable information for natural resource governance. [ABSTRACT FROM AUTHOR]

Digital data can be manipulated easily, so information related to the timestamp is important in establishing the reliability of the data. The time values for a certain file can be extracted following the analysis of the filesystem metadata or file internals, and the information can be utilized to organize a timeline for a digital investigation. Suppose the reversal of a timestamp is found on a mobile device during this process. In this case, a more detailed analysis is required due to the possibility of anti-forensic activity, but little previous research has investigated the handling and possible manipulation of timestamps on mobile devices. Therefore, in this study, we determine how time values for multimedia files are handled according to the operating system or filesystem on mobile devices. We also discuss five types of timestamps--file created (C), last modified (M), last accessed (A), digitalized (Di), and filename (FN) of multimedia files, and experimented with their operational features across multiple devices such as smartphones and cameras. [ABSTRACT FROM AUTHOR]

Objective: Identifying the risk factors for persistent pain despite proper conservative treatment in adult symptomatic accessory navicular may reduce the need for surgical treatment. The aim of this study was to identify any such risk factors. Design: Cohort study. Setting: University hospital foot and ankle clinic. Patients: A retrospective review of 313 patients who presented with adult symptomatic accessory navicular was performed. Assessment of Risk Factors: Potential risk factors were identified via medical records and foot radiographs. The possible risk factors included age, gender, body mass index, smoking status, occurrence/cause of symptoms, occupation, type of accessory navicular, and radiographic foot parameters. Main Outcome Measures: Predictors that relate to persistent pain requiring surgical treatment in adult accessory navicular were analyzed using logistic regression analysis. Results: Of the 313 patients included, 30 (9.6%) underwent surgical treatment due to failure of conservative treatment. The odds of needing surgical treatment decreased by 0.96 per year of age at symptom onset (P = 0.030), but those odds were 8.52 times higher in patients who had a type IIB accessory navicular (P = 0.001). Other variables did not reach statistical significance. Conclusions: Younger age at symptom onset and type IIB were the risk factors for persistent pain requiring surgical treatment in adult symptomatic accessory navicular. [ABSTRACT FROM AUTHOR]

Jianjun Yuan,* Yan Liu,* Quan Zhang, Zhishuai Ren, Guang Li, Rong Tian Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, 300121, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong TianDepartment of Spine Surgery, Tianjin Union Medical Center, No. 190, Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of ChinaTel +86-022-27557253Email tufeqj@163.comBackground: Circular RNAs (circRNAs) are implicated in the chemoresistance of human cancers. However, the functions of circRNA PR/SET domain 2 (circPRDM2) in the resistance of osteosarcoma (OS) to doxorubicin (DXR) are unknown.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the levels of circPRDM2, microRNA-760 (miR-760) and enhancer of zeste homolog 2 (EZH2). RNase R assay was used to analyze the characteristics of circPRDM2. IC50 of DXR was estimated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed for cell colony formation ability. Wound-healing assay and transwell assay were utilized for cell migration and invasion. Flow cytometry analysis was conducted for cell apoptosis. Western blot assay was employed for protein levels. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were adopted to analyze the relationships among circPRDM2, miR-760 and EZH2. Murine xenograft model assay was utilized to explore DXR resistance in vivo.Results: CircPRDM2 level was enhanced in DXR-resistant OS tissues and cells. CircPRDM2 deficiency inhibited IC50 of DXR, colony formation, migration and invasion and facilitated apoptosis in DXR-resistant OS cells in vitro. CircPRDM2 was identified as the sponge for miR-760. MiR-760 inhibition reversed the inhibitory effects of circPRDM2 knockdown on DXR resistance and cell progression in DXR-resistant OS cells. Moreover, EZH2 was identified as the target gene of miR-760 and EZH2 overexpression abolished miR-760-mediated impacts on DXR sensitivity and malignant behaviors in DXR-resistant OS cells. Also, circPRDM2 silencing improved DXR sensitivity in vivo.Conclusion: Our study demonstrated the role of circPRDM2/miR-760/EZH2 axis in enhancing DXR resistance.Keywords: OS, DXR, circPRDM2, miR-760, EZH2

Abstract Background Oral squamous cell carcinoma (OSCC) is one of the most common maligancies of the head and neck. The prognosis was is significantly different among OSCC patients. This study aims to identify new biomarkers to establish a prognostic model to predict the survival of OSCC patients. Methods The mRNA expression and corresponding clinical information of OSCC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Additionally, a total of 26 hypoxia-related genes were also obtained from a previous study. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal hypoxia-related genes which were associated with the prognosis of OSCC. to establish the predictive model (Risk Score) was established for estimating the patient's overall survival (OS). Multivariate Cox regression analysis was used to determine whether the Risk Score was an independent prognostic factor. Based on all the independent prognostic factors, nomogram was established to predict the OS probability of OSCC patients. The relative proportion of 22 immune cell types in each patient was evaluated by CIBERSORT software. Results We determined that a total of four hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA were significantly associated with the prognosis of OSCC patients. The nomogram established based on all the independent factors could reliably predict the long-term OS of OSCC patients. In addition, our resluts indicated that the inferior prognosis of OSCC patients with high Risk Score might be related to the immunosuppressive microenvironments. Conclusion This study shows that high expression of hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA is associated with poor prognosis in OSCC patients, and they can be used as potential markers for predicting prognosis in OSCC patients.

Objective: To determine the frequency of Ten-Eleven-Translocation-2 (TET2) gene mutation in Myeloproliferative Neoplasms (MPNs) and to generate a local data for evaluation of disease behavior in ten-eleven-translocation-2 positive and negative Patients. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Apr 2017 to Apr 2018. Methodology: A total of 50 adult myeloproliferative neoplasms patients (>18 years of age), diagnosed according to WHO 2016 diagnostic criteria for myeloproliferative neoplasms were included in the study. Mutational screening for ten-eleven-translocation-2 gene was performed by flourescent in situ hybridization technique using Meta Systems XL-TET2 Deletion probe REF D-5038- 100-OG, LOT 18181, manufactured by Meta-Systems GmbH, Robert-Bosch - Germany. Bone marrow samples were used for Fluorescence in situ hybridization analysis. A total of 500 interphases were examined in each of the specimen. Data was entered and analyzed using SPSS-22. Distinctive demographic, haematological and molecular results are summarized by descriptive statistics. Results: Total 50 cases of myeloproliferative neoplasms (14 CML, 10 PV, 12 essential thrombocythemia (ET) and 14 primary myelofibrosis (PMF) were analyzed. On fluorescent in situ hybridization studies, ten-eleven-translocation-2 mutation was detected in 8 (16%) patients. The mutational frequency among different myeloproliferative neoplasm entities was 4 (28.5%) in chronic myeloid leukemia (CML), 2 (20%) in Polycythemia Vera (PV), 1 (8.3%) in essential thrombocythemia and 1 (7.1%) in primary myelofibrosis respectively. Among the 15 cases, 36 (72%) patients were positive for JAK2V617F mutation while 14 (28%) were positive for BCR-ABL1 mutation. Ten-eleven-translocation-2 mutation observed...................

Emerging evidence has shown that circular RNAs (circRNAs) are vital regulators in osteosarcoma (OS) progression. However, the effects of circ_WWC3 in OS have not been explored. In this research, the functions and mechanisms of circ_WWC3 in OS were investigated.

In this work, we have performed a theoretical calculation to investigate the structural, mechanical, electronic, lattice dynamics, and thermodynamic properties of Ta T Si (T = Rh, Os, Ir) within the full potential linearized augmented plane wave method. Both (a) TaRhSi and (b) TaIrSi exhibit a reduction in the density of states at the Fermi energy, resulting from a pseudogap-like feature nearby the Fermi energy. This reduction is likely to suppresses the superconductivity of TaRhSi and TaIrSi. In contrast, (c) TaOsSi demonstrates a relatively higher density of states at the Fermi energy, which could account for its superconducting properties. [Display omitted] • The full potential linearized augmented plane wave method was used. • The elastic mechanical, electronic, thermodynamic, and lattice dynamics properties. • of TaRhSi and TaOsSi, and TaIrSi, were predicted. • TaRhSi and TaIrSi exhibit a pseudogap-like feature in the density of states nearby. • the Fermi energy. • The elastic anisotropy of TaRhSi and TaOsSi, and TaIrSi were observed. We have performed a theoretical calculation, based on density functional theory, to investigate the structural, mechanical, electronic, lattice dynamics, and thermodynamic properties of Ta T Si (T = Rh, Os, Ir) within the full potential linearized augmented plane wave method. The calculated values of the lattice constant and unit cell volume are in excellent agreement with the available experimental data. The mechanical stability is substantiated by our calculated elastic constants, while the mechanical properties are subsequently derived. The results indicate that the compounds are ductile materials, except for TaRhSi which exhibits quasi-ductile behavior; however, all of them exhibit elastic anisotropy. In addition, the electronic density of states of the Ta T Si (T = Rh, Os, Ir) compounds reveal that all these materials have a metallic character. Moreover, the dynamical stability is confirmed by our calculated phonon spectra. Finally, we present temperature-dependent thermodynamic properties including free energy, internal energy, entropy, and heat capacity. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the second most common cause of cancer related death worldwide. In Egypt, gastric cancer is the 12th most common cancer. The incidence rises with age and 55% of cases occur between 50 and 70 years of age. The complete resection partial or total gastrectomy is based on tumor location, stage, histology, and surgical margins. The extent of regional lymphadenectomy required has been a matter of debate. Neo-adjuvant chemotherapy could increase the curative resection rate, improve the tumor down staging possibilities. Aim of Work: assess the role of the neo-adjuvant chemotherapy for surgical management of gastric cancer patients. Patients and Methods: A prospective analysis of sixty patients with ranging age (18-60 years) who are diagnosed with gastric adenocarcinoma, received neo-adjuvant chemotherapy patients with minimal follow up 16 months, treated at the upper gastro-intestinal surgeries unit, Ain Shams University Hospitals. Primary end points include assessing overall survival, R0 resection rate, local recurrence, rate of pathological complete response. Results: Patients aged (22-60 years old), mean age 46.67 ±12.76, the median DFS was 6 months, the mean OS is 26.3 months, recorded 1 year, 2 years OS rate was 75.8% and 67.9% respectively. However, the median OS was not reached. Conclusion: This study favors the idea of Neo-adjuvant chemotherapy usage prior to surgical intervention in multiple stages of gastric cancer. However, there were other studies that questions its role and demand a reconsideration about the clinical outcome which require further investigation. [ABSTRACT FROM AUTHOR]

• Excellent survival outcomes and low rates of ultimate failure were discovered. • HPV+ /p16 + patients had significantly better outcomes than remaining patients. • The study revealed low rates of adjuvant therapy. • Outcomes between patients treated with or without adjuvant therapy were identical. • Single modality transoral robotic surgery was a successful curative therapy. The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades, driven by infection with human papillomavirus (HPV). Transoral robotic surgery (TORS) and neck dissection (ND) has been employed as an alternative to radiotherapy/chemoradiotherapy. The current literature is lacking studies providing an exhaustive overview of recurrence characteristics and long-term outcomes in TORS-treated OPSCC-patients. All patients treated for OPSCC with primary TORS + ND in Eastern Denmark between 2013 and 2020 were included in the study. The aim was to explore overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and ultimate failure rate (UFR). OS and RFS were examined using the Kaplan-Meier method. Cox proportional regression analyses were employed to examine effect of different variables on risk of death and recurrence. The study included 153 patients of which 88.9 % (n = 136) were treated with TORS alone while 11.1 % (n = 17) received adjuvant therapy. The 1-, 3-, and 5-year OS were 97.4 %, 94.1 %, and 87.6 % while 1-, 3-, and 5-year RFS were 96.6 %, 87.8 %, and 84.9 %. The UFR was 6.5 % in the cohort. Patients with HPV+/p16 + OPSCC had a significantly better 5-year OS of 92.3 % than patients with discordant or double-negative HPV/p16 status (OS = 73.3 %). No differences in outcomes between patients treated with or without adjuvant therapy were found in regression analysis. Excellent survival and disease control was obtained with TORS + ND in this cohort, despite lesser application of adjuvant therapy than other TORS-centers, implying that TORS without adjuvant therapy can be successfully applied in treatment of early-stage OPSCC. [ABSTRACT FROM AUTHOR]

Unresectable renal cell carcinoma continues to be a great challenge due to our limit ed understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. Material and methods: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC. [ABSTRACT FROM AUTHOR]

Background: Tumor mutational burden (TMB) is a genomic biomarker that can predict favorable responses to immune checkpoint inhibitors (ICIs). Although we have better understanding of TMB in cancer immunity and cancer immunotherapy, the relationship between TMB and the clinical efficacy of ICIs remains unknown in the treatment of melanoma patients. Here, we conduct a systematic review and meta-analysis to evaluate the predictive value of TMB on the efficacy of ICIs in patients with melanoma. Methods: We systematically collected data from PubMed, Embase, Cochrane Library, CNKI, China Biomedical Database (CBM), and Wanfang Database. The end date was set to 26 June 2021. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival and/or progression-free survival according to TMB. Data for 1,493 patients from 15 studies were included. In addition, pooled effect size, heterogeneity analysis, sensitivity analysis, publication bias detection, and subgroup analysis were performed based on the included data. Results: Patients with high TMB showed significantly improved OS (HR = 0.49, 95% CI: 0.33, 0.73; p = 0.001) and PFS (HR = 0.47, 95% CI: 0.33, 0.68; p < 0.001) compared with patients with low TMB. This association was very good in patients treated with monotherapy, that is, anti-CTLA-4 or anti-PD-(L)-1 inhibitors, but not for the patients treated with a combination of the two drugs. The subgroup analysis results showed that heterogeneity was substantial in the targeted next-generation sequencing (NGS) group. Publication bias was detected, and the results were visualized using the funnel chart. And sensitivity analysis and trim-and-fill method analysis showed that our results were stable and reliable. Conclusion: High TMB is associated with improved OS and PFS in melanoma patients treated with mono-drug ICIs. TMB determined by NGS should be standardized to eliminate heterogeneity. Therefore, the role of TMB in identifying melanoma patients who may benefit from ICI should be further determined in more randomized controlled trials in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • L'autophagie est un mécanisme d'élimination et de recyclage de composants cellulaires permettant un contrôle qualité dans la cellule. • L'autophagie peut aussi être augmentée en cas de stress dans un but de survie. • L'autophagie est un processus essentiel à la différenciation et à la fonction des cellules osseuses. • Un défaut d'autophagie dans les cellules osseuses est impliqué dans le développement de pathologies telles que l'ostéoporose, l'ostéopétrose, ou la maladie de Paget. • La modulation de l'autophagie apparaît comme une nouvelle voie de recherche très prometteuse pour le développement de nouvelles stratégies thérapeutiques dans les pathologies osseuses. L'autophagie est un processus cellulaire ubiquitaire, permettant l'élimination et le recyclage des protéines et organelles endommagées. Au niveau basal, ce processus joue un rôle dans le contrôle qualité, participant ainsi à l'homéostasie cellulaire. L'autophagie peut également être induite par différents stress, tels que la privation de nutriments ou l'hypoxie, afin de permettre à la cellule de survivre le temps que les conditions s'améliorent. Ces dernières années, le rôle de ce processus a été largement étudié dans de nombreuses pathologies telles que les maladies neurodégénératives ou les cancers. Dans le tissu osseux, différents travaux ont montré que l'autophagie est impliquée dans la survie, la différenciation et l'activité des ostéoblastes, des ostéocytes et des ostéoclastes. L'évolution de ces connaissances a permis de mettre en évidence de nouveaux mécanismes moléculaires physiopathologiques dans les pathologies osseuses. Cette revue rapporte l'état actuel des connaissances sur le rôle de l'autophagie dans 4 pathologies osseuses : l'ostéoporose, qui semble être associée à une diminution de l'autophagie, l'ostéopétrose et la maladie de Paget où le déroulement du processus autophagique est perturbé, et enfin l'ostéosarcome où l'autophagie semble jouer un rôle protumoral. Une meilleure compréhension de l'implication de l'autophagie dans ces pathologies devrait à terme permettre d'identifier de nouvelles cibles thérapeutiques potentielles. [ABSTRACT FROM AUTHOR]

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs. [ABSTRACT FROM AUTHOR]

Aim: Tumor deposits (TDs) are an aggressive hallmark of rectal cancer, but their prognostic value has not been addressed in current staging systems. This study aimed to construct and validate a prognostic nomogram for rectal cancer patients with TDs. Methods: A total of 1,388 stage III–IV rectal cancer patients who underwent radical surgical resection from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed to identify the clinical value of TDs. TD-positive rectal cancer patients in the SEER database were used as the training set to construct a prognostic model, which was validated by Fujian Cancer Hospital. Three models were constructed to predict the prognosis of rectal cancer patients with TDs, including the least absolute shrinkage and selection operator regression (LASSO, model 1), backward stepwise regression (BSR, model 2), and LASSO followed by BSR (model 3). A nomogram was established among the three models. Results: In the entire cohort, TD was also identified as an independent risk factor for overall survival (OS), even after adjusting for baseline factors, stage, other risk factors, treatments, and all the included variables in this study (all P < 0.05). Among patients with TDs, model 3 exhibited a higher C-index and area under the curves (AUCs) at 3, 4, and 5 years compared with the American Joint Committee on Cancer staging system both in the training and validation sets (all P < 0.05). The nomogram obtained from model 3 showed good consistency based on the calibration curves and excellent clinical applicability by the decision curve analysis curves. In addition, patients were divided into two subgroups with apparently different OS according to the current nomogram (both P < 0.05), and only patients in the high-risk subgroup were found to benefit from postoperative radiotherapy (P < 0.05). Conclusion: We identified a novel nomogram that could not only predict the prognosis of rectal cancer patients with TDs but also provide reliable evidence for clinical decision-making. [ABSTRACT FROM AUTHOR]

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Antibiotics (ATBs) induce dysbiosis of the gut microbiota by altering the diversity and composition of the microbiota, which mediates the efficacy and toxicity of cancer therapy. The influence of dysbiosis induced by ATB administration on primary resistance to chemotherapy in patients with advanced gastric cancer (GC) has been rarely studied. We evaluated the effect of ATB administration on chemotherapy efficacy in patients with advanced GC. Patients with GC were divided into two groups according to the status of ATB administration: ATB-treated and control groups. Tumor responses, progression-free survival (PFS) and overall survival (OS) were assessed. We found that the incidence of progressive disease in the ATB-treated group was significantly higher when compared with that in the control group that received no ATB treatment (72.73% vs. 29.55%, p = 0.007). In addition, ATB administration was associated with shorter PFS [median PFS: 1.47 vs. 4.97 months, hazard ratio (HR): 2.296, 95% confidence interval (CI): 1.214 − 4.342, p = 0.011] and reduced OS (median OS: 9.97 vs. 13.3 months, HR: 2.101, 95% CI: 1.030 − 4.286, p = 0.041) based on univariate analysis. Subsequent multivariate analysis also indicated that ATB administration was an independent prognostic factor for PFS (HR: 3.361, 95% CI: 1.592 − 7.097, p = 0.001) and OS (HR: 2.280, 95% CI: 1.042 − 4.991, p = 0.039). ATB administration is associated with reduced chemotherapy efficacy and poor prognosis in patients with advanced GC. Modulations in ATB-related dysbiosis and gut microbiota composition improve the clinical outcomes of chemotherapy. Supplemental data for this article is available online at https://dx.doi.org/10.1080/13102818.2021.1953400 .

ObjectiveThe outcome of surgical treatment for thalamic tumors is poor. Hydrocephalus is one of the most frequent postoperative complications after unilateral thalamic tumor resection. This study examined the relationship between surgical approaches, pathological grade, image characteristics, preoperative complications, extent of resection, and incidence of postoperative hydrocephalus.MethodsThe study retrospectively reviewed clinical data from 80 patients who underwent resection of thalamic tumors between 2015 and 2021. Data on patient survival and disease progression status were obtained retrospectively to calculate overall survival (OS) and progression free survival (PFS).ResultsNo patients died during the perioperative period and two patients suffered postoperative coma. Tumors were totally resected in 44 cases (55 %), subtotally resected in 21 cases (26.25 %), and partially resected in 15 cases (18.75 %). Thirty-five cases of hydrocephalus occurred within 1 month after operation(43.75%). Surgical approaches associated with hydrocephalus were as follows: hydrocephalus occurred in seven cases after trans-frontal lateral ventricle approach for tumor resection (62.9%), in 17 cases after through parieto-occipital transventricular approach tumor resection (43.58%), and in one case after trans-frontal lateral ventricle approach for tumor resection + third ventriculostomy (7.1%). Postoperative muscle strength decrease occurred in 41 patients (51.25%). Longer PFS and OS were correlated with degree of resection in patients with thalamic glioblastoma (P < 0.05) and had no relationship with hydrocephalus.ConclusionSurgical treatment of thalamic tumors is an effective therapeutic method. The incidence of postoperative hydrocephalus is not associated with tumor size, degree of tumor enhancement, peritumoral edema, tumor invasion, midline crossing, and pathological grade. The incidence of postoperative hydrocephalus was higher in patients with preoperative hydrocephalus and low resection degree, and lower in patients with endoscopic third ventriculostomy. The risk of early postoperative hydrocephalus in thalamic tumors is high. Intraoperative third ventriculostomy could reduce the incidence of early postoperative hydrocephalus. PFS and OS were longer in patients with thalamic glioblastoma with a high resection degree (P < 0.05) and were not associated with hydrocephalus.

Background: Tumor mutational burden (TMB) is a genomic biomarker that can predict favorable responses to immune checkpoint inhibitors (ICIs). Although we have better understanding of TMB in cancer immunity and cancer immunotherapy, the relationship between TMB and the clinical efficacy of ICIs remains unknown in the treatment of melanoma patients. Here, we conduct a systematic review and meta-analysis to evaluate the predictive value of TMB on the efficacy of ICIs in patients with melanoma.Methods: We systematically collected data from PubMed, Embase, Cochrane Library, CNKI, China Biomedical Database (CBM), and Wanfang Database. The end date was set to 26 June 2021. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival and/or progression-free survival according to TMB. Data for 1,493 patients from 15 studies were included. In addition, pooled effect size, heterogeneity analysis, sensitivity analysis, publication bias detection, and subgroup analysis were performed based on the included data.Results: Patients with high TMB showed significantly improved OS (HR = 0.49, 95% CI: 0.33, 0.73; p = 0.001) and PFS (HR = 0.47, 95% CI: 0.33, 0.68; p < 0.001) compared with patients with low TMB. This association was very good in patients treated with monotherapy, that is, anti-CTLA-4 or anti-PD-(L)-1 inhibitors, but not for the patients treated with a combination of the two drugs. The subgroup analysis results showed that heterogeneity was substantial in the targeted next-generation sequencing (NGS) group. Publication bias was detected, and the results were visualized using the funnel chart. And sensitivity analysis and trim-and-fill method analysis showed that our results were stable and reliable.Conclusion: High TMB is associated with improved OS and PFS in melanoma patients treated with mono-drug ICIs. TMB determined by NGS should be standardized to eliminate heterogeneity. Therefore, the role of TMB in identifying melanoma patients who may benefit from ICI should be further determined in more randomized controlled trials in the future.

Abstract Background Hairy cell leukemia (HCL) is a rare chronic B‐cell neoplasm with good long‐term prognosis. First and second‐line therapies include purine nucleoside analogues (PNAs) and rituximab, but until recently, limited alternative options were available for patients with two or more relapses. Aim The aim of this study is to describe our real‐life experience with HCL patients in third and fourth‐line therapies. Methods and Results Data from 49 HCL patients with two or more relapses, including 16 patients with three or more relapses, were collected from the French retrospective HCL cohort covering the period from 1980 until 2011. They were analyzed to assess hematological response, relapse free survival (RFS) and overall survival (OS) after third (L3) and fourth line (L4). The median age at diagnosis was 53 years. PNAs were the most frequently used treatments. As L3 therapy, 29 patients received PNAs (66%) and 15 (34%) other treatments (rituximab [11%] or interferon [7%] alone or in combination [16%]). The distribution of L4 treatments was similar. The overall hematological response rate (OHRR) after L3 was 97% (complete hematological response 86%) with a 40% five‐year cumulative incidence of relapse (CIR), a median RFS of 104 months, and a median OS of 235 months. After L4, the OHRR was 94% with a two‐year CIR of fourth relapse of 27%. Eleven secondary cancers (5‐year cumulative incidence of 12%) were diagnosed in 10 patients. Patients with ≥2 relapses experience frequent further relapses, with increasingly shorter time to next treatment as the number of treatment lines increases. Furthermore, treatment strategies are associated with substantial toxicities. Conclusion All these points lead to the need for novel treatments.

AimTumor deposits (TDs) are an aggressive hallmark of rectal cancer, but their prognostic value has not been addressed in current staging systems. This study aimed to construct and validate a prognostic nomogram for rectal cancer patients with TDs.MethodsA total of 1,388 stage III–IV rectal cancer patients who underwent radical surgical resection from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed to identify the clinical value of TDs. TD-positive rectal cancer patients in the SEER database were used as the training set to construct a prognostic model, which was validated by Fujian Cancer Hospital. Three models were constructed to predict the prognosis of rectal cancer patients with TDs, including the least absolute shrinkage and selection operator regression (LASSO, model 1), backward stepwise regression (BSR, model 2), and LASSO followed by BSR (model 3). A nomogram was established among the three models.ResultsIn the entire cohort, TD was also identified as an independent risk factor for overall survival (OS), even after adjusting for baseline factors, stage, other risk factors, treatments, and all the included variables in this study (all P

Metastasis is the leading cause of cancer‑related death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stem‑cell phenotype and anoikis resistance in OS are mostly unknown. Fos‑like antigen 1 (FOSL1) is important in maintaining a stem‑like phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stem‑like properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumor‑sphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stem‑cell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1‑mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumor‑sphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemness‑related factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1‑mediated stem‑like properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem cell‑like phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.

Current studies in OS is usually between linux and windows these days. Both Windows and Linux are widely used PC operating systems (OS). Windows is an eye-catching operating system, but it is not as safe as Linux. With growing worries about OS security, Linux has become well-known among OS users for its security and efficiency. This paper manages two of the principal common types of operating systems (Linux, Windows) with the significance of the operating system in any device and, moreover, to direct the study over Linux and Windows. We've compared various characteristics concerning Windows and Linux that are utilized in various researches and directed a survey for this reason. The results of the survey related to Windows and Linux are analyzed. The findings indicate that Linux is more preferred when concerned with security, whereas Windows is preferred when userfriendliness is concerned. [ABSTRACT FROM AUTHOR]

In this study we have treated patients with low back pain and knee pain. The purpose of the study was to determine the association between these two issues, and their effect on disability. Many sources are responsible for LBP, including muscles, nerves, bones, and referred pain from abdominal organs, and LBP itself is a major comorbidity of knee OA. LBP possibly interacts with knee pain causing greater knee OA symptoms, that is, coexisting LBP and severe knee pain would have a stronger impact on disability than either alone. We treated this pathology with physical therapy modalities. Patients that were treated achieved excellent results from a severe condition such as LBP, managed to be back at work without functional obstacles. This study presents the connection between patient and physical therapist in achieving desirable results. Material and methods: This is a cohort retrospective study of all patients with primary complaints of LBP (30 cases) who were checked for the first time between January 2020 and January 2021 in our clinic of physiotherapy "Fizioterapia" in Prishtina and Ferizaj. The records of patients were reviewed in detail, including their medical histories, examinations, imaging (X-Ray, CT, MRI) and consultations with other specialists. Demographic data, such as age, gender and employment status were reviewed. We measured Visual Analogue Scale (VAS), the Straight Leg Raise (SLR) test (Lasegue sign) and knee flexion. We treated our patients with the same protocol: Results and discussion: The patients enrolled in this study consisted of 13 males (43%) and 17 females (57%). The mean age of the patients was 45.9±8.9 years (range: 27-64). Among the 30 cases for which the LBP was the primary complaint, 22 (73.3%) of those cases had knee pain presentation. The mean Visual Analogue Scale (VAS) was 7.2±1. The mean scale of knee flexion is 102°±10.6° (measured with goniometer). The mean scale of the Straight Leg Raise (SLR) test (Lasegue sign) was 71°±11.6° (measured with goniometer). [ABSTRACT FROM AUTHOR]

Background: Previous data have suggested that ginsenoside Rg3 (Rg3), isolated from the roots of Panax ginseng, plays a repressing role in multiple cancers, including osteosarcoma (OS). However, there is no any literature available about the role of circular RNA (circRNA) in Rg3-mediated OS development. The study aimed to explore the function of circ_0003074 in the anti-cancer effects of Rg3 on OS. Methods: RNA expression of circ_0003074, miR-516b-5p and karyopherin subunit alpha 4 (KPNA4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated by Western blotting or immunohistochemistry assay. Cell viability, proliferation, apoptosis, migration and invasion were investigated by cell counting kit-8, 5-ethynyl-29-deoxyuridine (EdU), flow cytometry analysis, wound-healing and transwell invasion assays, respectively. Dual-luciferase reporter and/or RNA immunoprecipitation assay was performed to confirm the interplay between miR-516b-5p and circ_0003074 or KPNA4. Xenograft mouse model assay was conducted to reveal the effect of Rg3 treatment on tumor formation. Results: Circ_0003074 and KPNA4 expression was significantly upregulated, while miR-516b-5p was downregulated in OS tissues and cells compared with controls. Rg3 treatment dramatically decreased circ_0003074 expression in OS cells. Rg3 treatment led to decreased cell proliferation, migration and invasion but increased cell apoptosis, which was attenuated after circ_0003074 overexpression. Besides, miR-516b-5p was a target miRNA of circ_0003074 and partially restored circ_0003074-mediated action under Rg3 treatment. Decreasing miR-516b-5p expression also promoted Rg3-treated OS cell malignancy through KPNA4, which was identified as a target mRNA of miR-516b-5p. Besides, circ_0003074 induced KPNA4 production owing to the decrease of miR-516b-5p expression. Furthermore, Rg3 treatment inhibited tumor formation by regulating circ_0003074 in vivo. Conclusion: Rg3 inhibited OS progression through circ_0003074/miR-516b-5p/KPNA4 axis, showing the potential of Rg3 as a therapeutic agent for OS. Highlights: Circ_0003074 expression was upregulated in OS tissues and cells. Rg3 treatment significantly decreased circ_0003074 expression in OS cells. Circ_0003074 overexpression rescued Rg3-induced inhibition in OS progression. Circ_0003074 induced KPNA4 production through miR-516b-5p under Rg3 treatment. [ABSTRACT FROM AUTHOR]

Aims: To compare the effectiveness, safety, and survival outcomes in patients with infiltrative hepatocellular carcinoma (HCC) who underwent hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE). Methods: A total of 160 patients with infiltrative HCCs who underwent initial TACE (n = 68) and HAIC (n = 92) treatment from January 2016 to March 2020. We applied the propensity score matching (PSM) to adjust for potential imbalances. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between two groups. Multivariate analysis was evaluated through the forward stepwise Cox regression model and β coefficients was applied for the nomogram construction. Results: The median follow-up duration for the study population was 20.8 months. After PSM, the median OS and PFS in the HAIC group were significantly higher than those in the TACE group (OS, 13.3 vs 10.8 months; p = 0.043; PFS, 7.8 vs 4.0 months; p = 0.035) and the ORR and DCR in the HAIC group were significantly higher than those in the TACE group (ORR, 34.8% vs 11.8%; p = 0.001; DCR, 54.3% vs 36.8%; p = 0.028). A nomogram model comprising albumin-bilirubin grade, treatment responses, sessions, and treatment modalities, showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.789; validation set, C-index of 0.757), which outperformed other staging systems and conventional indices. Conclusion: HAIC improve significantly survival compared to TACE in patients with infiltrative HCC. A prospective randomized trial is ongoing to confirm this finding. [ABSTRACT FROM AUTHOR]

Background: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC).Patients and Methods: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included.Results: As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients.Conclusion: Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs), a class of noncoding RNAs (ncRNAs), may modulate gene expression by binding to miRNAs. Additionally, recent studies show that circRNAs participate in some pathological processes. However, there is a large gap in the knowledge about circDOCK1 expression and its biological functions in osteogenic sarcoma (OS). Methods: Differentially expressed circRNAs in OS cell lines and tissues were identified by circRNA microarray analysis and quantitative real-time PCR (qRT–PCR). To explore the actions of circDOCK1 in vivo and in vitro, circDOCK1 was knocked down or overexpressed. To assess the binding and regulatory associations among miR-339-3p, circDOCK1 and IGF1R, we performed rescue experiments, RNA immunoprecipitation (RIP), RNA pulldown assays and dual-luciferase assays. Moreover, we performed apoptosis assays to reveal the regulatory effects of the circDOCK1/miR-339-3p/IGF1R axis on cisplatin sensitivity. Results: CircDOCK1 expression remained stable in the cytoplasm and was higher in OS tissues and cells than in the corresponding controls. Overexpression of circDOCK1 increased oncogenicity in vivo and malignant transformation in vitro. In the U2OS and MG63 cell lines, circDOCK1 modulated tumor progression by regulating IGF1R through sponging of miR-339-3p. Additionally, in the U2OS/DDP and MG63/DDP cell lines, cisplatin sensitivity was regulated by circDOCK1 via the miR-339-3p/IGF1R axis. Conclusions: CircDOCK1 can promote progression and regulate cisplatin sensitivity in OS via the miR-339-3p/IGF1R axis. Thus, the circDOCK1/miR-339-3p/IGF1R axis may be a key mechanism and therapeutic target in OS. [ABSTRACT FROM AUTHOR]

Background: Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were associated with clinical benefit in cancer patients of melanoma, a lung cancer. In the present study, we investigated the correlation between irAE and ICI efficacy in hepatocellular carcinoma (HCC) patients. Methods: We divided the HCC patients who received the anti-PD-1 antibody into two groups as irAE group and non-irAE group according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. The treatment efficacy of ICIs was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Result: Of the 65 HCC patients who received the anti-PD-1 antibody (monotherapy or combined with targeted medicine), median PFS in the irAE group was superior to that in the non-irAE group (302 days vs. 148 days, p = 0.004). Median OS in the irAE group was also better than that in the non-irAE group (374 days vs. 279 days, p = 0.038). Although the statistical difference for DCR in the irAE group and non-irAE group was not reached, the DCR of the irAE displayed a trend better than that of the non-irAE group (41.20% vs. 20.80%, p = 0.118). Multivariate analysis also demonstrated that the non-irAE group (HR = 6.410, 95% CI: 1.404 to 29.275) was associated independently with the poor prognosis. Conclusions: Development of irAEs was associated with clinical benefit for HCC patients who were treated with immune checkpoint inhibitors; irAE, particularly low-grade irAE, was a predictable marker for better ICI treatment efficiency in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Anti‐human T‐lymphocyte immunoglobulin is commonly used as prophylaxis for graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. Patients and Methods: Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. Results: The incidences of acute and chronic GVHD were statistically not different between three groups (p =.20 and p =.13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p =.007) and severe acute GVHD (p =.001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p =.04 and p =.037) with no difference between 20 and 30 mg/kg. Conclusion: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population. [ABSTRACT FROM AUTHOR]

La maladie des griffes du chat due à Bartonella henselae avec atteinte osseuse est rare. Le diagnostic est difficile et la prise en charge demeure non codifiée. Nous rapportons un cas de bartonellose disséminée avec ostéomyélite multifocale et atteintes viscérales multiples chez une adulte immunocompétente. La confirmation diagnostique était apportée par la PCR sur adénopathie. Avec notre observation, 31 cas de bartonellose avec atteinte osseuse ont été rapportés dans la littérature. Le diagnostic repose sur l'association de l'interrogatoire, de la sérologie et de la PCR sur tissu. Le traitement antibiotique permet dans tous les cas la guérison. La maladie des griffes du chat dans sa forme systémique avec atteinte osseuse est un diagnostic rare et difficile pour le clinicien et une approche invasive est souvent nécessaire pour obtenir le diagnostic. Cat scratch disease caused by Bartonella henselae with bone involvement is a rare presentation. We report a case of disseminated bartonellosis with multifocal osteomyelitis and multiple visceral involvement in an immunocompetent adult. Diagnostic confirmation was obtained by PCR on lymphadenopathy. In addition to our observation, 31 cases of bartonellosis with bone involvement were reported in the literature. Diagnosis is based on a combination of history, serology and PCR performed on tissue. The antibiotic treatment allows recovery in all cases. Cat scratch disease in its systemic form with bone involvement is a rare and difficult diagnosis for the clinician and an invasive approach is often required to obtain the diagnosis. [ABSTRACT FROM AUTHOR]

Background: The current study aimed to evaluate the serum pretreatment lactate dehydrogenase (LDH) and overall survival (OS) in small cell lung cancer (SCLC) patients who received first‐line platinum‐containing chemotherapy. Methods: A total of 234 SCLC patients, who received first‐line platinum‐based chemotherapy between 2013 and 2018, were retrospectively analyzed. The data of hematological characteristics, age, gender, ECOG score, staging, metastatic site, smoking history, chemotherapy cycle, thoracic radiotherapy and hyponatremia were collected. Overall survival was calculated using the Kaplan‐Meier method. The statistically significant factors in the univariate analysis were selected for the multivariate COX model analysis. Results: Age, ECOG score, stage, thoracic radiotherapy, hyponatremia, liver metastasis, brain metastasis, bone metastasis, LDH, NSE and neutrophil‐to‐lymphocyte ratio (NLR) were closely correlated to OS in the univariate analysis. Furthermore, the multivariate analysis revealed that age (<65 years), ECOG score (<2 points), limited‐stage (LD), thoracic radiotherapy and LDH <215.70 U/L were the independent prognostic factors for survival. The median OS time was worse for patients with LDH ≥215.70 U/L. In the subgroup analysis, LDH ≥215.70 U/L was significant for survival in both limited and extensive disease. Patients who achieved CR + PR in the first‐line treatment had lower initial LDH levels. It was found that the pretreatment LDH increased the incidence of patients with liver metastasis. Conclusions: Positive independent prognostic factors for SCLC patients were age < 65 years old, ECOG score < 2 points, LD‐SCLC, and pretreatment LDH <215.70 U/L. These factors may be useful for stratifying patients with SCLC for treatment approaches. Key points: Significant findings of the study: Age < 65 years old, ECOG score < 2 points, LD‐SCLC, and pretreatment LDH <215.70 U/L are the positive independent prognostic factors for SCLC patients. What this study adds: The current study provided more references for SCLC diagnosis and treatment and determined more factors for stratifying patients with SCLC for treatment approaches. [ABSTRACT FROM AUTHOR]

Purpose: Adolescent and young adult (AYA) pancreatic ductal adenocarcinoma (PDAC) occurs in patients below 40 years old. Whether AYA patients have worse outcomes compared with older patients is still controversial. The purpose of this study is to compare the outcomes of AYA patients and older patients after radical surgery for PDAC. Methods: A single-center, retrospective, cohort study was conducted in patients who underwent radical surgery for PDAC in Xiangya Hospital Central South University from January 2007 to December 2019. The clinicopathological data and results of patients with PDAC were collected and analyzed retrospectively. They were divided into AYA group and older group based on age (< 40, AYA group; ≥ 40, older group). Based on all the considered covariates except age, we estimated 1:2 case propensity score matching (PSM). Results: A total of 1033 cases were enrolled, 46 cases (4.45%) in the AYA group. Both before and after PSM, the AYA patients have a higher preoperative CA19-9 than the older patients (P < 0.001) and (P < 0.001). Pathological results showed that AYA group had a higher microvascular invasion rate (P < 0.001 and P = 0.045) than older group. The median time of overall survival (OS) in AYA group and older group were 13 months (95% CI = 11.50– 14.50) and 14 months (95% CI = 13.50– 14.50), respectively. Additionally, AYA group have a worse 2-year OS rate than older group (8.70% vs 25.23%, P = 0.011 and 8.70% vs 25.00%, P = 0.023). According to the Log rank test, AYA group have a worse cumulative OS rate than older group (P = 0.002) and (P = 0.030), respectively. Conclusion: PDAC might be more aggressive in AYA, and the cumulative OS after radical PDAC surgery in AYA patients is worse than that in older patients. [ABSTRACT FROM AUTHOR]

Objective: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression‐free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. Methods: Following induction therapy and high‐dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35‐day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. Results: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P =.0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non‐existent in the bortezomib consolidation arm but pronounced in the observation arm (P =.0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P =.0569). Conclusions: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards. [ABSTRACT FROM AUTHOR]

Abstract Background Circular RNAs (circRNAs) are important regulators in the pathogenesis of diseases and affects the occurrence and development of diseases. However, the role of circRNAs in osteosarcoma (OS) has not been fully elucidated. Methods The expression of circ_0000285, miR-409-3p and insulin-like growth factor binding protein 3 (IGFBP3) was detected using quantitative real-time PCR (qRT-PCR). The protein level of IGFBP3 was measured using western blot. CCK-8 and colony formation assays were used to determine cell proliferation. Flow cytometry was applied to measure cell cycle and cell apoptosis. Transwell assay was used to assess cell invasion and migration. Dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) assay were performed to determine the relationship among circ_0000285, miR-409-3p and IGFBP3. The animal experiments were performed to determine the function of circ_0000285 in vivo. Results In this study, we found that the expression of circ_0000285 was significantly increased in OS tissues and cells and was enriched in the cytoplasm. Knockdown of circ_0000285 inhibited OS growth in vitro and in vivo. Moreover, miR-409-3p was a target miRNA of circ_0000285 and miR-409-3p targets to IGFBP3 in OS. Besides, circ_0000285 could promote proliferation, migration, invasion and inhibit apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis. Conclusion In this study, circ_0000285 regulated proliferation, migration, invasion and apoptosis of OS cells by miR-409-3p/IGFBP3 axis, implying that circ_0000285 was a potential target for OS therapy.

Abstract Background Osteosarcoma (OS) is a common severe illness globally. Lupeol has been reported to participate in the pathophysiologic properties of various cancers, including OS. This study aimed to explore the effects of lupeol on proliferation, invasion, and apoptosis on OS cells and the underlying mechanism. Methods The cell viability of OS cells was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The expression levels of miR-212-3p and high-mobility group AT-hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS cells. The cell apoptosis and invasion were detected by flow cytometry and transwell invasion assays, respectively. The functional target of miR-212-3p was predicted by online software and confirmed by luciferase reporter assay. The protein level of HMGA2 was measured by western blot analysis. Results Lupeol suppressed cell viability and invasion, and promoted apoptosis by upregulating the expression of miR-212-3p in OS cells. Knockdown of miR-212-3p restored the anti-tumor effect of lupeol. Interestingly, miR-212-3p directly targeted HMGA2 and suppressed its expression. Moreover, HMGA2 reversed the inhibited impact on viability and invasion, and the promoted effect on apoptosis induced by upregulation of miR-212-3p. Also, lupeol administration exerts its anti-tumor effect by overexpression of miR-212-3p to suppress the expression of HMGA2 in OS cells. Conclusion Lupeol inhibited OS progression by modulating the miR-212-3p/HMGA2 axis in vitro.

Abstract Background Osteosarcoma (OS) is the most common bone malignant tumor in children, youth, and adolescents. Circular RNA hsa_circ_0005909 (circ_0005909) is involved in the progression of OS. Nevertheless, there are few reports on the role and mechanism of circ_0005909 in OS. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to examine the expression of circ_0005909, miR-936, and High Mobility Group Box 1 (HMGB1) mRNA in OS tissues and cells. Cell viability, colony formation, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), cell colony formation, or transwell assays. Cell epithelial-mesenchymal transition (EMT) and HMGB1 protein levels were assessed through western blot analysis. The role of circ_0005909 on tumor growth in vivo was verified by xenograft assay. The relationship between circ_0005909 or HMGB1 and miR-936 was confirmed with the dual-luciferase reporter or RNA pull-down assays. Results Circ_0005909 level was upregulated in OS tissues and cells. OS patients with high circ_0005909 expression had a lower survival rate. Circ_0005909 inhibition reduced tumor growth in vivo and constrained cell viability, colony formation, migration, invasion, and EMT of OS cells in vitro. Furthermore, circ_0005909 served as a sponge for miR-936 and the repressive impacts of circ_0005909 silencing on malignant behaviors of OS cells were abolished by miR-936 inhibitors. Also, HMGB1 acted as a target for miR-936 and was modulated by circ_0005909 via miR-936. Additionally, HMGB1 overexpression restored the inhibitory influence on the malignant behaviors of OS cells mediated by circ_0005909 inhibition. Conclusions Circ_0005909 inhibition impeded the progression of OS via downregulating HMGB1 via sponging miR-936.