Subgroup Γ0 Research Articles

Three-generation super no-scale models in heterotic superstrings

We derive the conditions for the one-loop contribution to the cosmological constant to be exponentially suppressed in a class of heterotic string compactifications with three generations of chiral matter, where supersymmetry is spontaneously broken à la Scherk-Schwarz. Using techniques of partial unfolding based on the Hecke congruence subgroup Γ0(2) of the modular group to extract the leading asymptotics, we show that the super no-scale condition nB=nF between the degeneracies of massless bosons nB and fermions nF in the full string spectrum is necessary but not sufficient, and needs to be supplemented by additional conditions which we identify. We use these results to construct three-generation Pati–Salam models with interesting phenomenological characteristics.

Expression and methylation status of MMR and MGMT in well-differentiated pancreatic neuroendocrine tumors and potential clinical applications.

Recent studies claim that immune checkpoint inhibitors are effective in defective mismatch repair (dMMR) cancers. This raises the question of whether similar therapies are effective in PanNETs (pancreatic neuroendocrine tumors); however, in general, assessment of MMR status in PanNETs has been inconsistent in previous studies. MGMT (O6-methylguanine-DNA methyltransferase) is potentially important for guiding temozolomide (TMZ) therapy in glioblastoma. The number of reports on MGMT expression and promoter methylation in PanNETs are limited. In this study we assessed the expression of MGMT and MMR proteins MSH2, MSH6, MLH1 and PMS2 in a series of PanNETs by IHC. The methylation status of MGMT and MMR genes in a subset of PanNETs was further assessed by MS-MLPA analysis. Survival curves were constructed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Multivariate Cox proportional hazards regression models were used to determine the prognostic value of the variables. According to evaluation criteria for mismatch repair defects, none of PanNETs shown nuclear staining loss for MSH2, MSH6, MLH1, and PMS2. MGMT low-intensity PanNETs were more commonly found in higher grade, higher Ki67 index and non-functional tumors (P < 0.05). In multivariate analysis, stage III-IV and low-intensity MGMT were shown to be independent risk factors for progression of PanNETs in the entire cohort, non-functioning subgroup and G2 subgroup (P < 0.05 for all). MGMT promoter methylation tended to be higher in the group with low expression of MGMT, However, methylation of MGMT did not statistically correlate with low expression of MGMT (P = 0.153). In conclusion, our study suggests that decreased expression of MGMT but not MMR is associated with a higher risk of progression of pancreatic neuroendocrine tumors.

Parametrization of Kloosterman sets and SL3-Kloosterman sums

We stratify the SL3 big cell Kloosterman sets using the reduced word decomposition of the Weyl group element, inspired by the Bott-Samelson factorization. Thus the SL3 long word Kloosterman sum is decomposed into finer parts, and we write it as a finite sum of a product of two classical Kloosterman sums. The fine Kloosterman sums end up being the correct pieces to consider in the Bruggeman-Kuznetsov trace formula on the congruence subgroup Γ0(N)⊆SL3(Z). Another application is a new explicit formula, expressing the triple divisor sum function in terms of a double Dirichlet series of exponential sums, generalizing Ramanujan's formula.

Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma.

Growing evidence indicates a link between retinoic acid (RA) metabolism and sarcoma progression or immunity in laboratory studies. However, a comprehensive analysis of RA abnormality in the sarcoma population is still lacking. Herein, we systematically analyzed the molecular features of 19 retinoic acid metabolism-related enzymes and sarcoma patients’ clinical information based on TCGA/TARGET/GSE datasets. We identified two RA expression subtypes, which were related to distinct clinical survival outcomes and exhibited different biological features. Gene set enrichment analysis indicated a set of immune pathways were enriched in G1 while oncogenic pathways were enriched in G2. Immune cell infiltration analysis using the TIMER algorithm revealed more CD4+ and CD8+ T cell infiltration in G1 subgroups than in G2. Moreover, we generated a seven genes signature to predict the RA metabolism index based on the LASSO-penalized Cox regression model. Survival analysis demonstrated the significant prognostic differences between high- and low-risk groups among different bone and soft tissue datasets. A higher risk index was associated with less T cell CD8+ infiltration. The predictive ability of the RA risk score was validated in 71 bone or soft tissue sarcoma clinical samples. These results indicated that RA-based classification could distinguish sarcoma patients with different clinical outcomes and immune statuses, which may help to explore better treatment decision-making for sarcoma patients.

Treatment tactics of new NET G3 subgroup in first line of therapy

Considering the fact that the group of neuroendocrine carcinomas (NECs) grade 3 is heterogenous, in the year of 2017 a new subgroup of welldifferentiated neuroendocrine tumors grade 3 (NETs G3) was described. NETs G3 are tumors with more favorable prognosis and less sensitive to platinum-based chemotherapy regimens than NECs, they also have peculiar morphogenetical qualities: lower ki‑67 index (mean 35.0 %), higher somatostatin receptors expression, absence of DAXX/ATRX/MEN 1 genes mutation, p53 expression in the absence of TP53 mutation. Nowadays treatment standard for NETs G3 subgroup is still remain unclear due to lack of prospective clinical trials. At the same time taking in note historical retrospective data, NETs G3 should be treated in line with NETs G1/G2 and only patients with higher ki‑67 index can be treated as NECs with platinum-based chemotherapy. In our non-randomised phase II prospective trial, we accessed the efficacy of different chemotherapy regimens in combination with somatostatin analogues in new NETs G3 subgroup. 153 patients with IHC-confirmed neuroendocrine neoplasm diagnose were included: NETs G3 n = 53 mean ki‑67 36.4 % [21.0–60.0 %], NETs G2 n = 50 mean ki‑67 15.7 % [2.1–20.0 %], NECs n = 50 mean ki‑67 69.0 % [38.0–96.0 %]). Patients from NETs G3 subgroup received 4 chemotherapy regimens: Aranose (n = 19), Aranose (arabinopiranosilmethyl nitrosocarbamide, ALK, – cytostatic drug with a chemical structure similar to Streptozotocin and Nitrosomethylurea, approved in Russian Federation for melanoma and welldifferentiated neuroendocrine tumors treatment), XELOX (n = 8), TemCAP (n = 11), EP/EC (n = 10). mPFS in Aranose-subgroup was 19.3 ± 5.9 months (95 % CI: 7.7–30.8), in XELOX – 10.8 ± 3.6 months (3.7–17.8), in TemCAP – 14.8 ± 4.2 months (6.6–23.1) and in platinum-based regimens – 4.4 ± 1.9 months (0.6–8.2) (p = 0.01). DCR in Aranose subgroup was 73.6 % and ORR – 36.8 %, PDR – 21.1 %, in XELOX subgroup ORR was 62.5 %, SDR was 50.0 % and PDR – 25.0 %, in TemCAP subgroup DCR was 63.6 %, ORR – 9.1 %, PDR – 18.2 % and in platinum-based regimens SDR was 40.0 %, PDR – 50.0 % (p = 0.05).

Propagating quasiconvexity from fibers

Let \(1 \to K \to G\,\mathop \to \limits^\pi \,Q\) be an exact sequence of hyperbolic groups. Let Q1 < Q be a quasiconvex subgroup and let G1 = π−1(Q1). Under relatively mild conditions (e.g. if K is a closed surface group or a free group and Q is convex cocompact), we show that infinite index quasiconvex subgroups of G1 are quasiconvex in G. Related results are proven for metric bundles, developable complexes of groups and graphs of groups.

Molecular Subclassification Based on Crosstalk Analysis Improves Prediction of Prognosis in Colorectal Cancer.

The poor performance of single-gene lists for prognostic predictions in independent cohorts has limited their clinical use. Here, we employed a pathway-based approach using embedded biological features to identify reproducible prognostic markers as an alternative. We used pathway activity score, sure independence screening, and K-means clustering analyses to identify and cluster colorectal cancer patients into two distinct subgroups, G2 (aggressive) and G1 (moderate). The differences between these two groups with respect to survival, somatic mutation, pathway activity, and tumor-infiltration by immunocytes were compared. These comparisons revealed that the survival rates in the G2 subgroup were significantly reduced compared to that in the G1 subgroup; further, the mutational burden rates in several oncogenes, including KRAS, DCLK1, and EPHA5, were significantly higher in the G2 subgroup than in the G1 subgroup. The enhanced activity of the critical pathways such as MYC and epithelial-mesenchymal transition may also lead to the progression of colorectal cancer. Taken together, we established a novel prognostic classification system that offers meritorious insights into the hallmarks of colorectal cancer.

Identification of Pathway-Based Biomarkers with Crosstalk Analysis for Overall Survival Risk Prediction in Breast Cancer

Recently, many studies have investigated the role of gene-signature on the prognostic assessment of breast cancer (BC), however, the tumor heterogeneity and sequencing noise have limited the clinical usage of these models. Pathway-based approaches are more stable to the perturbation of certain gene expression. In this study, we constructed a prognostic classifier based on survival-related pathway crosstalk analysis. We estimated pathway’s deregulation scores (PDSs) for samples collected from public databases to select survival-related pathways. After pathway crosstalk analysis, we conducted K-means clustering analysis to cluster the patients into G1 and G2 subgroups. The survival outcome of the G2 subgroup was significantly worse than the G1 subgroup. Internal and external dataset exhibits high consistency with the training dataset. Significant differences were found between G2 and G1 subgroups on pathway activity, gene mutation, immune cell infiltration levels, and in particular immune cells/pathway’s activities were significantly negatively associated with BC patient’s outcomes. In conclusion, we established a novel classifier reflecting the overall survival risk of BC and successfully validated its clinical usage on multiple BC datasets, which could offer clinicians inspiration in formulating the clinical treatment plan.

Reduction of dual-species biofilm after sonic- or ultrasonic-activated irrigation protocols: A laboratory study.

To evaluate the antibacterial effect of sonic- and ultrasonic-activated irrigation on bacterial reduction of a dual-species biofilm in root canals compared to nonactivated irrigation in a laboratory study. Two hundred and forty extracted human single-rooted maxillary anterior teeth were divided into two main groups (G, n=120) according to the initial preparation size of the root canal (G1: size 25, 0.06 taper, G2: size 40, 0.06 taper). Root canals were inoculated with Enterococcus faecalis and Streptococcus oralis. After 5days, G1 received combined instrumentation (up to size 40, 0.06 taper) and irrigation/activation, whereas G2 received solely irrigation/activation protocols. In both groups, irrigation was performed with sodium hypochlorite (NaOCl 1%) or physiological saline (NaCl 0.9%), using nonactivated syringe irrigation, sonic activation (2x30s) or ultrasonic activation (2x30s). Logarithmic reduction factors (LRFs) of colony-forming units were analysed separately for dentine-adherent and planktonic bacteria immediately after irrigation/activation protocols (time-point 1) or after 5days of further incubation (time-point 2) by analysis of variance (anova) and post hoc tests (Tukey's HSD, t-test). The significance level was set at 0.05. In G1subgroups (combined instrumentation with irrigation/activation), LRFs were significantly affected by the applied irrigation solution (p<.0001), but not by the activation method (p>.05; anova). In G2subgroups (solely irrigation/activation), both, irrigant solution and activation, significantly affected LRFs (p<.0001, anova). Sonic activation resulted in significantly higher LRFs than ultrasonic activation (p<.0001) which had significantly greater reductions than nonactivated irrigation (p<.05; Tukey's HSD). At T2, strong bacterial regrowth was observed in all groups; however, a significant bacterial reduction was detected for factors instrumentation, irrigant solution and activation (p<.0001; anova). Similar LRFs were found for dentine-adherent and planktonic bacterial cells in all groups (r=0.91 at T1, r=0.8 at T2). In this laboratory study on extracted maxillary anterior teeth high-frequency sonic activation resulted in a greater bacterial reduction compared to ultrasonic activation in groups receiving solely irrigation/activation protocols; however, irrigation using NaOCl and ultrasonic activation also contributed significantly to bacterial reduction compared to the control groups.

1431Dietary patterns and diet quality of Portuguese children and adolescents: the UPPER project

Abstract Background Based on a classification that considers the nature, extent and purpose of food processing, this study aims to identify dietary patterns (DPs) and their associations with diet quality. Methods Sample from the 2015-2016 National Food, Nutrition and Physical Activity Survey (n = 1153;3-17y). Dietary intake from 2 non-consecutive 24h-recalls. Foods classified by NOVA system into 42 subgroups from 4 groups: unprocessed/minimally processed (G1), processed culinary ingredients (G2), processed (G3) and ultra-processed (UPF) (G4). Percentage of grams related to total daily grams consumed were considered to identify DPs by latent class analysis. Adjusted linear regressions were performed to test association with nutritional indicators. Results Subjects followed 3 DPs: “Unhealthy” (51%), “Traditional” (36%), and “Dairy” (13%). Consumption in NOVA groups/subgroups differentiated them: “Unhealthy”, high in G4 and low in G1; “Traditional”, high in G1, G2 and G3, but also some subgroups from G4; and “Dairy”, high in milk, yogurt and milk-based beverages from G1 or G4 and low in most G3 subgroups. Energy from UPF represented 39% in “Unhealthy” and 34-35% in “Traditional” and “Dairy”. Compared to “Traditional” DP, “Unhealthy” was higher in free sugars, and lower in fibre, vitamin A, vitamin C, folates, sodium, potassium, magnesium, and iron. “Dairy” had lower total energy, energy density, fats and sodium, and higher carbohydrates, potassium, calcium, phosphorus and magnesium. Conclusions “Unhealthy” had the worst nutrient profile, although all DPs presented significant consumption of UPF. This should be considered in food-based interventions and school-feeding policies. Key messages Half of Portuguese &amp;lt;18 years presented an “Unhealthy” DP.

Alternative Lengthening of Telomeres Phenotype Predicts Progression Risk in Noninsulinomas in a Chinese Cohort

Introduction: Recent studies have suggested that alternative lengthening of telomeres (ALT) is associated with metastasis and poor survival in pancreatic neuroendocrine tumors (PanNETs). This study evaluated whether this association is applicable to Chinese patients as well as the potential somatic mutations associated with ALT. Methods: We assessed the prevalence of ALT by performing telomere-specific fluorescence in situ hybridization and analyzed DAXX/ATRX expression using immunohistochemistry in 112 Chinese patients with PanNETs to evaluate the association between ALT and clinical outcomes. A subset of the noninsulinoma samples (28/60) was subjected to Sanger sequencing and targeted sequencing. Results: The ALT-positive phenotype was identified in 23.2% (26/112) of the samples. The clinicopathologic factors significantly associated with progression in the noninsulinoma (n = 60) cohort were the female sex (p = 0.006), Ki-67 index (p < 0.001), World Health Organization grade (p = 0.031), and ALT positivity (p = 0.013). Patients with ALT-positive PanNETs had significantly shorter progression-free survival than those with ALT-negative PanNETs in the entire cohort (p < 0.001), noninsulinoma subgroup (p = 0.01), and G2 subgroup (p = 0.001). ALT-positive samples frequently harbored somatic mutations in DAXX, ATRX, MEN1, SETBP1, PRKDC, and GNAS. Conclusions: We confirmed that ALT positivity is an effective risk predictor, especially in the noninsulinoma and G2 subgroups. ALT is also related to somatic mutations in MEN1, SETBP1, PRKDC, and GNAS, in addition to DAXX and ATRX.

Natural Killer Receptor Ligand Expression By AML Blasts Determines Survival and Relapse Following Induction Chemotherapy

IntroductionNatural killer (NK) cells contribute to the immune surveillance of cancer and are capable of controlling acute myeloid leukemia (AML) in vitro and following allogeneic hematopoietic stem cell transplantation. NK cell activation is dependent on the balance of activating and inhibitory receptor-ligand interactions. The prognostic impact of the expression of NK receptor ligands (NKRL) on AML blasts at diagnosis has not been described. We investigated the impact of NKRL expression by AML on the outcome of newly diagnosed patients undergoing induction chemotherapy. We hypothesized that patients with AML that expressed NKRL that facilitated NK cell activation (low inhibitory and high activating ligand expression) have improved immune surveillance and a reduced relapse rate.MethodsCryopreserved bone marrow cells and clinical data of 66 AML patients who underwent induction chemotherapy between 2001 and 2013 were obtained from the Australasian Leukemia Lymphoma Group tissue bank. Patients were stratified by cytogenetics (CG) and mutation status (European LeukemiaNet criteria, ELN). Expression (by relative fluorescence intensity - RFI) of 6 activating (MICA, MICAB, CD155, CD112, ULBP1, ULBP2/5/6) and 3 inhibitory (HLA class I, PD-L1 and PD-L2) NKRL on AML blasts was analyzed by flow cytometry. A net score of activating minus inhibitory ligands was calculated, which stratified patients into 2 groups: G0 (inhibitory pattern) and G1 (activating pattern).ResultsThe median age of patients was 56 years. Cytogenetic risk was adverse (13), intermediate (46) and favorable (7); ELN risk incorporating mutational profile was adverse (25), intermediate (15), and favorable (20). 79% of patients received an anthracycline in combination with cytarabine as induction therapy. Among activating ligands, the MICA, CD112 and ULBP1 were frequently expressed by AML blasts (79%, 80% and 82% of patients respectively), and also demonstrated the greatest intensity of expression (mean RFI of 3, 4.2 and 6.5 respectively). When analyzed individually, only ULBP1 expression was significantly associated with improved overall survival (OS) (p<0.05), relapse free survival (RFS) (p<0.05) and lower relapse incidence (RI) (p<0.005). The intensity of ULBP1 expression was significantly associated with improved OS, RFS and RI in a stepwise fashion. Patients with the highest ULBP1 expression had a reduced hazard ratio of death (HR 0.20, p<0.05) or relapse (HR 0.24, p<0.05) compared with non-expressors. PD-L2 expression on AML cells was higher and more frequent than PD-L1 (85% vs 5%). All AML variably expressed HLA class I. According to RFI, 32 patients were assigned to G0 and 34 to G1. There was no difference in patient age or distribution of CG or ELN risk categories between patients in G0 or G1 subgroups. G1 was significantly associated with lower relapse incidence than G0 (p<0.005, 2-year-RI: G1 28% vs G0 71%, Fig. 1). G1 was associated with higher RFS (log-rank p<0.05; at 2 years: G1 52% vs G0 20%; Fig 2) and improved OS (log rank p<0.05; at 2 years: G1 56% vs G0 29%; Fig 3). The G1 phenotype remained significantly associated with lower RI when taking into account either CG or ELN risk.ConclusionsWe have identified an immunological risk stratification method based on NKRL expression which is independent of established cytogenetic and molecular prognostic factors. Expression of activating NK cell receptor ligands by AML blasts is associated with superior survival and reduced relapse following induction chemotherapy. Our findings suggest that AML blasts are effective targets for NK cell-mediated immune surveillance, and support investigation into therapeutic strategies to enhance NK cell activation as a means of maintaining remission. [Display omitted] DisclosuresRitchie:Amgen Inc.: Honoraria.

Effect of Endometrium Thickness on Clinical Outcomes in Luteal Phase Short-Acting GnRH-a Long Protocol and GnRH-Ant Protocol.

ObjectiveTo investigate the factors that influence luteal phase short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-antagonist (GnRH-ant) protocol on pregnancy outcome and quantify the influence. About the statistical analysis, it is not correct for the number of gravidities.MethodsInfertile patients (n = 4,631) with fresh in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer were divided into GnRH-a long protocol (n =3,104) and GnRH-ant (n =1,527) protocol groups and subgroups G1 (EMT ≤7mm), G2 (7 mm <EMT ≤10 mm), and G3 (EMT >10 mm) according to EMT on the trigger day. The data were analyzed.ResultsThe GnRH-ant and the GnRH-a long protocols had comparable clinical outcomes in the clinical pregnancy, live birth, and miscarriage rate after propensity score matching. In the medium endometrial thickness of 7–10 mm, the clinical pregnancy rate (61.81 vs 55.58%, P < 0.05) and miscarriage rate (19.43 vs 12.83%, P < 0.05) of the GnRH-ant regime were significantly higher than those of the GnRH-a regime. The EMT threshold for clinical pregnancy rate in the GnRH-ant group was 12 mm, with the maximal clinical pregnancy rate of less than 75% and the maximal live birth rate of 70%. In the GnRH-a long protocol, the optimal range of EMT was >10 mm for the clinical pregnancy rate and >9.5 mm for the live birth rate for favorable clinical outcomes, and the clinical pregnancy and live birth rates increased linearly with increase of EMT. In the GnRH-ant protocol, the EMT thresholds were 9–6 mm for the clinical pregnancy rate and 9.5–15.5 mm for the live birth rate.ConclusionsThe GnRH-ant protocol has better clinical pregnancy outcomes when the endometrial thickness is in the medium thickness range of 7–10 mm. The optimal threshold interval for better clinical pregnancy outcomes of the GnRH-ant protocol is significantly narrower than that of the GnRH-a protocol. When the endometrial thickness exceeds 12 mm, the clinical pregnancy rate and live birth rate of the GnRH-ant protocol show a significant downward trend, probably indicating some negative effects of GnRH-ant on the endometrial receptivity to cause a decrease of the clinical pregnancy rate and live birth rate if the endometrial thickness exceeds 12 mm.

Mdm-MIR393b-mediated adventitious root formation by targeted regulation of MdTIR1A expression and weakened sensitivity to auxin in apple rootstock

Adventitious root (AR) formation is of great significance for apple rootstock breeding. It is widely accepted that miR393 influences AR formation in many plant species; however, the molecular mechanism by which factors regulate AR formation remains insufficient. In this study, the evolutionary relationship of mdm-miR393 and candidate target genes MdTIR1/AFB was systematically identified, and the expression patterns were analysed. Multisequence alignment analysis of miR393 family members suggests that miR393 conservatively evolved between different species. The evolutionary relationship of the TIR1/AFBs can be divided into G1, G2 and G3 subgroups. During AR formation, the expression level of mdm-miR393a/b/c was significantly upregulated at 1 d and 7 d by exogenous auxin treatment. Furthermore, the expression levels of MdTIR1A, MdTIR1D, MdAFB1, MdAFB2, MdAFB3, MdAFB4 and MdAFB8 also appeared to be significantly changed by exogenous auxin induction. Subsequently, tissue-specific expression analysis showed that the expression levels of mdm-miR393 and MdTIR1/AFBs in different tissues exhibited significant differences. The promoter of mdm-miR393 contains multiple elements that respond to ABA, adversity and light signals; auxin treatment can activate the mdm-MIR393b promoter but is obviously inhibited by NPA treatment. The targeting relationship between mdm-MIR393b and MdTIR1A was verified by expression patterns, degradation group data, transient tobacco conversion results, and genes functions experiments. Heterologous overexpression of mdm-MIR393b (35S::mdm-MIR393b) decreased the number of ARs in the phenotype and reduced the expression level of the target gene NtTIR1 in tobacco. Compared to the wild type, the 35S::mdm-MIR393b transgenic plants demonstrated insensitivity to auxin. Furthermore, tir1 mutant exhibited reduced root system structure relative to the control. The above results illustrated that mdm-MIR393b is involved in mediating AR formation by targeted regulation of MdTIR1A expression in apple rootstock.

Femoroacetabular impingement: correlation between imaging parameters, sport activity and chondral damage

Femoroacetabular impingement is characterized by an abnormal contact between the acetabulum and the femoral head-neck junction. Femoroacetabular impingement shows three main clinical frameworks: pincer-FAI, cam-FAI and cam-pincer mixed form. The aim of the study was to investigate the correlation between femoroacetabular impingement, imaging, activity and chondral damages. Forty-one patients, undergoing arthroscopic chondroartroplasty for cam and cam-pincer mixed form were considered. All patients underwent an X-Ray hip evaluation (G1 group), while 15 patients also underwent a pelvis MRI evaluation (G2 subgroup). For G1 patients, the superior-inferior offset ratio and alpha angle were calculated from the X-Ray examinations. For G2 patients, the antero-posterior offset ratio was also calculated from pelvis MRI. Chondral damage was classified according to the Outerbridge Classification. The superior-inferior offset ratio and the antero-posterior offset ratio were respectively 0.50±0.23 and 0.33±0.19. The α angle predictive for a chondral damage of IV degree was 81.5°. The chondral damage of the patients suffering from cam-FAI and cam-pincer mixed form were respectively 3.53±0.80 and 3.00±1.41. From the results was possible to: 1) elaborate two tables providing a reliable indirect calculation of the alpha angle; 2) establish an alpha angle cut-off value indicative for a IV degree chondral damage; 3) show that pincer-FAI does not represent an aggravating factor for chondral damage; 4) show that the level of sports activity was related to the severity of chondral damage; and 5) show that a physically demanding occupation was not an aggravating factor for chondral damage.

Potential application value of PET/computed tomography in retroperitoneal leiomyosarcoma and a literature review.

To analyze the fluorine-18 fludeoxyglucose PET/computed tomography (18F-FDG PET/CT) findings of retroperitoneal leiomyosarcoma (RLMS) and the role of this method in differentiating between benign and malignant masses and classifying the malignant degree to improve the understanding of this rare disease. Eight leiomyomas (A group), 13 RLMSs (B group), and 20 postoperative recurrence/metastasis RLMSs (C group) were enrolled. PET/CT features of B group were analyzed. The differences of metabolic parameters between three groups were compared, receiver operating characteristic (ROC) curve analysis was performed to group A and B, and correlation analysis was performed to subgroup B. (1) The RLMS patients were more likely to be female, and PET/CT showed a high degree of heterogeneous metabolism in the soft tissue mass. (2) The standardized uptake value (SUV) of RLMS were significantly higher than those of benign leiomyomas (P < 0.05). The area under the ROC curve was 0.909, the sensitivity and specificity for diagnosing RLMS were 0.923 and 0.750, respectively, The SUVmax and SUVstd of primary RLMS were moderately associated with the Ki67 index. The mean SUVmax in the G1, G2 and G3 subgroups increased successively (4.15 ± 0.35, 6.47 ± 0.83, and 10.13 ± 4.29, respectively). (3) Primary RLMS was characterized by local invasion, but hematogenous metastasis and lymph node metastasis were rare. Postoperative recurrence/metastasis of RLMS was characterized by local recurrence and hematogenous metastasis, but lymph node metastasis was rare. PET/CT has potential value in the preoperative staging, benign and malignant differentiation, malignant degree classification and postoperative follow-up of RLMS.

A compact G2-calibrated manifold with first Betti number b1 = 1

We construct a compact, formal 7-manifold with a closed G2-structure and with first Betti number b1=1, which does not admit any torsion-free G2-structure, that is, it does not admit any G2-structure such that the holonomy group of the associated metric is a subgroup of G2. We also construct associative calibrated (hence volume-minimizing) 3-tori with respect to this closed G2-structure and, for each of those 3-tori, we show a 3-dimensional family of non-trivial associative deformations. We also construct a fibration of our 7-manifold over S2×S1 with generic fiber a (non-calibrated) coassociative 4-torus and some singular fibers.

High Stroma T-Cell Infiltration is Associated with Better Survival in Stage pT1 Bladder Cancer.

Stage pT1 bladder cancer (BC) shows highly diverse outcomes. Predictive markers are required to stratify patients for personalized treatment. The present study aimed to validate immune response quantification as a prognostic marker. Patients with pT1 BC (n = 167) treated by transurethral resection of the bladder (TURB) were enrolled. Formaldehyde-fixed paraffin-embedded material was stained for CD3 and CD8. Corresponding T cells were counted in three regions with the highest immune response. Numbers of tertiary lymphoid structures (TLS) and lymphocyte aggregates (LA) were quantified. High CD3+ stroma T-cell infiltration was associated with improved survival (p = 0.045), especially in the G3 subgroup (p = 0.01). Cluster with higher immune response showed less recurrence (p = 0.034) and favorable overall survival (OS) (p = 0.019). In contrast, higher CD3+ and CD8+ tumor T-cell infiltration seemed to have a negative impact on prognosis. TLS and LA were more frequently observed in G3 tumors, indicating an increased anti-tumoral immune response. We proved the role of immune cell infiltration and showed that higher infiltration numbers of CD3+ (not CD8+) lymphocytes in the stroma are associated with favorable outcome. Immune cell quantification could be used as a marker to help stratify patients’ risk and therefore, to optimize patients’ management and follow-up examination as well as possible therapies.

Trace dynamics and division algebras: towards quantum gravity and unification

Abstract We have recently proposed a Lagrangian in trace dynamics at the Planck scale, for unification of gravitation, Yang–Mills fields, and fermions. Dynamical variables are described by odd-grade (fermionic) and even-grade (bosonic) Grassmann matrices. Evolution takes place in Connes time. At energies much lower than Planck scale, trace dynamics reduces to quantum field theory. In the present paper, we explain that the correct understanding of spin requires us to formulate the theory in 8-D octonionic space. The automorphisms of the octonion algebra, which belong to the smallest exceptional Lie group G 2, replace space-time diffeomorphisms and internal gauge transformations, bringing them under a common unified fold. Building on earlier work by other researchers on division algebras, we propose the Lorentz-weak unification at the Planck scale, the symmetry group being the stabiliser group of the quaternions inside the octonions. This is one of the two maximal sub-groups of G 2, the other one being SU(3), the element preserver group of octonions. This latter group, coupled with U(1) em , describes the electrocolour symmetry, as shown earlier by Furey. We predict a new massless spin one boson (the ‘Lorentz’ boson) which should be looked for in experiments. Our Lagrangian correctly describes three fermion generations, through three copies of the group G 2, embedded in the exceptional Lie group F 4. This is the unification group for the four fundamental interactions, and it also happens to be the automorphism group of the exceptional Jordan algebra. Gravitation is shown to be an emergent classical phenomenon. Although at the Planck scale, there is present a quantised version of the Lorentz symmetry, mediated by the Lorentz boson, we argue that at sub-Planck scales, the self-adjoint part of the octonionic trace dynamics bears a relationship with string theory in 11 dimensions.

Toward a Stakeholder Perspective on Safety Risk Factors of Metro Construction: A Social Network Analysis

The rapid development of the metro has greatly relieved the traffic pressure on the urban ground system, but the frequency of metro construction accidents is also increasing year by year. Due to the complex construction process of the metro, once an accident occurs, casualties and property damage are extremely serious. The safety risk factors triggered by different stakeholders were the primary cause of accidents during the metro construction phase. This paper builts a social analysis network of safety risk factors in metro construction from a stakeholder’s perspective. Based on 42 accident cases and related literature, 6 stakeholders and 25 safety risk factors were identified and the relationships between stakeholders and safety risk factors were also determined. Through the application of social network analysis, a social network of safety risk factors in metro construction was constructed, and quantitative analysis was carried out based on density, degree centrality, betweenness centrality, and cohesive subgroup. The results showed that the key safety risk factors in the construction phase of the metro were in action of the contractor’s construction site managers, lack of safety protection at the construction site, insufficient detailed survey and design information provided by the designer, unfavorable government regulation, and bad weather. Moreover, the results of 20 cohesive subgroups illustrated the interrelationship between safety risk factors. S1H2 (“violations by operatives” related to contractor) and S1H4 (“lack of safety precautions” related to contractor) and S5H5 (“ineffective supervision” related to supervisor) both belonged to subgroup G1, which means that there is a high probability that these three safety risk factors would occur simultaneously. This paper provided a basis to improve the level of safety risk management and control from the stakeholder’s perspective.