bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients
Authors: Capone Mariaelena , Fratangelo Federica , Giannarelli Diana , Sorrentino Claudia , Turiello Roberta , Zanotta Serena , Galati Domenico , Madonna Gabriele , Tuffanelli Marilena , Scarpato Luigi , Grimaldi Antonio M. , Esposito Assunta , Azzaro Rosa , Pinto Antonio , Cavalcanti Ernesta , Pinto Aldo , Morello Silvana , Ascierto Paolo A. 
Published: March 2020

Abstract
Background
PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients.

Methods
PBMCs from 100 melanoma patients treated with nivolumab were collected at National Cancer Institute “G. Pascale” of Naples. Frequencies of CD8+ lymphocytes phenotypes were assessed by flow cytometry at baseline before nivolumab treatment, along with clinical characteristics and blood count parameters. Healthy controls (n = 20) were also analysed. Percentages of baseline T cells expressing PD-1 and CD73 were correlated with outcome after nivolumab treatment.

Results
Melanoma patients presented a lower frequency of total circulating CD8+ lymphocytes than control subjects (p = 0.008). Patients with low baseline percentage of circulating CD8+PD-1+CD73+ lymphocytes (< 2.3%) had better survival (22.4 months vs 6.9 months, p = 0.001). Patients (39%) with clinical benefit from nivolumab therapy presented a significantly lower frequency of circulating CD8+PD-1+CD73+ lymphocytes than patients who progressed to nivolumab treatment (p = 0.02).

Conclusions
Our observations suggest that baseline CD73 expression on circulating CD8+PD-1+ lymphocytes appear a promising biomarker of response to anti-PD-1 treatment in melanoma patients. Further investigations are needed for validation and for clarifying its role as prognostic or predictive marker.
Association between serum HER2/ErbB2 levels and coronary artery disease: a case–control study
Authors: Jian Wen , Wei Chun-Mei , Guan Jia-Hui , Mo Chang-Hua , Xu Yu-Tao , Zheng Wen-Bo , Li Lang , Gui Chun 
Published: March 2020

Abstract
Background
Research has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated.

Methods
We performed a case–control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders.

Results
Overall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13–1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15–1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m2 (OR per 1-SD increase: 2.143, 95% CI 1.37–3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m2 (OR per 1-SD increase: 1.225, 95% CI 0.90–1.67; P = 0.201).

Conclusion
Elevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.
Diagnostic performance of conventional ultrasound and quantitative and qualitative real-time shear wave elastography in musculoskeletal soft tissue tumors
Authors: Li Ao , Peng Xiao-Jing , Ma Qian , Dong Ye , Mao Cui-Lian , Hu Yu 
Published: March 2020

Abstract
Background
To explore the feasibility to identify malignant musculoskeletal soft tissue tumors using real-time shear wave elastography (rtSWE).

Methods
One hundred fifteen musculoskeletal soft tissue tumors in 92 consecutive patients were examined using both conventional ultrasonography (US) and rtSWE. For each patient, the rtSWE parameters including maximum elasticity (Emax), mean elasticity (Emean), minimum elasticity (Emin), standard deviation of the elasticity (Esd), and rtSWE image pattern were obtained. Eighty-one histopathologically confirmed tumors from 73 patients were subjected to analysis.

Results
The 81 lesions included in the study were histopathologically classified as malignant (n = 21) or benign (n = 60). The statistically significant differences between benign and malignant lesions were found in conventional US characters including size, depth, margin, echogenicity, mass texture, and power Doppler signal. Meanwhile, the significant differences were also found in quantitative rtSWE findings including Emax, Emean, Emin, and Esd values and in qualitative rtSWE parameter named rtSWE image pattern. Multivariate analysis showed that infiltrative margin (OR, 4.470), and size (OR, 1.046) were independent predictors for malignancy in US findings, while Esd value (OR, 9.047) was independent predictors for malignancy in quantitative rtSWE parameters. Areas under the ROC curve (Azs) for US features, Esd value, and rtSWE image pattern were 0.851, 0.795, and 0.792, respectively.

Conclusions
Conventional US and quantitative and qualitative rtSWE parameters are useful for malignancy prediction of musculoskeletal soft tissue tumors. rtSWE can be used to supplement conventional US to diagnose musculoskeletal soft tissue tumors.
Synergy at work: linking the metabolism of two lactic acid bacteria to achieve superior production of 2-butanol
Authors: Mar Mette J. , Andersen Joakim M. , Kandasamy Vijayalakshmi , Liu Jianming , Solem Christian , Jensen Peter R. 
Published: March 2020

Abstract
Background
The secondary alcohol 2-butanol has many important applications, e.g., as a solvent. Industrially, it is usually made by sulfuric acid-catalyzed hydration of butenes. Microbial production of 2-butanol has also been attempted, however, with little success as witnessed by the low titers and yields reported. Two important reasons for this, are the growth-hampering effect of 2-butanol on microorganisms, and challenges associated with one of the key enzymes involved in its production, namely diol dehydratase.

Results
We attempt to link the metabolism of an engineered Lactococcus lactis strain, which possesses all enzyme activities required for fermentative production of 2-butanol from glucose, except for diol dehydratase, which acts on meso-2,3-butanediol (mBDO), with that of a Lactobacillus brevis strain which expresses a functional dehydratase natively. We demonstrate growth-coupled production of 2-butanol by the engineered L. lactis strain, when co-cultured with L. brevis. After fine-tuning the co-culture setup, a titer of 80 mM (5.9 g/L) 2-butanol, with a high yield of 0.58 mol/mol is achieved.

Conclusions
Here, we demonstrate that it is possible to link the metabolism of two bacteria to achieve redox-balanced production of 2-butanol. Using a simple co-cultivation setup, we achieved the highest titer and yield from glucose in a single fermentation step ever reported. The data highlight the potential that lies in harnessing microbial synergies for producing valuable compounds.
Prevalence of and risk factors for periodontal disease among pregnant women in an antenatal care clinic in Khartoum, Sudan
Authors: Salih Yasir , Nasr Abubakr M. , Ahmed Abdel B. A. , Sharif Manal E. , Adam Ishag 
Published: March 2020

Abstract
Objectives
The aim was to investigate the prevalence of and factors associated with periodontal disease among pregnant Sudanese women. A cross-sectional study was conducted at the Antenatal Care Clinic of Saad Abualila Hospital (Khartoum, Sudan) from August to October 2018. Socioeconomic-demographic information and reproductive history were gathered using a questionnaire. Body mass index was computed from the weight and height. The diagnosis of periodontal disease was performed using criterion that also evaluated bleeding upon probing.

Results
Four hundred and four women were enrolled in the study, with a mean (SD) gestational age of 30.0 (8.7) weeks. Their mean (SD) age and parity were 27.0 (5.7) years and 1.6 (1.7), respectively. Ninety-seven (24.0%) of these 404 women had periodontal disease, which was mild, moderate and severe in 49 (12.1%), 36 (8.9%) and 12 (3.0%) women respectively, while 307 (76.0%) women had no periodontal disease. In logistic regression, age, parity, education, and brushing were not associated with periodontitis, but lower gestational age was associated with periodontal disease (OR = 0.96, 95% CI 0.94–0.99, P = 0.011).
Genetic modification of the protozoan Eimeria tenella using the CRISPR/Cas9 system
Authors: Tang Xinming , Suo Jingxia , Liang Lin , Duan Chunhui , Hu Dandan , Gu Xiaolong , Yu Yonglan , Liu Xianyong , Cui Shangjin , Suo Xun 
Published: March 2020

AbstractEimeria tenellahas emerged as valuable model organism for studying the biology and immunology of protozoan parasites with the establishment of the reverse genetic manipulation platform. In this report, we described the application of CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (endonuclease) system for efficient genetic editing inE. tenella, and showed that the CRISPR/Cas9 system mediates site-specific double-strand DNA breaks with a single guide RNA. Using this system, we successfully tagged the endogenous microneme protein 2 (EtMic2) by inserting the red fluorescent protein into the C-terminal of EtMic2. Our results extended the utility of the CRISPR/Cas9-mediated genetic modification system toE. tenella, and opened a new avenue for targeted investigation of gene functions in apicomplexan parasites.
Nonexistence of solutions for the quasilinear parabolic differential inequalities with singular potential term and nonlocal source
Authors: Xiao Suping , Fang Zhong Bo 
Published: March 2020

AbstractThis paper is devoted to proving some new nonexistence theorems for a class of quasilinear parabolic differential inequalities with a singular potential term and nonlocal source term in the case of homogeneous and non-homogeneous by the test function method.
Existence and uniqueness of positive solutions for a new class of coupled system via fractional derivatives
Authors: Afshari Hojjat , Sajjadmanesh Mojtaba , Baleanu Dumitru 
Published: March 2020

AbstractIn this paper we study the existence of unique positive solutions for the following coupled system:
$$\begin{aligned} \textstyle\begin{cases} D_{0^{+}}^{\alpha }x(\tau )+f_{1}(\tau ,x(\tau ),D_{0^{+}}^{\eta }x( \tau ))+g_{1}(\tau ,y(\tau ))=0, \\ D_{0^{+}}^{\beta }y(\tau )+f_{2}(\tau ,y(\tau ),D_{0^{+}}^{\gamma }y( \tau ))+g_{2}(\tau ,x(\tau ))=0, \\ \tau \in (0,1),\qquad n-1< \alpha ,\beta < n; \\ x^{(i)}(0)=y^{(i)}(0)=0,\quad i=0,1,2,\ldots ,n-2; \\ [D_{0^{+}}^{\xi }y(\tau ) ]_{\tau =1}=k_{1}(y(1)),\qquad [D_{0^{+}}^{\zeta }x(\tau ) ]_{\tau =1}=k_{2}(x(1)), \end{cases}\displaystyle \end{aligned}$$ {D0+αx(τ)+f1(τ,x(τ),D0+ηx(τ))+g1(τ,y(τ))=0,D0+βy(τ)+f2(τ,y(τ),D0+γy(τ))+g2(τ,x(τ))=0,τ∈(0,1),n−1<α,β<n;x(i)(0)=y(i)(0)=0,i=0,1,2,…,n−2;[D0+ξy(τ)]τ=1=k1(y(1)),[D0+ζx(τ)]τ=1=k2(x(1)), where the integer number $n>3$n>3 and $1\leq \gamma \leq \xi \leq n-2$1≤γ≤ξ≤n−2, $1\leq \eta \leq \zeta \leq n-2$1≤η≤ζ≤n−2, $f_{1},f_{2}:[0,1]\times \mathbb{R^{+}}\times \mathbb{R^{+}} \rightarrow \mathbb{R^{+}}$f1,f2:[0,1]×R+×R+→R+, $g_{1},g_{2}:[0,1]\times \mathbb{R^{+}}\rightarrow \mathbb{R^{+}}$g1,g2:[0,1]×R+→R+ and $k_{1},k_{2}:\mathbb{R^{+}}\rightarrow \mathbb{R^{+}}$k1,k2:R+→R+ are continuous functions, $D_{0^{+}}^{\alpha }$D0+α and $D_{0^{+}}^{\beta }$D0+β stand for the Riemann–Liouville derivatives. An illustrative example is given to show the effectiveness of theoretical results.
Childhood intellectual disability and parents' mental health: integrating social, psychological and genetic influences
Authors: Baker Kate , Devine Rory T. , Ng-Cordell Elise , Raymond F. Lucy ,   IMAGINE-ID consortium, Hughes Claire 
Published: March 2020

BackgroundIntellectual disability has a complex effect on the well-being of affected individuals and their families. Previous research has identified multiple risk and protective factors for parental mental health, including socioeconomic circumstances and child behaviour.AimsThis study explored whether genetic cause of childhood intellectual disability contributes to parental well-being.MethodChildren from across the UK with intellectual disability due to diverse genetic causes were recruited to the IMAGINE-ID study. Primary carers completed the Development and Well-being Assessment, including a measure of parental distress (Everyday Feeling Questionnaire). Genetic diagnoses were broadly categorised into aneuploidy, chromosomal rearrangements, copy number variants (CNVs) and single nucleotide variants.ResultsCompared with the UK general population, IMAGINE-ID parents (n = 888) reported significantly elevated emotional distress (Cohen's d = 0.546). Within-sample variation was related to recent life events and the perceived impact of children's difficulties. Impact was predicted by child age, physical disability, autistic characteristics and other behavioural difficulties. Genetic diagnosis also predicted impact, indirectly influencing parental well-being. Specifically, CNVs were associated with higher impact, not explained by CNV inheritance, neighbourhood deprivation or family structure.ConclusionsThe mental health of parents caring for a child with intellectual disability is influenced by child and family factors, converging on parental appraisal of impact. We found that genetic aetiologies, broadly categorised, also influence impact and thereby family risks. Recognition of these risk factors could improve access to support for parents, reduce their long-term mental health needs and improve well-being of individuals with intellectual disability.
How well do we communicate risk? An evaluation of AJCC version 6 and 7 staging systems for soft tissue sarcomas.
Authors: Maki Robert G. , Antonescu Cristina R. , Hameed Meera , Moraco Nicole H. , Singer Samuel , Brennan Murray F. 
Published: March 2020

10001 Background: Cancer staging systems allow physicians to communicate risks of a particular clinical situation with one another and with patients. Few data have been presented to support the update of a commonly employed staging system for soft tissue sarcoma (STS). We examined American Joint Committee on Cancer (AJCC) versions 6 (2002) and 7 (2010) staging systems for patients with primary STS using a single institution clinically annotated prospective database. Methods: Subsets of the prospectively collected Memorial Sloan-Kettering Cancer Center STS database of 8647 patients from 1982 to 2010 were examined with respect to criteria of the AJCC versions 6 and 7 staging systems. Results: Tumor size does not appear to be adequately addressed in version 6 or 7. Relapse-free survival was statistically worse for increasing size of primary STS <5, 5-10, 10-15, and >15 cm; in comparison, overall survival decreased over three size categories (<5, 5-10, >10 cm). Tumor depth, a statistically significant factor in patient outcomes that is included in version 6, is functionally omitted in version 7. Patients with node involvement without other metastases fare statistically worse than patients with large, high grade tumors without nodal metastasis, as shown previously. Version 6 and 7 criteria do not address effects of primary anatomic site and histology, even for tumors with same FNCLCC grade. Sarcoma subtypes defined after publication of FNCLCC criteria are difficult to incorporate into existing guidelines. Conclusions: Improved prognostication of STS outcomes is better achieved by staging according to anatomic primary site, depth, and a larger number of size categories. Histology-specific nomograms improve prognostic accuracy, such as those for liposarcoma, GIST, or rhabdomyosarcoma. Staging accuracy increases at the cost of portability and simplicity. The increasing difficulties with use of a single STS staging system highlight the potential benefit of newer techniques, such as patient-specific nomograms or Bayesian networks. Staging systems will require significant modifications to incorporate increasingly sophisticated molecular diagnostics.
An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment.
Authors: Ray-Coquard Isabelle , Gelderblom Hans , Chevreau Christine , Kroep Judith R. , Italiano Antoine , Stacchiotti Silvia , Le Cesne Axel , Piperno-Neumann Sophie , Ferraresi Virginia , Duffaud Florence , Penel Nicolas , Cassier Philippe A , Tatersall Martin , Hassan Andrew Bassim , Bui Nguyen Binh , Bourne Branchu Veronique , Guillemaut Severine , Cropet Claire , Perol David , Blay Jean-Yves 
Published: March 2020

10006 Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare pathological entity affecting the synovium in young adults. This neoplastic disease is driven by a t(1;2) translocation which results in the fusion of COL6A3 and M-CSF genes. Nilotinib has inhibitory properties on M-CSF receptor pathway which could be of therapeutic interest in pts with non resectable PVNS. Methods: In this open-label International, multicenter, non-randomized, phase II study the primary objective is to evaluate the efficacy of nilotinib treatment in patients (pts) with progressive or relapsing PVNS not amenable to surgery or in whom surgery would be mutilating, as measured by the 12-week progression-free rate (12-w PFR) validated by an independent committee. Using a Bayesian design with a stopping rule for futility, interim analyses were planned after the inclusion of 10 pts and then every 5 pts. Results: From December 2010 to November 2011, 33 pts with progressive disease from 17 institutions from Europe and Australia were enrolled. 14 pts (median age 37 y (range: 19-68), 7 males) were analyzed in the 2nd interim analysis. Median time since diagnosis was 4.4 years (range: 0.2-26). Primary tumour was located on a knee for 10 pts (71%) and on hip (1 pt, 7%), finger (7%), foot (7%), hand (7%), respectively. 69% of pts had a inoperable PVNS and 31% had a resectable tumour but requiring mutilating surgery. All pts started nilotinib at the planned dose of 800 mg/day. At a median follow-up of 8.9 months (range: 0.6-11), 2 pts had a dose reduction and 1 pt had discontinued nilotinib after 14 days due to toxicity. Nilotinib was well tolerated, with only 2 pts experiencing grade 3 adverse events (anorexia: 1 pt; hepatic failure: 1 pt).The 12-w PFR was 85.7% (95%CI, 57.2%-98.2%), in favour of the study continuation. No OR was observed at w-12; 1 pt (7%) was in PR at w-30. Updated results will be presented after the 3rd interim analysis. Conclusions: Nilotinib treatment induces disease stabilisation in a large proportion of PVNS patients with non resectable disease or in whom resection would be mutilating.
PALETTE: Final overall survival (OS) data and predictive factors for OS of EORTC 62072/GSK VEG110727, a randomized double-blind phase III trial of pazopanib versus placebo in advanced soft tissue sarcoma (STS) patients.
Authors: Van Der Graaf Winette T.A. , Blay Jean-Yves , Chawla Sant P. , Kim Dong-Wan , Bui Nguyen Binh , Casali Paolo Giovanni , Schoffski Patrick , Aglietta Massimo , Staddon Arthur P. , Beppu Yasuo , Le Cesne Axel , Gelderblom Hans , Judson Ian Robert , Araki Nobuhito , Ouali Monia , Marreaud Sandrine , Hodge Rachel , Dewji Mohamedraza , Dei Tos Angelo Paolo , Hohenberger Peter 
Published: March 2020

10009 Background: At ASCO 2011 we presented an increase in median progression-free survival (PFS) of pazopanib of 13 weeks (median 7 to 20 weeks; HR 0.31) in a randomized double-blind, placebo-controlled phase III trial in advanced non-adipocytic STS patients pretreated with chemotherapy. Now we present final OS data and predictive factors for OS, such as ethnicity, ancestry and well-known prognostic and predictive factors in STS patients treated with chemotherapy. Methods: At clinical cut-off median follow-up was 25 months. Comparison of both treatments for OS was performed using a two-sided log rank test stratified for number of prior lines of systemic therapy for advanced disease and WHO performance status (PS). HR was calculated with a 2-sided CI. A Kaplan-Meier OS curve was used. Baseline characteristics as potential predictive factors for OS were: PS (0 vs 1), number of lines of prior therapy for advanced disease (0-1 vs 2+), age (≤55 yrs vs > 55 yrs), gender, ethnicity (Hispano or Latino vs other), geographic ancestry (White Caucasian, Asian, other), tumour grade (1-2 vs 3), histology (leiomyosarcoma vs synovial sarcoma vs other). A Cox model was fitted with the investigated factor, treatment arm and associated interaction factor. Data of all 369 randomized patients (123 placebo, 246 pazopanib) were used for the analyses. Results: Median OS (95% CI) was 10.7 (8.7-12.8) in the placebo versus 12.5 (10.6-14.8) months in the pazopanib group, HR: 0.86 (0.67-1.1). Post study protocol systemic treatment was administered in 63% of placebo, and in 49% of pazopanib treated patients. None of the investigated factors showed any statistical significant predictive value for OS. Conclusions: Although pazopanib demonstrated a statically significant increase in PFS compared to placebo, final OS analysis, which showed a trend in favor of pazopanib in patients with metastatic non-adipocytic STS, did not reach statistical significance. The factors studied were not predictive for OS.