bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobilizing and chasing: The voter targeting of negative campaigning – lessons from the Swiss case
Authors: Stuckelberger Simon
Published: May 2019

There are two targeting objectives for an election campaign: mobilizing core voters and chasing undecided voters. According to most previous research, negative campaigning exclusively fulfils a chasing function; parties use it to convince swing voters. The article argues that parties consider the mobilization of core voters as a second important function of negative campaigning. It is based on interviews with party campaign officials and a content analysis of election newspaper advertisements and press releases from the 2011 and 2015 Swiss National Council elections. The interviews and the analysis of parties’ attack behaviour show that parties use negative campaigning for mobilizing purposes, and in the analysed Swiss elections, it seems to be a more popular strategy than chasing.
Integrated telerehabilitation approach in multiple sclerosis: A systematic review and meta-analysis
Authors: Di Tella Sonia , Pagliari Chiara , Blasi Valeria , Mendozzi Laura , Rovaris Marco , Baglio Francesca
Published: May 2019

Introduction

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system and a major cause of disability in young adults. Recently, there has been a growing interest in the development of innovative ways to deliver rehabilitation care outside of a hospital setting. The aim was to conduct a systematic review and a meta-analysis of the efficacy of an integrated telerehabilitation approach (ITA) on motor, cognitive and participation outcomes delivered to people with MS (pwMS).

Methods

We systematically searched for original manuscripts regarding ITA in pwMS. Efficacy on motor, cognitive and participation outcomes was measured as the standardized mean difference (Hedges' g) of pre and post training.

Results

Nine studies encompassing 716 pwMS diagnosis were included. The overall effect of ITA was: large for motor outcomes (g = 1.05; p = 0.013); small for cognitive performance outcomes (g = 0.16; p = 0.237); and small for participation outcomes (g = 0.15; p = 0.259). Domain-specific results showed that the effect on motor disability was large ( g = 1.18), while on gait and balance was medium ( g = 0.32 and g = 0.48, respectively). Moreover, all effects on single cognitive domains were small. Finally, among the single participation outcomes considered (depression, fatigue, daily functioning, quality of life and self-efficacy) only depression showed a nearly medium effect (g = 0.30).

Conclusions

PwMS can benefit from ITA in the treatment of motor symptoms according to the current model of continuity of care. However, the low efficacy of ITA on cognition and participation domains suggests the necessity to develop intervention models that include a broader spectrum of needs and objectives.
Human papillomavirus vaccination and respect for children’s developing autonomy: Results from a European Union wide study
Authors: Martakis Kyriakos , Alexander Denise , Schloemer Tamara , Blair Mitch , Rigby Michael , Schröder-Bäck Peter
Published: May 2019

Children’s rights to autonomy of choice are differently expressed throughout Europe. We explored differences regarding expressions of respect for children’s autonomy throughout Europe, using the procedure of human papillomavirus (HPV) vaccination offer as indicator. We used a mixed methods approach, utilizing an expert survey within the frame of “Models of Child Health Appraised” (MOCHA), among all 30 European Union (EU) and European Economic Area states. A questionnaire was designed using vignettes regarding the vaccine provision. Thirty MOCHA country agents were invited to respond from June 2017 to April 2018. In total, 28 country agents responded. We studied the following themes: (i) provision of informed consent, (ii) parental and medical paternalism, (iii) relevance of the child’s chronological age or maturity, and (iv) vaccination programs targeting boys. These are being handled differently across the region. We explored associations of these implemented practices with the national vaccine coverage rate across Europe. We used the processes of HPV vaccination to study child’s autonomy, the paradigm change toward libertarian paternalism and issues of sex-equity. Interestingly, greater respect for children’s autonomy tends to be associated with medium or high vaccination coverage rates and lower respect with lower rates. Respect and empowerment seem to have practical as well as moral benefits. Identifying and transferring the most suitable ethical approaches is crucial and should be strengthened.
Faster multi-defect detection system in shield tunnel using combination of FCN and faster RCNN
Authors: Gao Xinwen , Jian Ming , Hu Min , Tanniru Mohan , Li Shuaiqing
Published: May 2019

With the large-scale construction of urban subways, the detection of tunnel defects becomes particularly important. Due to the complexity of tunnel environment, it is difficult for traditional tunnel defect detection algorithms to detect such defects quickly and accurately. This article presents a deep learning FCN-RCNN model that can detect multiple tunnel defects quickly and accurately. The algorithm uses a Faster RCNN algorithm, Adaptive Border ROI boundary layer and a three-layer structure of the FCN algorithm. The Adaptive Border ROI boundary layer is used to reduce data set redundancy and difficulties in identifying interference during data set creation. The algorithm is compared with single FCN algorithm with no Adaptive Border ROI for different defect types. The results show that our defect detection algorithm not only addresses interference due to segment patching, pipeline smears and obstruction but also the false detection rate decreases from 0.371, 0.285, 0.307 to 0.0502, respectively. Finally, corrected by cylindrical projection model, the false detection rate is further reduced from 0.0502 to 0.0190 and the identification accuracy of water leakage defects is improved.
Effects of ATP administration on isolated swine hearts: Implications for ex vivo perfusion and cardiac transplantation
Authors: Seewald Maria S , Gaasedelen Erik N , Iles Tinen L , Mattison Lars M , Mattson Alexander R , Schmidt Megan M , Braun-Dullaeus Ruediger C , Iaizzo Paul A
Published: May 2019

Cardiac transplant outcomes can be compromised by the effects of global ischemia and associated reperfusion injury. In attempts to alleviate these phenomena, various pharmaceutical agents can be administered. Previous reports have shown that adenosine triphosphate (ATP) may act as either a postconditioning (PoC) or supplementary (Sup) therapy with cardiosupportive benefits. To further evaluate ATP’s relative effectiveness, we used an isolated swine heart four-chamber working model to monitor both hemodynamic and metabolic responses. We employed two strategies of ATP administration: (1) a postconditional (PoC) bolus just prior to reanimation, and (2) regular dosing throughout the assessment period (Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h monitoring period than controls. In contrast, PoC administration appeared to induce depressed cardiac function. The effects of ATP on cardiac function can have varied effects, dependent on when it is administered.

Impact statement

We employed an isolated swine heart four-chamber working model to investigate two potential strategies for adenosine triphosphate (ATP) administration as an ex vivo therapy: (1) application of a single bolus dose during reperfusion (postconditioning or PoC), and (2) repeated bolus dosing throughout the experiment (supplementary or Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h experimental monitoring period. In contrast, ATP administration in the PoC group appeared to induce a degree of depressed hemodynamic function. These data suggest varied functional roles of ATP administration relative to their use in ex vivo perfusion strategies. We consider that both treatment strategies, if appropriately administered and with further investigation of dosing paradigms, may eventually elicit value in various clinical scenarios, including heart transplantation and ex vivo heart perfusion to assess potential organs for transplantation and potentially increase the pool of viable donor hearts.
Stenting of symptomatic lateral sinus thrombosis refractory to mechanical thrombectomy
Authors: Lu Guangdong , Shin Jae Ho , Song Yunsun , Lee Deok Hee
Published: May 2019

Objective

Endovascular mechanical thrombectomy for the treatment of cerebral venous sinus thrombosis is not always successful. We present our experience of using self-expanding stents to facilitate effective recanalization of persistent lateral sinus thrombosis refractory to endovascular mechanical thrombectomy.

Methods

Data from patients who underwent endovascular mechanical thrombectomy for the treatment of acute symptomatic cerebral venous sinus thrombosis between August 2015 and July 2018 were evaluated. Patient demographics, procedural techniques, devices used and follow-up outcomes were assessed.

Results

A total of 14 patients underwent endovascular mechanical thrombectomy during the study period. Of these, stenting of the occluded sinus was performed in five patients with extensive sinus thrombosis after conventional endovascular mechanical thrombectomy. Three of the five patients had a variable degree of venous infarction and/or hemorrhage before treatment. The target lesion was located in the right lateral sinus in all five patients. Due to the length of the involved sinus, two stents were required in one patient and three stents in two patients. The only procedure-related complication was an asymptomatic tearing of the sinus wall in one patient. Stent patency could not be maintained in two patients due to stent buckling within the jugular foramen segment and an inability to maintain antiplatelet medication. Modified Rankin Scale scores at 2–16 months were zero in two patients, one in two patients, and five in one patient.

Conclusions

Stenting for the thrombotic occlusion of the lateral sinus is a feasible rescue method to overcome unsuccessful endovascular mechanical thrombectomy. However, currently available stenting systems may be unsuitable for use in the intracranial dural sinus system.
A preoperative predictive model for prolonged post-anaesthesia care unit stay after outpatient surgeries
Authors: Elsharydah Ahmad , Walters Daren R , Somasundaram Alwin , Bryson Trenton D , Minhajuddin Abu , Gabriel Rodney A , Grewal Gaganpreet K
Published: May 2019

Study objective

To create a preoperative predictive model for prolonged post-anaesthesia care unit (PACU) stay for outpatient surgery and compare with an existing (University of California-San Diego, UCSD) model.

Design

Retrospective observational study.

Setting

Post-anaesthesia care unit. Patients: Outpatient surgical patients discharged on the same day in a large academic institution. Preoperative data were collected. The study period was three months in 2016. Measurements: Prolonged PACU stay defined as a length of stay longer than the third quartile. We utilized multivariate regression analyses and bootstrapping statistical techniques to create a predictive model for prolonged PACU stay. Main results: Four strong predictors for prolonged PACU stay: general anaesthesia, obstructive sleep apnoea, surgical specialty and scheduled case duration. Our model had an excellent discrimination performance and a good calibration.

Conclusion

We developed a predictive model for prolonged PACU stay in our institution. This model is different from the UCSD model probably secondary to local and regional differences in outpatient surgery practice. Therefore, individual practice study outcomes may not apply to other practices without careful consideration of these differences.
Triterpenic Acid Content and Cytotoxicity of Some Salvia Species From Iran
Authors: Abdollahi-Ghehi Hoda , Sonboli Ali , Ebrahimi Samad Nejad , Esmaeili Mohammad Ali , Mirjalili Mohammad Hossein
Published: May 2019

For prosperous domestication, breeding, and cultivation of a herbal species, it is important to screen its medicinally valuable compounds as well as its referred biological activity. Salvia L. species (Lamiaceae), distributed throughout the world, contain a wide range of secondary metabolites including terpenoids and phenolic derivatives. Betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) are highly valuable triterpenic acids (TAs) because of their wide range of biological activities. The objective of the present work was to evaluate the BA, OA, and UA contents among 22 Salvia species native to Iran. TA content in the studied Salvia species was compared with that in Salvia officinalis as a commercial species. High-performance liquid chromatography with photodiode array detector results showed that the maximum content of BA (3.12 ± 0.03 mg/g dry weight [DW]) and OA (1.96 ± 0.05 mg/g DW) was determined in Salvia multicaulis. The highest content of UA (4.34 ± 0.1 mg/g DW) was quantified in S. officinalis L. followed by S. multicaulis (3.71 ± 0.08 mg/g DW). Salvia multicaulis exhibited significantly higher agro-morphological values than S. officinalis in traits related to plant width, leaf length, internode length, and inflorescence length. The cytotoxicities of both species were determined against human cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The methanolic extract of S. multicaulis and S. officinalis showed cytotoxic effects against SH-SY5Y and MCF-7 cell lines, respectively. Both species were equally cytotoxic against the HL-60 cell line. This study provides scope for the selection of high-yielding species and genetic improvement through breeding and biotechnological programs in the future.
High-Resolution Structural Studies Elucidate Antiatherogenic and Anti-Inflammatory Properties of Peptides Designed to Mimic Amphipathic α-Helical Domains of Apolipoprotein A-I
Authors: Mishra Vinod K. , Anantharamaiah Gattadahalli M.
Published: May 2019

Peptides designed to mimic the antiatherogenic and anti-inflammatory properties of apolipoprotein A-I show that although lipid association is required, not all lipid-associating peptides exhibit these properties. Our studies of a series of peptides showed that peptides with aromatic residues at the center of the nonpolar face were able to interact with inflammatory lipids and inhibited inflammation, which resulted in the amelioration of several lipid-mediated disorders such as lesion development, tumor formation, and Alzheimer’s plaque formation. The p K a values determined using 13C nuclear magnetic resonance (NMR) spectroscopy of K residues located at the polar-nonpolar interface provided the first clue to the relative orientations of the peptide helices with respect to each other and around the edge of the lipid discoidal complexes. High-resolution 1H-NMR studies of peptide-lipid discoidal complex confirmed the amphipathic α-helical structure of the peptide, location of aromatic residues of the peptide closer to the polar-nonpolar interface, and head-to-tail arrangement of the peptide helices around the edge of the disc. Amphipathic α-helical structure and the location of aromatic residues (F, W, Y) closer to the polar-nonpolar interface in a lipid environment allow the peptide to strongly bind oxidized lipids resulting in its anti-inflammatory properties.
Effect of Toxic Metal Binding on Tax-Interacting Protein1 (TIP1): A Protein Related to Brain Diseases
Authors: Chaudhary Bharat P. , Dahal Salik R. , Sayania Bhavendrasinh , Kumar Amit , Mohanty Smita
Published: May 2019

Human tax-interacting protein1 (TIP1), also known as glutaminase-interacting protein (GIP), is a small globular protein containing a PDZ domain. PDZ domains are the most common protein-protein interaction modules present in eukaryotes. In humans, TIP1 plays a very important role in many cellular pathways including β-catenin-mediated Wnt signaling, Rho-activator rhotekin-mediated Rho signaling pathway, and glutamate signaling pathway for the normal activity of the central nervous system. TIP1 also regulates potassium channel expression in the plasma membrane and is a binding partner to many proteins including viral oncoproteins, HTLV-1 Tax and HPV16 E6. Since TIP1 is at a pivotal point in many cellular processes through its interaction with a growing list of partner proteins, any impact on the proper functioning of this protein can have severe consequences on the well-being of a living system. Although metals are essential for plants and animals in trace amounts, elevated levels of heavy metals such as arsenic, cadmium, zinc, and lead are toxic causing various health problems including cardiovascular disorders, neuronal damage, renal injuries, and cancer. Here, we report the effect of heavy metals, arsenic and cadmium, on TIP1 conformation using circular dichroism and fluorescence spectroscopy techniques. Our study revealed these metals have a significant impact on the structure of TIP1 even at very low levels.
HIV-1 Virus Interactions With Host Proteins: Interaction of the N-terminal Domain of the HIV-1 Capsid Protein With Human Calmodulin
Authors: Tzou Ywh-Min , Shin Ronald , Rama Krishna N.
Published: May 2019

The human immunodeficiency virus (HIV-1 virus) exploits several host factors for assembly, infection, and replication within the infected cells. In this work, we describe the evidence for an interaction of the N-terminal domain of the HIV-1 capsid protein with human calmodulin. The precise role of this interaction within the life cycle of the HIV-1 virus is yet to be defined. Potential roles for this interaction in the viral capsid uncoating are discussed.
Enantiodiscrimination Using a Chiral Crown Ether as a Chiral Solvating Agent Using NMR Spectroscopy
Authors: Lee Wonjae , Bang Eunjung , Yun Ji-Hye , Paik Man-Jeong , Lee Weontae
Published: May 2019

For enantiomer separation of a variety of chiral compounds, a number of chiral selectors have been developed and applied. Among these chiral selectors are chiral crown ethers, a class of synthetic polyether molecules that bind protonated chiral primary amines with high selectivity. This article focuses on enantiodiscrimination using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a crown ether-type chiral solvating agent for nuclear magnetic resonance spectroscopic method in several chirotechnologies.
Peptidoglycan Recognition by Wheat Germ Agglutinin. A View by NMR
Authors: Biari Khouzaima el , Gaudioso Ángel , Fernández-Alonso M. Carmen , Jiménez-Barbero Jesús , Cañada F. Javier
Published: May 2019

Wheat germ agglutinin (WGA) is a lectin composed of 4 homologous hevein domains. It has been shown that WGA binds N-acetyl glucosamine (GlcNAc)-related oligosaccharides and has applications as commercial reagent to detect glycans containing such modified residues. Peptidoglycan (PGN), the main component of the bacterial cell wall, is a polymeric material made of repeating disaccharide units of GlcNAc- N-acetylmuramic acid cross-linked with short polypeptide fragments. Wheat germ agglutinin is able to bind bacterial cells, a phenomenon that could correlate with its plant-defense capacities, but there is no information at the molecular level about how WGA binds to the PGN. Herein, we present structural data on the binding of a short PGN fragment to WGA by means of saturation transfer difference nuclear magnetic resonance studies. The results show that the GlcNAc residue establishes the major contacts with WGA, followed by the N-acetylmuramic acid residue. In contrast, the peptide moiety displays minor contacts at the binding site.
Abietane Diterpenoids With Potent Cytotoxic Activities From the Resins of Populus euphratica
Authors: Cao Qian , Wang Shao-Xiang , Cheng Yong-Xian
Published: May 2019

A new abietane norditerpenoid, 5-(6-isopropyl-2-methylnaphthalen-1-yl)pentan-2-one (1), with a rare 4,5-seco-19-norabietane skeleton possessing a rearranged angular methyl group at C-5, 2 new naturally occurring compounds, 19-norabieta-4,6,8,11,13-penttaen-3-one (2) and 14-hydroxy-7-oxo ester (3), along with 10 known analogs (4−13) were isolated from the resins of Populus euphratica. The new structures were elucidated by spectroscopic analysis (one-/two-dimensional nuclear magnetic resonance and high-reolution electrospray ionization mass spectrometry). Biological evaluation showed that compounds 1 and 2 display low cytotoxicity against normal cells and appreciable cytotoxicity in cancer cells, with 2 to be more sensitive in HepG2 cells with a half-maximal inhibitory concentration value of 27.0 μM.
Isocoumarins and Dihydroisocoumarins From the Endophytic Fungus Biscogniauxia capnodes Isolated From the Fruits of Averrhoa carambola
Authors: Sritharan Thulasi , Savitri Kumar N. , Jayasinghe Lalith , Araya Hiroshi , Fujimoto Yoshinori
Published: May 2019

An endophytic fungus Biscogniauxia capnodes was isolated from a popular edible fruit Averrhoa carambola. The fungus was fermented in potato dextrose broth for 3 weeks, and then the culture broth and mycelium were extracted with ethyl acetate. Chromatographic separation of this extract furnished 2 isocoumarins, reticulol (1) and 6- O-methyl-reticulol (2), and 2 dihydroisocoumarins, 5-methylmellein (3) and 7-hydroxy-5-methylmellein (4). Compound 1 showed moderate antioxidant activity against 2,2′-diphenyl-1-picrylhydrazyl radicals (IC50 value, 58 μg/mL). This is the first report of the isolation of B. capnodes as an endophyte, as well as the compounds 1 to 4 from B. capnodes.
Postoperative Lyme Arthritis in the Orthopaedic Patient
Authors: Hess Matthew C. , Devilbiss Zachary , Ho Garry Wai Keung , Thal Raymond
Published: May 2019

Context:

Lyme disease is the most common tick-borne illness in North America and Europe, and Lyme arthritis is a frequent late-stage manifestation in the United States. However, Lyme arthritis has rarely been reported as a postoperative complication.

Evidence Acquisition:

The PubMed database was queried through June 2018, and restricted to the English language, in search of relevant articles.

Study Design:

Clinical review.

Level of Evidence:

Level 3.

Results:

A total of 5 cases of Lyme arthritis as a postoperative complication have been reported in the literature.

Conclusion:

These cases highlight the importance for providers practicing in Lyme-endemic regions to keep such an infection in mind when evaluating postoperative joint pain and swelling. We propose herein an algorithm for the workup of potential postoperative Lyme arthritis.

Strength of Recommendation Taxonomy (SORT):

C
Interview with Professor Meira Levinson: Democracy, dilemmas and educational ethics
Authors: Forster Daniella J , McPherson Amy , Douglas Samuel
Published: May 2019

In the following interview, Meira Levinson (Harvard Graduate School) discusses the field of educational ethics and how it can enhance justifiable youth activism to enact citizenship education and recover democracy. She introduces readers to her philosophical approach for developing normative case studies that aim to be inclusive of divergent views on knowledge and value in schooling. Professor Levinson visited the School of Education at the University of Newcastle, Australia, in August 2018, to advise the Educational Ethics: Dilemmas of Diversity Network project team. During her visit she discussed with local teachers and school leaders about how educational practices can ethically address differences, diversities and decision-making in pluralist democracies.
Colonic malignant peripheral nerve sheath tumour in a cat
Authors: Boland Lara , Setyo Laura , Sangster Cheryl , Brunel Laurencie , Foo Timothy , Bennett Peter
Published: May 2019

Case summary

A 14-year-old male neutered domestic mediumhair cat presented with a 4 month history of inappetence and weight loss. Pertinent abnormalities on haematology and biochemistry included a mild microcytic regenerative anaemia (packed cell volume [PCV] 24% [reference interval (RI) 30–45%], mean cell volume 30.8 fl [RI 40–45 fl], absolute reticulocyte count 326.8 × 1012) and increased alkaline phosphatase activity (76 IU/l; RI <50 IU/l). Abdominal ultrasound and CT scan revealed masses in the transverse colon (2.0 cm × 1.2 cm) and right medial liver lobe (5.0 cm diameter). Thoracic radiographs were unremarkable. Right medial liver lobe resection and colectomy were performed. Immunohistochemistry was positive for S-100 protein, vimentin and glial fibrillary acidic protein, very weakly positive for c-kit and negative for muscle-specific actin and CD18, consistent with a colonic malignant peripheral nerve sheath tumour (MPNST) with a hepatic metastasis. Postoperative treatment with metronomic cyclophosphamide was well tolerated. Eighteen months postoperatively the cat re-presented after 3 days of progressive lethargy and inappetence. Haematology revealed a marked non- or pre-regenerative anaemia (PCV 10%). Coagulation times were prolonged (prothrombin time 39 s [RI 15–22 s] and activated partial thromboplastin time >300 s [RI 65–119 s]). Abdominal ultrasound identified multiple renal and hepatic nodules. Euthanasia was performed and post-mortem examination confirmed metastasis of the MPNST.

Relevance and novel information

This report describes the treatment of a metastatic colonic peripheral nerve sheath tumour in a cat. Feline visceral MPNSTs are rare and little is known about prognosis or optimal treatment.
Linking Employer Brand Image and Work Engagement: Modelling Organizational Identification and Trust in Organization as Mediators
Authors: Kashyap Vaneet , Chaudhary Richa
Published: May 2019

Based on the theories of resource-based view, social exchange, social identity and social information processing, the current research propounds a model that investigates the role an employer’s brand image plays in influencing organizational identification, trust in organizations and work engagement. Data were collected from 508 employees serving in Indian public and private sector companies. Hypotheses were tested using regression analyses. Results suggest that work engagement is influenced directly by employer brand image, as well as indirectly through trust in organizations and organizational identification (mediators). Thus, it is logical that if an organization creates and maintains a unique employer brand image, then employees’ identification and trust with organizations would likely to increase and impact work engagement. Implications for theory and practice are discussed in this article.
Autologous Chondrocyte Implantation “Segmental-Sandwich” Technique for Deep Osteochondral Defects in the Knee: Clinical Outcomes and Correlation With Magnetic Resonance Imaging Findings
Authors: Ogura Takahiro , Merkely Gergo , Bryant Tim , Winalski Carl S. , Minas Tom
Published: May 2019

Background:

Symptomatic osteochondral defects are difficult to manage, especially in patients with deep (>8-10 mm) empty defects. The restoration of articular congruence is crucial to avoid the progression to osteoarthritis (OA).

Purpose:

To describe the autologous chondrocyte implantation (ACI) “segmental-sandwich” technique for restoration of the osteochondral unit and to evaluate midterm outcomes in patients treated with this procedure. Correlations between magnetic resonance imaging (MRI) and radiographic findings with outcomes were assessed.

Study Design:

Case series; Level of evidence, 4.

Methods:

Outcomes were evaluated for a consecutive cohort of 15 patients with symptomatic deep (>8 mm) osteochondral lesions who underwent autologous bone grafting plus the ACI segmental-sandwich technique performed by a single surgeon between 2003 and 2011. Patients with a minimum 2-year follow-up were included. All patients completed validated clinical outcome scales and a patient satisfaction survey. The Kellgren-Lawrence (K-L) grade was assessed for the progression to OA. The repair site was evaluated with the MOCART (magnetic resonance observation of cartilage repair tissue) score. Filling and tissue characteristics of the bone defect were analyzed with MRI.

Results:

All patients (mean age at surgery, 31.0 ± 9.1 years) were available for follow-up (mean follow-up, 7.8 ± 3.0 years; range, 2-15 years). The mean chondral lesion size was 6.0 ± 3.5 cm2 (range, 1.5-13.5 cm2), with a mean bone defect area of 1.7 cm2 (27%-40% of overall surface area treated by ACI) and depth of 1.0 cm. All patients had successful clinical outcomes, and all functional scores improved significantly ( P < .05). Patients reported a very high satisfaction rate (93%). The K-L grade demonstrated no significant progression to OA over a mean follow-up of 4.7 years. For 12 patients with MRI results available, the mean MOCART score at a mean of 3.3 years was 64.2 ± 19.9, with complete or near-complete (≥75% of defect volume) chondral defect filling (83%) and complete integration to adjacent cartilage (83%). Bone defects were completely filled in 83% of patients.

Conclusion:

The ACI segmental-sandwich technique provides significant functional improvements at midterm follow-up and excellent survival rates. This unique treatment allows for the resurfacing of cartilage defects and the repair of underlying segmental bone lesions.
A Systematic Review and Meta-Analysis of Prostate Cancer Utility Values of Patients and Partners Between 2007 and 2016
Authors: Magnus Anne , Isaranuwatchai Wanrudee , Mihalopoulos Cathrine , Brown Victoria , Carter Rob
Published: May 2019

Background. There is widespread agreement that both the length and quality of life matter when assessing new technologies and/or models of care in the treatment for cancer patients. Quality of life for partners/carers also matters, particularly for prostate cancer. Purpose. This systematic review aims to provide up-to-date utility values along the prostate cancer care continuum (i.e., from prescreening through to palliative care) for use where future trial-based or modelled economic evaluations cannot collect primary data from men and/or partners. Data Sources. A protocol was developed and registered on the international register of systematic reviews—PROSPERO. Databases searched included EBSCO Information Services (CINAHL, EconLit, Global Health, HEED, MEDLINE Complete, PsycINFO), Cochrane Database of Systematic Reviews, Web of Science, and Embase. Study Selection. Study selection terms included health-related quality of life, prostate cancer, and partners or carers. Data Extraction. The authors identified articles published between 2007 and 2016 that provided health state utility values, with statistical uncertainty, for men with or at risk of prostate cancer and/or their partner/carers. Data Synthesis and Results. Study quality and generalizability of utilities was evaluated and meta-analysis conducted against prespecified criteria. From 906 original articles, 29 recent primary studies met the inclusion/exclusion criteria. We tabulate all the utility values with uncertainty, along with considerable methodological detail and patient population characteristics. Limitations. Utility values pertaining to carers/partners were limited to one study. Conclusions. Studies varied in design, measurement instruments utilized, quality, and generalizability. There is sufficient qualitative and quantitative detail for the reported utility values to be readily incorporated into economic evaluations. More research is needed with carers/partners and with newly developing prostate cancer-specific quality of life tools.
Plasma metabolomic profiling of proliferative diabetic retinopathy
Authors: Zhu Xiao-Rong , Yang Fang-yuan , Lu Jing , Zhang Hui-rong , Sun Ran , Zhou Jian-Bo , Yang Jin-Kui
Published: May 2019

Background

Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy.

Methods

A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS).

Results

The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively.

Conclusions

This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy.
RETRACTED ARTICLE: Exosomes from the tumour-adipocyte interplay stimulate beige/brown differentiation and reprogram metabolism in stromal adipocytes to promote tumour progression
Authors: Wu Qi , Li Juanjuan , Li Zhiyu , Sun Si , Zhu Shan , Wang Lijun , Wu Juan , Yuan Jingping , Zhang Yimin , Sun Shengrong , Wang Changhua
Published: May 2019

Background

Emerging evidence supports the pivotal roles of adipocytes in breast cancer progression. Tumour induced beige/brown adipose tissue differentiation contributes to the hypermetabolic state of the breast cancer. However, the mediators and mechanisms remain unclear.

Methods

Survival probabilities were estimated using the Kaplan–Meier method based on immunohistochemistry results. Biochemical studies were performed to characterize the novel interrelation between breast cancer cells and adipocytes.

Results

We show that tumour-surrounding adipocytes exhibit an altered phenotype in terms of upregulated beige/brown characteristics and increased catabolism associated with an activated state characterized by the release of metabolites, including free fatty acids, pyruvate, lactate and ketone bodies. Likewise, tumour cells cocultivated with mature adipocytes exhibit metabolic adaptation and an aggressive phenotype in vitro and in vivo. Mechanistically, we show that tumour cells induce beige/brown differentiation and remodel metabolism in resident adipocytes by exosomes from the co-culture system that carry high levels of miRNA-144 and miRNA-126. miRNA-144 promotes beige/brown adipocyte characteristics by downregulating the MAP3K8/ERK1/2/PPARγ axis, and exosomal miRNA-126 remodels metabolism by disrupting IRS/Glut-4 signalling, activating the AMPK/autophagy pathway and stabilizing HIF1α expression in imminent adipocytes. In vivo inhibition of miRNA-144 or miRNA-126 decreases adipocyte–induced tumour growth.

Conclusions

These results demonstrate that by inducing beige/brown differentiation and enhancing catabolism in recipient adipocytes, exosomal miRNA-144 and miRNA-126 from the tumour-adipocyte interaction reprogram systemic energy metabolism to facilitate tumour progression.
3D vs. 4K Display System - Influence of “State-of-the-art”-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial
Authors: Wahba Roger , Datta Rabi Raj , Hedergott Andrea , Bußhoff Jana , Bruns Thomas , Kleinert Robert , Dieplinger Georg , Fuchs Hans , Giezelt Caroline , Möller Desdemona , Hellmich Martin , Bruns Christiane J. , Stippel Dirk L.
Published: May 2019

Background

Three-dimensional (3D) stereoscopic vision is crucial to perform any kind of manual task. The reduction from real life 3D to virtual two-dimensional (2D) sight is a major challenge in minimally invasive surgery (MIS). A 3D display technique has been shown to reduce operation time and mistakes and to improve the learning curve. Therefore, the use of a3D display technique seems to optimize surgical performance for novice and experienced surgeons. Inspired by consumer electronics, a 4K display technique was recently introduced to MIS. Due to its high resolution and zoom effect, surgeons should benefit from it. The aim of this study is to evaluate if “state-of-the-art” 3D- vs. 4K-display techniques could influence surgical performance.

Methods

A randomized, cross-over, single-institution, single-blinded trial is designed. It compares the primary outcome parameter “surgical performance”, represented by “performance time ”and “number of mistakes”, using a passive polarizing 3D and a 4K display system (two arms) to perform different tasks in a minimally invasive/laparoscopic training parkour. Secondary outcome parameters are the mental stress load (National Aeronautics and Space Administration (NASA) Task Load Index) and the learning curve. Unexperienced novices (medical students), non-board-certified, and board-certified abdominal surgeons participate in the trial (i.e., level of experience, 3 strata). The parkour consists of seven tasks (for novices, five tasks), which will be repeated three times. The 1st run of the parkour will be performed with the randomized display system, the 2nd run with the other one. After each run, the mental stress load is measured. After completion of the parkour, all participants are evaluated by an ophthalmologist for visual acuity and stereoscopic vision with five tests. Assuming a correlation of 0.5 between measurements per subject, a sample size of 36 per stratum is required to detect a standardized effect of 0.5 (including an additional 5% for a non-parametric approach) with a power of 80% at a two-sided type I error of 5%. Thus, altogether 108 subjects need to be enrolled.

Discussion

Complex surgical procedures are performed in a minimally invasive/laparoscopic technique. This study should provide some evidence to decide which display technique a surgeon could choose to optimize his performance.

Trial registration

ClinicalTrials.gov, NCT03445429. Registered on 7 February 2018.
Model-driven metronomic vinorelbine in heavily pre-treated metastatic NSCLC and PM patients: Results of a phase I/II study.
Authors: Ciccolini Joseph , Cousin Elissa , Deyme Laure , Imbs Diane-Charlotte , Bonnet Sylvanie , Serre Raphael , Barbolosi Matthieu , Greiller Laurent , Tomasini Pascale , Galloux Melissa , Lacarelle Bruno , Barbolosi Dominique , Barlesi Fabrice
Published: May 2019

e20505

Background: A phase I/II trial (NCT02555007) of oral metronomic Vinorelbine derived from a mathematical model was performed in heavily pretreated metastatic Non-Small Cell Lung Cancer or Pleural Mesothelioma patients. Progression free survival, toxicity and PK/PD endpoints were the main objectives. Methods: Metronomic scheduling was selected using a simplified phenomenological model to identify the best continuous scheduling and dosing of oral vinorelbine with a total dose of 150 mg QW. Patients were monitored on a weekly basis, efficacy was evaluated by CT scans (RECIST). Toxicity was monitored using standard CTCAE criteria. Total tumor size (TTS) was the sum of diamaters of all lesions. Computation of individual PK parameters was done with Monolix software using population approach. Results: The PK/PD model proposed the following schedule: 60 mg D1, 30 mg D2, 60 mg D4. A total of 36 patients (30 evaluable) were enrolled (22M, 13F, 24 NSCLC, 11 mesothelium, median age 69.5, range 33-85.2). Patients were all heavily pre-treated (median 3 lines, range 1-9). Grade 3+ Neutropenia was observed in 30% patients. Median PFS was 11 weeks (range: 6-16.9). Best responses included 4 PR (13%) and 18 SD (60%). Baseline total tumor size was associated with reduced PFS (HR: 1.09, p = 0.026). A large variability in drug exposure (AUC 53 %, range 26 – 501 ng.h/ml) and PK parameters (Cl 82 %, range 45-605 l/h) was observed among patients. Exposure was not associated with efficacy, apart in patients with larger TTS (i.e., > 70 mm) who seemed to have longer PFS (125 days VS. 40 days, p = 0.057). Vinorelbine exposure tended to be associated with higher risk for grade 2+ neutropenia, especially in patients with BSA < 1.8 m² (60% VS. 25.5%, p = 0.055). A non-significant trend towards baseline NLR and PFS was observed (i.e., NLR < 4: 80 days, NLR > 4: 60 days, p = 0.077). Conclusions: Metronomic vinorelbine was characterized by huge variability in drug exposure among patients. However and despite being all heavily pre-treated, 60% of stable disease and 13% of PR were achieved in these patients. Plasma exposure yielded conflicting results depending on the initial tumor burden, suggesting that patients should be carefully selected prior to be scheduled for metronomic regimen. Possible role NLR could play as a predictive marker is intriguing and should be confirmed in larger cohort.
Costs and hazard ratios of commonly used drugs in advanced/metastatic lung cancer at Cancer Free Foundation, Dana Point, California.
Authors: Guirgis Helmy M.
Published: May 2019

e20508

Background: The American Cancer Society of Clinical Oncology used hazard ratios (HR) in its value framework as indicators of clinical response. Bevacizumab (Bev) and Pemetrexed (Peme) were introduced for non-squamous metastatic lung cancer prior to epidermal growth factor recognition. Objective: Analyze drug costs and HR in 1st-line advanced/metastatic lung cancer. Methods: Costs of Bev, Peme, Pembrolizumab (Pembro) and Atezolizumab (Atezo) were calculated x one year. Protocols and HR at 95% confidence intervals were quoted. Results: Median drug HR was 0.73. Bev costs were $132,314 and HR 0.79 (A. Sandler, 2006). Peme costs were $97,947, HR 0.63 (M. Zuchin, 2013) and 0.78 (PARAMOUNT). Costs of Pembro 2mg/Kg x 80 Kg were $125,770 compared with $157,313, the currently used 200 mg flat dose. Proportionate savings were noted over the 90-50 Kg weight. Pembro costs x 35 cycles increased to $317,450. In tumor progression score (TPS) > 50% (KEYNOTR-24), Pembro HR was 0.60. In KEYNOTE-042, HR in > 1.0% was 0.81 and improved to 0.69 in 50% with a net benefit of 14%. In squamous cell (KEYNOTE-407), Pembro+chemo HR was 0.64. Pembro+Peme+chemo costs were $255,160. In KEYNOTE-189, irrespective of program death receptor-ligand-1 (PD-L1), HR was 0.49, < 1.0% 0.59 and > 50% 0.42. The net benefit was 28%. Atezo+Bev combination costs were $287,314 and HR 0.78 (IMPOWER 150). In extensive small-cell, Atezo+chemo costs were $150,604 and HR 0.70 (IMPOWER 133). Conclusions: Pembro weight-adjusted dose resulted in significant cost saving over the fit-all 200mg. In 1st-line advanced/metastatic lung cancer, Pembro-Peme, irrespective of PD-L1, offered incomparable 0.49 HR at yearly costs of $255,160.
Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel with or without bevacizumab as second-line therapy or beyond for patients with metastatic non-small-cell lung cancer.
Authors: Zhang Fan , Li Tao , Zhang Yuzi , Cai Shangli , Zhao Lei , Jiao Shun Chang , Hu Yi
Published: May 2019

e20517

Background: Immunotherapy combined with platinum-based chemotherapy is now standard first line treatment for NSCLC patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Therefore, a retrospective study was conducted to assess whether immunotherapy plus nab-paclitaxel with or without bevacizumb could improve efficacy compared with immune monotherapy as second line therapy or beyond for NSCLC patients. Methods: Patients with metastatic NSCLC receiving anti-PD-1/PD-L1 monotherapy or combination therapy from 2015 to 2018 were identified in Chinese People’s Liberation Army General Hospital. Patients who received PD-1/PD-L1 inhibitors as first-line therapy or combined with therapies other than nab-paclitaxel and bevacizumab were excluded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Results: Of 59 patients, 42 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel with or without bevacizumab. With a median follow-up of 8.2 months, combination therapy group showed significantly longer PFS compared with monotherapy group (8.4m vs. 3.7m, P = 0.047). When adjusted by covariates in COX proportional regression model, both treatment group (P = 0.007, Hazard ration [HR] 0.32; 95%CI 0.14-0.73) and performance status (P = 0.018, HR 0.44; 95%CI 0.22-0.87) demonstrated significant contribution to longer PFS. In addition, ORR was 23.5% (4/17) in the combination therapy group versus 12.8% (5/39) in the monotherapy group (P = 0.265) and the DCR was 88.2% (15/17) in the combination therapy group versus 61.5% (24/39) in the monotherapy group (P = 0.061). The incidence of grade 3/4 adverse events were 23.5% (4/17) in the combination therapy group and 4.8% (2/42) in monotherapy group (P = 0.052). Conclusions: PD-1/PD-L1 inhibitor plus nab-paclitaxel with or without bevacizumab resulted in significantly longer PFS and higher DCR as second line therapy of beyond in metastatic NSCLC patients. These findings need to be further explored by randomized controlled studies.