bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Efficacy of Endoglin-Targeting Antibody–Drug Conjugates for the Treatment of Ewing Sarcoma
Authors: Puerto-Camacho Pilar , Amaral Ana Teresa , Lamhamedi-Cherradi Salah-Eddine , Menegaz Brian A. , Castillo-Ecija Helena , Ordóñez José Luis , Domínguez Saioa , Jordan-Perez Carmen , Diaz-Martin Juan , Romero-Pérez Laura , Lopez-Alvarez Maria , Civantos-Jubera Gema , Robles-Frías María José , Biscuola Michele , Ferrer Cristina , Mora Jaume , Cuglievan Branko , Schadler Keri , Seifert Oliver , Kontermann Roland , Pfizenmaier Klaus , Simón Laureano , Fabre Myriam , Carcaboso Ángel M. , Ludwig Joseph A. , de Álava Enrique
Published: November 2018

Purpose:

Endoglin (ENG; CD105) is a coreceptor of the TGFβ family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFβ, and as a soluble matricellular protein (sENG) when cleaved by matrix metalloproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease.

Experimental Design:

We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody–drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma.

Results:

Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line–derived xenografts and patient-derived xenografts in a dose-dependent manner.

Conclusions:

Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma.
E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
Authors: Tarhini Ahmad A. , Lee Sandra J. , Li Xiaoxue , Rao Uma N.M. , Nagarajan Arun , Albertini Mark R. , Mitchell Jerry W. , Wong Stuart J. , Taylor Mark A. , Laudi Noel , Truong Phu V. , Conry Robert M. , Kirkwood John M.
Published: November 2018

Purpose:

Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis.

Patients and Methods:

E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3.

Results:

For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7–8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1–11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6–7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1–13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8–20.2) in arm A, 6.2 months (95% CI, 2.7–25.7) in B, 5.7 months (95% CI, 1.5–11.1) in C, and 2.8 months (95% CI, 2.6–5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10.

Conclusions:

Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks.
Targeting Purinergic Receptor P2Y2 Prevents the Growth of Pancreatic Ductal Adenocarcinoma by Inhibiting Cancer Cell Glycolysis
Authors: Hu Li-Peng , Zhang Xiao-Xin , Jiang Shu-Heng , Tao Ling-Ye , Li Qing , Zhu Li-Li , Yang Ming-Wei , Huo Yan-Miao , Jiang Yong-Sheng , Tian Guang-Ang , Cao Xiao-Yan , Zhang Yan-Li , Yang Qin , Yang Xiao-Mei , Wang Ya-Hui , Li Jun , Xiao Gary Guishan , Sun Yong-Wei , Zhang Zhi-Gang
Published: November 2018

Purpose:

Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP–P2RY2 axis could be a potential therapeutic approach for PDAC treatment.

Experimental Design:

Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression.

Results:

P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT–mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice.

Conclusions:

These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.
Predicting Novel Therapies and Targets: Regulation of Notch3 by the Bromodomain Protein BRD4
Authors: Villar-Prados Alejandro , Wu Sherry Y. , Court Karem A. , Ma Shaolin , LaFargue Christopher , Chowdhury Mamur A. , Engelhardt Margaret I. , Ivan Cristina , Ram Prahlad T. , Wang Ying , Baggerly Keith , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , Yang Shyh-Ming , Maloney David J. , Yoshioka Makoto , Strovel Jeffrey W. , Roszik Jason , Sood Anil K.
Published: November 2018

Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer.

Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling.

Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P < 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo. BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1. Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter.

Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.

The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.
Neutrophil to Lymphocyte Ratio as a Prognostic Factor in European Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Treated with Tyrosine Kinase Inhibitors
Authors: Aguiar-Bujanda David , Dueñas-Comino Arancha , Saura-Grau Salvador , Ros-Sanjuan Laura , Blanco-Sanchez Maria J. , Hernandez-Sosa Maria , Mori-De Santiago Marta , Galvan-Ruiz Saray , Lorenzo-Barreto Jose E. , Vargas-Prado Ana M. , Bohn-Sarmiento Uriel
Published: November 2018

Background: A high neutrophil to lymphocyte ratio (NLR) has been associated with adverse outcomes in non-small cell lung cancer (NSCLC). However, information on epidermal growth factor receptor (EGFR)-mutant advanced NSCLC is scarce, and most of the studies published have been conducted in Asian populations. We aimed to assess the influence of pretreatment NLR on progression-free survival (PFS) and overall survival (OS) in Western European patients treated with EGFR tyrosine kinase inhibitors (TKIs). Methods: A retrospective evaluation of 41 patients with EGFR-mutant advanced NSCLC treated with EGFR TKIs between June 2010 and May 2016 was carried out. The association between several prognostic factors including pretreatment NLR and survival was analyzed. Results: Median PFS and OS were 10.58 and 20.84 months, respectively. OS for patients with a high NLR was 7.4 months, compared to 24.6 months for patients with a low NLR (p = 0.0122). In multivariate analysis, poor performance status (ECOG PS ≥ 2) and presence of ≥ 3 metastatic locations were identified as significant independent prognostic factors for worse PFS. For OS, unfavorable prognostic factors were a high NLR and central nervous system metastasis at diagnosis. Conclusion: Pretreatment NLR is an independent prognostic factor for OS in Western European patients with EGFR-mutant NSCLC treated with EGFR TKIs.
Patients' Perspective: What has Changed in Deciding about Breast-Conserving Surgery for Early-Stage Breast Cancer in Turkey?
Authors: Yüksel Ergün , Güven H. Erhan , Dogan Lütfi
Published: November 2018

Background: This study aims to describe patients' perception of early breast cancer, factors influencing the choice of operation, patients' sources of information about the disease and the seriousness with which this information is considered, and to address what surgeons can do to enlighten their patients prior to decision-making. Methods: Patients were asked to complete a questionnaire consisting of 3 sections: The first section addressed influential factors during the decision-making process; the second pertained to the role of surgeons or health facilities in the process; and the third asked patients to revisit their initial choice of surgery. Results: 237 patients were included in the study. Statistical analyzes regarding demographic features showed that nulliparous, younger than 50 years, never or <5 years married, highly educated, business-owning, employed, and stage I breast cancer patients preferred breast-conserving surgery (BCS) to mastectomy. Conclusion: Although the rate of BCS is a technical quality indicator for breast cancer centers, providing sufficient patient counseling, involving the patient in the decision-making process, and offering every possible surgical option are key to improving quality of life. Systematic counseling should be provided to breast cancer patients who have primary tumors that are eligible for BCS.
Cutaneous Ewing Sarcoma and Ewing Sarcoma of the Bone: Distinct Diseases
Authors: Tavakkoli Montreh , Mueller Lisa
Published: November 2018

Ewing sarcoma is an aggressive mesenchymal malignancy. It is the second most common bone tumor among children and adolescents and less commonly presents as a soft tissue or primary skin lesion. Cutaneous Ewing sarcoma has only been reported in case reports and case series. In this article, we describe a 12-year-old Hispanic female cured of localized, cutaneous Ewing sarcoma (pT1aN0M0) at the 40-month follow-up following surgical resection and adjuvant chemotherapy according to the COG AEWS1031 protocol for Ewing sarcoma of the bone. To our knowledge, this is the first article to provide a potential biological explanation for the differences in the prognosis of Ewing sarcoma of the bone, soft tissue, and skin.
Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis
Authors: Hakobyan Mariam , Dijkman Koen P. , Laroche Sabrina , Naulaers Gunnar , Rijken Monique , Steiner Katerina , van Straaten Henrica L.M. , Swarte Renate M.C. , ter Horst Hendrik J. , Zecic Alexandra , Zonnenberg Inge A. , Groenendaal Floris
Published: November 2018

Background: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis. Objectives: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis. Methods: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1–42.6 weeks and birth weight 2,280–5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome. Results: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis. Conclusion: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants.
Esophageal Adenocarcinoma with Extensive Metastasis to Unexpected Sites: A Case Report
Authors: Mendiola Vincent Louie , Willis Maurice
Published: November 2018

Background: Esophageal cancer (EC) with unexpected metastasis (UM) to unusual sites have been increasingly reported. EC with metastasis in general has a very high mortality and morbidity rate, and those with UM to unusual sites present another specific field that needs to be further studied in order to understand and manage the presentation. An extensive systematic review was recently completed regarding this field which identified characteristics and findings concerning patients with EC with UM sites. Case Presentation: We report a 61 year old Hispanic male who had an EC, adenocarcinoma subtype, with UM to an extensive number of sites such as the soft tissue of the cheek, subcutaneous forehead and scalp with penetration of the calvarium, occipital bone, base of tongue, neck muscles, paraspinal and iliopsoas musculature and, more typically, to an adrenal gland followed by a questionable new-onset finding of subcutaneous shoulder and flank nodules not initially identified by imaging. Discussion/Conclusion: The case reports a patient who not only had EC with UM to unusual sites, but also to a considerable number. The patient correlated well in terms of clinical features identified by the systematic review of this particular field, but his case also showed a new finding, another unexpected metastasis site. This case also shows an example of why the type of imaging is important when dealing with UM sites. With this, we hope to further add to the data in this particular field and provide some opinion on this matter.
Water bugs (Insecta: Hemiptera: Heteroptera) of Himalayan and sub-Himalayan regions of West Bengal, India
Authors: Basu Srimoyee , Chandra Kailash , Subramanian Kumrapuram Apadodharanan , Saha Goutam Kumar
Published: November 2018

The present study reports a total of 61 Species belonging to 34 genera and 14 families from Darjeeling Himalaya and Jalpaiguri sub Himalaya regions of West Bengal.  The study documented 11 new species to science, which were already published, 15 new records to the state and one new record to India. The study showed that the Nepomorphan families are mostly restricted to the slow flowing or to the stagnant ecosystems like ponds or lakes and the running waters are dominated mainly by the Gerromorpha. The key to all family, genera and species of aquatic Hemiptera are provided with their distribution in India and globally.  The description of all species with their detail photographs and distribution map were also presented here. The diagnostic characters supported with photographs for each species are also presented here.
An exploratory study on open adoptions from foster care in NSW, Australia: Adoptees’ psychosocial functioning, adoptive relationships, post-adoption contact and supports
Authors: del Pozo de Bolger Andrea , Dunstan Debra , Kaltner Melissa
Published: November 2018

This is an exploratory study focused on open adoptions from foster care conducted through the public child protection agency in New South Wales, Australia. The results from an online survey completed by 23 respondents indicated that most of the adoptees were reportedly in the normative range of adjustment, had positive relationships with their adoptive parents and had ongoing contact with their birth families. Most of the adoptive parents had received pre-adoption supports to encourage post-adoption contact. These preliminary results are encouraging, but larger and preferably longitudinal studies are needed to guide decision-making regarding adoptions from foster care. The new challenge for the child welfare system is how to collect reliable data about the well-being of children already living in this permanent type of care and how best to support them.
Perceived Unfair Treatment by Police, Race, and Telomere Length: A Nashville Community-based Sample of Black and White Men
Authors: McFarland Michael J. , Taylor John , McFarland Cheryl A. S. , Friedman Katherine L.
Published: November 2018

Police maltreatment, whether experienced personally or indirectly through one’s family or friends, represents a structurally rooted public health problem that disproportionately affects minorities. Researchers, however, know little about the physiological mechanisms connecting unfair treatment by police (UTBP) to poor health. Shortened telomeres due to exposure to this stressor represent one plausible mechanism. Using data from a community sample of black (n = 262) and white (n = 252) men residing in Nashville-Davidson County, we test four hypotheses: (1) Black men will be more likely to report UTBP than white men, (2) those reporting UTBP will have shorter telomeres than those not reporting UTBP, (3) this association will be more pronounced among black men, and (4) these hypotheses will extend to those who report vicarious UTBP. Results reveal support for all hypotheses. The implications for our findings are discussed as they pertain to debates on policing practices and health disparities research.
The Global Unions and global governance: Analysing the dialogue between the international trade union organizations and the international financial institutions
Authors: Rueckert Yvonne
Published: November 2018

The article examines the dialogue between the Global Unions, the World Bank and the International Monetary Fund, which was formalized in 2002 and was originally initiated by the Global Unions. The dialogue takes place at three levels: headquarters, sector and country level. The Global Unions try to use the dialogue to persuade the international financial institutions to change their policies to promote and integrate a stronger social component within the system of global governance. The article focuses on the headquarters-level dialogue and examines some of the factors which promote and hinder the success of the dialogue from the perspective of the Global Unions.
Three dimensions of employees acquiring shares in their firms: Personal characteristics, motives and type of ownership
Authors: Faigen Benjamin , Mygind Niels , Sigurjonsson Throstur Olaf , Arnardottir Audur Arna
Published: November 2018

This study is based on a survey and interviews in six Icelandic firms in which share purchases by employees have transpired. The focus is on employees’ characteristics and motives in becoming shareowners as well as the reasons for non-participation. The article’s contribution is to add to the theory and empirical evidence regarding the individual-level antecedents to employee ownership across both majority and minority variants. The results reveal that income, tenure and age influence ownership status. There is some support for expectations that employees place greater emphasis on stakeholder goals and collective goals in majority employee-owned firms and on financial goals in minority employee-owned firms. Employees were hindered from becoming owners due to a lack of funds or internal exclusionary barriers.
How do Turkey-origin immigrant workers in Germany represent themselves through trade unions and works councils?
Authors: Korkmaz Emre Eren
Published: November 2018

This article analyses the representation of Turkey-origin immigrant workers in trade unions and works councils in the Ruhr region (Germany). Based on a field study in the Ruhr including surveys, in-depth interviews and focus groups between November 2015 and January 2016, this study aims to gain a deeper understanding of the dynamics of immigrant–native/citizen relations. The article demonstrates the importance of trade unions and works councils in the integration of immigrants and stresses the adverse outcomes of trade unions’ persistence to maintain their ‘German, white and male’ character. It also discusses how the internal polarisation among immigrants from Turkey affects workplace level relations. Based on the experiences of Turkey-origin immigrant workers, whose history of immigration to Western Europe spans nearly 60 years, the research focuses on the role of social organisations for the representation and participation of immigrants within the democratic system alongside natives/citizens.
Systematic fast-track transition from oncological treatment to dyadic specialized palliative home care: DOMUS – a randomized clinical trial
Authors: Nordly Mie , Skov Benthien Kirstine , Vadstrup Eva S , Kurita Geana P , von Heymann-Horan Annika B , von der Maase Hans , Johansen Christoffer , Timm Helle , Kjellberg Jakob , Sjøgren Per
Published: November 2018

Background:

The focus of specialized palliative care is to improve quality of life for patients with incurable cancer and their relatives including an increased opportunity to make their own choice of place of care and death.

Aim:

To investigate whether a systematic fast-track transition from oncological treatment to specialized palliative care at home for patients with incurable cancer reinforced with a psychological dyadic intervention could result in more time spent at home and death at home. Secondary aims were to investigate effects on quality of life, symptomatology and survival.

Design:

A prospective, single-centre, randomized controlled trial ( Clinicaltrials.gov : NCT01885637).

Setting/participants:

In all, 340 patients with incurable cancer and no or limited antineoplastic treatment options.

Results:

No statistically significant difference was found regarding number of deaths (4%, p = 0.460) and time spent at home (3%, p = 0.491). The secondary outcomes indicated that the intervention resulted in improved quality of life (−11.6 ± 25.5, p = 0.005, effect size = −0.44, 95% confidence interval = −0.77; −0.11), social functioning (−15.8 ± 31.4, p = 0.001, effect size = −0.50, 95% confidence interval = −0.84; −0.17) and emotional functioning (−9.1 ± 21.2, p = 0.039, effect size = −0.43, 95% confidence interval = −0.76; −0.10) after 6 months. A linear mixed-effect regression model confirmed a possible effect on emotional and social functioning at 6 months. Regarding survival, no differences were found between groups ( p = 0.605). No adverse effects were seen as consequence of the intervention.

Conclusions:

The main findings indicated that the intervention had no effect on time spent at home or place of death. However, the intervention resulted in a weak improvement of quality of life, social functioning and emotional functioning after 6 months.
Preoperative smoking history is associated with decreased risk of early postoperative cognitive dysfunction in patients of advanced age after noncardiac surgery: a prospective observational cohort study
Authors: Wang Runjia , Wang Gongming , Liu Yang , Zhang Mengyuan
Published: November 2018

Objective

Prevention of postoperative cognitive dysfunction (POCD) in patients of advanced age remains unclear. Studies have shown that the cholinergic anti-inflammatory pathway contributes to a decreased risk of POCD and that nicotine stimulates the cholinergic anti-inflammatory pathway. We investigated whether patients of advanced age with a preoperative smoking history have a decreased risk of POCD.

Methods

In total, 382 patients (190 smokers, 192 nonsmokers) aged ≥60 years who underwent major noncardiac surgery were enrolled. Cognitive function was assessed, and multivariate logistic regression analyses were performed to identify risk factors.

Results

On postoperative days 5 and 7, 111 (29.05%) and 90 (23.56%) patients exhibited POCD, respectively. A preoperative smoking history was significantly correlated with a decreased risk of POCD. A high serum tumor necrosis factor-α (TNF-α) level on the operative day was significantly associated with an increased risk of POCD. Early POCD was significantly associated with the sufentanil dosage, age, and education level. The hospital stay in patients with and without POCD was 10.54 ± 2.03 and 8.33 ± 1.58 days, respectively.

Conclusion

A preoperative smoking history was associated with a decreased risk of early POCD, and a high serum TNF-α level was significantly associated with an increased risk of POCD.
Human Subacromial Bursal Cells Display Superior Engraftment Versus Bone Marrow Stromal Cells in Murine Tendon Repair
Authors: Dyrna Felix , Zakko Philip , Pauzenberger Leo , McCarthy Mary Beth , Mazzocca Augustus D. , Dyment Nathaniel A.
Published: November 2018

Background:

Bone marrow aspirate is a primary source for cell-based therapies with increasing value in the world of orthopaedic surgery, especially in revision cases of tendon and ligament repairs. However, cells within peritendinous structures, such as the paratenon and surrounding bursa, contribute to the native tendon-healing response and offer promising cell populations for cell-based repair strategies. Therefore, the purpose of this study is to investigate the efficacy of cells derived from human subacromial bursa as compared with the current gold standard, bone marrow stromal cells (BMSCs), for tendon repairs in an established in vivo immunodeficient murine patellar tendon defect model.

Hypothesis:

Subacromial bursal cells will show superior survival and engraftment into the host tissue as compared with BMSCs.

Study Design:

Controlled laboratory study.

Methods:

Human subacromial bursal and bone marrow aspirate were harvested from the same donor undergoing rotator cuff repair. Cells were transfected with a fluorescent lentiviral vector to permanently label the cells, encapsulated into fibrin gel, and implanted into bilateral full-length central-width patellar tendon defects of immunodeficient mice. Additional surgery was performed on control mice comparing fibrin without cells and natural healing. At the time of sacrifice, all limbs were scanned on a multiphoton microscope to monitor the engraftment of the human donor cells. Afterward, limbs were assigned to either immunohistochemical or biomechanical analysis.

Results:

As compared with BMSCs, implanted subacromial bursal cells displayed superior tissue engraftment and survival. The main healing response in this defect model was the creation of new healing tissue over the anterior surface of the defect space. The implantation of cells significantly increased the thickness of the anterior healing tissue as compared with control limbs that did not receive cells. Cell proliferation was also increased in limbs that received implanted cells, suggesting that the donor cells stimulated a more robust healing response. Finally, these changes in the healing response did not lead to significant changes in mechanical properties.

Conclusion:

The subacromial bursa, while often removed during rotator cuff repair, may harbor a more suitable cell source for tendon repair than BMSCs, as bursal cells display superior engraftment and survival in tendon tissue. In addition, the subacromial bursa may be a more accessible cell source than bone marrow aspirate.

Clinical Relevance:

The subacromial bursa contains a cell population that responds to tendon injury and may provide a more optimal cell source for tendon repair and regeneration strategies. Therefore, cells could be harvested from this tissue in the future, as opposed to the current practice of bursectomy and debridement.
Femoral Tunnel Drilling Method: Risk of Reoperation and Revision After Anterior Cruciate Ligament Reconstruction
Authors: Tejwani Samir G. , Prentice Heather A. , Wyatt Ronald W.B. , Maletis Gregory B.
Published: November 2018

Background:

The femoral tunnel in anterior cruciate ligament reconstruction (ACLR) can be created by the transtibial (TT) or tibial-independent (TI) methods. An anatomically located femoral tunnel can be more consistently achieved by TI methods, which include the anteromedial portal and lateral (outside-in, retrodrill) techniques. Nonanatomic graft placement in ACLR can result in postoperative instability and meniscal or chondral injury. An anatomically located graft is subjected to higher postoperative physiologic forces than one placed nonanatomically.

Purpose:

To examine isolated primary ACLR and determine the risk of aseptic revision and reoperation based on femoral tunnel drilling method.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

The ACLR registry of an integrated US health care system was used to identify primary isolated unilateral ACLRs from 2009 to 2014. Multivariable Cox proportional hazard regression models were used to evaluate risk for aseptic revision for graft failure and aseptic reoperation for meniscal or chondral injury according to femoral tunnel drilling method: TI versus TT. Models included age, sex, body mass index (BMI), race, graft type, and femoral fixation type as covariates.

Results:

The cohort included 19,059 patients with primary ACLR. The mean age was 28.9 years (SD, 11.5), 6991 patients (36.8%) were younger than 22 years, 11,795 patients (61.9%) were male, 7648 patients (40.1%) had a BMI less than 25 kg/m2, 8913 patients (46.8%) were white, and 7357 patients (38.6%) received an allograft. Median follow-up was 2.30 years (interquartile range, 1.08-3.77). TI techniques were used for 12,342 (64.8%) of the ACLRs, and the TT method was used for 6717 (35.2%). Use of TI techniques increased from 33.6% of all ACLRs in 2009 to 83.4% in 2014. After adjustment for covariates, the TI group had a higher risk for aseptic revision than the TT group (hazard ratio [HR], 1.28; 95% CI, 1.04-1.56), and this risk was 1.41 times higher in patients younger than 22 years specifically. The 5-year cumulative reoperation probability was lower in the TI group (4.50%; 95% CI, 3.78%-5.36%) compared with the TT group (5.06%; 95% CI, 4.31-5.94%). After adjustment for the covariates, no difference in risk for aseptic reoperation was observed (HR, 1.08; 95% CI, 0.85-1.39).

Conclusion:

In the largest known study of its type examining femoral tunnel drilling method for primary ACLR, after adjustment for age, sex, BMI, race, graft type, and femoral fixation, TI techniques were found to carry higher risk of aseptic revision compared with the TT method, while no difference was observed in risk for aseptic reoperation.
Biceps Detachment Preserves Joint Function in a Chronic Massive Rotator Cuff Tear Rat Model
Authors: Chen Mengcun , Shetye Snehal S. , Huegel Julianne , Riggin Corinne N. , Gittings Daniel J. , Nuss Courtney A. , Weiss Stephanie N. , Kuntz Andrew F. , Soslowsky Louis J.
Published: November 2018

Background:

Lesions of the long head of the biceps tendon are often associated with massive rotator cuff tears (MRCTs), and biceps tenotomy is frequently performed for pain relief and functional reservation. However, the efficacy and safety of biceps tenotomy regarding the effects on the surrounding tissues in chronic MRCT are unclear.

Hypothesis:

Biceps tenotomy would result in improved mechanical and histological properties of the intact subscapularis tendon and improved in vivo shoulder function while not compromising glenoid cartilage properties.

Study Design:

Controlled laboratory study.

Methods:

Right supraspinatus and infraspinatus tendons were detached in 25 male Sprague-Dawley rats, followed by 4 weeks of cage activity to create a chronic MRCT condition. Animals were randomly divided into 2 groups and received either biceps tenotomy (n = 11) or sham surgery (n = 14) and were sacrificed 4 weeks thereafter. Forelimb gait and ground-reaction forces were recorded 1 day before the tendon detachment (baseline), 1 day before the surgical intervention (biceps tenotomy or sham), and 3, 7, 10, 14, 21, and 28 days after the intervention to assess in vivo shoulder joint function. The subscapularis tendon and glenoid cartilage were randomly allocated for mechanical testing or histologic assessment after the sacrifice.

Results:

Compared with sham surgery, biceps tenotomy partially restored the in vivo shoulder joint function, with several gait and ground-reaction force parameters returning closer to preinjury baseline values at 4 weeks. With biceps tenotomy, mechanical properties of the subscapularis tendons were improved, while mechanical properties and histological Mankin scores of the glenoid cartilage were not diminished when compared with the sham group.

Conclusion:

Biceps tenotomy in the presence of chronic MRCT partially preserves overall shoulder function and potentially restores subscapularis tendon health without causing detrimental effects to joint cartilage. This laboratory study adds to the growing literature regarding the protective effects of biceps tenotomy on the shoulder joint in a chronic MRCT model.

Clinical Relevance:

This study provides important basic science evidence supporting the use of biceps tenotomy in patients with massive rotator cuff tears.
Preparation and application of α-Fe2O3@MIL-101(Cr)@TiO2 based on metal–organic framework for photocatalytic degradation of paraquat
Authors: Khodkar Asghar , Khezri Seyed Mostafa , Pendashteh Alireza , Khoramnejadian Shahrzad , Mamani Leila
Published: November 2018

In this study, a new magnetic α-Fe2O3@MIL-101(Cr)@TiO2 photocatalyst was successfully synthesized. The material synthesized had been fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and Brunauer–Emmett–Teller isotherm methods. The X-ray diffraction analysis corroborates that nanoparticles are polycrystalline with rhombohedral and tetragonal crystal structures for Fe2O3 and TiO2, respectively. In addition, the photocatalytic degradation of the herbicide paraquat in the presence of α-Fe2O3@MIL-101(Cr)@TiO2 under ultraviolet (UV) irradiation was studied. The effect of experimental parameters such as the initial concentration of catalyst, the pH, and the initial paraquat was investigated. The optimal conditions were achieved for concentration of catalyst 0.2 g L−1, pH 7, and concentration of paraquat 20 mg L−1. The photocatalytic degradation efficiency was 88.39% after 15 min with α-Fe2O3@MIL-101(Cr)@TiO2 under UV irradiation. The pseudo-second-order kinetic model for photocatalytic degradation of paraquat was obtained. The catalysts could be recovered and reused without any loss of efficiency for five times in the consequent reactions. To the best of our knowledge, this is the first report on the photocatalytic degradation of paraquat using new α-Fe2O3@MIL-101(Cr)@TiO2 photocatalyst under UV irradiation condition.
Wear behavior of glass–polyamide reinforced epoxy hybrid composites
Authors: Selmy AI , Abd El-baky MA , Hegazy DA
Published: November 2018

The abrasive wear performance of glass–polyamide fibers/epoxy composites was experimentally studied using a pin-on-disc wear tester at different applied normal loads. Specimens were fabricated in inter-ply configuration using the hand layup technique. Specimens were subjected to distilled water and sea water immersion at room temperature for 200 days. The effects of the reinforcement hybridization, stacking sequence, and relative fiber amounts on the wear behavior of dry and wet specimens were discussed. Temperature rise at the specimen pin–disc interface has been measured. The morphologies of the worn surfaces were investigated with scanning electron microscopy (SEM). Results showed that distilled water and sea water uptake of glass/epoxy composite is 2.5 and 2 times those of polyamide/epoxy counterparts. Correction factor decreases the diffusion coefficient by about 24% and 26% for, respectively, polyamide/epoxy and glass/epoxy composites. Hybridizing glass fiber composite with polyamide fiber could reduce the specimen’s weight loss during wear test for dry and wet specimens. Water uptake induces a significant decrease in wear resistance of the studied composites. Stacking sequence has a slight effect on wear resistance, while relative fiber amounts have a noticeable effect. The maximum temperature at the specimen pin–disc interface (21.5°C) was noticed for glass/epoxy composite under applied load of 10 N. As the applied load and the sliding time increase, the wear resistance of the composites decreases but the temperature at the specimen pin–disc interface increases. SEM observations show debonding, cracks, fiber fracture, and debris formation.
Impact of Selected Macroeconomic Determinants on Economic Growth in India: An Empirical Study
Authors: Sharma Rajesh , Kautish Pradeep , Kumar D. Suresh
Published: November 2018

Due to the socio-economic, infrastructural and governance peculiarities, identification of key macroeconomic factors determining the economic growth in developing countries becomes a complicated case. The present study attempts to assess the impact of foreign aid, government consumption expenditure, foreign direct investment, trade openness, exchange rate, human capital development, and inflation on economic growth in India by using yearly data for the period of 46 years, that is, from 1971 to 2016. An autoregressive distributed lag (ARDL) bounds model enables to examine the short-run and long-run impact of selected determinants on economic growth during the study period. The outcomes of the study find that in the long run, foreign aid, the government’s final consumption expenditure and foreign direct investment have a positive and significant impact on economic growth, whereas, economic growth has been negatively influenced by exchange rate and human capital development. Contrary to the long run, foreign aid has a negative and significant impact on economic growth in the short run. The short-run outcomes show that all the selected macroeconomic determinants have either negative or positive influence on economic growth. To ensure the long-run economic growth, besides regulating the exchange rate fluctuations, policies related to export -import and human capital development need to be re-examined.
Running for Korea: Rethinking of sport migration and in/flexible citizenship
Authors: Choi Yeomi
Published: November 2018

Human migration is one of the defining features of a transnational age. Challenging the conventional knowledge that identity and citizenship are connected to one territorial state, both migrant and repositioned subjects create a new understanding of identity, belonging, and citizenship within multiple transnational connectivities. Sport particularly produces a new version of belonging referred to as flexible citizenship, including various kinds of skilled workers crossing national borders. In the process of migration, governments play a crucial and a decisive role by determining permission via specific legislation enactment; South Korea’s immigration policy, Special Naturalization, is a notable example. Despite the legally encouraged mobility that favors flexible citizenship by state power, this repositioning is regulated and limited by the intricate socio-political logics of race, class, and national identity. Focusing on the controversial issues of the Kenyan-born marathoner Wilson Loyanae Erupe and his bid for Korean citizenship, this study critically examines the tensions surrounding sport migration, flexible citizenship, race, and nationalism. Drawing on the theoretical ideas of critical race studies, specifically, it queries the conflicting encounters of transnational migration and being a Korean citizen to illuminate the structures of racial domination in Korea often seen as a racially and ethnically homogeneous society.
When a right-wing extremist political party appeals to European integration and a constitutional court takes the national perspective…A comment on the Nationaldemokratische Partei Deutschlands judgment BVerfG, 2 BvB 1/13
Authors: Reinke Benedikt
Published: November 2018

With Regulation 1141/2014, the EU has inaugurated a truly transnational political party system as well as a potential conflict between national and European governance – or so the Nationaldemokratische Partei Deutschlands has recently argued when faced with party ban proceedings before the German Federal Constitutional Court. The party contended that its representation in the European Parliament and membership in a political party at European level established exclusive European governance and denied the competence of the Federal Constitutional Court for national proceedings. The court, by contrast, summarily dismissed the Nationaldemokratische Partei Deutschlands’s arguments, maintaining its own exclusive authority, and failed to engage in a substantive legal assessment of recent developments in European party law. In this paper, I argue that precisely such a thorough analysis of the newly emerging intertwinement between national and European law as a consequence of Regulation 1141/2014 would have been in order. The Nationaldemokratische Partei Deutschlands’s arguments need to be taken more seriously than the Federal Constitutional Court allows, despite, or perhaps more accurately because, of their highly strategic invocation of European integration: the European argument cannot rest with the extremist party alone, who, elsewhere a most imminent opponent of the European idea, now uses it to challenge national law.
Child’s Religiosity, Ethnic Origin, and Gender: A Randomized Experimental Examination of Risk Assessment and Placement Decisions in Cases of Ambiguous Risk to Children From Low SES Families
Authors: Enosh Guy , Nouman Hani , Schneck Chana
Published: November 2018

Social workers are called upon as expert witnesses to assess risk to children and recommend interventions. It is hypothesized that risk assessments and decisions are influenced by the risk-to-child as well as personal attitudes and biases. We examined the role of the ethnic origin, religiosity, and child gender on assessments and recommendation.

Methods:

The current study used a survey-based balanced crossover experimental design. One hundred and twenty Israeli social workers responded to case descriptions of ambiguous risk cases of children from low socioeconomic status families. Design was based on eight vignettes. Manipulated factors included child’s gender, family religiosity, and ethnic origin. Participants assessed the child risk level and reported placement recommendation.

Results:

Male, ultraorthodox-Jewish child of Mizrahi origin had higher likelihood for risk assessment. Risk assessment predicted placement recommendation.

Implications:

Social workers tend to perceive child’s male gender, ultrareligiosity, and Mizrahi origin as risk factors. Such cultural biases indirectly affected the placement recommendation. Awareness of social workers regarding these potential biases may reduce the influence of heuristics on the professional decision-making process.
Larval survival of Aelurostrongylus abstrusus lungworm in cat litters
Authors: Abbate Jessica M , Arfuso Francesca , Gaglio Gabriella , Napoli Ettore , Cavalera Maria A , Giannetto Salvatore , Otranto Domenico , Brianti Emanuele
Published: November 2018

Objectives

The dehydrating power of cat litters may reduce the vitality of first-stage larvae (L1s) of feline lungworms, limiting copromicroscopical diagnosis. This study assessed the effect of the most commonly used cat litters on Aelurostrongylus abstrusus L1 survival.

Methods

Four types of cat litters were used: clumpling clay (group A); non-clumpling clay (group B); silica crystals (group C); and biodegradable (group D). A control group without litter (group E) was also included. On study day 0 (T0), L1s were obtained by the Baermann–Wetzel technique from the faeces of a naturally infected cat and ~100 larvae were injected in each of the 20 lungworm larvae-free faecal samples (~2 g each). Thereafter, four faecal samples per group were transferred into plastic cups containing the four different types of cat litters, or into empty cups (group E). The survival of L1s was assessed in each group after 3 (T3), 6 (T6), 12 (T12) and 24 (T24) h, using the Baermann–Wetzel technique.

Results

A decreasing trend of L1 survival was observed in all groups, with highest significant values at T0 compared with T3, T6, T12 and T24 ( P <0.001). However, at T24, a significantly higher number ( P <0.05) of L1s was extracted from faeces of the control group compared with the four groups with cat litters.

Conclusions and relevance

This study demonstrates how the survival of A abstrusus L1s, and therefore diagnosis, may be negatively influenced by the litter. The effect is time dependent, with a reduction in the number of vital larvae according to the type of litter, over time. False-negative results may be obtained, especially in cases of low parasitic load or when the sample is collected many hours after the emission.
Melatonin Improves Mood Status and Quality of Life and Decreases Cortisol Levels in Fibromyalgia
Authors: Castaño M. Yolanda , Garrido Maria , Rodríguez Ana Beatriz , Gómez M. Ángeles
Published: November 2018

Background:

Mood disturbances are implicated in the pathogenesis of fibromyalgia. The aim of this study was to assess the effect of different doses of melatonin on quality of life, mood status, pain, anxiety, and urinary cortisol levels in patients with fibromyalgia.

Methods:

After a 10-day baseline period for the collection of data about participants’ initial status, participants took different doses of melatonin for 10 consecutive days each, with placebo given during the 10 days either before or between melatonin doses. Participants’ moods, quality of life, and pain levels were assessed using the Fibromyalgia Impact Questionnaire (FIQ), a Numerical Pain Scale (NPS), the State-Trait Anxiety Test (STAI), a Visual Analog Scale (VAS), and the Short Form-36 Health Survey (SF-36). Urinary cortisol levels were measured using enzyme-linked immunoassay.

Results:

Doses of 9, 12, and 15 mg of melatonin were associated with decreases in the total score of the FIQ, NPS scores, and urinary cortisol levels. The State-Anxiety subscale of the STAI improved after the 12 mg dose. The scores on the VAS improved after the 9 mg dose. The dimensions evaluated in the SF-36 questionnaire improved after the 9 mg dose.

Conclusion:

Melatonin improved mood, anxiety levels, and quality of life while decreasing cortisol levels in patients with fibromyalgia.