bluuebunny/crossref_metadata_2025 huggingface dataset:
Biweekly triplet chemotherapy with gemcitabine, cisplatin and vinorelbine for advanced chemotherapy naïve non-small cell lung cancer
Authors: Keskin Serkan , Tas Faruk , Ekenel Meltem , Kilic Leyla , Sen Fatma , Yildiz Ibrahim , Karabulut Senem , Ciftci Rumeysa , Vatansever Sezai
Published: February 2018

Aims and background

To investigate the efficacy and tolerability of biweekly scheduled triplet chemotherapy consisting of gemcitabine, cisplatin and vinorelbine for chemotherapy-naïve advanced non-small cell lung cancer.

Methods and study design

Patients with stage IIIB/IV non-small cell lung cancer and performance status of 0–2 were eligible. Patients who had brain metastasis and of an older age were also enrolled in the study. The triplet combination chemotherapy consisted of gemcitabine, cisplatin and vinorelbine at the doses of 1000 mg/m2, 25 mg/m2 and 50 mg/m2, respectively, were administered on day 1 and 14, every 28 days, up to 6 cycles.

Results

Thirty patients were enrolled in the study. Median age was 60 years (range, 42–74). Most of the patients (83%) had metastatic disease and 7 patients (23%) had brain metastasis. In assessing 24 patients for response evaluation, none had complete response. Partial responses were achieved in 18 (60%) patients. Four patients (13%) had stable disease and 2 (7%) progressed. Thirteen percent and 20% of the patients developed severe (grade 3–4) neutropenia and anemia, respectively. Febrile neutropenia, severe thrombocytopenia, hepatic and renal toxicity were not seen. Overall and progression-free survival were 8.15 and 7.15 months, respectively. Patients who had no brain metastasis (P = 0.069), who had more than 3 courses of chemotherapy (P <0.001), and who had chemotherapy applied without dose reduction (P = 0.018) had better survivals.

Conclusions

The biweekly schedule of the triplet chemotherapy combination including gemcitabine, cisplatin and vinorelbine was effective in advanced, mostly metastatic non-small cell lung cancer with acceptable and manageable side effects.
Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer
Authors: Schveigert Diana , Valuckas Konstantinas Povilas , Kovalcis Viktorija , Ulys Albertas , Chvatovic Genovefa , Didziapetriene Janina
Published: February 2018

Background

The aim of the study was to assess the expression of the MMP-9 gene and –1562 C/T polymorphism in MMP-9 gene promoter in relation to clinicopathological parameters in predicting the clinical outcome of prostate cancer patients.

Methods

A total of 82 patients with histopathologically diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism variants were determined by the polymerase chain reaction-based restriction fragment length polymorphism method.

Results

MMP-9 expression and MMP-9 –1562 polymorphism variants in relation to disease pathological stage (P = 0.006; P <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001, respectively), were statistically significant. Only MMP-9 –1562 polymorphism variants in relation to tumor differentiation grade (P = 0.044) were found to be statistically significant. Positive MMP-9 gene expression was associated with 5-year survival rate of prostate cancer patients with pathological stage III (P = 0.036) and for the patients in prognostic group III (P = 0.012). Patients with tumor differentiation grade G2 and with the identified CC variant had a significantly longer survival time than patients with the identified TT variant (P = 0.007).

Conclusions

MMP-9 gene expression and MMP-9 –1562 polymorphism variants were associated with prostate cancer pathological stage and prognostic group. MMP-9 –1562 polymorphism CC variant was associated with prostate cancer tumor differentiation grade. Five-year survival analysis showed the relationship between MMP-9 gene expression and pathological stage III, as well as prognostic group III, whereas MMP-9 –1562 polymorphism variants, with tumor differentiation grade G2.
Nontuberculous mycobacterial infection after therapy with temsirolimus for metastatic renal cell carcinoma
Authors: Buchler Tomas , Homolka Jiri , Fencl Pavel , Rosova Blanka , Hytych Vladislav , Abrahamova Jitka
Published: February 2018

We describe the case of a patient with metastatic renal cell carcinoma (mRCC) who developed a nontuberculous mycobacteria (NTM)-related pulmonary nodule during therapy with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus. After discontinuation of temsirolimus treatment, a small pulmonary nodule with increased glucose uptake was detected on a positron emission tomography (PET) scan. A lung resection carried out to confirm and treat the suspected solitary metastasis of RCC yielded the surprising finding of a caseating granuloma containing NTM.

A single PET-positive nodule presents a significant differential diagnostic dilemma in the setting of mRCC treated with mTOR inhibitors. Although the treatment of mRCC with temsirolimus can lead to immunosuppression and opportunistic infections, there is no report to our knowledge on the occurrence of NTM infections in mRCC patients treated with mTOR inhibitors. These infections should be included in the differential diagnosis of lung nodules. Interestingly, there is strong preclinical evidence pointing to direct and indirect antimycobacterial activity of mTOR inhibitors. We therefore hypothesize that while the seeding of NTM can occur during temsirolimus therapy due to T-lymphocyte suppression, the infection may only become active after the discontinuation of mTOR inhibitor treatment.
Vanishing Bile Duct Syndrome as a Manifestation of Hodgkin's Lymphoma: A Case Report and Review of the Literature
Authors: Nader Kamyar , Mok Shaffer , Kalra Ankur , Harb Antoine , Schwarting Roland , Ferber Andres
Published: February 2018

Vanishing bile duct syndrome (VBDS) is characterized by cholestasis and progressive destruction of the intrahepatic bile ducts (ductopenia). The current definition of ductopenia is the loss of interlobular bile ducts in more than 50% of portal tracts. Ductopenia is believed, at a molecular level, to result from the misbalance in cell regeneration and apoptosis. In the literature various etiologies have been reported to cause ductopenia, with Hodgkin's lymphoma (HL) being listed as a rare example. How HL causes ductopenia remains ambiguous, and seems to be related to a paraneoplastic phenomenon causing cytokine release from lymphoma cells, not tumor infiltration or obstructive lymphadenopathy. VBDS is generally considered irreversible, unlike its histopathological counterpart, idiopathic cholestasis, where ductopenia is not present and liver function improves with therapy. Therefore, a distinction between the two is warranted. There have been only 19 case reports in the English literature associating VBDS with HL. Here we report a 64-year-old female patient who presented with distributive shock and jaundice. Initial laboratory values revealed leukocytosis, mild transaminase elevation with significantly elevated alkaline phosphatase, along with direct hyperbilirubinemia. During hospital stay, the patient's liver function progressively worsened. Further workup did not reveal ductal dilation or obstruction and there were unremarkable results for infectious and autoimmune etiologies. Imaging studies with biopsy revealed extensive lymphadenopathy consistent with HL; liver biopsy showed cholestasis and ductopenia. Despite chemotherapy the patient succumbed to progressive liver failure and sepsis.
Solitary Fibrous Tumors of the Pleura: A Case Report and Review of the Literature
Authors: Mordenti Patrizia , Di Cicilia Roberto , Delfanti Rocco , Capelli Patrizio , Paties Carlo , Cavanna Luigi
Published: February 2018

Background

Solitary fibrous tumors of the pleura are rare and slow-growing neoplasms originating from the mesenchymal tissue underlying the mesothelial layer of the pleura. These tumors may have an unpredictable clinical course. Most cases occur in the sixth or seventh decades of life with no gender predilection, and more than 80% of cases are benign. The predominant clinical symptoms and signs are dyspnea, cough, chest pain, finger clubbing and hypoglycemia. However, because many patients are asymptomatic, the incidence rates are affected by the likelihood of its incidental detection, often through medical imaging of the chest. Surgical resection is the treatment of choice and is usually curative, even though local recurrence can occur many years after an adequate resection.

Methods

We reviewed the literature by performing a computerized search of MEDLINE, CANCERLIT and Embase with the terms fibrous tumor, pleura, surgery, immunohistochemical analysis. Articles and abstracts were also identified by back-referencing from other relevant papers.

Results

The clinical, radiological and pathological features of a 48-year-old woman with a primary solitary fibrous tumor of the pleura are reviewed and a literature search for other reported cases has been performed.

Conclusions

Although localized fibrous tumors of the pleura are considered histologically benign, there is a risk of recurrence and malignant transformation. Complete surgical resection is mandatory and long-term clinical and radiological follow-up is indicated in all patients. For malignant cases complete surgical resection may not be adequate and studies are needed to define the role of preoperative and postoperative systemic treatment. Diagnosis is very difficult in limited samples such as fine-needle aspiration or needle-core tissue biopsy, and immunohistochemical analysis may be useful to differentiate solitary fibrous tumor of the pleura from mesothelioma and other similar tumors.
Pharyngolaryngeal location of Kaposi's sarcoma with airway obstruction in an HIV-negative patient
Authors: Torretta Sara , Gaffuri Michele , Recalcati Sebastiano , Marzano Angelo Valerio , Cantarella Giovanna , Iofrida Elisabetta , Pignataro Lorenzo
Published: February 2018

Kaposi's sarcoma (KS) is a human herpes virus-8 (HHV-8)-associated angioproliferative disorder, and its occurrence may be favored by human immunodeficiency virus (HIV) infection and iatrogenic immunosuppression. It has also been postulated that a chronic inflammatory disease of the skin can pave the way to its development. KS generally involves mucosal and cutaneous sites, including the head and neck. An oropharyngeal location is quite common, but laryngeal involvement with possible upper airway obstruction and respiratory distress requiring tracheotomy is rare, and no hypopharyngeal locations have yet been reported.

We describe the case of a 68-year-old male patient who developed KS after immunosuppressive treatment for pemphigus vulgaris, an autoimmune bullous disease presenting with blisters and erosions on the skin and the oral mucosa. KS was initially localized to the oral cavity and oropharynx, but subsequent involvement of the laryngeal and hypopharyngeal tract led to acute airway obstruction and the need for tracheotomy. This unique case of pharyngolaryngeal KS suggests that clinicians faced with purple nodular lesions should consider a differential diagnosis of KS in immunocompromised patients, even if they are HIV negative, and should carefully manage the patency of the upper airways.
Reversible Bilateral Blepharoptosis following Oxaliplatin Infusion: A Case Report and Literature Review
Authors: Fanetti Giuseppe , Ferrari Laura AM , Pietrantonio Filippo , Buzzoni Roberto
Published: February 2018

Oxaliplatin, a platinum analogue employed in the treatment of colorectal cancer and various other neoplasms, is characterized by a broad range of adverse events. Peripheral neuropathy is probably the most peculiar and clinically relevant toxicity associated with its use and can be distinguished into two types: acute and chronic neurotoxicity. We report a case of acute reversible bilateral palpebral ptosis and dyspnea without bronchospasm or laryngospasm which occurred at the end of the third administration of adjuvant oxaliplatin by infusion for stage III colon cancer in a 54-year-old woman. Chlorphenamine and hydrocortisone were administered with fast resolution of dyspnea and slight improvement of ptosis. Complete resolution with no sequelae occurred in one hour. No further recurrence of blepharoptosis was described during the following days. The subsequent cycles were prescribed at reduced dosage without acute complications.
Surgical resection of locally advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma after gefitinib and review of the literature
Authors: Marech Ilaria , Vacca Angelo , Gnoni Antonio , Silvestris Nicola , Lorusso Vito
Published: February 2018

Gefitinib is the current first-line treatment for advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutations. The possibility of using gefitinib as neoadjuvant therapy is interesting because of the low toxicity profile of tyrosine kinase inhibitors. Here we report the case of a 67-year-old nonsmoking woman affected by locally advanced lung adenocarcinoma, in whom one-year treatment with gefitinib rendered the tumor amenable to surgical removal. The results of ongoing clinical trials exploring the ability of preoperative gefitinib to achieve better results than can be obtained with chemotherapy in patients selected on the basis of EGFR mutations are urgently awaited.
Optimal Local Control and Tolerability of Three-Dimensional Conformal Radiation Therapy in Prostate Cancer: A Single Institutional Experience of Dose Escalation in 125 Patients
Authors: Ferrera Giuseppe , Caminiti Giovanni , Grillo Antonietta , Alongi Filippo , Evangelista Giovanna , Greco Emanuela , Cucchiara Teresa , Bono Michele , Mortellaro Gianluca , Cirrincione Antonio , Dalia Francesca , Iacoviello Giuseppina , Caputo Vittorio , Midiri Massimo , Sciumè Francesco
Published: February 2018

Aims

To evaluate long-term late side effects, clinical and biochemical relapse in non-metastatic prostate cancer patients treated with dose escalation, from 74 to 78 Gy, by means of three dimensional conformal radiation therapy.

Materials and Methods

Clinical data of 125 patients with prostate cancer who underwent three-dimensional conformal radiation therapy were retrospectively evaluated. All patients were stratified, according to the NCCN classification, in low, intermediate and high risk, and all of them showed histologically proven adenocarcinoma stage T1–T3 with at least 2 years of follow-up. Late toxicity was analyzed using a modified Radiation Therapy Oncology Group toxicity scale.

Results

With a median of follow-up of 48 months, grade ≥2 late genitourinary toxicity was reported in 18% and grade ≥2 gastrointestinal toxicity was detected in 12%. The PSA relapse rate was 20% in the high-risk group, 7% in the intermediate-risk group, and 3% in the low-risk group.

Conclusions

Late side effects and tumor control in patients with non-metastatic prostate cancer in dose escalation from 74 to 78 Gy was acceptable. Three-dimensional conformal radiation therapy still represents a valid therapeutic option for departments where intensity-modulated radiation therapy or image-guided radiation therapy is still not available.
Sunitinib therapy in metastatic papillary thyroid cancer
Authors: Gori Stefania , Foglietta Jennifer , Rossi Marta , Hamzaj Alketa , Stocchi Lucia , Galuppo Carla , Picece Vincenzo , Puxeddu Efisio , Furlani Lino
Published: February 2018

We present the case of a 51-year-old woman with a follicular variant of papillary thyroid carcinoma. After surgery she experienced a relapse. Chemotherapy treatment led only to disease stabilization. In August 2009, we decided to start therapy with sunitinib 50 mg daily in an intermittent schedule (4 weeks on/2 weeks off). A CT scan after 3 months of treatment showed partial remission of disease according to the RE-CIST criteria. The patient continued sunitinib until January 2011, when CT evidenced progression in the mediastinal lymph nodes and pleura. Genetic analyses were carried out to determine if the clinical response in our patient was correlated with the presence of RET or BRAF mutations. No RET/PTC rearrangements or BRAF-V600E mutation, which are the two most common genetic alterations detected in papillary thyroid carcinoma, were found. It can be hypothesized that the activity of sunitinib in this patient was due to its antiangiogenic properties.
The Electronic Cigarette: Potential Health Benefit or Mere Business?
Authors: De Marco Cinzia , Invernizzi Giovanni , Bosi Sandra , Pozzi Paolo , Di Paco Adriano , Mazza Roberto , Ruprecht Ario Alberto , Munarini Elena , Boffi Roberto
Published: February 2018

Electronic cigarettes (e-cigarettes) have attracted considerable attention as a possible alternative to tobacco cigarettes, but uncertainties about their impact on health and indoor air quality as well as their commercial success without a clear regulatory framework are arousing concern. We have therefore tried to summarize the health-related implications of the use of e-cigarettes in order to help physicians and health professionals provide accurate information on this device. Given the lack of unequivocal scientific data on their toxicity and safety, we conclude that at the moment there is no reason to approve e-cigarettes as a safe alternative to tobacco smoke.
Ipilimumab in the Treatment of Metastatic Melanoma: A Summary of Recent Studies
Authors: Ascierto Paolo A
Published: February 2018

In the last 20 years, the survival and quality of life outcomes for patients with metastatic melanoma have been poor, with unsatisfactory results of chemotherapy and immunotherapy-based regimens. No drug or combination of drugs had any impact on survival until 2011, when ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), was approved for clinical use. Phase III trials have shown, for the first time ever, an overall survival benefit of ipilimumab compared with standard treatment, with a manageable toxicity profile. This review will discuss the mechanism of action of ipilimumab and the clinical trials that led to its approval.
Pilot Study of Intense Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: Retrospective Review of a Phase II Study
Authors: Xu Ben-hua , Chi Pan , Guo Jin-hua , Guan Guo-xian , Tang Tian-lan , Yang Ying-hong , Chen Ming-qiu , Song Jian-yuan , Feng Chang-yin
Published: February 2018

Aims and Background

Locally advanced rectal adenocarcinoma is typically treated with neoadjuvant chemoradiotherapy and surgery. We assessed the effect of an additional cycle of capecitabine/oxaliplatin chemotherapy before surgery in 57 patients with T3/4, N+/- or T1/2, N+ rectal cancer.

Materials and Study Design

Radiotherapy (total dose, 50.4 Gy) was combined with three cycles of chemotherapy (two cycles concomitant with radiotherapy), and each cycle consisted of oxaliplatin (130 mg/m2 on day 1) and capecitabine (825 mg/m2, twice per day from day 1 to day 14) for 21 days. In addition to assessing the safety of this treatment, the primary endpoint was pathological complete response (pCR). The secondary endpoint was the change in primary tumor and node stage from pre-treatment to post-surgery.

Results

Eleven patients (19%) experienced complete tumor regression and 23 patients (40%) experienced tumor regression grade 3. Tumor down-staging occurred in 31 patients (54.4%) and down-staging of nodes occurred in 25 patients (43.9%). There was a significant difference in tumor stage between pre-treatment and post-surgery (P <0.001). Patients with less advanced N stages had significantly better recurrence-free survival but similar metastasis-free survival and overall survival. Tumor regression grade was not associated with overall survival, recurrence-free survival or metastasis-free survival. The most common adverse events were pulmonary infection (n = 6, 10.5%) and intestinal obstruction (n = 6, 10.5%).

Conclusions

An additional cycle of chemotherapy given after chemoradiotherapy and before surgery provided good efficacy and had a satisfactory safety profile in patients with locally advanced rectal cancer.
Tumor Volume Reduction Assessed by Planning Computed Tomography in Patients with Rectal Cancer during Preoperative Chemoradiation: Impact of Residual Tumor Volume on the Prediction of Pathologic Tumor Regression
Authors: Lee Jung Ae , Yang DaeSik , Yoon Won Sup , Park Young Je , Kim Chul Yong , Moon Hong-young , Lee Sun-il
Published: February 2018

Aims and Background

To determine whether the residual tumor volume measured using the Eclipse treatment planning system correlates with pathologic tumor regression grade after preoperative chemoradiotherpy for rectal cancer.

Materials and Methods

The study included 30 patients with rectal cancer who had undergone preoperative chemoradiotherpy followed by surgery from June 2008 to April 2011 at the Korea University Guro Hospital. The tumor volume was measured using the Eclipse treatment planning system in the initial simulation computed tomography and boost planning computed tomography. The correlation between the residual tumor volume in boost planning computed tomography and the pathologic tumor regression grade was analyzed. Tumor regression grade defined in the American Joint Committee on Cancer 7th edition was used.

Results

The mean and median residual tumor volume was 57.34% ± 20.37% and 52.35% (range, 18.42%-95.79%), respectively. After surgery, pathologic complete response (tumor regression grade 0) occurred in 4 patients (13.33%), moderate response (tumor regression grade 1) in 18 patients (60%), minimal response (tumor regression grade 2) in 4 patients (13.33%), and poor response (tumor regression grade 3) in 4 patients (13.33%). When residual tumor volume was categorized into two groups (<50% and ≥50%), complete or moderate regression (tumor regression grade 0 or 1) was significantly greater for patients with a residual tumor volume <50% (P <0.05). The mean residual tumor volume of tumor regression grade 0 or 1 was 49.07% ± 18.39% and that of tumor regression grade 2 or 3 was 76.31% ± 16.94% (P <0.05).

Conclusions

Residual tumor volume measured using routine boost planning computed tomography during preoperative chemoradiotherpy correlated significantly with pathologic tumor regression grade after surgery.
Mono-institutional Italian Experience with a Double-lumen Balloon-brachytherapy Device for Early Breast Cancer: Results at a 5-year Minimum follow-up
Authors: Fozza Alessandra , Giannelli Flavio , Blandino Gladys , Bosetti Davide , Milanese Marialetizia , Agostinelli Stefano , Garelli Stefania , Corvò Renzo , Guenzi Marina
Published: February 2018

Aims and Background

To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed.

Methods

Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity.

Results

Median follow-up was 80.5 months (range, 60–98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy seven percent of the patients were satisfied with their cosmetic results.

Conclusions

Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.
Sexual Satisfaction Assessment in 194 Nonmetastatic Cancer Patients on Treatment or in follow-up
Authors: Maruelli Alice , Ripamonti Carla , Bandieri Elena , Miccinesi Guido , Pessi Maria Adelaide , Buonaccorso Loredana
Published: February 2018

Aims and Background

Sexuality is an important aspect of quality of life, but health care professionals still avoid discussing sexual issues with cancer patients.

Methods and Study Design

We present a secondary analysis of sexuality issues according to the results of a survey on 266 patients with early-stage cancer. The aim of the survey was to ascertain the feasibility and clinical usefulness of questionnaires (Patient Dignity Inventory, PDI; Hospital Anxiety and Depression Scale, HADS; Edmonton Symptom Assesssment Scale, ESAS; FACIT-spiritual well-being scale, FACITSP; System of Belief Inventory, SBI-15R) investigating aspects such as dignity, hope and research of meaning in life. The present study is an ancillary analysis of the full sample, and we have focused on the results of FACIT-SP about the correlation between sexual satisfaction and clinical characteristics in 108 patients having solid tumors and 86 having hematological malignancies with no metastases who were on active cancer treatment or in follow-up in four different cancer treatment settings during the first half of 2011.

Results

The median age of the 194 patients was 65 years, 112 were women, 155 were undergoing treatment and 39 were in follow-up. Eighty-three patients were above the cutoff score for HADS. Among the 171 believers, 80 were churchgoers and 91 were nonchurchgoers, whereas the nonbelievers among the patients were 23. Thirty-five percent of the patients did not respond to the sexuality item of the questionnaire. Among the responders (n = 126), 36% reported having no sexual satisfaction (score = 0). Sexual dissatisfaction was greater in older patients (47% vs 31%, not significant [NS]), women (43% vs 27%, NS), patients on treatment (38% vs 25%, NS), patients who requested psychological support (53% vs 25%, P = 0.001), patients with high levels of anxiety and depression, i.e., HADS scores >10 (44% vs 30%, NS), nonbelievers (61% vs 34% among churchgoers, 29% among believers but nonchurchgoers, P = 0.046).

Conclusions

One out of 3 patients did not respond to the item on sexuality. Among the responders, 1 out of 3 reported having no sexual satisfaction. Half of the patients receiving psychological support considered their sexual life not satisfying. Clinical interviews and specific questionnaires on sexuality should be used to investigate this particular aspect.
Coworking spaces in mid-sized cities: A partner in downtown economic development
Authors: Jamal Audrey C
Published: February 2018

The 21st century economy is knowledge-intensive, creative and flourishing in larger urban centres. Less is known about how smaller urban centres are faring in this new economy. This research aims to fill that gap by exploring whether mid-sized cities, in a designated growth area in Ontario, Canada, can leverage the knowledge economy and foster local economic development to help revitalize their ailing downtowns. Through a case study approach, this research looks at the role that coworking, or shared workspaces, can play in the local economy of mid-sized cities in Ontario. Recognizing the role that community-based actors play in urban affairs, this paper uses a local economic development framework to explore the role of coworking spaces in the urban economic fabric of mid-sized city downtowns. Survey responses and interviews, coupled with insights from global surveys on coworking and a literature review, begin to tell the story of how economic change is playing out in mid-sized cities, illustrating the importance of an innovative, collaborative and inclusive approaches to city building and local economic development.
A Literature Review of Academic Interventions for College Students With Learning Disabilities
Authors: Zeng Wen , Ju Song , Hord Casey
Published: February 2018

The number of students with learning disabilities (LD) enrolling in postsecondary education has increased rapidly over the past decade. It is imperative to investigate what interventions have been used to assist students with LD in achieving academic success. To examine the interventions currently used to support students with LD in postsecondary education, the authors reviewed the relevant literature from 2000 to 2016. Four primary types of interventions were identified from 12 articles: assistive technology, direct assistance, strategy instruction, and comprehensive support program. The findings indicate that the student-centered approach is an important characteristic of current academic interventions for students with LD in postsecondary education. The authors also provide implications for researchers and practitioners for improving postsecondary interventions on students with LD.
S–N curves for fatigue life estimation of friction stir welded 19501 aluminum alloy T-joint
Authors: Gope Prakash Chandra , Kumar Harshit , Purohit Himanshu , Dayal Manish
Published: February 2018

In this study, the mechanical properties and fatigue life of 19501 aluminum alloy friction stir welded T-joint is investigated. Tensile properties of friction stir welded joint show that there is a marginal reduction of about 5% in strength and ductility as compared to unwelded 19501 aluminum alloy. Fatigue test results of T-joint specimen at two stress ratios of 0 and -1 show that there is a reduction of 15% in fatigue strength due to change of stress ratio from -1 to 0. Also, higher variation is seen in fatigue strength in low cycle zone than the high cycle zone. Effect of mean stress on fatigue life is discussed on the basis of different mean stress effect models. Morrow’s mean stress effect model is found to be better than other models. Micrographs from the fracture surfaces of retreating side, mid weld zone, and advancing side of the T-joint indicates that fracture surfaces are cleavage fracture. Different sizes of inter-metallic bonding are seen in the micrographs, which indicate that fracture is initiated due to breaking of the brittle inter-metallic bonding.
Serum soluble CD25 as a risk factor of renal impairment in systemic lupus erythematosus — a prospective cohort study
Authors: Zhang R J , Zhang X , Chen J , Shao M , Yang Y , Balaubramaniam B , Sun X L , Ambrus J L , He J , Li Z G
Published: February 2018

Objective

Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE).

Methods

Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs). All patients were followed up for 24 weeks, and sCD25 was measured by enzyme-linked immunosorbent assay. Clinical and laboratory data were recorded at baseline and then every two weeks until week 24. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI)-2K was adopted for assessing disease activity at all visits.

Results

Serum sCD25 levels were significantly increased in SLE patients compared to those in HCs ( p < 0.001). More patients in the high-sCD25 group had lupus nephritis, arthritis and vasculitis ( p = 0.010, p = 0.023 and p = 0.042, respectively). SLEDAI-2K, erythrocyte sedimentation rate, C-reactive protein and 24-hour urinary protein excretion were all associated with high levels of sCD25 ( p < 0.001, p = 0.002, p = 0.038 and p = 0.029, respectively). During the 24-week follow-up, more patients in the high-sCD25 group developed renal impairment (48% vs 6.2%, p = 0.005), and higher levels of sCD25 ( p = 0.033) were found at the time of onset of renal disease.

Conclusions

Serum sCD25 is a hallmark of disease activity and a predictor of renal disease in patients with SLE.
Market-based but state-led: The role of public development banks in shaping market-based finance in the European Union
Authors: Mertens Daniel , Thiemann Matthias
Published: February 2018

This paper examines the European Union’s strategy of governing the economy through financial markets by focusing on the largely unacknowledged role of public development banks, including the multilateral European Investment Bank. It argues that these state-owned financial institutions have moved into a key position in the recent evolution of the European financial system and economic governance. Since the crisis, policy makers have used them to address the intrinsic volatility and excess liquidity of contemporary financial markets, as well as offset the constraints on public investment imposed by institutionalized fiscal austerity. The paper provides evidence for this claim through an analysis of the emergent policy nexus between the Investment Plan for Europe and the Action Plan on Building a Capital Markets Union. Based on official documents and interview data, it specifically traces the risk-sharing devices for small- and medium-sized enterprise and infrastructure finance set up by development banks within these initiatives. Equipped with public guarantees, they have been instrumental for the promotion of securitization markets and public–private partnerships through increased multilevel collaborations among development banks. The anchor role of such quasi-fiscal state actors in shaping capital markets, the paper concludes, has profound political implications, and therefore warrants further scholarly attention.
Soft affirmative action lacking traction? An early qualitative exploration of the RecruitAbility Scheme performance within the Australian Public Service
Authors: Mellifont Damian
Published: February 2018

Politicians are challenged to increase economic opportunities for citizens with disabilities. Today, the employment of persons with disabilities within the Australian Government is being supported through a RecruitAbility Scheme. With full implementation of the Scheme underway, it is a timely research exercise to critically explore early progress. Enabling such exploration, this study has applied qualitative content analysis to 12 publicly available texts that collectively assess early (i.e. pilot and first year full implementation) program performance. Findings of this critical analysis should be of particular interest to policymakers, practitioners, and persons with disabilities. The findings reveal that despite policy rhetoric, the Scheme is making only modest achievements. This exploratory study supports a biopsychosocial model inspired approach, which aims to improve the recruitment, retainment, and career development of individuals with disabilities across the Australian Public Service.
Drug-Induced Restless Legs Syndrome
Authors: Patatanian Edna , Claborn Melanie K.
Published: February 2018

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.
Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis
Authors: Boyce Eric G. , Rogan Edward L. , Vyas Deepti , Prasad Neel , Mai Yvonne
Published: February 2018

Major Objectives: To review the efficacy, safety, and economics of sarilumab, an interleukin-6 (IL-6) receptor antagonist, in the treatment of rheumatoid arthritis (RA). Data Sources: PubMed (1966 to January 2018), Clinicaltrials.gov (January 2018), and Scopus (1970 to January 2018) were searched using sarilumab, Kevzara, REGN88, and SAR153191. Study Selection and Data Extraction: Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety. Data Synthesis: Data from randomized, double-blind, controlled, published clinical studies weeks demonstrated statistically significantly higher American College of Rheumatology (ACR) 20, ACR50, and Disease Activity Score-28 (DAS28) remission response rates and improvements in DAS28 and Health Assessment Questionnaire–Disability Index scores for sarilumab monotherapy versus adalimumab monotherapy (P < 0.05) and for sarilumab versus placebo in patients receiving methotrexate or other conventional synthetic disease-modifying antirheumatic drugs (DMARDs); P < 0.05. The ACR20 and ACR50 response rates were, respectively, 56-72% and 35-46% for sarilumab, 58% and 30% for adalimumab, and 33-34% and 15-18% for placebo. DAS28 remission rates were 20-34% for sarilumab, 7% for adalimumab, and 7-10% for placebo. Sarilumab has a higher risk for neutropenia than tocilizumab, the other IL-6 inhibitor, but a lower risk for dyslipidemia, injection site reactions, and gastrointestinal perforation. The acquisition costs of sarilumab are expected to be similar to those of most other biologic DMARDs. Conclusion: Sarilumab is an alternative to biologic DMARDs or targeted synthetic DMARDs in patients with moderate to severely active RA who have not responded adequately to prior conventional synthetic DMARDs or tumor necrosis factor-α inhibitors.
Multifocal Cytokeratin Expression in a Dedifferentiated Solitary Fibrous Tumor With Heterologous Rhabdomyosarcomatous Differentiation: A Challenging Diagnosis!
Authors: Creytens David , Ferdinande Liesbeth , Van Dorpe Jo
Published: February 2018

We report the case of a dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation in a 74-year-old male presenting with a rapidly growing, large soft tissue tumoral mass in the gluteal muscles of the right hip. Dedifferentiation in solitary fibrous tumor had not been recognized until very recently and is an extremely rare phenomenon in this tumor type. In the present case, the diagnosis of dedifferentiated solitary fibrous tumor was difficult because of the absence of areas of conventional solitary fibrous tumor with a predominantly poorly differentiated, anaplastic tumor component in the incision biopsy composed of heterogeneous areas with small blue round cell (Ewing sarcoma-like), rhabdoid, epithelioid, and pleomorphic morphology. Moreover, the “unforeseen” strong patchy to multifocal positivity for cytokeratin AE1/AE3 and desmin made the diagnosis of a dedifferentiated solitary fibrous tumor even more challenging in this case. The morphology (presence of branching thin-walled, hemangiopericytoma-like blood vessels) and the immunohistochemical profile (including STAT6 and GRIA2 positivity) were very useful to differentiate this very challenging case of a cytokeratin-positive dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation from a broad list of differential diagnoses.
Potential Role of ADRA2A Genetic Variants in the Etiology of ADHD Comorbid With Tic Disorders
Authors: Xu Defeng , Liu Lu , Li Haimei , Sun Li , Yang Li , Qian Qiujin , Wang Yufeng
Published: February 2018

Objective: To evaluate the role of the adrenergic receptor alpha-2A gene ( ADRA2A) in the genetic etiology of ADHD comorbid with tic disorders (ADHD+TD). Method: Two single nucleotide polymorphisms (SNPs) of ADRA2A were genotyped and analyzed in 936 normal controls and 1,815 ADHD probands, including 1,249 trios. Approximately 16% of the ADHD probands also had a diagnosis of TD. Results: No significant association was found between ADRA2A and ADHD in general. Case-control analyses indicated different allelic and genotypic distributions of rs553668 between ADHD+TD and controls in males. Family-based association tests showed that the G allele of rs1800544, the A allele of rs553668, and the GA haplotype consisting of these two SNPs were overtransmitted in the ADHD+TD trios, especially in males. Moreover, the allelic/genotypic distribution and allelic transmission were different between ADHD+TD and ADHD without TD. Conclusion: ADRA2A may be associated with ADHD+TD, especially in males.
Axial crushing and transverse bending responses of sandwich structures with lattice core
Authors: Taghipoor Hossein , Damghani Nouri Mohammad
Published: February 2018

The performance of sandwich structure with expanded metal sheets as the core was studied under axial crushing and transverse impact bending. Relationships between the force and displacement at the mid-span of the sandwich beams were obtained from the experiments. Numerical simulations were carried out using ABAQUS/EXPLICIT and the results were thoroughly compared with the experimental results. Then, the influence of the cell orientation and size of the cell were investigated. It was shown that the cell orientation was a critical parameter affecting the failure mode and energy absorption capability, leading to the increase in the peak load and specific energy absorption during the axial crushing tests. Specific energy absorption of the sandwich beams with lattice core under axial crushing ranges from 117 to 2934 J/kg, which is higher than that of beams under transverse bending. The results showed that the increase in cell angle up to ϴ = 90 increased the energy absorption by 624.4%. It was found that effects of the cell size and cell orientation on the energy absorption were dependent on each other governing the low-velocity impact response of the sandwich beams with lattice cores.
Stranger in a Strange Land: Using Heterotopic Transplantations to Study Nature vs Nurture in Brain Development
Authors: Petros Timothy J
Published: February 2018

The mammalian brain develops from a simple sheet of neuroepithelial cells into an incredibly complex structure containing billions of neurons with trillions of synapses. Understanding how intrinsic genetic programs interact with environmental cues to generate neuronal diversity and proper connectivity is one of the most daunting challenges in developmental biology. We recently explored this issue in forebrain GABAergic inhibitory interneurons, an extremely diverse population of neurons that are classified into distinct subtypes based on morphology, neurochemical markers, and electrophysiological properties. Immature interneurons were harvested from one brain region and transplanted into a different region, allowing us to assess how challenging cells in a new environment affected their fate. Do these grafted cells adopt characteristics of the host environment or retain features from the donor environment? We found that the proportion of interneuron subgroups is determined by the host region, but some interneuron subtypes maintain features attributable to the donor environment. In this commentary, I expound on potential mechanisms that could underlie these observations and explore the implications of these findings in a greater context of developmental neuroscience.
Development of Molecularly Targeted Agents and Immunotherapies in Glioblastoma: A Personalized Approach
Authors: Coleman Niamh , Ameratunga Malaka , Lopez Juanita
Published: February 2018

Over the past decade, precision cancer medicine has driven major advances in the management of advanced solid tumours with the identification and targeting of putative driver aberrations transforming the clinical outcomes across multiple cancer types. Despite pivotal advances in the characterization of genomic landscape of glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. Immunotherapy strategies similarly have had limited success. Multiple deficiencies still exist in our knowledge of this complex disease, and further research is urgently required to overcome these critical issues. This review traces the path undertaken by the different therapeutics assessed in glioblastoma and the impact of precision medicine in this disease. We highlight challenges for precision medicine in glioblastoma, focusing on the issues of tumour heterogeneity, pharmacokinetic-pharmacodynamic optimization and outline the modern hypothesis-testing strategies being undertaken to address these key challenges.
Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis
Authors: Roostaei Tina , Sadaghiani Shokufeh , Mashhadi Rahil , Falahatian Masih , Mohamadi Esmaeil , Javadian Nina , Nazeri Aria , Doosti Rozita , Naser Moghadasi Abdorreza , Owji Mahsa , Hashemi Taheri Amir Pejman , Shakouri Rad Ali , Azimi Amirreza , Voineskos Aristotle N , Nazeri Arash , Sahraian Mohammad Ali
Published: February 2018

Background:

Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity.

Objectives:

To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures.

Methods:

In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90).

Results:

While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele.

Conclusion:

C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.