bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Riluzole Influence Bone Formation?
Authors: Schroeder Gregory D. , Kepler Christopher K. , Grad Sibylle , Alini Mauro , Fang Taolin , Markova Dessislava Z. , Koerner John D. , Rajasekaran Shanmuganathan , Chapman Jens , Kandziora Frank , Schnake Klaus J. , Dvorak Marcel F. , Oner F. Cumhur , Vaccaro Alexander R. 
Published: March 2019

Study Design.
A post-test design biological experiment.

Objective.
The aim of this study was to evaluate the osteogenic effects of riluzole on human mesenchymal stromal cells and osteoblasts.

Summary of Background Data.
Riluzole may benefit patients with spinal cord injury (SCI) from a neurologic perspective, but little is known about riluzole's effect on bone formation, fracture healing, or osteogenesis.

Methods.
Human mesenchymal stromal cells (hMSCs) and human osteoblasts (hOB) were obtained and isolated from healthy donors and cultured. The cells were treated with riluzole of different concentrations (50, 150, 450 ng/mL) for 1, 2, 3, and 4 weeks. Cytotoxicity was evaluated as was the induction of osteogenic differentiation of hMSCs. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and with Alizarin red staining. Osteogenic gene expression of type I collagen (Col1), ALP, osteocalcin (Ocn), Runx2, Sox9, Runx2/Sox9 ratio were measured by qRT-PCR.

Results.
No cytotoxicity or increased proliferation was observed in bone marrow derived hMSCs and primary hOBs cultured with riluzole over 7 days. ALP activity was slightly increased in hMSCs after treatment for 2 weeks with riluzole 150 ng/mL and slightly upregulated by 150% (150 ng/mL) and 90% (450 ng/mL) in hMSCs at 3 weeks. In hOBs, ALP activity almost doubled after 2 weeks of culture with riluzole 150 ng/mL (P < 0.05). More pronounced 2.6-fold upregulation was noticed after 3 weeks of culture with riluzole at both 150 ng/mL (P = 0.05) and 450 ng/mL (P = 0.05). No significant influence of riluzole on the mRNA expression of osteocalcin (OCN) was observed.

Conclusion.
The effect of riluzole on bone formation is mixed; low-dose riluzole has no effect on the viability or function of either hMSCs or hOBs. The activity of ALP in both cell types is upregulated by high-dose riluzole, which may indicate that high-dose riluzole can increase osteogenic metabolism and subsequently accelerate bone healing process. However, at high concentrations, riluzole leads to a decrease in osteogenic gene expression, including Runx2 and type 1 collagen.

Level of Evidence: N/A
Pathologic Response to Neoadjuvant Therapy is Associated With Improved Long-term Survival in High-risk Primary Localized Malignant Peripheral Nerve Sheath Tumors
Authors: Shurell-Linehan Elizabeth , DiPardo Benjamin J. , Elliott Irmina A. , Graham Danielle S. , Eckardt Mark A. , Dry Sarah M. , Nelson Scott D. , Singh Arun S. , Kalbasi Anusha , Federman Noah , Bernthal Nicholas M. , Eilber Fritz C. 
Published: March 2019

Background:
Malignant peripheral nerve sheath tumors (MPNSTs) comprise a rare, aggressive subtype of soft tissue sarcoma. While surgery is the mainstay of therapy for this disease, the role of neoadjuvant therapy remains undefined.

Methods:
This study reviewed patients 16 years of age and older who underwent surgical treatment for MPNST between 1974 and 2012 at the authors’ institution. Univariate and multivariate analyses were performed of clinicopathologic and treatment variables predictive of disease-specific survival (DSS) and disease-free survival.

Results:
Eighty-eight patients with primary localized MPNST underwent surgical treatment between 1974 and 2012 at our institution. Of these, 38 (43%) underwent neoadjuvant chemotherapy and had tissue available for analysis. Neoadjuvant radiation was given to 25 patients (68%). The median follow-up time for survivors was 12.5 years (range, 4 to 27 y). Nine patients (23%) had underlying MPNST. With a cutoff of ≥90% pathologic necrosis and/or fibrosis defining response, we identified 14 responders (36%). On univariate analysis, patient age, tumor size, and pathologic response were significantly associated with DSS (P=0.015, 0.011, and 0.030, respectively).

Conclusions:
Although the impact of neoadjuvant chemotherapy on the outcome of primary localized MPNST patients continues to be debated, this study shows that a pathologic response to therapy is associated with a significant improvement in DSS. The challenge moving forward is to determine upfront which patients will be “responders” to standard systemic therapy and which patients should be considered for newer investigational agents as part of a clinical trial.
BCLC-B Subclassification and the Hong Kong Liver Cancer System in Intermediate Hepatocellular Carcinoma
Authors: Longo Larisse , Rodrigues de Freitas Laura B. , Santos Deivid , Grivicich Ivana , Álvares-da-Silva Mário R. 
Published: March 2019

Introduction:
The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC).

Objective:
To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients.

Patients and Methods:
A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC.

Results:
A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%).

Conclusion:
In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.
Sentinel Lymph Node Biopsy in Patients With Acral Melanoma: Analysis of 201 Cases From the Brazilian National Cancer Institute
Authors: Nunes Luiz Fernando , Mendes Gélcio L.Q. , Koifman Rosalina J. 
Published: March 2019

BACKGROUND
Sentinel lymph node biopsy (SLNB) is the most powerful predictor of relapse-free survival (RFS) and overall survival (OS). No studies have evaluated survival of acral melanoma (AM) undergoing SLNB in Brazil.

OBJECTIVE
The objective of this study was to investigate the factors associated with the survival of patients with AM undergoing SLNB.

MATERIALS AND METHODS
Patients diagnosed with AM and submitted to SLNB were included in this study. We evaluated the epidemiologic, clinical, and histopathological data. Overall survival and RFS curves were estimated using the Kaplan–Meier method. Multivariable analyses were conducted using the Cox regression model.

RESULTS
Among the 201 patients, 117 (58.2%) were female. The median age was 64 years old. Median tumor depth was 5.0 mm. Lesions were ulcerated in 134 (66.7%). Five-year OS and RFS rates were 44.6% and 38.6%, respectively. Median follow-up time was 39 months. The factors associated with OS were Breslow thickness, ulceration, and SLNB status, and for RFS, they were Breslow thickness and SLNB status.

CONCLUSION
This is the largest series of AM submitted to SLNB. The 5-year OS and RFS rates were low (44.6% and 38.6%, respectively), and the main prognostic factors for OS were Breslow thickness, ulceration, and the status of SLNB.
Utilization pattern of hormone therapy in UK general practice between 1996 and 2015: a descriptive study
Authors: Burkard Theresa , Moser Manon , Rauch Marlene , Jick Susan S. , Meier Christoph R. 
Published: March 2019

Abstract

Objective:
To describe the long-term trends in hormone therapy (HT) use in UK general practice after evidence of associated increased risks of cardiovascular disease (CVD) and breast cancer, subsequent guideline changes in 2003/2004 advising individualized HT prescribing, and halving of HT use between 2002 and 2005.

Methods:
We conducted a descriptive study to quantify annual proportions of overall and new HT use in women aged 40 to 79 years, using the UK-based Clinical Practice Research Datalink (1996-2015). We further described HT utilization patterns (drug type, administration route, dose) within 2-year blocks overall and within subpopulations with pre-existing CVD or breast cancer.

Results:
Overall HT use continued to decline from 9.4% in 2006 to 7.5% in 2015. Between 1998 and 2001, the proportion of HT initiation was around 1.7%, which halved by 2005 (0.8%), and increased again up until 2015 (1.0%). The mean age of HT users increased from 54.7 in 1996/1997 to 56.6 in 2002/2003, and leveled off at 57 to 58 years in 2014/2015. The prevalence of CVD in HT users decreased from a peak of 5.8% in 2002/2003 to 4.5% in 2014/2015, whereas breast cancer prevalence continuously increased from 0.9% in 1996/1997 to 1.9% in 2014/2015. Overall, we observed trends towards use of estrogen therapy, vaginal HT, and lower HT dose after 2002/2003, which were stronger among subpopulations with pre-existing CVD or breast cancer.

Conclusion:
Our study suggests that the HT guideline changes implemented in UK clinical practice resulted in safer HT use, particularly in women with pre-existing CVD or breast cancer.
Depression Is Associated With Reduced Outpatient Cardiac Rehabilitation Completion Rates
Authors: Edwards Brooke L. , Sydeman Sumner J. 
Published: March 2019

Purpose:
Depression is associated with recurrent cardiac events and death in patients with coronary heart disease and congestive heart failure. Furthermore, depression may be associated with reduced completion of outpatient cardiac rehabilitation (CR), an empirically supported treatment for patients with coronary heart disease and congestive heart failure that reduces recurrent coronary events and cardiac mortality. The goal of the current systematic review and meta-analysis was to explore the association between depression and outpatient CR completion.

Method:
A systematic literature review cross-referenced 3 electronic databases (PsycINFO, MEDLINE, and Dissertation Abstracts International) from inception through February 15, 2015. Studies quantifying an association between depression and outpatient CR completion were identified for review. A random-effects model was used to pool quantitative data, moderators were tested, and publication bias was analyzed.

Results:
Seventeen studies with 19 independent samples consisting of 30 586 cardiac patients were included in the meta-analysis. A moderate inverse relationship between depression and outpatient CR completion was observed (g = −0.44; 95% CI, −0.59 to −0.29), indicating that depressed CR patients were significantly less likely to complete their prescribed CR programs. No significant moderator variables were identified. A minor amount of publication bias was detected.

Conclusion:
Depression is associated with reduced outpatient CR completion rates. Future research should focus on attendance interventions for depressed CR patients, as completion of outpatient CR reduces cardiac and all-cause mortality.
AUSTRALIAN AND NEW ZEALAND STUDY OF PHOTODYNAMIC THERAPY IN CHOROIDAL AMELANOTIC MELANOMA
Authors: O'Day Roderick F. , Pejnovic Tanya M. , Isaacs Tim , Muecke James S. , Glasson William J. , Campbell William G. 
Published: March 2019

Purpose:
To evaluate the safety and efficacy of primary photodynamic therapy (PDT) for posterior choroidal amelanotic melanomas.

Methods:
Patients with posterior choroidal amelanotic melanomas up to 6 mm in height were treated with PDT using verteporfin as the photosensitizing agent. Treatment was repeated every 3 months until the tumor was flat up to a maximum of 6 treatments. Tumor response and recurrence was assessed by clinical examination, photography, and ultrasonography. Patients were monitored 3 monthly for a minimum of 3 years.

Results:
Thirty-six of 41 (88%) patients had complete regression after an initial course of PDT. Of them, 20 (56%) had no recurrence, 3 (8%) had recurrences that were successfully treated with further PDT, and 13 (36%) had recurrences that failed or were not amenable to further PDT. None of the measured baseline characteristics predicted treatment outcomes. There was no reduction in visual acuity due to PDT. The mean follow-up time was 3.5 years.

Conclusion:
In this large series, primary PDT was highly effective in achieving initial regression of posterior choroidal amelanotic melanomas. Photodynamic therapy is a vision-preserving treatment option for these tumors; however, patients need to be followed up closely because there is a significant rate of recurrence.
Anatomical and Visual Effects of the MyoRing Implantation Measured by the ABCD Keratoconus Grading System
Authors: Sedaghat Mohammad-Reza , Momeni-Moghaddam Hamed , Belin Michael W. , Akbarzadeh Reyhaneh , Sakhaee Mehdi , Armanfar Fatemeh , Shahri Farkhondeh , Akhavan Rezayat Amir 
Published: March 2019

Objective:
To assess the anatomical changes produced by implantation of the complete intracorneal ring (MyoRing; DIOPTEX, GmbH, Linz, Austria) on the different corneal anatomical layers as measured by the ABCD keratoconus staging system 6 months after operation.

Methods:
Seventeen eyes of 17 keratoconic patients implanted with MyoRing using the femtosecond laser were assessed preoperatively and postoperatively. Distance uncorrected visual acuity and distance corrected visual acuity (DCVA), refraction, and Scheimpflug tomography with Pentacam HR were determined for each patient. The 4 ABCD parameters were recorded, which include the anterior and posterior radius of curvature from a 3.0-mm optical zone centered on the thinnest point (TP) (A & B, respectively), the thinnest corneal thickness (C), and DCVA (D).

Results:
Statistically significant improvement (preoperatively vs. postoperatively) in the DCVA (0.40±0.21 vs. 0.67±0.20 in decimal notation, P=0.001) associated with significant flattening effect was observed in both anterior (6.02±0.40 vs. 7.18±0.54 mm, P<0.001) and posterior (4.49±0.41 vs. 4.66±0.40 mm, P=0.001) radius of curvature. There was no significant change in the corneal thickness at the TP (P=0.981). The largest magnitude of change occurred on the anterior surface as measured by the “A” parameter. The average ABCD keratoconus staging before MyoRing implantation was A4B4C2D2 and changed to A1B4C2D1 6 months after ring implantation.

Conclusion:
Despite the placement of MyoRings in the posterior one-third of the cornea, the greatest changes in curvature occurred on the anterior corneal surface. The ABCD classification and staging system allows for a differential assessment of the different anatomical layers and may prove useful in better understanding of the geometric (structural) and functional changes after MyoRing implantation, as well as with other corneal procedures.
Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen
Authors: Mueller Alexander , Starobova Hana , Morgan Michael , Dekan Zoltan , Cheneval Olivier , Schroeder Christina I. , Alewood Paul F. , Deuis Jennifer R. , Vetter Irina 
Published: March 2019

Abstract
Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, postsurgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute postsurgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively antiallodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects. In addition, the selective NaV1.7 inhibitors ProTx-II and PF-04856264 as well as the clinical candidate CNV1014802 also reduced mechanical allodynia. Interestingly, co-administration of the opioid receptor antagonist naloxone completely reversed analgesic effects of Pn3a, indicating an involvement of endogenous opioids in the analgesic activity of Pn3a. In addition, we found superadditive antinociceptive effects of subtherapeutic Pn3a doses not only with the opioid oxycodone but also with the GABAB receptor agonist baclofen. Transcriptomic analysis of gene expression changes in dorsal root ganglia of mice after surgery did not reveal any changes in mRNA expression of endogenous opioids or opioid receptors; however, several genes involved in pain, including Runx1 (Runt related transcription factor 1), Cacna1a (CaV2.1), and Cacna1b (CaV2.2), were downregulated. In summary, these findings suggest that pain after surgery can be successfully treated with NaV1.7 inhibitors alone or in combination with baclofen or opioids, which may present a novel and safe treatment strategy for this frequent and poorly managed condition.
Forensic Medical Examinations: Imagining Justice
Authors: Ekroos Rachell A. , Shannon Sarah E. 
Published: March 2019

ABSTRACT
Depending on the type of physical contact involved during a sexual assault offense, samples collected from a suspect's body may carry greater probative value than samples collected from a victim's body. However, unlike forensic medical examinations for persons identified as victims of a sexual assault, no professional consensus exists for what constitutes a high-quality forensic medical examination standard for persons identified as suspects, or the accused. The purpose of this article is to explore underlying assumptions that may contribute to disparate practices and inequalities in the provision of forensic medical examinations for persons suspected of committing a sexual offense and persons identified as victims of a sexual offense.
Forensic Staff Attitudes Toward Men Who Have Sexually Offended: A General Public Comparison
Authors: Challinor Laura , Duff Simon 
Published: March 2019

ABSTRACT

Objectives:
The aim of this study was to explore the attitudes toward men who have sexually offended (MSO) between the general public and professionals and paraprofessionals in forensic settings.

Background:
Existing research shows a number of different factors that appear to be important in the development, maintenance, and deterioration of attitudes toward MSO. The exploration of such factors requires further exploration.

Method:
A convenience sample was used for the cross-sectional study. Five hundred fifty-three participants were recruited from the general public and forensic hospitals, both private and National Health Service. An online version of the Attitudes Towards Sex Offenders scale (Hogue, 1993) was distributed via email and social media.

Results:
Gender was not found to have any impact on the attitudes individuals held toward MSO. The general public was found to have significantly more negative attitudes when compared with those exposed to MSO at work (professional and paraprofessional staff). Duration of employment did not make attitudes any more or less positive.

Conclusion:
The clinical and societal implications of the research are important for MSO to reduce risk within forensic establishments and be supported to reintegrate successfully into the community. Without the support from both staff and the general public at each stage of rehabilitation, desistance is less likely to be maintained. Research continues to provide varying results regarding the factors that influence the nature of attitudes toward MSO.
Chinese Version of the Assessment of Survivor Concerns Scale for Gynecological Cancer Survivors: A Psychometric Study in Taiwan
Authors: TSAI Li-Yun , WANG Kung-Liahng , TSAI Jung-Mei , TSAY Shiow-Luan 
Published: March 2019

ABSTRACT

Background:
Most gynecological cancer survivors outlive the acute stage, and many reach permanent survival. However, the fear of cancer recurrence (FCR) is stressful and affects quality of life.

Purpose:
This study was designed to validate a Chinese version of the Assessment of Survivor Concerns (ASC) questionnaire in terms of its ability to assess FCR in gynecological cancer survivors.

Methods:
A two-stage study procedure was employed. The first stage involved the translation of the ASC questionnaire from English into Chinese using the methods proposed by Guillemin, which include translation, back-translation, consensus meetings, and a trial of potential users. In the second stage, a pilot study was completed with 37 gynecological cancer survivors followed by a psychometric property study with 287 gynecological cancer survivors. Construct validity was determined using confirmatory factor analysis (CFA) with structural equation modeling. Convergent validity was determined using composite reliability and the average variance extracted values of the ASC model. Discriminant validity was determined by comparing the model fitness of the ASC model against the model fitness of a one-construct model. Concurrent criterion validity was assessed using the European Organization for Research and Treatment of Cancer's Quality-of-Life Questionnaire Core 30 as the auxiliary instrument. Reliability was determined by measuring the internal consistency reliability using Cronbach's α in addition to the 3-week test–retest reliability with a 95% confidence interval of the intraclass correlation coefficient.

Results:
The process of translation and back-translation was performed to ensure the conceptual equivalence of the Chinese version with the original ASC questionnaire. For CFA, the fit indices of the ASC model (χ2 = 9.87, p > .05; root mean square error of approximation = .03. comparative fit index = 1, nonnormed fit index = 1) indicated appropriate model fitness. For convergent validity, the composite reliability and average variance extracted values of the ASC model were satisfactory. For discriminant validity, the model fitness of the ASC model was significantly improved over the one-construct model. For concurrent criterion validity, the ASC scores correlated negatively with the scores of the global quality of life and the five functions (physical, role, cognition, emotions, and social) of the European Organization for Research and Treatment of Cancer's Quality-of-Life Questionnaire Core 30, as hypothesized. For reliability, the Cronbach's α and the 95% confidence interval of intraclass correlation coefficient for the ASC model were .91 and [.18, .68], respectively.

Conclusions/Implications for Practice:
The Chinese version of the ASC questionnaire is a valid and reliable instrument that is suitable for assessing FCR in gynecological cancer survivors in clinical and research settings.