bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Rationale to Target Highly Expressed CDK7 Conferring Poor Outcomes in Triple-Negative Breast Cancer
Authors: Li Bo , Ni Chonghaile Triona , Fan Yue , Madden Stephen F. , Klinger Rut , O'Connor Aisling E. , Walsh Louise , O'Hurley Gillian , Mallya Udupi Girish , Joseph Jesuchristopher , Tarrant Finbarr , Conroy Emer , Gaber Alexander , Chin Suet-Feung , Bardwell Helen A. , Provenzano Elena , Crown John , Dubois Thierry , Linn Sabine , Jirstrom Karin , Caldas Carlos , O'Connor Darran P. , Gallagher William M. 
Published: April 2017

Abstract
Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and high relapse after treatment, but there remains a lack of biomarkers and effective targeted therapies for this disease. Here, we report evidence highlighting the cell-cycle–related kinase CDK7 as a driver and candidate therapeutic target in TNBC. Using publicly available transcriptomic data from a collated set of TNBC patients (n = 383) and the METABRIC TNBC dataset (n = 217), we found CDK7 mRNA levels to be correlated with patient prognosis. High CDK7 protein expression was associated with poor prognosis within the RATHER TNBC cohort (n = 109) and the METABRIC TNBC cohort (n = 203). The highly specific CDK7 kinase inhibitors, BS-181 and THZ1, each downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition, with THZ1 exhibiting 500-fold greater potency than BS-181. Mechanistic investigations revealed that the survival of MDA-MB-231 TNBC cells relied heavily on the BCL-2/BCL-XL signaling axes in cells. Accordingly, we found that combining the BCL-2/BCL-XL inhibitors ABT-263/ABT199 with the CDK7 inhibitor THZ1 synergized in producing growth inhibition and apoptosis of human TNBC cells. Collectively, our results highlight elevated CDK7 expression as a candidate biomarker of poor prognosis in TNBC, and they offer a preclinical proof of concept for combining CDK7 and BCL-2/BCL-XL inhibitors as a mechanism-based therapeutic strategy to improve TNBC treatment. Cancer Res; 77(14); 3834–45. ©2017 AACR.
A Road Map for Precision Cancer Medicine Using Personalized Models
Authors: Picco Gabriele , Garnett Mathew J. 
Published: May 2017

Abstract
Summary: A study by Pauli and colleagues in this issue of Cancer Discovery describes the creation of a precision cancer platform for patients with advanced disease, integrating DNA sequencing of patient tumors with the generation of patient-derived organoids and xenografts. They propose the use of this platform for drug testing to nominate therapeutic options for individual patients and for therapeutic biomarker discovery. Cancer Discov; 7(5); 456–8. ©2017 AACR.
See related article by Pauli et al., p. 462.
Optimizing Next-Generation AML Therapy: Activity of Mutant IDH2 Inhibitor AG-221 in Preclinical Models
Authors: Thomas Daniel , Majeti Ravindra 
Published: May 2017

Abstract
Summary: AG-221 or enasidenib is a first-in-class selective inhibitor of mutated isocitrate dehydrogenase 2 (IDH2) with early demonstrated clinical efficacy in acute myeloid leukemia as a single agent, yet with persistence of mutant IDH2 clones. Two articles in this issue of Cancer Discovery provide further insight into the biological activity of AG-221 in promoting differentiation of IDH2-mutant cells and reversing aberrant DNA methylation over time, and demonstrating preclinical activity in combination with a targeted FLT3 kinase inhibitor to eliminate IDH2-mutant clones. Cancer Discov; 7(5); 459–61. ©2017 AACR.
See related article by Yen et al., p. 478.
See related article by Shih et al., p. 494.
Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis)
Authors: Derdeyn Colin P. , Fiorella David , Lynn Michael J. , Turan Tanya N. , Cotsonis George A. , Lane Bethany F. , Montgomery Jean , Janis L. Scott , Chimowitz Marc I. 
Published: April 2017

Background and Purpose—
The purpose of this study was to investigate the frequency of symptomatic in-stent restenosis (ISR) and its contribution to nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis).

Methods—
Patients without a periprocedural primary end point were followed up to determine the occurrence of any of the following events: ischemic stroke, cerebral infarct with temporary signs, or transient ischemic attack in the territory of the stented artery. Vascular imaging performed after these events was reviewed for ISR. Annual rates for symptomatic ISR were calculated using Kaplan–Meier estimates.

Results—
Of 183 patients in the stenting group without a periprocedural primary end point, 27 (14.8%) had a symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16 (8.7%) had transient ischemic attack alone in the territory during a median follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone. Adequate vascular imaging to evaluate ISR was available in 24 patients with infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort were 9.6% (6.1%–14.9%), 11.3% (7.5%–17.0%), and 14.0% (9.6%–20.2%), respectively.

Conclusions—
Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by 3 years of follow-up and was likely responsible for the majority of nonprocedural cerebral infarctions.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT00576693.
Oxygenation-Sensitive Magnetic Resonance Imaging in Acute Ischemic Stroke Using T2′/R2′ Mapping
Authors: Seiler Alexander , Deichmann Ralf , Nöth Ulrike , Pfeilschifter Waltraud , Berkefeld Joachim , Singer Oliver C. , Klein Johannes C. , Wagner Marlies 
Published: April 2017

Background and Purpose—
Quantitative T2′/R2′ mapping detect locally increased concentrations of deoxygenated hemoglobin—causing a decrease of T2′ and increase of R2′—and might reflect increased cerebral oxygen extraction fraction. Because increases of (relative) cerebral blood volume (rCBV) may influence T2′ and R2′ through accumulation of deoxygenated hemoglobin, we aimed to investigate the impact of rCBV on T2′/R2′ in patients with ischemic stroke.

Methods—
Data from patients with acute internal carotid artery and middle cerebral artery occlusion were analyzed. T2′, R2′, and rCBV were measured within the ischemic core, slightly and severely hypoperfused areas, and their relationship was examined.

Results—

A strong negative correlation with rCBV was found for R2′ (
r
=−0.544;
P
=0.002), and T2′ correlated positively with rCBV (
r
=0.546;
P
=0.001) in time-to-peak–delayed areas. T2′/R2′ within hypoperfused tissue remained unchanged at normal or elevated rCBV levels.

Conclusions—
T2′ decrease/R2′ increase within hypoperfused areas in ischemic stroke is not caused by local elevations of rCBV but most probably only by increased cerebral oxygen extraction fraction. However, considering rCBV is crucial to assess extent of oxygen extraction fraction changes by means of T2′/R2′.
Green Approaches to Enhancing Rural Communities in Romania: Case Studies from Maramureş and Sibiu Counties
Authors: Regoli Francesca , Vincze Mária , Segrè Andrea , Vittuari Matteo 
Published: April 2017

The concept of development evolves following the transformations and new challenges communities have to face. In this framework, in the past twenty years, development discourse has covered questions about the interrelations among its different dimensions (economic, human, social, environmental, institutional), about the transition from linear to circular models, and about the role (and importance) of endogenous resources. This evolution has increased the attention given to local development strategies and their role in the promotion of sustainability and socio-economic growth by recognizing and reorganizing local resources.
This article grounds the concept of territorial capital to Maramureş County (Romania) with the aim of understanding its role and of assessing its potential as a driving force to guide local communities in the exploitation of endogenous resources. Through a comparative analysis of the case studies of the Tâvarna Mare Natura 2000 site (Sibiu County) and Oaş Gutai (Maramureş County), the work also aims to provide general insights to inform local development policies.
The research is based on multiple research methods including secondary data analysis, a survey, and a set of interviews with local stakeholders and rural development experts, and it is developed through a comparative analysis between the case studies.
Using text-based synchronous chat to offer therapeutic support to students: A systematic review of the research literature
Authors: Ersahin Zehra , Hanley Terry 
Published: May 2017

Objective: Counselling within educational settings has now become commonplace. As with the advent of the use of new technologies in teaching, such developments are also impacting the broader support structures available to students. One development is the move of schools to offer pupils access to online counselling services. To date, such practices have received little attention, and this paper synthesises the existing empirical research literature in this area. Design: A systematic review of the literature was conducted which focused upon synchronous chat counselling for 11- to 25-year-olds. Method: Key bibliographic databases were searched for relevant papers. These were assessed for relevance and quality prior to being included into the analysis. The final selection of studies was analysed for key themes. Results: In all, 19 papers met the inclusion criteria. The thematic synthesis identified four higher order themes: (1) developing safe and youth-friendly online services, (2) online client characteristics, (3) in-session online processes and (4) session alliance and outcome. Conclusion: These themes outline the varied challenges and opportunities present within this developing practice. Each is initially discussed alongside existing literature related to online counselling before the implications for educational providers are explicitly considered. Ultimately, it is concluded that online counselling for students has much potential, however, those commissioning such services need to be mindful of common pitfalls.
Knowledge and Practices of Diabetes Foot Care and Risk of Developing Foot Ulcers in México May Have Implications for Patients of Méxican Heritage Living in the US
Authors: Bohorquez Robles Rosa , Compeán Ortiz Lidia G. , González Quirarte Nora H. , Berry Diane C. , Aguilera Pérez Paulina , Piñones Martínez Socorro 
Published: April 2017

Purpose The purpose of the study was to examine the relationship between knowledge and foot care practices among adults with type 2 diabetes. Methods A descriptive correlational study examined 200 patients with type 2 diabetes in México. Data collected included the Knowledge and Practices Self-Care Questionnaire and a Podiatry Examination Questionnaire. Data analysis included Pearson’s correlations and chi-square tests. Results More than half of the participants had poor knowledge and poor foot care practices. A significant negative correlation between knowledge and practices of foot care and risk of developing diabetes foot ulcers was found. There was no relationship between sociodemographic variables and the risk of developing diabetes foot ulcers. Conclusions Patients with type 2 diabetes served in an outpatient clinic had poor knowledge and practices of foot care. They demonstrated decreased knowledge and practice of foot care and therefore showed a greater risk of developing diabetes foot, which may predispose patients to early complications.
Use of powered mobility for a young adult with profound and multiple learning disabilities: a practice analysis
Authors: Benford Francesca 
Published: April 2017

Statement of context Powered mobility has reported benefits as a learning tool for individuals limited in independent mobility. The majority of literature focuses on early years populations and there remains a need to address powered mobility for adults with profound and multiple learning disabilities. This article explores the experience of switch-operated powered mobility training for one young adult with profound and multiple learning disabilities. Critical reflection on practice Powered mobility provided a motivating medium through which previously unseen skills, such as upper limb use, were demonstrated. Use of switches, rather than typically used joysticks, allowed successful participation. Implication for practice Providing the right equipment, environment and appropriate challenge for an individual can facilitate unexpected achievement.
Graft Diameter as a Predictor for Revision Anterior Cruciate Ligament Reconstruction and KOOS and EQ-5D Values: A Cohort Study From the Swedish National Knee Ligament Register Based on 2240 Patients
Authors: Snaebjörnsson Thorkell , Hamrin Senorski Eric , Ayeni Olufemi R. , Alentorn-Geli Eduard , Krupic Ferid , Norberg Fredrik , Karlsson Jón , Samuelsson Kristian 
Published: May 2017

Background: Anterior cruciate ligament (ACL) reconstruction (ACLR) using a hamstring tendon (HT) autograft is an effective and widespread method. Recent studies have identified a relationship between the graft diameter and revision ACLR. Purpose: To evaluate the influence of the graft diameter on revision ACLR and patient-reported outcomes in patients undergoing primary ACLR using HT autografts. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective cohort study was conducted using the Swedish National Knee Ligament Register (SNKLR) involving all patients undergoing primary ACLR using HT autografts. Patients with graft failure who needed revision surgery (cases) were compared with patients not undergoing revision surgery (controls). The control group was matched for sex, age, and graft fixation method in a 3:1 ratio. Conditional logistic regression was performed to produce odds ratios and 95% CIs. Univariate linear regression analyses were performed for patient-related outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS) and EuroQol 5 dimensions questionnaire (EQ-5D) values were obtained. Results: A total of 2240 patients were included in which there were 560 cases and 1680 controls. No significant differences between the cases and controls were found for sex (52.9% male), mean age (21.7 years), and femoral and tibial fixation. The mean graft diameter for the cases was 8.0 ± 0.74 mm and for the controls was 8.1 ± 0.76 mm. In the present cohort, the likelihood of revision surgery for every 0.5-mm increase in the HT autograft diameter between 7.0 and 10.0 mm was 0.86 (95% CI, 0.75-0.99; P = .03). Univariate linear regression analysis found no significant regression coefficient for the change in KOOS or EQ-5D values. Conclusion: In a large cohort of patients after primary ACLR with HT autografts, an increase in the graft diameter between 7.0 and 10.0 mm resulted in a 0.86 times lower likelihood of revision surgery with every 0.5-mm increase. This study provides further evidence of the importance of the HT autograft size in intraoperative decision making.
How are sexual health clinics in England managing men who have sex with men who refuse to be tested for HIV?
Authors: Hoyos Miller Juan , Clarke Emily , Patel Raj , Kell Philip , Desai Monica , Nardone Anthony 
Published: April 2017

The aim of this study was to ascertain the existence of written policies and common clinical practices in sexual health clinics in England for the management of men who have sex with men who refuse to test for HIV. All sexual health clinics in England ( n = 223) were invited to complete an online questionnaire in August–September 2014. The questionnaire covered the four domains of clinic policies, management practices, training and monitoring. We assess differences by region. Overall, 92 clinics participated. Only three clinics reported having a written policy. In contrast, most reported having a common agreed practice (94% in London vs. 71.6% elsewhere). When encountering a refusal, 72.2% of the London clinics and 53.4% of the clinics from elsewhere offered a less invasive option. Few clinics (17.4%) provided information on home sampling kits and 74.4% informed about other testing options. Eighty-seven per cent of the clinics recorded the occurrence of refusals, but only 37.8% reviewed the collected data. Providing staff with training was more common in London (94.1% vs. 73.8%). Clear policies should be developed to guide professionals when encountering men who have sex with men who refuse an HIV test. Offering less invasive testing options and information on alternative testing options could be easily introduced into routine practice. Efforts should be made to review monitoring data in order to identify implications of test refusals and introduce improvements in management of refusals.
Multilevel growth curve models that incorporate a random coefficient model for the level 1 variance function
Authors: Goldstein Harvey , Leckie George , Charlton Christopher , Tilling Kate , Browne William J 
Published: May 2017

Aim To present a flexible model for repeated measures longitudinal growth data within individuals that allows trends over time to incorporate individual-specific random effects. These may reflect the timing of growth events and characterise within-individual variability which can be modelled as a function of age. Subjects and methods A Bayesian model is developed that includes random effects for the mean growth function, an individual age-alignment random effect and random effects for the within-individual variance function. This model is applied to data on boys’ heights from the Edinburgh longitudinal growth study and to repeated weight measurements of a sample of pregnant women in the Avon Longitudinal Study of Parents and Children cohort. Results The mean age at which the growth curves for individual boys are aligned is 11.4 years, corresponding to the mean ‘take off’ age for pubertal growth. The within-individual variance (standard deviation) is found to decrease from 0.24 cm2 (0.50 cm) at 9 years for the ‘average’ boy to 0.07 cm2 (0.25 cm) at 16 years. Change in weight during pregnancy can be characterised by regression splines with random effects that include a large woman-specific random effect for the within-individual variation, which is also correlated with overall weight and weight gain. Conclusions The proposed model provides a useful extension to existing approaches, allowing considerable flexibility in describing within- and between-individual differences in growth patterns.
Effectiveness of Total Contact Orthosis for Plantar Pressure Redistribution in Neuropathic Diabetic Patients During Different Walking Activities
Authors: Nouman Muhammad , Leelasamran Wipawan , Chatpun Surapong 
Published: April 2017

Background: Using a total contact orthosis (TCO) is an effective method to offload in diabetic patients with foot neuropathy. However, the redistribution of peak plantar pressure is mostly observed during level walking, which may differ from other walking activities. The aim of this study was to investigate the plantar pressure from 4 regions of the foot during different walking activities (level walking, ramp ascending, ramp descending, stair ascending, and stair descending) in neuropathic diabetic patients with and without a TCO. Methods: Sixteen neuropathic diabetic patients aged 40 to 60 years with calluses and hallux valgus were included in this study and were provided with TCOs made up of multifoam, Plastazote, and microcellular rubber. The plantar pressure and contact area with the TCO and without the TCO were recorded using the Pedar X system during different walking activities. Results: A significant reduction of plantar pressure during different walking activities at the toes and forefoot regions was observed while walking with the TCO compared with walking without the TCO (control condition). Plantar pressure increased at the midfoot region when walking with the TCO, and no significant difference was observed at the hindfoot region between the control and TCO conditions. Furthermore, maximum contact area was observed during level walking with the TCO compared with other walking activities. Conclusion: The TCO significantly reduced and redistributed the peak plantar pressure from the sites where the ulceration rate is higher at the toes and forefoot compared with the other regions of the foot. Level of evidence: Therapeutic level II, lesser quality randomized controlled trial
Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies
Authors: Crul M , Simons-Sanders K 
Published: April 2017

Background To prevent occupational exposure of hospital staff to cytostatics, a mandatory national guideline describing a set of safety measures was issued in the Netherlands in 2004. The guideline includes, among other directives, obligatory annual wipe testing to assess the efficacy of the local cleaning protocol. Full implementation of this guideline was executed in all Dutch hospital pharmacies over the next couple of years. Objective We aimed to investigate the effect of the national guideline on contamination levels, and specifically on the phenomenon of carry-over of traces of antineoplastic drugs through contact with surfaces, since this is a potential route of exposure. Methods From a database including wipe sample results of 9 hospitals over 10 years, we extracted all sampled locations in the compounding areas as well as in adjacent or bypass rooms and locks. We considered only the locations outside safety cabinets or isolators, to examine the containment of contamination and to address possible routes of how a contamination can migrate through the preparation and distribution areas. The dataset consisted of 2647 wipe samples. Results In adjacent rooms, 18 out of 275 wipe samples were contaminated (6%). Inside the compounding room, the extracted locations away from the safety workbench showed a positive percentage for contamination of 13% (39 out of 297). When stratifying the data to sample year, it was shown that contaminations outside the preparation room were no longer detectable after 2008. Conclusion With this study, we show that implementation of a set of guidelines on safety measures can prevent spreading of cytostatic traces from the compounding area in hospital pharmacies.