bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability of Gross Tumor Volume Delineation for Stereotactic Body Radiotherapy of the Lung With Tri-60Co Magnetic Resonance Image-Guided Radiotherapy System (ViewRay): A Comparative Study With Magnetic Resonance- and Computed Tomography-Based Target Delineation
Authors: Wee Chan Woo , An Hyun Joon , Kang Hyun-Cheol , Kim Hak Jae , Wu Hong-Gyun 
Published: July 2018

Introduction: To evaluate the intra-/interobserver variability of gross target volumes between delineation based on magnetic resonance imaging and computed tomography in patients simulated for stereotactic body radiotherapy for primary lung cancer and lung metastasis. Materials and Methods: Twenty-five patients (27 lesions) who underwent computed tomography and magnetic resonance simulation with the MR-60Co system (ViewRay) were included in the study. Gross target volumes were delineated on the magnetic resonance imaging (GTVMR) and computed tomography (GTVCT) images by 2 radiation oncologists (RO1 and RO2). Volumes of all contours were measured. Levels of intraobserver (GTVMR_RO vs GTVCT_RO) and interobserver (GTVMR_RO1 vs GTVMR_RO2; GTVCT_RO1 vs GTVCT_RO2) agreement were evaluated using the generalized κ statistics and the paired t test. Results: No significant volumetric difference was observed between all 4 comparisons (GTVMR_RO1 vs GTVCT_RO1, GTVMR_RO2 vs GTVCT_RO2, GTVMR_RO1 vs GTVMR_RO2, and GTVCT_RO1 vs GTVCT_RO2; P > .05), with mean volumes of GTVs ranging 5 to 6 cm3. The levels of agreement between those 4 comparisons were all substantial with mean κ values of 0.64, 0.66, 0.74, and 0.63, respectively. However, the interobserver agreement level was significantly higher for GTVCT compared to GTVMR ( P <.001). The mean κ values significantly increased in all 4 comparisons for tumors >5 cm3 compared to tumors ≤5 cm3 (all P < .05). Conclusion: No significant differences in volumes between magnetic resonance- and computed tomograpghy-based Gross target volumes were found among 2 ROs. Magnetic resonance-based GTV delineation for lung stereotactic body radiotherapy also demonstrated acceptable interobserver agreement. Tumors >5 cm3 show higher intra-/interobserver agreement compared to tumors <5 cm3. More experience should be accumulated to reduce variability in magnetic resonance-based Gross target volumes delineation in lung stereotactic body radiotherapy.
DNA methylation changes in CD4+ T cells isolated from multiple sclerosis patients on dimethyl fumarate
Authors: Maltby Vicki E , Lea Rodney A , Ribbons Karen A , Sanders Katherine A , Kennedy Daniel , Min Myintzu , Scott Rodney J , Lechner-Scott Jeannette 
Published: July 2018

Background Dimethyl fumarate is an oral treatment for multiple sclerosis, whose mechanism of action is not fully understood. Objective To investigate the effects of dimethyl fumarate on DNA methylation in the CD4+ T cells of multiple sclerosis patients. Methods We performed Illumina EPIC arrays to investigate the DNA methylation profiles of CD4+ T cells derived from multiple sclerosis patients before and after dimethyl fumarate treatment. Results Treatment with dimethyl fumarate resulted in 97% of differentially methylated positions showing hypermethylation. Four genes, SNORD1A, SHTN1, MZB1 and TNF had a differentially methylated region located within the transcriptional start site. Conclusion This study investigates the effect of dimethyl fumarate on DNA methylation in multiple sclerosis patients.
Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: a new treatment strategy for ibrutinib-resistant CLL
Authors: Reiff Sean D. , Muhowski Elizabeth M. , Guinn Daphne , Lehman Amy , Fabian Catherine A. , Cheney Carolyn , Mantel Rose , Smith Lisa , Johnson Amy J. , Young Wendy B. , Johnson Adam R. , Liu Lichuan , Byrd John C. , Woyach Jennifer A. 
Published: July 2018

Key Points
Inhibition of the ibrutinib-resistant C481S BTK mutant can be achieved by the reversible BTK inhibitor GDC-0853. BTK inhibitors, which lack ITK inhibition, preserve natural killer cell–mediated cellular cytotoxicity to CD20 directed monoclonal antibodies.
CD44 is a RAS/STAT5-regulated invasion receptor that triggers disease expansion in advanced mastocytosis
Authors: Mueller Niklas , Wicklein Daniel , Eisenwort Gregor , Jawhar Mohamad , Berger Daniela , Stefanzl Gabriele , Greiner Georg , Boehm Alexandra , Kornauth Christoph , Muellauer Leonhard , Sehner Susanne , Hoermann Gregor , Sperr Wolfgang R. , Staber Philipp B. , Jaeger Ulrich , Zuber Johannes , Arock Michel , Schumacher Udo , Reiter Andreas , Valent Peter 
Published: July 2018

Key Points
CD44 is a RAS/STAT5-dependent target in neoplastic mast cells and correlates with aggressiveness of mastocytosis. Depletion of CD44 in neoplastic mast cells is associated with reduced invasion and prolonged survival in SCID mice.
Exploration of 3D printing to create zero-waste sustainable fashion notions and jewelry
Authors: Pasricha Anupama , Greeninger Rachel 
Published: July 2018

AbstractThis research followed design as a research paradigm to apply zero-waste principles to 3D printing in efforts to ensure sustainable applications of 3D technology in the apparel and fashion industry. Researchers used Rhinoceros 5, Tinkercad, MakerBot Replicator 2 desktop 3D printer, and polylactic acid filament to create elaborate designs. This design research is the first successful attempt at 3D printing for biodegradable zero-waste fashion notions and accessories. The researcher employed design thinking and strategies to create objects without the use of rafts and supporters removing waste creation. Multiple attempts resulted in an acceptable outcome of five pendant designs for necklaces, two earring designs, and nine layer-designed buttons. The buttons were attached to a draped cape design utilizing 95% of the fabric. There is a considerable potential to use this disruptive technology in designing and creating fashions that are unique, sustainable (zero-waste), and made on demand.
A Qualitative Exploration of the Experiences and Perceptions of Women Living With a Diagnosis of Breast Cancer in Barbados: Financial Loss
Authors: Vigilance Jacqueline , Harewood Heather , Greaves Natalie 
Published: July 2018

Abstract 45 Background Cancer is one of the leading causes of morbidity and mortality in Latin America and the Caribbean. It is the second leading cause of death in Barbados and has an age standardized mortality rate of 117.7 and 179.3 per 100,000 in females and males, respectively. Breast cancer has the highest incidence and mortality rates for cancers among women in Barbados. Little research has been done on the factors influencing cancer survivorship in Barbados. Aims This study sought to examine the lived experiences of patients diagnosed and treated for breast cancer in Barbados with a view to identifying health system, societal and individual characteristics that facilitate or inhibit survivorship. Methods Individual, face-to-face semi-structured interviews were conducted until the point of saturation (12th interview). Participants were purposively selected with the assistance of a cancer charity on the island. All participants were female aged 27-69 years. All interviews were audio-taped and transcribed verbatim. Data was analyzed using thematic analysis with constant comparison. ATLAS.ti (8) data management software used. Results Patient survivorship was affected by a complex interaction between: a) health system characteristics b) patient characteristics (inner resilience), and c) societal acceptance (namely perceptions and experiences of stigma and social support). The results presented in this paper highlight the health system characteristics related to the financing of cancer care. Patients experienced financial hardship although primary health care is free to citizens at the point of access. Public cancer care was not always timely; with care via the private sector requiring out-of-pocket spending, this often led to catastrophic financial hardship and dependence on social networks that facilitated care access. The experience of financial loss due to personal financing of care was further exacerbated by diminished employability and job-related discrimination due to cancer diagnosis. Significance These results highlighted the need for financial support structures for cancer patients in small island developing states such as Barbados as part of universal access to health care. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.
The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ
Authors: Derakhshan Arash , Korevaar Tim I M , Taylor Peter N , Levie Deborah , Guxens Monica , Jaddoe Vincent W V , Nelson Scott M , Tiemeier Henning , Peeters Robin P 
Published: July 2018

Abstract

Context
Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation.

Objective
To study the association of maternal TPOAb positivity during pregnancy with child IQ.

Design, Setting, and Participants
This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC).

Main Outcome Measures
Child IQ at 5 to 10 years of age.

Results
In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results.

Conclusion
TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.
Balanced Rac1 activity controls formation and maintenance of neuromuscular acetylcholine receptor clusters
Authors: Bai Yanyang , Guo Daji , Sun Xiaoyu , Tang Genyun , Liao Tailin , Peng Yinghui , Xu Junyu , Shi Lei 
Published: July 2018

ABSTRACT
Rac1, an important Rho GTPase that regulates the actin cytoskeleton, has long been suggested to participate in acetylcholine receptor (AChR) clustering at the postsynaptic neuromuscular junction. However, how Rac1 is regulated and how it influences AChR clusters have remained unexplored. This study shows that breaking the balance of Rac1 regulation, by either increasing or decreasing its activity, led to impaired formation and maintenance of AChR clusters. By manipulating Rac1 activity at different stages of AChR clustering in cultured myotubes, we show that Rac1 activation was required for the initial formation of AChR clusters, but its persistent activation led to AChR destabilization, and uncontrolled hyperactivation of Rac1 even caused excessive myotube fusion. Both AChR dispersal and myotube fusion induced by Rac1 were dependent on its downstream effector Pak1. Two Rac1 GAPs and six Rac1 GEFs were screened and found to be important for normal AChR clustering. This study reveals that, although general Rac1 activity remains at low levels during terminal differentiation of myotubes and AChR cluster maintenance, tightly regulated Rac1 activity controls normal AChR clustering.
Changing the name of the NBPF/DUF1220 domain to the Olduvai domain
Authors: Sikela James M. , van Roy Frans 
Published: July 2018

We are jointly proposing a new name for a protein domain of approximately 65 amino acids that has been previously termed NBPF or DUF1220. Our two labs independently reported the initial studies of this domain, which is encoded almost entirely within a single gene family. The name Neuroblastoma Breakpoint Family (NBPF) was applied to this gene family when the first identified member of the family was found to be interrupted in an individual with neuroblastoma. Prior to this discovery, the Pfam database had termed the domain DUF1220, denoting it as one of many protein domains of unknown function. It has been Pfam’s intention to use “DUF” nomenclature to serve only as a temporary placeholder until more appropriate names are proposed based on research findings. We believe that additional studies of this domain, primarily from our laboratories over the past 10 years, have resulted in furthering our understanding of these sequences to the point where proposing a new name for this domain is warranted. Because of considerable data linking the domain to human-specific evolution, brain expansion and cognition, we believe a name reflecting these findings would be appropriate. With this in mind, we have chosen to name the domain (and the repeat that encodes it) Olduvai. The gene family will remain as NBPF for now. The primary domain subtypes will retain their previously assigned names (e.g. CON1-3; HLS1-3), and the three-domain block that expanded dramatically in the human lineage will be termed the Olduvai triplet. The new name refers to Olduvai Gorge, which is a site in East Africa that has been the source of major anthropological discoveries in the early-mid 1900’s. We also chose the name as a tribute to the scientists who made important contributions to the early studies of human origins and our African genesis.
Measuring Decreasing and Increasing Impatience
Authors: Rohde Kirsten I. M. 
Published: July 2018

Many studies show that time preference data from experiments and surveys are related to field behavior. Time preference measures in these studies typically depend simultaneously on utility curvature, the level of impatience, and the change in the level of impatience. Thus, these studies do not allow one to establish which of these three components drive(s) the field behavior of interest. Of these components, the change in the level of impatience is theoretically thought to be the main driver of time inconsistencies and self-control problems. To test this theoretical presumption, one has to measure the change in the level of impatience independently from utilities and levels of impatience. This paper introduces a measure of the degree of decreasing impatience, the DI-index. It measures the change of impatience independently from the level of impatience and independently from utility. It can also be used to test various discounting models. An experiment finds no correlation between the degree of decreasing impatience and self-reported self-control problems in daily life, suggesting that changing impatience is not the sole driver of self-control problems. Data and the supplementary material are available at https://doi.org/10.1287/mnsc.2017.3015 . This paper was accepted by Manel Baucells, decision analysis.
A purpose-designed monofilament-fibre pad for debridement of hard-to-reach wounds: experience in clinical practice
Authors: Dissemond Joachim , Eberlein Thomas , Bültemann Anke , Riepe Gunnar , Stoffels Ingo , Stephen-Haynes Jackie , Roes Claas , Abel Martin 
Published: July 2018

Objective: Effective and comfortable debridement is an important part of managing complex wounds. This user test evaluated a monofilament-fibre pad (with handle) (Debrisoft Lolly, Lohmann & Rauscher GmbH & Co. KG) in the debridement of various hard-to-reach wounds. Method: The multicentre, international user test was performed by experienced physicians and nurses in Germany and the UK, who used the monofilament-fibre pad in their clinical practice. After debridement, using the monofilament-fibre pad, the clinicians completed an evaluation questionnaire. The assessment comprised of performance, usability, tolerability, safety and suitability of the device for debridement, comparing it with standard methods used in the clinicians' centres. Results: A total of 23 clinicians in 20 centres each treated between six and 10 patients with the monofilament-fibre pad (a total of 155 wounds of different aetiologies). Most participating patients had deep wounds (n=63 (41%)) or cavity (n=31 (20%)) wounds. When compared with the standard debridement method used at the centres, the tested device was scored as ‘easier’ or ‘equally easy’ to use in all cases. When comparing the standard debridement procedure with the monofilament-fibre pad, debridement duration was reported as equal to or shorter than the standard method in 90% of cases when using the monofilament-fibre pad. Debridement efficacy was scored by the clinician as ‘better’ or ‘equal’ for the monofilament-fibre pad in 67% of cases. Overall, patients reported that the study device was comfortable. Conclusion: The monofilament-fibre pad effectively, easily and safely removed slough and debris from wounds of various aetiologies and was effective in wounds of different shapes, such as in cavity wounds and those in hard-to-reach locations.
Use of a gelling fibre dressing in complex surgical or chronic wounds: a case series
Authors: Ivins Nicola , Braumann Chris , Kirchhoff Jan-Birger , Waldemar Uhl , Jones Nia J. 
Published: July 2018

Objective:To evaluate the safety and performance of a gelling fibre dressing, with respect to wound exudate management, maceration and periwound skin conditions.Method:Complex (non-healing) surgical or chronic wounds healing by secondary intention were treated with a gelling fibre dressing (Biosorb, Acelity) as part of a prospective, two-centre case series product evaluation study. Dressing performance was evaluated at each change, and weekly for up to four weeks or until the wound healed, if this was in less than four weeks. The main outcome measure was dressing performance, wound bed and periwound skin condition.Results:A total of 15 patients, aged 26–87 years, were enrolled; 10 patients (66.7%) presented with chronic wounds including venous leg ulcers (VLUs), arterial leg ulcer, one mixed leg ulcer, pressure ulcer (PU), and diabetic foot ulcers (DFUs). The remaining wounds (33.3%) were postsurgical complex wounds healing by secondary intention, located in the upper leg, foot, abdomen, and sacrum. Mean wound area was 22.6±36.6cm2(range: 1.3–144.0cm2). Treated wounds showed complete granulation in eight (53.0%) wounds, 75% granulation coverage in two (13.3%) wounds, 50% coverage in three (20.3%), and 25% coverage in two (13.3%) wounds. Patients evaluated the dressing effectiveness as ‘excellent’ or ‘very good’ in 45% of cases, ‘moderate’ in 45%, and ‘poor’ in 10% of cases. Results of Visual Analogue Scale (VAS) showed 70% of patients rated their pain as ‘low’ and 30% as ‘moderate’ at dressing removal. Clinicians' evaluation of dressing ability to absorb and retain wound exudate was rated ‘excellent’ or ‘very good’ in 80% of cases, and moderate in 20% and poor in 10% of cases. Overall, clinicians' impression of the dressing performance was reported as ‘excellent’ or ‘very good’ in 80% of cases and ‘moderate’ in 20% of cases. No patient had to be removed from the study due to adverse events directly related to the dressing or its performance.Conclusion:These clinical findings suggest the new gelling fibre dressing to be safe and effective in wound treatment of complex (non-healing) surgical or chronic wounds, to manage exudate effectively, and to optimise the conditions of wounds healing by secondary intention
State-of-the-art diagnosis and surgical treatment of acute peri-prosthetic joint infection following primary total hip arthroplasty
Authors: Slullitel Pablo A. , Oñativia José I. , Buttaro Martin A. , Sánchez Marisa L. , Comba Fernando , Zanotti Gerardo , Piccaluga Francisco 
Published: July 2018

Acute peri-prosthetic joint infection (PJI) following total hip arthroplasty (THA) is a potentially devastating and undesired complication, with a prevalence of 0.3% to 2.9%. Its suspicion begins with a meticulous physical examination and anamnesis. Diagnosis should be made on the basis of the Musculoskeletal Infection Society criteria. Serum and synovial biomarkers are very useful tools when major criteria are absent. Although sometimes not possible due to medical conditions, surgery is usually the first line of treatment. Although its outcome is highly correlated with the isolated microorganism, irrigation and debridement with implant retention (DAIR) is the gold standard for treatment. Ideally, the prior approach should be proximally and distally extended to augment the field of view and remove all of the prosthetic modular components, that is, femoral head and acetabular insert. Given DAIR’s unclear control of infection, with successful outcomes in the range of 30% to 95%, one- or two-stage revision protocols may play a role in certain cases of acute infections; nonetheless, further prospective, randomized studies are necessary to compare long-term outcomes between DAIR and revision surgeries. Following surgical treatment, length of antibiotherapy is in the range of six weeks to six months, without any difference in outcomes between short and long protocols. Treatment should be adjusted to the isolated bacteria and controlled further with post-operative serum biomarker levels. Cite this article: EFORT Open Rev 2018;3:434-441. DOI: 10.1302/2058-5241.3.170032
Evaluation of Preanalytical Conditions and Implementation of Quality Control Steps for Reliable Gene Expression and DNA Methylation Analyses in Liquid Biopsies
Authors: Zavridou Martha , Mastoraki Sofia , Strati Areti , Tzanikou Eleni , Chimonidou Maria , Lianidou Evi 
Published: July 2018

Abstract

BACKGROUND
Liquid biopsy provides important information for the prognosis and treatment of cancer patients. In this study, we evaluated the effects of preanalytical conditions on gene expression and DNA methylation analyses in liquid biopsies.

METHODS
We tested the stability of circulating tumor cell (CTC) messenger RNA by spiking MCF-7 cells in healthy donor peripheral blood (PB) drawn into 6 collection-tube types with various storage conditions. CTCs were enriched based on epithelial cell adhesion molecule positivity, and RNA was isolated followed by cDNA synthesis. Gene expression was quantified using RT-quantitative PCR for CK19 and B2M. We evaluated the stability of DNA methylation in plasma under different storage conditions by spiking DNA isolated from MCF-7 cells in healthy donor plasma. Two commercially available sodium bisulfite (SB)-conversion kits were compared, in combination with whole genome amplification (WGA), to evaluate the stability of SB-converted DNA. SB-converted DNA samples were analyzed by real-time methylation-specific PCR (MSP) for ACTB, SOX17, and BRMS1. Quality control was assessed using Levey–Jennings graphs.

RESULTS
RNA-based analysis in CTCs is severely impeded by the preservatives used in many PB collection tubes (except for EDTA), as well as by time to analysis. Plasma and SB-converted DNA samples are stable and can be used safely for MSP when kept at −80 °C. Downstream WGA of SB-converted DNA compensated for the limited amount of available sample in liquid biopsies.

CONCLUSIONS
Standardization of preanalytical conditions and implementation of quality control steps is extremely important for reliable liquid biopsy analysis, and a prerequisite for routine applications in the clinic.