bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality Evaluation of Zirconium Dioxide Frameworks Produced in Five Dental Laboratories from Different Countries
Authors: Schneebeli Esther , Brägger Urs , Scherrer Susanne S. , Keller Andrea , Wittneben Julia G. , Hicklin Stefan P. 
Published: December 2015

AbstractPurposeThe aim of this study was to assess and compare quality as well as economic aspects of CAD/CAM high strength ceramic three‐unit FDP frameworks ordered from dental laboratories located in emerging countries and Switzerland.Material and MethodsThe master casts of six cases were sent to five dental laboratories located in Thailand (Bangkok), China (Peking and Shenzhen), Turkey (Izmir), and Switzerland (Bern). Each laboratory was using a different CAD/CAM system. The clinical fit of the frameworks was qualitatively assessed, and the thickness of the framework material, the connector height, the width, and the diameter were evaluated using a measuring sensor. The analysis of the internal fit of the frameworks was performed by means of a replica technique, whereas the inner and outer surfaces of the frameworks were evaluated for traces of postprocessing and damage to the intaglio surface with light and electronic microscopes. Groups (dental laboratories and cases) were compared for statistically significant differences using Mann‐Whitney U‐tests after Bonferroni correction.ResultsAn acceptable clinical fit was found at 97.9% of the margins produced in laboratory E, 87.5% in B, 93.7% in C, 79.2% in A, and 62.5% in D. The mean framework thicknesses were not statistically significantly different for the premolar regions; however, for the molar area 4/8 of the evaluated sites were statistically significantly different. Circumference, surface, and width of the connectors produced in the different laboratories were statistically significantly different but not the height. There were great differences in the designs for the pontic and connector regions, and some of the frameworks would not be recommended for clinical use. Traces of heavy postprocessing were found in frameworks from some of the laboratories. The prices per framework ranged from US$177 to US$896.ConclusionsBy ordering laboratory work in developing countries, a considerable price reduction was obtained compared to the price level in Switzerland. Despite the use of the standardized CAD/CAM chains of production in all laboratories, a large variability in the quality aspects, such as clinical marginal fit, connector and pontic design, as well as postprocessing traces was noted. Recommended sound handling of postprocessing was not applied in all laboratories. Dentists should be aware of the true and factitious advantages of CAD/CAM production chains and not lose control over the process.
Characteristics of Farm Equipment‐Related Crashes Associated With Injury in Children and Adolescents on Farm Equipment
Authors: Toussaint Maisha , Faust Kayla , Peek‐Asa Corinne , Ramirez Marizen 
Published: December 2015

AbstractPurposeOperating or riding on farm equipment is one of the leading causes of farm‐related injuries and fatalities among children and adolescents. The aim of this study is to examine environment, crash, vehicle, and occupant characteristics and the probability of injury, given a crash, in youth under age 18 on farm equipment.MethodData from the Departments of Transportation on farm equipment‐related crashes across 9 Midwestern states from 2005‐2010 were used. Odds ratios were calculated using logistic regression to assess the relationship between environment, crash, vehicle, and occupant characteristics and the probability of injury, given a crash.FindingsA total of 434 farm equipment‐related crashes involved 505 child or adolescent occupants on farm equipment: 198 passengers and 307 operators. Passengers of farm equipment had 4.1 higher odds of injury than operators. Occupants who used restraints had significantly lower odds of injury than those who did not. Furthermore, occupants on farm equipment that was rear‐ended or sideswiped had significantly lower odds of injury compared to occupants on farm equipment involved in noncollision crashes. Likewise, occupants on farm equipment that was impacted while turning had significantly lower odds of injury compared to those on equipment that was impacted while moving straight.ConclusionPrecautions should be taken to limit or restrict youth from riding on or operating farm equipment. These findings reiterate the need to enforce policies that improve safety measures for youth involved in or exposed to agricultural tasks.
Geographic Variation in Treatment and Outcomes Among Patients With AMI: Investigating Urban‐Rural Differences Among Hospitalized Patients
Authors: Bechtold Daniel , Salvatierra G.G. , Bulley Emily , Cypro Alex , Daratha Kenn B. 
Published: December 2015

AbstractBackgroundThe value of early invasive revascularization for patients suffering acute myocardial infarction (AMI) is well known. However, access to revascularization services varies geographically and demographically. Previous studies have not examined the influence of rural residence on revascularization rates and outcomes among patients hospitalized with AMI.MethodsOur retrospective cohort study included patients hospitalized in Washington State with a primary diagnosis of AMI from 2009 to 2012. Urban or rural residence was determined using rural‐urban commuting area (RUCA) codes. Multivariable models were used to evaluate geographic variation in rates of invasive versus medical management, in‐hospital mortality, rehospitalization, and subsequent revascularization procedures.ResultsOur study included 25,156 urban dwellers and 2,770 rural residents. Adjusted models found rural patients to be at increased odds of undergoing invasive revascularization during the initial episode of AMI care (OR = 1.11; 95% CI: 1.01‐1.21; P = .02) compared to urban dwelling patients. Rural patients were more likely to be transferred for care (OR = 4.28; 95% CI: 3.93‐4.66; P < .001) and more likely to undergo coronary artery bypass grafting (CABG) (OR = 1.55; 95% CI: 1.35‐1.78; P < .001) compared to the urban cohort. We found no significant geographic cohort differences in in‐hospital mortality or subsequent revascularization rates.ConclusionOur findings suggest that despite limited access to cardiac care facilities, rural patients are accessing revascularization services. However, rural residents are more likely to undergo CABG during their index admission. High transfer rates suggest that rural regions rely on effective transfer networks to access invasive cardiac services.
What is the Role of Culture in the Association of Relationships with Health?
Authors: Campos Belinda 
Published: December 2015

AbstractThere is now widespread recognition that relationships have important implications for health. To better understand this linkage, scholars have called for greater bridging between relationship science and the study of health. The goal of this paper is to raise awareness of another factor that needs to be incorporated into this area of study: culture. I recommend three steps that researchers can take to systematically incorporate culture into the study of relationships and health. First, I suggest four possible culture patterns to study: similarity, moderation, mediation, and novel constructs. Second, I suggest that theoretically meaningful cultural variation and multiple cultures be concurrently studied. The value of this strategy is highlighted via examples from three contexts that emphasize distinct approaches to self and emotion in relationships. Third, I suggest that key relationship processes in families and couples, two relationships with extensive implications for health, be studied. Selected studies of four relationship processes known to be relevant for health – expectations, formation and maintenance, emotions, and social support – are briefly reviewed to highlight the value of this focus. The theoretical and applied benefit of incorporating culture into the study of the association of relationships with health is discussed.
BrachyView, a novel in‐body imaging system for HDR prostate brachytherapy: Experimental evaluation
Authors: Safavi‐Naeini M. , Han Z. , Alnaghy S. , Cutajar D. , Petasecca M. , Lerch M. L. F. , Franklin D. R. , Bucci J. , Carrara M. , Zaider M. , Rosenfeld A. B. 
Published: December 2015

Purpose:This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in‐body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented.Methods:The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom.Results:More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst‐case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results.Conclusions:The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView's image processing algorithms.
Improving the quality of the surgical preoperative assessment in a district general hospital
Authors: Koris Jacob , Hopkins Catherine 
Published: December 2015

AbstractAt Leicester General Hospital, England, patients are assessed by a team of junior doctors for elective colorectal and hepatobiliary procedures. After a number of same day cancellations, a large discrepancy was identified between the findings at the preoperative assessment clinic and the anaesthetic assessment on the day of surgery. After a multidisciplinary meeting was held, three interventions were decided on with an aim to bring the preoperative assessment in line with the anaesthetic assessment. Firstly, a set of guidelines was written and introduced for the junior doctors to use as a reference when assessing patients. Secondly, a proforma was designed specifically to prompt users to include essential details which were being missed in the assessment, having audited 100 patients' notes. Thirdly, a preoperative investigation "calculator" was recommended for each patient to simplify compliance with the National Institute for Health and Care Excellence (NICE) guidance for preoperative assessment.Before and after each intervention was introduced, a cohort of 50 patients were followed looking for differences in findings in the history, examination, investigations, and fitness for surgery between the preoperative assessment in clinic and the anaesthetic assessment on the day of surgery. Initially 68% of patients were compliant for details in the history, 76% for examination, 32% for choice of preoperative investigations, and 100% for fitness for surgery decision. After all three interventions had been introduced, 96% of patients were compliant for history, 94% for examination findings, 88% had the correct choice of preoperative investigations, and 100% had the same decision on fitness for surgery.The interventions described proved to be cheap and effective methods of improving the quality of the preoperative assessment, bringing it in line with the anaesthetic assessment and reducing the risk of same day cancellations.
How safe is our "place of safety"? Clinical guidance promoting safer medical care of patients detained under section 136 of the Mental Health Act
Authors: Mouko Josie , Goddard Aurielle , Nimmo-Smith Victoria 
Published: December 2015

AbstractA new four-bed unit was opened in Bristol, UK, in 2014, for people detained under section 136 of the Mental Health Act. Police bring individuals posing a risk to themselves or others to a Place of Safety (PoS) in order to receive a mental health assessment. Individuals may be held for up to 72 hours, but cannot receive treatment against their will, unless assessed as lacking the capacity to refuse treatment. Issues requiring medical input arose in more than a third of patients, yet there was little guidance for trainees around the PoS.We conducted a survey which confirmed that robust clinical guidance was needed for junior doctors around medical assistance in this unique environment. We identified specific concerns around patient safety in relation to alcohol withdrawal, uncertainties around legislation and lack of clarity of who to call out of hours. Trainees felt they were working outside of their expertise.We collaborated with a variety of professionals to produce clinical guidance in line with best evidence, and made this easily accessible. We also gained a consensus that more experienced core trainees (SHOs) in Psychiatry should be the first point of contact.We then conducted a survey in June 2015, and found that doctors covering the PoS now felt there was sufficient guidance on most clinical scenarios, 100% consensus on who to contact and improved confidence in their ability to manage issues arising.In August 2015 we held an informal training session for the new intake of trainees on the rota. A subsequent survey revealed similarly positive results.Through this project, we were able to identify defects in a system, provide needed guidance to enable safer and more equitable care to a vulnerable group, and foster closer collaboration between junior doctors and managers in the design and use of services.
SLC46A3 Is Required to Transport Catabolites of Noncleavable Antibody Maytansine Conjugates from the Lysosome to the Cytoplasm
Authors: Hamblett Kevin J. , Jacob Allison P. , Gurgel Jesse L. , Tometsko Mark E. , Rock Brooke M. , Patel Sonal K. , Milburn Robert R. , Siu Sophia , Ragan Seamus P. , Rock Dan A. , Borths Christopher J. , O'Neill Jason W. , Chang Wesley S. , Weidner Margaret F. , Bio Matthew M. , Quon Kim C. , Fanslow William C. 
Published: December 2015

Abstract
Antibody–drug conjugates (ADC) target cytotoxic drugs to antigen-positive cells for treating cancer. After internalization, ADCs with noncleavable linkers are catabolized to amino acid-linker-warheads within the lysosome, which then enter the cytoplasm by an unknown mechanism. We hypothesized that a lysosomal transporter was responsible for delivering noncleavable ADC catabolites into the cytoplasm. To identify candidate transporters, we performed a phenotypic shRNA screen with an anti-CD70 maytansine-based ADC. This screen revealed the lysosomal membrane protein SLC46A3, the genetic attenuation of which inhibited the potency of multiple noncleavable antibody–maytansine ADCs, including ado-trastuzumab emtansine. In contrast, the potencies of noncleavable ADCs carrying the structurally distinct monomethyl auristatin F were unaffected by SLC46A3 attenuation. Structure–activity experiments suggested that maytansine is a substrate for SLC46A3. Notably, SLC46A3 silencing led to relative increases in catabolite concentrations in the lysosome. Taken together, our results establish SLC46A3 as a direct transporter of maytansine-based catabolites from the lysosome to the cytoplasm, prompting further investigation of SLC46A3 as a predictive response marker in breast cancer specimens. Cancer Res; 75(24); 5329–40. ©2015 AACR.
Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer
Authors: Davidson Laurie A. , Callaway Evelyn S. , Kim Eunjoo , Weeks Brad R. , Fan Yang-Yi , Allred Clinton D. , Chapkin Robert S. 
Published: December 2015

Abstract
p53 has been shown to mediate cancer stem–like cell function by suppressing pluripotency and cellular dedifferentiation. However, there have been no studies to date that have addressed the specific effects of p53 loss in colonic adult stem cells. In this study, we investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5+ stem cell population on tumor initiation and progression in the colon. In a mouse model of carcinogen (AOM)-induced colon cancer, tamoxifen-inducible Lgr5-driven deletion of p53 reduced apoptosis and increased proliferation of crypt stem cells, but had no effect on tumor incidence or size. Conversely, in a mouse model of colitis-associated cancer, in which mice are exposed to AOM and the potent inflammation inducer DSS, stem cell–specific p53 deletion greatly enhanced tumor size and incidence in the colon. These novel findings suggest that the loss of p53 function in stem cells enables colonic tumor formation only when combined with DNA damage and chronic inflammation. Furthermore, we propose that stem cell targeting approaches are valuable for interrogating prevention and therapeutic strategies that aim to specifically eradicate genetically compromised stem cells. Cancer Res; 75(24); 5392–7. ©2015 AACR.
Mechanistic Investigation of Bone Marrow Suppression Associated with Palbociclib and its Differentiation from Cytotoxic Chemotherapies
Authors: Hu Wenyue , Sung Tae , Jessen Bart A. , Thibault Stephane , Finkelstein Martin B. , Khan Nasir K. , Sacaan Aida I. 
Published: December 2015

Abstract
Purpose: Palbociclib (PD-0332991) is the first selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved for metastatic breast cancer. Hematologic effects, especially neutropenia, are dose-limiting adverse events for palbociclib in humans.
Experimental Design: Reversible hematologic effects and bone marrow hypocellularity have been identified in toxicology studies in rats and dogs after palbociclib treatment. To understand the mechanism by which the hematologic toxicity occurs, and to further differentiate it from the myelotoxicity caused by cytotoxic chemotherapeutic agents, an in vitro assay using human bone marrow mononuclear cells (hBMNC) was utilized.
Results: This work demonstrated that palbociclib-induced bone marrow suppression occurred through cell-cycle arrest, with no apoptosis at clinically relevant concentrations, was not lineage-specific, and was reversible upon palbociclib withdrawal. In contrast, treatment with chemotherapeutic agents (paclitaxel and doxorubicin) resulted in DNA damage and apoptotic cell death in hBMNCs. In the presence or absence of the antiestrogen, palbociclib-treated hBMNCs did not become senescent and resumed proliferation following palbociclib withdrawal, consistent with pharmacologic quiescence. The breast cancer cells, MCF-7, conversely, became senescent following palbociclib or antiestrogen treatment with additive effects in combination and remained arrested in the presence of antiestrogen.
Conclusions: Palbociclib causes reversible bone marrow suppression, clearly differentiating it from apoptotic cell death caused by cytotoxic chemotherapeutic agents. This study also distinguished the cell-cycle arresting action of palbociclib on normal bone marrow cells from the senescent effects observed in breast cancer cells. These results shed light on the mechanism and support risk management of palbociclib-induced bone marrow toxicity in the clinic. Clin Cancer Res; 22(8); 2000–8. ©2015 AACR.
Genetic Effect of Chemotherapy Exposure in Children of Testicular Cancer Survivors
Authors: Kryukov Gregory V. , Bielski Craig M. , Samocha Kaitlin , Fromer Menachem , Seepo Sara , Gentry Carleen , Neale Benjamin , Garraway Levi A. , Sweeney Christopher J. , Taplin Mary-Ellen , Van Allen Eliezer M. 
Published: December 2015

Abstract
Purpose: Cancer survivors express anxiety that chemotherapy exposure may lead to transmissible genetic damage in posttreatment children. Preclinical models suggest that chemotherapy exposure may result in considerable genomic alterations in postexposure progeny. Epidemiologic studies have not demonstrated a significant increase in congenital abnormalities in posttreatment children of cancer survivors, but the inherited genome-wide effect of chemotherapy exposure in humans is unknown.
Experimental Design: Two testicular cancer survivors cured with chemotherapy who had children pre- and postexposure without sperm banking were identified. Familial germline whole genome sequencing (WGS) was performed for these families, and analytic methods were utilized to identify de novo alterations, including mutations, recombinations, and structural rearrangements in the pre- and postexposure offspring.
Results: No increase in de novo germline mutations in postexposure children compared with their preexposure siblings was found. Furthermore, there were no increased short insertion/deletions, recombination frequency, or structural rearrangements in these postexposure children.
Conclusions: In two families of male cancer survivors, there was no transmissible genomic impact of significant mutagenic exposure in postexposure children. This study may provide possible reassuring evidence for patients undergoing chemotherapy who are unable to have pretreatment sperm cryopreservation. Expanded cohorts that utilize WGS to identify environmental exposure effects on the inherited genome may inform the generalizability of these results. Clin Cancer Res; 22(9); 2183–9. ©2015 AACR.
Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems
Authors: Hogwood John , Gray Elaine , Komorowicz Erzsébet , Varjú Imre , Varga Zoltán , Kolev Krasimir , Longstaff Colin 
Published: December 2015

SummaryNeutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 μg/ml histones in APTT and 4.6 μg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 μg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 μg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.