bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions and attitudes of patients towards medication-related osteonecrosis of the jaw (MRONJ): a qualitative study in England
Authors: Sturrock Andrew , Preshaw Philip M , Hayes Catherine , Wilkes Scott 
Published: March 2019

ObjectiveTo explore the impact of medication-related osteonecrosis of the jaw (MRONJ) on quality of life and to explore the attitudes and perceptions of patients towards the multidisciplinary approach to the prevention of the condition.DesignInterpretivist methodology using qualitative semistructured interviews.SettingPrimary care general medical practices and secondary care dental services in England.Participants23 patients; 6 with MRONJ, 13 prescribed bisphosphonates, 4 with osteoporosis not currently prescribed any medication.ResultsPatients felt that MRONJ had a significant negative impact on their quality of life and had poor knowledge of the preventive strategies recommended in the literature. Patients demonstrated positive attitudes towards a multidisciplinary approach to care; however, they perceived prescribers as having the key role in articulating risk. Four salient and inter-related themes emerged from the interviews: (1) perception of knowledge, indicating limited awareness of the condition, risk factors and preventive strategies; (2) quality of life, indicating the lived experiences of patients and the physical, psychological and social impacts of MRONJ; (3) interprofessional management, indicating a perceived organisational hierarchy, professional roles and responsibilities, prioritising aspects of care, articulation of risk and communication and (4) wider context, indicating demands on National Health Service resources and barriers to dental care.ConclusionsMRONJ has a significant detrimental impact on quality of life, yet appropriate preventative education is not apparent. Effective interprofessional patient education and prevention to mitigate against the risk of developing MRONJ is required.
Outcomes of patients with heart failure after primary prevention ICD unit generator replacement
Authors: Looi Khang-Li , Gavin Andrew , Cooper Lisa , Dawson Liane , Slipper Debbie , Lever Nigel 
Published: March 2019

ObjectiveData describing outcomes after implantable cardioverter-defibrillator (ICD) unit generator replacement in patients with heart failure (HF) with primary prevention devices are limited.MethodData on patients with HF who underwent primary prevention ICD/cardiac resynchronisation therapy-defibrillator (CRT-D) implantation from 2007 until mid-2015 who subsequently received unit generator replacement were analysed. Outcomes assessed were mortality, appropriate ICD therapy and shock, and procedural complications.Results61 of 385 patients with HF with primary prevention ICD/CRT-D undergoing unit generator replacement were identified. Follow-up period was 1.8±1.5 years after replacement. 43 (70.5%) patients had not received prior appropriate ICD therapy prior to unit replacement. The cumulative risks of appropriate ICD therapy at 1, 3 and 5 years after unit replacement in those without prior ICD therapy were 0%, 6.2% and 50% compared with 6.2%, 59.8% and 86.6%, respectively (p=0.005) in those with prior ICD therapies. No predictive factors associated with appropriate ICD therapy after replacement could be identified. 41 (32.8%) patients no longer met guideline indications at the time of unit replacement but risks of subsequent appropriate ICD interventions were not different compared with those who continued to meet primary prevention ICD indications.The 5-year mortality risk after unit replacement was 18.4% and there were high procedural complication rates (9.8%).ConclusionNo predictive marker successfully stratified patients no longer needing ICD support prospectively. Finding such a marker is important in decision-making about device replacement particularly given the concerns about the complication rates. These factors should be considered at the time of ICD unit replacement.
Control of multiple-resistant waterhemp [Amaranthus tuberculatus (Moq.) Sauer] with preemergence and postemergence herbicides in corn in Ontario
Authors: Benoit Lauren , Soltani Nader , Hooker David C. , Robinson Darren E. , Sikkema Peter H. 
Published: March 2019

Waterhemp is a competitive, summer annual, broadleaf weed that poses a considerable threat to Ontario grain farmers. Populations with multiple resistance to Group 2 (ALS-inhibitors), Group 5 (photosystem II inhibitors), and Group 9 (EPSPS inhibitors) herbicides have been confirmed in Ontario. If left uncontrolled, waterhemp competition can result in corn yield losses of up to 74%. The objective of this research was to evaluate preemergence (PRE) and postemergence (POST) herbicides for control of multiple-herbicide resistant (MR) waterhemp. Two field studies at two locations (Cottam and Walpole Island) were conducted in 2016 and 2017. Fifteen PRE and 12 POST herbicides were evaluated for waterhemp control, density, and aboveground biomass and corn yield. At 8 wk after application (WAA), S-metolachlor/mesotrione/atrazine (1393/139/524 g a.i. ha−1) and S-metolachlor/mesotrione/bicyclopyrone/atrazine (1259/140/35/588 g a.i. ha−1) applied PRE were the most efficacious, controlling MR waterhemp 87% and 91%, respectively. At 8 WAA, the most efficacious POST herbicides were mesotrione + atrazine and dicamba/atrazine, controlling MR waterhemp 92% and 87%, respectively. Reduced waterhemp interference with the PRE herbicides evaluated resulted in corn yield that was similar to the weed-free control.
Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression
Authors: Han Sang-Yong , Kim Yun-Kyung 
Published: March 2019

Osteoporosis is a common disorder of bone remodeling, marked by excessive osteoclast formation. Recent studies indicated that berberine (BBR) is a potential natural drug for the treatment of various bone diseases. However, it still needs to be further studied for the treatment of osteoporosis. The current study investigated the inhibitory effects of BBR on receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in vitro and in vivo. Cell-based assays were performed using osteoclasts generated in cultures of murine bone marrow-derived macrophages (BMMs) treated with RANKL and M-CSF. The effects of BBR on in vivo lipopolysaccharide (LPS)-mediated bone loss were evaluated using ICR mice. BBR significantly inhibited TRAP-positive osteoclast formation induced by RANKL. BBR also inhibited RANKL-induced Akt, p38 and ERK phosphorylation and I[Formula: see text]B degradation, and suppressed RANKL-induced expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which is a key transcription factors for osteoclast formation. BBR reduced the mRNA levels of osteoclast markers, including TRAP, osteoclast-associated receptor (OSCAR), cathepsin K, and ATPase H[Formula: see text] transporting V0 subunit d2 (ATP6v0d2). Moreover, BBR prevented LPS-mediated bone loss in vivo. We suggest BBR as a natural compound that can be a potential therapeutic agent for osteoclast-related bone diseases.
Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats
Authors: Schmuck Eric G. , Hacker Timothy A. , Schreier David A. , Chesler Naomi C. , Wang Zhijie 
Published: March 2019

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis, we induced PAH in adult rats with SU5416 and chronic hypoxia exposure; treated with rat MSCs delivered by intravenous injection, intramyocardial injection, or epicardial placement of a bioscaffold; and then examined treatment effectiveness by in vivo pressure-volume measurement, echocardiography, histology, and immunohistochemistry. Our results showed that compared with other treatment groups, only the MSC-seeded bioscaffold group resulted in RV functional improvement, including restored stroke volume, cardiac output, and improved stroke work. Diastolic function indicated by end-diastolic pressure-volume relationship was improved by the local MSC treatments or bioscaffold alone. Cardiomyocyte hypertrophy and RV fibrosis were both reduced, and von Willebrand factor expression was restored by the MSC-seeded bioscaffold treatment. Overall, our study suggests a potential new regenerative therapy to rescue the pressure-overload failing RV with persistent pulmonary vascular disease, which may improve quality of life and/or survival of PAH patients. NEW & NOTEWORTHY We explored the effects of mesenchymal stem cell-seeded bioscaffold on right ventricles (RVs) of rats with established pulmonary arterial hypertension (PAH). Some beneficial effects were observed despite persistent PAH, suggesting that this may be a new therapy for RV to improve quality of life and/or survival of PAH patients.
Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies
Authors: Schäfer Michal , Ivy D. Dunbar , Abman Steven H. , Stenmark Kurt , Browne Lorna P. , Barker Alex J. , Mitchell Max B. , Morgan Gareth J. , Wilson Neil , Shah Anar , Kollengode Madhukar , Naresh Nivedita , Fonseca Brian , DiMaria Michael , Buckner J. Kern , Hunter Kendall S. , Kheyfets Vitaly , Fenster Brett E. , Truong Uyen 
Published: March 2019

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults ( n = 10) and children ( n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult ( n = 10) and pediatric ( n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA ( P = 0.020) and MPA-LPA ( P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.
MUC1-C Integrates Chromatin Remodeling and PARP1 Activity in the DNA Damage Response of Triple-Negative Breast Cancer Cells
Authors: Yamamoto Masaaki , Jin Caining , Hata Tsuyoshi , Yasumizu Yota , Zhang Yan , Hong Deli , Maeda Takahiro , Miyo Masaaki , Hiraki Masayuki , Suzuki Yozo , Hinohara Kunihiko , Rajabi Hasan , Kufe Donald 
Published: March 2019

Abstract

The oncogenic MUC1-C protein is overexpressed in triple-negative breast cancer (TNBC) cells and contributes to their epigenetic reprogramming and chemoresistance. Here we show that targeting MUC1-C genetically or pharmacologically with the GO-203 inhibitor, which blocks MUC1-C nuclear localization, induced DNA double-strand breaks and potentiated cisplatin (CDDP)-induced DNA damage and death. MUC1-C regulated nuclear localization of the polycomb group proteins BMI1 and EZH2, which formed complexes with PARP1 during the DNA damage response. Targeting MUC1-C downregulated BMI1-induced H2A ubiquitylation, EZH2-driven H3K27 trimethylation, and activation of PARP1. As a result, treatment with GO-203 synergistically sensitized both mutant and wild-type BRCA1 TNBC cells to the PARP inhibitor olaparib. These findings uncover a role for MUC1-C in the regulation of PARP1 and identify a therapeutic strategy for enhancing the effectiveness of PARP inhibitors against TNBC.

Significance:
These findings demonstrate that targeting MUC1-C disrupts epigenetics of the PARP1 complex, inhibits PARP1 activity, and is synergistic with olaparib in TNBC cells.
Preclinical Development of a WT1 Oral Cancer Vaccine Using a Bacterial Vector to Treat Castration-Resistant Prostate Cancer
Authors: Kitagawa Koichi , Gonoi Reina , Tatsumi Maho , Kadowaki Masahide , Katayama Takane , Hashii Yoshiko , Fujisawa Masato , Shirakawa Toshiro 
Published: March 2019

AbstractPreviously, we constructed a recombinant Bifidobacterium longum displaying a partial mouse Wilms' tumor 1 (WT1) protein (B. longum 420) as an oral cancer vaccine using a bacterial vector and demonstrated that oral administration of B. longum 420 significantly inhibited tumor growth compared with the Db126 WT1 peptide vaccine in the TRAMP-C2, mouse castration-resistant prostate cancer (CRPC) syngeneic tumor model. The present study demonstrated that oral administration of 1.0×109 colony-forming units of B. longum 420 induced significantly higher cytotoxicity against TRAMP-C2 cells than intraperitoneal injection of 100 μg of Db126, and the in vivo antitumor activity of B. longum 420 in the TRAMP-C2 tumor model could be augmented by intraperitoneal injections of 250 μg of anti–PD-1 antibody. For the clinical development, we produced the B440 pharmaceutical formulation, which is lyophilized powder of inactivated B. longum 440 displaying the partially modified human WT1 protein. We confirmed that B. longum 440 could induce cellular immunity specific to multiple WT1 epitopes. In a preclinical dosage study, B440 significantly inhibited growth of the TRAMP-C2 tumors compared with that of the control groups (PBS and B. longum not expressing WT1) at all dosages (1, 5, and 10 mg/body of B440). These mouse doses were considered to correspond with practical oral administration doses of 0.2, 1, and 2 g/body for humans. Taken together, these results suggest that the B440 WT1 oral cancer vaccine can be developed as a novel oral immuno-oncology drug to treat CRPC as a monotherapy or as an adjunct to immune checkpoint inhibitors.
Metabolism Drives Carcinogenesis and Maintenance of Pancreatic Tumors
Authors: Halbrook Christopher J. , Nelson Barbara S. , Lyssiotis Costas A. 
Published: March 2019

Abstract

Summary:
In this issue of Cancer Discovery, Carrer and colleagues find that early events in pancreatic tumorigenesis are driven by altered acetyl-CoA metabolism, where targeting this axis in established cancer models impairs tumor growth. This work provides new insights into the roles of acetyl-CoA in pancreatic cancer and underscores the value of studying early events in carcinogenesis to yield new treatment strategies.
See related article by Carrer et al., p. 416.
Temporal Trends in Incident Mortality in Dialysis Patients: Focus on Sex and Racial Disparities
Authors: Shah Silvi , Leonard Anthony C. , Meganathan Karthikeyan , Christianson Annette L. , Thakar Charuhas V. 
Published: March 2019

<b><i>Background:</i></b> Racial minorities and women constitute substantial portions of the incident and prevalent end-stage renal disease (ESRD) population in the United States. Although ESRD is characterized by high mortality, temporal trends, and race and sex differences in mortality have not been studied. <b><i>Methods:</i></b> We evaluated 944,650 adult patients who initiated dialysis between January 1, 2005 and December 31, 2014, using the United States Renal Data System, for sex-related and race-related trends in mortality. Logistic regression models adjusted for pre-dialysis health status were used to examine associations among the predictors’ sex, race, and year of incident dialysis, and the outcome all-cause mortality at 1-year post ESRD. <b><i>Results:</i></b> The mean age was 65 ± 14 years. The 1-year crude mortality rates in incident ESRD patients decreased by 28% from 2004 to 2015. Risk-adjusted 1-year mortality decreased by 3% for each later year of incident ESRD (<i>p </i>&#x3c; 0.001). In general, from 2005 to 2014, mortality rates decreased across both sexes, and all races. White patients experienced the lowest reduction in adjusted 1-year mortality rates (16%). While women experienced a survival advantage over men in 2005, by 2014 it was reversed to survival advantage for men. Combining all years, the adjusted risk of dying at 1-year after initiating dialysis was lower in women than men (OR 0.98; 95% CI 0.97–0.99), and as compared to whites, was lower in blacks (OR 0.73; 95% CI ­0.72–0.74), Hispanics (OR 0.64; 95% CI 0.63–0.65), Asians (OR 0.55; 95% CI 0.53–0.56), and Native Americans (OR 0.67; 95% CI 0.63–0.71). <b><i>Conclusion:</i></b> The 1-year mortality rates among patients with ESRD have decreased steadily during a recent 10-year period across both men and women, and in all 5 races. Women have only a 2% lower risk of dying at 1-year after dialysis initiation than men. White patients had higher mortality as compared to other races. Our results suggest the need for sex, and race-specific treatment strategies in ESRD care.
Toward Computational Simulations of Behavior During Automated Driving Takeovers: A Review of the Empirical and Modeling Literatures
Authors: McDonald Anthony D. , Alambeigi Hananeh , Engström Johan , Markkula Gustav , Vogelpohl Tobias , Dunne Jarrett , Yuma Norbert 
Published: March 2019

Objective: This article provides a review of empirical studies of automated vehicle takeovers and driver modeling to identify influential factors and their impacts on takeover performance and suggest driver models that can capture them. Background: Significant safety issues remain in automated-to-manual transitions of vehicle control. Developing models and computer simulations of automated vehicle control transitions may help designers mitigate these issues, but only if accurate models are used. Selecting accurate models requires estimating the impact of factors that influence takeovers. Method: Articles describing automated vehicle takeovers or driver modeling research were identified through a systematic approach. Inclusion criteria were used to identify relevant studies and models of braking, steering, and the complete takeover process for further review. Results: The reviewed studies on automated vehicle takeovers identified several factors that significantly influence takeover time and post-takeover control. Drivers were found to respond similarly between manual emergencies and automated takeovers, albeit with a delay. The findings suggest that existing braking and steering models for manual driving may be applicable to modeling automated vehicle takeovers. Conclusion: Time budget, repeated exposure to takeovers, silent failures, and handheld secondary tasks significantly influence takeover time. These factors in addition to takeover request modality, driving environment, non-handheld secondary tasks, level of automation, trust, fatigue, and alcohol significantly impact post-takeover control. Models that capture these effects through evidence accumulation were identified as promising directions for future work. Application: Stakeholders interested in driver behavior during automated vehicle takeovers may use this article to identify starting points for their work.
Overdiagnosis of pulmonary embolism: definition, causes and implications
Authors: Dobler Claudia C. 
Published: March 2019

Overuse of computed tomography pulmonary angiography to diagnose pulmonary embolism in people who have only a low pre-test probability of pulmonary embolism has received significant attention in the past. The issue of overdiagnosis of pulmonary embolism, a potential consequence of overtesting, has been less explored. The term “overdiagnosis”, used in a narrow sense, describes a correct (true positive) diagnosis in a person but without any associated harm. The aim of this review is to summarise literature on the topic of overdiagnosis of pulmonary embolism and translate this epidemiological concept into the clinical practice of respiratory professionals. The review concludes that the location of pulmonary embolism at a subsegmental level, rather than whether a diagnosis was made incidentally or following an investigation for suspected pulmonary embolism, is the best predictor for situations in which anticoagulation may not be necessary. In the absence of strong evidence of the optimal management of subsegmental pulmonary embolism, treatment decisions should be made case by case, taking into account the patient's situation and preference.Key pointsSince the introduction of computed tomography pulmonary angiography in 1998, there has been a steep increase in the diagnosis of pulmonary embolism (PE).An increased incidence of PE diagnoses, but an almost stable mortality from PE in the population, together with a decreased case fatality, point towards overdiagnosis (in the absence of more effective treatment).Whether PE is diagnosed as an incidental finding or following an investigation for suspected PE does not appear to influence the need for anticoagulation therapy.An isolated subsegmental PE may not require anticoagulation therapy, and treatment decisions should be made case by case, taking into account the patient's situation and preference.A suggested definition of overdiagnosis of PE: a diagnosis of PE that, if left untreated, would not lead to more harm than if it were treated with anticoagulation therapy, independent of symptoms.Educational aimsTo understand the term “overdiagnosis” based on its narrow definition and be able to apply it to PE.To outline the diagnostic approach to PE.To summarise what is known about the treatment of incidentally detected PE.To summarise what is known about the treatment of subsegmental PE.To understand in which situations anticoagulation therapy for PE may not be beneficial.