bluuebunny/crossref_metadata_2025_split huggingface dataset:
Many people in Scotland now benefit from anticipatory care before they die: an after death analysis and interviews with general practitioners
Authors: Tapsfield Julia , Hall Charlie , Lunan Carey , McCutcheon Hazel , McLoughlin Peter , Rhee Joel , Leiva Alfonso , Spiller Juliet , Finucane Anne , Murray Scott A 
Published: April 2016

BackgroundKey Information Summaries (KIS) were introduced throughout Scotland in 2013 so that anticipatory care plans written by general practitioners (GPs) could be routinely shared electronically and updated in real time, between GPs and providers of unscheduled and secondary care.AimsWe aimed to describe the current reach of anticipatory and palliative care, and to explore GPs’ views on using KIS.MethodsWe studied the primary care records of all patients who died in 2014 in 9 diverse Lothian practices. We identified if anticipatory or palliative care had been started, and if so how many weeks before death and which aspects of care had been documented. We interviewed 10 GPs to understand barriers and facilitating factors.ResultsOverall, 60% of patients were identified for a KIS, a median of 18 weeks before death. The numbers identified were highest for patients with cancer, with 75% identified compared with 66% of those dying with dementia/frailty and only 41% dying from organ failure. Patients were more likely to die outside hospital if they had a KIS. GPs identified professional, patient and societal challenges in identifying patients for palliative care, especially those with non-cancer diagnoses.ConclusionsGPs are identifying patients for anticipatory and palliative care more equitably across the different disease trajectories and earlier in the disease process than they were previously identifying patients specifically for palliative care. However, many patients still lack care planning, particularly those dying with organ failure.
Transfer Learning to Infer Social Ties across Heterogeneous Networks
Authors: Tang Jie , Lou Tiancheng , Kleinberg Jon , Wu Sen 
Published: April 2016

Interpersonal ties are responsible for the structure of social networks and the transmission of information through these networks. Different types of social ties have essentially different influences on people. Awareness of the types of social ties can benefit many applications, such as recommendation and community detection. For example, our close friends tend to move in the same circles that we do, while our classmates may be distributed into different communities. Though a bulk of research has focused on inferring particular types of relationships in a specific social network, few publications systematically study the generalization of the problem of predicting social ties across multiple heterogeneous networks.
In this work, we develop a framework referred to as TranFG for classifying the type of social relationships by learning across heterogeneous networks. The framework incorporates social theories into a factor graph model, which effectively improves the accuracy of predicting the types of social relationships in a target network by borrowing knowledge from a different source network. We also present several active learning strategies to further enhance the inferring performance. To scale up the model to handle really large networks, we design a distributed learning algorithm for the proposed model.
We evaluate the proposed framework (TranFG) on six different networks and compare with several existing methods. TranFG clearly outperforms the existing methods on multiple metrics. For example, by leveraging information from a coauthor network with labeled advisor-advisee relationships, TranFG is able to obtain an F1-score of 90% (8%--28% improvements over alternative methods) for predicting manager-subordinate relationships in an enterprise email network. The proposed model is efficient. It takes only a few minutes to train the proposed transfer model on large networks containing tens of thousands of nodes.
Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors
Authors: Kress Theresia R. , Pellanda Paola , Pellegrinet Luca , Bianchi Valerio , Nicoli Paola , Doni Mirko , Recordati Camilla , Bianchi Salvatore , Rotta Luca , Capra Thelma , Ravà Micol , Verrecchia Alessandro , Radaelli Enrico , Littlewood Trevor D. , Evan Gerard I. , Amati Bruno 
Published: April 2016

Abstract
Tumors driven by activation of the transcription factor MYC generally show oncogene addiction. However, the gene expression programs that depend upon sustained MYC activity remain unknown. In this study, we employed a mouse model of liver carcinoma driven by a reversible tet-MYC transgene, combined with chromatin immunoprecipitation and gene expression profiling to identify MYC-dependent regulatory events. As previously reported, MYC-expressing mice exhibited hepatoblastoma- and hepatocellular carcinoma–like tumors, which regressed when MYC expression was suppressed. We further show that cellular transformation, and thus initiation of liver tumorigenesis, were impaired in mice harboring a MYC mutant unable to associate with the corepressor protein MIZ1 (ZBTB17). Notably, switching off the oncogene in advanced carcinomas revealed that MYC was required for the continuous activation and repression of distinct sets of genes, constituting no more than half of all genes deregulated during tumor progression and an even smaller subset of all MYC-bound genes. Altogether, our data provide the first detailed analysis of a MYC-dependent transcriptional program in a fully developed carcinoma and offer a guide to identifying the critical effectors contributing to MYC-driven tumor maintenance. Cancer Res; 76(12); 3463–72. ©2016 AACR.
A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors
Authors: Tolcher Anthony W. , Bendell Johanna C. , Papadopoulos Kyriakos P. , Burris Howard A. , Patnaik Amita , Fairbrother Wayne J. , Wong Harvey , Budha Nageshwar , Darbonne Walter C. , Peale Franklin , Mamounas Michael , Royer-Joo Stephanie , Yu Ron , Portera Chia C. , Infante Jeffrey R. 
Published: April 2016

Abstract
Purpose: To determine the dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetics, and preliminary evidence of antitumor activity of CUDC-427 (formerly GDC-0917), a selective antagonist of inhibitor of apoptosis (IAP) proteins.
Experimental Design: Patients with advanced solid malignancies were treated with escalating doses of CUDC-427 orally on a daily 14-day on/7-day off schedule in 21-day cycles using a modified continuous reassessment method design. Blood samples were assayed to determine the pharmacokinetic properties, pharmacodynamic alterations of cellular IAP levels in peripheral blood mononuclear cells (PBMC), and monocyte chemoattractant protein-1 (MCP-1) levels.
Results: Forty-two patients received 119 cycles of CUDC-427. Overall, the most common treatment-related toxicities were fatigue, nausea, vomiting, and rash. One DLT (grade 3 fatigue) occurred in a patient at 450 mg dose level during cycle 1, and 5 patients experienced AEs related to CUDC-427 that led to discontinuation and included grade 3 pruritus, and fatigue, and grade 2 drug hypersensitivity, pneumonitis, rash, and QT prolongation. The maximum planned dose of 600 mg orally daily for 2 weeks was reached, which allometrically scaled to exceed the IC90 in preclinical xenograft studies. Significant decreases in cIAP-1 levels in PBMCs were observed in all patients 6 hours after initial dosing. Responses included durable complete responses in one patient with ovarian cancer and one patient with MALT lymphoma.
Conclusions: CUDC-427 can be administered safely at doses up to 600 mg daily for 14 days every 3 weeks. The absence of severe toxicities, inhibition of cIAP-1 in PBMC, and antitumor activity warrant further studies. Clin Cancer Res; 22(18); 4567–73. ©2016 AACR.
Epithelial–Mesenchymal Transition and Immune Evasion during Lung Cancer Progression: The Chicken or the Egg?
Authors: Datar Ila , Schalper Kurt A. 
Published: April 2016

Abstract
Epithelial–mesenchymal transition (EMT) is a complex process involved in metastasis. Immune evasion is required for tumor progression and is characterized by an ineffective antitumor immune response and upregulation of immune-suppressive signals. The coexistence of EMT and adaptive immune evasion opens the possibility of a mechanistic link between these processes. Clin Cancer Res; 22(14); 3422–4. ©2016 AACR.
See related article by Lou et al., p. 3630
Alternative Polyadenylation: Another Foe in Cancer
Authors: Erson-Bensan Ayse Elif , Can Tolga 
Published: April 2016

Abstract
Advancements in sequencing and transcriptome analysis methods have led to seminal discoveries that have begun to unravel the complexity of cancer. These studies are paving the way toward the development of improved diagnostics, prognostic predictions, and targeted treatment options. However, it is clear that pieces of the cancer puzzle are still missing. In an effort to have a more comprehensive understanding of the development and progression of cancer, we have come to appreciate the value of the noncoding regions of our genomes, partly due to the discovery of miRNAs and their significance in gene regulation. Interestingly, the miRNA–mRNA interactions are not solely dependent on variations in miRNA levels. Instead, the majority of genes harbor multiple polyadenylation signals on their 3′ UTRs (untranslated regions) that can be differentially selected on the basis of the physiologic state of cells, resulting in alternative 3′ UTR isoforms. Deregulation of alternative polyadenylation (APA) has increasing interest in cancer research, because APA generates mRNA 3′ UTR isoforms with potentially different stabilities, subcellular localizations, translation efficiencies, and functions. This review focuses on the link between APA and cancer and discusses the mechanisms as well as the tools available for investigating APA events in cancer. Overall, detection of deregulated APA-generated isoforms in cancer may implicate some proto-oncogene activation cases of unknown causes and may help the discovery of novel cases; thus, contributing to a better understanding of molecular mechanisms of cancer. Mol Cancer Res; 14(6); 507–17. ©2016 AACR.
Quantification of the Effect of Pressure Wire Drift on the Diagnostic Performance of Fractional Flow Reserve, Instantaneous Wave-Free Ratio, and Whole-Cycle Pd/Pa
Authors: Cook Christopher M. , Ahmad Yousif , Shun-Shin Matthew J. , Nijjer Sukhjinder , Petraco Ricardo , Al-Lamee Rasha , Mayet Jamil , Francis Darrel P. , Sen Sayan , Davies Justin E. 
Published: April 2016

Background—
Small drifts in intracoronary pressure measurements (±2 mm Hg) can affect stenosis categorization using pressure indices. This has not previously been assessed for fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and whole-cycle distal pressure/proximal pressure (Pd/Pa) indices.

Methods and Results—Four hundred forty-seven

stenoses were assessed with FFR, iFR, and whole-cycle Pd/Pa. Cut point values for significance were predefined as ≤0.8, <0.90, and <0.93, respectively. Pressure wire drift was simulated by offsetting the distal coronary pressure trace by ±2 mm Hg. FFR, iFR, and whole-cycle Pd/Pa indices were recalculated and stenosis misclassification quantified. Median (±median absolute deviation) values for FFR, iFR, and whole-cycle Pd/Pa were 0.81 (±0.11), 0.90 (±0.07), and 0.93 (±0.06), respectively. For the cut point of FFR, iFR, and whole-cycle Pd/Pa, 34.6% (155), 50.1% (224), and 62.2% (278) of values, respectively, lay within ±0.05 U. With ±2 mm Hg pressure wire drift, 21% (94), 25% (110), and 33% (148) of the study population were misclassified with FFR, iFR, and whole-cycle Pd/Pa, respectively. Both FFR and iFR had significantly lower misclassification than whole-cycle Pd/Pa (
P
<0.001). There was no statistically significant difference between the diagnostic performance of FFR and iFR (
P
=0.125).

Conclusions—
In a substantial proportion of cases, small amounts of pressure wire drift are enough to cause stenoses to change classification. Whole-cycle Pd/Pa is more vulnerable to such reclassification than FFR and iFR.
Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial
Authors: Menon Bijoy K. , Sajobi Tolulope T. , Zhang Yukun , Rempel Jeremy L. , Shuaib Ashfaq , Thornton John , Williams David , Roy Daniel , Poppe Alexandre Y. , Jovin Tudor G. , Sapkota Biggya , Baxter Blaise W. , Krings Timo , Silver Frank L. , Frei Donald F. , Fanale Christopher , Tampieri Donatella , Teitelbaum Jeanne , Lum Cheemun , Dowlatshahi Dar , Eesa Muneer , Lowerison Mark W. , Kamal Noreen R. , Demchuk Andrew M. , Hill Michael D. , Goyal Mayank 
Published: April 2016

Background—
The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial.

Methods and Results—

Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% (
P
=0.006). Symptom onset-to-imaging time was not associated with outcome (
P
>0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes).

Conclusions—
Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01778335.
Paternal behaviour in a socially monogamous but sexually promiscuous passerine bird
Authors: Chutter Christopher M. , Redmond Lucas J. , Cooper Nathan W. , Dolan Amy C. , Duffield Deborah , Murphy Michael T. 
Published: April 2016

We documented parental behaviour and paternity of eastern kingbirds (Tyrannus tyrannus) to test the predictions that paternal care would decline with increasing loss of paternity, increasing nesting density (a proxy for probability of paternity loss), male quality, and number of fertile females available in the population. Extra-pair young were found in 58% of 45 nests for which behaviour was recorded and a higher proportion of young were extra-pair as nesting density increased. Male feeding rate declined with increasing nesting density and male quality, but neither feeding rate nor a composite measure of paternal behaviour varied with number of fertile females or paternity. Although alternative explanations exist, one interpretation of the reduced paternal care at high nesting density was that it was a response to perceived threats of paternity loss. The ultimate basis for the lower paternal effort of higher quality males is unclear but we discuss several possible explanations.
Flying the Needles
Authors: Haslbeck Andreas , Hoermann Hans-Juergen 
Published: April 2016

Objective: The aim of this study was to evaluate the influence of practice and training on fine-motor flying skills during a manual instrument landing system (ILS) approach. Background: There is an ongoing debate that manual flying skills of long-haul crews suffer from a lack of flight practice due to conducting only a few flights per month and the intensive use of automation. However, objective evidence is rare. Method: One hundred twenty-six randomly selected airline pilots had to perform a manual flight scenario with a raw data precision approach. Pilots were assigned to four equal groups according to their level of practice and training by fleet (short-haul, long-haul) and rank (first officer, captain). Results: Average ILS deviation scores differed significantly in relation to the group assignments. The strongest predictor variable was fleet, indicating degraded performance among long-haul pilots. Conclusion: Manual flying skills are subject to erosion due to a lack of practice on long-haul fleets: All results support the conclusion that recent flight practice is a significantly stronger predictor for fine-motor flying performance than the time period since flight school or even the total or type-specific flight experience. Application: Long-haul crews have to be supported in a timely manner by adequate training tailored to address manual skills or by operational provisions like mixed-fleet flying or more frequent transitions between short-haul and long-haul operation.
Mental health services use among adults with or without mental disorders: Do development stages matter?
Authors: Huỳnh Christophe , Caron Jean , Fleury Marie-Josée 
Published: April 2016

Background: Mental health services (MHS) use is a complex behaviour that does not only concern individuals with current mental disorder. To date, few studies have examined age-related contextualisation of MHS use. Reasons for seeking help may vary according to development stages in adulthood. Aims: This study aimed to determine which predisposing, enabling and need factors, using Andersen’s model, were associated with MHS use according to adult development stages among individuals with or without current psychiatric diagnosis. Methods: Three age groups were examined: 18- to 29-year-olds ( n = 775), 30- to 49-year-olds ( n = 1,560) and 50- to 64-year-olds ( n = 960). Data were obtained from the Montreal Longitudinal Catchment Area Study. Bivariate and multivariate logistic regression analyses were conducted for each age group separately to determine which predisposing, enabling and need factors were associated with MHS use in the past 12 months. Results: For 18- to 29-year-olds, one enabling factor (Internet search) and two need factors (presence of major depressive disorder and number of stressful events) were positively associated with MHS use. For 30- to 49-year-olds, one predisposing factor (family history of mental disorder), four enabling factors (not currently working or in school, perceiving neighbourhood disorder, social cohesion and Internet searching) and one need factor (major depressive disorder) correlated with help seeking. For 50- to 64-year-olds, two predisposing factors (family history of mental disorder and higher self-perceived stigma), two enabling factors (low satisfaction in personal relationship and Internet searching) and one need factor (alcohol dependence) were associated with MHS use. Conclusions: Factors associated with MHS use differ according to adult development stages. Programmes and policies should be based on age-related contextualisation to increase MHS use.
Strain Response of the Anterior Cruciate Ligament to Uniplanar and Multiplanar Loads During Simulated Landings
Authors: Kiapour Ata M. , Demetropoulos Constantine K. , Kiapour Ali , Quatman Carmen E. , Wordeman Samuel C. , Goel Vijay K. , Hewett Timothy E. 
Published: April 2016

Background: Despite basic characterization of the loading factors that strain the anterior cruciate ligament (ACL), the interrelationship(s) and additive nature of these loads that occur during noncontact ACL injuries remain incompletely characterized. Hypothesis: In the presence of an impulsive axial compression, simulating vertical ground-reaction force during landing (1) both knee abduction and internal tibial rotation moments would result in increased peak ACL strain, and (2) a combined multiplanar loading condition, including both knee abduction and internal tibial rotation moments, would increase the peak ACL strain to levels greater than those under uniplanar loading modes alone. Study Design: Controlled laboratory study. Methods: A cadaveric model of landing was used to simulate dynamic landings during a jump in 17 cadaveric lower extremities (age, 45 ± 7 years; 9 female and 8 male). Peak ACL strain was measured in situ and characterized under impulsive axial compression and simulated muscle forces (baseline) followed by addition of anterior tibial shear, knee abduction, and internal tibial rotation loads in both uni- and multiplanar modes, simulating a broad range of landing conditions. The associations between knee rotational kinematics and peak ACL strain levels were further investigated to determine the potential noncontact injury mechanism. Results: Externally applied loads, under both uni- and multiplanar conditions, resulted in consistent increases in peak ACL strain compared with the baseline during simulated landings (by up to 3.5-fold; P ≤ .032). Combined multiplanar loading resulted in the greatest increases in peak ACL strain ( P < .001). Degrees of knee abduction rotation ( R2 = 0.45; β = 0.42) and internal tibial rotation ( R2 = 0.32; β = 0.23) were both significantly correlated with peak ACL strain ( P < .001). However, changes in knee abduction rotation had a significantly greater effect size on peak ACL strain levels than did internal tibial rotation (by ~2-fold; P < .001). Conclusion: In the presence of impulsive axial compression, the combination of anterior tibial shear force, knee abduction, and internal tibial rotation moments significantly increases ACL strain, which could result in ACL failure. These findings support multiplanar knee valgus collapse as one the primary mechanisms of noncontact ACL injuries during landing. Clinical Relevance: Intervention programs that address multiple planes of loading may decrease the risk of ACL injury and the devastating consequences of posttraumatic knee osteoarthritis.