bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Impact of Tumor DNA Repair Expression and T-cell Infiltration in Breast Cancers
Authors: Green Andrew R. , Aleskandarany Mohammed A. , Ali Reem , Hodgson Eleanor Grace , Atabani Suha , De Souza Karen , Rakha Emad A. , Ellis Ian O. , Madhusudan Srinivasan 
Published: March 2017

Abstract
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1,269 breast cancers and validated our findings in an independent estrogen receptor–negative (ER−) cohort (n = 279). Patients with tumors that expressed low XRCC1, low ATM, and low BRCA1 were not only associated with high numbers of CD8+ tumor-infiltrating lymphocytes, but were also linked to higher grades, high proliferation indexes, presence of dedifferentiated cells, ER− cells, and poor survival (all P ≤ 0.01). PD-1+ or PD-L1+ breast cancers with low XRCC1 were also linked to an aggressive phenotype that was high grade, had high proliferation indexes, contained dedifferentiated cells and ER− (all with P values ≤ 0.01), and poor survival (P = 0.00021 and P = 0.00022, for PD-1+ and PD-L1+ cancers, respectively) including in an independent ER− validation cohort (P = 0.007 and P = 0.047, respectively). We conclude that the interplay between DNA repair, CD8, PD-L1, and PD-1 can promote aggressive tumor phenotypes. XRCC1-directed personalization of immune checkpoint inhibitor therapy may be feasible and warrants further investigation in breast cancer. Cancer Immunol Res; 5(4); 292–9. ©2017 AACR.
E-Prostanoid 3 Receptor Mediates Sprouting Angiogenesis Through Suppression of the Protein Kinase A/β-Catenin/Notch Pathway
Authors: Chen Di , Tang Juan , Wan Qiangyou , Zhang Jian , Wang Kai , Shen Yujun , Yu Ying 
Published: March 2017

Objective—
Angiogenesis is a hallmark of embryonic development and various ischemic and inflammatory diseases. Prostaglandin E2 receptor subtype 3 (EP3) plays an important role in pathophysiologic angiogenesis; however, the precise mechanisms remain unknown. Here, we investigated the role of EP3 in zebra fish embryo and mouse retina angiogenesis and evaluated the underlying mechanisms.

Approach and Results—
The EP3 receptor was highly expressed in the vasculature in both zebra fish embryos and murine fetal retinas. Pharmacological inhibition or genetic deletion of EP3 significantly reduced vasculature formation in zebra fish embryos and mouse retinas. Further characterization revealed reduced filopodia extension of tip cells in embryonic retinas in EP3-deficient mice. EP3 deletion activated Notch activity by upregulation of delta-like ligand 4 expression in endothelial cells (ECs). Inhibition of Notch signaling rescued the angiogenic defects in EP3-deficient mouse retinas. Moreover, EP3 deficiency led to a significant increase in β-catenin phosphorylation at Ser675 and nuclear accumulation of β-catenin in ECs. Knockdown or inhibition of β-catenin restored the impaired sprouting angiogenesis resulting from EP3 deficiency in ECs. The EP3 receptor depressed protein kinase A activity in ECs by coupling to Gαi. Inhibition of protein kinase A activity significantly reduced Ser675 phosphorylation and nuclear translocation of β-catenin, abolished the increased delta-like ligand 4 expression, and subsequently restored the impaired angiogenic capacity of EP3-deficient ECs both in vitro and in vivo.

Conclusions—
Activation of the EP3 receptor facilitates sprouting angiogenesis through protein kinase A–dependent Notch signaling, suggesting that EP3 and its downstream pathways maybe potential therapeutic targets in the treatment of ischemic diseases.
EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia
Authors: Ghori Adnan , Freimann Florian B. , Nieminen-Kelhä Melina , Kremenetskaia Irina , Gertz Karen , Endres Matthias , Vajkoczy Peter 
Published: March 2017

Objective—
Cerebral edema caused by the disruption of the blood–brain barrier is a major complication after stroke. Therefore, strategies to accelerate and enhance neurovascular recovery after stroke are of prime interest. Our main aim was to study the role of ephrinB2/EphB4 signaling in mediating the vascular repair and in blood–brain barrier restoration after mild cerebral ischemia occlusion/reperfusion.

Approach and Results—
Here, we show that the guidance molecule ephrinB2 plays a key role in neurovascular protection and blood–brain barrier restoration after stroke. In a focal stroke model, we characterize the stroke-induced damage to cerebral blood vessels and their subsequent endogenous repair on a cellular, molecular, and functional level. EphrinB2 and its tyrosine kinase receptor EphB4 are upregulated early after stroke by endothelial cells and perivascular support cells, in parallel to their reassembly during neurovascular recovery. Using both retroviral and pharmacological approaches, we show that the inhibition of ephrinB2/EphB4 signaling suppresses post-middle cerebral artery occlusion neurovascular repair mechanisms resulting in an aggravation of brain swelling. In contrast, the activation of ephrinB2 after brain ischemia leads to an increased pericyte recruitment and increased endothelial–pericyte interaction, resulting in an accelerated neurovascular repair after ischemia.

Conclusions—
We show that reducing swelling could result in improved outcome because of reduction in damaged brain tissue. We also identify a novel role for ephrinB2/EphB4 signaling in the maintenance of the neurovascular homeostasis and provide a novel therapeutic approach in reducing brain swelling after stroke.
Optimizing a Drone Network to Deliver Automated External Defibrillators
Authors: Boutilier Justin J. , Brooks Steven C. , Janmohamed Alyf , Byers Adam , Buick Jason E. , Zhan Cathy , Schoellig Angela P. , Cheskes Sheldon , Morrison Laurie J. , Chan Timothy C. Y. 
Published: March 2017

Background:
Public access defibrillation programs can improve survival after out-of-hospital cardiac arrest, but automated external defibrillators (AEDs) are rarely available for bystander use at the scene. Drones are an emerging technology that can deliver an AED to the scene of an out-of-hospital cardiac arrest for bystander use. We hypothesize that a drone network designed with the aid of a mathematical model combining both optimization and queuing can reduce the time to AED arrival.

Methods:
We applied our model to 53 702 out-of-hospital cardiac arrests that occurred in the 8 regions of the Toronto Regional RescuNET between January 1, 2006, and December 31, 2014. Our primary analysis quantified the drone network size required to deliver an AED 1, 2, or 3 minutes faster than historical median 911 response times for each region independently. A secondary analysis quantified the reduction in drone resources required if RescuNET was treated as a large coordinated region.

Results:
The region-specific analysis determined that 81 bases and 100 drones would be required to deliver an AED ahead of median 911 response times by 3 minutes. In the most urban region, the 90th percentile of the AED arrival time was reduced by 6 minutes and 43 seconds relative to historical 911 response times in the region. In the most rural region, the 90th percentile was reduced by 10 minutes and 34 seconds. A single coordinated drone network across all regions required 39.5% fewer bases and 30.0% fewer drones to achieve similar AED delivery times.

Conclusions:
An optimized drone network designed with the aid of a novel mathematical model can substantially reduce the AED delivery time to an out-of-hospital cardiac arrest event.
Echocardiographic Screening for Rheumatic Heart Disease in Indigenous Australian Children: A Cost–Utility Analysis
Authors: Roberts Kathryn , Cannon Jeffrey , Atkinson David , Brown Alex , Maguire Graeme , Remenyi Bo , Wheaton Gavin , Geelhoed Elizabeth , Carapetis Jonathan R. 
Published: March 2017

Background

Rheumatic heart disease (
RHD
) remains a leading cause of cardiovascular morbidity and mortality in children and young adults in disadvantaged populations. The emergence of echocardiographic screening provides the opportunity for early disease detection and intervention. Using our own multistate model of
RHD
progression derived from Australian
RHD
register data, we performed a cost–utility analysis of echocardiographic screening in indigenous Australian children, with the dual aims of informing policy decisions in Australia and providing a model that could be adapted in other countries.

Methods and Results

We simulated the outcomes of 2 screening strategies, assuming that
RHD
could be detected 1, 2, or 3 years earlier by screening. Outcomes included reductions in heart failure, surgery, mortality, disability‐adjusted life‐years, and corresponding costs. Only a strategy of screening all indigenous 5‐ to 12‐year‐olds in half of their communities in alternate years was found to be cost‐effective (incremental cost‐effectiveness ratio less than AU$50 000 per disability‐adjusted life‐year averted), assuming that
RHD
can be detected at least 2 years earlier by screening; however, this result was sensitive to a number of assumptions. Additional modeling of improved adherence to secondary prophylaxis alone resulted in dramatic reductions in heart failure, surgery, and death; these outcomes improved even further when combined with screening.

Conclusions

Echocardiographic screening for
RHD
is cost‐effective in our context, assuming that
RHD
can be detected ≥2 years earlier by screening. Our model can be adapted to any other setting but will require local data or acceptable assumptions for model parameters.
Ice-Phase Precipitation
Authors: Gultepe I. , Heymsfield A. J. , Field P. R. , Axisa D. 
Published: March 2017

AbstractIce-phase precipitation occurs at Earth’s surface and may include various types of pristine crystals, rimed crystals, freezing droplets, secondary crystals, aggregates, graupel, hail, or combinations of any of these. Formation of ice-phase precipitation is directly related to environmental and cloud meteorological parameters that include available moisture, temperature, and three-dimensional wind speed and turbulence, as well as processes related to nucleation, cooling rate, and microphysics. Cloud microphysical parameters in the numerical models are resolved based on various processes such as nucleation, mixing, collision and coalescence, accretion, riming, secondary ice particle generation, turbulence, and cooling processes. These processes are usually parameterized based on assumed particle size distributions and ice crystal microphysical parameters such as mass, size, and number and mass density. Microphysical algorithms in the numerical models are developed based on their need for applications. Observations of ice-phase precipitation are performed using in situ and remote sensing platforms, including radars and satellite-based systems. Because of the low density of snow particles with small ice water content, their measurements and predictions at the surface can include large uncertainties. Wind and turbulence affecting collection efficiency of the sensors, calibration issues, and sensitivity of ground-based in situ observations of snow are important challenges to assessing the snow precipitation. This chapter’s goals are to provide an overview for accurately measuring and predicting ice-phase precipitation. The processes within and below cloud that affect falling snow, as well as the known sources of error that affect understanding and prediction of these processes, are discussed.
Process-Based Decomposition of the Decadal Climate Difference between 2002–13 and 1984–95
Authors: Hu Xiaoming , Li Yana , Yang Song , Deng Yi , Cai Ming 
Published: March 2017

This study examines at the process level the climate difference between 2002–13 and 1984–95 in ERA-Interim. A linearized radiative transfer model is used to calculate the temperature change such that its thermal radiative cooling would balance the energy flux perturbation associated with the change of an individual process, without regard to what causes the change of the process in the first place. The global mean error of the offline radiative transfer model calculations is 0.09 K, which corresponds to the upper limit of the uncertainties from a single term in the decomposition analysis. The process-based decomposition indicates that the direct effect of the increase of CO2 (0.15 K) is the largest contributor to the global warming between the two periods (about 0.27 K). The second and third largest contributors are the cloud feedback (0.14 K) and the combined effect of the oceanic heat storage and evaporation terms (0.11 K), respectively. The largest warming associated with the oceanic heat storage term is found in the tropical Pacific and Indian Oceans, with relatively weaker warming over the tropical Atlantic Ocean. The increase in atmospheric moisture adds another 0.1 K to the global surface warming, but the enhancement in tropical convections acts to reduce the surface warming by 0.17 K. The ice-albedo and atmospheric dynamical feedbacks are the two leading factors responsible for the Arctic polar warming amplification (PWA). The increase of atmospheric water vapor over the Arctic region also contributes substantially to the Arctic PWA pattern.
The Effect of Metatarsal Padding on Pain and Functional Ability in Metatarsalgia
Authors: Männikkö K. , Sahlman J. 
Published: March 2017

Background and Aims: Many kinds of insoles and pads are commonly used as a conservative treatment of metatarsalgia. However, earlier studies of insole treatment provide contradictory results, and the natural progression of metatarsalgia is still unknown. The aims of this study were to (1) determine whether simple custom-made metatarsal pad insoles reduce pain and improve functional ability, (2) find out patients’ satisfaction with padding treatment, and (3) investigate predisposing factors for metatarsalgia. Material and Methods: All metatarsalgia patients provided with metatarsal pad insoles during a 2-year period at Kuopio University Hospital (n = 45) were included in the study and observed at least a year. In all, 25 patients were interviewed about their situation before and after treatment. The Numeric Rating Scale for pain and American Orthopaedic Foot & Ankle Society forefoot questionnaire included questions about predisposing factors, other diseases, exercise, work, shoes, and satisfaction with insoles. Foot X-rays taken from 45 patients during treatment were analyzed. Results: The mean age of the patients was 56 years (range 34–84 years); 87% of them were women. In all, 47% of patients had osteoarthritic changes in the first metatarsophalangeal joint, and 42% had hallux valgus. In the interviewed subgroup (n = 25) body mass index was normal in 44%, and 36% were mildly overweight. High-heeled shoes were used by 40% daily, and 68% had done standing work for several years. Pain decreased significantly on the Numeric Rating Scale: 3.2 points in all patients ( p < 0.001), 3.1 points among women, and 4.25 points among men. The American Orthopaedic Foot & Ankle Society score improved 24.2 points in all patients ( p < 0.001, range 0–100), among women 19 points, and among men 29 points. Conclusion: Metatarsalgia affects mostly women and is often preceded by extensive use of high heels and standing work. Also, a high association of first metatarsophalangeal arthrosis and hallux valgus was found. Metatarsal pads reduce pain and improve the American Orthopaedic Foot & Ankle Society score. We recommend metatarsal padding as a safe and inexpensive alternative in treating metatarsalgia patients.
Elevated Levels of Procalcitonin and Interleukin-6 are Linked with Postoperative Complications in Cardiac Surgery
Authors: Brocca A. , Virzì G. M. , de Cal M. , Giavarina D. , Carta M. , Ronco C. 
Published: March 2017

Background: Cardiac surgery–associated acute kidney injury is a frequent and serious postoperative complication of cardiac surgery and is associated with an increased risk of morbidity, mortality, and length stay. In this study, we hypothesized that persistent elevation in inflammation in the first 48 h might be a powerful predictor of clinical outcome. Our aim was to elucidate the usefulness of interleukin-6 and procalcitonin postoperative levels in predicting mortality and renal complications in cardiac surgery patients. Methods: A total of 122 cardiac surgery patients were enrolled. Procalcitonin and interleukin-6 concentrations were measured on the second postoperative day, and their levels were evaluated versus a number of conditions and endpoints. Results: Procalcitonin has a good predictive value for adverse renal outcome (p < 0.05). Interleukin-6 has a good predictive value for 30 days and overall mortality in cardiac surgery population (p < 0.05). We did not observe a significant difference in procalcitonin and interleukin-6 levels among patients with different types of surgery and different extracorporeal circulation time, but the levels of both the molecules increase significantly depending on number of transfusions received by patients (p < 0.01). Conclusion: We speculated that procalcitonin and interleukin-6 could be two effective biomarkers. There is a possibility of having a combined inflammatory multi-biomarker panel, with procalcitonin for predicting renal outcome and interleukin-6 for predicting mortality.
Cervical vertebral injuries associated with the ossification of the posterior longitudinal ligament: Imaging features
Authors: Nakayama Tetsuo , Ehara Shigeru 
Published: March 2017

Background Spinal injuries associated with ossification of the posterior longitudinal ligament (OPLL) have been characterized. However, the imaging features of traumatic cervical spine fractures in patients with OPLL have not been assessed adequately. Purpose To characterize the patterns of traumatic cervical spine fractures associated with different types of OPLL. Material and Methods We retrospectively analyzed the patterns of fractures resulting from cervical spine injury in patients with OPLL of different types and assessed the fracture patterns in patients with ankylosed segments. Results Twenty-six patients (23 men, 3 women; median age, 67.0 years; age range, 43–87 years) were included. Fall from a height <3 m was the most common trauma. Contiguous type OPLL was seen in 11 patients (42%), segmental type in 11 (42%), and mixed type in four (15%). Four of the contiguous OPLL and one of the mixed OPLL patients had ankylosed segments. The incidence of cervical fractures was 69% (16/26): seven (64%) in contiguous OPLL, five (46%) in segmental OPLL, and in all four patients with mixed OPLL. Unilateral interfacetal fracture-dislocation was most common (4/16); the others were bilateral interfacetal fracture-dislocation, fractures through the ankylosed segment, transdiscal fractures, isolated facet fractures, and compression fractures. Cervical fractures were exclusively observed in the C4 to C7, except in one case occurred at the C2 level. Conclusion Interfacetal fracture-dislocation in the lower cervical vertebrae constitutes the most common injury resulting from minor trauma.
Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production
Authors: Du Jing , Paz Katelyn , Flynn Ryan , Vulic Ante , Robinson Tara M. , Lineburg Katie E. , Alexander Kylie A. , Meng Jingjing , Roy Sabita , Panoskaltsis-Mortari Angela , Loschi Michael , Hill Geoffrey R. , Serody Jonathan S. , Maillard Ivan , Miklos David , Koreth John , Cutler Corey S. , Antin Joseph H. , Ritz Jerome , MacDonald Kelli P. , Schacker Timothy W. , Luznik Leo , Blazar Bruce R. 
Published: March 2017

Key Points
Pirfenidone ameliorates cGVHD in murine models with distinct pathophysiology. The efficacy of pirfenidone is associated with inhibition of macrophage infiltration and TGF-β production.
Computed tomography derived bone density measurement in the diabetic foot
Authors: Barwick Alex , Tessier John , Mirow James , de Jonge Xanne Janse , Chuter Vivienne 
Published: March 2017

AbstractBackgroundThe accurate and reliable measurement of foot bone density is challenging and there is currently no gold standard technique. Such measurement is particularly valuable in populations at risk of foot bone pathology such as in those with long term diabetes. With research and development, computed tomography may prove to be a useful tool for this assessment. The aim of this study was to establish the reliability of a novel method of foot bone density measurement in people with diabetes using computed tomography.MethodsTen feet in people with diabetes were scanned with computed tomography twice with repositioning. Bone density (in Hounsfield units) was assessed in the trabecular and cortical bone in all tarsals and metatarsals. Reliability was assessed with intra‐class correlation coefficients (95% confidence intervals), limits of agreement and standard error of measurement.ResultsThe reliability of the trabecular density of most bones was excellent with intra‐class correlation coefficients ranging from 0.68 to 0.91. Additionally, cortical bone density showed fair to good reliability at the talus (0.52), calcaneus (0.59), navicular (0.70), cuboid (0.69), intermediate cuneiform (0.46) and first metatarsal (0.61).ConclusionsThe study established the reliability of a practical method of assessing the trabecular and cortical foot bone density using computed tomography scanning. This methodology may be useful in the investigation of foot bone disease occurring in diabetes and its early diagnosis, intervention and assessment of treatment efficacy. Further development of this method is warranted.
Emplacement of intrusions of the Tarim Flood Basalt Province and their impacts on oil and gas reservoirs: A 3D seismic reflection study in Yingmaili fields, Tarim Basin, northwest China
Authors: Gao Zhongbo , Tian Wei , Wang Lei , Shi Yongmin , Pan Mao 
Published: March 2017

A basaltic dike-sill network is emplaced into the shallow subsurface of the Yingmai-2 dome, northern Tarim Basin, northwest China. The 3D seismic reflection imaging suggests that these dikes and sills are fed from an intrusion at the focal area of the dome. This basaltic intrusion has a width of approximately 3000 m and thickness of approximately 1000 m, and it is connected with a much larger Early Permian igneous body in the northern Tarim Basin. An unconformity between the Permian basalt lava flows and the base Triassic conglomerates truncates the dome, meaning that the dome must have developed prior to the Triassic. The basaltic intrusion that emplaced beneath the dome likely pushed the surrounding middle Cambrian salts away and instigated uplift of the overlying upper Cambrian to the lower Permian strata. In most cases, igneous activity plays a negative role on formation of oil and gas reservoirs. However, in the Yingmai-2 case, intrusive magmatic activity has caused “forced folding” of the overburdened strata and controlled the formation of a large commercial oil trap. We suggest that the magmatic activity thus also acts as a positive role on the local formation of a producing petroleum system.