bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintaining Tumor Heterogeneity in Patient-Derived Tumor Xenografts
Authors: Cassidy John W. , Caldas Carlos , Bruna Alejandra 
Published: July 2015

Abstract
Preclinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumor xenografts (PDX) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumor is governed by both cell-autonomous (e.g., genetic and epigenetic heterogeneity) and non–cell-autonomous (e.g., stromal heterogeneity) drivers. Although PDXs can largely recapitulate the polygenomic architecture of human tumors, they do not fully account for heterogeneity in the tumor microenvironment. Hence, these models have substantial utility in basic and translational research in cancer biology; however, study of stromal or immune drivers of malignant progression may be limited. Similarly, PDX models offer the ability to conduct patient-specific in vivo and ex vivo drug screens, but stromal contributions to treatment responses may be under-represented. This review discusses the sources and consequences of intratumor heterogeneity and how these are recapitulated in the PDX model. Limitations of the current generation of PDXs are discussed and strategies to improve several aspects of the model with respect to preserving heterogeneity are proposed. Cancer Res; 75(15); 2963–68. ©2015 AACR.
Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing
Authors: Placencio Veronica R. , DeClerck Yves A. 
Published: July 2015

AbstractDespite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that has led to the testing of small-molecule PAI-1 inhibitors, initially developed as antithrombotic agents, in animal models of cancer. The review discusses the challenges and the opportunities that lay ahead to the development of efficacious and nontoxic PAI-1 inhibitors as anticancer agents. Cancer Res; 75(15); 2969–74. ©2015 AACR.
HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance
Authors: Jin Kideok , Park Sunju , Teo Wei Wen , Korangath Preethi , Cho Sean Soonweng , Yoshida Takahiro , Győrffy Balázs , Goswami Chirayu Pankaj , Nakshatri Harikrishna , Cruz Leigh-Ann , Zhou Weiqiang , Ji Hongkai , Su Ying , Ekram Muhammad , Wu Zhengsheng , Zhu Tao , Polyak Kornelia , Sukumar Saraswati 
Published: July 2015

Abstract
Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor-α (ERα) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 chromatin immunoprecipitation analysis followed by validation showed that HOXB7 physically interacts with ERα, and that the HOXB7–ERα complex enhances transcription of many ERα target genes, including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR–HER2 signaling, inhibits transcription of miR-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER target genes, and HER2. Repressing MYC using small-molecule inhibitors reverses these events and causes regression of breast cancer xenografts. The MYC–HOXB7–HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer.
Significance: HOXB7 acts as an ERα cofactor regulating a myriad of ER target genes, including HER2, in tamoxifen-resistant breast cancer. HOXB7 expression is controlled by MYC via transcriptional regulation of the HOXB7 repressor miR-196a; consequently, antagonists of MYC cause reversal of selective ER modulator resistance both in vitro and in vivo. Cancer Discov; 5(9); 944–59. ©2015 AACR.
See related commentary by Heideman et al., p. 909.
This article is highlighted in the In This Issue feature, p. 893
Prosodic Realization of Focus in Bilingual Production of Southern Min and Mandarin
Authors: Chen Ying , Xu Yi , Guion-Anderson Susan 
Published: July 2015

AbstractPreviously post-focus compression (PFC) - the lowering of fundamental frequency (F0) and intensity of post-focal words to below those of the same words in identical sentences with neutral focus - was found in Beijing Mandarin but not in Taiwan Southern Min and Taiwan Mandarin. This study investigated whether the presence of PFC would vary with age and language use of societal bilinguals of Southern Min and Mandarin. Three groups of bilingual speakers of Quanzhou Southern Min and Mandarin, age around 20, 40 and 60, were examined for their prosodic realization of focus. All the speakers acquired Southern Min first, followed by Mandarin in childhood, but the younger speakers used more Mandarin than the older speakers. Comparisons of duration, intensity and F0 in focused, prefocus and post-focus words indicated that all groups produced Taiwan-like focus, i.e., without PFC, in Southern Min, but the youngest group produced Beijing-like PFC in Mandarin. These findings reveal that increased language experience, such as greater amount of second language (L2) use, correlates with increased ability to produce native-like PFC in L2, suggesting that PFC can be used as an indicator in assessing L2 speech acquisition.
Fundamental Frequency Range in Japanese and English: The Case of Simultaneous Bilinguals
Authors: Graham Calbert 
Published: July 2015

AbstractThis article reports an experiment to test whether Japanese and English speakers vary their fundamental frequency (f0) range as a function of the language spoken. Speech samples of Japanese-(American) English simultaneous bilinguals (5 males, 5 females; all undergraduates at UC Berkeley) performing comparable reading tasks in their two native languages were analysed. The study builds on a relatively new approach to measuring f0 range that computes its high and low points from tonal targets in the intonational phonology. Unlike in most previous studies where f0 range is traditionally treated as a one-dimensional measure, f0 range in this study is measured along two quasi-independent dimensions: level and span. Findings revealed statistically significant crosslanguage differences between Japanese and English in both dimensions. This provides new insights into the relation between prosodic structure and f0 range in these two typologically different prosodic systems.
Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in
D374Y
-PCSK9 Hypercholesterolemic Minipigs
Authors: Pedrigi Ryan M. , Poulsen Christian Bo , Mehta Vikram V. , Ramsing Holm Niels , Pareek Nilesh , Post Anouk L. , Kilic Ismail Dogu , Banya Winston A.S. , Dall’Ara Gianni , Mattesini Alessio , Bjørklund Martin M. , Andersen Niels P. , Grøndal Anna K. , Petretto Enrico , Foin Nicolas , Davies Justin E. , Di Mario Carlo , Fog Bentzon Jacob , Erik Bøtker Hans , Falk Erling , Krams Rob , de Silva Ranil 
Published: July 2015

Background—
Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma.

Methods and Results—

D374Y
-PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery (
P
<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (
P
<0.002) and multidirectional (
P
<0.002) shear stress. Thin cap fibroatheroma regions demonstrated significantly lower shear stress that persisted over the duration of the study in comparison with other plaque types (
P
<0.005).

Conclusions—
These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma.
Impact of Fine Particulate Matter (PM
2.5
) Exposure During Wildfires on Cardiovascular Health Outcomes
Authors: Haikerwal Anjali , Akram Muhammad , Del Monaco Anthony , Smith Karen , Sim Malcolm R. , Meyer Mick , Tonkin Andrew M. , Abramson Michael J. , Dennekamp Martine 
Published: July 2015

Background

Epidemiological studies investigating the role of fine particulate matter (
PM
2.5
; aerodynamic diameter <2.5 μm) in triggering acute coronary events, including out‐of‐hospital cardiac arrests and ischemic heart disease (
IHD
), during wildfires have been inconclusive.

Methods and Results

We examined the associations of out‐of‐hospital cardiac arrests,
IHD
, acute myocardial infarction, and angina (hospital admissions and emergency department attendance) with
PM
2.5
concentrations during the 2006–2007 wildfires in Victoria, Australia, using a time‐stratified case‐crossover study design. Health data were obtained from comprehensive health‐based administrative registries for the study period (December 2006 to January 2007). Modeled and validated air exposure data from wildfire smoke emissions (daily average
PM
2.5
, temperature, relative humidity) were also estimated for this period. There were 457 out‐of‐hospital cardiac arrests, 2106 emergency department visits, and 3274 hospital admissions for
IHD
. After adjusting for temperature and relative humidity, an increase in interquartile range of 9.04 μg/m
3
in
PM
2.5
over 2 days moving average (lag 0‐1) was associated with a 6.98% (95% CI 1.03% to 13.29%) increase in risk of out‐of‐hospital cardiac arrests, with strong association shown by men (9.05%,95%CI 1.63% to 17.02%) and by older adults (aged ≥65 years) (7.25%, 95%
CI
0.24% to 14.75%). Increase in risk was (2.07%, 95%
CI
0.09% to 4.09%) for
IHD
‐related emergency department attendance and (1.86%, 95%
CI
: 0.35% to 3.4%) for
IHD
‐related hospital admissions at lag 2 days, with strong associations shown by women (3.21%, 95%
CI
0.81% to 5.67%) and by older adults (2.41%, 95%
CI
0.82% to 5.67%).

Conclusion

PM
2.5
exposure was associated with increased risk of out‐of‐hospital cardiac arrests and
IHD
during the 2006–2007 wildfires in Victoria. This evidence indicates that
PM
2.5
may act as a triggering factor for acute coronary events during wildfire episodes.
Idealized Numerical Experiments on Cyclone Development in the Tropical, Subtropical, and Extratropical Environments
Authors: Yanase Wataru , Niino Hiroshi 
Published: July 2015

Abstract
The development of cyclones, particularly in the Southern Hemisphere summer, is active in the tropics and extratropics but is inactive in the subtropics. To elucidate the influence of environmental fields on the cyclone development in the tropics, subtropics, and extratropics, idealized numerical experiments are conducted using a nonhydrostatic channel model. The experiments examine the development of a weak initial vortex within a zonally uniform environmental field that consists of five factors: the Coriolis parameter, zonal wind, potential temperature, relative humidity, and surface temperature difference between the ocean and atmosphere. The idealized experiments successfully reproduce the significant cyclone development in the tropical and extratropical environment as well as no cyclone development in the subtropical environment. This result confirms the dominant role of the environmental field in controlling the cyclone development. To clarify which environmental factor is responsible for the suppression of cyclone development in the subtropics, a series of sensitivity experiments is performed. A tropical cyclone cannot develop in the subtropics because of low temperature, strong stratification, and strong vertical shear compared to the tropics. On the other hand, an extratropical cyclone cannot develop in the subtropics because of the small Coriolis parameter and weak vertical shear compared to the extratropics. The relative humidity and surface temperature difference play only secondary roles. These results provide useful insights into the climatological distribution of various types of synoptic-scale cyclones.
Austral Spring Southern Hemisphere Circulation and Temperature Changes and Links to the SPCZ
Authors: Clem Kyle R. , Renwick James A. 
Published: July 2015

Abstract
Significant austral spring trends have previously been observed in West Antarctica and Antarctic Peninsula temperatures and in atmospheric circulation across the southern Pacific and Atlantic. Here, physical mechanisms for the observed trends are investigated through analysis of monthly circulation and temperatures from the ERA-Interim dataset and outgoing longwave radiation (OLR) data. The negative pressure trend over the South Pacific during spring is strongest in September, while the positive pressure trend over the South Atlantic is strongest in October. Pressure trends in November are generally nonsignificant. The authors demonstrate that a significant September trend toward increased convection (reduced OLR) in the poleward portion of the South Pacific convergence zone (SPCZ) is statistically related to Rossby wave–like circulation changes across the southern oceans. The wave response is strongest over the South Pacific in September and propagates eastward to the South Atlantic in October. OLR-related changes are linearly congruent with around half of the observed total changes in circulation during September and October and are consistent with observed trends in South Pacific sea ice concentration and surface temperature over western West Antarctica and the western Antarctic Peninsula. These results suggest SPCZ variability in early spring, especially on the poleward side of the SPCZ, is an important contributor to circulation and surface temperature trends across the South Pacific/Atlantic and West Antarctica.
Medial and Superior Orbital Decompression
Authors: Poczos Pavel , Kurbanov Almaz , Keller Jeffrey T. , Zimmer Lee A. 
Published: July 2015

Objective: Visualization by Draf I-III endoscopic access to the frontal sinus via drainage pathways is sometimes inadequate. We compare lateral frontal sinus exposures by Draf approaches versus our modification of removing the medial-superior wall of the orbit while preserving the periorbita. Methods: Twenty cadaveric heads dissected using Draf IIB, III, and modified Draf III with medial and superior orbital decompression (MSOD) underwent thin-cut computed tomography (CT) scanning. Under image guidance, measurements extended from the midline crista gali to the most lateral point of the frontal sinus. A case report shows the modified Draf III improved frontal sinus access. Results: Comparing Draf IIB and III with Draf III with MSOD, respectively, distances between midline and most lateral point averaged 19.1 mm, 23.7 mm, and 30.4 mm (left) and 18.7 mm, 25.1 mm, and 32.2 mm (right). Differences between Draf III with/without MSOD were 6.65 mm (left) and 7.09 mm (right); 12 heads were excluded because of under-pneumatization of the sinuses. Conclusions: Draf III with MSOD extended surgical access to lateral regions of the frontal sinus. This extension achieved better visualization and instrumentation with minimal removal of the frontal bone’s orbital segment anterior and superior to the anterior ethmoidal artery while preserving the periorbita.
Inpatient Complications After Transsphenoidal Surgery in Cushing’s Versus Non-Cushing’s Disease Patients
Authors: Svider Peter F. , Raikundalia Milap D. , Pines Morgan J. , Baredes Soly , Folbe Adam J. , Liu James K. , Eloy Jean Anderson 
Published: July 2015

Objective: Transsphenoidal surgery (TSS) harbors a potential for hypopituitarism, cerebrospinal fluid (CSF) leaks, and other complications. We utilized the Nationwide Inpatient Sample Database (NIS) to compare inpatient complication rates between Cushing’s disease (CD) and non-Cushing’s disease (NCD) patients undergoing TSS. Methods: Inpatient hospitalization data for 960 CD and 12 110 NCD patients who underwent TSS between 2002 and 2010 were accessed. Demographic information, outcomes, and complication rates were evaluated. Results: Patients with CD had a female predilection (81.7%) and were younger (40.5 ± 14.4 years) than NCD patients (47.8% female; 52.1 ± 16.3 years) ( P < .001). Length of stay and total charges did not differ between groups. Patients with CD had significantly greater postoperative diabetes insipidus rates (14.0% vs 9.6%, P < .001) and urinary/renal complications (1.7% vs 0.9%, P = .027). After adjusting for possible confounders, the relationship between urinary/renal complications and CD status strengthened. There was no difference in rates of CSF leak and iatrogenic pituitary disorders overall. Conclusion: No differences were noted in the rate of early CSF leaks between postoperative TSS CD and NCD patients. Postoperative diabetes insipidus did not significantly differ between groups after adjusting for confounders. Only odds of urinary/renal complications in CD patients was significant after adjustment.
Impact of Maternal Incarceration on the Criminal Justice Involvement of Adult Offspring
Authors: Muftić Lisa R. , Bouffard Leana A. , Armstrong Gaylene S. 
Published: July 2015

Objectives: This note examines the relationship between maternal incarceration and adverse outcomes for offspring in early adulthood. Methods: Utilizing data derived from the National Longitudinal Survey of Adolescent Health, a series of multivariate models are conducted to examine the impact maternal incarceration has on criminal justice involvement among young adults. To control for selection effects that may be associated with maternal imprisonment, propensity score matching is utilized. Results: Respondents whose mothers had served time in prison were significantly more likely to have an adult arrest, conviction, and incarceration, even after controlling for important demographic factors and correlates of criminal behavior. This effect persisted following matching. Conclusions: Maternal incarceration had a substantial effect on the offspring’s adult involvement in the criminal justice system. These findings bolster contentions regarding the unintended consequences of maternal incarceration that include long-term collateral damage to their children.
Relation of platelet indices to severity of coronary artery disease in patients undergoing primary percutaneous coronary intervention
Authors: Akin Fatih , Ayca Burak , Kose Nuri , Altun Ibrahim , Avsar Murat , Celik Omer , Satilmis Seckin , Eksik Abdurrahman , Okuyan Ertugrul 
Published: July 2015

Aim: We investigated the association between platelet indices and the severity of coronary artery disease (CAD) in patients with ST-segment–elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI). Methods: A total of 484 consecutive patients who were routinely referred to coronary angiography for STEMI and 81 age- and gender-matched patients with normal coronary arteries were included in the present study. We analyzed the relation between the platelet distribution width (PDW) and the angiographic severity of CAD. The SYNTAX score was used for assessing the severity of coronary atherosclerosis. Results: The mean platelet volume (MPV), the plateletcrit (PCT) and the neutrophil levels were significantly higher in the STEMI group than in the control group. Patients with an elevated SYNTAX score (>32) had higher PDW values. The levels of plateletcrit and the estimated glomerular filtration rate (eGFR) were lower in the high SYNTAX score group compared to the moderate-to-low SYNTAX score group. The PDW was positively correlated with age (r = 0.128, p=0.004) and SYNTAX score (r = 0.209, p<0.001). There was a mild, significant inverse association between the PDW level and the eGFR (r = -0.101, p=0.049), the mean platelet volume (MPV) (r = −290, p<0.001) and the PCT (r = −345, p<001). Using multivariate logistic regression analysis, we found that age (OR = 1.046, 95% CI 1.013–1.079, p=0.005), diabetes (OR = 4.779, 95% CI 2.339-9.767, p<0.001) and PDW (OR = 1.229, 95% CI 1.072–1409, p=0.003) were independent correlates of high SYNTAX score. Conclusion: Platelet distribution width, an inexpensive and easily measurable laboratory variable, is independently associated with high SYNTAX score.
Comparison of the INR Values Measured by CoaguChek XS Coagulometer and Conventional Laboratory Methods in Patients on VKA Therapy
Authors: Kalçık Macit , Yesin Mahmut , Gürsoy Mustafa Ozan , Gündüz Sabahattin , Karakoyun Süleyman , Astarcıoğlu Mehmet Ali , Bayam Emrah , Cerşit Sinan , Özkan Mehmet 
Published: July 2015

Background: Warfarin, which is a widely used oral anticoagulant, has a narrow therapeutic window and requires regular international normalized ratio (INR) monitoring to maintain optimal anticoagulation. Recently, several portable coagulometers have been developed to measure INR levels. Objective: To compare the INR results obtained by a portable coagulometer (CoaguChek XS) and a standard laboratory method (STAGO STA-R). Methods: Overall, 433 consecutive patients (male: 191, median age: 61 [44-86] years) who were admitted to outpatient anticoagulation clinic were enrolled in this study. Each patient was tested for INR using portable CoaguChek XS and STAGO STA-R automatic laboratory coagulometer. Correlation between methods was assessed using the Pearson correlation test and Cohen κ test. Bland-Altman plot was used to identify mean difference and 95% limits of agreement. Results: The mean INR values for CoaguChek XS and STAGO STA-R were 2.54 ± 1.17 and 2.79 ± 1.39, respectively. There was a strong positive correlation between the 2 methods ( r = .966; 95% confidence interval [CI]: 0.95-0.97, P < .001). The Bland-Altman analysis gave a mean difference of 0.26 ± 0.40 between the 2 methods, with a 95% limit of agreement of −0.54 to 1.05. In patients with INR values >5.0, there was only a moderate correlation ( r = .676; 95% CI: 0.38-0.89, P = .002), and the mean difference of INR tended to increase as mean INR values increased. There was a high overall agreement between the 2 methods (κ = .751; 95% CI: 0.69-0.80; P < .001). Conclusion: There was good consistency between traditional laboratory testing and CoaguChek XS coagulometer, which provides rapid and reliable INR analysis.