bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Therapeutic Efficacy and Memory of Tumor-Specific CD8 T Cells by Ex Vivo PI3K-δ Inhibition
Authors: Abu Eid Rasha , Ahmad Shamim , Lin Yuan , Webb Mason , Berrong Zuzana , Shrimali Rajeev , Kumai Takumi , Ananth Sudha , Rodriguez Paulo C. , Celis Esteban , Janik John , Mkrtichyan Mikayel , Khleif Samir N. 
Published: June 2017

Abstract
Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating antitumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T-cell differentiation and assessed the potential use of PI3K isoform–specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen–specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors. Inhibition of PI3K-δ, but not PI3K-α or PI3K-β, delayed terminal differentiation of CD8+ T cells and maintained the memory phenotype, thus enhancing their proliferative ability and survival while maintaining their cytokine and granzyme B production ability. This effect was preserved in vivo after ex vivo PI3K-δ inhibition in CD8+ T cells destined for adoptive transfer, enhancing their survival and also the antitumor therapeutic activity of a tumor-specific peptide vaccine. Our results outline a mechanism by which inhibitions of a single PI3K isoform can enhance the proliferative potential, function, and survival of CD8+ T cells, with potential clinical implications for adoptive cell transfer and vaccine-based immunotherapies. Cancer Res; 77(15); 4135–45. ©2017 AACR.
Cancer and Central Nervous System Tumor Surveillance in Pediatric Neurofibromatosis 1
Authors: Evans D. Gareth R. , Salvador Hector , Chang Vivian Y. , Erez Ayelet , Voss Stephan D. , Schneider Kami Wolfe , Scott Hamish S. , Plon Sharon E. , Tabori Uri 
Published: June 2017

Abstract
Although the neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, NF1 represents a multisystem pleiotropic condition very different from the other two. NF1 is a genetic syndrome first manifesting in childhood; affecting multiple organs, childhood development, and neurocognitive status; and presenting the clinician with often complex management decisions that require a multidisciplinary approach. Molecular genetic testing (see article for detailed discussion) is recommended to confirm NF1, particularly in children fulfilling only pigmentary features of the diagnostic criteria. Although cancer risk is not the major issue facing an individual with NF1 during childhood, the condition causes significantly increased malignancy risks compared with the general population. Specifically, NF1 is associated with highly elevated risks of juvenile myelomonocytic leukemia, rhabdomyosarcoma, and malignant peripheral nerve sheath tumor as well as substantial risks of noninvasive pilocytic astrocytoma, particularly optic pathway glioma (OPG), which represent a major management issue. Until 8 years of age, clinical assessment for OPG is advised every 6 to 12 months, but routine MRI assessment is not currently advised in asymptomatic individuals with NF1 and no signs of clinical visual pathway disturbance. Routine surveillance for other malignancies is not recommended, but clinicians and parents should be aware of the small risks (&lt;1%) of certain specific individual malignancies (e.g., rhabdomyosarcoma). Tumors do contribute to both morbidity and mortality, especially later in life. A single whole-body MRI should be considered at transition to adulthood to assist in determining approaches to long-term follow-up. Clin Cancer Res; 23(12); e46–e53. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood
Authors: Schultz Kris Ann P. , Rednam Surya P. , Kamihara Junne , Doros Leslie , Achatz Maria Isabel , Wasserman Jonathan D. , Diller Lisa R. , Brugières Laurence , Druker Harriet , Schneider Katherine A. , McGee Rose B. , Foulkes William D. 
Published: June 2017

Abstract
PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years. DICER1 syndrome includes risk for pleuropulmonary blastoma, cystic nephroma, ovarian sex cord–stromal tumors, and multinodular goiter and thyroid carcinoma as well as brain tumors including pineoblastoma and pituitary blastoma. Individuals with HLRCC may develop multiple cutaneous and uterine leiomyomas, and they have an elevated risk of renal cell carcinoma. For each of these syndromes, a summary of the key syndromic features is provided, the underlying genetic events are discussed, and specific screening is recommended. Clin Cancer Res; 23(12); e76–e82. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells
Authors: Souchek Joshua J. , Davis Amanda L. , Hill Tanner K. , Holmes Megan B. , Qi Bowen , Singh Pankaj K. , Kridel Steven J. , Mohs Aaron M. 
Published: June 2017

Abstract
Taxane-based therapy provides a survival benefit in patients with metastatic prostate cancer, yet the median survival is less than 20 months in this setting due in part to taxane-associated resistance. Innovative strategies are required to overcome chemoresistance for improved patient survival. Here, NanoOrl, a new experimental nanoparticle formulation of the FDA-approved drug, orlistat, was investigated for its cytotoxicity in taxane-resistant prostate cancer utilizing two established taxane-resistant (TxR) cell lines. Orlistat is a weight loss drug that inhibits gastric lipases, but is also a potent inhibitor of fatty acid synthase (FASN), which is overexpressed in many types of cancer. NanoOrl was also investigated for its potential to synergize with taxanes in TxR cell lines. Both orlistat and NanoOrl synergistically inhibited cell viability when combined with paclitaxel, docetaxel, and cabazitaxel in PC3-TxR and DU145-TxR cells, yet these combinations were also additive in parental lines. We observed synergistic levels of apoptosis in TxR cells treated with NanoOrl and docetaxel in combination. Mechanistically, the synergy between orlistat and taxanes was independent of effects on the P-glycoprotein multidrug resistance protein, as determined by an efflux activity assay. On the other hand, immunoblot and immunofluorescence staining with an anti-detyrosinated tubulin antibody demonstrated that enhanced microtubule stability was induced by combined NanoOrl and docetaxel treatment in TxR cells. Furthermore, TxR cells exhibited higher lipid synthesis, as demonstrated by 14C-choline incorporation that was abrogated by NanoOrl. These results provide a strong rationale to assess the translational potential of NanoOrl to overcome taxane resistance. Mol Cancer Ther; 16(9); 1819–30. ©2017 AACR.
Direct Transport to a Percutaneous Cardiac Intervention Center and Outcomes in Patients With Out-of-Hospital Cardiac Arrest
Authors: Kragholm Kristian , Malta Hansen Carolina , Dupre Matthew E. , Xian Ying , Strauss Benjamin , Tyson Clark , Monk Lisa , Corbett Claire , Fordyce Christopher B. , Pearson David A. , Fosbøl Emil L. , Jollis James G. , Abella Benjamin S. , McNally Bryan , Granger Christopher B. 
Published: June 2017

Background—
Practice guidelines recommend regional systems of care for out-of-hospital cardiac arrest. However, whether emergency medical services should bypass nonpercutaneous cardiac intervention (non-PCI) facilities and transport out-of-hospital cardiac arrest patients directly to PCI centers despite longer transport time remains unknown.

Methods and Results—
Using the Cardiac Arrest Registry to Enhance Survival with geocoding of arrest location, we identified out-of-hospital cardiac arrest patients with prehospital return of spontaneous circulation and evaluated the association between direct transport to a PCI center and outcomes in North Carolina during 2012 to 2014. Destination hospital was classified according to PCI center status (catheterization laboratory immediately accessible 24/7). Inverse probability-weighted logistic regression accounting for age, sex, emergency medical services response time, clustering of county, transport time to nearest PCI center, initial heart rhythm, and prehospital ECG information was performed. Of 1507 patients with prehospital return of spontaneous circulation, 1359 (90.2%) were transported to PCI centers, of whom 873 (57.9%) bypassed the nearest non-PCI hospital and 148 (9.8%) were transported to non-PCI hospitals. Discharge survival was higher among those transported to PCI centers (33.5% versus 14.6%; adjusted odds ratio, 2.47; 95% confidence interval, 2.08–2.92). Compared with patients taken to non-PCI hospitals, odds of survival were higher for patients taken to the nearest hospital with PCI center status (odds ratio, 3.07; 95% confidence interval, 1.90–4.97) and for patients bypassing closer hospitals to PCI centers (odds ratio, 3.02; 95% confidence interval, 2.01–4.53). Adjusted survival remained significantly better across transport times of 1 to 5, 6 to 10, 11 to 20, 21 to 30, and >30 minutes.

Conclusions—
Direct transport to a PCI center is associated with better outcomes for out-of-hospital cardiac arrest patients, even when bypassing nearest hospital and regardless of transport time.
Historical) Drift in Frisian and German Translations of the Bible (Nwfries. iersykje ‘Ähren lesen’, rispje ‘ernten’ und Wortfeldvarianten: eine (historische) Wanderung in friesischen und germanischen Bibelübersetzungen
Authors: de Grauwe Luc 
Published: June 2017

The first complete Bible translations in Westerlauwers Frisian only date from 1943 (“Wumkes”) and 1978 (“Nije Fryske Bibeloersetting”). Both of them employ specifically Frisian vocabulary, such as in the semantic field of gathering and harvesting crops. The Frisian incorporating verb iersiikje/iersykje corresponds to Dutch aren lezen and German Ähren lesen (literally ‘to gather ears’), whereas the notion of ‘harvesting’ is usually represented by rispje. The latter descends from an Old Germanic strong verb with initial hr- that meant ‘to tear’, which restricted its meaning to ‘reap’ and is continued in OE hrespan ‘to reap’ and Early OHG hrespen ‘to pluck, pinch’. The resulting MoWF weak verb rispje is at the same time the product of semantic widening. Its popularity is also shown by its usage in a number of formulae in which it competes with sichtsje (denominal to sichte ‘small scythe’), rarely with meane ‘to mow’. This must have been accompanied for semantic reasons by “paronymic attraction” between original hr- and r-forms. The latter are found in OE rípan/MoE reap, as well as in the weak verb OE rýpan ‘to pillage’ = Gothic raupjan and German (aus)raufen ‘to tear out’.
Die ersten Vollbibel-Übersetzungen ins Westfriesische (Westerlauwersk Frysk) datieren erst von 1943 (“Wumkes”) und 1978 (“Nije Fryske Bibeloersetting”). Beiden ist gemeinsam, dass sie dem Friesischen ganz eigene Wörter verwenden, wie etwa im Wortfeld des Lesens und Erntens von Feldfrüchten. So entspricht dem ndl. aren lezen bzw. dem dt. Ähren lesen das Inkorporationskompositum iersiikje/iersykje, während der Begriff ‘ernten’ in der Regel von rispje vertreten wird. Letzteres erweist sich als Nachkomme eines noch in nordaltenglisch hrespan ‘ernten’ und frühahd. dito ‘(aus)rupfen’ vorliegenden, altwgm. starken, mit hr- anlautenden Verbs mit Grundbedeutung ‘reißen’, die sich zu ‘ernten’ verengt hat. Im Neuwestfriesischen ist das daraus resultierende schwache rispje auch Produkt einer Bedeutungsausweitung. Auf seine Beliebtheit weist auch seine Verwendung in manchen Formeln hin, in denen es konkurriert mit sichtsje (denominal zu sichte ‘kleine Sense’), nur selten mit meane ‘mähen’. Damit muss eine durch die semantische Nähe bedingte “paronymische Attraktion” zwischen ursprünglichen hr- und r-Formen einhergegangen sein. Letztere liegen vor in ae. rípan / ne. reap ‘ernten’, sowie im schwachen Verb ae. rýpan ‘plündern’ = gotisch raupjan und dt. (aus)raufen ‘ausreißen’.
This article is in German.
Year-Long Vertical Velocity Statistics Derived from Doppler Lidar Data for the Continental Convective Boundary Layer
Authors: Berg Larry K. , Newsom Rob K. , Turner David D. 
Published: June 2017

AbstractOne year of coherent Doppler lidar data collected at the U.S. Department of Energy’s Atmospheric Radiation Measurement site in Oklahoma was analyzed to provide profiles of vertical velocity variance, skewness, and kurtosis for cases of cloud-free convective boundary layers. The variance was normalized by the Deardorff convective velocity scale, which was successful when the boundary layer depth was stationary but failed in situations in which the layer was changing rapidly. In this study, the data are sorted according to time of day, season, wind direction, surface shear stress, degree of instability, and wind shear across the boundary layer top. The normalized variance was found to have its peak value near a normalized height of 0.25. The magnitude of the variance changes with season, shear stress, degree of instability, and wind shear across the boundary layer top. The skewness was largest in the top half of the boundary layer (with the exception of wintertime conditions). The skewness was also found to be a function of the season, shear stress, and wind shear across the boundary layer top. Like skewness, the vertical profile of kurtosis followed a consistent pattern, with peak values near the boundary layer top. The normalized altitude of the peak values of kurtosis was found to be higher when there was a large amount of wind shear at the boundary layer top.
Combined Space and Ground Radars for Improving Quantitative Precipitation Estimations in the Eastern Downstream Region of the Tibetan Plateau. Part I: Variability in the Vertical Structure of Precipitation in ChuanYu Analyzed from Long-Term Spaceborne Observations by TRMM PR
Authors: Zhong Lingzhi , Yang Rongfang , Chen Lin , Wen Yixin , Li Ruiyi , Tang Guoqiang , Hong Yang 
Published: June 2017

AbstractThis study presents a statistical analysis of the variability of the vertical structure of precipitation in the eastern downstream region of the Tibetan Plateau as measured by the Precipitation Radar (PR) on the National Aeronautics and Space Administration Tropical Rainfall Measuring Mission (TRMM) satellite. Data were analyzed over an 11-yr time span (January 2004–December 2014). The results show the seasonal and spatial variability of the storm height, freezing level, and bright band for different types of precipitation as well as the characteristics of intensity-related and type-related vertical profiles of reflectivity (VPR). Major findings were as follows: About 90% of the brightband peak reflectivity of stratiform precipitation was less than 32 dBZ, and 40% of the maximum reflectivity of convective precipitation exceeded 35 dBZ. The intensity of surface rainfall rates also depended on the shapes of VPRs. For stratiform precipitation, ice–snow aggregation was faster during moderate and heavy rainfall than it was in light rainfall. Since both the moisture and temperature are lower in winter, the transformation efficiency of hydrometeors becomes slower. Typical Ku-band representative climatological VPRs (CPRs) for stratiform precipitation have been created on the basis of the integration of normalized VPR shape for the given area and the rainfall intensity. All of the findings indicate that the developed CPRs can be used to improve surface precipitation estimates in regions with complex terrain where the ground-based radar net has limited visibility at low levels.
Precipitation, Temperature, and Teleconnection Signals across the Combined North American, Monsoon Asia, and Old World Drought Atlases
Authors: Baek Seung H. , Smerdon Jason E. , Coats Sloan , Williams A. Park , Cook Benjamin I. , Cook Edward R. , Seager Richard 
Published: June 2017

Abstract
The tree-ring-based North American Drought Atlas (NADA), Monsoon Asia Drought Atlas (MADA), and Old World Drought Atlas (OWDA) collectively yield a near-hemispheric gridded reconstruction of hydroclimate variability over the last millennium. To test the robustness of the large-scale representation of hydroclimate variability across the drought atlases, the joint expression of seasonal climate variability and teleconnections in the NADA, MADA, and OWDA are compared against two global, observation-based PDSI products. Predominantly positive (negative) correlations are determined between seasonal precipitation (surface air temperature) and collocated tree-ring-based PDSI, with average Pearson’s correlation coefficients increasing in magnitude from boreal winter to summer. For precipitation, these correlations tend to be stronger in the boreal winter and summer when calculated for the observed PDSI record, while remaining similar for temperature. Notwithstanding these differences, the drought atlases robustly express teleconnection patterns associated with El Niño–Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO), the Pacific decadal oscillation (PDO), and the Atlantic multidecadal oscillation (AMO). These expressions exist in the drought atlas estimates of boreal summer PDSI despite the fact that these modes of climate variability are dominant in boreal winter, with the exception of the AMO. ENSO and NAO teleconnection patterns in the drought atlases are particularly consistent with their well-known dominant expressions in boreal winter and over the OWDA domain, respectively. Collectively, the findings herein confirm that the joint Northern Hemisphere drought atlases robustly reflect large-scale patterns of hydroclimate variability on seasonal to multidecadal time scales over the twentieth century and are likely to provide similarly robust estimates of hydroclimate variability prior to the existence of widespread instrumental data.
Improving LADCP Velocity with External Heading, Pitch, and Roll
Authors: Thurnherr A. M. , Goszczko I. , Bahr F. 
Published: June 2017

AbstractData collected with acoustic Doppler current profilers installed on CTD rosettes and lowered through the water column [lowered ADCP (LADCP) systems] are routinely used to derive full-depth profiles of ocean velocity. In addition to the uncertainties arising from random noise in the along-beam velocity measurements, LADCP-derived velocities are commonly contaminated by bias errors due to imperfectly measured instrument attitude (heading, pitch, and roll). Of particular concern are the heading measurements, because it is not usually feasible to calibrate the internal ADCP compasses with the instruments installed on a CTD rosette, away from the magnetic disturbances of the ship. Heading data from dual-headed LADCP systems, which consist of upward- and downward-pointing ADCPs installed on the same rosette, commonly indicate heading-dependent compass errors with amplitudes exceeding 10°. In an attempt to reduce LADCP velocity errors, several dozen profiles of simultaneous LADCP and magnetometer/accelerometer data were collected in the Gulf of Mexico. Agreement between the LADCP profiles and simultaneous shipboard velocity measurements improves significantly when the former are processed with external attitude measurements. Another set of LADCP profiles with external attitude data was collected in a region of the Arctic Ocean where the horizontal geomagnetic field is too weak for the ADCP compasses to work reliably. Good agreement between shipboard velocity measurements and Arctic LADCP profiles collected at magnetic dip angles exceeding and processed with external attitude measurements indicate that high-quality velocity profiles can be obtained close to the magnetic poles.
Evaluation of NCAR’s AutoNowCaster for Operational Application within the National Weather Service
Authors: Ba Mamoudou , Xin Lingyan , Crockett John , Smith Stephan B. 
Published: June 2017

Abstract
NCAR’s AutoNowCaster (ANC) was modified to run over a large domain that encompasses the air traffic management hubs of Chicago, Illinois; New York City, New York; and Atlanta, Georgia. ANC produces nowcasts of convective likelihood (CL), with higher values delineating areas where storms are likely to form and be sustained, and vice versa. This paper presents the results of verifying ANC’s 60-min nowcasts of CL over the study area using data collected from 11 June to 30 September 2012. To reduce the high sensitivity of statistical scores to small errors in location and timing, spatial and temporal relaxation techniques were explored. The results show that, at a spatial scale of roughly 50 km and with no temporal relaxation, a CL value of 0.6 is an optimum threshold for nowcasting the general areas both where new storms may initiate and where existing storms will be sustained. Moreover, at that same spatial scale and with temporal relaxation (45–90 min from the nowcast issuance time), a CL value of 0.7 is a good threshold for nowcasting convective initiation alone.
Assessing attachment in school-aged children: Do the School-Age Assessment of Attachment and Family Drawings work together as complementary tools?
Authors: Carr-Hopkins Rebecca , De Burca Calem , Aldridge Felicity A 
Published: June 2017

Aims: Our goal was to identify an assessment package that could improve treatment planning for troubled children and their families. To assess the validity of our tools, we tested the relations among the School-Age Assessment of Attachment, the Family Drawing and children’s risk status. We used the Dynamic-Maturational Model of Attachment and Adaptation to interpret the assessments in the hope of identifying a gradient of risk, and explore whether a new coding method improved the validity of Family Drawings and their utility as a tool to complement the School-Age Assessment of Attachment. Method: The participants were 89 children, aged between 5 and 12 years; 32 children were involved with mental health services or child protection. Each child completed a School-Age Assessment of Attachment and a Family Drawing. Results: Both assessments differentiated between clinical and normative referrals with moderate effect sizes when dichotomizing risk versus non-risk attachment. When the analysis incorporated a gradient of six attachment classifications, the effect sizes decreased, but specificity of risk increased. Conclusions: The School-Age Assessment of Attachment had greater validity for discriminating risk, and type of risk, than the Family Drawings. With a School-Age Assessment of Attachment and family history, the Family Drawing can provide information about distress that some children do not provide verbally. Integration of the two assessment tools alongside information about parental and family functioning appears to be the key to formulating children’s problems.