bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer
Authors: Yearley Jennifer H. , Gibson Christopher , Yu Ni , Moon Christina , Murphy Erin , Juco Jonathan , Lunceford Jared , Cheng Jonathan , Chow Laura Q.M. , Seiwert Tanguy Y. , Handa Masahisa , Tomassini Joanne E. , McClanahan Terrill 
Published: June 2017

Abstract
Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1–directed immunotherapy. However, PD-L1–negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated.
Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay. In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma (HNSCC) with recurrent or metastatic disease, treated with pembrolizumab.
Results: PD-L2 expression was observed in all tumor types and present in stromal, tumor, and endothelial cells. The prevalence and distribution of PD-L2 correlated significantly with PD-L1 (P = 0.0012–&lt;0.0001); however, PD-L2 was detected in the absence of PD-L1 in some tumor types. Both PD-L1 and PD-L2 positivity significantly predicted clinical response to pembrolizumab on combined tumor, stromal and immune cells, with PD-L2 predictive independent of PD-L1. Response was greater in patients positive for both PD-L1 and PD-L2 (27.5%) than those positive only for PD-L1 (11.4%). PD-L2 status was also a significant predictor of progression-free survival (PFS) with pembrolizumab independent of PD-L1 status. Longer median times for PFS and overall survival were observed for PD-L2–positive than PD-L2–negative patients.
Conclusions: Clinical response to pembrolizumab in patients with HNSCC may be related partly to blockade of PD-1/PD-L2 interactions. Therapy targeting both PD-1 ligands may provide clinical benefit in these patients. Clin Cancer Res; 23(12); 3158–67. ©2017 AACR.
The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis
Authors: Xu Lei , Mao Xueying , Guo Tianyu , Chan Pui Ying , Shaw Greg , Hines John , Stankiewicz Elzbieta , Wang Yuqin , Oliver R. Tim D. , Ahmad Amar Sabri , Berney Daniel , Shamash Jonathan , Lu Yong-Jie 
Published: June 2017

AbstractPurpose: To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer.Experimental Design: Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model.Results: The majority of vimentin (VIM)+/CD45− cells were malignant, with genomic alterations in several genomic regions. The number of cytokeratin (CK)−/VIM+/CD45− CTCs correlated with disease burden, tumor aggressiveness, and poorer survival. Meanwhile, CK+/VIM+/CD45− CTCs were associated with metastases better than other subtypes of CTCs in these limited samples. Combination of PSA level and the number of CK+/VIM+/CD45− CTCs enhanced the prediction of cancer metastases [AUC, 0.921; 95% confidence interval (CI), 0.858–0.985]. The number of circulating megakaryocytes was potentially associated with good patient survival in advanced prostate cancer (HR, 0.849; 95% CI, 0.628–1.146, per cell increase), and the difference between the number of mesenchymal CTCs and megakaryocytes strongly correlated to poor survival (HR, 10.17; 95% CI, 2.164–47.789, if score ≥2.0).Conclusions: This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression. Clin Cancer Res; 23(17); 5112–22. ©2017 AACR.
Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome
Authors: Foulkes William D. , Kamihara Junne , Evans D. Gareth R. , Brugières Laurence , Bourdeaut Franck , Molenaar Jan J. , Walsh Michael F. , Brodeur Garrett M. , Diller Lisa 
Published: June 2017

Abstract
Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU). SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in SUFU mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive “rhabdoid” term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, each of which encodes a chromatin remodeling family member. SMARCA4 mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. Clin Cancer Res; 23(12); e62–e67. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers
Authors: Paik Paul K. , Shen Ronglai , Berger Michael F. , Ferry David , Soria Jean-Charles , Mathewson Alastair , Rooney Claire , Smith Neil R. , Cullberg Marie , Kilgour Elaine , Landers Donal , Frewer Paul , Brooks Nigel , André Fabrice 
Published: June 2017

Abstract
Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts.
Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses.
Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3–related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon.
Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366–73. ©2017 AACR.
Ormeloxifene Suppresses Prostate Tumor Growth and Metastatic Phenotypes via Inhibition of Oncogenic β-catenin Signaling and EMT Progression
Authors: Hafeez Bilal Bin , Ganju Aditya , Sikander Mohammed , Kashyap Vivek K. , Hafeez Zubair Bin , Chauhan Neeraj , Malik Shabnam , Massey Andrew E. , Tripathi Manish K. , Halaweish Fathi T. , Zafar Nadeem , Singh Man M. , Yallapu Murali M. , Chauhan Subhash C. , Jaggi Meena 
Published: June 2017

AbstractOrmeloxifene is a clinically approved selective estrogen receptor modulator, which has also shown excellent anticancer activity, thus it can be an ideal repurposing pharmacophore. Herein, we report therapeutic effects of ormeloxifene on prostate cancer and elucidate a novel molecular mechanism of its anticancer activity. Ormeloxifene treatment inhibited epithelial-to-mesenchymal transition (EMT) process as evident by repression of N-cadherin, Slug, Snail, vimentin, MMPs (MMP2 and MMP3), β-catenin/TCF-4 transcriptional activity, and induced the expression of pGSK3β. In molecular docking analysis, ormeloxifene showed proficient docking with β-catenin and GSK3β. In addition, ormeloxifene induced apoptosis, inhibited growth and metastatic potential of prostate cancer cells and arrested cell cycle in G0–G1 phase via modulation of cell-cycle regulatory proteins (inhibition of Mcl-1, cyclin D1, and CDK4 and induction of p21 and p27). In functional assays, ormeloxifene remarkably reduced tumorigenic, migratory, and invasive potential of prostate cancer cells. In addition, ormeloxifene treatment significantly (P &lt; 0.01) regressed the prostate tumor growth in the xenograft mouse model while administered through intraperitoneal route (250 μg/mouse, three times a week). These molecular effects of ormeloxifene were also observed in excised tumor tissues as shown by immunohistochemistry analysis. Our results, for the first time, demonstrate repurposing potential of ormeloxifene as an anticancer drug for the treatment of advanced stage metastatic prostate cancer through a novel molecular mechanism involving β-catenin and EMT pathway. Mol Cancer Ther; 16(10); 2267–80. ©2017 AACR.
Zu den Einwohnerbezeichnungen mit dem ja-Suffix im Altniederländischen
Authors: Quak Arend 
Published: June 2017

There are some compostive place-names which seem not to have a genitive element, like ODu. Godolfhem [802–7]. The question is, whether they were actual stem-compositions or lost their genitive element. Gysseling (1973) explained them as originally containing the suffix PGm. *-ja, which was lost in the course of time. In that case there must be remains of the suffix in some place-names. This article argues that remains are to be found in place-names with -e like Notleuenes [C12] and even -a and -o like Fengrimahuson [918–48] and *Baltremothorp [C9]. Most of them are derivations from personal names, but there are also derivations from place-names like Heslemaholt [918–48]. The majority of these names seem to occur in the coastal areas, although there are also instances in Germany. Weakening in unaccented syllables made the derivation unclear and led to the loss of vowels, or sometimes to replacement by clearer suffixes like -er.
Bei Ortsnamen findet man ab und zu solche, die scheinbar kein genitivisches Element besitzen wie etwa anl. Godolfhem [802–17]. Die Frage ist dann, ob es sich hier um Stammkomposition handelt oder ob doch irgendwann eine Genitivendung vorhanden war. Gysseling (1973) hat versucht, sie dadurch zu erklären, dass sie mit einem Suffix pgm. *-ja gebildet wurden, das im Laufe der Zeit verschwunden ist. Wenn das stimmt, sollten sich eventuell noch Spuren nachweisen lassen. Es erweist sich, dass es tatsächlich Spuren gibt. So bestehen Formen mit -e wie Notluenes [12.Jh.] und mit -o und -a: Fengrimahuson [918–48] und *Baltremothorp [9. Jh.], gebildet zu Personennamen und Heslemaholt [918–48] zu einem Ortsnamen. Obwohl es auch in Deutschland beispiele gibt, stammen die meisten Namen eher aus den Küstengebieten. Da durch die Abschwächung der Vokale in unbetonten Silben diese Bildung undeutlich wurde, dürfte sie in späterer Zeit verschwunden oder durch deutlichere Bildungen wie die mit -er ersetzt sein.
This article is in German.
Binna skelde: zur Deutung eines Ausdrucks des friesischen Fehdewesens
Authors: Vries Oebele 
Published: June 2017

In this article we will try to clarify the expression binna skelde (literally ‘within the shield’ or ‘within the debt’), which features in Old Frisian juridical language, and which has not yet received a satisfactory explanation. We arrive at the following results. Firstly, the (inflected) form skelde undoubtedly means ‘shield’. Secondly, the context of most of the relevant passages—some being unclear—proves that the expression belongs to the field of Frisian feud terminology, which has its own specific characteristics. Finally, the data suggest that the best way to paraphrase binna skelde is ‘under the liability of the feud leader(s)’ or, alternatively ‘under his (or: their) liability as (a) feud leader(s)’.
In diesem Aufsatz wird der Versuch gewagt, einen bislang nicht befriedigend gedeuteten Begriff der altfriesischen Rechtssprache, und zwar die Wendung binna skelde (wortwörtlich ‚innerhalb des Schildes‘ oder ‚innerhalb der Schuld‘), zu klären. Es lässt sich Folgendes feststellen. Erstens ist mit skelde (flektierte Form) zweifelsohne ‚Schild‘ gemeint. Weiterhin lässt sich aus dem Kontext der meisten der vorhandenen Belegstellen – die übrigen sind unklar – schließen, dass der Ausdruck der teilweise ganz eigenständigen friesischen Fehdeterminologie zuzuordnen ist. Letztendlich wird aus den vorliegenden Daten gefolgert, dass eine angemessene Umschreibung der Bedeutung des Ausdruckes ‚unter der Haftung des Fehdeleiters‘ oder auch ‚unter seiner (bzw. ihrer) Haftung als Fehdeleiter‘ ist.
This article is in German.
Redescription of the Philippine leafhopper genus Iposcopus Baker (Hemiptera: Cicadellidae: Idiocerinae)
Authors: XUE QINGQUAN , MCKAMEY STUART H. , ZHANG YALIN 
Published: June 2017

The Philippine leafhopper genus Iposcopus Baker is redescribed. The male and female genitalia of I. breviceps and I. distanti are described and illustrated for the first time. Baker (1915) established the genus Iposcopus and included two new species, I. breviceps and I. distanti (the type species) from the Philippines. Previously, only the external morphology and color have been described, not the genitalia. Here we first give a more complete description of the species, including male and female genitalia.
Long-Range Persistence in Global Surface Temperatures Explained by Linear Multibox Energy Balance Models
Authors: Fredriksen Hege-Beate , Rypdal Martin 
Published: June 2017

Abstract
The temporal fluctuations in global mean surface temperature are an example of a geophysical quantity that can be described using the notions of long-range persistence and scale invariance/scaling, but this description has suffered from lack of a generally accepted physical explanation. Processes with these statistical signatures can arise from nonlinear effects, for instance, through cascade-like energy transfer in turbulent fluids, but they can also be produced by linear models with scale-invariant impulse–response functions. This paper demonstrates that, on time scales from months to centuries, the scale-invariant impulse–response function of global surface temperature can be explained by simple linear multibox energy balance models. This explanation describes both the scale invariance of the internal variability and the lack of a characteristic time scale of the response to external forcings. With parameters estimated from observational data, the climate response is approximately scaling in these models, even if the response function is not chosen to be scaling a priori. It is also demonstrated that the differences in scaling exponents for temperatures over land and for sea surface temperatures can be reproduced by a version of the multibox energy balance model with two distinct surface boxes.
Investigating the Determinants and Effects of Local Drought Awareness
Authors: Switzer David , Vedlitz Arnold 
Published: June 2017

Abstract
Literature in environmental public opinion has recently focused on the linkages between biophysical conditions and opinion formation. Where environmental issues and weather are more severe, individuals have been shown to have greater perception of environmental risk and greater support for environmental protection. Perceptions, however, do not always reflect actual weather, and perceptions may actually matter more when it comes to the formation of opinions. This paper explores this possibility in the context of drought, examining what variables determine individual awareness of drought and further exploring how drought awareness influences risk perception and policy preferences. Using data from two nationally representative probability-based panel surveys, as well as data from the U.S. Drought Monitor, the analysis indicates that while drought severity is the largest predictor of drought awareness, ideological and demographic variables also play a role. Importantly, drought awareness is actually a stronger predictor of concern for water shortages and support for water policy than drought severity, showing that understanding what determines drought awareness may be crucial for building policy support.
An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study
Authors: Norkuviene Eleonora , Petraitis Mykolas , Apanaviciene Indre , Virviciute Dalia , Baranauskaite Asta 
Published: June 2017

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice.
Perception of Symmetry in Aesthetic Rhinoplasty Patients: Anthropometric, Demographic, and Psychological Analysis
Authors: Abbas Ozan Luay , Kurkcuoglu Ayla , Aytop Cigdem Derya , Uysal Cengiz , Pelin Can 
Published: June 2017

Visual perception of symmetry is a major determinant of satisfaction after aesthetic rhinoplasty. In this study, we sought to investigate the existence of any relationship between anthropometric characteristics of the face and visual perceptions of asymmetry among rhinoplasty patients and to evaluate tools that can shed light on patients who appear at high risk for exaggerating potential asymmetries. In the first part, 168 rhinoplasty patients were asked to fill out the demographic questionnaire, nasal shape evaluation scale, and the somatosensory amplification scale. In the second part, we examined the relationship between anthropometric characteristics of the face and visual perceptions of asymmetry using standardized photographs of 100 medical students. In the third part, patients answered the rhinoplasty outcome evaluation questionnaire 6 months after the surgery. Objectively, no symmetrical face was observed in the anthropometric evaluation. Subjectively, only 73% and 54% of the faces were considered asymmetrical by the rhinoplasty and the control groups, respectively. The rate of asymmetry perception was significantly greater in revision patients when compared with primary rhinoplasty patients. The relationship between the rate of subjective perception of asymmetry and the somatosensory amplification scale scores was statistically significant. We found a significant inverse relationship between the rate of asymmetry perception and the rhinoplasty outcome evaluation scores. Plastic surgeons should be aware of this high selectivity in asymmetry perception, which is associated with poor postoperative satisfaction. Somatosensory amplification scale may help identify rhinoplasty patients at a high risk for exaggerating potential asymmetries. Level of Evidence: III.
Developmental coordination disorders and sensory processing and integration: Incidence, associations and co-morbidities
Authors: Allen Susan , Casey Jackie 
Published: June 2017

IntroductionChildren with developmental coordination disorder or sensory processing and integration difficulties face challenges to participation in daily living. To date there has been no exploration of the co-occurrence of developmental coordination disorders and sensory processing and integration difficulties.MethodRecords of children meeting Diagnostic and Statistical Manual – V criteria for developmental coordination disorder ( n = 93) age 5 to 12 years were examined. Data on motor skills (Movement Assessment Battery for Children – 2) and sensory processing and integration (Sensory Processing Measure) were interrogated.ResultsOf the total sample, 88% exhibited some or definite differences in sensory processing and integration. No apparent relationship was observed between motor coordination and sensory processing and integration. The full sample showed high rates of some difficulties in social participation, hearing, body awareness, balance and motion, and planning and ideation. Further, children with co-morbid autistic spectrum disorder showed high rates of difficulties with touch and vision.ConclusionMost, but not all, children with developmental coordination disorder presented with some difficulties in sensory processing and integration that impacted on their participation in everyday activities. Sensory processing and integration difficulties differed significantly between those with and without co-morbid autistic spectrum disorder.