bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factors affecting treatment success in ganglion impar block applied in chronic coccygodynia
Authors: Celenlioglu Alp Eren , Sir Ender 
Published: June 2022

BackgroundThis study aimed to determine the predictive factors affecting the success of ganglion impar block applied in chronic coccygodynia.MethodsPatients who received ganglion impar block to treat coccygodynia between January 1, 2018 and January 1, 2021 were retrospectively screened. Of the 195 patients, 102 met the final analysis criteria and were included in the study. Demographic data, coccygodynia etiology, coccygodynia symptom duration, history of coccyx fracture, regular opioid use, and presence of other musculoskeletal chronic pain conditions accompanying coccygodynia were obtained from patient records. In addition, coccyx radiography was examined, and coccyx curvature type, permanent subluxation, and posterior spicule presence were evaluated. The criterion for treatment success was set as ≥50% reduction in Numerical Rating Scale pain scores in the third month after treatment.ResultsTreatment was successful of the patients in 69.6% (95% CI 60.4% to 78.7%). A significant cut-off value (24.5 months) was determined for coccygodynia symptom duration using receiver operating characteristic analysis. Symptom duration above the cut-off value was defined as prolonged symptom duration. Multivariable logistic regression analysis was performed to determine the predictive factors affecting treatment success in the third month after injection. In the final model, the presence of permanent subluxation (yes vs no), and the prolonged symptom duration (yes vs no) were found to have significant effects on treatment success (OR 9.56, 95% CI 1.44 to 63.40, p=0.02; OR 137.00, 95% CI 19.59 to 958.03, p<0.001).ConclusionTreatment success of ganglion impar block for coccygodynia is high. However, longer preprocedure symptom duration and the presence of permanent subluxation were associated with a decrease likelihood of treatment success.
A Relative Information Gain-based Query Performance Prediction Framework with Generated Query Variants
Authors: Datta Suchana , Ganguly Debasis , Mitra Mandar , Greene Derek 
Published: June 2022

Query performance prediction (QPP) methods, which aim to predict the performance of a query, often rely on evidences in the form of different characteristic patterns in the distribution of Retrieval Status Values (RSVs). However, for neural IR models, it is usually observed that the RSVs are often less reliable for QPP because they are bounded within short intervals, different from the situation for statistical models. To address this limitation, we propose a model-agnostic QPP framework that gathers additional evidences by leveraging information from the characteristic patterns of RSV distributions computed over a set ofautomatically generatedquery variants, relative to that of the current query. Specifically, the idea behind our proposed method—Weighted Relative Information Gain (WRIG), is that a substantial relative decrease or increase in the standard deviation of the RSVs of the query variants is likely to be a relative indicator of how easy or difficult the original query is. To cater for the absence of human-annotated query variants in real-world scenarios, we further propose an automatic query variant generation method. This can produce variants in a controlled manner by substituting terms from the original query with new ones sampled from a weighted distribution, constructed either via a relevance model or with the help of an embedded representation of query terms. Our experiments on the TREC-Robust, ClueWeb09B, and MS MARCO datasets show that WRIG, by the use of this relative changes in QPP estimate, leads to significantly better results than a state-of-the-art baseline method that leverages information from (manually created) query variants by the application of additive smoothing [64]. The results also show that our approach can improve the QPP effectiveness of neural retrieval approaches in particular.
Leveraging Clinical Trial Populations and Data from the Children's Oncology Group for Cancer Survivorship Research
Authors: Chow Eric J. , Winestone Lena E. , Lupo Philip J. , Diller Lisa R. , Henderson Tara O. , Kadan-Lottick Nina S. , Levine Jennifer M. , Ness Kirsten K. , Bhatia Smita , Armenian Saro H. 
Published: June 2022

AbstractChildren and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship research with several unique strengths: (i) a huge catchment to ascertain relatively rare but important adverse events, (ii) study populations that are otherwise too rare to study in smaller consortia, including access to highly diverse patient populations, (iii) long-term follow-up of clinical trial populations linked to the original trial data, and (iv) a natural platform for intervention research. Enhancements in COG infrastructure facilitate survivorship research, including a COG patient registry (Project:EveryChild), availability of a long-term follow-up tracking resource, and successful deployment of various remote-based study procedures to reduce the burden on participants and participating institutions.
Osimertinib plus Selumetinib in EGFR-Mutated Non–Small Cell Lung Cancer After Progression on EGFR-TKIs: A Phase Ib, Open-Label, Multicenter Trial (TATTON Part B)
Authors: Yang James Chih-Hsin , Ohe Yuichiro , Chiu Chao-Hua , Ou Xiaoling , Cantarini Mireille , Jänne Pasi A. , Hartmaier Ryan J. , Ahn Myung Ju 
Published: June 2022

Abstract

Purpose:
MEK/ERK inhibition can overcome acquired resistance to osimertinib in preclinical models. Osimertinib [EGFR–tyrosine kinase inhibitor (TKI)] plus selumetinib (MEK1/2 inhibitor) was assessed in the global TATTON study.

Patients and Methods:
This multicenter, open-label, phase Ib study expansion cohort enrolled patients (aged ≥18 years) with MET-negative, EGFRm advanced NSCLC who had progressed on EGFR-TKIs. Patients were assigned to one of two cohorts by prior first- or second-generation or T790M-directed EGFR-TKI and received osimertinib 80 mg every day and intermittent selumetinib 75 mg twice a day orally. Safety and tolerability (primary objective) and antitumor activity determined by objective response rate (ORR), and progression-free survival (PFS) using RECIST v1.1 were assessed. Data cutoff: March 4, 2020.

Results:
Forty-seven patients received treatment (prior first- or second-generation EGFR-TKI, n = 12; prior T790M-directed EGFR-TKI, n = 35). Forty-four (94%) patients were Asian; 30 (64%) had baseline exon 19 deletion. Most common AEs were diarrhea (89%), decreased appetite (40%), and stomatitis (32%); 11/47 patients (23%) had an AE Grade ≥3 possibly causally selumetinib-related. ORR was 66.7% [95% confidence interval (CI), 34.9–90.1] in the prior first- or second-generation EGFR-TKI group, 22.9% (95% CI, 10.4–40.1) in the prior T790M-directed EGFR-TKI group, and 34.0% (95% CI, 20.9–49.3) overall; median PFS was 15.0 (95% CI, 2.7–33.0), 2.8 (95% CI, 1.6–5.5), and 4.2 months (95% CI, 2.7–7.2), respectively.

Conclusions:
In this small study, AEs and tolerability of osimertinib plus selumetinib were as expected, on the basis of previous studies. The combination demonstrated antitumor activity supportive of further investigation in patients with MET-negative, EGFRm advanced NSCLC who had progressed on a previous EGFR-TKI.
OLIG2 Is a Determinant for the Relapse of MYC-Amplified Medulloblastoma
Authors: Xu Zhenhua , Murad Najiba , Malawsky Daniel , Tao Ran , Rivero-Hinojosa Samuel , Holdhof Dörthe , Schüller Ulrich , Zhang Peng , Lazarski Christopher , Rood Brian R. , Packer Roger , Gershon Timothy , Pei Yanxin 
Published: June 2022

Abstract

Purpose:
Patients with MYC-amplified medulloblastoma (MB) have poor prognosis and frequently develop recurrence, thus new therapeutic approaches to prevent recurrence are needed.

Experimental Design:
We evaluated OLIG2 expression in a panel of mouse Myc-driven MB tumors, patient MB samples, and patient-derived xenograft (PDX) tumors and analyzed radiation sensitivity in OLIG2–high and OLIG2–low tumors in PDX lines. We assessed the effect of inhibition of OLIG2 by OLIG2-CRISPR or the small molecule inhibitor CT-179 combined with radiotherapy on tumor progression in PDX models.

Results:
We found that MYC-associated MB can be stratified into OLIG2–high and OLIG2–low tumors based on OLIG2 protein expression. In MYC-amplified MB PDX models, OLIG2–low tumors were sensitive to radiation and rarely relapsed, whereas OLIG2–high tumors were resistant to radiation and consistently developed recurrence. In OLIG2–high tumors, irradiation eliminated the bulk of tumor cells; however, a small number of tumor cells comprising OLIG2– tumor cells and rare OLIG2+ tumor cells remained in the cerebellar tumor bed when examined immediately post-irradiation. All animals harboring residual-resistant tumor cells developed relapse. The relapsed tumors mirrored the cellular composition of the primary tumors with enriched OLIG2 expression. Further studies demonstrated that OLIG2 was essential for recurrence, as OLIG2 disruption with CRISPR-mediated deletion or with the small molecule inhibitor CT-179 prevented recurrence from the residual radioresistant tumor cells.

Conclusions:
Our studies reveal that OLIG2 is a biomarker and an effective therapeutic target in a high-risk subset of MYC-amplified MB, and OLIG2 inhibitor combined with radiotherapy represents a novel effective approach for treating this devastating disease.
FDA Approval Summary: Cabozantinib for Differentiated Thyroid Cancer
Authors: Duke Elizabeth S. , Barone Amy K. , Chatterjee Somak , Mishra-Kalyani Pallavi S. , Shen Yuan-Li , Isikwei Emasenyie , Zhao Hong , Bi Youwei , Liu Jiang , Rahman Nam Atiqur , Wearne Emily , Leighton John K. , Stephenson Maritsa , Ojofeitimi Idara , Scepura Barbara , Nair Abhilasha , Pazdur Richard , Beaver Julia A. , Singh Harpreet 
Published: June 2022

Abstract
On September 17, 2021, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine (RAI)-refractory or ineligible. This is the first approval for patients with RAI-refractory locally advanced or metastatic DTC who have progressed following prior therapy and the first approval in pediatric patients with DTC. The approval was based on data from COSMIC-311 (Study XL184-311, NCT03690388), an international, randomized, double-blind trial in which patients with locally advanced or metastatic RAI-refractory DTC that progressed during or following treatment with at least one VEGFR-targeting tyrosine kinase inhibitor were treated with either cabozantinib 60 mg orally once daily (N = 170) or placebo with best supportive care (N = 88). The primary efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) by blinded independent central review per RECIST 1.1. The median PFS was 11.0 months [95% confidence interval (CI), 7.4–13.8] in the cabozantinib arm compared with 1.9 months (95% CI, 1.9–3.7) in the control arm, with an HR of 0.22 (95% CI, 0.15–0.31). The endpoint of ORR was not met. No new safety signals were identified with the exception of hypocalcemia, which was added as a warning in the product labeling.
Phenotype, Function, and Clinical Significance of CD26+ and CD161+Tregs in Splenic Marginal Zone Lymphoma
Authors: Tang Xinyi , Yang Zhi-Zhang , Kim Hyo Jin , Anagnostou Theodora , Yu Yue , Wu Xiaosheng , Chen Jun , Krull Jordan E. , Wenzl Kerstin , Mondello Patrizia , Bhardwaj Vaishali , Wang Junwen , Novak Anne J. , Ansell Stephen M. 
Published: June 2022

Abstract

Purpose:
Regulatory T-cells (Treg) are essential to Tregs homeostasis and modulate the antitumor immune response in patients with lymphoma. However, the biology and prognostic impact of Tregs in splenic marginal zone lymphoma (SMZL) have not been studied.

Experimental Design:
Biopsy specimens from 24 patients with SMZL and 12 reactive spleens (rSP) from individuals without lymphoma were analyzed by using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), CyTOF (mass cytometry) analysis, and flow cytometry to explore the phenotype, transcriptomic profile, and clinical significance of intratumoral Tregs and their subsets. The biological characteristics and cell signaling pathways of intratumoral Treg subsets were confirmed by in vitro functional assays.

Results:
We found that Tregs are more abundant in SMZL patients' spleens than rSP, and Tregs from patients with SMZL and rSP can be separated into CD161+Treg and CD26+Treg subsets. CD161+Tregs are increased in SMZL but have dysregulated immune function. We found that CD161+Treg and CD26+Tregs have unique gene expression and phenotypic profiles and are differentially correlated with patient outcomes. Specifically, increased CD161+Tregs are significantly associated with a favorable prognosis in patients with SMZL, whereas CD26+Tregs are associated with a poor prognosis. Furthermore, activation of the IL2/STAT5 pathway contributes to the induction of CD26+Tregs and can be reversed by STAT5 inhibition.

Conclusions:
IL2/STAT5-mediated expansion of CD26+Tregs contributes to a poor clinical outcome in SMZL and may represent a therapeutic opportunity in this disease.
YES1: A Novel Therapeutic Target and Biomarker in Cancer
Authors: Garmendia Irati , Redin Esther , Montuenga Luis M. , Calvo Alfonso 
Published: June 2022

Abstract
YES1 is a nonreceptor tyrosine kinase that belongs to the SRC family of kinases (SFK) and controls multiple cancer signaling pathways. YES1 is amplified and overexpressed in many tumor types, where it promotes cell proliferation, survival, and invasiveness. Therefore, YES1 has been proposed as an emerging target in solid tumors. In addition, studies have shown that YES1 is a prognostic biomarker and a predictor of dasatinib activity. Several SFKs-targeting drugs have been developed, and some of them have reached clinical trials. However, these drugs have encountered challenges to their utilization in the clinical practice in unselected patients due to toxicity and lack of efficacy. In the case of YES1, novel specific inhibitors have been developed and tested in preclinical models, with impressive antitumor effects. In this review, we summarize the structure and activation of YES1 and describe its role in cancer as a target and prognostic and companion biomarker. We also address the efficacy of SFKs inhibitors that are currently in clinical trials, highlighting the main hindrances for their clinical use. Current available information strongly suggests that inhibiting YES1 in tumors with high expression of this protein is a promising strategy against cancer.
Inhibition of the Translation Initiation Factor eIF4A Enhances Tumor Cell Radiosensitivity
Authors: Lehman Stacey L. , Wechsler Theresa , Schwartz Kayla , Brown Lauren E. , Porco John A. , Devine William G. , Pelletier Jerry , Shankavaram Uma T. , Camphausen Kevin , Tofilon Philip J. 
Published: June 2022

Abstract
A fundamental component of cellular radioresponse is the translational control of gene expression. Because a critical regulator of translational control is the eukaryotic translation initiation factor 4F (eIF4F) cap binding complex, we investigated whether eIF4A, the RNA helicase component of eIF4F, can serve as a target for radiosensitization. Knockdown of eIF4A using siRNA reduced translational efficiency, as determined from polysome profiles, and enhanced tumor cell radiosensitivity as determined by clonogenic survival. The increased radiosensitivity was accompanied by a delayed dispersion of radiation-induced γH2AX foci, suggestive of an inhibition of DNA double-strand break repair. Studies were then extended to (-)-SDS-1–021, a pharmacologic inhibitor of eIF4A. Treatment of cells with the rocaglate (-)-SDS-1–021 resulted in a decrease in translational efficiency as well as protein synthesis. (-)-SDS-1–021 treatment also enhanced the radiosensitivity of tumor cell lines. This (-)-SDS-1–021-induced radiosensitization was accompanied by a delay in radiation-induced γH2AX foci dispersal, consistent with a causative role for the inhibition of double-strand break repair. In contrast, although (-)-SDS-1–021 inhibited translation and protein synthesis in a normal fibroblast cell line, it had no effect on radiosensitivity of normal cells. Subcutaneous xenografts were then used to evaluate the in vivo response to (-)-SDS-1–021 and radiation. Treatment of mice bearing subcutaneous xenografts with (-)-SDS-1–021 decreased tumor translational efficiency as determined by polysome profiles. Although (-)-SDS-1–021 treatment alone had no effect on tumor growth, it significantly enhanced the radiation-induced growth delay. These results suggest that eIF4A is a tumor-selective target for radiosensitization.
Dichotomous Roles of Smooth Muscle Cell–Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis
Authors: Owsiany Katherine M. , Deaton Rebecca A. , Soohoo Karen G. , Tram Nguyen Anh , Owens Gary K. 
Published: June 2022

Background:
Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect plaque stability and, therefore, the likelihood of myocardial infarction or stroke. However, the mechanisms by which these cells affect stability are only beginning to be explored.

Methods:

In this study, we investigated the contribution of inflammatory MCP1 (monocyte chemoattractant protein 1) produced by both classical Myh11 (myosin heavy chain 11)
+
SMCs and SMCs that have transitioned through an Lgals3 (galectin 3)
+
state in atherosclerosis using smooth muscle lineage tracing mice that label all Myh11
+
cells and a dual lineage tracing system that targets Lgals3-transitioned SMC only.

Results:

We show that loss of MCP1 in all Myh11
+
smooth muscle results in a paradoxical increase in plaque size and macrophage content, driven by a baseline systemic monocytosis early in atherosclerosis pathogenesis. In contrast, knockout of MCP1 in Lgals3-transitioned SMCs using a complex dual lineage tracing system resulted in lesions with an increased Acta2 (actin alpha 2, smooth muscle)
+
fibrous cap and decreased investment of Lgals3-transitioned SMCs, consistent with increased plaque stability. Finally, using flow cytometry and single-cell RNA sequencing, we show that MCP1 produced by Lgals3-transitioned SMCs influences multiple populations of inflammatory cells in late-stage plaques.

Conclusions:
MCP1 produced by classical SMCs influences monocyte levels beginning early in disease and was atheroprotective, while MCP1 produced by the Lgals3-transitioned subset of SMCs exacerbated plaque pathogenesis in late-stage disease. Results are the first to determine the function of Lgals3-transitioned inflammatory SMCs in atherosclerosis and highlight the need for caution when considering therapeutic interventions involving MCP1.
Forecaster (Mis-)Behavior
Authors: Broer Tobias , Kohlhas Alexandre N. 
Published: June 2022

Abstract
We document two stylized facts in expectational survey data. First, professional forecasters overrevise their macroeconomic expectations. Second, such overrevisions mask evidence of both over- and underreactions to public signals. We show that the first fact is inconsistent with standard models of noisy rational expectations, but consistent with behavioral and strategic models. The second fact, in contrast, presents a puzzle for existing theories. We propose an extension of noisy rational expectations that allows forecasters to be overconfident in their information. We show that this feature when combined with the endogeneity of public signals leads to over- and undereactions consistent with the data.
Higher Education and Local Educational Attainment: Evidence from the Establishment of U.S. Colleges
Authors: Russell Lauren C. , Yu Lei , Andrews Michael J. 
Published: June 2022

Abstract
We investigate how the presence of a college affects local educational attainment. As counterfactuals for current college locations, we use historical “runner-up” locations that were strongly considered to become college sites but were ultimately not chosen. We find that winning counties today have college degree attainment rates 56% higher than runner-up counties and more private-sector employment in human-capital-intensive industries. These effects are not driven primarily by recent in-migration of educated adults, and alternative public investments did not have similar effects on local educational attainment. The results indicate that colleges played an important role in shaping long-run local outcomes.
Behavioral Biases among Producers: Experimental Evidence of Anchoring in Procurement Auctions
Authors: Ferraro Paul J. , Messer Kent D. , Shukla Pallavi , Weigel Collin 
Published: June 2022

Abstract
Experimental research in behavioral economics focuses on consumer behaviors. Similar experimental research on profit-maximizing producers is rare. In three field experiments involving commercial agricultural producers in the United States, we detect evidence of anchoring in competitive auctions for conservation contracts related to nutrient and pest management that were worth, on average, nearly $9,000. In these auctions, the value of the starting cost-share bid was randomized to be either 0% or 100%. When the starting value was 100%, final bids were 46% higher, on average. We find weak evidence that experience with conservation contracts may modestly attenuate the anchoring effect.
Administrative philosophies in the discourse and decisions of the New Zealand public service: is post-New Public Management still a myth?
Authors: Scott Rodney J , Donadelli Flavia , Merton Eleanor RK 
Published: June 2022

New Zealand is frequently cited as the archetypical example of New Public Management (NPM), having gone ‘further and faster’ than other jurisdictions in radically reforming their public service in the late 1980s. These reforms have been credited with significant gains in efficiency and responsiveness, while introducing new challenges. Successive reforms over the past 30 years tinkered with the model without fundamentally altering the underlying paradigm, such that authors refer to the ‘myth of post-NPM in New Zealand’. In 2020, New Zealand repealed and replaced its main public service legislation. By textually analysing government documents, this article explores the different theoretical roots of New Zealand's ongoing administrative reforms and debates the extent of their theoretical coherence. The Act directly dialogues with and draws inspiration from recent academic debates, drawing from a range of sources (such as New Public Governance, Digital Era Governance, and the New Public Service). Points for practitioners New Zealand has long been regarded as the purest example of New Public Management (NPM). Legislation passed in 2020 saw New Zealand adopt a range of reforms described in the literature as ‘post-NPM’, while also reaffirming features associated with Traditional Public Administration (TPA). While New Zealand has moved away from a pure NPM model and adopted features associated with Post-NPM, Post-NPM is not a coherent doctrine and it may only be possible to identify administrative doctrines retrospectively. We may be entering a period of ‘New Public Complexity’, where administrative doctrines are blended and layered.