bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical evidence of the impact of study characteristics on the performance of prediction models: a meta-epidemiological study
Authors: Damen Johanna A A G , Debray Thomas P A , Pajouheshnia Romin , Reitsma Johannes B , Scholten Rob J P M , Moons Karel G M , Hooft Lotty 
Published: April 2019

ObjectivesTo empirically assess the relation between study characteristics and prognostic model performance in external validation studies of multivariable prognostic models.DesignMeta-epidemiological study.Data sources and study selectionOn 16 October 2018, we searched electronic databases for systematic reviews of prognostic models. Reviews from non-overlapping clinical fields were selected if they reported common performance measures (either the concordance (c)-statistic or the ratio of observed over expected number of events (OE ratio)) from 10 or more validations of the same prognostic model.Data extraction and analysesStudy design features, population characteristics, methods of predictor and outcome assessment, and the aforementioned performance measures were extracted from the included external validation studies. Random effects meta-regression was used to quantify the association between the study characteristics and model performance.ResultsWe included 10 systematic reviews, describing a total of 224 external validations, of which 221 reported c-statistics and 124 OE ratios. Associations between study characteristics and model performance were heterogeneous across systematic reviews. C-statistics were most associated with variation in population characteristics, outcome definitions and measurement and predictor substitution. For example, validations with eligibility criteria comparable to the development study were associated with higher c-statistics compared with narrower criteria (difference in logit c-statistic 0.21(95% CI 0.07 to 0.35), similar to an increase from 0.70 to 0.74). Using a case-control design was associated with higher OE ratios, compared with using data from a cohort (difference in log OE ratio 0.97(95% CI 0.38 to 1.55), similar to an increase in OE ratio from 1.00 to 2.63).ConclusionsVariation in performance of prognostic models across studies is mainly associated with variation in case-mix, study designs, outcome definitions and measurement methods and predictor substitution. Researchers developing and validating prognostic models should realise the potential influence of these study characteristics on the predictive performance of prognostic models.
CAP
Authors: Chen Xinlei , Wang Yu , He Jiayou , Pan Shijia , Li Yong , Zhang Pei 
Published: April 2019

Context-aware mobile application (App) usage prediction benefits a variety of applications such as precise bandwidth allocation, App launch acceleration, etc. Prior works have explored this topic through individual data profiles and contextual information. However, it is still a challenging problem because of the following three aspects: i. App usage behavior is usually influenced by multiple factors, especially temporal and spatial factors. ii. It is difficult to describe individuals' preferences, which are usually time-variant. iii. A single user's data is sparse on the spatial domain and only covers a limited number of locations. Prediction becomes more difficult when the user appears at a new location.
This paper presents CAP, a context-aware App usage prediction algorithm that takes both contextual information (location & time) and attribution (App with type information) into consideration. We find that the relationships between App-location, App-time, and App-App type are essential to prediction and propose a heterogeneous graph embedding algorithm to map them into the common comparable latent space. In addition, we create a user profile for each user with App usage and trajectory history to describe the individual dynamic preference for personalized prediction. We evaluate the performance of our proposed CAP with two large-scale real-world datasets. Extensive evaluations demonstrate that CAP achieves 30% higher accuracy than a state-of-the-art method Personalized Ranking Metric Embedding (PRME) in terms of Accuracy@5. In terms of mean reciprocal rank (MRR), CAP achieves 1.5× higher than the straightforward baseline Sta and 2× higher than PRME. Our investigation enables a range of applications to benefit from such timely predictions, including network operators, service providers, and etc.
Temozolomide Treatment Induces lncRNA MALAT1 in an NF-κB and p53 Codependent Manner in Glioblastoma
Authors: Voce David J. , Bernal Giovanna M. , Wu Longtao , Crawley Clayton D. , Zhang Wei , Mansour Nassir M. , Cahill Kirk E. , Szymura Szymon J. , Uppal Abhineet , Raleigh David R. , Spretz Ruben , Nunez Luis , Larsen Gustavo , Khodarev Nikolai N. , Weichselbaum Ralph R. , Yamini Bakhtiar 
Published: April 2019

AbstractAlkylating chemotherapy is a central component of the management of glioblastoma (GBM). Among the factors that regulate the response to alkylation damage, NF-κB acts to both promote and block cytotoxicity. In this study, we used genome-wide expression analysis in U87 GBM to identify NF-κB–dependent factors altered in response to temozolomide and found the long noncoding RNA (lncRNA) MALAT1 as one of the most significantly upregulated. In addition, we demonstrated that MALAT1 expression was coregulated by p50 (p105) and p53 via novel κB- and p53-binding sites in the proximal MALAT1 coding region. Temozolomide treatment inhibited p50 recruitment to its cognate element as a function of Ser329 phosphorylation while concomitantly increasing p53 recruitment. Moreover, luciferase reporter studies demonstrated that both κB and p53 cis-elements were required for efficient transactivation in response to temozolomide. Depletion of MALAT1 sensitized patient-derived GBM cells to temozolomide cytotoxicity, and in vivo delivery of nanoparticle-encapsulated anti-MALAT1 siRNA increased the efficacy of temozolomide in mice bearing intracranial GBM xenografts. Despite these observations, in situ hybridization of GBM specimens and analysis of publicly available datasets revealed that MALAT1 expression within GBM tissue was not prognostic of overall survival. Together, these findings support MALAT1 as a target for chemosensitization of GBM and identify p50 and p52 as primary regulators of this ncRNA.Significance:These findings identify NF-κB and p53 as regulators of the lncRNA MALAT1 and suggest MALAT1 as a potential target for the chemosensitization of GBM.
Antagonism between HTRA3 and TGFβ1 Contributes to Metastasis in Non–Small Cell Lung Cancer
Authors: Zhao Jingya , Feng Mingxiang , Liu Dong , Liu Haixia , Shi Mengmeng , Zhang Jing , Qu Jieming 
Published: April 2019

Abstract

High temperature requirement A3 (HTRA3, long and short isoforms) is a member of the HtrA family and has been implicated as a tumor suppressor in cancer progression in multiple cancer types, yet its molecular functions in non–small cell lung cancer (NSCLC) are not well understood. Here, we report that decreased levels of HTRA3 negatively correlate with elevated TGFβ1 in lung tumor tissue with metastasis. Furthermore, high expression of HTRA3 indicated better prognosis independent of TGFβ1 expression. In NSCLC cell lines, exogenous TGFβ1 significantly downregulated the level of HTRA3, especially the long isoform, during induction of epithelial–mesenchymal transition (EMT). Mechanistically, c-Jun, which is elevated by TGFβ1, directly bound the promoter of HTRA3-L and inhibited its transcription. As a negative feedback loop, overexpression of HTRA3-L attenuated TGFβ1-mediated invasion-metastasis cascades via activation of SMAD2/3 and sensitized cells to anti-PD-L1 treatment. Taken together, our findings suggest that in the early stages of cancer, overexpressed HTRA3 acts as a brake on the oncogenic effects of TGFβ1 and inhibits tumor metastasis. In later stages, the role of HTRA3 is weakened and TGFβ1 efficiently promotes EMT in the absence of the HTRA3 brake.

Significance:
This study provides new mechanistic insight of the interaction between HTRA3 and TGFβ in lung cancer by illustrating that HTRA3 is a novel mediator acting as a suppressor of TGFβ1-related oncogenic effects.
Surgical Outcomes for the Treatment of Velopharyngeal Insufficiency in 22q11.2 Deletion Syndrome
Authors: Bohm Lauren A. , Miller Jessa E. , Morrell Noëlle , Sidman James D. , Roby Brianne B. 
Published: April 2019

This study aimed to compare outcomes of concomitant palatoplasty and sphincter pharyngoplasty with pharyngeal flap and sphincter pharyngoplasty alone for the treatment of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome. Thirty‐one cases were identified for inclusion in the study. Patients were separated into 3 surgical groups: combined palatoplasty and sphincter pharyngoplasty (n = 11), pharyngeal flap (n = 7), and sphincter pharyngoplasty (n = 13). Outcome measures included perceptual speech analyses, surgical complications, and revision rates. There were no differences in preoperative speech analysis scores (P =. 31). The combined palatoplasty and sphincter pharyngoplasty procedure had similar speech outcomes compared to pharyngeal flap, and both were significantly better than sphincter pharyngoplasty alone. Complication rates (P =. 61) and the need for revision surgery (P =. 25) were similar among all 3 groups. Concomitant palatoplasty and sphincter pharyngoplasty may be an alternative treatment for velopharyngeal insufficiency in children with 22q11.2 deletion syndrome.
Predicting visual outcomes in patients treated with aflibercept for neovascular age-related macular degeneration: Data from a real-world clinical setting
Authors: Fulcher Corinne , Hazel Charlotte A , Pacey Ian , Ali Hasan , Ghanchi Faruque D 
Published: April 2019

Background/objectives: There is a significant variation in the way neovascular age-related macular degeneration patients respond to anti–vascular endothelial growth factor treatment. Both the financial and time cost of treatment are significant. As such, being able to predict patient response to treatment is valuable. Subjects/methods: 72 eyes treated with intravitreal aflibercept were retrospectively included in analysis. For each subject, visual acuity (letters) and central retinal thickness (µm) at baseline, second, third and fourth visits, as well as 12-month visits, were collated; a plot of visual acuity versus time was generated and a slope of the first three (slope3) and first four (slope4) visits was calculated. Differences in visual acuity at each visit compared to baseline were determined, as well as percentage differences in central retinal thickness at each visit compared to baseline. Lesion sub-type and the presence of fluid and haemorrhage were also recorded. Results: The average change in visual acuity over 12 months was +3.2 ± 13.4 letters with 91.2% of patients losing <15 letters. Slope4 was the only significant predictive factor for ‘visual acuity change over 12 months’ ( p < 0.001). Change in central retinal thickness, lesion sub-type, haemorrhage at baseline and the location of fluid at baseline were not useful predictive factors in long-term outcome. Conclusion: Aflibercept is an effective treatment option for neovascular age-related macular degeneration; however, the long-term response should not be predicted until at least three loading dose injections have been given. Visual acuity measures at each visit should be examined, as it is the trend in visual acuity across the first four visits (slope4) rather than the difference in visual acuity between two visits that is the predictive factor.
Early results of micropulse transscleral cyclophotocoagulation for the treatment of glaucoma
Authors: Nguyen Alexander T , Maslin Jessica , Noecker Robert J 
Published: April 2019

Purpose: To describe our clinical experience with the efficacy and safety of micropulse transscleral cyclophotocoagulation as a treatment for glaucoma. Methods: In this retrospective case series, we reviewed the charts of 95 consecutive patients with various glaucoma subtypes who underwent micropulse transscleral cyclophotocoagulation. Patients were offered micropulse transscleral cyclophotocoagulation if they had perimetric glaucoma refractory to intraocular pressure–lowering topical medications and who were poor candidates for traditional filtering surgery. Eligible patients were treated with the Micropulse P3 device (IQ 810 Laser Systems; Iridex, Mountain View, CA, USA) at 2.0–2.5 W for a duration of 90 s per hemisphere at a 31.3% duty cycle. If a retreatment was needed, the power was increased to up to 3.0 W with other parameters remaining the same. Patients were considered successfully treated if their intraocular pressure was lowered by at least 20% compared to their baseline. The main outcome measure was post-operative intraocular pressure; secondary outcome measures included the number of adverse events and complications that occurred with treatment. Results: The glaucoma subtypes treated included primary open-angle glaucoma (n = 51), exfoliation glaucoma (n = 24), chronic angle-closure glaucoma (n = 15), and congenital/juvenile glaucoma (n = 5). The mean pre-operative intraocular pressure was 25.1 ± 5.3 mm Hg and the mean post-operative intraocular pressure at 12 months was 17.5 ± 5.1 mm Hg (p = 0.004). The mean number of intraocular pressure–lowering medications used preoperatively was 3.0 ± 1.1; the mean number of medications used at the 12-month post-operative visit was 1.4 ± 1.0 (p = 0.03). Success with one treatment was achieved in 73 (76.8%) of patients. With multiple treatments, all patients had significant intraocular pressure–lowering compared to baseline. The maximum number of treatments received by any single patient was 5. There were no instances of prolonged intraocular inflammation or long-term hypotony. Conclusion: Micropulse transscleral cyclophotocoagulation appears to be a safe and efficacious treatment for glaucoma. Given its improved safety profile compared to continuous-wave transscleral cyclophotocoagulation, it deserves consideration as a primary procedure.
Long-Term Results of Endovascular Treatment of Chronic Iliofemoral Venous Obstructive Lesions
Authors: Ignatyev Igor M. , Pokrovsky Anatolii , Gradusov Evgenii 
Published: April 2019

Objective: To evaluate the long-term results in endovascular treatment of iliofemoral venous obstructive lesions. Methods: From January 2009 to March 2017, 75 patients were admitted for endovascular treatment of chronic obstructive lesions of the iliofemoral veins. Of these, 60 patients underwent stenting of postthrombotic obstructions and 15 patients stenting of nonthrombotic obstructive lesions of the iliac veins (May-Thurner syndrome in 11, for tumor-induced compression and cicatricial stenosis in 4). Dynamic control of stent patency was carried out by means of duplex ultrasound. Efficacy of endovascular intervention was evaluated by measuring the venous pressure gradient and malleolar circumference. The clinical result was determined by the Venous Clinical Severity Score (VCSS). Results: Technical success of endovascular intervention in postthrombotic occlusions of iliac vein was 92% and in nonthrombotic iliac vein lesions was 100%. Cumulative primary and secondary patency in postthrombotic lesions at 60 months amounted to 72% and 81%, respectively, in nonthrombotic lesions to 85% (primary patency). Reinterventions were successfully performed in 6 patients including catheter-directed thrombolysis (3 patients) and stenting (3 patients). The mean VCSS score fell from 14.2 (4.2) to 7.5 (2.6; P < .001). The quality of life was improved; its mean score decreased from 62.6 (18.7) to 48.7 (12.8; P < .01). Conclusion: Endovascular angioplasty and stenting for obstructive lesions of the iliofemoral veins is a minimally invasive, safe, and highly effective method of treatment, which is confirmed by a significant improvement of the limb’s condition and good long-term results of patency of the restored venous segments.
Multimodal treatments for resectable esophagogastric junction cancer: a systematic review and network meta-analysis
Authors: Cheng Ji , Cai Ming , Shuai Xiaoming , Gao Jinbo , Wang Guobin , Tao Kaixiong 
Published: April 2019

Background: Currently, preoperative chemoradiotherapy, perioperative chemotherapy and preoperative chemotherapy are recommended by NCCN, ESMO and Japanese guidelines respectively for resectable esophageal and junctional cancer. However, these recommendations are mainly based on esophageal cancer research. Therefore, specific for esophagogastric junction cancer, we conducted the first systematic review and network meta-analysis to rank all potential treatments simultaneously and hierarchically. Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO and ESMO Meeting Library from inception to September 2018. Regarding time-to-event survival data, randomized controlled trials featuring comparisons between different multimodal treatments against resectable esophagogastric junction cancer were eligible. Overall survival was the endpoint. Network calculation was based on a random-effects model and the relative ranking of each node was numerically indicated by P-score (CRD42018110369, registration identifier of the meta-analysis in PROSPERO.). Results: Eight studies were included in our systematic review, corresponding to 1218 patients. Regarding overall survival, ‘PreCRT’ (preoperative chemoradiotherapy) topped the hierarchy (HR 1.00, P-score = 0.823), better than ‘PeriCT’ (perioperative chemotherapy; HR 1.32, P-score = 0.591) and ‘PreCT’ (preoperative chemotherapy; HR 1.54, P-score = 0.428). In sensitivity analyses, irrespective of interchanging to fixed-effects model or removing potentially heterogeneous studies, relative rankings remained stable and ‘PreCRT’ was still the optimal node. Conclusion: Preoperative chemoradiotherapy could potentially be the optimal multimodal treatment, which displayed more overall survival benefits than perioperative chemotherapy and preoperative chemotherapy among resectable esophagogastric junction cancer patients. To further verify our pooled results, more randomized trials will be needed to compare preoperative chemoradiotherapy with perioperative chemotherapy (especially FLOT-based regimens).
Regulating Private Tutoring in China: Uniform Policies, Diverse Responses
Authors: Zhang Wei 
Published: April 2019

Purpose: This article examines responses from the tutoring sector to Chinese national and local government regulations on private supplementary tutoring. It adds to the literature on policy enactment, showing the importance of context and noting the diversity of tutoring providers compared with schools. Design/Approach/Methods: The article draws on semi-structured and informal interviews with 11 tutors, 15 managers of tutoring enterprises, 5 members and managers of professional organizations, 5 government officials, 5 school managers, 5 teachers, and 20 parents. Data from interviewees were triangulated with observations, news reports, blogs written by tutoring analysts, and ad hoc research by industrial observers. Findings: Policy enactment in the tutoring sector is even more complex than that for schooling. Standardized policies do not necessarily achieve the aspired goals. Originality/Value: The article adds to the literature not only in China but also internationally. It highlights the importance of distinguishing between aspirations and realities in this domain. It also proposes conceptual considerations for regulating tutoring, given its diverse and fluid nature.
Ocular instillation of vitamin A–coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD
Authors: Ohigashi Hiroyuki , Hashimoto Daigo , Hayase Eiko , Takahashi Shuichiro , Ara Takahide , Yamakawa Tomohiro , Sugita Junichi , Onozawa Masahiro , Nakagawa Masao , Teshima Takanori 
Published: April 2019

AbstractChronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A–coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.
Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma
Authors: Sahin Ilyas , Kawano Yawara , Sklavenitis-Pistofidis Romanos , Moschetta Michele , Mishima Yuji , Manier Salomon , Sacco Antonio , Carrasco Ruben , Fonseca Rafael , Roccaro Aldo M. , Witzig Thomas , Ghobrial Irene M. 
Published: April 2019

Abstract
Citron Rho-interacting serine/threonine kinase (CIT) is a serine/threonine kinase that acts as a key component of the midbody and is essential for cytokinesis. CIT has been reported to be highly expressed in some tumor tissues and to play a role in cancer proliferation; however, the significance of CIT has not been investigated in multiple myeloma (MM). Here, we identified, by protein microarray and immunohistochemistry, that CIT is 1 of the upregulated proteins in the plasma cells of MM patients compared with healthy controls. Analysis of a gene expression profile data set showed that MM patients with high CIT gene expression had significantly worse overall survival compared with MM patients with low CIT gene expression. CIT silencing in MM cell lines induced cytokinesis failure and resulted in decreased MM cell proliferation in vitro and in vivo. TP53 expression was found to be an independent predictor of CIT dependency, with low-TP53 cell lines exhibiting a strong dependency on CIT. This study provides the rationale for CIT being a potential therapeutic target in MM in future trials.
Germline deletion of ETV6 in familial acute lymphoblastic leukemia
Authors: Rampersaud Evadnie , Ziegler David S. , Iacobucci Ilaria , Payne-Turner Debbie , Churchman Michelle L. , Schrader Kasmintan A. , Joseph Vijai , Offit Kenneth , Tucker Katherine , Sutton Rosemary , Warby Meera , Chenevix-Trench Georgia , Huntsman David G. , Tsoli Maria , Mead R. Scott , Qu Chunxu , Leventaki Vasiliki , Wu Gang , Mullighan Charles G. 
Published: April 2019

Abstract
Recent studies have identified germline mutations in TP53, PAX5, ETV6, and IKZF1 in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of ETV6 identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation. The ETV6 deletion was also identified by optimal structural variant analysis of exome sequencing data. These findings identify a new mechanism of germline predisposition in ALL and implicate ETV6 germline variation in predisposition to lymphoma. Importantly, these data highlight the importance of germline structural variant analysis in the search for germline variants predisposing to familial leukemia.