bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antileukemia Effects of Notch-Mediated Inhibition of Oncogenic PLK1 in B-Cell Acute Lymphoblastic Leukemia
Authors: Kannan Sankaranarayanan , Aitken Marisa J.L. , Herbrich Shelley M. , Golfman Leonard S. , Hall Mandy G. , Mak Duncan H. , Burks Jared K. , Song Guangchun , Konopleva Marina , Mullighan Charles G. , Chandra Joya , Zweidler-McKay Patrick A. 
Published: June 2019

Abstract
In B-cell acute lymphoblastic leukemia (B-ALL), activation of Notch signaling leads to cell-cycle arrest and apoptosis. We aimed to harness knowledge acquired by understanding a mechanism of Notch-induced cell death to elucidate a therapeutically viable target in B-ALL. To this end, we identified that Notch activation suppresses Polo-like kinase 1 (PLK1) in a B-ALL–specific manner. We identified that PLK1 is expressed in all subsets of B-ALL and is highest in Philadelphia-like (Ph-like) ALL, a high-risk subtype of disease. We biochemically delineated a mechanism of Notch-induced PLK1 downregulation that elucidated stark regulation of p53 in this setting. Our findings identified a novel posttranslational cascade initiated by Notch in which CHFR was activated via PARP1-mediated PARylation, resulting in ubiquitination and degradation of PLK1. This led to hypophosphorylation of MDM2Ser260, culminating in p53 stabilization and upregulation of BAX. shRNA knockdown or pharmacologic inhibition of PLK1 using BI2536 or BI6727 (volasertib) in B-ALL cell lines and patient samples led to p53 stabilization and cell death. These effects were seen in primary human B-ALL samples in vitro and in patient-derived xenograft models in vivo. These results highlight PLK1 as a viable therapeutic target in B-ALL. Efficacy of clinically relevant PLK1 inhibitors in B-ALL patient-derived xenograft mouse models suggests that use of these agents may be tailored as an additional therapeutic strategy in future clinical studies.
Curved Laryngopharyngoscope With Flexible Next-Generation Robotic Surgical System for Transoral Hypopharyngeal Surgery: A Preclinical Evaluation
Authors: Eguchi Kohtaro , Chan Jason Y. K. , Tateya Ichiro , Shimizu Akira , Holsinger F. Christopher , Sugimoto Taro 
Published: June 2019

Objectives: The indication of transoral robotic surgery for hypopharyngeal cancer is limited because of poor accessibility. The aim of this study was to explore the efficacy of a curved laryngopharyngoscope used in combination with a next-generation flexible robotic surgical system for accessing and resecting the hypopharynx. Methods: A comparative evaluation of the curved laryngopharyngoscope versus standard straight-blade retractors using the flexible robotic surgical system was conducted on 2 cadavers. End points measured included visualization, accessibility, and ease of dissection for accessing and resecting the hypopharynx. Results: Visualization, accessibility, and dissection were superior with the curved laryngopharyngoscope in all subareas of the hypopharynx. The advantages of accessibility and visualization were much more evident in the cadaver with a high body mass index. Conclusions: These preclinical data suggest that using a curved laryngopharyngoscope in combination with a flexible robotic surgical system may lead to technical innovations concerning transoral surgery of the hypopharynx.
LncRNA-NEF is downregulated in postmenopausal osteoporosis and is related to course of treatment and recurrence
Authors: Ma Xiaoyong , Guo Zhixue , Gao Wenshan , Wang Jianzhong , Liu Yong , Gao Fei , Sun Shaosong , Zhou Xiaozhe , Yang Zhaoyu , Zheng Wenkui 
Published: June 2019

Objectives We investigated the role of long non-coding (lnc) RNA-NEF (neighboring enhancer of FoxA2), a characterized oncogene in cancer biology, in postmenopausal osteoporosis and its diagnostic and prognostic value in this disease. Methods Expression of lncRNA-NEF in plasma was detected by RNA extraction and real-time quantitative PCR. The diagnostic value of lncRNA-NEF and interleukin (IL)-6 for postmenopausal osteoporosis was evaluated by receiver operating characteristic curve analysis, with postmenopausal osteoporosis patients as true positive cases and healthy volunteers as true negative cases. Results We showed that plasma lncRNA-NEF was downregulated and plasma IL-6 was upregulated in postmenopausal osteoporosis patients compared with healthy controls. Altered plasma levels of lncRNA-NEF and IL-6 separated postmenopausal osteoporosis patients from healthy controls, and lncRNA-NEF and IL-6 were inversely and significantly correlated in osteoporosis patients. Patients were divided into high (n = 68) and low lncRNA-NEF (n = 73) groups according to Youden’s index. Patients with high lncRNA-NEF levels required a significantly shorter treatment course and had a lower post-treatment recurrence rate. Conclusion We showed that lncRNA-NEF is downregulated in postmenopausal osteoporosis and is related to course of treatment and recurrence. The involvement of lncRNA-NEF in postmenopausal osteoporosis is likely related to IL-6.
Impact of Function Focused Care and Physical Activity on Falls in Assisted Living Residents
Authors: Resnick Barbara , Galik Elizabeth , Boltz Marie , Zhu Shijun , Fix Steven , Vigne Erin 
Published: June 2019

BackgroundThere continues to be a belief among nurses, patients, and families that physical activity increases the risk of falling.PurposeThe purpose of this study was to test the hypothesis that controlling for age, function, cognition, medication use, gender, comorbidities, and cognition, residents who are exposed to Function Focused Care for Assisted Living (FFC-AL-EIT) and engage in moderate levels of physical activity would not be more likely to fall.MethodsThis was a secondary data analysis using data from the first two cohorts of a randomized trial testing FFC-AL-EIT in the United States.ResultsThe study included 381 residents, the majority of whom were female (70%), white (97%), with a mean age of 87.72 (standard deviation = 7.47). Those who engaged in more moderate-intensity physical activity were 1% less likely to fall (odds ratio = .99, p = .03). There was no significant association between exposure to function focused care and falling (odds ratio = 1.58, p = .09).ConclusionThere was no indication that those who were exposed to function focused care or those who engaged in moderate-level physical activity were more likely to fall. In fact, engaging in moderate-level physical activity was noted to be slightly protective of falling.
‘Indian Stock Market Volatility’: A Study of Inter-linkages and Spillover Effects
Authors: (Pal) Suparna Nandy , Chattopadhyay Arup Kr. 
Published: June 2019

The article attempts to examine interdependence between Indian stock market and other domestic financial markets, namely, foreign exchange market, bullion market, money market, and also Foreign Institutional Investor (FII) trade and foreign stock markets comprising one regional stock market represented by Nikkei of Japan and other stock market for the rest of the world represented by Standard & Poor’s (S&P) 500 of the USA. Attempts are also made to examine asymmetric volatility spillover, first, between the Indian stock market and other domestic financial markets and second, between the Indian stock market and global stock markets (represented by Nikkei and S&P 500) along with the foreign exchange market. To measure linear interdependence among multiple time series of financial markets multivariate Vector Autoregression (VAR) analysis, Granger causality test, impulse response function and variance decomposition techniques are used. For estima-ting the volatility spillover among the aforesaid markets Dynamic Conditional Correlation-Multivriate-Threshold Autoregressive Condi-tional Heteroscedastic (DCC-MV-TARCH) (1, 1) model is applied on daily data for a quite long period of time from 01 April 1996 to 31 March 2012. The results of multi­variate VAR analysis, Granger causality test, variance decomposition analysis and impulse response function estimation establish significant interdependence between domestic stock market and different other financial markets in India and abroad. The results of DCC-MV-TARCH (1, 1) model estimation further show signi- ficant asymmetric volatility spillover between the domestic stock market and the foreign exchange market and also from the domestic stock market to bullion market and changes in gross volume of FII trade. We also find (a) both way asymmetric volatility spillover between the domestic stock market and the Asian stock market and (b) its unidirectional movement from the world stock market to the domestic stock market. The results of the study may help market regulators in setting regulatory policies considering the inter-linkages and pattern of volatility spillovers across different financial markets. JEL Classification: G15, G17
Opinions of Speech-Language Pathologists Regarding Speech Management for Children With Cleft Lip and Palate
Authors: Hardin-Jones Mary , Jones David L. , Dolezal Riley C. 
Published: June 2019

Objective: The purpose of the present study was to examine practice patterns and opinions that speech-language pathologists (SLPs) have about speech-language intervention for children with cleft lip and palate. Methods: One hundred seven speech-language pathology members of the American Speech-Language-Hearing Association Special Interest Group 5: Craniofacial and Velopharyngeal Disorders Special Interest Group completed a 37-item online survey that examined common practices in early intervention as well as opinions about speech characteristics, assessment, and management strategies for children with cleft lip and palate. Results: The overwhelming majority of respondents (96%) agreed that speech-language pathologists (SLPs) should meet with parents before palatal surgery to discuss speech-language issues. Although 90% of the SLPs identified increasing consonant inventory as an early intervention goal, lack of consensus was evident regarding the type of consonant to stimulate. Respondents agreed that while blowing activities are not useful in strengthening labial, lingual, or velopharyngeal movements, they are useful in heightening awareness of oral airflow for children with cleft palate. A large degree of variability was evident in opinions regarding prevalence and treatment of compensatory articulations as well as the effectiveness of treatment strategies designed to reduce perceived hypernasality and audible nasal emission. Conclusions: The findings of this study indicate a large degree of variability in opinions of SLP respondents regarding assessment and treatment of children with cleft lip and palate.
The Massachusetts Hepatitis C Testing Cascade, 2014-2016
Authors: Vo Quynh T , Onofrey Shauna , Church Daniel , Cranston Kevin , DeMaria Alfred , Klevens R Monina 
Published: June 2019

Objectives: To characterize hepatitis C testing in Massachusetts and guide stakeholders in addressing the needs of people living with hepatitis C. Methods: All persons with a positive laboratory report for anti-hepatitis C virus (HCV) antibody, between 2014 and 2016, were included in the testing cascade. Outcomes were HCV tests received after a positive anti-HCV antibody test: nucleic acid test or genotype test. Logistic regression analyses were performed to determine factors associated with progression through the HCV testing cascade. Results: Among those reported anti-HCV antibody positive, a total of 13 194 (61%) cases had a subsequent RNA-based test, and 79% (10 374/13 194) were confirmed with current, active HCV infection. For confirmed HCV cases, 44% (4557/10 374) had a genotype identified. The median time from an antibody-positive test to a RNA-based test was 29 days (interquartile range [IQR] = 7-151). Differences in moving through the testing cascade were observed by birth cohort and race/ethnicity. Conclusions: Improved surveillance capture of demographic information is needed to help public health agencies ensure equity in HCV diagnosis and linkage to care.
Knowledge-Based Statistical Inference Method for Plan Quality Quantification
Authors: Zhang Jiang , Wu Q. Jackie , Ge Yaorong , Wang Chunhao , Sheng Yang , Palta Jatinder , Salama Joseph K. , Yin Fang-Fang , Zhang Jiahan 
Published: June 2019

Aim: The aim of the study is to develop a geometrically adaptive and statistically robust plan quality inference method. Methods and Materials: We propose a knowledge-based plan quality inference method that references to similar plans in the historical database for patient-specific plan quality evaluation. First, a novel plan similarity metric with high-dimension geometrical difference quantification is utilized to retrieve similar plans. Subsequently, dosimetric statistical inferences are obtained from the selected similar plans. Two plan quality metrics—dosimetric result probability and dose deviation index—are proposed to quantify plan quality among prior similar plans. To evaluate the performance of the proposed method, we exported 927 clinically approved head and neck treatment plans. Eight organs at risk, including brain stem, cord, larynx, mandible, pharynx, oral cavity, left parotid and right parotid, were analyzed. Twelve suboptimal plans identified by dosimetric result probability were replanned to validate the capability of the proposed methods in identifying inferior plans. Results: After replanning, left and right parotid median doses are reduced by 31.7% and 18.2%, respectively; 83% of these cases would not be identified as suboptimal without the proposed similarity plan selection. Analysis of population plan quality reveals that average parotid sparing has been improving significantly over time (21.7% dosimetric result probability reduction from year 2006-2007 to year 2016-2017). Notably, the increasing dose sparing over time in retrospective plan quality analysis is strongly correlated with the increasing dose prescription ratios to the 2 planning targets, revealing the collective trend in planning conventions. Conclusions: The proposed similar plan retrieval and analysis methodology has been proven to be predictive of the current plan quality. Therefore, the proposed workflow can potentially be applied in the clinics as a real-time plan quality assurance tool. The proposed metrics can also serve the purpose of plan quality analytics in finding connections and historical trends in the clinical treatment planning workflow.
Minimizing Variability in Interpretation Modality Among Spanish-Speaking Patients With Limited English Proficiency
Authors: Villalona Seiichi , Jeannot Christian , Yanez Yuncosa Mery , Webb W. Alex , Boxtha Carol , Wilson Jason W. 
Published: June 2019

Introduction: Provider–patient language discrepancies can lead to misunderstandings about follow-up care instructions and decreased adherence to treatment that may contribute to disparities in health outcomes among patients with limited English proficiency (LEP). This observational study aimed to understand how emergency department (ED) staff went about treating patients with LEP and examine the impact of consistent interpretation modality on overall patient satisfaction and comprehension. Method: A cross-sectional study was conducted among Spanish-speaking patients with LEP presenting to the ED. A survey was administered at two different time points: after patients provided their history of present illness and after the patient received information regarding follow-up treatment. Results: Analysis of average visual analog scale (VAS) scores by consistency of interpretation suggested higher overall scores among participants that received care via the same communication modalities during both the history of present illness and at disposition, when compared with patients that did not. At both time points, video-based interpretation was associated with higher VAS scores in comparison to other modalities, whereas phone-based interpretation was associated with lower VAS scores. Conclusion: Providing consistent modes of interpretation to patient’s with LEP throughout their ED visits improved their overall satisfaction of care provided and understandings of discharge instructions.
Nebuliser cleaning and disinfection practice in the home among patients with cystic fibrosis
Authors: MacFarlane Mary , Carson Lesley , Crossan Amanda , Bell Jane , Moore John E , Millar B Cherie 
Published: June 2019

Background: Nebulised delivery of different classes of drugs is of fundamental importance in therapeutic regimens relating to both the management of disease progression in cystic fibrosis disease and its associated complications. The aim of this study was to determine if current nebuliser hygiene practices in the home environment by paediatric and adult cystic fibrosis populations are appropriate to ensure appropriate infection control and prevention measures have been addressed. Methods: An Audit Questionnaire Study was completed with adult cystic fibrosis patients ( n=20) or with parents of cystic fibrosis children ( n=24), through a healthcare professional interview on a one-to-one basis, during either a home visit or during patient/parent attendance at cystic fibrosis clinic. Results: Hygienic practices relating to nebuliser care varied, with paediatric carers more likely to clean and disinfect their devices. This study suggests there is much variation and confusion with regard to how to clean and disinfect nebulisers, as well as who is responsible for delivering this advice. Conclusion: The adult cystic fibrosis community in particular needs to be educated on practicalities associated with nebuliser hygiene and the reasons why this is important. Furthermore, to date there is a lack of a universally recommended guideline suitable for all types of cystic fibrosis nebulisers that all relevant pharmaceutical manufacturers advocate.
Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors
Authors: Wesolowski Robert , Sharma Neelesh , Reebel Laura , Rodal Mary Beth , Peck Alexandra , West Brian L. , Marimuthu Adhirai , Severson Paul , Karlin David A. , Dowlati Afshin , Le Mai H. , Coussens Lisa M. , Rugo Hope S. 
Published: June 2019

Purpose: To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods: In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results: A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3–4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug–drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57–100%. Conclusions: The combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration.
Integrative Analysis of Genome-Wide Association Studies and DNA Methylation Profile Identified Genetic Control Genes of DNA Methylation for Kashin-Beck Disease
Authors: Li Ping , Wu Cuiyan , Guo Xiong , Wen Yan , Liu Li , Liang Xiao , Du Yanan , Zhang Lu , Ma Mei , Cheng Shiqiang , Cheng Bolun , Wang Sen , Zhang Feng 
Published: June 2019

Objective Epigenetic modifications of DNA are regarded as a crucial factor for understanding the molecular basis of complex phenotypes. This study aims to uncover insight into the epigenetic modifications for Kashin-Beck disease (KBD) by integrating genome-wide association studies (GWAS), methylation quantitative trait loci (meQTLs), and DNA methylation profiles data. Design The knee articular cartilages of 5 KBD patients and 5 healthy controls were collected for DNA methylation profiling, using Illumina Infinium HumanMethylation450 BeadChip. Mass spectrograph validation of identified differently methylated genes was conducted using independent samples of 4 KBD patients and 3 healthy controls, together with a previous sample of 2743 Han Chinese individuals of GWAS study for KBD and a study of 697 normal subjects for meQTLs annotation datasets. KBD GWAS single nucleotide polymorphisms (SNPs) and normal meQTLs SNPs were integrated with DNA methylation profiles of KBD articular cartilage to identify genetic control (GC) genes of DNA methylation for KBD. Quantitative polymerase chain reaction (qPCR) was performed to validate the mRNA expression of several identified candidate genes. Results A total of 162 CpG sites, 253 SNPs, and 123 GC genes for KBD were identified. Enrichment analysis detected 642 marked GO terms and 19 KEGG pathways ( P < 0.05). Six potential key GC genes were conducted for qPCR experiment (ERG, MN1, MITF, WISP1, TRIO, and NOSTRIN). Conclusions The results suggest that GC genes of DNA methylation may lead to the erosion of cartilage in KBD, which may help us in understanding the epigenetic alteration of KBD.
Pharmacokinetics and tolerability of inhaled levodopa from a new dry-powder inhaler in patients with Parkinson’s disease
Authors: Luinstra Marianne , Rutgers Wijnand , van Laar Teus , Grasmeijer Floris , Begeman Anja , Isufi Valmira , Steenhuis Luc , Hagedoorn Paul , de Boer Anne , Frijlink Henderik W. 
Published: June 2019

Background: Inhaled levodopa may quickly resolve off periods in Parkinson’s disease. Our aim was to determine the pharmacokinetics and tolerability of a new levodopa dry-powder inhaler. Methods: A single-centre, single-ascending, single-dose–response study was performed. Over three visits, eight Parkinson’s disease patients (not in the ‘off state’) received by inhalation 30 mg or 60 mg levodopa, or their regular oral levodopa. Maximum levodopa plasma concentration ( Cmax), time to maximum plasma concentration (Tmax) and area under the concentration time curve 0–180 min were determined. Spirometry was performed three times at each visit. Results: After inhalation, levodopa Tmax occurred within 15 min in all participants, whereas after oral administration, Tmax ranged from 20 min to 90 min. The bioavailability of inhaled levodopa without carboxylase inhibitor was 53% relative to oral levodopa with carboxylase inhibitor. No change in lung-function parameters was observed and none of the patients experienced cough or dyspnoea. No correlation was observed between inhalation parameters and levodopa pharmacokinetic parameters. Conclusion: Inhaled levodopa is well tolerated, absorbed faster than oral levodopa, and can be robustly administered over a range of inhalation flow profiles. It therefore appears suitable for the treatment of off periods in Parkinson’s disease.