bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and efficient copper-mediated 18F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying
Authors: Lahdenpohja Salla Orvokki , Rajala Noora Annika , Rajander Johan , Kirjavainen Anna Kaarina 
Published: October 2019

Abstract

Background
Copper-mediated radiofluorination is a straightforward method to produce a variety of [18F]fluoroarenes and [18F]fluoroheteroarenes. To minimize the number of steps in the production of 18F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free 18F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.

Results
Solid phase extraction with Cu (OTf)2 in dimethylacetamide is a suitable activation method for [18F]fluoride. Elution efficiency with Cu (OTf)2 is up to 79% and radiochemical yield (RCY) of a variety of model molecules in the crude reaction mixture has reached over 90%. Clinically relevant molecules, norepinephrine transporter tracer [18F]NS12137 and monoamine transporter tracer [18F]CFT were produced with 16.5% RCY in 98 min and 5.3% RCY in 64 min, respectively.

Conclusions
Cu (OTf)2 is a suitable elution agent for releasing [18F]fluoride from an anion exchange cartridge. The method is fast and efficient and the Cu-complex is customizable after the release of [18F]fluoride. Alterations in the [18F]fluoride elution techniques did not have a negative effect on the subsequent labelling reactions. We anticipate this improved [18F]fluoride elution technique to supplant the traditional azeotropic drying of [18F]fluoride in the long run and to concurrently enable the variations of the copper-complex.
Translation and validation of the Indian Takayasu clinical activity score (ITAS2010) for the Brazilian Portuguese language
Authors: Fritsch Scheila , Copes Rafaela Martinez , Savioli Bruna , de Aguiar Mariana Freitas , Ciconelli Rozana Mesquita , Azevedo Valderílio Feijó , de Souza Alexandre W. S. 
Published: October 2019

Abstract

Background
The Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil.

Methods
For this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement.

Results
The correlation coefficient for the ITAS2010 score between the two raters was high (r = 0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828–0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r = 0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292–0.790). The ITAS2010 at baseline was compared with the physician’s global assessment (PGA) and with Kerr’s criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0–3.0) vs. 0.0 (0.0–0.0); p = 0.0025]. Patients with active disease according to the Kerr’s criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0–7.0) vs. 0.0 (0.0–0.0); p = 0.0068].

Conclusions
The Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.
Evaluation of a programming algorithm for deep brain stimulation in dystonia used in a double-blind, sham-controlled multicenter study
Authors:   for the DBS study group for dystonia, Steigerwald Frank , Kirsch Anna Dalal , Kühn Andrea A. , Kupsch Andreas , Mueller Joerg , Eisner Wilhelm , Deuschl Günther , Falk Daniela , Schnitzler Alfons , Skogseid Inger Marie , Vollmer-Haase Juliane , Ip Chi W. , Tronnier Volker , Vesper Jan , Naumann Markus , Volkmann Jens 
Published: October 2019

Abstract

Background
Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia.

Methods
A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming.

Results
The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (n = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (n = 63) and 53 ± 31% at 5 years (n = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (n = 9) correlated significantly with improvement after 3 years, but not 5 years.

Conclusions
Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome.

Trial registration
ClinicalTrials.gov NCT00142259.
An automatic nuclei segmentation method based on deep convolutional neural networks for histopathology images
Authors: Jung Hwejin , Lodhi Bilal , Kang Jaewoo 
Published: October 2019

AbstractBackgroundSince nuclei segmentation in histopathology images can provide key information for identifying the presence or stage of a disease, the images need to be assessed carefully. However, color variation in histopathology images, and various structures of nuclei are two major obstacles in accurately segmenting and analyzing histopathology images. Several machine learning methods heavily rely on hand-crafted features which have limitations due to manual thresholding.ResultsTo obtain robust results, deep learning based methods have been proposed. Deep convolutional neural networks (DCNN) used for automatically extracting features from raw image data have been proven to achieve great performance. Inspired by such achievements, we propose a nuclei segmentation method based on DCNNs. To normalize the color of histopathology images, we use a deep convolutional Gaussian mixture color normalization model which is able to cluster pixels while considering the structures of nuclei. To segment nuclei, we use Mask R-CNN which achieves state-of-the-art object segmentation performance in the field of computer vision. In addition, we perform multiple inference as a post-processing step to boost segmentation performance. We evaluate our segmentation method on two different datasets. The first dataset consists of histopathology images of various organ while the other consists histopathology images of the same organ. Performance of our segmentation method is measured in various experimental setups at the object-level and the pixel-level. In addition, we compare the performance of our method with that of existing state-of-the-art methods. The experimental results show that our nuclei segmentation method outperforms the existing methods.ConclusionsWe propose a nuclei segmentation method based on DCNNs for histopathology images. The proposed method which uses Mask R-CNN with color normalization and multiple inference post-processing provides robust nuclei segmentation results. Our method also can facilitate downstream nuclei morphological analyses as it provides high-quality features extracted from histopathology images.
Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice
Authors: Kang Ju-Bin , Park Dong-Ju , Shah Murad-Ali , Kim Myeong-Ok , Koh Phil-Ok 
Published: October 2019

Abstract
Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.
The effect of duration of dependence and daily dose of tramadol in tramadol dependent patients on cognitive performance
Authors: Ahmad Hossam Eddin Khalifa , Darweesh Alaa Eldin Mohamed , Hassaan Shehab Hassan Mahmoud , Nooman Mostafa , Shaaban Islam , Sayed Sayed Mostafa 
Published: October 2019

Abstract

Background
Tramadol dependence represents a major medical and legal hazardous phenomenon in the last decade. It is a synthetic opiate analgesic which exerts its therapeutic effect by its action on μ opioid receptors. It has a weak dependence ability. The present study investigated the effect of duration of dependence and daily dose of tramadol on cognitive performance. Cognitive functions were assessed using the following: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) test, Brief Visuospatial Memory Test–Revised (BVMT-R), Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the P300 (ERP), and conventional electroencephalogram.

Results
There was a non-significant negative correlation between the daily dose of tramadol and cognitive performance as regards IQ, Mini-Mental State Examination, MoCA score, P300 reaction time (μs), and deterioration index (r = − 0.08, P = 0.689; r = − 0.02, P = 0.896; r = − 0.11, P = 0.554; r = − 0.11, P = 0.581, r = − 0.17; P = 0.368, respectively). Additionally, the results showed non-significant negative correlation between the duration of dependence and the cognitive performance (r = − 0.19, P = 0.325; r = − 0.15, P = 0.424; r = − 0.30, P = 0.108; r = − 0.02, P = 0.909; r = − 0.02, P = 0.937, respectively).

Conclusion
Daily dose and duration of tramadol dependence have a negative but non-significant effect on cognitive performance.
Changes in employment and insurance for patients with cancer receiving safety net services.
Authors: Caston Nicole , Williams Courtney , Balch Alan James , Gallagher Kathleen D. , Rocque Gabrielle Betty 
Published: October 2019

104 Background: Under-resourced patients with cancer often face financial burdens due, not only to costs of treatment, but also from side effects that prevent individuals’ ability to work, which impact employment status and may cause insurance coverage loss. Financial assistance may be sought from safety net programs, which provide both material support and financial counseling. However, knowledge of the impact of cancer on employment and insurance in a population seeking safety net services is limited. Methods: This observational, cross-sectional study uses data on safety net services from a nationwide survey conducted in July 2017 and distributed by the Patient Advocate Foundation (PAF). The survey respondents included patients with cancer who received services from PAF from July 2016 to June 2017. Descriptive statistics were calculated using frequencies for categorical variables. Results: A total of 508 patients with cancer completed the survey. Most patients had a diagnosis of breast cancer (47%), followed by myeloma (13%), and prostate cancer (8%). The majority of patients reported that their illness affected their employment (67%); by either job loss (13%), income loss (24%), or inability to work as usual (27%). Of these patients, 27% lost their insurance coverage. Those able to enroll in a new insurance plan reported having more expensive rates (40%) and fewer covered services (36%) compared to their previous coverage. The most commonly utilized governmental safety net services were Social Security Disability Insurance (19%) and Medicaid (12%). Non-governmental safety net services such as financial assistance from non-profits (27%) and free medication from drug companies (13%) were also frequently used. Beyond their insurance coverage, cancer patients still needed assistance paying for diagnostic tests (18%), clinic visit fees (23%), and prescription drugs (15%) from the safety net program. Conclusions: Cancer patients commonly experience financial burden due to losses in employment and insurance, resulting in need for safety net programs. Further work is needed to identify approaches to reducing the adverse financial impact of cancer care.
Risk factors for healthcare utilization in patients with newly diagnosed advanced lung cancer.
Authors: Ray Emily Miller , Hinton Sharon Peacock , Reeder-Hayes Katherine Elizabeth 
Published: October 2019

111 Background: Advanced lung cancer (ALC) is a symptomatic disease often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve care delivery. We aimed to identify newly diagnosed ALC patients at highest risk for subsequent healthcare utilization. Methods: We identified patients in SEER-Medicare with: ALC (stage IIIB-IV SCLC or NSCLC), diagnosed 2007-13; continuous enrollment -6 months from diagnosis through death or 12/2014; and an index hospitalization within 7 days of ALC diagnosis. Our primary outcomes were 30-day re-hospitalization and emergency department (ED) use. We used a time-to-event model with multivariate regression to identify risk factors. Results: Of ALC patients in SEER-Medicare, 54% (n=28,976) had an index hospitalization. Of those who survived to discharge, by 6 months, 47% had been re-hospitalized, and 50% had enrolled in hospice. Only 37% of patients ever received systemic treatment for their cancer, and the median time to treatment was 46 days. The 30-day ED visit and readmission rates were 13% and 35%, respectively. Pre-cancer ED use or hospitalization, SCLC, and prolonged length of stay were associated with higher risk of 30-day utilization. Palliative care consultation and discharge to hospice were associated with substantially lower risk of 30-day readmission. Conclusions: Many newly diagnosed ALC patients experience an early return to the hospital. These patients may benefit from increased access to palliative and other supportive care during index hospitalization to prevent subsequent healthcare utilization. [Table: see text]
Value appraisal of FDA approved cancer drugs over the past decade.
Authors: Huey Ryan , Anand Seerat , Rogers Jane Elizabeth , Dasari Arvind , Varadhachary Gauri Rajani , Gothwal Anirudh , Loree Jonathan M. , Ellis Lee M. , Overman Michael J. , Raghav Kanwal Pratap Singh 
Published: October 2019

115 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.
Capturing discrete complete staging elements in EPIC for new and progressing breast (B) and prostate (P) cancer patients: A quality training program pilot.
Authors: Bosserman Linda D. , Morse Denise , McNeese Kathleen , Atcha Ridaa , Patel Niki Himat 
Published: October 2019

117 Background: Staging is a fundamental quality metric. Entry of discrete elements of staging in the EHR supports & improves efficiencies for clinical notes, therapy summaries, survivorship plans, clinical decision making, pathway use, timely authorizations, clinical trial eligibility evaluations, as well as clinical, financial & quality outcomes. Staging of all new & progressing patients in our EPIC EHR was set as a priority in 2018 but baseline entry through 2018 was below target goals. Methods: A Staging QTP project group was formed & participated in the COH-ASCO QTP Fall training. Baseline capture of staging data in EPIC for campus and community (enterprise) sites for Breast (B) & Prostate (P) patients was collected. QTP processes were used to develop and implement a 12-week pilot with PDSA cycles at weeks 8 and 12. B & P cancer patients seen by 3 B & 2 P medical oncologists (MO), 5B surgeons (S) & 3P urologists (U) agreed to participate in a pilot study. Disease leads determined the elements of complete staging: 9-10 for B & 8 for P. Training was done for all campus APPs & for doctors in the pilot. Follow up by the QTP team was done at clinics during the pilot. Reports were built to capture specific staging elements for B & P patients by doctor. Reports were sent out starting week 9 indicating patients without complete staging with missing elements. A survey about the process was done by participant MDs & APPS weeks 8 & 12. Results: Baseline enterprise wide complete staging in Epic was 6% for B cancer & 3% for P cancer. 6 week PDSA showed capture of complete staging for B-MO & S was 20% and for P-MO & U was 12%. QTP Pilot ends 6/19 & abstract data will be updated for the staging & survey results. Additional results on complete staging for progressing patients is being captured. Conclusions: Complete staging in the EHR requires definition, training, resourcing, leadership support and feedback. Initial results show all new patients had initial staging data entered and complete staging rates increased significantly for new B & P cancer patients before weekly feedback was sent. Analysis of survey results will inform future PDSA cycles & plans for complete staging enterprise wide.
Changing treatment patterns in patients with stage IV non-small cell lung cancer (NSCLC) from United States community-based oncology practices.
Authors: Yong Candice , Seal Brian , Coutinho Anna D. , Lunacsek Orsolya , Dean Bonnie B. , Willey Joanne P. , Eaddy Michael , Cotarla Ion , Mehra Ranee 
Published: October 2019

13 Background: This study evaluated the shift in treatment patterns in Stage IV NSCLC following the approval of immune-oncology (IO) agents in the US. Methods: A retrospective cohort study was performed using structured data from a US community-based oncology electronic medical record (EMR) database for care received from Jan 2015-May 2018. The study sample included patients with Stage IV NSCLC, ≥18 years of age initiating first-line (1L) treatment with chemotherapy (chemo) or IO agents and classified into 3 groups: chemo alone, IO alone, or chemo+IO. Treatment patterns in 1L and treatment switch patterns in second-line (2L) are reported. A sub-group analysis of patients initiating 1L therapy during the last 6 months of the study period (Dec 2017-May 2018) was conducted to explore changes in 1L treatment patterns in the post-IO approval setting. Chart reviews were done for a subset of patients initiating 1L from Jan 2017-May 2018 to extract information on programmed cell death ligand 1 (PD-L1) testing and evaluate the association of PD-L1 expression levels with receipt of IO therapy. Results: Between Jan 2015-May 2018, 1,969 patients received 1L therapy with a chemo or IO agent. Mean age (SD) was 69.0 (10.1) years, with 44.7% female. The majority of patients (79%, n = 1570) initiated 1L therapy with chemo alone and 21% initiated IO (alone [14%, n = 271] or in combination with chemo [7%, n = 128]). Of 1L patients, 41% (n = 809) were treated with 2L therapy. Of the 1L chemo alone group, 37% (n = 580) received IO in 2L. The use of IO agents in 1L increased from 21% to 48% (n = 147) in the sub-group analysis of 305 patients initiating therapy Dec 2017-May 2018. In the subset of 62 patients whose charts were reviewed, 87% (n = 54) had their tumor tested for PD-L1, of which 37% (n = 20) had high (≥50%) expression values. The majority of high-PD-L1 patients were treated in 1L with IO alone (80%, n = 16), followed by chemo+IO (15%; n = 3), and only 5% (n = 1) received chemo alone. Conclusions: Initially, IO was used as 2L treatment for Stage IV NSCLC, but IO use shifted to 1L setting in the US by the end of 2017. The use of IO therapy alone or with chemotherapy in 1L was more likely in patients with ≥50% PD-L1 expression level.