bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer–Containing Antibody–Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies
Authors: Flynn Michael J. , Zammarchi Francesca , Tyrer Peter C. , Akarca Ayse U. , Janghra Narinder , Britten Charles E. , Havenith Carin E.G. , Levy Jean-Noel , Tiberghien Arnaud , Masterson Luke A. , Barry Conor , D'Hooge Francois , Marafioti Teresa , Parren Paul W.H.I. , Williams David G. , Howard Philip W. , van Berkel Patrick H. , Hartley John A. 
Published: August 2016

AbstractDespite the many advances in the treatment of hematologic malignancies over the past decade, outcomes in refractory lymphomas remain poor. One potential strategy in this patient population is the specific targeting of IL2R-α (CD25), which is overexpressed on many lymphoma and leukemic cells, using antibody–drug conjugates (ADC). ADCT-301 is an ADC composed of human IgG1 HuMax-TAC against CD25, stochastically conjugated through a dipeptide cleavable linker to a pyrrolobenzodiazepine (PBD) dimer warhead with a drug–antibody ratio (DAR) of 2.3. ADCT-301 binds human CD25 with picomolar affinity. ADCT-301 has highly potent and selective cytotoxicity against a panel of CD25-expressing human lymphoma cell lines. Once internalized, the released warhead binds in the DNA minor groove and exerts its potent cytotoxic action via the formation of DNA interstrand cross-links. A strong correlation between loss of viability and DNA cross-link formation is demonstrated. DNA damage persists, resulting in phosphorylation of histone H2AX, cell-cycle arrest in G2–M, and apoptosis. Bystander killing of CD25-negative cells by ADCT-301 is also observed. In vivo, a single dose of ADCT-301 results in dose-dependent and targeted antitumor activity against both subcutaneous and disseminated CD25-positive lymphoma models. In xenografts of Karpas 299, which expressed both CD25 and CD30, marked superiority over brentuximab vedotin (Adcetris) is observed. Dose-dependent increases in DNA cross-linking, γ-H2AX, and PBD payload staining were observed in tumors in vivo indicating a role as relevant pharmacodynamic assays. Together, these data support the clinical testing of this novel ADC in patients with CD25-expressing tumors. Mol Cancer Ther; 15(11); 2709–21. ©2016 AACR.
Expression of Genes Involved in Vascular Morphogenesis and Maturation Predicts Efficacy of Bevacizumab-Based Chemotherapy in Patients Undergoing Liver Resection
Authors: Stremitzer Stefan , Zhang Wu , Yang Dongyun , Ning Yan , Sunakawa Yu , Matsusaka Satoshi , Parekh Anish , Okazaki Satoshi , Hanna Diana , Astrow Stephanie H. , Moran Miriana , Hernandez Jose , Stephens Craig , Scherer Stefan J. , Stift Judith , Wrba Friedrich , Gruenberger Thomas , Lenz Heinz-Josef 
Published: August 2016

Abstract
Angiogenesis-related gene expression is associated with the efficacy of anti-VEGF therapy. We tested whether intratumoral mRNA expression levels of genes involved in vascular morphogenesis and early vessel maturation predict response, recurrence-free survival (RFS), and overall survival (OS) in a unique cohort of patients with colorectal liver metastases (CLM) treated with bevacizumab-based chemotherapy followed by curative liver resection. Intratumoral mRNA was isolated from resected bevacizumab-pretreated CLM from 125 patients. In 42 patients, a matching primary tumor sample collected before bevacizumab treatment was available. Relative mRNA levels of 9 genes (ACVRL1, EGFL7, EPHB4, HIF1A, VEGFA, VEGFB, VEGFC, FLT1, and KDR) were analyzed by RT-PCR and evaluated for associations with response, RFS, and OS. P values for the associations between the individual dichotomized expression level and RFS were adjusted for choosing the optimal cut-off value. In CLM, high expression of VEGFB, VEGFC, HIF1A, and KDR and low expression of EGFL7 were associated with favorable RFS in multivariable analysis (P &lt; 0.05). High ACVRL1 levels predicted favorable 3-year OS (P = 0.041) and radiologic response (PR = 1.093, SD = 0.539, P = 0.002). In primary tumors, low VEGFA and high EGFL7 were associated with radiologic and histologic response (P &lt; 0.05). High VEGFA expression predicted shorter RFS (10.1 vs. 22.6 months; HR = 2.83, P = 0.038). High VEGFB (46% vs. 85%; HR = 5.75, P = 0.009) and low FLT1 (55% vs. 100%; P = 0.031) predicted lower 3-year OS rates. Our data suggest that intratumoral mRNA expression of genes involved in vascular morphogenesis and early vessel maturation may be promising predictive and/or prognostic biomarkers. Mol Cancer Ther; 15(11); 2814–21. ©2016 AACR.
Evaluation of the AMPS Boundary Layer Simulations on the Ross Ice Shelf with Tower Observations
Authors: Wille Jonathan D. , Bromwich David H. , Nigro Melissa A. , Cassano John J. , Mateling Marian , Lazzara Matthew A. , Wang Sheng-Hung 
Published: August 2016

AbstractFlight operations in Antarctica rely on accurate weather forecasts aided by the numerical predictions primarily produced by the Antarctic Mesoscale Prediction System (AMPS) that employs the polar version of the Weather Research and Forecasting (Polar WRF) Model. To improve the performance of the model’s Mellor–Yamada–Janjić (MYJ) planetary boundary layer (PBL) scheme, this study examines 1.5 yr of meteorological data provided by the 30-m Alexander Tall Tower! (ATT) automatic weather station on the western Ross Ice Shelf from March 2011 to July 2012. Processed ATT observations at 10-min intervals from the multiple observational levels are compared with the 5-km-resolution AMPS forecasts run daily at 0000 and 1200 UTC. The ATT comparison shows that AMPS has fundamental issues with moisture and handling stability as a function of wind speed. AMPS has a 10-percentage-point (i.e., RH unit) relative humidity dry bias year-round that is highest when katabatic winds from the Byrd and Mulock Glaciers exceed 15 m s−1. This is likely due to nonlocal effects such as errors in the moisture content of the katabatic flow and AMPS not parameterizing the sublimation from blowing snow. AMPS consistently overestimates the wind speed at the ATT by 1–2 m s−1, in agreement with previous studies that attribute the high wind speed bias to the MYJ scheme. This leads to reduced stability in the simulated PBL, thus affecting the model’s ability to properly simulate the transfer of heat and momentum throughout the PBL.
New Tools for Comparing Beliefs about the Timing of Recurrent Events with Climate Time Series Datasets
Authors: Stiller-Reeve Mathew Alexander , Stephenson David B. , Spengler Thomas 
Published: August 2016

Abstract
For climate services to be relevant and informative for users, scientific data definitions need to match users’ perceptions or beliefs. This study proposes and tests novel yet simple methods to compare beliefs of timing of recurrent climatic events with empirical evidence from multiple historical time series. The methods are tested by applying them to the onset date of the monsoon in Bangladesh, where several scientific monsoon definitions can be applied, yielding different results for monsoon onset dates. It is a challenge to know which monsoon definition compares best with people’s beliefs. Time series from eight different scientific monsoon definitions in six regions are compared with respondent beliefs from a previously completed survey concerning the monsoon onset.
Beliefs about the timing of the monsoon onset are represented probabilistically for each respondent by constructing a probability mass function (PMF) from elicited responses about the earliest, normal, and latest dates for the event. A three-parameter circular modified triangular distribution (CMTD) is used to allow for the possibility (albeit small) of the onset at any time of the year. These distributions are then compared to the historical time series using two approaches: likelihood scores, and the mean and standard deviation of time series of dates simulated from each belief distribution.
The methods proposed give the basis for further iterative discussion with decision-makers in the development of eventual climate services. This study uses Jessore, Bangladesh, as an example and finds that a rainfall definition, applying a 10 mm day−1 threshold to NCEP–NCAR reanalysis (Reanalyis-1) data, best matches the survey respondents’ beliefs about monsoon onset.
Sympathy, empathy, and compassion: A grounded theory study of palliative care patients’ understandings, experiences, and preferences
Authors: Sinclair Shane , Beamer Kate , Hack Thomas F , McClement Susan , Raffin Bouchal Shelley , Chochinov Harvey M , Hagen Neil A. 
Published: August 2016

Background: Compassion is considered an essential element in quality patient care. One of the conceptual challenges in healthcare literature is that compassion is often confused with sympathy and empathy. Studies comparing and contrasting patients’ perspectives of sympathy, empathy, and compassion are largely absent. Aim: The aim of this study was to investigate advanced cancer patients’ understandings, experiences, and preferences of “sympathy,” “empathy,” and “compassion” in order to develop conceptual clarity for future research and to inform clinical practice. Design: Data were collected via semi-structured interviews and then independently analyzed by the research team using the three stages and principles of Straussian grounded theory. Setting/participants: Data were collected from 53 advanced cancer inpatients in a large urban hospital. Results: Constructs of sympathy, empathy, and compassion contain distinct themes and sub-themes. Sympathy was described as an unwanted, pity-based response to a distressing situation, characterized by a lack of understanding and self-preservation of the observer. Empathy was experienced as an affective response that acknowledges and attempts to understand individual’s suffering through emotional resonance. Compassion enhanced the key facets of empathy while adding distinct features of being motivated by love, the altruistic role of the responder, action, and small, supererogatory acts of kindness. Patients reported that unlike sympathy, empathy and compassion were beneficial, with compassion being the most preferred and impactful. Conclusion: Although sympathy, empathy, and compassion are used interchangeably and frequently conflated in healthcare literature, patients distinguish and experience them uniquely. Understanding patients’ perspectives is important and can guide practice, policy reform, and future research.
Spot fluoroscopy: a novel innovative approach to reduce radiation dose in neurointerventional procedures
Authors: Borota Ljubisa , Jangland Lars , Åslund Per-Erik , Ronne-Engström Elisabeth , Nyberg Christoffer , Mahmoud Ehab , Sakaguchi Takuya , Patz Andreas 
Published: August 2016

Background Increased interest in radiation dose reduction in neurointerventional procedures has led to the development of a method called “spot fluoroscopy” (SF), which enables the operator to collimate a rectangular or square region of interest anywhere within the general field of view. This has potential advantages over conventional collimation, which is limited to symmetric collimation centered over the field of view. Purpose To evaluate the effect of SF on the radiation dose. Material and Methods Thirty-five patients with intracranial aneurysms were treated with endovascular coiling. SF was used in 16 patients and conventional fluoroscopy in 19. The following parameters were analyzed: the total fluoroscopic time, the total air kerma, the total fluoroscopic dose-area product, and the fluoroscopic dose-area product rate. Statistical differences were determined using the Welch’s t-test. Results The use of SF led to a reduction of 50% of the total fluoroscopic dose-area product (CF = 106.21 Gycm2, SD = 99.06 Gycm2 versus SF = 51.80 Gycm2, SD = 21.03 Gycm2, p = 0.003884) and significant reduction of the total fluoroscopic dose-area product rate (CF = 1.42 Gycm2/min, SD = 0.57 Gycm2/s versus SF = 0.83 Gycm2/min, SD = 0.37 Gycm2/min, p = 0.00106). The use of SF did not lead to an increase in fluoroscopy time or an increase in total fluoroscopic cumulative air kerma, regardless of collimation. Conclusion The SF function is a new and promising tool for reduction of the radiation dose during neurointerventional procedures.
Comparative tolerability of treatments for acute migraine: A network meta-analysis
Authors: Thorlund Kristian , Toor Kabirraaj , Wu Ping , Chan Keith , Druyts Eric , Ramos Elodie , Bhambri Rahul , Donnet Anne , Stark Richard , Goadsby Peter J 
Published: August 2016

IntroductionMigraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified.MethodsWe performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting.ResultsOur search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes.DiscussionIn summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.
Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine
Authors: Lee Jeungchan , Lin Richard L , Garcia Ronald G , Kim Jieun , Kim Hyungjun , Loggia Marco L , Mawla Ishtiaq , Wasan Ajay D , Edwards Robert R , Rosen Bruce R , Hadjikhani Nouchine , Napadow Vitaly 
Published: August 2016

BackgroundImpaired sensory processing in migraine can reflect diminished habituation, increased activation, or even increased gain or amplification of activity from the primary synapse in the brainstem to higher cortical/subcortical brain regions.MethodsWe scanned 16 episodic migraine (interictal) and 16 healthy controls (cross-sectional study), and evaluated brain response to innocuous air-puff stimulation over the right forehead in the ophthalmic nerve (V1) trigeminal territory. We further evaluated habituation, and cortical/subcortical amplification relative to spinal trigeminal nucleus (Sp5) activation.ResultsMigraine subjects showed greater amplification from Sp5 to the posterior insula and hypothalamus. In addition, while controls showed habituation to repetitive sensory stimulation in all activated cortical regions (e.g. the bilateral posterior insula and secondary somatosensory cortices), for migraine subjects, habituation was not found in the posterior insula. Moreover, in migraine, the habituation slope was correlated with the amplification ratio in the posterior insula and secondary somatosensory cortex, i.e. greater amplification was associated with reduced habituation in these regions.ConclusionsThese findings suggest that in episodic migraine, amplified information processing from spinal trigeminal relay nuclei is linked to an impaired habituation response. This phenomenon was localized in the posterior insula, highlighting the important role of this structure in mechanisms supporting altered sensory processing in episodic migraine.
Reversible cerebral vasoconstriction syndrome precipitated by airplane descent: Case report
Authors: Hiraga Akiyuki , Aotsuka Yuya , Koide Kyosuke , Kuwabara Satoshi 
Published: August 2016

Background Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasospasm. Vasoactive agents and childbirth have been reported as precipitating factors for RCVS; however, RCVS induced by altitude change or air travel has rarely been reported. Case We present a case of a 74-year-old woman who presented with thunderclap headache during airplane descent. Magnetic resonance angiography demonstrated segmental vasoconstriction that improved 9 days after onset. Conclusion These findings indicate that airplane descent may be a trigger of RCVS. The time course of headache in the present case was similar to that of prolonged headache attributed to airplane travel, indicating that RCVS during air travel may have previously been overlooked and that some headache attributed to airplane travel cases may represent a milder form of RCVS.
Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China
Authors: Guo Qinyue , Fan Ping , Luo Jing , Wu Shufang , Sun Hongzhi , He Lan , Zhou Bo 
Published: August 2016

Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20–30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1–L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.
Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosus
Authors: Cramarossa G , Urowitz M B , Su J , Gladman D , Touma Z 
Published: August 2016

Background Systemic lupus erythematosus (SLE) patients are often treated with glucocorticoids, which place them at risk of bone loss. Objectives The objectives of this article are to determine: (1) the prevalence of low bone mineral density (BMD) and factors associated with low BMD and (2) the prevalence of symptomatic fragility fractures in inception patients of the Toronto Lupus Cohort (TLC). Methods Prospectively collected data from the TLC (1996–2015) of inception patients’ first BMD were analyzed. For pre-menopausal women/males <50 years, BMD ‘below expected range for age’ was defined by Z-score ≤ −2.0 SD. For post-menopausal women/males age 50 or older, osteoporosis was defined by T-score ≤ −2.5 SD and low bone mass by T-score between −1.0 and −2.5 SD. Patients’ BMDs were defined as abnormal if Z-score ≤ −2.0 or T-score < −1.0 SD, and the remainder as normal. Descriptive analysis and logistic regression were employed. Results Of 1807 patients, 286 are inception patients with BMD results (mean age 37.9 ± 13.7 years); 88.8% are female. The overall prevalence of abnormal BMD is 31.5%. In pre-menopausal women ( n = 173), the prevalence of BMD below expected range is 17.3%. In post-menopausal women ( n = 81), the prevalence of osteoporosis and low BMD are 12.3% and 43.2%, respectively. Age and cumulative dose of glucocorticoids are statistically significantly associated with abnormal BMD in multivariate analysis. Of 769 inception patients from TLC, 11.1% experienced symptomatic fragility fractures (peripheral and vertebral) over the course of their disease. Conclusion The prevalence of low BMD is high in SLE patients, and is associated with older age and higher cumulative glucocorticoid dose.
Electromyographic activity of the shoulder muscles during rehabilitation exercises in subjects with and without subacromial pain syndrome: a systematic review
Authors: Kinsella Rita , Pizzari Tania 
Published: August 2016

Background Subacromial pain syndrome (SPS) is a common cause of shoulder pain and muscle activity deficits are postulated to contribute to the development and progression of the disorder. The purpose of this systematic review was to definitively determine whether evidence exists of differences in electromyography (EMG) characteristics between subjects with and without SPS. Methods Six key databases were searched: MEDLINE, EMBASE, CINAHL, SPORTdiscus, PEDro and The Cochrane Library (inception to May 2016). The search yielded 1414 records using terms relating to shoulder impingement, EMG, scapular and rotator cuff muscles. Twenty-two papers remained once duplicates were removed and selection criteria applied. Data extraction, quality assessment and data synthesis were performed. Effect sizes and 95% confidence intervals were calculated. Results There was limited evidence that serratus anterior has lower amplitude, delayed activation and earlier termination in SPS participants. For the majority of muscles, regardless of task, load or arm position, significant differences were not demonstrated or results were contradictory. Conclusions The understanding of SPS is changing and EMG appears unable to capture the complexities associated with this condition. Addressing aberrant movement patterns and facilitating balanced activation of all shoulder muscles may be a more appropriate treatment direction for the future.