bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab
Authors: Voors-Pette Christine , Lebozec Kristell , Dogterom Peter , Jullien Laurie , Billiald Philippe , Ferlan Pauline , Renaud Lionel , Favre-Bulle Olivier , Avenard Gilles , Machacek Matthias , Plétan Yannick , Jandrot-Perrus Martine 
Published: April 2019

Objective—
ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT017 in healthy subjects.

Approach and Results—
Six cohorts of 8 healthy male and female subjects each received ascending single doses of ACT017 (n=6) or placebo (n=2) as a 6-hour intravenous infusion, with ¼ of the total dose administered within 15 minutes and the rest of the dose (¾ of the total dose) administered within 5 hours and 45 minutes. The 6 investigated doses ranged from 62.5 to 2000 mg. All doses of ACT017 were well tolerated, and no serious adverse events occurred during the study. None of the subjects reported an infusion site reaction. Template bleeding time was not affected in a clinically significant manner by any of the ACT017 doses. Plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, increased linearly with the dose received as were the established pharmacokinetics values. There was no change in the platelet count, platelet GPVI expression assessed by flow cytometry, or plasma levels of soluble GPVI assessed by ELISA. In contrast, administration of ACT017 inhibited collagen-induced platelet aggregation measured by light transmission aggregometry on platelet-rich plasma, and the extent and duration of the effect were dose-dependent.

Conclusions—
The novel antiplatelet agent ACT017 has consistent pharmacokinetic/pharmacodynamic properties and favorable safety and tolerability profiles warranting further clinical development.
Determinants of Early Versus Delayed Neurological Deterioration in Intracerebral Hemorrhage
Authors: You Shoujiang , Zheng Danni , Delcourt Candice , Sato Shoichiro , Cao Yongjun , Zhang Shihong , Yang Jie , Wang Xia , Lindley Richard I. , Robinson Thompson , Anderson Craig S. , Chalmers John ,   for the INTERACT-2 Investigators*
Published: April 2019

Background and Purpose—
We investigated factors associated with early and delayed neurological deterioration (END and DND, respectively) after acute spontaneous intracerebral hemorrhage in the main INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial)-2.

Methods—
INTERACT-2 was a randomized trial of early intensive versus guideline-recommended blood pressure lowering in hypertensive intracerebral hemorrhage (<6 hours from symptom onset) patients. END and DND were defined as a ≥4-point increase on the National Institutes of Health Stroke Scale or ≥2-point decrease on Glasgow Coma Scale, in periods baseline to 24 hours and 24 hours to 7 days, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and 90-day outcomes (death and dependency on the modified Rankin Scale).

Results—

Of 2598 participants, 450 (17.3%) had either END or DND. Non-China recruitment, higher systolic blood pressure, larger baseline hematoma volume, left hemisphere hematoma location, intraventricular hemorrhage, subarachnoid extension, heterogeneous hematoma density, and cerebral white matter lesions, were predictors of END (all
P
≤0.045). Higher systolic blood pressure, lower diastolic blood pressure, higher glucose, larger baseline hematoma volume, intraventricular hemorrhage, lobar location, brain atrophy, and heterogeneous hematoma density were predictors of DND (all
P
≤0.042). END and DND were both related to death, and death or major disability (modified Rankin Scale scores of 3–6), in adjusted analyses (
P
<0.001).

Conclusions—
Common variables, most directly related to the intracerebral hemorrhage morphology and underlying cerebral features, determine END and DND and their influence on poor outcomes of death and major disability.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00716079.
A new species of Acianthera (Pleurothallidinae, Orchidaceae) from Brazil
Authors: PONERT JAN , CHUMOVÁ ZUZANA , MANDÁKOVÁ TEREZIE , TRÁVNÍČEK PAVEL 
Published: April 2019

Acianthera sudae is newly described based on cultivated material from Brazil. It belongs to section Cryptophoranthae and differs from all others in this group by the larger flowers and sepals fused apically for more than half length, and a green-brown abaxial side of sepals with purple dots. Chromosome number (2n = 40) and genome size estimation (1C-value = 1.18 pg) is provided and its phylogenetic placement under the genus is supported with reconstruction of a molecular phylogeny using nuclear ribosomal ITS.
Assessing the nephrotoxicity of intravenous iodinated contrast agents in patients with chronic renal failure in the absence of interfering acute disease
Authors: Gallardo Xavier , Almirall Jaume , Castaner Eva , Andreu Marta , Gonzalez Elena , Consola Beatriz 
Published: April 2019

Background The existence of contrast-induced nephropathy is widely accepted. Recent studies suggest its incidence has been overestimated. Purpose To determine the effect of intravenous iodinated contrast agents on renal function in patients with chronic renal failure without acute disease that can interfere with the assessment of renal function. Material and Methods We prospectively analyzed changes in serum creatinine levels after intravenous administration of iodinated contrast agents in all patients with chronic renal failure (creatinine clearance < 60 mL/min by the CKD-EPI Equation) without acute disease referred for computed tomography (CT) follow-up of aortic aneurysm. Between March 2010 and December 2016, a total of 108 patients met the inclusion criteria. The first 35 patients randomly underwent both contrast-enhanced and unenhanced CT examinations six months apart; the 73 following patients underwent only contrast-enhanced CT examinations. Serum creatinine levels were recorded immediately before and 48–72 h after CT examinations. Contrast-induced nephropathy was defined as an increase of ≥25% in serum creatinine from baseline levels. Results In the first 35 patients, mean changes in creatinine levels after unenhanced and enhanced CT examinations were similar. From the total of 108 patients who underwent contrast-enhanced CT, serum creatinine increased > 25% with respect to baseline in only two patients, in one case after contrast-enhanced CT examination and in the other after unenhanced CT examination; in a third patient, serum creatinine decreased >25% after contrast-enhanced CT examination. Conclusion No relevant contrast-induced nephrotoxicity was detected in this group of patients with chronic renal failure without acute disease.
Optimizing patient education of oncology medications: A quantitative analysis of the patient perspective
Authors: Kaupp Kristin , Scott Samantha , Minard Laura V , Lambourne Tessa 
Published: April 2019

Background With the ever-increasing complexity of cancer treatments, oncology medication patient education is becoming a progressively important component of cancer care. Despite this, cancer patients frequently report that they receive inadequate information and feel that their education needs have not been met. Objective To explore patients' perspectives of optimal oncology medication education across Nova Scotia. Methods This was a descriptive survey of adult medical, hematological and gynaecological oncology outpatients receiving intravenous chemotherapy within the Nova Scotia Health Authority between January 26 and April 30, 2018. Results One hundred forty-two responses were included; 41% and 47% of respondents reported being satisfied or very satisfied with their oncology medication education, respectively; 30% and 43% of respondents would like the opportunity to receive education or follow-up from a hospital pharmacist, respectively. Respondents with post-secondary education were found to have 2.82 higher odds of wanting to make an appointment for education with a hospital pharmacist. Conclusions Patients were generally satisfied with their oncology medication education despite the majority not receiving education from a hospital pharmacist. Patients with a higher level of formal education were more likely to want the opportunity to schedule an appointment for education with and/or receive follow-up from a hospital pharmacist. The oncology medication education participants received in the past appeared to align with their education preferences. Findings from this research can be used to optimize the limited time healthcare professionals have to provide meaningful and effective oncology medication patient education and improve patient-centered care.
The Chinatown Patient Navigation Program: Adaptation and Implementation of Breast and Cervical Cancer Patient Navigation in Chicago’s Chinatown
Authors: Simon Melissa A , Tom Laura S , Leung Ivy , Wong Esther , Knightly Eileen E , Vicencio Daniel P , Yau Ann , Ortigara Karen , Dong XinQi 
Published: April 2019

Background: As health care reform continues within the United States, navigators may play increasingly diverse and vital roles across the health care continuum. The growing interest in patient navigation programs for underserved populations calls for detailed descriptions of intervention components to facilitate implementation and dissemination efforts. Methods: In Chicago’s Chinatown, Chinese immigrant women face language, cultural, and access barriers in obtaining breast and cervical cancer screening and follow-up. These barriers spurred the research partnership between Northwestern University, the Chinese American Service League, Mercy Hospital & Medical Center, and Rush University Medical Center to formalize the Chinatown Patient Navigation Collaborative for adapting and implementing previously developed patient navigation models. Results: In this report, we describe the adaptation of patient navigation to build the Chinatown Patient Navigation Collaborative’s community-based patient navigation program for breast and cervical cancer. We offer insights into the roles of community patient navigators in safety net hospital and underserved Chinese immigrant communities, and describe implications for patient navigation initiatives to maximize community benefits by improving access to health care for vulnerable populations. Conclusions: Our adaptation and implementation of a patient navigation intervention in Chicago’s Chinatown illustrates promising approaches for future navigator research.
Case–Control Research Study of Auto-Brewery Syndrome
Authors: Cordell Barbara Jean , Kanodia Anup , Miller Gregory K 
Published: April 2019

Background Auto-brewery syndrome (ABS), also known as Gut Fermentation Syndrome and Endogenous Ethanol Fermentation, is afflicting people worldwide, but little is known about ABS patients’ demographics, health history, lifestyle factors, and diet. Method We conducted a broad-based case–control survey study on 52 patients known to have a diagnosis of ABS and their household members. The research compares the symptomatic group (N = 28) to the asymptomatic group (N = 18) regarding lifestyle and health, diet, and medical history. Results With a response rate of 88% and using rank-sum tests, the data demonstrate that patients with ABS have significant differences compared to people without ABS in lower quality bowel movements ( P = .048), more frequent bowel movements ( P = .038), more reports of malodorous breath ( P = .0001), and self-classify as having poorer health ( P = .009). Furthermore, participants with ABS consume more water ( P = .038), consume less tea and coffee ( P = .033), eat fewer dairy products ( P = .0185), eat less candy ( P = .032), eat out less and rely on food prepared at home ( P = .043), have more aversion to starch ( P = .008), and have more food sensitivities ( P = .043) than the group without ABS. The ABS group also reports more diarrhea ( P = .048), higher amounts of yeast in their gastrointestinal tract ( P = .015), and using acne medication for a longer time ( P = .037) than the control group. Conclusion Patients with ABS have significant differences in their lifestyle and health, diet, and medical history compared to non-ABS participants and these differences warrant further research.
Quantifying the magnitude of pharyngeal obstruction during sleep using airflow shape
Authors: Mann Dwayne L. , Terrill Philip I. , Azarbarzin Ali , Mariani Sara , Franciosini Angelo , Camassa Alessandra , Georgeson Thomas , Marques Melania , Taranto-Montemurro Luigi , Messineo Ludovico , Redline Susan , Wellman Andrew , Sands Scott A. 
Published: April 2019

Rationale and objectivesNon-invasive quantification of the severity of pharyngeal airflow obstruction would enable recognition of obstructiveversuscentral manifestation of sleep apnoea, and identification of symptomatic individuals with severe airflow obstruction despite a low apnoea–hypopnoea index (AHI). Here we provide a novel method that uses simple airflow-versus-time (“shape”) features from individual breaths on an overnight sleep study to automatically and non-invasively quantify the severity of airflow obstruction without oesophageal catheterisation.Methods41 individuals with suspected/diagnosed obstructive sleep apnoea (AHI range 0–91 events·h−1) underwent overnight polysomnography with gold-standard measures of airflow (oronasal pneumotach: “flow”) and ventilatory drive (calibrated intraoesophageal diaphragm electromyogram: “drive”). Obstruction severity was defined as a continuous variable (flow:drive ratio). Multivariable regression used airflow shape features (inspiratory/expiratory timing, flatness, scooping, fluttering) to estimate flow:drive ratio in 136 264 breaths (performance based on leave-one-patient-out cross-validation). Analysis was repeated using simultaneous nasal pressure recordings in a subset (n=17).ResultsGold-standard obstruction severity (flow:drive ratio) varied widely across individuals independently of AHI. A multivariable model (25 features) estimated obstruction severity breath-by-breath (R2=0.58versusgold-standard, p<0.00001; mean absolute error 22%) and the median obstruction severity across individual patients (R2=0.69, p<0.00001; error 10%). Similar performance was achieved using nasal pressure.ConclusionsThe severity of pharyngeal obstruction can be quantified non-invasively using readily available airflow shape information. Our work overcomes a major hurdle necessary for the recognition and phenotyping of patients with obstructive sleep disordered breathing.
Circulating free DNA concentration as a marker of disease recurrence and metastatic potential in lung cancer
Authors: Mirtavoos‐Mahyari Hanifeh , Ghafouri‐Fard Soudeh , Khosravi Adnan , Motevaseli Elahe , Esfahani‐Monfared Zahra , Seifi Sharareh , Salimi Babak , Oskooei Vahid Kholghi , Ghadami Mohsen , Modarressi Mohammad Hossein 
Published: April 2019

AbstractBackgroundPlasma circulating cell‐free (cf) DNA is regarded as a source of tumor DNA. Based on availability of blood tissue for the purposes of early detection of cancer and patients’ follow‐up, several studies have evaluated concentration of cf DNA in cancer patients in association with tumor features. In the present study, we assessed concentration of cf DNA in lung cancer patients with two commercial kits (MN and QIAGEN) to find whether it can be used as a prognostic biomarker.ResultsPrimary cf DNA concentrations as measured by QIAGEN kit was significantly higher in patients who died in the follow‐up period compared with alive patients (P = 0.007). Moreover, the concentrations as measured by both methods were higher in patients who experienced recurrence in the follow‐up period compared with patients without recurrence (P = 0.008 and 0.007 for MN and QIAGEN kits respectively). Significant associations were also found between cf DNA concentrations and tumor stage (P = 0.005 and 0.02 for MN and QIAGEN kits respectively). Notably, cf DNA concentration was higher in metastatic tumors compared with non‐metastatic tumors in association with number of involved organs. Based on the AUC values, both kits could differentiate metastatic cancers from non‐metastatic ones with accuracy of 98%.ConclusionsThe current study highlights the accuracy of cf DNA concentrations for prediction of disease course in lung cancer patients.
Higher incubation temperatures produce long-lasting upward shifts in cold tolerance, but not heat tolerance, of hatchling geckos
Authors: Abayarathna Theja , Murray Brad R. , Webb Jonathan K. 
Published: April 2019

ABSTRACT
Heatwaves are a regular occurrence in Australia, and are predicted to increase in intensity and duration in the future. These changes may elevate temperatures inside lizard nests, shortening the incubation period, so that hatchlings are more likely to emerge during heatwaves. Potentially, developmental plasticity or heat hardening could buffer hatchings from future warming. For example, higher incubation temperatures could shift critical thermal maxima upwards, enabling lizards to withstand higher temperatures. To investigate whether developmental plasticity affects hatchling thermal tolerance, we incubated eggs of the velvet gecko Amalosia lesueurii under two fluctuating incubation treatments to mimic current (mean=24.3°C, range 18.4–31.1°C) and future ‘hot’ (mean=28.9°C, range 19.1–38.1°C) nest temperatures. We maintained the hatchlings under identical conditions, and measured their thermal tolerance (CTmax) aged 14 days and 42 days. We then released hatchlings at field sites, and recaptured individually marked lizards aged 6 months, to determine whether incubation induced shifts in thermal tolerance were transitory or long-lasting. We found that at age 14 days, hatchlings from hot-temperature incubation had higher CTmax [mean=39.96±0.25°C (s.d.)] than hatchlings from current-temperature incubation [mean=39.70±0.36°C (s.d.)]. Hatchlings from the current-incubation treatment also had significantly higher heat hardening capacity [mean=0.79±0.37°C (s.d.)] than hatchlings from hot-temperature incubation treatment [mean=0.47±0.17°C (s.d. )]. However, both of these incubation-induced effects did not persist into later life. By contrast, incubation treatment had significant and long-lasting effects on the cold tolerance of hatchlings. At age 14 days, current-incubated hatchlings tolerated colder temperatures [CTmin=11.24±0.41°C (s.d.)] better than hot-incubated hatchlings [CTmin=14.11±0.25°C (s.d.)]. This significant difference in cold tolerance persisted into the juvenile life stage, and was present in 6-month-old lizards that we recaptured from field sites. This finding indicates that upward shifts in cold tolerance caused by higher incubation temperatures might affect overwinter survival of lizards, but field studies linking fitness to thermal tolerance are necessary to test this idea. Overall, our results suggest that developmental plasticity for heat tolerance is unlikely to buffer lizard populations from higher temperatures.
This article has an associated First Person interview with the first author of the paper.
Posttranslational modifications and proteinopathies: how guardians of the proteome are defeated
Authors: Olzscha Heidi 
Published: April 2019

Abstract
Protein folding is one of the fundamental processes in life and therefore needs to be tightly regulated. Many cellular quality control systems are in place to ensure that proteostasis is optimally adjusted for a changing environment, facilitating protein folding, translocation and degradation. These systems include the molecular chaperones and the major protein degradation systems, namely the ubiquitin proteasome system and autophagy. However, the capacity of the quality control systems can be exhausted and protein misfolding and aggregation, including the formation of amyloids, can occur as a result of ageing, mutations or exogenous influences. There are many known diseases in which protein misfolding and aggregation can be the underlying cause of the pathological condition; these are referred to as proteinopathies. Over the last decade, it has become clear that posttranslational modifications can govern and modulate protein folding, and that aberrant posttranslational modifications can cause or contribute to proteinopathies. This review provides an overview of protein folding and misfolding and the role of the major protein quality control systems. It focusses on different posttranslational modifications and gives examples of how these posttranslational modifications can alter protein folding and cause or accompany proteinopathies.
Usefulness of transcutaneous bilirubin assessment measured in non-photo-exposed skin to guide the length of phototherapy: an observational study
Authors: Castro Abdón , Zozaya Carlos , Cuesta Mª Teresa , González Marina , Villar Gema , Alcaraz Andrés 
Published: April 2019

Abstract

Background
Transcutaneous bilirubinometers are a non-invasive tool to estimate serum bilirubin. However, once on phototherapy (PHT) and after PHT, its usefulness is precluded. The objective of this study was to prove the hypothesis that transcutaneous bilirubin (TcB) assessment in a covered skin area during PHT could be used to guide the duration of PHT in term and moderate-late preterm infants with non-isoimmune hyperbilirubinemia.

Methods
A small area of parasternal skin was covered before starting on PHT. Total serum and TcB (both in exposed and non-exposed areas) were determined before starting treatment, every 12 h once on PHT and 12 h after its discontinuation. Pearson’s correlation coefficient and paired mean differences between TcB and total serum bilirubin (TSB) were calculated. Bland-Altman plots were obtained. The percentage of correct treatment decisions made based on non-exposed TcB values was calculated.

Results
During PHT, there was a relatively good correlation between TSB and non-exposed TcB (0.74) estimates, in contrast to exposed TcB estimates (0.52). However, even when comparing non-exposed TcB with TSB, there was a wide range of agreement limits (−3.8 to 4.6 mg/dL). Decisions based on non-exposed TcB values would have been incorrect in 26.6% of the cases.

Conclusion
Although there is a relatively strong correlation between total serum and TcB in non-PHT-exposed regions, the difference is not narrow enough to be utilized in guiding clinical decisions on the duration of PHT.
Reflections on the relation between direct/indirect methods and explicit/implicit attitudes
Authors: Pharao Nicolai , Kristiansen Tore 
Published: April 2019

Abstract
The paper discusses the relation between direct/indirect methods and explicit/implicit attitudes against the background of how the issue of consciousness (or awareness) is understood and treated in a great deal of research. We focus on the use of techniques that purport to probe the implicit language attitudes held by respondents, and discuss some recent suggestions to modifications of traditional indirect methods. Our main point is that the use of indirect methods does not per se tap into implicit language attitudes in the sense of unconscious language attitudes. In that regard, aspects of how the indirect elicitation is designed and conducted are of pivotal importance. Our insistence on adding the consciousness perspective to the methods-and-attitudes issue derives from our experiences with describing and explaining the recent radical linguistic transformation (homogenization) of the Danish language and speech community. We have found unconscious attitudes – or what we prefer to call subconsciously offered attitudes – to have been a main driving force in that transformation. In investigations with other research interests than sociolinguistic change, an insistence on the importance of securing subconsciously offered attitudes in addition to the consciously offered ones may be of less relevance.