bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning for identification of fasciculation from muscle ultrasound images
Authors: Nodera Hiroyuki , Takamatsu Naoko , Yamazaki Hiroki , Satomi Ryutaro , Osaki Yusuke , Mori Atsuko , Izumi Yuishin , Kaji Ryuji 
Published: May 2019

AbstractBackgroundDetection of fasciculation plays a significant role in the early diagnosis of amyotrophic lateral sclerosis (ALS). Although ultrasound (US) has been reported to be superior to needle electromyography (EMG) and visual inspection in terms of detection rates, other similar movements could lower the reliability of the result. Artificial intelligence, such as deep learning, promises to enhance the classification of visual data.AimTo classify fasciculation and its mimics by deep learning.MethodsUsing an 11‐MHz linear‐array transducer, muscle US was recorded from the biceps brachii and tibialis anterior muscles. Fasciculation for patients with ALS, and movements of voluntary muscles or the recording probe of healthy individuals were recorded. Background subtraction was performed to obtain binary images to infer movements. Deep learning was performed using five different networks with and without pre‐trained weights.ResultsThree groups of images were divided into training, validation, and test (fasciculation: N = 1473; voluntary movement: N = 861; probe movement: N = 1626). The accuracy of detection with pre‐trained weights (fine‐tuning) ranged from 0.959 to 1.0. The best accuracy was obtained by VGG16/19 convolutional neural networks and the ResNet‐152 network. Accuracy of prediction was considerably lower without the pre‐trained weights. The mean white pixels (inferring movements) were lower in fasciculation than in the voluntary and probe movement groups; however, the non‐fasciculation groups showed similar pixel counts (P = 0.95).ConclusionsUS accurately distinguished between fasciculation and its mimics by deep learning. Pixel counting could be a reliable quantitative method to detect fasciculation.
Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease
Authors: Xu Chenqi , Kasimumali Ayijiaken , Guo Xiangjiang , Lu Renhua , Xie Kewei , Zhu Mingli , Qian Yingying , Chen Xiaohuan , Pang Huihua , Wang Qin , Fan Zhuping , Dai Huili , Mou Shan , Ni Zhaohui , Gu Leyi 
Published: May 2019

ABSTRACTAimMuscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post‐translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle.MethodsTwenty patients with stage 4–5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other eight non‐CKD surgical subjects’ muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real‐time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology.ResultsCKD patients had lower HGS than non‐CKD subjects, and HGS was correlated with gender, age, haemoglobin and albumin. Mitochondria were decreased in end‐stage renal disease (ESRD) patients muscle. Mfn‐1 expression and phospho‐Drp1(S637)/Drp1 ratio were inhibited in the ESRD group, implicating dysfunctional mitochondrial dynamics. Muscle PDH activity and phospho‐PDH(S293) were decreased in ESRD patient muscle, while PDK4 protein level was up regulated.ConclusionDecreased mitochondria and PDH deficiency caused by up regulation of PDK 4 contribute to muscle dysfunction, and could be responsible for muscle weakness in CKD patients.
The sucrose‐to‐malate ratio correlates with the faster CO2 and light stomatal responses of angiosperms compared to ferns
Authors: Lima Valéria F. , Anjos Letícia dos , Medeiros David B. , Cândido‐Sobrinho Silvio A. , Souza Leonardo P. , Gago Jorge , Fernie Alisdair R. , Daloso Danilo M. 
Published: May 2019

Summary

Stomatal responses to environmental signals differ substantially between ferns and angiosperms. However, the mechanisms that lead to such different responses remain unclear.

Here we investigated the extent to which leaf metabolism contributes to coordinate the differential stomatal behaviour among ferns and angiosperms.

Stomata from all species were responsive to light and CO2 transitions. However, fern stomatal responses were slower and minor in both absolute and relative terms. Angiosperms have higher stomatal density, but this is not correlated with speed of stomatal closure. The metabolic responses throughout the diel course and under different CO2 conditions differ substantially among ferns and angiosperms. Higher sucrose content and an increased sucrose‐to‐malate ratio during high CO2‐induced stomatal closure was observed in angiosperms compared to ferns. Furthermore, the speed of stomatal closure was positively and negatively correlated with sugars and organic acids, respectively, suggesting that the balance between sugars and organic acids aids in explaining the faster stomatal responses of angiosperms.

Our results suggest that mesophyll‐derived metabolic signals, especially those associated with sucrose and malate, may also be important to modulate the differential stomatal behaviour between ferns and angiosperms, providing important new information that helps in understanding the metabolism‐mediated mechanisms regulating stomatal movements across land plant evolution.
Evaluating a smartwatch notification system in a simulated nursing home
Authors: Ali Haneen , Li Huiyang 
Published: May 2019

AbstractAimsThis paper evaluates a high‐fidelity prototype of a smartwatch‐based communication system for nursing homes. The system could improve communication between residents and caregivers, thus reducing staff response time and improving residents' safety.BackgroundAcross the country, nursing homes are often cited as having serious quality and safety issues. Deficiencies in the communication systems that connect residents with caregivers significantly impact the quality of care. Most nursing homes still use traditional call light systems, that give visual and auditory cues to caregivers, who may or may not be in proximity to the system. This study evaluates a smartwatch communication system developed to quickly relay a resident's requests for assistance to staff anywhere in the nursing home.MethodCertified Nursing Assistants (CNAs) employed by nursing homes were recruited to perform routine tasks using both a traditional system and a smart system. Response time to call lights, staff performance and outcomes were measured through direct and recorded observations and through the surveys of participants.ResultsThe smartwatch system reduced staff response time to call lights from bedrooms by 40%, from bathrooms by 58% and from bed exit alarms by 29%. The smartwatch system also reduced perceived workload by about 50% and was highly accepted by the CNAs.ConclusionA smartwatch‐based notification system may increase staff performance and decrease workload, thus leading to greater staff and patient satisfaction, which could ultimately lead to better quality of care and patient safety.Relevance to clinical practiceThis study provides empirical evidence for the usefulness of smartwatches in facilitating the notification and communication processes in healthcare settings and is also among the first to actually examine a smartwatch system in a healthcare setting.
A qualitative assessment of a dog program for youth offenders in an adult prison
Authors: Smith Hayden P. , Smith Holly 
Published: May 2019

AbstractObjectiveDog programs occurring in prison tend to generate positive public opinion and media portrayals, yet they often lack empirical validation. This is the first study to examine the key themes that drive a dog program aimed at incarcerated youth serving time in an adult prison.Design and SampleA sample of male youth (n = 31) were provided survey questions on a rescue dog program. A grounded qualitative approach was employed with open‐ended responses.ResultsThe following themes emerged: the symbolism of the dog its role in therapy, perceptions of positive behaviors and rehabilitation, a sense of normality, and universal support by inmates.ConclusionThis study supports the potential for utilizing rescue dogs in therapeutic interventions in which the vulnerable inmate can discuss early trauma, interpersonal dysfunction and histories of deviance. The dog symbolized the potential for incarcerated youth to engage in discussion of sensitive topics in a safe manner. Policy implications also include the function of dogs in creating a normalizing effect on the prison unit itself, one that can promote rehabilitation. There was universal support for the program which is rare in the prison milieu. Theoretically, positive outcomes occurred in an indirect manner, though more research is needed.
Age‐related physical and technical match performance changes in elite soccer players
Authors: Sal de Rellán‐Guerra Alejandro , Rey Ezequiel , Kalén Anton , Lago‐Peñas Carlos 
Published: May 2019

The age of peak performance is likely to vary between sports and competitions, affected by the specific skills and attributes needed to succeed in the particular competition. However, no studies using modern tracking techniques have examined the effects of age on competitive match play performance. Thus, the purpose of this study was to evaluate the effects of age on match physical and technical performance using a large‐scale analysis of match performance in professional soccer players. A total of 14 546 individual match observations were undertaken in the first German league (Bundesliga) during the 2012‐2013, 2013‐2014, and 2014‐2015 seasons using a computerized tracking system (VISTRACK, by Impire Corp.). Differences in physical and technical match performance of soccer players were analyzed for the following variables: total distance covered, number of fast runs, number of sprints, and percentage of successful passes. Professional soccer players aged >30 years showed a significant lower performance in the total distance covered, the number of fast runs, and the number of sprints compared with younger players (≤30 years). Conversely, the player's ability to make successful passes increased with age. These effects were observed in all positional roles except wide midfielders. These findings may help coaches and managers to better understand the effects of age on match‐related physical and technical performance and may have the potential to assist in decisions such as, when a new contract would be signed, the duration of the contract, the salary, or when to replace or transfer a player depending on their age.
Transferability of faculty development resources
Authors: Olupeliyawa Asela M. , Venkateswaran Sunil , Wai Nyunt , Mendis Kumara , Flynn Eleanor , Hu Wendy 
Published: May 2019

SUMMARYBackgroundAdapting existing training resources for clinical teachers is more efficient than creating resources de novo. There is limited evidence on how to effectively use and ensure the relevance of training materials originally developed for different contexts and audiences. We tested in Sri Lanka and Malaysia the transferability of scenario‐based training videos and session plans developed for Australian medical schools, to identify those aspects which need adaptation, and make recommendations to enhance transferability.MethodsStaff involved in student support from three medical schools were invited to participate in five workshops facilitated by an Australian educator. Video discussion triggers of students presenting with concerns were used in workshop activities, including written exercises, group discussions and reflection. The quantitative and qualitative data collected included categorical and free‐text participant responses to questionnaires and structured field notes from local faculty developers using peer observation.FindingsAcademic and clinician‐teacher participants predominated in the workshops. Of 66 participant questionnaires (92% response rate), over 90% agreed that the workshop was relevant, and over 95% agreed that the videos facilitated discussion and the sharing of experiences. Field notes confirmed that participants were engaged by the videos, but identified that one student scenario and the approaches for seeking support in others were not immediately transferable to local contexts. The adaptation of facilitation techniques used in Australian workshops was needed to address audience responses.DiscussionOur findings confirm faculty development principles of content relevancy and incorporation of reflection. To enhance transferability, we recommend co‐facilitation with local faculty members, the explicit signposting of topics and re‐contextualising key concepts through reflective discussion.
P66 Characterization of the pharmacokinetics of acetaminophen and its metabolites in the fetus through integration of placental transfer in a physiologically based pharmacokinetic model
Authors: Mian P , Allegaert K , Conings S , Annaert P , Tibboel D , Pfister M , van Calsteren K , van den Anker JN , Dallmann A 
Published: May 2019

BackgroundLittle is known about fetal acetaminophen (paracetamol) pharmacokinetics and its potential for toxicity, despite the frequent use of acetaminophen during pregnancy. The aim of this study was to develop a feto-maternal physiologically based pharmacokinetic model (f-m PBPK) to predict placental transfer and PK of acetaminophen and its metabolites in fetus at term pregnancy.MethodsPreviously, a pregnancy PBPK model was developed for prediction of maternal PK of acetaminophen and its metabolites. This model was structurally extended with the fetal liver, and quantitative information on the maturation of relevant enzymes was integrated. Three different approaches (ex vivo placenta perfusion experiments, scaling of passive diffusion transfer rates, and the Mobi® default method) to describe placental drug transfer were tested. Predicted maternal and fetal acetaminophen concentrations were compared with those observed in the literature. umbilical cord data at birth.ResultsThe 3 different approaches to predicted acetaminophen PK in the umiblical vein were found to yield broadly similar results. Acetaminophen exposure was similar in maternal blood compared to venous umbilical cord blood. Prediction of the median dose fraction of acetaminophen converted to its metabolites (fm) revealed higher maternal acetaminophen-glucuronide formation clearance and sulphate formation compared to that in the fetal liver (fm_glucuronide52.2 vs 0% and fm_sulphate30.4 vs 0.8%, respectively) and higher fraction of acetaminophen converted to the reactive metabolite N-acetyl-p-benzoquinone-imine (fm_NAPQI, 6.5 vs 0.06%) in pregnant women compared to their fetus.ConclusionNo differences were observed in the 3 approaches for integration of placental drug transfer. Differences in acetaminophen biotransformation to its metabolites between pregnant women and their fetuses were quantitatively predicted.Disclosure(s)Paola Mian received a Short term Minor (STM-2017) grant from the Stichting Sophia Kinderziekenhuis fonds to conduct this research.
P67 Impact of enantiomer-specific maturational changes in pharmacokinetics on the racemic ketorolac target trough concentration
Authors: Cloesmeijer M , Krekels E , van Esdonk M , Lynn A , Smits A , Tibboel D , Daali Y , Olkkola K , Allegaert K , Mian P 
Published: May 2019

IntroductionKetorolac is a racemic drug with analgesic effects specific to its S-enantiomer. This study aimed to describe enantiomer-specific maturational pharmacokinetics (PK). Simulations were performed to describe how S-ketorolac exposure in infants differs from adults, and how this affects the adult racemic analgesic trough threshold EC50 (EC50thr-adult, 0.37 mg/L) in infants (EC50thr-infant)when the same S-target is applied.MethodsA population PK analysis (NONMEM 7.3) was performed based on 1020 plasma samples from 5 studies including 80 patients (adults, children, infants) following single intravenous ketorolac administration.ResultsS-ketorolac PK was best described with a 2-compartment model in infants and 3-compartment model in adults, while R-ketorolac PK was best described with a 2-compartment model in all. S-ketorolac clearance [mean population value: 3.45 L/h/56 kg] and central volume of distribution (V1) [4.27 L/56kg] increased exponentially with bodyweight (0.75, 0.59 respectively). R-ketorolac clearance [0.93 L/h/56kg], peripheral volume of distribution (V2) and inter-compartmental clearance (Q) increased exponentially with bodyweight (0.62, 1.20, 0.76 respectively), V1 [4.11 L/56kg] linearly with bodyweight. Simulations revealed EC50thr-adult (0.37 mg/L) contained 0.048 mg/L S-ketorolac as mean in typical adults (BW 48.6–99.6 kg), while EC50thr-adult contained 0.032–0.036 mg/L S-ketorolac in typical infants (BW 5.3–10.6 kg). To reach adult S-enantiomer concentration (0.048 mg/L) in typical infants (BW 5.3–10.6 kg), EC50thr-infant should be 0.49–0.46 mg/L, respectively.ConclusionEnantiomer-specific maturational PK of ketorolac were described. Subsequent simulations displayed differences in proportion of S- and R-ketorolac on the racemic threshold EC50. A The same S-ketorolac concentration necessitates a higher EC50thr-infant to EC50thr-adult.Disclosure(s)Nothing to disclose
P71 Population pharmacokinetics and pharmacogenetics of caffeine in Chinese premature infants with apnoea of prematurity
Authors: Ni S , Gao X-B , Y-E Hu , Wang C-H , Jiang Z-H , Yang F , Zheng Y , Zhao W 
Published: May 2019

BackgroundCaffeine is commonly regarded as the treatment of choice for neonatal apnoea. However, limited data on the developmental pharmacokinetics and pharmacogenetics were available in Chinese premature infants. The objective of this study was to develop a population pharmacokinetic model of caffeine after intravenous administration to Chinese neonates with apnoea of prematurity (AOP) and evaluate the impact of developmental pharmacogenetics of CYP1A2.MethodsSparse pharmacokinetic samples were collected from AOP newborns receiving caffeine citrate at a loading dose of 20 mg/kg/d and maintenance dose of 5–10 mg/kg/d. Population pharmacokinetic-pharmacogenetic analysis of caffeine was performed using NONMEM. Eight CYP1A2 polymorphisms were genotyped.ResultsA total of 99 newborns with a mean (SD) postmenstrual age of 32.0 (2.16) (range 22.3 - 38.0) weeks were included in the present study. Pharmacokinetic data fitted an one-compartment model with first-order absorption and elimination. Current weight, postmenstrual age and serum creatinine concentration were significant covariates influencing caffeine clearance. None of tested CYP1A2 polymorphisms had significant impact on caffeine pharmacokinetics.ConclusionThe population pharmacokinetics-pharmacogenetics of caffeine was evaluated in Chinese AOP premature infants. This developmental pharmacokinetic model can be helpful to individualize caffeine therapy.Disclosure(s)Nothing to disclose
P72 Maturation of sildenafil clearance in prematurely born infants with BPD associated pulmonary hypertension
Authors: Nikrawesh H , Engbers AGJ , Völler S , Simons SHP , Koch BCP , Knibbe CAJ , Reiss IKM , Flint RB 
Published: May 2019

BackgroundSildenafil is used as an off-label treatment for bronchopulmonary dysplasia (BPD) associated pulmonary hypertension in prematurely born infants. As there is only limited information on the pharmacokinetics (PK) of sildenafil in this population, the aim of this study is to investigate the PK of sildenafil in prematurely born infants with BPD associated pulmonary hypertension.MethodIn this multicentre study, a population PK model for sildenafil in prematurely born infants was developed based on samples obtained using opportunistic sampling during clinical use of sildenafil. Data of seven subjects (42 plasma samples) were analysed by nonlinear mixed-effect modelling (NONMEM®7.3). Median (range) gestational age (GA) was 26.1 (24.1–27.6) weeks, current bodyweight 1960 (632–3157) grams, birthweight 635 (465–1125) grams and postnatal age (PNA) at start of therapy 64.9 (10.9–89) days. The median (range) treatment duration was 4.9 (1.6–13.1) weeks, with six subjects receiving oral doses of median 2.6 mg/kg/day (1.5–5.3) in three doses and one subject receiving oral and intravenous doses of 6.7 mg/kg/day in two doses.ResultsThe plasma concentration time profiles of sildenafil were best described by a one compartment model. Clearance (CL) and volume of distribution (Vd) for a child with a PNA of 64.9 days and bodyweight of 1.96 kg was 4.42 L/h ((RSE) 11%) and 29.5 L (32%), respectively. PNA was found to significantly influence CL, resulting in an increase of 10.7% in a week, and 43% in a month for a 65-day old infant. No other covariates (i.e. bodyweight, birthweight, GA, postmenstrual age and sex) were identified for CL or Vd.ConclusionIn this PK study, we characterised the pharmacokinetics of sildenafil in prematurely born infants and found that clearance increases with PNA. Due to the limited sample size in this study, further research in a larger population is needed to extend these findings.Disclosure(s)Nothing to disclose
P76 The effect of the pregnancy and lactation labeling rule on prescribing information of FDA-approved drugs
Authors: Patel A , Mazer-Amirshahi M , Fusch G , Chan A , van den Anker J , Samiee-Zafarghandy S 
Published: May 2019

BackgroundThe U.S. Food and Drug Administration implemented the new Pregnancy and Lactation Labeling Rule (PLLR) in June 2015. Under PLLR, all new drug applications were to present a narrative risk assessment (as opposed to letter category), while drug approvals after June 2001, were required to phase in by June 2020. The purpose of this study was to assess the quality of presented pregnancy and lactation data in the drug labeling and degree of adherence to the PLLR.Design/MethodsWe reviewed the labeling data of all new molecular entities (NMEs) approved from 1999–2017. The pregnancy and lactation information was classified as: 1. Harmful to use 2. Safe to use 3. Consideration of safety and efficacy. For drugs approvals after June 2001, presence of pregnancy letter category system was noted.ResultsOf the 456 NMEs, 131 (29%) were classified as harmful to use in pregnancy and 207 (45%) as harmful to use during lactation. This number did not follow any specific pattern over the course of 19 years. Less than 1% of drugs were deemed to be safe during pregnancy or lactation. Human data was the source of pregnancy or lactation information for only 2% of drugs. Up to 70% of drugs belonged to each implementation schedule has yet to meet the PLLR compliance requirement.Conclusion(s)Pregnant and lactating women are mostly advised against use of medications that might be needed for their health and health of their infants based on very limited data. Pharmaceutical companies lagged behind the required adherence rule for labeling updates on pregnancy and lactation information.Disclosure(s)Nothing to disclose