bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial
Authors: Sathe Abhishek G. , Underwood Ellen , Coles Lisa D. , Elm Jordan J. , Silbergleit Robert , Chamberlain James M. , Kapur Jaideep , Cock Hannah R. , Fountain Nathan B. , Shinnar Shlomo , Lowenstein Daniel H. , Rosenthal Eric S. , Conwit Robin A. , Bleck Thomas P. , Cloyd James C. 
Published: February 2021

AbstractObjectiveThis study was undertaken to describe patterns of benzodiazepine use as first‐line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second‐line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).MethodsPatients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second‐line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline‐recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second‐line agent.ResultsFour hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second‐line medications in these benzodiazepine‐refractory seizures.SignificanceBenzodiazepines as first‐line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.)
miR‐467 regulates inflammation and blood insulin and glucose
Authors: Gajeton Jasmine , Krukovets Irene , Yendamuri Revanth , Verbovetskiy Dmitriy , Vasanji Amit , Sul Lidiya , Stenina‐Adognravi Olga 
Published: February 2021

AbstractObesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR‐467a‐5p, a miRNA induced by hyperglycaemia, in regulating inflammation and blood glucose handling. We previously demonstrated that miR‐467a‐5p is induced by hyperglycaemia and inhibits the production of thrombospondin‐1 (TSP‐1), a protein implicated in regulating inflammation. To investigate the role of miR‐467 in blood glucose handling and tissue inflammation, WT C57BL/6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR‐467a‐5p antagonist. Inhibiting miR‐467a‐5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 ng/mL vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP‐1 lost some but not all of the miR‐467 effects, suggesting Thbs1 (and other unknown transcripts) are targeted by miR‐467 to regulate inflammation. miR‐467a‐5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.
EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway
Authors: Kong Wencui , Chen Ying , Zhao Zhongquan , Zhang Lei , Lin Xiandong , Luo Xingguang , Wang Shuiliang , Song Zhengbo , Lin Xiangwu , Lai Guoxiang , Yu Zongyang 
Published: February 2021

AbstractDNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation‐expression‐pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta‐catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV‐939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.
Stocks and flows of buildings: Analysis of existing, demolished, and constructed buildings in Tampere, Finland, 2000–2018
Authors: Huuhka Satu , Kolkwitz Mario 
Published: February 2021

AbstractResearch has identified cities as potential urban mines for recovering secondary construction materials. Studies typically focus on stocks or flows of bulk materials on high abstraction levels. To enable a shift of focus toward higher levels of circular economy, such as waste minimization, there is a need for a more detailed understanding of the dynamics that contribute to the waste flows, building replacement in particular. This paper examines the characteristics and location of the stocks and flows of buildings, both residential and non‐residential, in the city of Tampere, Finland, over the last 20 years. Statistical and geographical analyses are performed on the building stock, new construction, and demolition in Tampere to unveil patterns pertaining to stock change and building replacement. The study shows that these patterns vary significantly between buildings of different function. Spatially confined redevelopment areas within the city structure, that is, brownfields and grayfields, whose industrial and commercial functions yield to housing and mixed residential–commercial use, make up major arenas for replacement. Policy‐making should acknowledge that urban planning stirs these waste flows and incorporate their conscious prevention and management on its agenda.
A pilot study of minimal invasion combined PDL/Nd:YAG laser in treating facial epidermoid cyst
Authors: Fu Hongyi , Luo Fuling , Zhao Hengguang 
Published: February 2021

AbstractObjectivesTo compare the efficacy and complication of minimal invasion and combined pulsed dye laser/Nd:YAG laser and traditional surgical excision in the treatment of facial epidermoid cyst.MethodsA total of 100 patients with facial epidermoid cyst aged from 16 to 65 years and cyst diameter ranged from 0.3 to 3.0 cm were treated and followed up. Patients were divided into the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment group and traditional surgical excision group. All patients were followed up for 12 months including scar size, recurrence rate, incidence of complications, and patient global satisfaction.ResultsThe mean operative time in the minimal invasion and combined pulsed dye laser/Nd:YAG laser treatment was 15.23 ± 7.02 minutes, which is significantly shorter than that of surgical excision (27.26 ± 10.12 minutes, P < .05). After 12 months, the average scar size in minimal invasion and combined pulsed dye laser/Nd:YAG laser group was 0.54 ± 0.35 cm, while that of traditional surgical excision group was 1.77 ± 0.81 cm (P < .05). No statistical difference was found between two groups in the wounds split, hematoma, early and late recurrence rates (P > .05), while the patients' global satisfaction in the pulsed dye laser/Nd:YAG laser group is much higher than that of the traditional surgical excision group.ConclusionThe treatment of minimal invasion and combined pulsed dye laser/Nd:YAG laser is effective and safe for medium‐size facial epidermoid cysts. For facial epidermoid cyst ranging for 0.3 cm to 3.0 cm, considering the cosmetic factors, minimal invasion and combined pulsed dye laser/Nd:YAG laser should be particularly recommended.
Brain Structural Changes in Patients with Pulmonary Arterial Hypertension
Authors: Roy Bhaswati , Vacas Susana , Ehlert Luke , McCloy Kathy , Saggar Rajan , Kumar Rajesh 
Published: February 2021

ABSTRACTBACKGROUND AND PURPOSEPatients with pulmonary arterial hypertension (PAH) frequently present with anxiety, depression, autonomic, and cognitive deterioration, which may indicate brain changes in regions that control these functions. However, the precise regional brain‐injury in sites that regulate cognitive, autonomic, and mood functions in PAH remains unclear. We examined the shifts in regional gray matter (GM) volume, using high‐resolution T1‐weighted images, and brain tissue alterations, using T2‐relaxometry procedures, in PAH compared to healthy subjects.METHODSWe collected two high‐resolution T1‐weighted series, and proton‐density and T2‐weighted images using a 3.0‐Tesla magnetic resonance imaging scanner from 9 PAH and 19 healthy subjects. Both high‐resolution T1‐weighted images were realigned and averaged, partitioned to GM tissue type, normalized to a common space, and smoothed. Using proton‐density and T2‐weighted images, T2‐relaxation maps were calculated, normalized to a common space, and smoothed. Whole‐brain GM volume and T2‐relaxation maps were compared between PAH and controls using analysis of covariance (covariates, age, sex, and total‐brain‐volume; false discover rate corrections).RESULTSSignificantly decreased GM volumes, indicating tissue injury, emerged in multiple brain regions, including the hippocampus, insula, cerebellum, parahippocampus, temporal, frontal, and occipital gyri, cingulate, amygdala, and thalamus. Higher T2‐relaxation values, suggesting tissue damage, appeared in the cerebellum, hippocampus, parahippocampus, frontal, lingual, and temporal and occipital gyri, and cingulate areas in PAH compared to healthy subjects.CONCLUSIONSPAH patients showed significant GM injury and brain tissue changes in sites that regulate cognition, autonomic, and mood functions. These findings indicate a brain structural basis for functional deficits in PAH patients.
Emotional and behavioural problems in children and adolescents: The role of constipation
Authors: dos Santos Ivana R , de Abreu Glícia E , Dourado Eneida R , Martinelli Braga Ana A N , Lobo Victoria A , de Carvalho Isabella W B , Bastos Netto José M , Barroso Ubirajara 
Published: February 2021

AimThe functional constipation (FC) is a source of an expressive suffering in children, negatively affecting their emotional, social, and physical well‐being. The objective of this study is to describe the clinical and behavioural characteristics of children/adolescents with FC.MethodsA cross‐sectional, observational, analytical study was conducted in public places by interviewing parents of children/adolescents about their child's bowel habits and psychological profile. Bowel symptoms were investigated using the Rome IV criteria. The Strengths and Difficulties Questionnaire (SDQ) was used to evaluate the emotional and behavioural problems.ResultsOf 799 children/adolescents included, 424 (53.1%) were female. Mean age was 9.1 ± 2.7 years. FC prevalence was 20.4%. The most common symptoms in Rome IV criteria were ‘painful or hard bowel movements’ (n = 110; 67.5%; 95% confidence interval: 60.0–74.3) and ‘retentive posturing or excessive volitional stool retention’ (n = 89; 54.6%; 95% confidence interval: 46.9–62.1). Median scores for internalising symptoms (7; interquartile range (IQR): 4–9 vs. 5; IQR: 2–7; P < 0.001) and externalising symptoms (7; IQR 4–11 vs. 6; IQR 3–9; P < 0.001) were higher in constipated children compared to non‐constipated participants, respectively. The SDQ domains that were associated with FC were emotional symptoms (median 4, P < 0.001) and conduct problems (median 3, P < 0.001). No association was found between faecal incontinence and median scores for the internalising/externalising symptoms. All Rome IV criteria were associated with abnormal overall SDQ scores.ConclusionChildren and adolescents with FC had more emotional and behavioural problems irrespective of whether faecal incontinence was present or not, with higher scores for internalising and externalising symptoms compared to non‐constipated children.
Descriptive assessment of adverse events associated with midazolam‐etomidate versus saline‐etomidate in healthy hydromorphone premedicated dogs
Authors: Jones T. L. , Calbay R. , da Cunha A. F. , Hofmeister E. H. 
Published: February 2021

ObjectivesTo determine the frequency, severity and duration of adverse events including myoclonus, pain on injection, hypersalivation, regurgitation and apnoea after administration of midazolam or saline followed by etomidate in hydromorphone premedicated dogs.Materials and MethodsDogs undergoing elective dental prophylaxis or soft tissue surgeries were enrolled in this randomised trial. Dogs were premedicated with hydromorphone 0.1 mg/kg IV. Sixty seconds later, midazolam 0.3 mg/kg or saline at an equivalent volume was administered IV. Sixty seconds after that, etomidate 1.5 mg/kg IV was administered over 60 seconds. Additional doses of 0.5 mg/kg etomidate were administered until endotracheal intubation was successful. Observers were blinded to the treatment. Frequency, duration and a severity score of 0 to 3 were recorded for myoclonus, pain on injection, hypersalivation and regurgitation. Duration of apnoea and frequency of any additional complications was recorded.ResultsForty variable breed healthy dogs were enrolled in the study. Myoclonus, pain on injection, regurgitation, hypersalivation, gagging, tachypnoea and pigmenturia occurred, respectively, in 10%, 40%, 0%, 15%, 35%, 25% and 5% of dogs in the saline group and 0%, 65%, 0%, 10%, 45%, 15% and 5% of dogs in the midazolam group. Apnoea occurred for 115 seconds (range 0 to 660 seconds) and 160 seconds (range 0 to 600 seconds) in the saline and midazolam groups, respectively. Two dogs developed pigmenturia. The trial was stopped early due to the occurrence of pigmenturia.Clinical SignificanceDue to early stopping of the trial, the predefined sample size was not reached. Further investigation is needed to determine if midazolam reduced the incidence of adverse events or improved the induction quality when combined with hydromorphone and etomidate.
Pharmacokinetics of levofloxacin mesylate in healthy adult giant panda after single‐dose administration via different routes
Authors: Wang Chengdong , Deng Linhua , Zhu Yanqiu , Wu Kai , Wei Ming , Huang Shang , Wei Rongping , Liu Weiping , Huang Yan , Zhang Hemin , Li Desheng 
Published: February 2021

AbstractThe pharmacokinetics of levofloxacin mesylate in healthy adult giant panda is unknown. In this study, the pharmacokinetics of levofloxacin after intramuscular administration at a dose of 2 mg/kg and oral administration at a dose of 3 mg/kg in healthy adult giant pandas was determined. Levofloxacin concentrations in plasma were determined using liquid chromatography. In the levofloxacin intramuscular administration group, the absorption and elimination half‐lives of the drug were determined to be 0.123 (range: 0.02) hr and 5.402 (range: 0.70) hr, respectively. In the levofloxacin oral administration group, the absorption and elimination half‐lives were determined to be 0.325 (range: 0.02) hr and 7.143 (range: 0.63) hr, respectively. Furthermore, the blood–drug concentration of levofloxacin was found to be above 1 μg/ml after 8 hr of intramuscular administration and above 0.5 μg/ml after 12 hr of oral administration. In this study, HPLC conditions and pretreatment methods of plasma samples were optimized and a detection method was established. Our results indicated that in healthy adult giant pandas, levofloxacin was rapidly absorbed and slowly eliminated. This study will therefore provide to be a guide in veterinary research and will be helpful in the rational use of levofloxacin in giant panda.
Be careful with ecological associations
Authors: Roumeliotis Stefanos , Abd ElHafeez Samar , Jager Kitty J. , Dekker Friedo W. , Stel Vianda S. , Pitino Annalisa , Zoccali Carmine , Tripepi Giovanni 
Published: February 2021

AbstractEcological studies are observational studies commonly used in public health research. The main characteristic of this study design is that the statistical analysis is based on pooled (i.e., aggregated) rather than on individual data. Thus, patient‐level information such as age, gender, income and disease condition are not considered as individual characteristics but as mean values or frequencies, calculated at country or community level. Ecological studies can be used to compare the aggregated prevalence and incidence data of a given condition across different geographical areas, to assess time‐related trends of the frequency of a pre‐defined disease/condition, to identify factors explaining changes in health indicators over time in specific populations, to discriminate genetic from environmental causes of geographical variation in disease, or to investigate the relationship between a population‐level exposure and a specific disease or condition. The major pitfall in ecological studies is the ecological fallacy, a bias which occurs when conclusions about individuals are erroneously deduced from results about the group to which those individuals belong. In this paper, by using a series of examples, we provide a general explanation of the ecological studies and provide some useful elements to recognize or suspect ecological fallacy in this type of studies.
Localised laccase activity modulates distribution of lignin polymers in gymnosperm compression wood
Authors: Hiraide Hideto , Tobimatsu Yuki , Yoshinaga Arata , Lam Pui Ying , Kobayashi Masaru , Matsushita Yasuyuki , Fukushima Kazuhiko , Takabe Keiji 
Published: February 2021

Summary

The woody stems of coniferous gymnosperms produce specialised compression wood to adjust the stem growth orientation in response to gravitropic stimulation. During this process, tracheids develop a compression‐wood‐specific S2L cell wall layer with lignins highly enriched with p‐hydroxyphenyl (H)‐type units derived from H‐type monolignol, whereas lignins produced in the cell walls of normal wood tracheids are exclusively composed of guaiacyl (G)‐type units from G‐type monolignol with a trace amount of H‐type units. We show that laccases, a class of lignin polymerisation enzymes, play a crucial role in the spatially organised polymerisation of H‐type and G‐type monolignols during compression wood formation in Japanese cypress (Chamaecyparis obtusa).

We performed a series of chemical‐probe‐aided imaging analysis on C. obtusa compression wood cell walls, together with gene expression, protein localisation and enzymatic assays of C. obtusa laccases.

Our data indicated that CoLac1 and CoLac3 with differential oxidation activities towards H‐type and G‐type monolignols were precisely localised to distinct cell wall layers in which H‐type and G‐type lignin units were preferentially produced during the development of compression wood tracheids.

We propose that, not only the spatial localisation of laccases, but also their biochemical characteristics dictate the spatial patterning of lignin polymerisation in gymnosperm compression wood.
Influences of exercise interventions on overweight and obesity in children and adolescents
Authors: Lee Junga 
Published: February 2021

AbstractPurposeConflicting findings of the effects of exercise on body fat, free fat mass, insulin, insulin resistance, and physical fitness for overweight and obesity in children and adolescents. The purpose of this meta‐analysis was to investigate the effects of exercise interventions in children and adolescents with overweight and obesity depending on exercise type and to build effective exercise interventions to reduce risks of metabolic disorders.MethodsDatabases were used to find eligible studies regarding the effects of exercise interventions on overweight and obesity in children and adolescents in randomized controlled trails. Effect size was calculated using the standardized mean difference statistic and heterogeneity across studies was estimated using the Q statistic.ResultsA total of 27 studies met the inclusion criteria. Children and adolescents with overweight and obesity who participated in aerobic exercise had reduced body mass index, % body fat, fasting insulin, free fat mass, TNF‐α, and IL‐6, and increased physical fitness compared with control groups. Reduced free fat mass in resistance exercise was not found. Glucose, insulin resistance, blood pressure, C‐reactive protein (CRP), and blood markers including total cholesterol (TC), triglyceride, LDL, and HDL did not have significant change. Average exercise interventions were aerobic exercise, 3 times/week, 60 min, and 36 weeks of exercise period.ConclusionsAerobic exercise may be beneficial to reduce body fat, fasting insulin, and inflammatory markers, and increased physical fitness for overweight and obesity in childhood and adolescence, but resistance exercise may be added, which can help avoid muscle loss in children and adolescents with overweight and obesity.
Overview of human papillomavirus vaccination policy changes and its impact in the United States: Lessons learned and challenges for the future
Authors: Kim Deogwoon , Lee Haeok , Kim Minjin 
Published: February 2021

AbstractBackgroundThe HPV vaccination is effective and safe for preventing HPV infection and HPV attributable cancers. Despite this fact, the uptake rate of the vaccination in the United States has remained below the national target of 80%. Health policy focused on allocating resources and creating vaccine‐promoting environments can influence HPV vaccination coverage rates. There is a scarcity of information about the HPV vaccination‐related health policy and its impact on the outcome of vaccine uptake.MethodWe conducted a comprehensive review of HPV vaccination‐related health policies at the federal, state, and professional organization levels and examined their impact on population health by reviewing national data on HPV vaccination uptake rates.ResultsThe review revealed that (a) HPV vaccination recommendations, which serve as the federal‐level HPV vaccination policy, have changed frequently in terms of gender, age criteria, and dosing schedule, and (b) the frequent changes of the policy have resulted in low uptake rates among male and young adult populations.DiscussionThe uptake rate should be continuously followed to evaluate the impact of recent changes to the federal‐level HPV vaccination policy. State‐level policies and healthcare professionals, including nurses, are important to the promotion of HPV vaccinations and decreasing HPV vaccination disparities.