bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beurteilung der Geschäftsfähigkeit und Testierfähigkeit bei Schlaganfallpatienten mit Aphasie
Authors: Dreßing Andrea , Weiller Cornelius , Foerster Klaus , Dreßing Harald 
Published: January 2019

ZusammenfassungObwohl Aphasien nach ischämischen Schlaganfällen oder Hirnblutungen häufig auftreten, hat sich weder die medizinische Wissenschaft noch die obergerichtliche Rechtsprechung intensiver mit der praktisch bedeutsamen Frage beschäftigt, welche Auswirkungen diese Störung auf die Geschäftsfähigkeit hat.Mit Hilfe moderner Bildgebungsstudien ist eine differenzierte Betrachtung der unterliegenden Pathologien der erworbenen Sprachstörungen, der daraus resultierenden unterschiedlichen klinischen Bilder der Aphasie sowie dem Erholungsverlauf möglich. Auf der Basis dieser Befunde sowie dem Konzept der „Inneren Sprache“ wird untersucht, inwieweit Aphasien die Geschäftsfähigkeit beeinträchtigen könnten und ein Phasenmodell zur Beurteilung der Geschäftsfähigkeit bei Aphasie vorgeschlagen, welches die grundsätzlichen Möglichkeiten der Erholung im Rahmen neuronaler Reorganisation berücksichtigt.Die gutachtliche Beurteilung der Voraussetzungen zur Annahme einer Geschäftsfähigkeit oder -unfähigkeit bei Aphasie erfordert eine interdisziplinäre Zusammenarbeit von Neurologen, Psychiatern und Sprachtherapeuten. Da Gutachten zur Geschäftsunfähigkeit häufig ex-post erstellt werden müssen, ist der Gutachter auf eine detaillierte Befunddokumentation von Fähigkeiten und Defiziten bei Vorliegen einer Aphasie angewiesen. Um die bisherigen Limitationen in der Begutachtung der Geschäftsfähigkeit von Patienten mit Aphasien zu verbessern, wäre eine standardisierte Beschreibung der Aphasie und assoziierter neuropsychologischer Symptome als obligater Bestandteil eines Arztbriefes nach einer neurologischen Akut- und Rehabilitationsbehandlung wünschenswert.
Antibiotikaverbrauch auf einer Intensivstation für
Schwerbrandverletzte
Authors: Steinke Björn , Sablotzki Armin , Kremer Thomas , Bethge Angela , Glas Annette , Gille Jochen 
Published: January 2019

Zusammenfassung
Hintergrund Brandverletzte Patienten unterliegen einem besonders hohen
Infektionsrisiko. Daraus könnte sich ein erhöhter Antibiotika-Verbrauch ergeben.
In Deutschland existieren hierzu keine Daten. Ziel dieser Untersuchung war die
Ermittlung der Antibiotikaverbrauchsdichte (AVD) bei Schwerbrandverletzten und
der Vergleich mit operativen Intensivstationen.
Patienten und Methode In die retrospektive Untersuchung wurden 136
Patienten eingeschlossen, die im Zeitraum von 2013 bis 2016 aufgrund einer
schweren Verbrennung auf der Intensivstation des Schwerbrandverletztenzentrums
(SBVZ) des Klinikums St. Georg Leipzig behandelt wurden. Die Anwendung von
Antibiotika wurde anhand der elektronischen Krankenakte erfasst und die Anzahl
der Tagesdosen in Recommended Daily Dose (RDD) und Defined Daily Dose (DDD)
bezogen auf die Patiententage errechnet.
Ergebnisse Medianes Patientenalter und verbrannte Körperoberfläche (VKOF)
waren 56,5 Jahre [42; 75] bzw. 17 % [8,75; 31] bei einem ABSI von 7 [6; 9]. Eine
Antibiotikatherapie erhielten 82 Patienten (60,3 %). Die AVD betrug insgesamt
77,38 RDD/100 PT bzw. 937,64 DDD/1000 PT und war damit etwas geringer als für
operative Intensivstationen. Dabei wurden am häufigsten Fluorchinolone (16,90
RDD/100 PT; 259,91 DDD/1000 PT) verabreicht, gefolgt von Carbapenemen (12,76
RDD/100 PT; 128,44 DDD/1000 PT) und Aminopenicillinen/ BLI (11,54 RDD/100 PT;
115,39 DDD/1000 PT). Die am häufigsten nachgewiesenen Erreger waren
Staphylococcus aureus (54,4 %), Enterococcus faecalis (54,4 %), E. coli (37,5 %)
und Pseudomonas aeruginosa (36,8 %).
Schlussfolgerung Der Gesamtverbrauch an Antibiotika bei
Schwerbrandverletzten war im Vergleich zu anderen operativen Intensivpatienten
nicht erhöht. Hinsichtlich einzelner Substanzklassen lassen sich aufgrund des
besonderen Keimspektrums Besonderheiten feststellen.
Real-World Adequacy of Glycaemic Control in Treatment-Naïve
Greek Patients with Type 2 Diabetes Mellitus Initiating Treatment with Metformin
Monotherapy at the Maximum Tolerated Dose: The Reload Study
Authors: Tsimihodimos Vasilis , Bargiota Alexandra , Pagkalos Emmanouil M. , Manes Christos , Papas Aggelos , Karamousouli Eugenia , Voss Bernd , Elisaf Moses S 
Published: January 2019

Abstract
Background Metformin, in the absence of contraindications or
intolerance, is recommended as first-line treatment for patients with type 2
diabetes mellitus (T2DM). This observational, retrospective study assessed
the real-world adequacy of glycaemic control in Greek patients with T2DM
initiating metformin monotherapy at maximum tolerated dose.
Methods Included patients received metformin monotherapy for
≥24 months; relevant patient data were collected immediately prior
to metformin initiation (baseline) and at other prespecified time points.
The primary objective was to report, after 9 months of metformin treatment,
the percentage of patients with baseline glycated haemoglobin
(HbA1c) levels ≥6.5%
(≥48 mmol/mol) achieving
HbA1c<6.5%. Secondary objectives included the
assessment of time spent with poor glycaemic control and time to treatment
intensification. A sensitivity analysis assessed the percentage of patients
with baseline HbA1c≥7%
(≥53 mmol/mol) achieving
HbA1c<7%
(<53 mmol/mol).
Results Of the enrolled patients (N=316), 247 had baseline
HbA1c ≥6.5%; following 9 months on metformin,
90 (36.4%) patients achieved HbA1c<6.5%
(mean HbA1c change−1.3%
[−14 mmol/mol]). Median time of exposure to
HbA1c ≥6.5% was 23.4 months and time to
treatment intensification was 28.0 months. The sensitivity analysis revealed
that the proportion of patients achieving
HbA1c<7.0% was 50% (mean
HbA1cpy for up to 24 months. Addressing clinical inertia could
improve disease outcomes and, possibly, economic burden.
Effect of the type of packaging on the oxidative stability of pine nuts (Pinus pinea L.) grown in Chile
Authors: Henríquez  , Loewe  , Saavedra  , Córdova  , Lutz  
Published: January 2019

Pine nut (Pinus pinea L.) is a nutritious, expensive tree nut. During storage, it is exposed to a wide range of environmental deteriorative conditions. This study describes the oxidative stability of pine nuts kept in pouches made of three different packaging materials and stored
at three different temperatures. The packaging materials evaluated were low-density polyethylene (LDP), high-density polyethylene (HDP), and high-barrier metallized film (MF). Temperatures evaluated were 4, 20, and 60°C. In addition, a control unpacked sample was also evaluated in identical
conditions. The oxidative parameters evaluated were acid value and peroxide value. Data analyses include a shelf-life study and a principal component analysis. The results obtained indicate what the best packaging material at 20°C was MF with a shelf-life of 703 d. At 4°C, the
shelf-life of pine nuts stored in HDP was 1148 d. It is concluded that it is fundamental to use an adequate packaging to protect the seeds from environmental conditions that promote deterioration.
Exosomes derived from clinical‐grade oral mucosal epithelial cell sheets promote wound healing
Authors: Sjöqvist Sebastian , Ishikawa Taichi , Shimura Daisuke , Kasai Yoshiyuki , Imafuku Aya , Bou‐Ghannam Sophia , Iwata Takanori , Kanai Nobuo 
Published: January 2019

ABSTRACTThe oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal‐like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical‐grade production of OMEC sheets from healthy human donors (n = 8), aiming to evaluate the clinical potential of the exosomes to stimulate epithelial regeneration and to improve understanding of the mode‐of‐action of the cells. Exosomes were isolated from conditioned (cExo) and non‐conditioned (ncExo) media. Characterization was performed using Western blot for common exosomal‐markers: CD9 and flotillin were positive while annexin V, EpCam and contaminating marker GRP94 were negative. Nanoparticle tracking analysis revealed a diameter of ~120 nm and transmission electron microscopy showed a corresponding size and spherical appearance. Human skin fibroblasts exposed to exosomes showed dose‐dependent reduction of proliferation and a considerable increase of growth factor gene expression (HGF, VEGFA, FGF2 and CTGF). The results were similar for both groups, but with a trend towards a larger effect from cExo. To study adhesion, fluorescently labelled exosomes were topically applied to pig oesophageal wound‐beds ex vivo and subsequently washed. Positive signal could be detected after as little as 1 min of adhesion, but increased adhesion time produced a stronger signal. Next, labelled exosomes were added to full‐thickness skin wounds in rats and signal was detected up to 5 days after application. cExo significantly reduced the wound size at days 6 and 17. In conclusion, exosomes from OMEC sheets showed pro‐regenerative effects on skin wound healing. This is the first time that the healing capacity of the oral mucosa is studied from an exosome perspective. These findings might lead to a combinational therapy of cell sheets and exosomes for future patients with early oesophageal cancer.
Functional recovery in photo‐damaged human dermal fibroblasts by human adipose‐derived stem cell extracellular vesicles
Authors: Choi Ji Suk , Lee Cho Woo , Choi Yeo Jin , Kim Jae Dong , Park Hyun‐A , Kim Su Yeon , Park Jae Hyung , Jo Dong‐Gyu , Cho Yong Woo 
Published: January 2019

ABSTRACTUltraviolet‐B (UVB) irradiation causes imbalance between dermal matrix synthesis and degradation through aberrant upregulation of matrix metalloproteinases (MMPs), which leads to overall skin photoaging. We investigated the effects of extracellular vesicles (EVs) derived from human adipose‐derived stem cells (HASCs) on photo‐damaged human dermal fibroblasts (HDFs). EVs were isolated from conditioned media of HASCs with tangential flow filtration and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), western blotting, micro RNA (miRNA) arrays, cytokine arrays and liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS). The effects of EVs on the UVB‐irradiated HDFs were evaluated using scratch assay, ELISA and real‐time PCR. Microarrays exhibited that EVs are rich in various miRNAs and proteins, and that these EV contents are linked to a broad range of biological functions, including fibroblast proliferation, UV protection, collagen biosynthesis, DNA repair and cell ageing. A scratch assay showed that HASC‐EVs enhanced the migration ability of UVB‐irradiated HDFs. Real‐time RT‐PCR and ELISA analyses revealed that the HASC‐derived EVs significantly suppressed the overexpression of MMP‐1, ‐2, ‐3 and ‐9 induced by UVB irradiation and enhanced the expression of collagen types I, II, III and V and elastin. In particular, tissue inhibitor of metalloproteinase (TIMP)‐1 and transforming growth factor (TGF)‐β1, which are important factors involved in MMP suppression and ECM synthesis, were upregulated in EV‐treated HDFs after UVB irradiation. Overall results suggest that diverse components that are enriched in HASC‐derived EVs could act as a biochemical cue for recovery from skin photoaging.
DiffNetFDR: differential network analysis with false discovery rate control
Authors: Zhang Xiao-Fei , Ou-Yang Le , Yang Shuo , Hu Xiaohua , Yan Hong 
Published: January 2019

Abstract

Summary
To identify biological network rewiring under different conditions, we develop a user-friendly R package, named DiffNetFDR, to implement two methods developed for testing the difference in different Gaussian graphical models. Compared to existing tools, our methods have the following features: (i) they are based on Gaussian graphical models which can capture the changes of conditional dependencies; (ii) they determine the tuning parameters in a data-driven manner; (iii) they take a multiple testing procedure to control the overall false discovery rate; and (iv) our approach defines the differential network based on partial correlation coefficients so that the spurious differential edges caused by the variants of conditional variances can be excluded. We also develop a Shiny application to provide easier analysis and visualization. Simulation studies are conducted to evaluate the performance of our methods. We also apply our methods to two real gene expression datasets. The effectiveness of our methods is validated by the biological significance of the identified differential networks.

Availability and implementation
R package and Shiny app are available at https://github.com/Zhangxf-ccnu/DiffNetFDR.

Supplementary information
Supplementary data are available at Bioinformatics online.
NEMO: cancer subtyping by integration of partial multi-omic data
Authors: Rappoport Nimrod , Shamir Ron 
Published: January 2019

Abstract

Motivation
Cancer subtypes were usually defined based on molecular characterization of single omic data. Increasingly, measurements of multiple omic profiles for the same cohort are available. Defining cancer subtypes using multi-omic data may improve our understanding of cancer, and suggest more precise treatment for patients.

Results
We present NEMO (NEighborhood based Multi-Omics clustering), a novel algorithm for multi-omics clustering. Importantly, NEMO can be applied to partial datasets in which some patients have data for only a subset of the omics, without performing data imputation. In extensive testing on ten cancer datasets spanning 3168 patients, NEMO achieved results comparable to the best of nine state-of-the-art multi-omics clustering algorithms on full data and showed an improvement on partial data. On some of the partial data tests, PVC, a multi-view algorithm, performed better, but it is limited to two omics and to positive partial data. Finally, we demonstrate the advantage of NEMO in detailed analysis of partial data of AML patients. NEMO is fast and much simpler than existing multi-omics clustering algorithms, and avoids iterative optimization.

Availability and implementation
Code for NEMO and for reproducing all NEMO results in this paper is in github: https://github.com/Shamir-Lab/NEMO.

Supplementary information
Supplementary data are available at Bioinformatics online.
A nonparametric test for the association between longitudinal covariates and censored survival data
Authors: Oller Ramon , Gómez Melis Guadalupe 
Published: January 2019

SummaryMany biomedical studies focus on the association between a longitudinal measurement and a time-to-event outcome while quantifying this association by means of a longitudinal-survival joint model. In this article we propose using the $LLR$ test — a longitudinal extension of the log-rank test statistic given by Peto and Peto (1972) — to provide evidence of a plausible association between a time-to-event outcome (right- or interval-censored) and a time-dependent covariate. As joint model methods are complex and hard to interpret, it is wise to conduct a preliminary test such as $LLR$ for checking the association between both processes. The $LLR$ statistic can be expressed in the form of a weighted difference of hazards, yielding a broad class of weighted log-rank test statistics known as $LWLR$, which allow a specific emphasis along the time axis of the effects of the time-dependent covariate on the survival. The asymptotic distribution of $LLR$ is derived by means of a permutation approach under the assumption that the censoring mechanism is independent of the survival time and the longitudinal covariate. A simulation study is conducted to evaluate the performance of the test statistics $LLR$ and $LWLR$, showing that the empirical size is close to the nominal significance level and that the power of the test depends on the association between the covariates and the survival time. A data set together with a toy example are used to illustrate the $LLR$ test. The data set explores the study Epidemiology of Diabetes Interventions and Complications (Sparling and others, 2006) which includes interval-censored data. A software implementation of our method is available on github (https://github.com/RamonOller/LWLRtest).
Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects
Authors: Knopman David S , Lundt Emily S , Therneau Terry M , Vemuri Prashanthi , Lowe Val J , Kantarci Kejal , Gunter Jeffrey L , Senjem Matthew L , Mielke Michelle M , Machulda Mary M , Boeve Bradley F , Jones David T , Graff-Radford Jon , Albertson Sabrina M , Schwarz Christopher G , Petersen Ronald C , Jack Clifford R 
Published: January 2019

AbstractAs more biomarkers for Alzheimer’s disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.
Population Pharmacokinetics of Intravenous Colistin in Pediatric Patients: Implications for the Selection of Dosage Regimens
Authors: Ooi Mong How , Ngu Sing Jiat , Chor Yek Kee , Li Jian , Landersdorfer Cornelia B , Nation Roger L 
Published: January 2019

Abstract

Background
Intravenous colistin is widely used to treat infections in pediatric patients. Unfortunately, there is a paucity of pharmacological information to guide the selection of dosage regimens. The daily dose recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) is the same body weight–based dose traditionally used in adults. The aim was to increase our understanding of the patient factors that influence the plasma concentration of colistin, and assess the likely appropriateness of the FDA and EMA dosage recommendations.

Methods
There were 5 patients, with a median age of 1.75 (range 0.1–6.25) years, a median weight of 10.7 (2.9–21.5) kg, and a median creatinine clearance of 179 (44–384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20–0.21) million international units/kg, equivalent to 6.8 (6.5–6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.

Results
The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41–3.50 mg/L), even though all patients received the same body weight–based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.

Conclusions
The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.
Low statin use in nondialysis-dependent chronic kidney disease in the absence of clinical atherosclerotic cardiovascular disease or diabetes
Authors: Markossian Talar W , Kramer Holly J , Burge Nicholas J , Pacold Ivan V , Leehey David J , Huo Zhiping , Schneider Julia , Ling Benjamin , Stroupe Kevin T 
Published: January 2019

Abstract

Background
Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD. Unless physicians recognize the heightened ASCVD risk in this population, statins may not be prescribed in the absence of clinical cardiovascular disease or diabetes, a recognized ASCVD risk equivalent. We examined statin use in adults with nondialysis-dependent CKD and examined whether the use differed in the presence of clinical ASCVD and diabetes.

Methods
This study ascertained statin use from pharmacy dispensing records during fiscal years 2012 and 2013 from the US Department of Veterans Affairs Healthcare System. The study included 581 344 veterans aged ≥50 years with nondialysis-dependent CKD Stages 3–5 with no history of kidney transplantation or dialysis. The 10-year predicted ASCVD risk was calculated with the pooled risk equation.

Results
Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P &lt; 0.001). The 10-year predicted ASCVD risk was ≥7.5% in 95.1% of veterans with CKD, regardless of diabetes status.

Conclusions
Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.