bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wissensstand zur Anaphylaxie und Umgang mit Adrenalinautoinjektoren in Apotheken
Authors: Worm Margitta , Molaie Novin , Dölle Sabine 
Published: November 2018

ZusammenfassungHintergrundAdrenalin intramuskulär mit Hilfe eines Autoinjektors ist das Mittel der Wahl zur Selbstbehandlung schwerer allergischer Reaktionen. Zahlen aus dem Anaphylaxie‐Register zeigen, dass Adrenalinautoinjektoren selten von Patienten eingesetzt werden. Apotheker sind eine wichtige Schnittstelle zwischen verordnendem Arzt und Patienten.Patienten und MethodikZiel der vorliegenden Arbeit war es, den Wissensstand bei Apothekern zur Anaphylaxie und deren Behandlung mittels definierter Wissensfragen strukturiert zu erheben. Hierzu wurden Daten von einer standardisierten Fragebogenerhebung von 213 Apotheken analysiert.ErgebnisseDie Daten zeigen, dass Apotheker die Anaphylaxie als eine Erkrankung mit reduzierter Lebensqualität einschätzen. Die Benennung der häufigsten Auslöser einer Anaphylaxie durch die Apotheker entspricht den Daten aus dem Anaphylaxie‐Register (Insektengift, Nahrungsmittel und Medikamente). Die Auswertung zum Wissensstand der Apotheker zeigt, dass Fallbeschreibungen einer Anaphylaxie richtig zugeordnet werden können. Es bestehen jedoch Wissensdefizite bei Fragen zur Behandlung einer Anaphylaxie mit Adrenalin und zu den Leitlinien.SchlussfolgerungenDie vorliegende Untersuchung zeigt, dass der Wissensstand von Apothekern zur Anaphylaxie verbessert werden kann. Da Apotheker eine wesentliche Schnittstelle bei der Versorgung von Patienten mit allergischen Erkrankungen darstellen, sollte Ziel weiterführender Maßnahmen sein, diese Schnittstelle durch Aufklärungs‐ und Schulungsmodule zu verstärken, um somit die Patientenversorgung zu verbessern.
Therapeutisches Management bei Vitiligo
Authors: Bleuel Rachela , Eberlein Bernadette 
Published: November 2018

ZusammenfassungVitiligo ist eine erworbene Hauterkrankung, an der weltweit 0,5 % der Bevölkerung erkranken und die eine große Herausforderung in der dermatologischen Versorgung darstellt. Die Erkrankung geht für Betroffene oftmals aufgrund der fleckigen Depigmentierung mit einer kosmetischen Entstellung und großem Leidensdruck einher. Pathophysiologisch werden als Hauptursachen für den Verlust funktionierender Melanozyten eine genetische Prädisposition, autoimmune Mechanismen und oxidativer Stress angesehen. Vorgestellt werden die Therapieempfehlungen der europäischen Leitlinie in Ergänzung mit Empfehlungen aus aktuellen Übersichtsarbeiten zu Vitiligo. Bisherige therapeutische Optionen greifen auf drei Wegen: (1.) Regulation der Autoimmunantwort mit topischen und systemischen immunmodulierenden Pharmaka (Kortikosteroide und Calcineurininhibitoren), (2.) Reduktion des melanozytären, oxidativen Stress mittels topischer und systemischer Antioxidantien sowie (3.) Aktivierung der Melanozytenregeneration durch Phototherapie (v. a. UVB) und Transplantation von pigmentierten Zellen. Darüber hinaus sollten dem Patienten Techniken zur Camouflage angeboten werden. Nach erfolgreicher Repigmentierung ist eine Rezidivprophylaxe mit Calcineurininhibitoren sinnvoll. Kombinationstherapien oben genannter Therapieansätze werden generell als erfolgreicher angesehen als Monotherapien. Auch ist ein möglichst früher Therapiebeginn prognostisch günstig. Mit Hilfe der genannten Therapieansätze kann es gelingen das Fortschreiten der Erkrankung aufzuhalten, depigmentierte Herde zu stabilisieren und eine Repigmentierung zu erreichen. Nur in Ausnahmefällen kommt eine dauerhafte Depigmentierung in Frage. Weiterreichende Erkenntnisse zur Pathogenese der Erkrankung lassen auf neue Therapieansätze hoffen.
Komorbidität von lokalisierter Sklerodermie und primär biliärer Cholangitis
Authors: Bali Gábor , Szilvási Anikó , Inotai Dóra , Varga Ágnes , Sárdy Miklós , Kárpáti Sarolta , Medvecz Márta , Szegedi Anna , Hidvégi Bernadett 
Published: November 2018

ZusammenfassungHintergrund und ZieleMorphaea ist häufig mit anderen Autoimmunerkrankungen assoziiert. Über den Zusammenhang zwischen Morphaea und primär biliärer Cholangitis (PBC) ist nur wenig bekannt. Das Ziel dieser Fallstudie war die Untersuchung eines möglichen Zusammenhangs sowie die Identifizierung der Risikofaktoren.Patienten und MethodikWir testeten Morphaea‐Patienten mittels indirekter Immunfluoreszenz und/oder Immunblot auf antimitochondriale Antikörper (AMA). Bei den AMA‐positiven Patienten wurde durch Genotypisierung des Humanen Leukozytenantigens (HLA)‐ und Deep Sequencing die HLA DRB1‐Untergruppe bestätigt.ErgebnisseSechs (6,6%) von 91 Patienten waren AMA‐positiv, bei 4 (4,39%) lag eine PBC vor. Das Durchschnittsalter der AMA‐positiven Patienten lag bei 69,0 Jahren. Bei zwei der 6 AMA‐positiven Patienten wurden gemeinsame prädisponierende Allele (HLA DRB1*15: 01 und HLA DRB1*08) festgestellt. Ein Patient hatte ein für PBC prädisponierendes Allel. Alle Patienten waren weiblich, in der Menopause und zeigten eine Tendenz zur Remission der Morphaea.SchlussfolgerungDie Koexistenz von Morphaea, AMA‐Positivität und PBC ist eine seltene, aber mögliche Assoziation. Gemeinsame prädisponierende HLA‐Allele könnten bei einer solchen Manifestation miteinander interagieren. Bei weiblichen Patienten mit generalisierter Morphaea empfehlen wir vor einer Metothrexat‐Therapie ein AMA‐Screening.
CANadian CAnagliflozin REgistry: Effectiveness and safety of canagliflozin in the treatment of type 2 diabetes mellitus in Canadian clinical practice
Authors: Woo Vincent , Bell Alan , Clement Maureen , Noronha Luis , Tsoukas Michael A. , Camacho Fernando , Traina Shana , Georgijev Natasha , Culham Matthew D. , Rose Jennifer B. , Rapattoni Wally , Bajaj Harpreet S. 
Published: November 2018

AimThere is limited information concerning the effects of canagliflozin (CANA), a sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) in a real‐world clinical setting in Canada. CanCARE is a 12‐month, prospective, observational analysis to demonstrate the effectiveness and safety of CANA in usual clinical practice in Canada.Materials and methodsSGLT2i‐naïve adult patients with type 2 diabetes mellitus (T2DM) (n = 527) on a stable antihyperglycemic agent (AHA) regimen with glycated hemoglobin (A1C) ≥ 7%, an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, were initiated on CANA as part of their usual treatment approach, and were followed for a period of 12 months. The primary effectiveness objective was the mean change in HbA1c from baseline to 6 and 12 months.ResultsSignificant improvement from baseline in mean HbA1c levels were observed at 6 months (−0.90%; 95% CI, −1.02, −0.78) and at 12 months (−1.04%; 95% CI, −1.15, −0.92), regardless of duration of diabetes or background AHA treatment regimen. Similarly, significant decreases in systolic blood pressure (−4.65 mm Hg); body weight (−3.24 kg), waist circumference (−2.91 cm) and body mass index (−1.15 kg/m2) were observed at 12 months. Additionally, 40.5% of patients achieved the double endpoint (≥0.5% HbA1c reduction and ≥ 3% weight loss), while 24.3% of patients achieved the triple composite endpoint (≥0.5% HbA1c reduction, ≥3% weight loss and ≥ 4 mm Hg systolic blood pressure reduction). No unexpected adverse events were reported.ConclusionCANA provided sustained clinically meaningful improvements in cardiometabolic parameters in this study in a real‐world setting, confirming findings from randomized controlled trials.
Double‐blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase‐4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT‐I Study
Authors: Roussel Ronan , Duran‐García Santiago , Zhang Yilong , Shah Suneri , Darmiento Carolyn , Shankar R. Ravi , Golm Gregory T. , Lam Raymond L. H. , O'Neill Edward A. , Gantz Ira , Kaufman Keith D. , Engel Samuel S. 
Published: November 2018

AimsTo compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine.Materials and methodsEligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase‐4 (DPP‐4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP‐4 inhibitors and sulphonylureas) and stabilized during a run‐in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L.ResultsA total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and −20.5 mmol/mol (−1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and −15.5 mmol/mol (−1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was −5.0 mmol/mol (−0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups.ConclusionWhen initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.
Cognitive outcomes following epilepsy in infancy: A longitudinal community‐based study
Authors: O'Reilly Helen , Eltze Christin , Bennett Kate , Verhaert Kristien , Webb Rebecca , Merrett Anna , Scott Rod C. , Whitney Andrea , Helen Cross J. , de Haan Michelle 
Published: November 2018

SummaryObjectiveOnset of epilepsy before 2 years of age is associated with poor cognitive outcome; however, the natural course of the range of epilepsies that occur at this age is unknown. The aim of this prospective community‐based study was to investigate the neuropsychological development of infants with newly diagnosed epilepsy longitudinally and to identify the clinical factors that predict long‐term impairment.MethodsSixty‐six infants <24 months of age were enrolled in the baseline phase of this study; 40 were seen again at 1‐year follow‐up and 40 at 3‐year follow‐up. Children underwent a neurological and neuropsychological assessment at each time point.ResultsMore than 55% of children demonstrated impaired cognitive functioning at each assessment, with a similar percentage showing impaired memory and attention at 3‐year follow‐up. Cognitive scores obtained at each time point were correlated. More than 20 seizures/seizure clusters prior to assessment and an abnormal neurologic examination predicted poor cognitive functioning at baseline, whereas continuing seizures and baseline cognitive score predicted 3‐year intelligence quotient (IQ)/cognitive score.SignificanceThese findings demonstrate the following: (1) infants who are performing poorly at baseline continue to display impaired development at follow‐up, (2) these children are delayed across a range of neuropsychological functions, and (3) a high number of seizures close to initial diagnosis and continuing seizures at follow‐up independently predict cognitive impairment. These findings help to identify those infants with new‐onset epilepsy who are most at risk for poor developmental outcome and suggest that multimodal interventions should be instituted early in the course of the disorder to improve outcomes.
Surgical and developmental outcomes of corpus callosotomy for West syndrome in patients without MRI lesions
Authors: Baba Hiroshi , Toda Keisuke , Ono Tomonori , Honda Ryoko , Baba Shiro 
Published: November 2018

SummaryObjectiveThis retrospective study was designed to assess the impact of corpus callosotomy (CC) in patients with intractable West syndrome (WS) without lesions on magnetic resonance imaging (MRI).MethodsThis study involved 56 patients with WS who underwent CC between January 2000 and December 2014. Seizure outcomes and changes in psychomotor development were analyzed.ResultsMean age at the onset of epilepsy and at the time of CC was 5.1 and 22.6 months, respectively. Mean duration of epilepsy before CC was 17.6 months. Video‐electroencephalography (EEG) monitoring showed bilateral ictal and interictal abnormalities before CC. Mean follow‐up duration was 36.6 months. At final follow‐up, seizure outcomes after CC were seizure‐free in 18 patients (32.1%), excellent (E: >80% reduction in seizure frequency) in 15 (26.8%), good (G: >50% reduction) in 10 (17.9%), and poor (P: <50% reduction) in 13 (23.2%). Epileptic spasms (ES) were eliminated in 24 patients (42.9%). However, tonic seizure (TS) outcomes were poor (P < 0.05). Of preoperative predictive factors related to seizure outcome, developmental delay before epilepsy onset correlated with poor outcome (P < 0.05). One year post‐CC, 6 patients (10.7%) had no epileptic abnormality on EEG, 19 (33.9%) had lateralized epileptic abnormalities, and 31 (55.4%) had bilateral asynchronous epileptic abnormalities. All patients without epileptic discharge achieved seizure freedom. Fifteen of 19 (78.9%) patients in the lateralized group and 12 of 31 (38.7%) in the bilateral asynchronous group had worthwhile outcomes (F + E). The patterns of EEG changes after CC correlated with seizure outcome (P < 0.01). Progressive declines in developmental quotient were prevented in patients with worthwhile outcomes.SignificanceCC represents an important therapeutic option for patients with WS without resectable MRI lesions. Transcallosal seizure bilateralization is critical for bilateral ES generation. Early identification of potential CC candidates and surgical intervention are important for better seizure control and cognitive capacity preservation before severe developmental delay development.
Does the Court of Justice own the Treaties? Interpretative pluralism as a solution to over‐constitutionalisation
Authors: Davies Gareth 
Published: November 2018

AbstractIt is often assumed that Court of Justice interpretations of EU law are definitive and binding. However, this conflicts with conventional ideas about the trias politica, as well as with the principle of conferral, and rests on no more than the Court's own assertion. It also has harmful policy consequences, forcing national courts into constitutional resistance and, in claiming to fix the meaning of the Treaties, smothering Union politics. Interpretative pluralism, by contrast, insists on the possibility of diverging interpretations. That allows for wider participation in the construction of EU law, while retaining the integrity of Union law through commitment to shared texts and a balance of power between institutions. Institutional disagreements are reframed, not as conflicts between legal orders, but as conflicts about the meaning of a shared one. This approach is more profoundly integrative than the Court's top‐down approach, and also allows for greater diversity and experiment.
Integrated Surface and Subsurface Hydrological Modeling with Snowmelt and Pore Water Freeze–Thaw
Authors: Schilling Oliver S. , Park Young‐Jin , Therrien René , Nagare Ranjeet M. 
Published: November 2018

AbstractFor the simulation of winter hydrological processes a gap in the availability of flow models existed: one either had the choice between (1) physically‐based and fully‐integrated, but computationally very intensive, or (2) simplified and compartamentalized, but computationally less expensive, simulators. To bridge this gap, we here present the integration of a computationally efficient representation of winter hydrological processes (snowfall, snow accumulation, snowmelt, pore water freeze–thaw) in a fully‐integrated surface water‐groundwater flow model. This allows the efficient simulation of catchment‐scale hydrological processes in locations significantly influenced by winter processes. Snow accumulation and snowmelt are based on the degree‐day method and pore water freeze–thaw is calculated with a vertical heat conduction approach. This representation of winter hydrological processes is integrated into the fully‐coupled surface water‐groundwater flow model HydroGeoSphere. A benchmark for pore water freeze–thaw as well as two illustrative examples are provided.
Azorean macroalgae (Petalonia binghamiae, Halopteris scoparia and Osmundea pinnatifida) bioprospection: a study of fatty acid profiles and bioactivity
Authors: Campos Ana M. , Matos Joana , Afonso Cláudia , Gomes Romina , Bandarra Narcisa M. , Cardoso Carlos 
Published: November 2018

SummaryThe Azorean macroalgae Petalonia binghamiae, Halopteris scoparia and Osmundea pinnatifida are undervalued and require further study regarding their potential use as food. These three seaweed species had low fat contents, and their fatty acid (FA) profiles were characterised by a high proportion of saturated FA (SFA) in the case of O. pinnatifida and similar weights of SFA and polyunsaturated FA (PUFA) in the other two species. Within the PUFAs, the ω3 PUFAs were the most prominent in O. pinnatifida and P. binghamiae, yielding ω3/ω6 ratios that were higher than one. Eicosapentaenoic acid (EPA, 20:5 ω3) was the most important ω3 PUFA (10–14%). Regarding the other bioactive compounds, the polyphenols were found to reach non‐negligible levels (140–220 mg/100 g dw). Significant antioxidant activity was detected. Ethanolic extracts of H. scoparia and aqueous extracts of P. binghamiae showed cyclooxygenase‐2 (COX‐2) inhibitory capacities between 40% and 79%, indicating anti‐inflammatory activity.
Molecular differences in Alzheimer's disease between male and female patients determined by integrative network analysis
Authors: Sun Lin‐Lin , Yang Song‐Lin , Sun Hui , Li Wei‐Da , Duan Shu‐Rong 
Published: November 2018

AbstractAlzheimer's disease (AD) is a complex neurodegenerative disease and the most common cause of dementia among the elderly. There has been increasing recognition of sex differences in AD prevalence, clinical manifestation, disease course and prognosis. However, there have been few studies on the molecular mechanism underlying these differences. To address this issue, we carried out global gene expression and integrative network analyses based on expression profiles (GSE84422) across 17 cortical regions of 125 individuals with AD. There were few genes that were differentially expressed across the 17 regions between the two sexes, with only four (encoding glutamate metabotropic receptor 2, oestrogen‐related receptor beta, kinesin family member 26B, and aspartoacylase) that were differentially expressed in three regions. A pan‐cortical brain region co‐expression network analysis identified pathways and genes (eg, glycogen synthase kinase 3β) that were significantly associated with clinical characteristics of AD (such as neurofibrillary score) in males only. Similarity analyses between region‐specific networks indicated that male patients exhibited greater variability, especially in the superior parietal lobule, dorsolateral prefrontal cortex and occipital visual cortex. A network module analysis revealed an association between clinical traits and crosstalk of sex‐specific modules. An examination of temporal and spatial patterns of sex differences in AD showed that molecular networks were more conserved in females than in males in different cortical regions and at different AD stages. These findings provide insight into critical molecular pathways governing sex differences in AD pathology.
Serum Metrnl is associated with the presence and severity of coronary artery disease
Authors: Liu Zheng‐Xia , Ji Hui‐Hong , Yao Min‐Peng , Wang Li , Wang Yue , Zhou Ping , Liu Ying , Zheng Xi‐Feng , He Hui‐Wei , Wang Lian‐Sheng , Gao Wei , Lu Xiang 
Published: November 2018

AbstractMeteorin‐like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissue. Metrnl stimulates energy expenditure and improves glucose tolerance in rodents. However, whether Metrnl plays a role in coronary artery disease (CAD) remains to be elucidated. The present study aimed to investigate the association of serum Metrnl with CAD in Chinese patients. A total of 193 patients with CAD and 156 control subjects were enrolled in this study. Serum Metrnl concentration was measured by enzyme‐linked immunosorbent assay. Anthropometric phenotypes, fasting glucose, serum lipids, and inflammatory cytokines were measured. Serum Metrnl was lower in CAD patients when compared to those controls (132.41 vs 173.17 pg/mL, P < 0.001). Serum Metrnl was negatively correlated with metabolic parameters, including body mass index, total cholesterol, and low‐density lipoprotein cholesterol as well as inflammatory markers including high‐sensitivity C‐reactive protein, IL‐1β, and IL‐11 even after adjustment for potential confounding variables (P < 0.05). In multivariable logistic regression analyses, compared to those in the highest tertile of serum Metrnl levels, subjects in the lowest tertile had the highest risks for CAD (adjusted OR = 2.63, 95% CI = 1.46‐4.27, P = 0.001). After adjustment for potential confounding variables, serum Metrnl was also decreased as the number of stenosed vessels increased (P < 0.001). Furthermore, decreased Metrnl level was negatively correlated with the severity of CAD quantified by the Gensini score. This first case‐control study shows significant associations of serum Metrnl with the presence and severity of CAD, suggesting Metrnl might be a new promising therapeutic target for CAD.
CPT1A‐mediated succinylation of S100A10 increases human gastric cancer invasion
Authors: Wang Chao , Zhang Chen , Li Xiang , Shen Jiajia , Xu Yue , Shi Hui , Mu Xianmin , Pan Jinshun , Zhao Ting , Li Mengjing , Geng Biao , Xu Che , Wen Hao , You Qiang 
Published: November 2018

AbstractGastric cancer (GC) is a malignancy of the lining of the stomach and is prone to distant metastasis, which involves a variety of complex molecules. The S100 proteins are a family of calcium‐binding cytosolic proteins that possess a wide range of intracellular and extracellular functions and play pivotal roles in the invasion and migration of tumour cells. Among these, S100A10 is known to be overexpressed in GC. Lysine succinylation, a recently identified form of protein post‐translational modification, is an important regulator of cellular processes. Here, we demonstrated that S100A10 was succinylated at lysine residue 47 (K47), and levels of succinylated S100A10 were increased in human GC. Moreover, K47 succinylation of S100A10 was stabilized by suppression of ubiquitylation and subsequent proteasomal degradation. Furthermore, carnitine palmitoyltransferase 1A (CPT1A) was found to function as a lysine succinyltransferase that interacts with S100A10. Succinylation of S100A10 is regulated by CPT1A, while desuccinylation is regulated by SIRT5. Overexpression of a succinylation mimetic mutant, K47E S100A10, increased cell invasion and migration. Taken together, this study reveals a novel mechanism of S100A10 accumulation mediated by succinylation in GC, which promotes GC progression and is regulated by the succinyltransferase CPT1A and SIRT5‐mediated desuccinylation.