bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between Fas and Fas ligand gene polymorphism and preeclampsia risk
Authors: Wang Tingting , Lian Yunyun 
Published: February 2019

Abstract
Preeclampsia is an idiopathic multisystem disorder with partial genetic and immunological etiology. Several studies investigated the association between various single-nucleotide polymorphisms (SNPs) in Fas and Fas ligand (FasL) genes and the risk of preeclampsia. However, they achieved inconsistent results. Therefore, we conducted a meta-analysis by systematically searching the Cochrane Library, PubMed and Embase databases and assessed this association by calculating pooled odds ratios with 95% confidence interval to reach a more trustworthy conclusion. Subgroup analyses by genotype methods and source of controls (SOC) were also conducted. Seven citations containing nine studies were included for four SNPs (Fas -670 A/G, FasL 124A/G, FasL -844C/T, Fas -1377 G/A) in this meta-analysis. Our data suggested the G allele and genotype GG of the Fas -670 A/G polymorphism, GG genotype of the FasL 124A/G polymorphism, and TT genotype of the FasL -844C/T polymorphism increased the risk of preeclampsia. Stratification analyses by genotype methods and SOC also indicated that Fas -670 A/G polymorphism was related to increased risk for preeclampsia. In conclusion, Fas and FasL gene polymorphisms play important roles in the development of preeclampsia. Further well-designed studies in other races are needed to confirm the findings of this meta-analysis.
Inhibition of PAK1 alleviates cerulein-induced acute pancreatitis via p38 and NF-κB pathways
Authors: Zhu Minghui , Xu Yan , Zhang Wenbin , Gu Tianyi , Wang Daming 
Published: February 2019

AbstractAcute pancreatitis is a life-threatening disease accompanied by systemic inflammatory response. NF-κB and p38 signal pathways are activated in AP induced by cerulein. And PAKs are multifunctional effectors of Rho GTPases with kinase activity. In the present study, the function of P21-activated kinase 1 (PAK1) in AP was investigated, and found that PAK1 was up-regulated in pancreas of AP mice model, and led to NF-κB and p38 pathway activation. PAK1 inhibition by shRNA or small molecule inhibitor FRAX597 decreased NF-κB and p38 activity, also alleviated the pathological damage in the pancreas of AP mice model, including decreasing the amylase and lipase levels in serum, decreasing the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in AP. These results suggested that PAK1 inhibition protects against AP by inhibiting NF-κB and p38 pathways, and indicated that PAK1 is a potential therapy to alleviate AP patients in clinic, and these need to be explored further.
Aminosäuren und chronische Erschöpfung – Welche Möglichkeiten zur Besserung gibt es?
Authors: Meister Doris 
Published: February 2019

ZusammenfassungDauerstress kann physische, psychische und kognitive Auswirkungen haben, das soziale Verhalten beeinflussen und sich in einer endokrinen Insuffizienz manifestieren. Eine aktuelle Studie an Personen mit chronisch-psychologischer Stressbelastung und Erschöpfung untersuchte den Einfluss einer definierten Aminosäuren-Mineralstoffmischung auf das Stressempfinden und die endokrin-kardiometabolische Situation. In der Verumgruppe zeigten sich ein signifikanter Rückgang des subjektiv wahrgenommenen Stresses sowie ein positiver Einfluss auf serotonerges System und Magnesiumstoffwechsel. Unter Placebo kam es zu einem Anstieg von kardiometabolischen Risikofaktoren.
Metabolic Tuning statt Doping: Ausgewählte Mikronährstoffe im Leistungssport
Authors: Gröber Uwe 
Published: February 2019

ZusammenfassungEine unzureichende Versorgung mit Mikronährstoffen resultiert bei Sportlern in einer geringeren Leistungs- und Regenerationsfähigkeit sowie einer erhöhten Infektanfälligkeit. Wegen ihrer Bedeutung für Energiehaushalt, Wachstum und Leistungsfähigkeit der Muskulatur sowie bei der Sauerstoffverwertung haben u. a. Vitamin D, Kalium, Eisen und Aminosäuren zentralen Stellenwert im Leistungssport. Mangelzustände aufgrund gesteigerten Bedarfs oder erhöhter Ausscheidung mit Schweiß und Urin sind durch angepasste Ernährung und Supplementierung auszugleichen, um sportliche und mentale Leistungsfähigkeit des Athleten zu optimieren.
Fallbericht 39-jährige III. Gravida, III. Para mit Inversio uteri nach Steißgeburt
Authors: Findeklee Sebastian 
Published: February 2019

ZusammenfassungDie Inversio uteri bezeichnet das Umstülpen der Gebärmutter in die Scheide postpartal. Sie ist äußerst selten, aber stellt einen geburtshilflichen Notfall dar. Die Gefahr für die Gebärende besteht in einer Uterusatonie mit dem Verlust großer Mengen Blut in kurzer Zeit. Dies kann, wenn keine rechtzeitige Therapie erfolgt, zum hypovolämischen Schock bis zum Herz-Kreislaufversagen führen. Die Therapie erfolgt durch eine Uterus-Reposition in Vollnarkose mit anschließender manueller Plazentalösung. Anschließend folgen die Kürettage und die Gabe von hochpotenten Uterotonika wie Sulproston. Durch den in der Regel hohen Blutverlust kommt es häufig zu einer Störung des Gerinnungssystems, sodass eine Substitution von Antifibrinolytika wie Tranexamsäure, Gerinnungsfaktoren und/oder Erythrozytenkonzentraten erforderlich wird. Gelingt keine vaginale Reposition des Uterus, so bleiben als Ultima Ratio nur die Reposition per Laparotomie oder die Hysterektomie. Wir berichten über eine 39-jährige III. Gravida, III. Para mit 36+3 Schwangerschaftswochen (SSW), bei der es nach spontaner Steißgeburt bei Placenta accreta zur Inversio uteri kam, die vaginal reponiert werden konnte.
Akute myeloische Leukämie bei Erwachsenen – Ein Update zu Diagnostik, Risikoklassifikation und Therapie
Authors: Spiekermann Karsten , Shen Anne-Sophie 
Published: February 2019

ZusammenfassungMittlerweile sind viele neuartige und zielgerichtete Substanzen in der Therapie der AML verfügbar. Durch die Fortschritte in der Molekulargenetik lassen sich zielgerichtete Therapieoptionen ableiten. Umso wichtiger sind eine präzise und vor allem rasche zyto- und molekulargenetische Charakterisierung der AML sowie die Risikobestimmung. Dieser Beitrag legt den Schwerpunkt auf Neuerungen in der Klassifikation und bei den Therapieansätzen.
Chronische Myeloische Leukämie
Authors: Hochhaus Andreas , Eigendorff Ekkehard , Ernst Thomas 
Published: February 2019

ZusammenfassungVom fachlichen Standpunkt aus gesehen, stellt die chronische myeloische Leukämie (CML) eine Modellerkrankung für Diagnostik und Therapie neoplastischer Erkrankungen dar. Die zugrundeliegende zytogenetische Aberration, das Philadelphia-Chromosom mit der Genfusion sowie der mehrstufige Verlauf ermöglichen es, molekular-zytogenetische Erkenntnisse auf die klinische Anwendung zu übertragen. Dabei spielen nicht nur „Meilensteine“ eine Rolle.
Erfolgreiche Zelltherapie mit virusspezifischen T-Zellen vom HLA-teilkompatiblen Drittspender bei disseminierter Adenovirus-Infektion früh nach allogener Stammzelltransplantation
Authors: Kafa Kinan , Tischer Sabine , Heuft Hans-Gert , Blasczyk Rainer , Priesner Christoph , Klusmann Jan-Henning , Eiz-Vesper Britta , Maecker-Kolhoff Britta 
Published: February 2019

ZusammenfassungAdenovirus-Infektionen (AdV-Infektionen) nach pädiatrischer hämatopoetischer Stammzelltransplantation sind häufig und treten in 10 – 20 % aller allogenen Transplantationen auf (bis 30 % der T-Zell-depletierten Transplantationen). Sie sind mit einer hohen Rate an Morbidität und Mortalität verbunden. Da die antivirale Therapie nur virostatisch wirkt und durch erhebliche Toxizität eine limitierende Behandlungsoption darstellt, ist die virusspezifische T-Zell-Therapie als sichere und gut verträgliche komplikationsarme Option sehr attraktiv. Unsere 4-jährige Patientin entwickelte 3 Wochen nach allogener hämatopoetischer Transplantation vom 10/10-HLA-passenden Registerspender eine disseminierte AdV-Infektion (Enteritis, persistierendes Fieber, Sepsis). Eine antivirale Therapie mit Cidofovir zeigte eine gute Wirksamkeit, musste aber wegen erheblicher Nephrotoxizität abgebrochen werden. Unter einer Überbrückungstherapie bis zur geplanten Gabe AdV-spezifischer T-Zellen mit Brincidofovir (BCV) stabilisierte sich die AdV-Last im Blut, blieb aber signifikant hoch. AdV-spezifische T-Zellen der HLA-haploidenten Mutter wurden nach Stimulation mit AdV-Hexon-Peptid-Gemisch über Interferon-γ-Zytokinsekretion (Interferon-γ: IFN-γ) und immunmagnetische Separation aufgereinigt und 1-malig in einem Frischpräparat mit einer Dosis von 2,5 × 104CD3+-Zellen/kg Körpergewicht verabreicht. Die Anwendung verlief komplikationslos und führte zu einer schnellen Elimination des Virus im Blut (ca. nach 2 Wochen). Nahezu zeitgleich (ca. 3 Wochen nach der AdV-spezifischen T-Zell-Gabe) konnten erstmals AdV-spezifische T-Zellen im Patientenblut nachgewiesen werden. Der adoptive Transfer AdV-spezifischer T-Zellen vom HLA-teilpassenden Familienspender als „Third-Party-Spender“ stellt eine rasch verfügbare und wenig toxische Behandlungsoption für Patienten mit refraktärer AdV-Erkrankung dar.
Cochlear Implantation for Single-Sided Deafness: A New Treatment Paradigm
Authors: Zeitler Daniel , Dorman Michael 
Published: February 2019

AbstractUnilateral severe-to-profound sensorineural hearing loss (SNHL), also known as single sided deafness (SSD), is a problem that affects both children and adults, and can have severe and detrimental effects on multiple aspects of life including music appreciation, speech understanding in noise, speech and language acquisition, performance in the classroom and/or the workplace, and quality of life. Additionally, the loss of binaural hearing in SSD patients affects those processes that rely on two functional ears including sound localization, binaural squelch and summation, and the head shadow effect. Over the last decade, there has been increasing interest in cochlear implantation for SSD to restore binaural hearing. Early data are promising that cochlear implantation for SSD can help to restore binaural functionality, improve quality of life, and may faciliate reversal of neuroplasticity related to auditory deprivation in the pediatric population. Additionally, this new patient population has allowed researchers the opportunity to investigate the age-old question “what does a cochlear implant (CI) sound like?.”
Disciplinary registers in a first-year program
Authors: Ferreira Alfredo A. , Zappa-Hollman Sandra 
Published: February 2019

AbstractWith notable exceptions, few studies of teaching and learning of scholarly registers and genres to users of English as an additional language focus on curriculum. For a contextualized understanding of register-curriculum relations, this study investigates disciplinary registers in the Academic English Program at Vantage College, a new alternative-entry, first-year program at the University of British Columbia, Canada. In integrating content and language instruction, the curriculum adopts systemic functional linguistics as the informing theory of language. Program registers and their relations are investigated usingMatthiessen’s (2015)context-based register typology. This novel case study highlights register-curriculum relations in key aspects, including discipline-specific variation in register instruction, planned learning trajectories, faculty collaborations, and relations between English for general and specific academic purposes.
Transverse structure and energy deposition by a subTW femtosecond laser in air: from single filament to superfilament
Authors: Pushkarev D , Mitina E , Shipilo D , Panov N , Uryupina D , Ushakov A , Volkov R , Karabutov A , Babushkin I , Demircan A , Morgner U , Kosareva O , Savel’ev A 
Published: February 2019

Abstract
We traced experimentally transition from a single air filament to the superfilament under action of powerful loosely focused (NA ∼ 0.0021) femtosecond beam. Two regimes were exploited with multifilament formation by artificial amplitude or intrinsic amplitude/phase front modulation of the beam having 10–60 critical powers P
cr. Transverse spatial structure and energy density in the filament were studied using wideband acoustic detection and beam mode imaging single shot techniques at different distances along the optical path. We showed that with intrinsic front modulation a single extremely long ionized channel is formed provided peak power P of the initial beam does not exceed 20P
cr. Its volumetric energy density is ∼1.5–3 times higher than in the single filament, while linear energy density is almost 10 times higher. Artificial amplitude modulation leads to formation of either a single long filament or two closely spaced filaments at the same initial conditions. Maximal volumetric energy density was the same in both cases and slightly less than without this modulation. A few closely spaced filaments are generated at higher peak powers P with volumetric and linear energy densities experiencing fast nonlinear increase with P. Highest linear energy density achieved was 600 μJ cm−1, i.e. almost 100 times higher than that of the single filament with increase in energy 10 times only. The volumetric energy density also increases by a factor of 10 to ∼800 mJ cm−3 proving huge increase in intensity and electron density that is characteristic feature of the superfilamentation. These findings were supported by the numerical simulations based on the Forward Maxwell equation with resolved driver of the field that showed superfilament splitting and confirmed energy densities estimated from the experimental data.
Functional connectivity associated with tau levels in ageing, Alzheimer’s, and small vessel disease
Authors: Franzmeier Nicolai , Rubinski Anna , Neitzel Julia , Kim Yeshin , Damm Alexander , Na Duk L , Kim Hee Jin , Lyoo Chul Hyoung , Cho Hana , Finsterwalder Sofia , Duering Marco , Seo Sang Won , Ewers Michael ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2019

Abstract
In Alzheimer’s disease, tau pathology spreads hierarchically from the inferior temporal lobe throughout the cortex, ensuing cognitive decline and dementia. Similarly, circumscribed patterns of pathological tau have been observed in normal ageing and small vessel disease, suggesting a spatially ordered distribution of tau pathology across normal ageing and different diseases. In vitro findings suggest that pathological tau may spread ‘prion-like’ across neuronal connections in an activity-dependent manner. Supporting this notion, functional brain networks show a spatial correspondence to tau deposition patterns. However, it remains unclear whether higher network-connectivity facilitates tau propagation. To address this, we included 55 normal aged elderly (i.e. cognitively normal, amyloid-negative), 50 Alzheimer’s disease patients (i.e. amyloid-positive) covering the preclinical to dementia spectrum, as well as 36 patients with pure (i.e. amyloid-negative) vascular cognitive impairment due to small vessel disease. All subjects were assessed with AV1451 tau-PET and resting-state functional MRI. Within each group, we computed atlas-based resting-state functional MRI functional connectivity across 400 regions of interest covering the entire neocortex. Using the same atlas, we also assessed within each group the covariance of tau-PET levels among the 400 regions of interest. We found that higher resting-state functional MRI assessed functional connectivity between any given region of interest pair was associated with higher covariance in tau-PET binding in corresponding regions of interest. This result was consistently found in normal ageing, Alzheimer’s disease and vascular cognitive impairment. In particular, inferior temporal tau-hotspots, as defined by highest tau-PET uptake, showed high predictive value of tau-PET levels in functionally closely connected regions of interest. These associations between functional connectivity and tau-PET uptake were detected regardless of presence of dementia symptoms (mild cognitive impairment or dementia), amyloid deposition (as assessed by amyloid-PET) or small vessel disease. Our findings suggest that higher functional connectivity between brain regions is associated with shared tau-levels, supporting the view of prion-like tau spreading facilitated by neural activity.
Fairy Tales versus Facts: Genre Matters to the Developing Brain
Authors: Aboud Katherine S , Bailey Stephen K , Del Tufo Stephanie N , Barquero Laura A , Cutting Laurie E 
Published: February 2019

Abstract
Neurobiological studies of discourse comprehension have almost exclusively focused on narrative comprehension. However, successful engagement in modern society, particularly in educational settings, also requires comprehension with an aim to learn new information (i.e., “expository comprehension”). Despite its prevalence, no studies to date have neurobiologically characterized expository comprehension as compared with narrative. In the current study, we used functional magnetic resonance imaging in typically developing children to test whether different genres require specialized brain networks. In addition to expected activations in language and comprehension areas in the default mode network (DMN), expository comprehension required significantly greater activation in the frontoparietal control network (FPN) than narrative comprehension, and relied significantly less on posterior regions in the DMN. Functional connectivity analysis revealed that, compared with narrative, the FPN robustly correlated with the DMN, and this inter-network communication was higher with increased reading expertise. These findings suggest that, relative to narrative comprehension, expository comprehension shows (1) a unique configuration of the DMN, potentially to support non-social comprehension processes, and (2) increased utilization of top-down regions to help support goal-directed comprehension processes in the DMN. More generally, our findings reveal that different types of discourse-level comprehension place diverse neural demands on the developing brain.
Epidermal growth factor-like repeats of SCUBE1 derived from platelets are critical for thrombus formation
Authors: Liao Wei-Ju , Wu Meng-Ying , Peng Chen-Chung , Tung Yi-Chung , Yang Ruey-Bing 
Published: February 2019

Abstract

Aims
SCUBE1 [signal peptide-CUB-epidermal growth factor (EGF) domain-containing protein 1], expressed in endothelial cells (ECs) and platelets, exists in soluble or membrane forms. We previously showed that soluble SCUBE1 is a biomarker for platelet activation and also an active participant of thrombosis. However, whether the adhesive module of its EGF-like repeats is essential and the specific contribution of SCUBE1 synthesized in ECs or platelets to thrombosis in vivo remain unclear.

Methods and results
We generated new mutant (Δ2) mice lacking the entire EGF-like repeats to evaluate the module’s functional importance during thrombogenesis in vivo. The Δ2 platelet-rich plasma showed markedly impaired platelet aggregation induced by agonists including adenosine diphosphate, collagen, the thrombin agonist PAR-4 peptide and the thromboxane A2 analogue U46619. Consistently, genetic ablation of the EGF-like repeats diminished arterial thrombosis and protected Δ2 mice against lethal thromboembolism. On flow chamber assay, whole blood isolated from Δ2 or wild-type (WT) mice pre-treated with blocking antibodies against the EGF-like repeats showed a significant decrease in platelet deposition and thrombus formation on collagen-coated surfaces under arterial shear rates. Moreover, we created animals expressing SCUBE1 only in ECs (S1-EC) or platelets (S1-PLT) by reciprocal bone-marrow transplantation between WT and Δ2 mice. The time of carotid arterial thrombosis induced by ferric chloride was normal in S1-PLT chimeric mice but much prolonged in S1-EC animals.

Conclusions
We demonstrate that platelet-derived SCUBE1 plays a critical role in arterial thrombosis via its adhesive EGF-like repeats in vivo and suggest targeting these adhesive motifs of SCUBE1 for potential anti-thrombotic strategy.
Echocardiographic predictors of reoperation for subaortic stenosis in children and adults
Authors: Theocharis Paraskevi , Viola Nicola , Papamichael Nikolaos D , Kaarne Markku , Bharucha Tara 
Published: February 2019

Abstract

OBJECTIVES
Subaortic stenosis (SAS) can present as various types of obstruction of the left ventricular outflow tract (LVOT) below the level of the aortic valve. Even though corrective surgery has been identified as the most effective treatment, SAS more frequently reoccurs requiring reoperation in a significant proportion of the patients. Previous studies have focused on predictors of recurrence in various subgroups of patients with SAS, but rarely in the overall population of patients with SAS. The aim of this study was to determine the predictors of recurrence of SAS after initial corrective surgery.

METHODS
Patients from the database of the Congenital Cardiology Department of the University Hospital of Southampton with significant SAS requiring corrective surgery were included in the study. Data retrieved were obtained and used to determine the predictors of SAS recurrence after the initial corrective surgery.

RESULTS
Eighty-two patients (paediatric, n = 72 and adult, n = 10) who underwent initial successful resection were included in the analysis. Thirty patients required reoperation for recurrent SAS. These were significantly younger (median age 3.0 vs 6.7 years, P = 0.002). The recurrence of SAS was more common in patients with an interrupted aortic arch (23.3% vs 3.8%, P = 0.010) and unfavourable left ventricle geometry (43.3% vs 7.6%, P < 0.001), with steeper aortoseptal angle (131.0° ± 8.7° vs 136.1° ± 8.6°, P = 0.030), shorter distance between the point of obstruction of the LVOT and the aortic valve annulus in systole and diastole (median 4.30 vs 5.90 mm, P = 0.003 and 3.65 vs 4.95 mm, P = 0.006, respectively) and in those who had higher residual peak and mean LVOT gradients postoperatively (29.3 ± 16.0 vs 19.8 ± 10.7 mmHg, P = 0.006 and 15.9 ± 8.3 vs 10.1 ± 5.8 mmHg, P = 0.002, respectively). Overall, the presence of an interrupted aortic arch [odds ratio (OR) 10.34, 95% confidence interval (CI) 1.46–73.25; P < 0.019] and unfavourable left ventricle geometry (OR 10.42, 95% CI 1.86–58.39; P < 0.008) could independently predict reoperation for SAS after initial successful resection.

CONCLUSIONS
Patients who have initial corrective surgery for SAS at a younger age, unfavourable left ventricle geometry, an interrupted aortic arch and higher early postoperative LVOT gradients are more likely to have recurrent SAS requiring reoperation.