bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis
Authors: Strnad Pavel , Buch Stephan , Hamesch Karim , Fischer Janett , Rosendahl Jonas , Schmelz Renate , Brueckner Stefan , Brosch Mario , Heimes Carolin V , Woditsch Vivien , Scholten David , Nischalke Hans Dieter , Janciauskiene Sabina , Mandorfer Mattias , Trauner Michael , Way Michael J , McQuillin Andrew , Reichert Matthias C , Krawczyk Marcin , Casper Markus , Lammert Frank , Braun Felix , von Schönfels Witigo , Hinz Sebastian , Burmeister Greta , Hellerbrand Claus , Teufel Andreas , Feldman Alexandra , Schattenberg Joern M , Bantel Heike , Pathil Anita , Demir Muenevver , Kluwe Johannes , Boettler Tobias , Ridinger Monika , Wodarz Norbert , Soyka Michael , Rietschel Marcella , Kiefer Falk , Weber Thomas , Marhenke Silke , Vogel Arndt , Hinrichsen Holger , Canbay Ali , Schlattjan Martin , Sosnowsky Katharina , Sarrazin Christoph , von Felden Johann , Geier Andreas , Deltenre Pierre , Sipos Bence , Schafmayer Clemens , Nothnagel Michael , Aigner Elmar , Datz Christian , Stickel Felix , Morgan Marsha Yvonne , Hampe Jochen , Berg Thomas , Trautwein Christian 
Published: August 2018

ObjectiveHomozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants (‘Pi*Z’ and ‘Pi*S’), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse.DesignWe analysed multicentric case–control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed.ResultsThe Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)).ConclusionThe Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%–4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals.
Review of diagnostic error in anatomical pathology and the role and value of second opinions in error prevention
Authors: Peck Martyn , Moffat David , Latham Bruce , Badrick Tony 
Published: August 2018

AimsDiagnostic/interpretative accuracy can be challenging in anatomical pathology due to the subjective element of the diagnostic process. This can lead to false-negative or false-positive diagnoses of malignancy, variations in grading and diagnostic misclassification of a condition.It is imperative that an accurate diagnosis is achieved so that an appropriate and timely treatment is administered to the patient, for example, the success of targeted molecular therapeutic options for treatment of cancer is dependent on accurate anatomical pathology diagnoses being issued.MethodsA literature review of diagnostic accuracy in selected specimen categories was undertaken and was compared with data on metropolitan and regional pathologist diagnostic proficiency performance in an external quality assurance programme from surveys provided 2015–2017. For each specimen category, cases having attracted a diagnostic inaccuracy (ie, major discordance) of ≥20% and cases attracting a combined error rate (ie, major and minor discordance) of ≥30% are reviewed and discussed.ResultsThe rate of inaccurate diagnoses (assessed as a major discordance) ranged from 3% to 9% among the different specimen groups, with highest mean percentage of inaccurate diagnoses in gynaecology, dermatopathology and gastrointestinal specimens.ConclusionsIt was possible to ascertain that gynaecology, dermatopathology and gastrointestinal specimens had presented the greatest diagnostic challenge to the participant pathologists, determined as highest rate of diagnostic inaccuracy, that is, major discordance with respective case target diagnoses.Through a combination of routine second opinions, directed retrospective peer review and participation in appropriate external quality assurance schemes, the risk associated with these diagnoses can be minimised.
Measuring the impact of genetic knowledge on intentions and attitudes of the community towards expanded preconception carrier screening
Authors: Ong Royston , Howting Denise , Rea Alethea , Christian Hayley , Charman Pauline , Molster Caron , Ravenscroft Gianina , Laing Nigel George 
Published: August 2018

BackgroundPreconception carrier screening (PCS) provides the potential to empower couples to make reproductive choices before having an affected child. An important question is what factors influence the decision to use or not use PCS.MethodsWe analysed the relationship between knowledge, attitudes and intentions to participate in PCS using logistic regression in 832 participants in Western Australia.ResultsTwo-thirds of participants said they would take the test, with 92% of these supporting screening for diseases reducing the lifespan of children and infants. Those who had good genetic knowledge were seven times more likely to intend to use PCS (p≤0.001), while those with high genetic knowledge were four times more likely to (p=0.002) and raised concerns such as insurance and confidentiality.Decreasing genetic knowledge correlated positively with religiosity and apprehension (p≤0.001), which correlated negatively with intention to use PCS (p≤0.001). Increasing genetic knowledge correlated positively with factors representing positive attitudes (p≤0.001), which correlated positively with intention to use PCS (p≤0.001). Many participants with good genetic knowledge nevertheless answered questions that tested understanding incorrectly.80% of participants stated they would prefer to access the test through their general practitioners and 30% would pay up to $A200.ConclusionsKnowledge is instrumental in influencing participation. Having good genetic knowledge may not be enough to understand core concepts of PCS and may impact informed decision-making. This study recommends that continuous education of health professionals and thus the community, in PCS is crucial to reduce misconceptions.
Development of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments
Authors: Gourlay Terence , Simpson C , Robertson C A 
Published: August 2018

IntroductionUncontrolled haemorrhage is the leading cause of death on the battlefield, and two-thirds of these deaths result from non-compressible haemorrhage. Blood salvage and autotransfusion represent an alternative to conventional blood transfusion techniques for austere environments, potentially providing blood to the casualty at point of injury. The aim of this paper is to describe the design, development and initial proof-of-concept testing of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments.MethodA manually operable, dual-headed pump was developed that removes blood from site of injury to a collection reservoir (upper pump) and back to casualty (lower pump). Theoretical flow rate calculations determined pump configuration and a three-dimensionally printed peristaltic pump was manufactured. Flow rates were tested with fresh bovine blood under laboratory conditions representative of the predicted clinical environment.ResultsMathematical modelling suggested flow rates of 3.6 L/min and 0.57 L/min for upper and lower pumps. Using fresh bovine blood, flow rates produced were 2.67 L/min and 0.43 L/min. To mimic expected battlefield conditions, upper suction pump flow rate was calculated using a blood/air mixture.ConclusionThe authors believe that this technology can potentially enhance survivability for casualties in austere and deployed military settings through autotransfusion and cell concentration. It reduces negative effects of blood donation on the conventional donor pool, and potentially negates the logistical constraints associated with allogenic transfusions.
Periprocedural heparin use in acute ischemic stroke endovascular therapy: the TREVO 2 trial
Authors: Winningham Melanie J , Haussen Diogo C , Nogueira Raul G , Liebeskind David S , Smith Wade S , Lutsep Helmi L , Jovin Tudor G , Xiang Bin , Nahab Fadi 
Published: August 2018

BackgroundThe use of periprocedural heparin has previously been reported to be safe and potentially beneficial during thrombectomy with older generation devices. We aimed to evaluate the safety and clinical outcomes of heparin use in the stent retriever era.MethodsA post hoc analysis of the TREVO 2 trial was performed comparing baseline characteristics and clinical outcomes between patients who received (HEP+) and those who did not receive periprocedural heparin (HEP−) while undergoing MERCI or TREVO clot retrieval.ResultsOf 173 patients, 58 (34%) received periprocedural heparin including 40 who received one preprocedural bolus (median 3000 units). Baseline characteristics among HEP+ and HEP− patients were similar except HEP+ patients had a lower NIH Stroke Scale (NIHSS) score (17 vs 19; p=0.04), lower IV tissue plasminogen activator use (38% vs 64%; p<0.01), and a higher median ASPECTS score (8.0 vs 7.0; p=0.02). HEP+ patients were more likely to have vertebrobasilar and middle cerebral artery (MCA)-M1 occlusions but less likely to have internal carotid artery and MCA-M2 occlusions (p=0.04). Time from symptom onset to puncture was similar in the two groups while procedure duration was longer in HEP+ patients (99 vs 83 min; p<0.01). Thrombolysis In Cerebral Infarction (TICI) 2b–3 reperfusion rates, embolization to unaffected territories, access site complications, and intracranial hemorrhages were similar between the groups. In multivariable logistic regression, a good outcome (90-day modified Rankin Scale score 0–2) was independently associated with heparin bolus use (OR 5.30; 95% CI 1.70 to 16.48), TICI 2b–3 reperfusion (OR 6.56; 95% CI 2.29 to 18.83), stent retriever use (OR 3.54; 95% CI 1.38 to 9.03) and inversely associated with intubation (OR 0.10; 95% CI 0.03 to 0.33), diabetes (OR 0.11; 95% CI 0.03 to 0.39), NIHSS (OR 0.84; 95% CI 0.75 to 0.93), time from symptom onset to puncture (OR 0.64; 95% CI 0.45 to 0.89), and heart failure (OR 0.23; 95% CI 0.06 to 0.83).ConclusionsThe use of periprocedural heparin in stent retriever thrombectomy is associated with a good clinical outcome at 90 days and similar rates of symptomatic intracranial hemorrhage. Further studies are warranted.Clinical trial registrationURL:http://www.clinicaltrials.gov. Unique identifier:NCT01270867; Post-results.
SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism
Authors: Liu Mingna , Shi Rebecca , Hwang Hongik , Han Kyung Seok , Wong Man Ho , Ren Xiaobai , Lewis Laura D. , Brown Emery N. , Xu Weifeng 
Published: August 2018

The postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD/DLG-MAGUK) family of proteins scaffold α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complexes to the postsynaptic compartment and are postulated to orchestrate activity-dependent modulation of synaptic AMPAR functions. SAP102 is a key member of this family, present from early development, before PSD-95 and PSD-93, and throughout life. Here we investigate the role of SAP102 in synaptic transmission using a cell-restricted molecular replacement strategy, where SAP102 is expressed against the background of acute knockdown of endogenous PSD-95. We show that SAP102 rescues the decrease of AMPAR-mediated evoked excitatory postsynaptic currents (AMPAR eEPSCs) and AMPAR miniature EPSC (AMPAR mEPSC) frequency caused by acute knockdown of PSD-95. Further analysis of the mini events revealed that PSD-95-to-SAP102 replacement but not direct manipulation of PSD-95 increases the AMPAR mEPSC decay time. SAP102-mediated rescue of AMPAR eEPSCs requires AMPAR auxiliary subunit cornichon-2, whereas cornichon-2 knockdown did not affect PSD-95-mediated regulation of AMPAR eEPSC. Combining these observations, our data elucidate that PSD-95 and SAP102 differentially influence basic synaptic properties and synaptic current kinetics potentially via different AMPAR auxiliary subunits. NEW & NOTEWORTHY Synaptic scaffold proteins postsynaptic density (PSD)-95-like, disk-large (DLG) membrane-associated guanylate kinase (PSD-MAGUKs) regulate synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. However, the functional diversity among different PSD-MAGUKs remains to be categorized. We show that distinct from PSD-95, SAP102 increase the AMPAR synaptic current decay time, and the effect of SAP102 on synaptic AMPAR function requires the AMPAR auxiliary subunit cornichon-2. Our data suggest that PSD-MAGUKs target and modulate different AMPAR complexes to exert specific experience-dependent modification of the excitatory circuit.
CD30 Characterizes Polylobated Lymphocytes and Disease Progression in HTLV-1–Infected Individuals
Authors: Nakashima Makoto , Yamochi Tadanori , Watanabe Mariko , Uchimaru Kaoru , Utsunomiya Atae , Higashihara Masaaki , Watanabe Toshiki , Horie Ryouichi 
Published: August 2018

AbstractPurpose: Although expression of CD30 is reported in a subset of adult T-cell leukemia/lymphoma cases, its clinicopathologic significance is poorly understood. We aimed to characterize CD30-positive cells and clarify their tumorigenic role in human T-cell lymphotropic virus type 1 (HTLV-1)–infected cells.Experimental Design: CD30-positive peripheral blood mononuclear cells from individuals with differing HTLV-1 disease status were characterized, and the role of CD30 signaling was examined using HTLV-1–infected cell lines and primary cells.Results: CD30-positive cells were detected in all samples examined, and the marker was coexpressed with both CD25 and CD4. This cell population expanded in accordance with disease progression. CD30-positive cells showed polylobation, with some possessing “flower cell” features, active cycling, and hyperploidy. CD30 stimulation of HTLV-1–infected cell lines induced these features and abnormal cell division, with polylobation found to be dependent on the activation of PI3K. The results thus link the expression of CD30, which serves as a marker for HTLV-1 disease status, to an active proliferating cell fraction featuring polylobation and chromosomal aberrations. In addition, brentuximab vedotin, an anti-CD30 monoclonal antibody conjugated with auristatin E, was found to reduce the CD30-positive cell fraction.Conclusions: Our results indicate that CD30-positive cells act as a reservoir for tumorigenic transformation and clonal expansion during HTLV-1 infection. The CD30-positive fraction may thus be a potential molecular target for those with differing HTLV-1 disease status. Clin Cancer Res; 24(21); 5445–57. ©2018 AACR.
Local Phototherapy Synergizes with Immunoadjuvant for Treatment of Pancreatic Cancer through Induced Immunogenic Tumor Vaccine
Authors: Zhou Feifan , Yang Jingxuan , Zhang Yuqing , Liu Mingyang , Lang Mark L. , Li Min , Chen Wei R. 
Published: August 2018

AbstractPurpose: To develop a synergistic combination therapy for advanced pancreatic cancer, using local phototherapy and immunotherapy, and to determine the efficacy and mechanism of the novel combination therapy using a highly metastatic pancreatic tumor model in mice.Experimental Design: Mice bearing Panc02-H7 pancreatic tumors (both subcutaneous and orthotopic) were treated with noninvasive or interventional photothermal therapy, followed by local application of an immunoadjuvant. Tumor growth and animal survival were assessed. Immune cell populations within spleen and tumors were evaluated by FACS and IHC, and cytokine levels were determined by ELISA.Results: Up to 75% of mice bearing subcutaneous tumors treated with combination therapy had complete tumor regression. Local photothermal therapy exposed/released damage-associated molecular patterns, which initiated an immunogenic tumor cell death, resulting in infiltration of antigen-presenting cells and Th1 immunity. Concomitant application of immunoadjuvant amplified Th1 immunity, especially the tumor-specific cytotoxic T lymphocyte response, with increased quantity and quality of T cells. Combination therapy also induced tumor-specific immune memory, as demonstrated by resistance to tumor rechallenge and production of memory T cells. For the treatment of orthotopic tumor, the combination therapy significantly reduced the primary tumors and metastases, and prolonged the animal survival time.Conclusions: This study indicated that combination of local phototherapy and immunotherapy induced a systemic immunity against established tumors and metastases in an aggressive, preclinical pancreatic tumor model, leading to a potential clinical method for patients with advanced pancreatic cancer. Clin Cancer Res; 24(21); 5335–46. ©2018 AACR.
A Journey through Tafuri’s Unsolvable Contradictions
Authors: Corna Luisa Lorenza 
Published: August 2018

AbstractMarco Biraghi’sProject of Crisisprovides a broad introduction to the thought and working-methods of historian Manfredo Tafuri. It also explores how this framework informed his studies of contemporary architecture. This review foregrounds the most distinctive aspects of Biraghi’s analysis, focusing upon its attention to the diversity of Tafuri’s philosophical sources. However, it argues that the author’s decision to focus upon the letter of Tafuri’s texts pushes questions of cultural and political context into the background. On occasion, this obscures the formative role that a set of historical, political and cultural changes had upon Tafuri’s work. It also undermines Biraghi’s capacity to grasp the political entanglements and limitations of Tafuri’s thought.
The World as Manifestation of Spirit: Mysticism and Metaphysics in West African Religions
Authors: Brodnicka Monika 
Published: August 2018

Abstract
This paper focuses on the concept of the world as interpreted by Amadou Hampaté Bâ, an initiated scholar, from his experience with Fulani and Bamana religions. It examines the meaning of the world as a manifestation of spirit through Bâ’s mystical concept of the ‘living tradition’. Bâ looks at the complex interaction of the material and spiritual dimensions of the universe as it manifests itself in the physical world through symbols, and as it is informed through invisible forces communicated by the Supreme Being. Based on his understanding of Fulani and Bamana traditions, Bâ uses notions of history and art to better highlight the specific relationship between the spiritual and material realms that illustrate this sacred connection. I argue that Bâ’s mystical approach to understanding this metaphysics offers another method of thinking about some of the diverse African indigenous religions through their underlying esoteric connections.
La seconde patrie of a Basel Missionary: Inscription, Inclination, and Initiative in the Life of Edmond Perregaux among the Akan
Authors: McCaskie T.C. 
Published: August 2018

AbstractThis paper explores the life of the Basel missionary Edmond Perregaux (1868-1905) in Switzerland and among the Akan of Ghana. It is concerned with the construction and expression of his selfhood in and between two different worlds in the later nineteenth century under the aegis of an ever advancing globalization. In brief, the paper looks at a Swiss missionary as an actor in Africa and among Africans and reflects upon the matter of reconciling and integrating these two arenas of experience in the formation of his individual subjectivity. It is aimed at creating a much needed bridge between the discrete concerns of Missionary and Africanist historians, and to suggest within the framework of a single individual life the possibilities for a richer, more textured understanding of personhood when all due attention is paid to the interactions between the shaping environments of both home and abroad.
Time and Evil in the Confessions of Augustine and the Talmud
Authors: Kovelman Arkady , Gershowitz Uri 
Published: August 2018

Abstract
To solve the aporia of suffering and evil, the framers of Bavli Berakhot as well as Augustine combined the idea of love for God with the notion of making the moment linger. According to Augustine, evil prevents man from praising God. Evil derives from perverted human will and poisons a soul. Instead of being distended between the past and the future, a soul should forget the past, concentrate on the present, and extend the present as much as possible. By concentration, the present can be extended to approximate eternity, which is the messianic future. The idea of making a moment linger is salient in Bavli Berkahot as well. The close correlation between redemption and ritual presumes the lingering of time, achieved by prolonging the recitation, concentrating on the text, and merging the blessings. Prolonging halakhic time at any cost hastens the coming of the ultimate meta-historical event. Thus Aqiba’s protracting of the word ehad brings him into a meta-historical context, into the future world. The moment of reading the word ehad lingers amidst torture, spasm, and ecstasy. That ecstasy is the consummation of love with God.
Evaluation of Forecasts of a Convectively Generated Bore Using an Intensively Observed Case Study from PECAN
Authors: Johnson Aaron , Wang Xuguang , Haghi Kevin R. , Parsons David B. 
Published: August 2018

Abstract
This paper presents a case study from an intensive observing period (IOP) during the Plains Elevated Convection at Night (PECAN) field experiment that was focused on a bore generated by nocturnal convection. Observations from PECAN IOP 25 on 11 July 2015 are used to evaluate the performance of high-resolution Weather Research and Forecasting Model forecasts, initialized using the Gridpoint Statistical Interpolation (GSI)-based ensemble Kalman filter. The focus is on understanding model errors and sensitivities in order to guide forecast improvements for bores associated with nocturnal convection. Model simulations of the bore amplitude are compared against eight retrieved vertical cross sections through the bore during the IOP. Sensitivities of forecasts to microphysics and planetary boundary layer (PBL) parameterizations are also investigated. Forecasts initialized before the bore pulls away from the convection show a more realistic bore than forecasts initialized later from analyses of the bore itself, in part due to the smoothing of the existing bore in the ensemble mean. Experiments show that the different microphysics schemes impact the quality of the simulations with unrealistically weak cold pools and bores with the Thompson and Morrison microphysics schemes, cold pools too strong with the WDM6 and more accurate with the WSM6 schemes. Most PBL schemes produced a realistic bore response to the cold pool, with the exception of the Mellor–Yamada–Nakanishi–Niino (MYNN) scheme, which creates too much turbulent mixing atop the bore. A new method of objectively estimating the depth of the near-surface stable layer corresponding to a simple two-layer model is also introduced, and the impacts of turbulent mixing on this estimate are discussed.