bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic AAV9 gene therapy using the synapsin I promoter rescues a mouse model of neuronopathic Gaucher disease but with limited cross-correction potential to astrocytes
Authors: Massaro Giulia , Hughes Michael P , Whaler Sammie M , Wallom Kerri-Lee , Priestman David A , Platt Frances M , Waddington Simon N , Rahim Ahad A 
Published: December 2019

Abstract
Gaucher disease is caused by mutations in the GBA gene, which encodes for the lysosomal enzyme β-glucocerebrosidase (GCase), resulting in the accumulation of storage material in visceral organs and in some cases the brain of affected patients. While there is a commercially available treatment for the systemic manifestations, neuropathology still remains untreatable. We previously demonstrated that gene therapy represents a feasible therapeutic tool for the treatment of the neuronopathic forms of Gaucher disease (nGD). In order to further enhance the therapeutic affects to the central nervous system, we systemically delivered an adeno-associated virus (AAV) serotype 9 carrying the human GBA gene under control of a neuron-specific promoter to an nGD mouse model. Gene therapy increased the life span of treated animals, rescued the lethal neurodegeneration, normalized the locomotor behavioural defects and ameliorated the visceral pathology. Together, these results provided further indication of gene therapy as a possible effective treatment option for the neuropathic forms of Gaucher disease.
Is surgical resection of primary tumour superior to exploratory thoracotomy without resection in treating lung cancer patients with unexpected pleural metastasis detected during operation?
Authors: Deng Han-Yu , Zheng Xi , Zhu Da-Xing , Zhou Qinghua 
Published: December 2019

Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was ‘In lung cancer patients with unexpected pleural metastasis detected during operation, is surgical resection of primary tumour superior to exploratory thoracotomy without resection in improving long-term survival?’. Altogether, 1443 papers were found using the reported search, of which 1 meta-analysis and 10 retrospective observational cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. One meta-analysis and 9 cohort studies found that surgical resection of the primary tumour, on the discovery of pleural metastases, yielded a better overall survival than exploratory thoracotomy alone, while 1 cohort study showed no difference. Six studies found that main tumour resection was an independent favourable prognostic factor for overall survival in lung cancer patients with unexpected pleural metastasis detected during operation, while 3 cohort studies also showed improved progression-free survival over exploratory thoracotomy. Therefore, we conclude that surgical resection of the primary tumour is superior to exploratory thoracotomy in treating lung cancer patients with unexpected pleural metastasis detected during operation.
Measuring Real-Time Response in Real-Life Settings
Authors: Waldvogel Thomas , Metz Thomas 
Published: December 2019

Abstract
Real-time response (RTR) measurement is an important technique to assess human processing of information. Ever since Maier et al. verified the reliability and validity of physical RTR devices in this journal a decade ago, there has been a growing trend toward virtual measurement platforms to overcome the limitations of conventional, laboratory-based methods. We introduce the Debat-O-Meter, a novel online RTR platform for mobile devices, which allows researchers to measure how viewers perceive political debates in the setting of their private homes. We draw on a large study (N = 5,660) conducted during the 2017 German general election campaign and show that virtualized measurement indeed facilitates diverse and large N field studies while simultaneously conforming to established standards of reliability and validity.
The updated outcomes of bladder-preserving trimodal therapy using a real-time tumor-tracking radiotherapy system for patients with muscle-invasive bladder cancer
Authors: Miyata Haruka , Osawa Takahiro , Abe Takashige , Kikuchi Hiroshi , Matsumoto Ryuji , Maruyama Satoru , Nishioka Kentaro , Shimizu Shinichi , Hashimoto Takayuki , Shirato Hiroki , Shinohara Nobuo 
Published: December 2019

Abstract

Objective
Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system.

Methods
Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan–Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival.

Results
The median duration of the follow-up period was 28 months (range: 3–161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15–10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32–16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09–8.30].

Conclusions
Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy.
Authoritarian Powers and Norm Contestation in the Liberal International Order: Theorizing the Power Politics of Ideas and Identity
Authors: Bettiza Gregorio , Lewis David 
Published: December 2019

AbstractAre rising authoritarian powers such as China and Russia converging towards or challenging the normative structures of the liberal international order? This article argues that scholarship on norm contestation provides a fruitful theoretical avenue for addressing this question. It finds, however, that this literature has problematically tended to either overlook or externalize power dynamics from norm contestation. The article therefore proposes and develops a power political approach to norm contestation that, informed by a realpolitik sensibility, more explicitly and consistently makes power central to the analysis. A power political perspective conceptualizes norm contestation as the expression of battles for influence in world politics that take place at the ideational level and through symbolic instruments. It understands these struggles as occurring in the context of an international system profoundly marked by conflicting interests, cultural pluralism, hierarchical structures, and power asymmetries. This power political lens is then used to identify four modes of contestation that Russian and Chinese actors are engaged in: liberal performance, liberal mimicry, civilizational essentialization, and counter-norm entrepreneurship. It empirically explores how these contestatory practices express themselves at different intensity levels—applicatory, meaning, and validity—and display specific power political logics—fragmenting and integrative—with the goal of undermining the ideational hegemony of liberal Western-based actors and structures in world politics, and advancing alternative non-liberal visions of domestic and international order. Along with contributing to the literature on norms, this article also makes a broader intervention in current debates about rising powers and the future of the liberal international order.
Deep learning–based detection and segmentation-assisted management of brain metastases
Authors: Xue Jie , Wang Bao , Ming Yang , Liu Xuejun , Jiang Zekun , Wang Chengwei , Liu Xiyu , Chen Ligang , Qu Jianhua , Xu Shangchen , Tang Xuqun , Mao Ying , Liu Yingchao , Li Dengwang 
Published: December 2019

Abstract

Background
Three-dimensional T1 magnetization prepared rapid acquisition gradient echo (3D-T1-MPRAGE) is preferred in detecting brain metastases (BM) among MRI. We developed an automatic deep learning–based detection and segmentation method for BM (named BMDS net) on 3D-T1-MPRAGE images and evaluated its performance.

Methods
The BMDS net is a cascaded 3D fully convolution network (FCN) to automatically detect and segment BM. In total, 1652 patients with 3D-T1-MPRAGE images from 3 hospitals (n = 1201, 231, and 220, respectively) were retrospectively included. Manual segmentations were obtained by a neuroradiologist and a radiation oncologist in a consensus reading in 3D-T1-MPRAGE images. Sensitivity, specificity, and dice ratio of the segmentation were evaluated. Specificity and sensitivity measure the fractions of relevant segmented voxels. Dice ratio was used to quantitatively measure the overlap between automatic and manual segmentation results. Paired samples t-tests and analysis of variance were employed for statistical analysis.

Results
The BMDS net can detect all BM, providing a detection result with an accuracy of 100%. Automatic segmentations correlated strongly with manual segmentations through 4-fold cross-validation of the dataset with 1201 patients: the sensitivity was 0.96 ± 0.03 (range, 0.84–0.99), the specificity was 0.99 ± 0.0002 (range, 0.99–1.00), and the dice ratio was 0.85 ± 0.08 (range, 0.62–0.95) for total tumor volume. Similar performances on the other 2 datasets also demonstrate the robustness of BMDS net in correctly detecting and segmenting BM in various settings.

Conclusions
The BMDS net yields accurate detection and segmentation of BM automatically and could assist stereotactic radiotherapy management for diagnosis, therapy planning, and follow-up.
NF1-like optic pathway gliomas in children: clinical and molecular characterization of this specific presentation
Authors: Lobón-Iglesias María Jesús , Laurendeau Ingrid , Guerrini-Rousseau Léa , Tauziède-Espariat Arnault , Briand-Suleau Audrey , Varlet Pascale , Vidaud Dominique , Vidaud Michel , Brugieres Laurence , Grill Jacques , Pasmant Eric 
Published: December 2019

Abstract

Background
Pediatric neurofibromatosis type 1 (NF1)–associated optic pathway gliomas (OPGs) exhibit different clinico-radiological features, treatment, and outcome compared with sporadic OPGs. While NF1-associated OPGs are caused by complete loss-of-function of the NF1 gene, other genetic alterations of the RAS-MAPK pathway are frequently described in the sporadic cases. We identified a group of patients who presented OPGs with typical radiological features of NF1-associated OPGs but without the NF1 diagnostic criteria. We aim to investigate into the possible molecular mechanisms underlying this “NF1-like” pediatric OPGs presentation.

Methods
We analyzed clinico-radiological features of 16 children with NF1-like OPGs and without NF1 diagnostic criteria. We performed targeted sequencing of the NF1 gene in constitutional samples (n = 16). The RAS-MAPK pathway major genes were sequenced in OPG tumor samples (n = 11); BRAF FISH and IHC analyses were also performed.

Results
In one patient’s blood and tumor samples, we identified a NF1 nonsense mutation (exon 50: c.7285C&gt;T, p.Arg2429*) with ~8% and ~70% VAFs, respectively, suggesting a mosaic NF1 mutation limited to the brain (segmental NF1). This patient presented signs of neurodevelopmental disorder. We identified a somatic alteration of the RAS-MAPK pathway in eight tumors: four BRAF activating p.Val600Glu mutations, three BRAF:KIAA oncogenic fusions, and one putative gain-of-function complex KRAS indel inframe mutation.

Conclusions
NF1-like OPGs can rarely be associated with mosaic NF1 that needs specific constitutional DNA analyses for diagnosis. Further studies are warranted to explore unknown predisposition condition leading to the NF1-like OPG presentation, particularly in patients with the association of a neurodevelopmental disorder.
The Attitudinal Opacity of Emotional Experience
Authors: Mitchell Jonathan 
Published: December 2019

AbstractAccording to some philosophers, when introspectively attending to experience, we seem to see right through it to the (apparent) objects outside, including their properties. This is called the transparency of experience. This paper examines whether, and in what sense, emotions are transparent. It argues that emotional experiences are opaque in a distinctive way: introspective attention to them does not principally reveal non-intentional somatic qualia but rather felt valenced intentional attitudes. As such, emotional experience is attitudinally opaque.
Correcting tree-ring δ13C time series for tree-size effects in eight temperate tree species
Authors: Vadeboncoeur Matthew A , Jennings Katie A , Ouimette Andrew P , Asbjornsen Heidi 
Published: December 2019

Abstract
Stable carbon isotope ratios (δ13C) in tree rings have been widely used to study changes in intrinsic water-use efficiency (iWUE), sometimes with limited consideration of how C-isotope discrimination is affected by tree height and canopy position. Our goals were to quantify the relationships between tree size or tree microenvironment and wood δ13C for eight functionally diverse temperate tree species in northern New England and to better understand the physical and physiological mechanisms underlying these differences. We collected short increment cores in closed-canopy stands and analyzed δ13C in the most recent 5 years of growth. We also sampled saplings in both shaded and sun-exposed environments. In closed-canopy stands, we found strong tree-size effects on δ13C, with 3.7–7.2‰ of difference explained by linear regression vs height (0.11–0.28‰ m−1), which in some cases is substantially stronger than the effect reported in previous studies. However, open-grown saplings were often isotopically more similar to large codominant trees than to shade-grown saplings, indicating that light exposure contributes more to the physiological and isotopic differences between small and large trees than does height. We found that in closed-canopy forests, δ13C correlations with diameter at breast height were nonlinear but also strong, allowing a straightforward procedure to correct tree- or stand-scale δ13C-based iWUE chronologies for changing tree size. We demonstrate how to use such data to correct and interpret multi-decadal composite isotope chronologies in both shade-regenerated and open-grown tree cohorts, and we highlight the importance of understanding site history when interpreting δ13C time series.
Educational Interventions to Improve Support for Family Presence During Resuscitation
Authors: Powers Kelly A. 
Published: December 2019

Background:
Family presence during resuscitation (FPDR) remains controversial among nurses. Individual studies have shown educational interventions can improve support for FPDR; however, a systematic review of the literature has not been performed to appraise and synthesize the evidence.

Objectives:
The aim of this systematic review was to appraise and synthesize studies conducted to test the effect of education on nurses’ and providers’ support for FPDR.

Methods:
Electronic searches of CINAHL, MEDLINE, and PubMed were performed. The PRISMA flow diagram and predetermined inclusion and exclusion criteria were used to guide article selection. Articles selected for inclusion were evaluated for rigor in study design, sample, setting, and data collection and analysis.

Results:
Sixteen articles met eligibility criteria. Study findings demonstrated educational interventions can improve support for FPDR, as well as intent to offer it as an option. Methodological limitations of existing research and a lack of comparative studies render the optimal approach (classroom, simulation, or online) to FPDR education unknown.

Discussion:
Nurse educators should consider implementing educational interventions to improve nurses’ support for FPDR and prepare them to implement it in clinical practice. More research on FPDR educational interventions is needed to be able to provide specific guidance on optimal approaches to FPDR education.
Oxidative Stress Alters Angiogenic and Antimicrobial Content of Extracellular Vesicles and Improves Flap Survival
Authors: Mayo John S. , Kurata Wendy E. , O’Connor Kelsey M. , Pierce Lisa M. 
Published: December 2019

Background:
Extracellular vesicles (EVs) secreted from adipose-derived mesenchymal stem cells (ADSCs) (ADSC-EVs) improve flap survival after ischemia–reperfusion injury. Exposure of parent ADSCs to oxidative stress has been shown to enhance this effect, but mechanisms are unclear. We aimed to determine whether angiogenesis-promoting protein and microRNA (miRNA) content is altered in EVs after preconditioning with hydrogen peroxide (H2O2 ADSC-EVs) and whether H2O2 ADSC-EVs can increase viability of random pattern skin flaps.

Methods:
EVs secreted by human ADSCs were isolated after culture in EV-depleted medium ± H2O2. Nanoparticle tracking analysis determined size and concentration of purified EVs. Mass spectrometry and small RNA next-generation sequencing were performed to compare proteomic and miRNA profiles. ADSC-EVs, H2O2 ADSC-EVs, or vehicle were injected into random pattern skin flaps of BALB/c mice (4–5 mice per group). Viable and necrotic areas were measured on day 7, and tissues underwent histologic analysis.

Results:
Angiogenic and antimicrobial protein content of EVs was altered with H2O2 preconditioning. Functional enrichment analysis identified constitutive photomorphogenesis 9 signalosome (known to direct vascular endothelial growth factor production) as the major enriched Gene Ontology term unique to H2O2 ADSC-EVs. Two miRNAs were increased, and 12 (including 10 antiangiogenic miRNAs) were reduced in H2O2 ADSC-EVs. Enhanced viability (P < 0.05) of flaps treated with H2O2 ADSC-EVs compared with vehicle corresponded to increased capillary density in the H2O2 group (P < 0.001).

Conclusion:
Altered protein and miRNA content in ADSC-EVs after H2O2 pretreatment likely contributes to enhanced therapeutic effects on flap survival observed in preclinical models.
FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY
Authors: Jaggi Damian , Solberg Yasmin , Dysli Chantal , Ebneter Andreas , Wolf Sebastian , Zinkernagel Martin S. 
Published: December 2019

Purpose:
The purpose of this study was to investigate fluorescence lifetime imaging ophthalmoscopy lifetimes after macula-off rhegmatogenous retinal detachment (RRD) repair.

Methods:
Fifty-eight patients with successful macula-off RRD reattachment surgery were included. Retinal autofluorescence was excited with 470 nm, and amplitude-weighted mean fluorescence lifetimes (Tm) were measured in a short spectral channel (SSC, 498–560 nm) and a long spectral channel (LSC, 560–720 nm). Tm were obtained within a standardized Early Treatment Diabetic Retinopathy Study grid and correlated with Tm. The unaffected fellow eye served as control.

Results:
Fifty-eight patients (age: 65 ± 1.6 years, 11 women) were imaged at median 1.5 months postoperatively. Tm were significantly prolongxxxed within areas of previously detached retina in the long spectral channel and particularly in the central subfield in the short spectral channel. Short lifetimes in the center of the Early Treatment Diabetic Retinopathy Study grid correlated with better visual acuity (short spectral channel; r2 = 0.18, P = 0.001, long spectral channel; r2 = 0.08, P = 0.03). Areas of residual subretinal fluid pockets in four RRD eyes displayed short fluorescence lifetimes.

Conclusion:
Areas of previously detached retina exhibit significant fluorescence lifetime changes. We found a significant correlation of fluorescence lifetimes within the fovea with visual acuity after successful RRD repair. Our data suggests that the prolongation of fluorescence lifetimes in the fovea is mainly driven by loss of macular pigment. Therefore, fluorescence lifetime imaging ophthalmoscopy may be useful in the prediction of long-term functional outcomes after macula-off RRD surgery.
The International Society for the Study of Vulvovaginal Disease Surgical Oncological Procedure Definitions Committee “Surgical Terminology for Vulvar Cancer Treatment”
Authors: Micheletti Leonardo , Haefner Hope , Zalewski Kamil , MacLean Allan , Gomez Cherey Facundo , Pereira Claudia , Sluga Celeste , Solé-Sedeno Josep M. , Vargas-Hernandez Victor M. , Preti Mario 
Published: December 2019

Objectives
The International Society for the Study of Vulvovaginal Disease (ISSVD) Surgical Oncological Procedure Definitions Committee propose a consistent terminology based on well-defined and reproducible anatomic landmarks that can be used by all who are involved in care of patients with vulvar conditions.

Materials and Methods
The fundamental principles behind the new terminology contained descriptions of the area extension and depth of the surgical procedure.

Results
Vulvar Surgical Topographic Anatomy Landmarks

Extension. The internal border of the vulva is the hymenal ring. The genitocrural folds are the external lateral borders.
The vertical line through the clitoris and the anus defines lateral portions of the vulva.
The horizontal line from the upper border of the hymenal ring defines anterior and posterior portion of the vulva.

Depth. The floor of the vulva is represented by the median perineal fascia or perineal membrane of the urogenital diaphragm.

A. Vulvectomy

1. Extension: partial/total vulvectomy. Removal of part/entire vulvar/perineal integument independent of the depth.

2. Depth: superficial/deep. Removal of the most superficial layer/removal of the vulvar tissue to the superficial aponeurosis of the urogenital diaphragm and/or pubic periosteum.
B. Inguinofemoral lymphadenectomy

1. Superficial inguinofemoral lymphadenectomy. Removal of the nodes located beside the inguinal ligament and along the great saphenous vein.

2. Deep femoral lymphadenectomy. Removal of the nodes below the cribriform lamina and medial to the femoral vein.

Conclusions
This terminology helps avoid confusion and promote better understanding and exchange of experiences among gynecologic oncologists involved in vulvar carcinoma care.