bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA-DRB1*15:02 Is Associated With Iodinated Contrast Media–Related Anaphylaxis
Authors: Chung Soo Jie , Kang Dong Yoon , Lee Whal , Lee Seung Bok , Kim Sujeong , Lee Seung-Eun , Sim Da Woon , Kang Min-Gyu , Park Kyung Hee , Jung Jae-Woo , Yun James , Kang Hye-Ryun 
Published: January 2020

Background
The incidence of severe reaction induced by iodinated contrast media (ICM) has increased over the years with an increasing use of imaging modalities. Although ICM anaphylaxis is rare, it can be life-threatening, but currently, there is no biomarker that can identify individuals at risk of ICM anaphylaxis.

Objective
The aim of this study is to investigate the genetic susceptibility of ICM anaphylaxis.

Methods
Patients who had ICM anaphylaxis were enrolled in the study, and their blood samples were collected for genotyping of human leukocyte antigen (HLA)-A, -B, -C, and -DR. The results were compared with those of healthy Korean general population. MRGPRX2 gene in ICM anaphylaxis group was also sequenced and compared with the Korean standard database of genetic polymorphism.

Results
The frequencies of 3 HLA alleles (B*52:01, C*12:02, and DRB1*15:02) were significantly higher in 47 patients with ICM anaphylaxis. In particular, HLA-DRB1*15:02 was 5 times more frequent in the ICM anaphylaxis group than the Korean general population (34.0% vs 6.6%; odds ratio, 7.306; 95% confidence interval, 3.622–14.740), and this difference was most pronounced in subjects with iohexol-induced anaphylaxis (odds ratio, 16.516; 95% CI, 5.241–52.047; P < 0.0001). Eight single nucleotide polymorphisms were identified in MRGPRX2 gene, but their frequencies were not different in those with ICM anaphylaxis compared with the general Korean population.

Conclusions
HLA-DRB1*15:02 is associated with ICM anaphylaxis in the Korean population.
Three-Dimensional Assessment of Pharyngeal Volume on Computed Tomography Scans: Applications to Anesthesiology and Endoscopy
Authors: Gibelli Daniele , Cellina Michaela , Gibelli Stefano , Oliva Antonio Giancarlo , Termine Giovanni , Sforza Chiarella 
Published: January 2020

Abstract
Pharyngeal volume is important in anesthesiology for correctly assessing intubation procedures. However, most of studies are based on patients in upright position and do not assess possible relationships between pharyngeal volume and cranial size. This study aims at measuring pharyngeal volume in CT-scans and to assess possible statistically significant differences according to sex.
Eighty healthy subjects (40 males and 40 females) aged between 21 and 86 years were retrospectively chosen from a hospital database of maxillofacial CT-scans; 3D segmentation was performed separately for naso-, oro- and laryngopharyngeal portion through ITK-SNAP software, and their volume was calculated. Three cranial measurements were obtained: distance between anterior and posterior nasal spine, upper facial height (nasion-prosthion) and biorbital breadth (ectoconchion-ectoconchion distance).
The effect of sex on volume for each pharyngeal portion was assessed through one-way ANCOVA test using each of the 3 cranial measurements as covariate (P < 0.05).
On average, the volume of nasopharynx, oropharynx and laryngopharynx was 7.2 ± 2.7 cm3, 7.5 ± 4.2 cm3, 3.5 ± 2.2 cm3 respectively in males, and 6.4 ± 2.9 cm3, 5.2 ± 2.1 cm3, 3.0 ± 1.8 cm3 in females. Statistically significant differences according to sex were found only for oropharyngeal volume, independently from cranial measurements (P < 0.05).
This study provides data concerning volume of pharyngeal air space in supine subjects: these reference standards can be useful for anaesthesiologic procedures.
Innate and Adaptive Immune Correlates of Chronic and Self-limiting EBV DNAemia in Solid-organ Transplant Recipients
Authors: Ferreira Victor H. , Batist Judah , Humar Atul , Kumar Deepali 
Published: January 2020

Background.
Epstein-Barr virus (EBV) DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited.

Methods.
Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting EBV DNAemia (SLD; n = 11) or chronic EBV DNAemia (CD; n = 19) at enrollment and 4–8 weeks later. Mass cytometry was used to characterize innate and T-cell immune correlates of EBV DNAemia. Furthermore, flow cytometry was used to measure the frequency of EBV-specific T-cell responses between groups following stimulation with an EBV-infected cell lysate.

Results.
Unsupervised analysis of the innate compartment (CD3–CD19– cells) identified 5 CD11c+ clusters at higher abundance in the SLD group (false discovery rate ≤ 1%). These clusters expressed CD11b, CD45RO, CD14, CD123, CD127, and CD38, among others. Unsupervised profiling of the T-cell compartment (CD3+CD19–) revealed 2 CD4+ T-cell clusters at higher frequency among those with SLD (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L—suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4+ TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ–producing EBV-specific CD4+ T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/106 cells; P = 0.015).

Conclusions.
CD is associated with a reduction of CD11c+ cells, CD4+ TN, and interferon-γ–producing EBV-specific CD4+ T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Mycophenolate Monotherapy in HLA-Matched Kidney Transplant Recipients: A Case Series of 20 Patients
Authors: Hennes Anthony J. , Holdener Kimberly E. , Burlingham William J. , Mandelbrot Didier A. , Parajuli Sandesh , Mohamed Maha A. , Garg Neetika , Aziz Fahad , Astor Brad C. , Djamali Arjang 
Published: January 2020

Background.
The ideal minimizing strategy for maintenance immunosuppression in HLA-matched kidney transplant recipients (KTR) is unknown. We hypothesized that mycophenolate (MPA) monotherapy is a safe and effective approach for maintenance therapy in this group of KTR.

Methods.
Data were abstracted for 6-antigen HLA-matched KTR between 1994 and 2013. Twenty recipients receiving MPA monotherapy secondary to infection, cancer, calcineurin inhibitor (CNI) side effects, or immunosuppression minimization strategies were evaluated in this case series.

Results.
MPA monotherapy had a low incidence of death-censored graft failure (3.19/100 person-y), rejection (0/100 person-y), hospitalization (1.62/100 person-y), malignancy (3.61/100 person-y), and infection (1.75/100 person-y). Further, 12-month mean or median serum creatinine (1.29 mg/dL), estimated glomerular filtration rate (64.3 mL/min/1.73 m2), urine protein creatinine ratio (143.2 mg/g), hemoglobin (13.9 g/dL), platelets (237.8 K/uL), and white blood cell count (9.04 K/uL) were favorable. There was a successful conversion rate of 90% (18 of 20) with 2 patients converting back to CNI-based regimens secondary to recurrence of membranous nephropathy and post-transplant lymphoproliferative disorder.

Conclusions.
Our findings indicate that MPA monotherapy may be a promising immunosuppression minimization strategy for HLA-matched KTR.
Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events
Authors: Rossin Elizabeth J. , Gilbert Aubrey L. , Koen Nicholas , Leslie-Mazwi Thabele M. , Cunnane Mary E. , Rizzo Joseph F. 
Published: January 2020

Background:
Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation.

Methods:
We report a retrospective, comparative, case–control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking.

Results:
We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors.

Conclusions:
We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.
Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma
Authors: Pasol Joshua , Mellon Eric A. , Feun Lynn G. , Saigal Gaurav M. , Diwanji Tejan P. , Komotar Ricardo J. 
Published: January 2020

Abstract:
An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.
Climate change, ecosystems and abrupt change: science priorities
Authors: Turner Monica G. , Calder W. John , Cumming Graeme S. , Hughes Terry P. , Jentsch Anke , LaDeau Shannon L. , Lenton Timothy M. , Shuman Bryan N. , Turetsky Merritt R. , Ratajczak Zak , Williams John W. , Williams A. Park , Carpenter Stephen R. 
Published: January 2020

Ecologists have long studied patterns, directions and tempos of change, but there is a pressing need to extend current understanding to empirical observations of abrupt changes as climate warming accelerates. Abrupt changes in ecological systems (ACES)—changes that are fast in time or fast relative to their drivers—are ubiquitous and increasing in frequency. Powerful theoretical frameworks exist, yet applications in real-world landscapes to detect, explain and anticipate ACES have lagged. We highlight five insights emerging from empirical studies of ACES across diverse ecosystems: (i) ecological systems show ACES in some dimensions but not others; (ii) climate extremes may be more important than mean climate in generating ACES; (iii) interactions among multiple drivers often produce ACES; (iv) contingencies, such as ecological memory, frequency and sequence of disturbances, and spatial context are important; and (v) tipping points are often (but not always) associated with ACES. We suggest research priorities to advance understanding of ACES in the face of climate change. Progress in understanding ACES requires strong integration of scientific approaches (theory, observations, experiments and process-based models) and high-quality empirical data drawn from a diverse array of ecosystems.This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’
Planning for climate change through additions to a national protected area network: implications for cost and configuration
Authors: Lawler Joshua J. , Rinnan D. Scott , Michalak Julia L. , Withey John C. , Randels Christopher R. , Possingham Hugh P. 
Published: January 2020

Expanding the network of protected areas is a core strategy for conserving biodiversity in the face of climate change. Here, we explore the impacts on reserve network cost and configuration associated with planning for climate change in the USA using networks that prioritize areas projected to be climatically suitable for 1460 species both today and into the future, climatic refugia and areas likely to facilitate climate-driven species movements. For 14% of the species, networks of sites selected solely to protect areas currently climatically suitable failed to provide climatically suitable habitat in the future. Protecting sites climatically suitable for species today and in the future significantly changed the distribution of priority sites across the USA—increasing relative protection in the northeast, northwest and central USA. Protecting areas projected to retain their climatic suitability for species cost 59% more than solely protecting currently suitable areas. Including all climatic refugia and 20% of areas that facilitate climate-driven movements increased the cost by another 18%. Our results indicate that protecting some types of climatic refugia may be a relatively inexpensive adaptation strategy. Moreover, although addressing climate change in conservation plans will have significant implications for the configuration of networks, the increased cost of doing so may be relatively modest.This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Co-producing ecosystem services for adapting to climate change
Authors: Lavorel Sandra , Locatelli Bruno , Colloff Matthew J. , Bruley Enora 
Published: January 2020

Ecosystems can sustain social adaptation to environmental change by protecting people from climate change effects and providing options for sustaining material and non-material benefits as ecological structure and functions transform. Along adaptation pathways, people navigate the trade-offs between different ecosystem contributions to adaptation, or adaptation services (AS), and can enhance their synergies and co-benefits as environmental change unfolds. Understanding trade-offs and co-benefits of AS is therefore essential to support social adaptation and requires analysing how people co-produce AS. We analysed co-production along the three steps of the ecosystem cascade: (i) ecosystem management; (ii) mobilization; and (iii) appropriation, social access and appreciation. Using five exemplary case studies across socio-ecosystems and continents, we show how five broad mechanisms already active for current ecosystem services can enhance co-benefits and minimize trade-offs between AS: (1) traditional and multi-functional land/sea management targeting ecological resilience; (2) pro-active management for ecosystem transformation; (3) co-production of novel services in landscapes without compromising other services; (4) collective governance of all co-production steps; and (5) feedbacks from appropriation, appreciation of and social access to main AS. We conclude that knowledge and recognition of co-production mechanisms will enable pro-active management and governance for collective adaptation to ecosystem transformation.
This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Understanding the value and limits of nature-based solutions to climate change and other global challenges
Authors: Seddon Nathalie , Chausson Alexandre , Berry Pam , Girardin Cécile A. J. , Smith Alison , Turner Beth 
Published: January 2020

There is growing awareness that ‘nature-based solutions' (NbS) can help to protect us from climate change impacts while slowing further warming, supporting biodiversity and securing ecosystem services. However, the potential of NbS to provide the intended benefits has not been rigorously assessed. There are concerns over their reliability and cost-effectiveness compared to engineered alternatives, and their resilience to climate change. Trade-offs can arise if climate mitigation policy encourages NbS with low biodiversity value, such as afforestation with non-native monocultures. This can result in maladaptation, especially in a rapidly changing world where biodiversity-based resilience and multi-functional landscapes are key. Here, we highlight the rise of NbS in climate policy—focusing on their potential for climate change adaptation as well as mitigation—and discuss barriers to their evidence-based implementation. We outline the major financial and governance challenges to implementing NbS at scale, highlighting avenues for further research. As climate policy turns increasingly towards greenhouse gas removal approaches such as afforestation, we stress the urgent need for natural and social scientists to engage with policy makers. They must ensure that NbS can achieve their potential to tackle both the climate and biodiversity crisis while also contributing to sustainable development. This will require systemic change in the way we conduct research and run our institutions.This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Climate change mitigation and nature conservation both require higher protected area targets
Authors: Roberts Callum M. , O'Leary Bethan C. , Hawkins Julie P. 
Published: January 2020

Nations of the world have, to date, pursued nature protection and climate change mitigation and adaptation policies separately. Both efforts have failed to achieve the scale of action needed to halt biodiversity loss or mitigate climate change. We argue that success can be achieved by aligning targets for biodiversity protection with the habitat protection and restoration necessary to bring down greenhouse gas concentrations and promote natural and societal adaptation to climate change. Success, however, will need much higher targets for environmental protection than the present 10% of sea and 17% of land. A new target of 30% of the sea given high levels of protection from exploitation and harm by 2030 is under consideration and similar targets are being discussed for terrestrial habitats. We make the case here that these higher targets, if achieved, would make the transition to a warmer world slower and less damaging for nature and people.
This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions’.
Tipping positive change
Authors: Lenton Timothy M. 
Published: January 2020

Tipping points exist in social, ecological and climate systems and those systems are increasingly causally intertwined in the Anthropocene. Climate change and biosphere degradation have advanced to the point where we are already triggering damaging environmental tipping points, and to avoid worse ones ahead will require finding and triggering positive tipping points towards sustainability in coupled social, ecological and technological systems. To help with that I outline how tipping points can occur in continuous dynamical systems and in networks, the causal interactions that can occur between tipping events across different types and scales of system—including the conditions required to trigger tipping cascades, the potential for early warning signals of tipping points, and how they could inform deliberate tipping of positive change. In particular, the same methods that can provide early warning of damaging environmental tipping points can be used to detect when a socio-technical or socio-ecological system is most sensitive to being deliberately tipped in a desirable direction. I provide some example targets for such deliberate tipping of positive change.This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions'.
Large mosaic copy number variations confer autism risk
Authors: Sherman Maxwell A. , Rodin Rachel E. , Genovese Giulio , Dias Caroline , Barton Alison R. , Mukamel Ronen E. , Berger Bonnie , Park Peter J. , Walsh Christopher A. , Loh Po-Ru 
Published: January 2020

AbstractAlthough germline de novo copy number variants are a known cause of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. Here, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 ASD probands and 5,500 unaffected siblings in the Simons Simplex Collection (SSC) and Simons Powering Autism Research for Knowledge (SPARK) cohorts. We detected 46 mCNVs in probands and 19 mCNVs in siblings ranging from 49 kb to 249 Mb and affecting 2.8-73.8% of cells. In both cohorts, probands carried a significant burden of large (>4 Mb) mCNVs (P = 0.043 and P = 6.6 × 10−3 in SSC and SPARK, respectively), which were present in a total of 25 probands but only 1 sibling (OR=11.4, 95% CI=1.5-84.2). Surprisingly, we did not observe mosaic analogues of the short de novo CNVs recurrently observed in ASD. Event size positively correlated with severity of ASD symptoms (P = 0.016), and four probands exhibited clinical symptoms consistent with syndromes previously associated with genes or regions disrupted by their respective mosaic mutations. In analyses of post-mortem brain tissue from 60 additional probands, we further detected and experimentally validated two mCNVs including a complex 10.3 Mb duplication on chromosome 2. These results indicate that mosaic CNVs contribute a previously unexplained component of ASD risk.
Pilot study demonstrating changes in DNA hydroxymethylation enable detection of multiple cancers in plasma cell-free DNA
Authors: Bergamaschi Anna , Ning Yuhong , Ku Chin-Jen , Ellison Chris , Collin Francois , Guler Gulfem , Phillips Tierney , McCarthy Erin , Wang Wendy , Antoine Michael , Scott Aaron , Lloyd Paul , Ashworth Alan , Quake Steve , Levy Samuel 
Published: January 2020

ABSTRACTOur study employed the detection of 5-hydroxymethyl cytosine (5hmC) profiles on cell free DNA (cfDNA) from the plasma of cancer patients using a novel enrichment technology coupled with sequencing and machine learning based classification method. These classification methods were develoiped to detect the presence of disease in the plasma of cancer and control subjects. Cancer and control patient cfDNA cohorts were accrued from multiple sites consisting of 48 breast, 55 lung, 32 prostate and 53 pancreatic cancer subjects. In addition, a control cohort of 180 subjects (non-cancer) was employed to match cancer patient demographics (age, sex and smoking status) in a case-control study design.Logistic regression methods applied to each cancer case cohort individually, with a balancing non-cancer cohort, were able to classify cancer and control samples with measurably high performance. Measures of predictive performance by using 5-fold cross validation coupled with out-of-fold area under the curve (AUC) measures were established for breast, lung, pancreatic and prostate cancer to be 0.89, 0.84, 0.95 and 0.83 respectively. The genes defining each of these predictive models were enriched for pathways relevant to disease specific etiology, notably in the control of gene regulation in these same pathways. The breast cancer cohort consisted primarily of stage I and II patients, including tumors < 2 cm and these samples exhibited a high cancer probability score. This suggests that the 5hmC derived classification methodology may yield epigenomic detection of early stage disease in plasma. Same observation was made for the pancreatic dataset where >50% of cancers were stage I and II and showed the highest cancer probability score.