bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome
Authors: Kapadia Anish N , Elias Gavin J B , Boutet Alexandre , Germann Jürgen , Pancholi Aditiya , Chu Powell , Zhong Jidan , Fasano Alfonso , Munhoz Renato , Chow Clement , Kucharczyk Walter , Schwartz Michael L , Hodaie Mojgan , Lozano Andres M 
Published: July 2020

BackgroundMRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects.ObjectivesTo assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes.MethodsNinety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7.ResultsAcute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm3at day 1 vs 19.5±19.3 mm3at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm3trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence.ConclusionLesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent.Trial registration numberNCT02252380.
Blackhole in nonlocal gravity: comparing metric from Newmann–Janis algorithm with slowly rotating solution
Authors: Kumar Utkarsh , Panda Sukanta , Patel Avani 
Published: July 2020

AbstractThe strong gravitational field near massive blackhole is an interesting regime to test General Relativity (GR) and modified gravity theories. The knowledge of spacetime metric around a blackhole is a primary step for such tests. Solving field equations for rotating blackhole is extremely challenging task for the most modified gravity theories. Though the derivation of Kerr metric of GR is also demanding job, the magical Newmann–Janis algorithm does it without actually solving Einstein equation for rotating blackhole. Due to this notable success of Newmann–Janis algorithm in the case of Kerr metric, it has been being used to obtain rotating blackhole solution in modified gravity theories. In this work, we derive the spacetime metric for the external region of a rotating blackhole in a nonlocal gravity theory using Newmann–Janis algorithm. We also derive metric for a slowly rotating blackhole by perturbatively solving field equations of the theory. We discuss the applicability of Newmann–Janis algorithm to nonlocal gravity by comparing slow rotation limit of the metric obtained through Newmann–Janis algorithm with slowly rotating solution of the field equation.
Cilostazol for Secondary Prevention of Stroke and Cognitive Decline
Authors: McHutchison Caroline , Blair Gordon W. , Appleton Jason P. , Chappell Francesca M. , Doubal Fergus , Bath Philip M. , Wardlaw Joanna M. 
Published: July 2020

Background and Purpose:
Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.

Methods:
A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742).

Results:

We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81];
P
<0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29–0.64];
P
=0.0001), deaths (OR=0.64 [95% CI, 0.49–0.83],
P
<0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54–0.99];
P
=0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.

Conclusions:
Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.
Pathophysiology of Intracranial Aneurysms
Authors: Rodemerk Jan , Junker Andreas , Chen Bixia , Pierscianek Daniela , Dammann Philipp , Darkwah Oppong Marvin , Radbruch Alexander , Forsting Michael , Maderwald Stefan , Quick Harald H. , Zhu Yuan , Jabbarli Ramazan , Sure Ulrich , Wrede Karsten H. 
Published: July 2020

Background and Purpose:

The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H
2
, which, in turn, is isomerized to prostaglandin E
2
. In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI.

Methods:
The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm.

Results:

Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size (
P
=0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs (
P
=0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression (
P
=0.022).

Conclusions:
Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.
Post-rescue Innocent Passage by Non-governmental Search and Rescue Vessels in the Mediterranean
Authors: Schatz Valentin J. , Fantinato Marco 
Published: July 2020

Abstract
This article analyses the conformity of Italian legislation adopted in 2019 – and its implementation – with the regime of innocent passage in the territorial sea under Part II of the 1982 United Nations Convention on the Law of the Sea with respect to civil rescue vessels returning from rescue operations with rescued persons on board. It first gives a brief overview over the international legal regime applicable to search and rescue (SAR) operations. Next, the article introduces Italian legislation adopted in 2019, which establishes a legal basis for administrative orders prohibiting ships the entry into, transit through, and stopping in Italy’s territorial sea. In a third step, the article shows how the new Italian legislation has so far been implemented vis-à-vis SAR vessels of non-governmental organizations in post-rescue situations. This is followed by an analysis of the conformity of the Italian legislation and its implementation with the regime of innocent passage.
Sea Level Rise in the CESM Large Ensemble: The Role of Individual Climate Forcings and Consequences for the Coming Decades
Authors: Fasullo John T. , Gent Peter R. , Nerem R. Steven 
Published: July 2020

AbstractThe emergence of a spatial pattern in the externally forced response (FR) of dynamic sea level (DSL) during the altimeter era has recently been demonstrated using climate models but our understanding of its initial emergence, drivers, and implications for the future is poor. Here the anthropogenic forcings of the DSL pattern are explored using the Community Earth System Model Large Ensemble (CESM-LE) and Single-Forcing Large Ensemble, a newly available set of simulations where values of individual forcing agents remain fixed at 1920 levels, allowing for an estimation of their effects. Statistically significant contributions to the DSL FR are identified for greenhouse gases (GHGs) and industrial aerosols (AERs), with particularly strong contributions resulting from AERs in the mid-twentieth century and GHGs in the late twentieth and twenty-first century. Secondary, but important, contributions are identified for biomass burning aerosols in the equatorial Atlantic Ocean in the mid-twentieth century, and for stratospheric ozone in the Southern Ocean during the late twentieth century. Key to understanding regional DSL patterns are ocean heat content and salinity anomalies, which are driven by surface heat and freshwater fluxes, ocean dynamics, and the spatial structure of seawater thermal expansivity. Potential implications for the interpretation of DSL during the satellite era and the longer records from tide gauges are suggested as a topic for future research.
Effect of Osteosarcopenia on Postoperative Functional Outcomes and Subsequent Fracture in Elderly Hip Fracture Patients
Authors: Bae Gi Cheol , Moon Kyoung Ho 
Published: July 2020

Introduction: In this study, we evaluated how muscle mass and bone density affect postoperative functional scores and subsequent fracture rates and investigated the correlation between sarcopenia and osteoporosis by measuring preoperative psoas muscle indices (PMIs) and bone mineral densities (BMDs) in elderly patients followed for more 1 year after surgical treatment for hip fracture. Methods: Among patients older than 65 years who underwent surgery for hip fracture from January 2009 to November 2018, 154 patients with preoperative 3D pelvic bone computed tomography and dual-energy X-ray absorptiometry BMD data and followed postoperatively for at least 1 year were considered for the present study. One hundred twenty-six patients were finally included. These patients were divided into 4 groups based on PMIs and T-score, that is, to osteoporosis, sarcopenia, osteosarcopenia, or normal groups. To analyze outcomes after surgery, we measured functional activity levels using the Barthel index and Harris hip score (HHS) systems. In addition, we compared the rates of subsequent hip fracture ratio with patient’s characteristics, and analyzed the correlation between PMIs and BMDs using Pearson correlations analysis. Results: Barthel index and HHS score showed significant differences between the normal and osteosarcopenia group at 6 weeks, 3 months, and 1 year after surgery ( P < .001). Subsequent fracture incidences were significantly higher in the osteosarcopenia group than in the normal group ( P = .046), and T-score and PMI were found to be strongly correlated (a < 0.01; R = 0.763). Conclusion: Postoperative functional outcomes were significantly poorer and the subsequent fracture rate was significantly higher in the osteosarcopenia group than in the normal group. In addition, sarcopenia and osteoporosis were found to be highly correlated.
Structure basis of the FERM domain of kindlin-3 in supporting integrin αIIbβ3 activation in platelets
Authors: Sun Jiaojiao , Xiao Desheng , Ni Yuan , Zhang Tianlong , Cao Zhongyuan , Xu Zhou , Nguyen Huong , Zhang Jun , White Gilbert C. , Ding Jianping , Ma Yan-Qing , Xu Zhen 
Published: July 2020

Abstract
Kindlin-3, a protein 4.1, ezrin, radixin, and moesin (FERM) domain–containing adaptor in hematopoietic cells, is essentially required for supporting the bidirectional integrin αIIbβ3 signaling in platelets by binding to the integrin β3 cytoplasmic tail. However, the structural details of kindlin-3’s FERM domain remain unknown. In this study, we crystalized the kindlin-3’s FERM domain protein and successfully solved its 3-dimensional structure. The structure shows that the 3 kindlin-3’s FERM subdomains (F1, F2, and F3) compact together and form a cloverleaf-shaped conformation, which is stabilized by the binding interface between the F1 and F3 subdomains. Interestingly, the FERM domain of kindlin-3 exists as a monomer in both crystal and solution, which is different from its counterpart in kindlin-2 that is able to form a F2 subdomain-swapped dimer; nonetheless, dimerization is required for kindlin-3 to support integrin αIIbβ3 activation, indicating that kindlin-3 may use alternative mechanisms for formation of a functional dimer in cells. To evaluate the functional importance of the cloverleaf-like FERM structure in kindlin-3, structure-based mutations were introduced into kindlin-3 to disrupt the F1/F3 interface. The results show that integrin αIIbβ3 activation is significantly suppressed in platelets expressing the kindlin-3 mutant compared with those expressing wild-type kindlin-3. In addition, introduction of equivalent mutations into kindlin-1 and kindlin-2 also significantly compromises their ability to support integrin αIIbβ3 activation in CHO cells. Together, our findings suggest that the cloverleaf-like FERM domain in kindlins is structurally important for supporting integrin αIIbβ3 activation.
Phylogenetic and spatial distribution of evolutionary diversification, isolation, and threat in turtles and crocodilians (non-avian archosauromorphs)
Authors: Colston Timothy J. , Kulkarni Pallavi , Jetz Walter , Pyron R. Alexander 
Published: July 2020

Abstract
Background
The origin of turtles and crocodiles and their easily recognized body forms dates to the Triassic and Jurassic. Despite their long-term success, extant species diversity is low, and endangerment is extremely high compared to other terrestrial vertebrate groups, with ~ 65% of ~ 25 crocodilian and ~ 360 turtle species now threatened by exploitation and habitat loss. Here, we combine available molecular and morphological evidence with statistical and machine learning algorithms to present a phylogenetically informed, comprehensive assessment of diversification, threat status, and evolutionary distinctiveness of all extant species.

Results
In contrast to other terrestrial vertebrates and their own diversity in the fossil record, the recent extant lineages of turtles and crocodilians have not experienced any global mass extinctions or lineage-wide shifts in diversification rate or body-size evolution over time. We predict threat statuses for 114 as-yet unassessed or data-deficient species and identify a concentration of threatened turtles and crocodilians in South and Southeast Asia, western Africa, and the eastern Amazon. We find that unlike other terrestrial vertebrate groups, extinction risk increases with evolutionary distinctiveness: a disproportionate amount of phylogenetic diversity is concentrated in evolutionarily isolated, at-risk taxa, particularly those with small geographic ranges. Our findings highlight the important role of geographic determinants of extinction risk, particularly those resulting from anthropogenic habitat-disturbance, which affect species across body sizes and ecologies.

Conclusions
Extant turtles and crocodilians maintain unique, conserved morphologies which make them globally recognizable. Many species are threatened due to exploitation and global change. We use taxonomically complete, dated molecular phylogenies and various approaches to produce a comprehensive assessment of threat status and evolutionary distinctiveness of both groups. Neither group exhibits significant overall shifts in diversification rate or body-size evolution, or any signature of global mass extinctions in recent, extant lineages. However, the most evolutionarily distinct species tend to be the most threatened, and species richness and extinction risk are centered in areas of high anthropogenic disturbance, particularly South and Southeast Asia. Range size is the strongest predictor of threat, and a disproportionate amount of evolutionary diversity is at risk of imminent extinction.
Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study
Authors: Hsu Jimmy M. , Hass Aaron , Gingras Marc-Alexandre , Chong Jaron , Costiniuk Cecilia , Ezer Nicole , Fraser Richard S. , McDonald Emily G. , Lee Todd C. 
Published: July 2020

Abstract
Background
Pneumocystis jirovecii pneumonia (PJP) can be challenging to diagnose, often requiring bronchoscopy. Since most patients suspected of PJP undergo imaging, we hypothesized that the findings of these studies could help estimate the probability of disease prior to invasive testing.

Methods
We created a cohort of patients who underwent bronchoscopy specifically to diagnose PJP and conducted a nested case-control study to compare the radiographic features between patients with (n = 72) and without (n = 288) pathologically proven PJP. We used multivariable logistic regression to identify radiographic features independently associated with PJP.

Results
Chest x-ray findings poorly predicted the diagnosis of PJP. However, multivariable analysis of CT scan findings found that “increased interstitial markings” (OR 4.3; 95%CI 2.2–8.2), “ground glass opacities” (OR 3.3; 95%CI 1.2–9.1) and the radiologist’s impression of PJP being “possible” (OR 2.0; 95%CI 1.0–4.1) or “likely” (OR 9.3; 95%CI 3.4–25.3) were independently associated with the final diagnosis (c-statistic 0.75).

Conclusions
Where there is clinical suspicion of PJP, the use of CT scan can help determine the probability of PJP. Identifying patients at low risk of PJP may enable better use of non-invasive testing to avoid bronchoscopy while higher probability patients could be prioritized.
Copy number variation of IL17RA gene and its association with the ankylosing spondylitis risk in Iranian patients: a case-control study
Authors: Aghaei Hamideh , Farhadi Elham , Akhtari Maryam , Shahba Sara , Mostafaei Shayan , Jamshidi Ahmadreza , Poursani Shiva , Mahmoudi Mahdi , Nicknam Mohammad Hossein 
Published: July 2020

Abstract
Background
Ankylosing spondylitis (AS) is considered as a subtype of spondyloarthritis (SpA) that mainly leads to fatigue, stiffness, spinal ankylosis, and impaired physical functions with reduced quality of life. Interleukin (IL)-17A provokes additional inflammatory mediators and recruits immune cells to the inflamed site. IL17 expression increased in various inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, crohn’s disease, and ankylosing spondylitis. The current study aimed to evaluate the association of IL17RA copy number changes with the susceptibility to AS and their correlation to IL17RA expression in Iranian population.

Methods
IL17RA copy number genotyping assessments were carried out in 455 AS patients and 450 healthy controls, using custom TaqMan CNV assays. TaqMan primers and probe were located in Chr.22:17109553 based on pre-designed IL17RA Copy Number Assay ID, Hs02339506_cn. mRNA expression of IL17RA was also measured by SYBR Green real-time polymerase chain reaction (PCR).

Results
A IL17RA copy number loss (< 2) was associated with AS compared to 2 copies as reference (OR:2.18, 95% CI: (1.38–3.44), P-value < 0.001) and increased the risk of AS. IL17RA mRNA expression showed a significant increase in peripheral blood mononuclear cells (PBMCs) of all AS individuals than controls. The mRNA expression level of 2 copies was significantly higher in AS patients.

Conclusions
Our findings revealed that a low copy number of IL17RA might confer a susceptibility risk to AS. However, it is probably not directly involved in the regulation of IL17RA mRNA expression. Epigenetic mechanisms like DNA methylation, post-transcriptional, and -translational modifications that regulate the expression of the genes may contribute in upregulation of IL17RA mRNA expression in the loss of gene copy number condition.