bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chimeric antigen receptor-modified T cells strike back
Authors: Frigault Matthew J. , Maus Marcela V. 
Published: March 2016

Abstract
Chimeric antigen receptors (CARs) are engineered molecules designed to endow a polyclonal T-cell population with the ability to recognize tumor-associated surface antigens. In their simplest form, CARs comprise a targeting moiety in the form of a single-chain variable fragment from an antibody connected to various intracellular signaling domains allowing for T-cell activation. This powerful approach combines the specificity of an antibody with the cytotoxic ability of a T cell. There has been much excitement since early phase trials of CAR-T cells targeting CD19 expressed on B-cell malignancies demonstrated remarkable efficacy in inducing long-term, stable remissions in otherwise relapsed/refractory disease. Despite these successes, we have just begun to understand the intricacies of CAR biology with efforts underway to utilize this platform in the treatment of other, previously refractory malignancies. Challenges currently include identification of viable cancer targets, management strategies for potentially severe and irreversible toxicities and overcoming the immunosuppressive nature of the tumor microenvironment. This review will focus on basic CAR structure and function, previous success and new approaches aimed at the broader application of CAR-T-cell therapy.
Recipes no longer a piece of cake
Authors: Ryan Natalie S. , Rossor Martin N. 
Published: March 2016

Abstract
This case examines the clinical history, examination, and investigation findings of a patient with posterior cortical atrophy (PCA). This neurodegenerative syndrome, which is most commonly due to Alzheimer’s disease (AD), is an important cause of young onset dementia which often provokes diagnostic uncertainty as the clinical presentation is dominated by visual impairments. The symptoms and signs of PCA are described and ways of approaching the clinical assessment, investigation, and management of patients with PCA are discussed. Tests to perform in a focused cognitive assessment are suggested which, together with detailed history-tak ing and appropriate investigation, may allow the PCA syndrome to be readily recognized.
A delayed diagnosis in delirium
Authors: Michael Benedict D. , Stoeter David J. , Manji Hadi 
Published: March 2016

Abstract
This case describes the presentation and initial investigation and management of a patient who is ultimately diagnosed to have encephalitis due the herpes simplex virus (HSV). This illustrates some of the challenges faced in identifying the key clinical features which should raise suspicion of HSV encephalitis and the important emergency investigations, highlighting the importance of a lumbar puncture (LP). The definition, epidemiology, and aetiologies of encephalitis are described, and the most sporadic common cause, HSV, is discussed in more detail. Specific learning points are presented regarding when neuroimaging is not required before a LP can be performed, when one can exclude HSV encephalitis, the utility of electroencephalography, and potential complications.
Writer’s cramp
Authors: Sadnicka Anna , Edwards Mark J. , Bhatia Kailash P. 
Published: March 2016

Abstract
An interesting presentation of idiopathic dystonia is described to exemplify diagnostic and management challenges in this intriguing neurological condition. The classification of dystonia has recently been revised and this new framework is presented in order to update clinicians with the relevant terminology. Investigation and treatment strategies for dystonia are succinctly summarized in tabular format for future easy reference.
Being moved to tears
Authors: Virgo Jonathan D. , Wong Sui , Plant Gordon T. 
Published: March 2016

Abstract
A This case describes carotid cavernous fistula. It is a rare, but important, potentially fatal condition that is often mismanaged. The case includes a case report that highlights well several of the commonly encountered diagnostic and therapeutic challenges. The clinical tips and expert comments provide the reader with useful clinical pointers for diagnosis. Carotid cavernous fistula epidemiology and pathophysiology are reviewed in the learning points, together with diagnostic work-up and the therapeutic options.
A worsening acute psychosis
Authors: Vivekananda Umesh , Kullmann Dimitri M. 
Published: March 2016

Abstract
This chapter summarizes our increasing knowledge of the antibody-mediated encephalitides since the first diagnosis made in 1968. It focuses on anti-NMDA-receptor-mediated encephalitis (ANMDARE), and describes the diverse neurological manifestations that can be expected, its stereotypical progression, and the possible pathophysiological processes underlying the condition. It reviews recent ANMDARE case series including typical MRI, EEG, and CSF features seen on diagnostics, associated neoplasms to investigate, and a suggested pathway for treatment. It discusses other forms of antibody-mediated encephalitis, including paraneoplastic limbic encephalitis, limbic encephalitis associated with voltage-gated potassium-channel antibodies, stiff person syndrome (SPS) and its variants, and more recently found causative antibodies to AMPA and GABA receptors.
Will I walk again, doctor?
Authors: Ajina Sara , Gall Angela 
Published: March 2016

Abstract
This case examines the rehabilitation of a young woman with a spinal cord injury, its potential complications and prognosis, and how best to approach its management. It explains how to perform the international neurological classification of spinal cord injuries, and reviews the physiological consequences of injury according to the spinal level. It also describes key points for early rehabilitation to ensure an adequate assessment of the extent of injury, and appropriate prophylaxis and monitoring for complications. It details how to manage some of the more common clinical aspects, including spasticity, neurogenic bladder, and autonomic dysreflexia, as well as less frequently encountered issues such as sexual and reproductive function. In addition, the case explores some of the important psychological and ethical issues that can arise in this condition, which may also be relevant to the broader management of chronic neurological disorders.
Constraining turbulence mixing strength in transitional discs with
planets using SPHERE and ALMA
Authors: de Juan Ovelar M. , Pinilla P. , Min M. , Dominik C. , Birnstiel T. 
Published: March 2016

Abstract
We investigate the effect that the turbulent mixing strength parameter αturb plays on near-infrared polarimetric and sub-millimetre interferometric imaging observations of transitional discs (TDs) with a gap carved by a planet. We generate synthetic observations of these objects with ALMA and VLT/SPHERE-ZIMPOL by combining hydrodynamical, dust evolution, radiative transfer and instrument models for values of $\mbox{$\alpha _{\rm {turb}}$}=[10^{-4}, 10^{-3}, 10^{-2}]$. We find that, through a combination of effects on the viscosity of the gas, the turbulent mixing and dust evolution processes, αturb strongly affects the morphology of the dust distribution that can be traced with these observations. We constrain the value of αturb to be within an order of magnitude of 10−3 in TD sources that show cavities in sub-mm continuum images while featuring continuous distribution of dust or smaller cavities in NIR-polarimetric images.
On the stellar halo metallicity profile of Milky Way-like galaxies in the Auriga simulations
Authors: Monachesi Antonela , Gómez Facundo A. , Grand Robert J. J. , Kauffmann Guinevere , Marinacci Federico , Pakmor Rüdiger , Springel Volker , Frenk Carlos S. 
Published: March 2016

Abstract
A recent observational study of haloes of nearby Milky Way-like galaxies shows that only half (four out of eight) of the current sample exhibits strong negative metallicity ([Fe/H]) gradients. This is at odds with predictions from hydrodynamical simulations where such gradients are ubiquitous. In this Letter, we use high-resolution cosmological hydrodynamical simulations to study the [Fe/H] distribution of galactic haloes. We find that kinematically selected stellar haloes, including both in situ and accreted particles, have an oblate [Fe/H] distribution. Spherical [Fe/H] radial profiles show strong negative gradients within 100 kpc, in agreement with previous numerical results. However, the projected median [Fe/H] profiles along the galactic disc minor axis, typically obtained in observations, are significantly flatter. The median [Fe/H] values at a given radius are larger for the spherical profiles than for the minor axis profiles by as much as 0.4 dex within the inner 50 kpc. Similar results are obtained if only the accreted stellar component is considered indicating that the differences between spherical and minor axis profiles are not purely driven by heated disc star particles formed in situ. Our study highlights the importance of performing careful comparisons between models and observations of halo [Fe/H] distributions.
Discovery of a loose star cluster in the Large Magellanic Cloud
Authors: Piatti Andrés E. 
Published: March 2016

Abstract
We present results for an up-to-date uncatalogued star cluster projected towards the Eastern side of the Large Magellanic Cloud (LMC) outer disc. The new object was discovered from a search of loose star cluster in the Magellanic Clouds’ (MCs) outskirts using kernel density estimators on Washington CT1 deep images. Contrarily to what would be commonly expected, the star cluster resulted to be a young object (log(t yr−1) = 8.45) with a slightly subsolar metal content (Z = 0.013) and a total mass of 650 M⊙. Its core, half-mass and tidal radii also are within the frequent values of LMC star clusters. However, the new star cluster is placed at the Small Magellanic Cloud distance and at 11.3 kpc from the LMC centre. We speculate with the possibility that it was born in the inner body of the LMC and soon after expelled into the intergalactic space during the recent Milky Way/MCs interaction. Nevertheless, radial velocity and chemical abundance measurements are needed to further understand its origin, as well as extensive search for loose star clusters in order to constrain the effectiveness of star cluster scattering during galaxy interactions.
Nanotechnology development in China: challenges and opportunities
Authors: Qiu Jane 
Published: March 2016

Abstract
China has invested heavily in nanotechnology in the past decades. It's one of the key areas of focus in the medium and long-term scientific programmes between 2006 and 2020. In 2012, the country also launched a Strategic Pioneering Programme on nanotechnology, which has a budget of one billion yuan (US$152 million) over five years and is led by the Chinese Academy of Sciences (CAS) in Beijing. As a result of this long-term investment, China is now a major player in nanotechnology, ranking first worldwide in terms of the number of scientific papers and patents.
At the Sixth International Conference on Nanoscience and Technology—which was held in Beijing on 3–5 September, 2015—Chunli Bai, President of CAS and Editor-in-Chief of National Science Review (NSR), shared a platform with another five leading scientists, where they discussed recent progress of nanotechnology in China, the potential impact of nanoparticles on public health, as well as challenges and opportunities ahead.

Chunli Bai (Chair)
President of Chinese Academy of Sciences in Beijing

Minghua Liu
An expert on nano materials and molecular assembly and Director of National Center for Nanoscience and Technology, China, in Beijing

Zhongfan Liu
An expert on nanochemistry and graphene at Peking University

Chen Wang
An expert on nanomicroscopy and nanomedicine and Deputy Director of National Center for Nanoscience and Technology, China, in Beijing

Peidong Yang
An expert on nanomaterials and their application in energy research at the University of California at Berkeley, USA

Yuliang Zhao
An expert on nanomedicine and nanosafety at National Center for Nanoscience and Technology, China, and Chinese Academy of Sciences’ Institute of High Energy Physics
The demands and challenges of exascale computing: an interview with Zuoning Chen
Authors: Chen Wenguang 
Published: March 2016

Abstract
High-performance computing (HPC) is currently moving from the petaflops scale (1015 FLOPS) towards exascale (1018 FLOPS) computing. The leap up to exascale computing will not only be a milestone in the history of computer science, but will also bring the prospect of transformative progress in many areas, including energy, life sciences, materials chemistry and national security. Because of the vital roles played by supercomputers in science, engineering and national security, the global race to develop the first exascale supercomputer is intensifying. Since 2013, China Tianhe-2 has ranked as the fastest computer in the world. Questions now arise as to the demands and challenges to be faced in the path towards development of exascale computing capabilities, and with regard to China's prospects of continuing to have the world's leading supercomputer in the future. In an interview with NSR, Professor Zuoning Chen, senior engineer of the National Research Center of Parallel Computer Engineering and Technology and Academician of the Chinese Academy of Engineering, gives her insights into the most important issues in this field, including the technical challenges when designing and implementing exascale computers, fault tolerance issues, processor architectures, interconnect bandwidths, emerging technologies for the mitigation of memory problems and the challenges facing and advantages for China.
A Prospective, Randomized, Controlled Trial of Paravertebral Block versus General Anesthesia Alone for Prosthetic Breast Reconstruction
Authors: Wolf Omer , Clemens Mark W. , Purugganan Ronaldo V. , Crosby Melissa A. , Kowalski Alicia M. , Kee Spencer S. , Liu Jun , Goravanchi Farzin 
Published: March 2016

Background:
Paravertebral blocks have gained popularity because of ease of implementation and a shift toward ambulatory breast surgery procedures. Previous retrospective studies have reported potential benefits of paravertebral blocks, including decreased narcotic and antiemetic use.

Methods:
The authors conducted a prospective controlled trial of patients undergoing breast reconstruction over a 3-year period. The patients were randomized to either a study group of paravertebral blocks with general anesthesia or a control group of general anesthesia alone. Demographic and procedural data, in addition to data regarding pain and nausea patient-reported numeric scores and consumption of opioid and antiemetic medications, were recorded.

Results:
A total of 74 patients were enrolled to either the paravertebral block (n = 35) or the control group (n = 39). There were no significant differences in age, body mass index, procedure type, or cancer diagnosis between the two groups. Patients who received a paravertebral block required less opioid intraoperatively and postoperatively combined compared with patients who did not receive paravertebral blocks (109 versus 246 fentanyl equivalent units; p < 0.001), and reported significantly lower pain scores at 0 to 1 (3.0 versus 4.6; p = 0.02), 1 to 3 (2.0 versus 3.2; p = 0.01), and 3 to 6 (1.9 versus 2.7; p = 0.04) hours postoperatively. The study group also consumed less antiemetic medication (0.7 versus 2.1; p = 0.05).

Conclusions:
Incorporating paravertebral blocks carries considerable potential for improving pathways for breast cancer patients undergoing breast reconstruction—with minimal procedure-related morbidity. This is the first prospective study designed to assess paravertebral blocks in the setting of prosthetic breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Current Trends and Controversies in Breast Augmentation
Authors: Hidalgo David A. , Sinno Sammy 
Published: March 2016

Background:
A survey was conducted to study current attitudes and common practices in breast augmentation.

Methods:
A 35-item electronic questionnaire was sent to the entire active American Society of Plastic Surgeons membership. It was divided into current controversies, new technologies, common practices, secondary procedures, and member demographics.

Results:
There were 1067 respondents. Fifty percent of surgeons never use anatomically shaped implants and another 42 percent do so less than half the time. Autologous fat is used infrequently as a primary technique but more often as a supplemental technique. Approximately 7 percent report a case of anaplastic large cell lymphoma. Eighty-five percent do not use preoperative three-dimensional imaging. More than half of surgeons use acellular dermal matrix in secondary procedures. Approximately half do not use insertion funnels. Preoperative sizing with silicone implants, inframammary incisions, partial submuscular pockets, and smooth silicone implants larger than 300 cc are dominant practice preferences. Postoperative massage is still popular with over half of respondents. Just over half do not use pharmacologic agents for capsular contracture. Capsular contracture and size change were the most frequent reasons for reoperation. Capsular contracture is typically treated with anterior capsulectomy the first time, and either total capsulectomy or anterior capsulectomy with acellular dermal matrix use when recurrent. Almost half of respondents perform fewer than 50 breast augmentations yearly.

Conclusions:
There is an established most common approach to breast augmentation among respondents. Most surgeons are slow to embrace controversial practices and to adopt new technologies, although acellular dermal matrix use is becoming more popular. The 7 percent incidence of anaplastic large cell lymphoma was noteworthy.
Improvement in Pain After Lumbar Spine Surgery
Authors: Mancuso Carol A. , Reid M.C. , Duculan Roland , Girardi Federico P. 
Published: March 2016

Objectives:
Improvement in pain is a major expectation of patients undergoing lumbar spine surgery.

Materials and Methods:
Among 422 patients, the goal of this prospective study was to measure 2-year postoperative pain and to determine whether this outcome varied according to patient and clinical characteristics, including amount of pain relief expected preoperatively. Before surgery patients completed valid questionnaires that addressed clinical characteristics and expectations for pain improvement. Two years after surgery patients reported how much pain improvement they actually received.

Results:
The mean age was 56 years old and 55% were men. Two years after surgery 11% of patients reported no improvement in pain, 28% reported a little to moderate improvement, 44% reported a lot of improvement, and 17% reported complete improvement. In multivariable analysis, patients reported less pain improvement if, before surgery, they expected greater pain improvement (odds ratio [OR] 1.4), had a positive screen for depression (OR 1.7), were having revision surgery (OR 1.6), had surgery at L4 or L5 (OR 2.5), had a degenerative diagnosis (OR 1.6), and if, after surgery, they had another surgery (OR 2.8) and greater back (OR 1.3) and leg (OR 1.1) pain (all variables P≤0.05).

Conclusions:
Pain is not uncommon after lumbar surgery and is associated with a network of clinical, surgical, and psychological variables. This study provides evidence that patients’ expectations about pain are an independent variable in this network. Because expectations are potentially modifiable this study supports addressing pain-related expectations with patients before surgery through discussions with surgeons and through formal preoperative patient education.
Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration
Authors: Bergendal Annica , Kieler Helle , Sundström Anders , Hirschberg Angelica Lindén , Kocoska-Maras Ljiljana 
Published: March 2016

Abstract

Objective:
The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen.

Methods:
In this case-control study, conducted in Sweden between 2003 and 2009, we included 838 cases of VTE and 891 controls with a mean age of 55 years. Controls were matched by age to the cases and randomly selected from the population. We used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization.

Results:
Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21). In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10).

Conclusions:
The risk of VTE risk is higher in users of systemic combined estrogen–progestogen treatment than in users of estrogen only. Furthermore, the risk of VTE was lower for women who used local estrogen than among those using oral estrogen only. Transdermal estrogen only treatment and estrogen for local effect seem not to be related to an increased risk of VTE.
Actigraphically Measured Sleep-Wake Behavior After Mild Traumatic Brain Injury: A Case-Control Study
Authors: Allan Alicia C. , Edmed Shannon L. , Sullivan Karen A. , Karlsson Lina J. E. , Lange Rael T. , Smith Simon S. 
Published: March 2016

Objective:
To characterize and compare the sleep-wake behavior of individuals following a mild traumatic brain injury (mTBI) with that of noninjured healthy controls.

Setting:
Community.

Participants:
Fourteen participants with a recent mTBI (M
age = 28.07; SD = 10.45; n = 10 females) and 34 noninjured controls (M
age = 23.70; SD = 7.30; n = 31 females).

Design:
Cross-sectional.

Main Measures:
Battery of subjective sleep measures and 14 days of sleep-wake monitoring via actigraphy (objective measurement) and concurrent daily sleep diary.

Results:
Participants who had sustained an mTBI self-reported significantly higher sleep-related impairment, poorer nightly sleep quality, and more frequently met criteria for clinical insomnia, compared with controls (d = 0.76-1.11, large effects). The only significant between-group difference on objective sleep metrics occurred on sleep timing. On average, people with a recent history of mTBI fell asleep and woke approximately 1 hour earlier than did the controls (d = 0.62-0.92, medium to large effects).

Conclusion:
Participants with a history of mTBI had several subjective sleep complaints but relatively few objective sleep changes with the exception of earlier sleep timing. Future research is needed to understand the clinical significance of these findings and how these symptoms can be alleviated. Interventions addressing subjective sleep complaints (eg, cognitive behavior therapy for insomnia) should be tested in this population.