bluuebunny/crossref_metadata_2025 huggingface dataset:
Conventional transanal excision for a very low gastrointestinal stromal tumour
Authors: Sotiropoulos Georgios C , Stamopoulos Paraskevas , Kykalos Stylianos , Machairas Nikolaos
Published: April 2017

Gastrointestinal stromal tumour (GIST) represents a rare tumour entity, which has been more intensively investigated during the last decade. The rectum as the primary site of GIST is even uncommon. The space constraints in the pelvis renders optimal oncological surgery demanding and proximity of these lesions to the anal sphincter enhances the potential morbidity of any radical surgery. We herein report on a young patient with a >5 cm rectal GIST localised at 1 cm from the anorectal junction.
Brodie abscess of the femoral capital epiphysis in a 2-year-old child caused byKingella kingae
Authors: Hourston George JM , Kankam Hadyn KN , Mitchell Piers D , Latimer Mark David
Published: April 2017

We report the case of a Brodie abscess of the femoral capital epiphysis from whichKingella kingaewas isolated. This is to the best of our knowledge the first report of a Brodie abscess of the femoral capital epiphysis from whichK. kingaewas isolated.
Management of a case of myopic foveoschisis with phakic intraocular lens (pIOL) in situ: intraoperative challenges
Authors: Kumar Atul , Mehta Aditi , Ravani Raghav Dinesh , Kakkar Prateek
Published: April 2017

We describe the case of a 30-year-old man with pathological myopia with a phakic intraocular lens (IOL) (Visian ICL V4c model; STAAR, Monrovia, California, USA) in situ having complaints of metamorphopsia in the left eye with documented myopic foveoschisis on swept-source optical coherence tomography (DRI OCT Triton; Topcon, Tokyo, Japan). The patient underwent pars plana vitrectomy with internal limiting membrane peeling. This report discusses the intraoperative challenges occurring as a result of increased optical aberrations in the presence of a phakic IOL.
Exogenous Cushing's syndrome due to a Chinese herbalist’s prescription of ointment containing dexamethasone
Authors: Franke Viola , Scholtens Winnie Francien , von Rosenstiel Ines Alexandra , Walenkamp Marie Jose
Published: April 2017

Eczema in children is a chronic disabling condition. The impact of this condition on the lives of families is often underestimated by conventional physicians. As a consequence parents may investigate complementary treatment options. Close monitoring by a paediatrician is essential, considering that a variety of adverse effects can occur during the use of complementary treatment. We present a 5-year-old girl with eczema. She visited a Chinese herbalist who prescribed an ointment. The parents noticed that the eczema resolved fast, itching decreased and she was finally sleeping well. However, her behaviour changed and appetite increased. Undetectable levels of serum cortisol were found, which was indicative of exogenous Cushing's syndrome. Analysis of the ointment revealed the presence of dexamethasone. Hydrocortisone substitution and subsequently a reduction schedule were implemented, after which endogenous cortisol production recovered after 4 months. Physicians should be aware that unregistered herbal medicine can contain potent drugs such as glucocorticoids.
Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex antibody limbic encephalitis
Authors: Sweeney Michael , Galli Jonathan , McNally Scott , Tebo Anne , Haven Thomas , Thulin Perla , Clardy Stacey L
Published: April 2017

We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation. Following treatment with immunotherapy, the patient demonstrated clinical improvement. Repeat serum evaluation 4 months posthospitalisation remained seropositive for VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity. VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation. Our findings suggest that clinical symptoms can predate the detection of the antibody. We conclude that when suspicion for autoimmune encephalitis is high in the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2 seropositivity, early immunotherapy and repeat testing should be considered.
Primary malignant melanoma of the cervix: a rare disease
Authors: Julião Ivo , Carvalho Sonia Dias , Patricio Vanda , Raimundo Ana
Published: April 2017

Malignant melanoma (MM) arising primarily in the cervix is exceedingly rare and has a poor prognosis. We report the case of a primary MM of the cervix in a 64-year-old woman with vaginal bleeding. She presented with a cervical amelanotic lesion which on biopsy rendered the diagnosis of MM. The patient was staged as International Federation of Gynecology and Obstetrics IIB and underwent Wertheim-Meigshysterectomy followed by brachytherapy. One year later, she was diagnosed with a large pelvic relapse for which surgery was performed. She then presented with a vaginal relapse and an isolated hepatic lesion, both of which were proposed for surgery. The diagnosis of MM of the cervix is a clinical and pathological challenge due to its rarity and overlapping features. Cytology cannot accurately diagnose it. Moreover, amelanotic MMs must be distinguished from other poorly differentiated carcinomas by diagnosis that ultimately relies on immunohistochemical staining. Radical surgery is the only treatment showing predictive benefit.
Syndrome of inappropriate antidiuretic hormone accompanied by bilateral hypothalamic and anterior thalamic lesions with serum antiaquaporin 4 antibody
Authors: Inoue Kosuke , Nakayama Takahiro , Kamisawa Aya , Saito Jun
Published: April 2017

We described a rare case of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and severe unconsciousness accompanied by bilateral hypothalamic and anterior thalamic lesions with positive serum antiaquaporin 4 (AQP4) antibody. A 29-year-old man was admitted to our hospital due to the subacute progression of an unconscious state. He was observed to be hyponatraemic secondary to SIADH. Brain MRI showed bilateral hypothalamic and anterior thalamic lesions. Anti-AQP4 antibody was detected in his serum. After the administration of intravenous methylprednisolone pulse therapy, his symptoms improved with complete recovery from SIADH and regression of the hypothalamic and anterior thalamic lesions. The patient was transferred to another hospital for rehabilitation with 20 mg/day of oral prednisolone 127 days after admission. This case highlights the importance of testing for anti-AQP4 antibody in patients with unexplainable SIADH, subacute progressive unconsciousness and bilateral hypothalamic and anterior thalamic lesions.
Ten‐minute chat
Authors: Kelson Melissa
Published: April 2017

Melissa Kelson is a fourth year student at the Royal Veterinary College. She recently spent a week of her EMS with the BVA's journals.
Sodium–hydrogen exchangers in the nematodeCaenorhabditiselegans: investigations towards their potential role in hypodermal H+excretion, Na+uptake, and ammonia excretion, as well as acid–base balance
Authors: Adlimoghaddam Aida , O’Donnell Michael J. , Quijada-Rodriguez Alex , Weihrauch Dirk
Published: April 2017

Cation/proton exchangers of the cation proton antiporter 1 (CPA1) subfamily (NHEs, SLC 9) play an important role in many physiological processes, including cell volume regulation, acid–base homeostasis, and ammonia excretion. The soil nematode Caenorhabditis elegans (Maupas, 1900) (N2, 1968) expresses nine paralogues (NHX-1 to NHX-9). The current study was undertaken to investigate the role of the cation/proton exchanger in hypodermal Na+and H+fluxes, as well in ammonia excretion processes. Measurements using SIET (scanning ion-selective electrode technique) showed that the hypodermis promotes H+secretion and Na+uptake. Inhibitory effects on fluxes were observed upon application of amiloride but not EIPA, suggesting that NHXs are not involved in the transport processes. In response to stress induced by starvation or exposure to 1 mmol·L−1NH4Cl, pH 5.5, or pH 8.0, body pH stayed fairly constant, with changes in mRNA expression levels detected in intestinal NHX-2 and hypodermal NHX-3. In conclusion, the study suggest that hypodermal apically localized EIPA-sensitive Na+/H+exchangers do not likely play a role in ammonia excretion and Na+uptake in the hypodermis of C. elegans, whereas apical amiloride-sensitive Na+channels seem to be involved not just in hypodermal Na+uptake but indirectly also in NH4+and H+excretion.
DNA barcoding and traditional taxonomy: an integrated approach for biodiversity conservation
Authors: Sheth Bhavisha P. , Thaker Vrinda S.
Published: April 2017

Biological diversity is depleting at an alarming rate. Additionally, a vast amount of biodiversity still remains undiscovered. Taxonomy has been serving the purpose of describing, naming, and classifying species for more than 250 years. DNA taxonomy and barcoding have accelerated the rate of this process, thereby providing a tool for conservation practice. DNA barcoding and traditional taxonomy have their own inherent merits and demerits. The synergistic use of both methods, in the form of integrative taxonomy, has the potential to contribute to biodiversity conservation in a pragmatic timeframe and overcome their individual drawbacks. In this review, we discuss the basics of both these methods of biological identification (traditional taxonomy and DNA barcoding), the technical advances in integrative taxonomy, and future trends. We also present a comprehensive compilation of published examples of integrative taxonomy that refer to nine topics within biodiversity conservation. Morphological and molecular species limits were observed to be congruent in ∼41% of the 58 source studies. The majority of the studies highlighted the description of cryptic diversity through the use of molecular data, whereas research areas like endemism, biological invasion, and threatened species were less discussed in the literature.
Geometric models of Helium
Authors: Atiyah M. F.
Published: April 2017

A previous paper [M. F. Atiyah and N. S. Manton, arXiv:1609.02816 ] modeled atoms and their isotopes by complex algebraic surfaces with the projective plane modeling Hydrogen. In this paper, models of the stable isotopes Helium-4 and Helium-3 are constructed.
Predictions of ρ meson cross-sections between AdS/QCD and boosted Gaussian wave functions in the color glass condensate model
Authors: Xie Jianquan , Peng Hui
Published: April 2017

Exclusive [Formula: see text] meson production is computed in dipole model using two different light-cone wave functions in this paper. The Color-Glass-Condensate (CGC) model is implemented to compute the dipole cross-section. The two light-cone wave functions are AdS/QCD model and boosted Gaussian model. It can be seen that the predictions using the two light-cone wave functions are close to each other.
Illumination and Expression Invariant Face Recognition
Authors: Dhekane Manasi , Seal Ayan , Khanna Pritee
Published: April 2017

An illumination and expression invariant face recognition method based on uniform local binary patterns (uLBP) and Legendre moments is proposed in this work. The proposed method exploits uLBP texture features and Legendre moments to make a feature representation with enhanced discriminating power. The input images are preprocessed to extract the face region and normalized. From normalized image, uLBP codes are extracted to obtain texture image which overcomes the effect of monotonic temperature changes. Legendre moments are computed from this texture image to get the required feature vector. Legendre moments conserve the spatial structure information of the texture image. The resultant feature vector is classified using k-nearest neighbor classifier with [Formula: see text] norm. To evaluate the proposed method, experiments are performed on IRIS and NVIE databases. The proposed method is tested on both visible and infrared images under different illumination and expression variations and performance is compared with recently published methods in terms of recognition rate, recall, length of feature vector, and computational time. The proposed method gives better recognition rates and outperforms other recent face recognition methods.
On the prime graph question for almost simple groups with an alternating socle
Authors: Bächle Andreas , Caicedo Mauricio
Published: April 2017

Let [Formula: see text] be an almost simple group with socle [Formula: see text], the alternating group of degree [Formula: see text]. We prove that there is a unit of order [Formula: see text] in the integral group ring of [Formula: see text] if and only if there is an element of that order in [Formula: see text] provided [Formula: see text] and [Formula: see text] are primes greater than [Formula: see text]. We combine this with some explicit computations to verify the prime graph question for all almost simple groups with socle [Formula: see text] if [Formula: see text].
Scalar field quasinormal frequencies of Reissner–Nordström black hole surrounded by quintessence by using the continued fraction method
Authors: Wu Chen
Published: April 2017

We evaluate the quasinormal modes of massless scalar field around Reissner–Nordström black hole surrounded by a static and spherically symmetric quintessence using the continued fraction method. The appropriate Frobenius series for three special cases of the quintessence parameter [Formula: see text] and [Formula: see text] are derived successfully. We show the variation of quasinormal frequencies with charge of the black hole and the quintessential parameters. The numerical results show that quintessence field decreases oscillation frequencies of all angular momentum [Formula: see text] modes and increases the damping time of [Formula: see text] modes.
Crystal structure and nonlinear optical properties of 7,8-dihydroxyaminoacenaphthalene
Authors: Niu Meng-Xiao , Zhang Chao-Zhi
Published: April 2017

In this paper, 7,8-dihydroxyaminoacenaphthalene was synthesized by a convenient method. Its crystal structure was determined by X-ray diffraction. The crystal structure shows that the molecules aggregated to monoclinic crystal with space group [Formula: see text]. The semi-empirical method ZINDO was employed to study the static first hyperpolarizabilities of this compound. The static first hyperpolarizability value is [Formula: see text][Formula: see text]esu, which is 6.00 times as much as that of KH2PO4 (KDP) molecule. The results indicate that the title molecule would be potential nonlinear optical materials.
New type gray spatial solitons in two-photon photorefractive media with both the linear and quadratic electro-optic effects
Authors: Jiang Qichang , Su Yanli , Nie Hexian , Ma Ziwei , Li Yonghong
Published: April 2017

The numerical solutions of gray spatial solitons supported by linear and quadratic electro-optic (EO) effects in two-photon photorefractive (PR) media are deduced. The characteristics of the gray spatial soliton, soliton pair and soliton family are investigated by numerical method. The full width at half maximum of the gray spatial soliton increases gradually with the increase of the grayness, but decreases gradually with the increase of the soliton optical intensity and external electric field. Also, every soliton component in the gray–gray soliton pair or soliton family has the same full width at half maximum.
Influence of a few-atomic silver molecules on the high-order harmonic generation in the laser-produced plasmas
Authors: Ganeev R. A.
Published: April 2017

The plasmas containing small molecules of silver produced during ablation of the bulk silver and silver nanoparticles (NPs) at the conditions suitable for efficient harmonic generation of the ultrashort pulses propagating through the laser-produced plasmas (LPPs) were studied. The time-of-flight mass-spectroscopy studies of plasmas confirmed the presence of these species in the plasmas. We suggest that the harmonics generated during the ablation of nanoparticle and bulk targets could be enhanced due to the appearance of these small species (Ag2, Ag3) at the moment of propagation of the ultrashort laser pulses through such plasmas.
Bandwidth analysis of non-collinear fourth and fifth harmonic generation in nonlinear uniaxial crystals
Authors: Song Dongsheng , Zheng Yuanlin , Zhao Xiaohui , Cai Zengyan , Chen Xianfeng
Published: April 2017

The optimal angle bandwidth and wavelength bandwidth of fourth-harmonic generation (FHG) and fifth-harmonic generation (FIFHG) of the 1064[Formula: see text]nm laser are analyzed based on the numerical calculation results of non-collinear type-I and type-II phase matching processes for general nonlinear uniaxial crystals with 1[Formula: see text]cm length. The non-collinear phase matching angles and effective nonlinear coefficients of FHG and FIFHG are calculated. The optimal angle bandwidth and wavelength bandwidth are obtained. The results are beneficial to broadband and efficient non-collinear phase matching FHG and FIFHG experiments and studies.
3D RECONSTRUCTION AND SLM SURVEY FOR DENTAL IMPLANTS
Authors: ZHOU HONGFU , FAN QIN
Published: April 2017

This research studies an integrated dental 3D reconstruction scanning method which combines impression model scanning, intraoral camera scanning and CT scanning. In the dental integrated scanning, tooth root data is acquired from CT DICOM data and 3D reconstruction is processed by Mimics®software developed from Materialise. The tooth crown and the tooth bridge 3D data are obtained by scanning the tooth impression model or scanning with an intraoral scanner. Also, it surveys that the dental prosthesis are fabricated with traditional methods and printed with Select Laser Melting (SLM) technology. In the research, it presents that SLM additive manufacturing (AM) method can fabricate customized dental prosthesis with high dimensional accuracy.
Synthesizing large-scale species trees using the strict consensus approach
Authors: Moon Jucheol , Eulenstein Oliver
Published: April 2017

Supertree problems are a standard tool for synthesizing large-scale species trees from a given collection of gene trees under some problem-specific objective. Unfortunately, these problems are typically NP-hard, and often remain so when their instances are restricted to rooted gene trees sampled from the same species. While a class of restricted supertree problems has been effectively addressed by the parameterized strict consensus approach, in practice, most gene trees are unrooted and sampled from different species. Here, we overcome this stringent limitation by describing efficient algorithms that are adopting the strict consensus approach to also handle unrestricted supertree problems. Finally, we demonstrate the performance of our algorithms in a comparative study with classic supertree heuristics using simulated and empirical data sets.
Magnetic Proximity Effect Free Spin Hall Magnetoresistance in YIG∖Pd
Authors: d’Allivy Kelly O. , Collet M. , Jacquet E. , Mattana R. , Petroff F. , Bortolotti P. , Cros V. , Anane A. , Wilhelm F. , Ollefs K. , Rogalev A.
Published: April 2017

Magnetic Proximity Effect (MPE) at the interface of Y3Fe5O[Formula: see text] (YIG)[Formula: see text]Pd is investigated using X-ray Magnetic Circular Dichroism (XMCD) at the Pd-edges. No evidence of MPE is found even for Pd film thicknesses down to 0.5[Formula: see text]nm. The same bilayers have been thereafter used for inverse spin Hall Effect (ISHE) measurements using the spin-pumping technique. A large signal can be observed at the ferromagnetic resonance. The angular dependence of the Pd dc resistance has been measured as a function of the YIG magnetization direction. It shows the expected dependences for the spin Hall magnetoresistance (SMR). Our methodology allows to state that ISHE and SMR are intrinsic phenomena whose underlying physics is uncorrelated to MPE.
Using CoreSight PTM to Integrate CRA Monitoring IPs in an ARM-Based SoC
Authors: Lee Yongje , Lee Jinyong , Heo Ingoo , Hwang Dongil , Paek Yunheung
Published: April 2017

The ARM CoreSight Program Trace Macrocell (PTM) has been widely deployed in recent ARM processors for real-time debugging and tracing of software. Using PTM, the external debugger can extract execution behaviors of applications running on an ARM processor. Recently, some researchers have been using this feature for other purposes, such as fault-tolerant computation and security monitoring. This motivated us to develop an external security monitor that can detect control hijacking attacks, of which the goal is to maliciously manipulate the control flow of victim applications at an attacker’s disposal. This article focuses on detecting a special type of attack called
code reuse attacks
(CRA), which use a recently introduced technique that allows attackers to perform arbitrary computation without injecting their code by reusing only existing code fragments. Our external monitor is attached to the outside of the host system via the system bus and ARM CoreSight PTM, and is fed with execution traces of a victim application running on the host. As a majority of CRAs violates the normal execution behaviors of a program, our monitor constantly watches and analyzes the execution traces of the victim application and detects a symptom of attacks when the execution behaviors violate certain rules that normal applications are known to adhere. We present two different implementations for this purpose: a hardware-based solution in which all CRA detection components are implemented in hardware, and a hardware/software mixed solution that can be employed in a more resource-constrained environment where the deployment of full hardware-level CRA detection is burdensome.
HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis
Authors: Lang Michaela , Berry David , Passecker Katharina , Mesteri Ildiko , Bhuju Sabin , Ebner Florian , Sedlyarov Vitaly , Evstatiev Rayko , Dammann Kyle , Loy Alexander , Kuzyk Orest , Kovarik Pavel , Khare Vineeta , Beibel Martin , Roma Guglielmo , Meisner-Kober Nicole , Gasche Christoph
Published: April 2017

HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3′ untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of IBD and inflammatory colon cancer, augmented DSS-induced weight loss and increased tumor multiplicity, size, and invasiveness. MS-444 treatment also abrogated tumor cell apoptosis and depleted tumor-associated eosinophils, accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in APCMin mice, a model of FAP and colon cancer, diminished the number of small intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity, with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae. Taken together, our results indicate that HuR activation is an early event in FAP-adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a preclinical proof of concept for HuR inhibition as an effective means of FAP chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9); 2424–38. ©2017 AACR.
Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection
Authors: Tummers Willemieke S. , Warram Jason M. , Tipirneni Kiranya E. , Fengler John , Jacobs Paula , Shankar Lalitha , Henderson Lori , Ballard Betsy , Pfefer T. Joshua , Pogue Brian W. , Weichert Jamey P. , Bouvet Michael , Sorger Jonathan , Contag Christopher H. , Frangioni John V. , Tweedle Michael F. , Basilion James P. , Gambhir Sanjiv S. , Rosenthal Eben L.
Published: April 2017

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. Cancer Res; 77(9); 2197–206. ©2017 AACR.
Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma
Authors: Jariwala Nidhi , Rajasekaran Devaraja , Mendoza Rachel G. , Shen Xue-Ning , Siddiq Ayesha , Akiel Maaged A. , Robertson Chadia L. , Subler Mark A. , Windle Jolene J. , Fisher Paul B. , Sanyal Arun J. , Sarkar Devanand
Published: April 2017

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor-initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-κB signaling pathways in promoting TIC formation in Alb/SND1 mice. In human xenograft models of subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor 3′, 5′-deoxythymidine bisphosphate (pdTp), inhibited tumor formation without effects on body weight or liver function. Our work establishes an oncogenic role for SND1 in promoting TIC formation and highlights pdTp as a highly selective SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. Cancer Res; 77(12); 3306–16. ©2017 AACR.
Two-Dimensional Ultrasound Evaluation of the Fetal Cerebral Aqueduct: Improving the Antenatal Diagnosis and Counseling of Aqueductal Stenosis
Authors: Viñals Fernando , Ruiz Pilar , Quiroz Gabriel , Guerra Francisco A. , Correa Flavia , Martínez Daniel , Puerto Bienvenido
Published: April 2017

Objective: To describe a technique for the visualization and measurement of cerebral aqueduct diameter through a 2D sagittal median plane, and to report its aspect and measurement in fetuses with aqueductal stenosis (AS). Methods: This was a cross-sectional study of 207 morphologically normal fetuses in low-risk pregnancies between 20 and 36 weeks of gestation. The cerebral aqueduct was visualized transvaginally in a midsagittal plane, and measurements of its greatest diameter (ampulla) were taken independently by an expert and a nonexpert sonographer. In addition, the aqueduct morphology from 7 fetuses with AS and complete follow-up were compared to the reference range. Results: Aqueductal measurements were obtained in 206 of 207 normal fetuses. Aqueductal growth occurred linearly with gestational age. Our method demonstrated excellent interobserver reproducibility. Among the 7 fetuses with AS, the aqueductal lumen could not be identified in 6 and had a funneling aspect in 1. Discussion: Our study demonstrated that it is possible to visualize and measure the cerebral aqueduct directly through a 2D ultrasound median plane. In fetuses with severe ventriculomegaly, the morphology and width of this structure could represent a relevant tool in improving AS diagnosis, differentiating it from other causes of significant ventricular dilation that carry a different outcome.
Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study
Authors: Johansson Kristina , Jansson Jan-Håkan , Johansson Lars , Bylesjö Ingemar , Nilsson Torbjörn K. , Eliasson Mats , Söderberg Stefan , Lind Marcus
Published: April 2017

Background: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke. Methods: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011. Results: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99–2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03–2.21). Conclusion: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.
Unilateral Posterior Polymorphous Corneal Dystrophy Presented as Anisometropic Astigmatism: 3 Case Reports
Authors: Jeon Hyun Sun , Hyon Joon Young
Published: April 2017

Background: Posterior polymorphous corneal dystrophy (PPCD) is typically considered bilateral and asymptomatic. However, few case reports on patients with unilateral PPCD with asymmetric refractive error have mentioned anisometropic amblyopia development. In support of this, we report 3 cases of unilateral PPCD that presented as anisometropic astigmatism. Visual prognosis related to amblyopia development is discussed. Case Presentation: All 3 patients had a band lesion in the affected eye and a difference of at least 1.5 diopters in cylindrical refractive error between their eyes. The affected eye had a greater amount of astigmatism in all cases. Two patients (Cases 1 and 2) also had amblyopia in the affected eye. Case 1 was a 25-year-old male with a unilateral PPCD diagnosis and a band lesion involving the visual axis. Case 2 was an 11-year-old boy diagnosed with unilateral PPCD. The boy was treated with occlusion and atropine therapy over a 2-year period. Case 3 was a 4-year-old girl diagnosed with unilateral PPCD. The girl had a 30-month history of corrective spectacle use and had no amblyopia. In all cases, the corneal endothelial cell count was lower in the affected eye than in the unaffected contralateral eye. Conclusions: Practitioners should closely monitor patients with unilateral PPCD for astigmatic anisometropia and amblyopia development. Visual prognosis for patients with unilateral PPCD may be related to lesion position, age at diagnosis, astigmatism severity, and early-childhood corrective spectacle use.
Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation
Authors: Takano Mayumi , Nakata Masahiko , Murata Susumu , Sumie Masahiro , Morita Mineto
Published: April 2017

Introduction: This study aimed to investigate the risk factors, incidence, and influence on the perinatal outcome of chorioamniotic membrane separation (CMS) after fetoscopic laser photocoagulation (FLP). Material and Methods: This retrospective study included 312 women who underwent FLP for twin-to-twin transfusion syndrome (TTTS). Clinical records were used to review obstetrical examinations, complications, operative data, ultrasonographic findings, and perinatal and neonatal follow-up data in all patients. Results: A total of 260 cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only independent risk factor of CMS was performing FLP before 20 weeks of gestational age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal outcome, CMS was only related with increased risk of premature rupture of membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences in GA at delivery and survival rate. Discussion: In our cohort, the incidence of CMS after FLP was approximately 13%, with surgery before 20 weeks being the only risk factor identified. Although in our population CMS did not worsen perinatal outcome in terms of preterm delivery or survival, the preterm PROM rate was increased and this should be considered for the patients' management.
CMTM3 (CKLF-Like Marvel Transmembrane Domain 3) Mediates Angiogenesis by Regulating Cell Surface Availability of VE-Cadherin in Endothelial Adherens Junctions
Authors: Chrifi Ihsan , Louzao-Martinez Laura , Brandt Maarten , van Dijk Christian G.M. , Burgisser Petra , Zhu Changbin , Kros Johan M. , Duncker Dirk J. , Cheng Caroline
Published: April 2017

Objective—

Decrease in VE-cadherin adherens junctions reduces vascular stability, whereas disruption of adherens junctions is a requirement for neovessel sprouting during angiogenesis. Endocytosis plays a key role in regulating junctional strength by altering bioavailability of cell surface proteins, including VE-cadherin. Identification of new mediators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we assessed the function of CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously identified as highly expressed in Flk1
+
endothelial progenitor cells during embryonic development.

Approach and Results—

Using a 3-dimensional coculture of human umbilical vein endothelial cells-GFP (green fluorescent protein) and pericytes-RFP (red fluorescent protein), we demonstrated that siRNA-mediated CMTM3 silencing in human umbilical vein endothelial cells impairs angiogenesis. In vivo CMTM3 inhibition by morpholino injection in developing zebrafish larvae confirmed that CMTM3 expression is required for vascular sprouting. CMTM3 knockdown in human umbilical vein endothelial cells does not affect proliferation or migration. Intracellular staining demonstrated that CMTM3 colocalizes with early endosome markers EEA1 (early endosome marker 1) and Clathrin
+
vesicles and with cytosolic VE-cadherin in human umbilical vein endothelial cells. Adenovirus-mediated CMTM3 overexpression enhances endothelial endocytosis, shown by an increase in Clathrin
+
, EEA1
+
, Rab11
+
, Rab5
+
, and Rab7
+
vesicles. CMTM3 overexpression enhances, whereas CMTM3 knockdown decreases internalization of cell surface VE-cadherin in vitro. CMTM3 promotes loss of endothelial barrier function in thrombin-induced responses, shown by transendothelial electric resistance measurements in vitro.

Conclusions—

In this study, we have identified a new regulatory function for CMTM3 in angiogenesis. CMTM3 is involved in VE-cadherin turnover and is a regulator of the cell surface pool of VE-cadherin. Therefore, CMTM3 mediates cell–cell adhesion at adherens junctions and contributes to the control of vascular sprouting.
Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease
Authors: Herder Christian , de las Heras Gala Tonia , Carstensen-Kirberg Maren , Huth Cornelia , Zierer Astrid , Wahl Simone , Sudduth-Klinger Julie , Kuulasmaa Kari , Peretz David , Ligthart Symen , Bongaerts Brenda W.C. , Dehghan Abbas , Ikram M. Arfan , Jula Antti , Kee Frank , Pietilä Arto , Saarela Olli , Zeller Tanja , Blankenberg Stefan , Meisinger Christa , Peters Annette , Roden Michael , Salomaa Veikko , Koenig Wolfgang , Thorand Barbara
Published: April 2017

Objective—

Interleukin (IL)-1β represents a key cytokine in the development of cardiovascular disease (CVD). IL-1β is counter-regulated by IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor. This study aimed to identify population-based studies on circulating IL-1RA and incident CVD in a systematic review, estimate the association between IL-1RA and incident CVD in a meta-analysis, and to test whether the association between IL-1RA and incident CVD is explained by other inflammation-related biomarkers in the MONICA/KORA Augsburg case–cohort study (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg).

Approach and Results—

We performed a systematic literature search and identified 5 cohort studies on IL-1RA and incident CVD in addition to the MONICA/KORA Augsburg case–cohort study for a meta-analysis based on a total of 1855 CVD cases and 18 745 noncases with follow-up times between 5 and 16 years. The pooled standardized hazard ratio (95% confidence interval) for incident CVD was 1.11 (1.06–1.17) after adjustment for age, sex, anthropometric, metabolic, and lifestyle factors (
P
<0.0001). There was no heterogeneity in effect sizes (I
2
=0%;
P
=0.88). More detailed analyses in the MONICA/KORA study showed that the excess risk for CVD was attenuated by ≥10% after additional separate adjustment for serum levels of high-sensitivity C-reactive protein, IL-6, myeloperoxidase, soluble E-selectin, or soluble intercellular adhesion molecule-1.

Conclusions—

Serum IL-1RA levels were positively associated with risk of CVD after adjustment for multiple confounders in a meta-analysis of 6 population-based cohorts. This association may at least partially reflect a response to triggers inducing subclinical inflammation, oxidative stress, and endothelial activation.
Thresholds for Ambulatory Blood Pressure Among African Americans in the Jackson Heart Study
Authors: Ravenell Joseph , Shimbo Daichi , Booth John N. , Sarpong Daniel F. , Agyemang Charles , Beatty Moody Danielle L. , Abdalla Marwah , Spruill Tanya M. , Shallcross Amanda J. , Bress Adam P. , Muntner Paul , Ogedegbe Gbenga
Published: April 2017

Background:

Ambulatory blood pressure (BP) monitoring is the reference standard for out-of-clinic BP measurement. Thresholds for identifying ambulatory hypertension (daytime systolic BP [SBP]/diastolic BP [DBP] ≥135/85 mm Hg, 24-hour SBP/DBP ≥130/80 mm Hg, and nighttime SBP/DBP ≥120/70 mm Hg) have been derived from European, Asian, and South American populations. We determined BP thresholds for ambulatory hypertension in a US population-based sample of African American adults.

Methods:

We analyzed data from the Jackson Heart Study, a population-based cohort study comprised exclusively of African American adults (n=5306). Analyses were restricted to 1016 participants who completed ambulatory BP monitoring at baseline in 2000 to 2004. Mean SBP and DBP levels were calculated for daytime (10:00 am–8:00 pm), 24-hour (all available readings), and nighttime (midnight–6:00 am) periods, separately. Daytime, 24-hour, and nighttime BP thresholds for ambulatory hypertension were identified using regression- and outcome-derived approaches. The composite of a cardiovascular disease or an all-cause mortality event was used in the outcome-derived approach. For this latter approach, BP thresholds were identified only for SBP because clinic DBP was not associated with the outcome. Analyses were stratified by antihypertensive medication use.

Results:

Among participants not taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were 134/85 mm Hg, 130/81 mm Hg, and 123/73 mm Hg, respectively. The outcome-derived thresholds for daytime, 24-hour, and nighttime SBP corresponding to a clinic SBP ≥140 mm Hg were 138 mm Hg, 134 mm Hg, and 129 mm Hg, respectively. Among participants taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were 135/85 mm Hg, 133/82 mm Hg, and 128/76 mm Hg, respectively. The corresponding outcome-derived thresholds for daytime, 24-hour, and nighttime SBP were 140 mm Hg, 137 mm Hg, and 133 mm Hg, respectively, among those taking antihypertensive medication.

Conclusions:

On the basis of the outcome-derived approach for SBP and regression-derived approach for DBP, the following definitions for daytime, 24-hour, and nighttime hypertension corresponding to clinic SBP/DBP ≥140/90 mm Hg are proposed for African American adults: daytime SBP/DBP ≥140/85 mm Hg, 24-hour SBP/DBP ≥135/80 mm Hg, and nighttime SBP/DBP ≥130/75 mm Hg, respectively.
Toll-Like Receptor 4 Mediates Hemorrhagic Transformation After Delayed Tissue Plasminogen Activator Administration in In Situ Thromboembolic Stroke
Authors: García-Culebras Alicia , Palma-Tortosa Sara , Moraga Ana , García-Yébenes Isaac , Durán-Laforet Violeta , Cuartero Maria I. , de la Parra Juan , Barrios-Muñoz Ana L. , Díaz-Guzmán Jaime , Pradillo Jesús M. , Moro María A. , Lizasoain Ignacio
Published: April 2017

Background and Purpose—

Hemorrhagic transformation is the main complication of revascularization therapies after stroke. Toll-like receptor 4 (TLR4) is implicated in cerebral damage and inflammation in stroke. This study was designed to determine the role of TLR4 in hemorrhagic transformation development after tissue plasminogen activator (tPA) administration.

Methods—

Mice expressing (TLR4
+/+
) or lacking functional TLR4 (TLR4
−
/−
) were subjected to middle cerebral artery occlusion using an in situ thromboembolic model by thrombin injection into the middle cerebral artery, and tPA (10 mg/kg) was administered 20 minutes or 3 hours after ischemia. Infarct size, hemorrhages, IgG extravasation, matrix metalloproteinase 9 expression, and neutrophil infiltration were assessed 24 hours after ischemia.

Results—

In TLR4
+/+
, early reperfusion (tPA at 20 minutes) resulted infarct volume, whereas late recanalization (tPA at 3 hours) did not modify lesion size and increased the rate of the most severe hemorrhages. In TLR4
−
/−
mice, both early and late reperfusion did not modify lesion size. Importantly, late tPA administration did not result in worse hemorrhages and in an increased bleeding area as occurred in TLR4
+/+
group. In TLR4
−
/−
animals, late reperfusion produced a lesser increase in matrix metalloproteinase 9 expression when compared with TLR4
+/+
animals.

Conclusions—

Our results demonstrate TLR4 involvement in hemorrhagic transformation induced by delayed tPA administration, very likely by increasing matrix metalloproteinase 9 expression.
Integrative Modeling of Prefrontal Cortex
Authors: Alexander William H. , Vassena Eliana , Deraeve James , Langford Zachary D.
Published: April 2017

pFC is generally regarded as a region critical for abstract reasoning and high-level cognitive behaviors. As such, it has become the focus of intense research involving a wide variety of subdisciplines of neuroscience and employing a diverse range of methods. However, even as the amount of data on pFC has increased exponentially, it appears that progress toward understanding the general function of the region across a broad array of contexts has not kept pace. Effects observed in pFC are legion, and their interpretations are generally informed by a particular perspective or methodology with little regard with how those effects may apply more broadly. Consequently, the number of specific roles and functions that have been identified makes the region a very crowded place indeed and one that appears unlikely to be explained by a single general principle. In this theoretical article, we describe how the function of large portions of pFC can be accommodated by a single explanatory framework based on the computation and manipulation of error signals and how this framework may be extended to account for additional parts of pFC.
Foraging Value, Risk Avoidance, and Multiple Control Signals: How the Anterior Cingulate Cortex Controls Value-based Decision-making
Authors: Brown Joshua W. , Alexander William H.
Published: April 2017

Recent work on the role of the ACC in cognition has focused on choice difficulty, action value, risk avoidance, conflict resolution, and the value of exerting control among other factors. A main underlying question is what are the output signals of ACC, and relatedly, what is their effect on downstream cognitive processes? Here we propose a model of how ACC influences cognitive processing in other brain regions that choose actions. The model builds on the earlier Predicted Response Outcome model and suggests that ACC learns to represent specifically the states in which the potential costs or risks of an action are high, on both short and long timescales. It then uses those cost signals as a basis to bias decisions to minimize losses while maximizing gains. The model simulates both proactive and reactive control signals and accounts for a variety of empirical findings regarding value-based decision-making.