bluuebunny/crossref_metadata_2025 huggingface dataset:
Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis
Authors: Juge Pierre-Antoine , Gazal Steven , Constantin Arnaud , Mariette Xavier , Combe Bernard , Tebib Jacques , Dougados Maxime , Sibilia Jean , Le Loet Xavier , Dieudé Philippe
Published: September 2017

Background

The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5andIRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24).

Methods

Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variantTNFSF13Brs9514828 was previously found associated with RTX response in the same population, it was included in the analysis.

Results

The combination ofIRF5rs2004640,SPP1rs9138 andTNFSF13Brs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34×10−6, OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%.

Conclusion

Our results support the contribution of theIRF5,SPP1andTNFSF13Bgenotypic combination in the response to RTX for RA at W24.
Radiographic appearance of an osseous metastasis to the distal radius from a transitional cell carcinoma of the urinary bladder
Authors: Anesi Simone , Parry Andrew T , Monti Paola , Elliott James
Published: September 2017

An eight‐year‐old male entire springer spaniel diagnosed with transitional cell carcinoma (TCC) of the urinary bladder apex underwent partial, full‐thickness cystectomy and the mass was excised completely with 1 cm of clear histological margins.

Chemotherapy was initiated three months after surgery when ultrasound revealed probable early recurrence at the surgical site. Three doses of carboplatin were administered, but progressive disease was identified. Complete ultrasonographic response to vinblastine was noted after six treatments.

Five months after commencing chemotherapy, a persistent right thoracic limb lameness was noted. Radiographs revealed a lesion on the distal right radius that, despite a smooth periosteal reaction, had subtle features of malignancy. Fine needle aspirates of the lesion were consistent with metastatic TCC, and the patient was euthanased. There was no detectable neoplasia elsewhere.
Recurrent corneal ulceration in a young dog due to an ectopic cilium in an unusual location
Authors: Hamzianpour Negar , Pinheiro de Lacerda Rodrigo , Rhodes Michael
Published: September 2017

This is a report of an 11‐month‐old dog with recurrent corneal ulceration over the preceding three months. The cause was confirmed to be a single ectopic cilium in a rare location—the lower eyelid palpebral conjunctiva. Surgical excision of the aberrant hair was required for resolution of the disease process. This report demonstrates the importance of a systematic clinical approach to corneal ulceration in dogs, highlighting the importance of a complete history and ophthalmic examination. In non‐healing or recurrent corneal ulceration in young dogs, exploration for ectopic cilia is important. Magnification and a good light source are essential in such cases. Surgical excision is curative and the prognosis is good.
Renormalization scheme dependence and renormalization group summation
Authors: Chishtie F.A. , McKeon D.G.C.
Published: October 2017

We consider logarithmic contributions to the free energy, instanton effective action, and Laplace sum rules in QCD that are a consequence of radiative corrections. Upon summing these contributions by using the renormalization group, all dependence on the renormalization scale parameter μ cancels. The renormalization scheme dependence in these processes is examined, and a renormalization scheme is found in which the effect of higher-order radiative corrections is absorbed by the behaviour of the running coupling.
Effects of higher-order corrected entropy on the black hole physics
Authors: Pourhassan B. , Kokabi K.
Published: October 2017

In this paper we consider higher-order corrections of the BTZ and anti-de Sitter Schwarzschild black holes’ entropy and study corrected thermodynamics. We obtain some important thermodynamics quantities like internal and Helmholtz free energy and calculate specific heat. By using corrected specific heat we study black holes’ stability and investigate possible phase transition and critical points. Correction terms of the entropy are important when the size of a black hole is small and come from thermal fluctuations of statistical physics, hence one can interpret them as quantum corrections to the black hole thermodynamics. We show that the presence of corrections of entropy are very important for stability or instability of black holes.
Crustal architecture of the Laptev Rift System in the East Siberian Arctic based on 2D long-offset seismic profiles and gravity modelling
Authors: Drachev Sergey S. , Mazur Stanislaw , Campbell Simon , Green Christopher , Shkarubo Sergey I. , Tishchenko Andrii
Published: September 2017

The Laptev Shelf in the East Siberian Arctic represents a rare tectonic setting where an active oceanic spreading centre, the Gakkel Ridge, intersects a continental margin. The North America–Eurasia plate boundary follows the Gakkel Ridge and passes into a continental shelf; this has resulted in the development of a wide rift system that has been active since the Late Cretaceous. The new long-offset seismic profiles provide a reliable basis for deciphering the structural characteristics of this rift system. We use two new seismic profiles, along with one acquired in the 1990s, to examine the crustal architecture of the rift system. Our approach combines seismic interpretation, time to depth conversion of seismic profiles and 2D gravity forward modelling. The obtained results indicate the presence of hyperextended continental crust beneath the Ust' Lena Rift Basin and exhumed continental mantle at the base of the syn-rift succession along the rift axis. The upper crust was removed by brittle stretching, while the lower crust experienced extreme ductile thinning. Our results show that continental crust can be eliminated in the course of rifting without a considerable heat input from asthenospheric mantle.
Classification of Resilience Techniques Against Functional Errors at Higher Abstraction Layers of Digital Systems
Authors: Psychou Georgia , Rodopoulos Dimitrios , Sabry Mohamed M. , Gemmeke Tobias , Atienza David , Noll Tobias G. , Catthoor Francky
Published: October 2017

Nanoscale technology nodes bring reliability concerns back to the center stage of digital system design. A systematic classification of approaches that increase system resilience in the presence of functional hardware (HW)-induced errors is presented, dealing with higher system abstractions, such as the (micro)architecture, the mapping, and platform software (SW). The field is surveyed in a systematic way based on nonoverlapping categories, which add insight into the ongoing work by exposing similarities and differences. HW and SW solutions are discussed in a similar fashion so that interrelationships become apparent. The presented categories are illustrated by representative literature examples to illustrate their properties. Moreover, it is demonstrated how hybrid schemes can be decomposed into their primitive components.
Collateral Consequences of Punishment: A Critical Review and Path Forward
Authors: Kirk David S. , Wakefield Sara
Published: October 2017

The unprecedented growth of the penal system in the United States has motivated an expansive volume of research on the collateral consequences of punishment. In this review, we take stock of what is known about these collateral consequences, particularly in the domains of health, employment, housing, debt, civic involvement, families, and communities. Yet the full reckoning of the formal and informal consequences of mass incarceration and the tough-on-crime era is hindered by a set of thorny challenges that are both methodological and theoretical in nature. We examine these enduring challenges, which include (a) the importance of minimizing selection bias, (b) consideration of treatment heterogeneity, and (c) identification of causal mechanisms underlying collateral consequences. We conclude the review with a focused discussion on promising directions for future research, including insights into data infrastructure, opportunities for policy tests, and suggestions for expanding the field of inquiry.
NMR spectroscopy and electron microscopy identification of metabolic and ultrastructural changes to the kidney following ischemia-reperfusion injury
Authors: Chihanga Tafadzwa , Ma Qing , Nicholson Jenna D. , Ruby Hannah N. , Edelmann Richard E. , Devarajan Prasad , Kennedy Michael A.
Published: October 2017

Cellular, molecular, and ultrastructural nephron changes associated with ischemia-reperfusion injury-induced acute kidney injury (IRI-AKI) are not completely understood. Here, a multidisciplinary study was used to identify nephron changes in a mouse model of IRI-AKI. Histological analyses indicated distended Bowman’s glomerular spaces and proximal and distal tubules. Increased filtrate volume in nephrons was caused by reduced water reabsorption by severely damaged proximal tubule brush borders and blocked flow of filtrate into collecting tubules by mucoprotein casts in distal tubules. Immunohistochemistry revealed protein AKI biomarkers in proximal tubules and glomeruli but not in distal tubules. Nuclear magnetic resonance spectroscopy revealed several metabolites that increased such as valine, alanine, and lactate. Other metabolites such as trigonelline, succinate, 2-oxoisocaproate, and 1- methyl-nicotinamide decreased or were absent in urine following IRI due to altered kidney function or metabolism. Urinary glucose increased due to reduced reabsorption by damaged proximal tubule brush borders. Scanning electron microscopy revealed flattening of podocytes and pedicals surrounding glomerular capillaries, and transmission electron microscopy (TEM) revealed effacement of podocyte pedicals, both consistent with increased hydrostatic pressure in nephrons following IRI-AKI. TEM revealed shortened proximal tubule microvilli in IRI kidneys with diminished lamina propia. TEM showed dramatic loss of mitochondria in distal tubule epithelia of IRI kidneys and emergence of multivesicular bodies of endosomes indicating ongoing cellular death. Collectively, the data define ultrastructural changes to nephrons and altered kidney metabolism associated with IRI-AKI.
Convergence of linear acceleration and yaw rotation signals on non-eye movement neurons in the vestibular nucleus of macaques
Authors: Newlands Shawn D. , Abbatematteo Ben , Wei Min , Carney Laurel H. , Luan Hongge
Published: October 2017

Roughly half of all vestibular nucleus neurons without eye movement sensitivity respond to both angular rotation and linear acceleration. Linear acceleration signals arise from otolith organs, and rotation signals arise from semicircular canals. In the vestibular nerve, these signals are carried by different afferents. Vestibular nucleus neurons represent the first point of convergence for these distinct sensory signals. This study systematically evaluated how rotational and translational signals interact in single neurons in the vestibular nuclei: multisensory integration at the first opportunity for convergence between these two independent vestibular sensory signals. Single-unit recordings were made from the vestibular nuclei of awake macaques during yaw rotation, translation in the horizontal plane, and combinations of rotation and translation at different frequencies. The overall response magnitude of the combined translation and rotation was generally less than the sum of the magnitudes in responses to the stimuli applied independently. However, we found that under conditions in which the peaks of the rotational and translational responses were coincident these signals were approximately additive. With presentation of rotation and translation at different frequencies, rotation was attenuated more than translation, regardless of which was at a higher frequency. These data suggest a nonlinear interaction between these two sensory modalities in the vestibular nuclei, in which coincident peak responses are proportionally stronger than other, off-peak interactions. These results are similar to those reported for other forms of multisensory integration, such as audio-visual integration in the superior colliculus.

NEW & NOTEWORTHY This is the first study to systematically explore the interaction of rotational and translational signals in the vestibular nuclei through independent manipulation. The results of this study demonstrate nonlinear integration leading to maximum response amplitude when the timing and direction of peak rotational and translational responses are coincident.
“Gold” Pressed Essential Oil: An Essay on the Volatile Fragment fromCitrusJuice Industry By-Products Chemistry and Bioactivity
Authors: Kapsaski-Kanelli V. N. , Evergetis E. , Michaelakis A. , Papachristos D. P. , Myrtsi E. D. , Koulocheri S. D. , Haroutounian S. A.
Published: October 2017

Present essay explores the potentials ofCitrusjuice industry’s by-products as alternative bioactive natural products resources. Four crude Cold Pressed Essential Oils (CPEOs), derived from orange, lemon, grapefruit, and mandarin, were studied. All CPEOs were subjected to water distillation, in order to obtain the volatile fragment, which was further fractionated with respect to distillation period in two parts, concluding to eight samples. These samples along with the four original CPEOs were assessed in relation to their phytochemical content and their repellent and larvicidal properties against Asian Tiger Mosquito. The volatiles recovery rates ranged from 74% to 88% of the CPEO. Limonene presented a significant increase in all samples ranging from 8% to 52% of the respective CPEO’s content and peaked in mandarin’s 2nd volatile fragment which comprised 97% of the essential oil. The refinement process presented clear impacts on both bioassays: a significant increase in larvicidal potency was observed, annotated best by the improvement by 1100% and 1300% of the grapefruit volatile fractions; repellence testing provided only one significant result, the decrease of landings by 50% as a response to mandarin’s second volatile fraction. The applied methodology thus may be considered for the improvement ofCitrusjuice industry’s by-products chemistry and bioactivity.
The Transcriptional Network Structure of a Myeloid Cell: A Computational Approach
Authors: Espinal-Enríquez Jesús , González-Terán Daniel , Hernández-Lemus Enrique
Published: September 2017

Understanding the general principles underlying genetic regulation in eukaryotes is an incomplete and challenging endeavor. The lack of experimental information regarding the regulation of the whole set of transcription factors and their targets in different cell types is one of the main reasons to this incompleteness. So far, there is a small set of curated known interactions between transcription factors and their downstream genes. Here, we built a transcription factor network for human monocytic THP-1 myeloid cells based on the experimentally curated FANTOM4 database where nodes are genes and the experimental interactions correspond to links. We present the topological parameters which define the network as well as some global structural features and introduce a relative inuence parameter to quantify the relevance of a transcription factor in the context of induction of a phenotype. Genes like ZHX2, ADNP, or SMAD6 seem to be highly regulated to avoid an avalanche transcription event. We compare these results with those of RegulonDB, a highly curated transcriptional network for the prokaryotic organism E. coli, finding similarities between general hallmarks on both transcriptional programs. We believe that an approach, such as the one shown here, could help to understand the one regulation of transcription in eukaryotic cells.
Climate Change Impact on Monthly Precipitation Wet and Dry Spells in Arid Regions: Case Study over Wadi Al-Lith Basin
Authors: Almazroui Mansour , Balkhair Khaled S. , Islam M. Nazrul , Şen Zekai
Published: October 2017

Durations of monthly precipitation wet and dry spells are calculated using historical records and regional climate model (RCM) simulations for the Wadi Al-Lith basin in western Saudi Arabia. The characteristics of durations of wet and dry spells are based on the 50% risk level corresponding to the monthly records for average regional precipitation. The duration of wet spells in the model data is compared with observations for the base period 1971–2000. The impact of climate change on the durations of wet and dry spells is obtained using three global climate models projections with RCP4.5 and RCP8.5 scenarios downscaled by RCM. The probability distribution functions (PDFs) of the climate model scenarios and the precipitation records for the base period prove that climate change has a clear impact on the durations of wet and dry spells over the study area. There is an increase in wet spells frequency in the far future (2070–2099) compared to the near future (2020–2049). The increase in wet spells can be partly explained by the increase in extreme rainfall events and by the decrease in dry spells expected to occur over the study area towards the end of 21st century.
The Traumatic Tube: Bleeding Rectal Ulcer Caused by Flexi-Seal Device
Authors: Tiwari Abhinav , Sharma Himani , Qamar Khola , Alastal Yaseen , Sodeman Thomas , Nawras Ali
Published: October 2017

Diarrhea and fecal incontinence are common in critically ill patients and present a challenging problem in patient management. The Flexi-Seal® Fecal Management System is a device to divert the stools away from the patient, thus improving the care to patients with fecal incontinence. There have been only few case reports describing the complications with the use of this device. Here, we present a case of a 77-year-old woman who was admitted due to massive hematochezia while on anticoagulation. She was found to have a large rectal ulcer caused by the Flexi-Seal device, used during the last hospital stay for fecal incontinence. Flexi-Seal device can be effective for the management of incontinence; however, caution should be exercised during handling and pressure from the retention balloon should be relieved periodically.
An Unusual Subcutaneous Mass in an Otherwise Healthy Patient: A Case Report of Localized Histoplasmosis Diagnosed on Excisional Biopsy
Authors: Esquibel Brendon M. , Waller Christine J. , Agger William A.
Published: October 2017

Patients are commonly referred to general surgery clinics for evaluation of soft-tissue masses of the trunk and extremities. The primary goal of surgical referral is to confirm the presence of a mass, to assess the need for additional imaging and/or testing, and to gauge amenability to surgical biopsy, whether incisional or excisional. This is a case of a 67-year-old woman who was referred to surgery clinic for a small soft-tissue mass near her left elbow that had increased in size and pain over the past year. The mass had been present for several years. After MRI imaging revealed a nonspecific process, an excisional biopsy was performed. Following a careful review of the patient’s history, risk factors, and histological results, a diagnosis of localized subcutaneous Histoplasma capsulatum var. capsulatum infection was made. Without signs or symptoms of active, systemic disease, no further treatment was recommended. The patient was provided risk factor counseling for symptoms or signs of active histoplasmosis and outpatient follow-up. Histologically, most masses will return as benign and mesenchymal in origin. However, soft-tissue masses may arise from uncommon etiologies and a broad differential is needed to ensure appropriate management and recommendations.
Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade
Authors: Zboralski Dirk , Hoehlig Kai , Eulberg Dirk , Frömming Anna , Vater Axel
Published: September 2017

Immune checkpoint inhibitors promote T cell–mediated killing of cancer cells; however, only a subset of patients benefit from the treatment. A possible reason for this limitation may be that the tumor microenvironment (TME) is immune privileged, which may exclude cytotoxic T cells from the vicinity of cancer cells. The chemokine CXCL12 is key to the TME-driven immune suppression. In this study, we investigated the potential of CXCL12 inhibition by use of the clinical-stage l-RNA-aptamer NOX-A12 (olaptesed pegol) to increase the number of tumor-infiltrating lymphocytes. We used heterotypic tumor–stroma spheroids that mimic a solid tumor with a CXCL12-abundant TME. NOX-A12 enhanced the infiltration of T and NK cells in a dose-dependent manner. NOX-A12 and PD-1 checkpoint inhibition synergistically activated T cells in the spheroids, indicating that the agents complement each other. The findings were validated in vivo in a syngeneic murine model of colorectal cancer in which the addition of NOX-A12 improved anti–PD-1 therapy. Taken together, our work shows that CXCL12 inhibition can break the immune-privileged status of the TME by paving the way for immune effector cells to enter into the tumor, thereby broadening the applicability of checkpoint inhibitors in cancer patients. Cancer Immunol Res; 5(11); 950–6. ©2017 AACR.
Dabigatran versus Warfarin for Acute Venous Thromboembolism in Elderly or Impaired Renal Function Patients: Pooled Analysis of RE-COVER and RE-COVER II
Authors: Goldhaber Samuel , Schulman Sam , Eriksson Henry , Feuring Martin , Fraessdorf Mandy , Kreuzer Jörg , Schüler Elke , Schellong Sebastian , Kakkar Ajay
Published: October 2017

Management of acute venous thromboembolism (VTE) with anticoagulants in elderly patients and those with chronic kidney disease poses special challenges. The RE-COVER and RE-COVER II trials showed that dabigatran 150 mg twice daily was as effective as warfarin over 6 months in preventing recurrent VTE, with a lower bleeding risk. We now assess the effects of old age and renal impairment (RI) on pooled trial outcomes in 5,107 patients: 4,504 aged <75 years and 603 aged ≥75 years. The primary efficacy outcome was symptomatic VTE/VTE-related death. Safety outcomes were centrally adjudicated major bleeding events (MBEs), MBEs or clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeds. Baseline renal function was categorized as normal, mild RI or moderate RI. A total of 3,698 had normal renal function and 1,100 and 237 had mild and moderate RI, respectively (23 patients with severe RI and 49 with missing creatinine clearance data were not included). For dabigatran, VTE/VTE-related death decreased from 3.1% (normal renal function) to 1.9% for mild RI and to 0.0% for moderate RI. For warfarin, the event rates were 2.6, 1.6 and 4.1%, respectively. Overall, major bleeding increased with increasing RI (p = 0.0037) and with age (p = 0.4350), with no apparent difference between the dabigatran and warfarin patients. Dabigatran shows better efficacy than warfarin in RI and in the elderly patients, probably because of an increase in the concentration of dabigatran. However, bleeding risk increases with both dabigatran and warfarin in the presence of RI.
ПРОГНОЗУВАННЯ ЕФЕКТИВНОСТІ ЛІКУВАННЯ ХВОРИХ НА РАК ЯЄЧНИКІВ
Authors: Kolesnik O. O. , Rybin A. I.
Published: October 2017

Мета дослідження – вивчення медико-біологічних основ прогнозування ефективності платинової хіміотерапії та підвищення чутливості пухлини до хіміотерапії першої лінії.Матеріали та методи. З 2007 до 2011 року було обстежено 189 пацієнток з аденокарциномою яєчників III–IV стадії, яким після субоптимальної або неоптимальної циторедуктивної операції у післяопераційному періоді були проведені курси ад’ювантної хіміотерапії препаратами платини. Критерієм розподілу на групи була чутливість пухлини до препаратів платини. Результати дослідження та їх обговорення. Показано, що для пацієнток з РЯ є характерним напруження саногенетичних механізмів організму. Стан саногенезу в організмі пацієнток, хворих на рак яєчників, впливає на чутливість або рефрактерність пухлини до хіміотерапії препаратами платини. До маркерів прогнозу платинорезистентності відносяться генетична обтяженість (наявність мутантних алелів поліморфізмів BRCA1 5832insC та BRCA2 6174delAG у гетеро- та гомозиготному варіантах, мікросателітної нестабільності), висока активність циклінів D та E, підвищення рівнів катехоламінів, високий ступінь експресії оксиду азоту, ступінь гіперурикемії, активність експресії рецепторів до епідермального фактора росту та активність CAS 20q13. У жінок з наявністю вказаних факторів доцільно застосовувати медикаментозну корекцію дисрегуляційних порушень.Висновок. При ймовірній платинорезистентності доцільно на фоні стандартної терапії першої лінії застосовувати медикаментозну корекцію дисрегуляційних порушень (донатори оксиду азоту, детоксиканти, антиурикемічні засоби). При прогнозованій платиночутливості стандартна терапія першої лінії може бути доповнена засобами, які покращують переносимість терапії, але використання медикаментозної корекції дисрегуляційних порушень є недоцільним.
A produção social do conhecimento e as lições de Bourdieu para a Ciência da Informação
Authors: De Almeida Marco Antonio
Published: October 2017

Resenha de: MARTELETO, Regina M.; PIMENTA, Ricardo M. (Org.) Pierre Bourdieu e a produção social da cultura, do conhecimento e da informação. Garamond, 2017.LUCAS, Elaine R. O.; SILVEIRA, Murilo A. S. (Org.) A Ciência da Informação encontra Bourdieu. FEBAB UFPE, 2017
Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure
Authors: Bartolucci Jorge , Verdugo Fernando J. , González Paz L. , Larrea Ricardo E. , Abarzua Ema , Goset Carlos , Rojo Pamela , Palma Ivan , Lamich Ruben , Pedreros Pablo A. , Valdivia Gloria , Lopez Valentina M. , Nazzal Carolina , Alcayaga-Miranda Francisca , Cuenca Jimena , Brobeck Matthew J. , Patel Amit N. , Figueroa Fernando E. , Khoury Maroun
Published: October 2017

Rationale:

Umbilical cord–derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow–derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients.

Objective:

Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction.

Methods and Results:

Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10
6
cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow–derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC–treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC–treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography (
P
=0.0167 versus baseline) and cardiac MRI (
P
=0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%;
P
=0.028). In addition, at all follow-up time points, UC-MSC–treated patients displayed improvements of New York Heart Association functional class (
P
=0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire (
P
<0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy.

Conclusions:

Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov/ct2/show/NCT01739777
. Unique identifier: NCT01739777
Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Parikh Shan S. , Blackwell Daniel J. , Gomez-Hurtado Nieves , Frisk Michael , Wang Lili , Kim Kyungsoo , Dahl Christen P. , Fiane Arnt , Tønnessen Theis , Kryshtal Dmytro O. , Louch William E. , Knollmann Bjorn C.
Published: October 2017

Rationale:

Human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation–contraction coupling, and inefficient Ca-induced Ca release remain major limitations.

Objective:

Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote T-tubule development and mature excitation–contraction coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress).

Methods and Results:

hiPSC-CM were generated using a standard chemical differentiation method supplemented with T3 (triiodothyronine) and/or Dex (dexamethasone) during days 16 to 30 followed by single-cell culture for 5 days on Matrigel mattress. hiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, developed an extensive T-tubule network. Notably, Matrigel mattress was necessary for T-tubule formation. Compared with adult human ventricular cardiomyocytes, T-tubules in T3+Dex-treated hiPSC-CM were less organized and had more longitudinal elements. Confocal line scans demonstrated spatially and temporally uniform Ca release that is characteristic of excitation–contraction coupling in the heart ventricle. T3+Dex enhanced elementary Ca release measured by Ca sparks and promoted RyR2 (ryanodine receptor) structural organization. Simultaneous measurements of L-type Ca current and intracellular Ca release confirmed enhanced functional coupling between L-type Ca channels and RyR2 in T3+Dex-treated cells.

Conclusions:

Our results suggest a permissive role of combined thyroid and glucocorticoid hormones during the cardiac differentiation process, which when coupled with further maturation on Matrigel mattress, is sufficient for T-tubule development, enhanced Ca-induced Ca release, and more ventricular-like excitation–contraction coupling. This new hormone maturation method could advance the use of hiPSC-CM for disease modeling and cell-based therapy.
Meditation and Cardiovascular Risk Reduction
Authors: Levine Glenn N. , Lange Richard A. , Bairey‐Merz C. Noel , Davidson Richard J. , Jamerson Kenneth , Mehta Puja K. , Michos Erin D. , Norris Keith , Ray Indranill Basu , Saban Karen L. , Shah Tina , Stein Richard , Smith Sidney C. ,   the American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Hypertension
Published: September 2017

Despite numerous advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains a leading cause of morbidity and mortality. Novel and inexpensive interventions that can contribute to the primary and secondary prevention of cardiovascular disease are of interest. Numerous studies have reported on the benefits of meditation. Meditation instruction and practice is widely accessible and inexpensive and may thus be a potential attractive cost‐effective adjunct to more traditional medical therapies. Accordingly, this American Heart Association scientific statement systematically reviewed the data on the potential benefits of meditation on cardiovascular risk. Neurophysiological and neuroanatomical studies demonstrate that meditation can have long‐standing effects on the brain, which provide some biological plausibility for beneficial consequences on the physiological basal state and on cardiovascular risk. Studies of the effects of meditation on cardiovascular risk have included those investigating physiological response to stress, smoking cessation, blood pressure reduction, insulin resistance and metabolic syndrome, endothelial function, inducible myocardial ischemia, and primary and secondary prevention of cardiovascular disease. Overall, studies of meditation suggest a possible benefit on cardiovascular risk, although the overall quality and, in some cases, quantity of study data are modest. Given the low costs and low risks of this intervention, meditation may be considered as an adjunct to guideline‐directed cardiovascular risk reduction by those interested in this lifestyle modification, with the understanding that the benefits of such intervention remain to be better established. Further research on meditation and cardiovascular risk is warranted. Such studies, to the degree possible, should utilize randomized study design, be adequately powered to meet the primary study outcome, strive to achieve low dropout rates, include long‐term follow‐up, and be performed by those without inherent bias in outcome.
Comprehensive Metabolomic Profiling and Incident Cardiovascular Disease: A Systematic Review
Authors: Ruiz‐Canela Miguel , Hruby Adela , Clish Clary B. , Liang Liming , Martínez‐González Miguel A. , Hu Frank B.
Published: September 2017

Background

Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (
CVD
).

Methods and Results

We searched
MEDLINE
and
EMBASE
from inception to January 2016. Studies were eligible if they pertained to adult humans; followed an agnostic and/or comprehensive approach; used serum or plasma (not urine or other biospecimens); conducted metabolite profiling at baseline in the context of examining prospective disease; and included myocardial infarction, stroke, and/or
CVD
death in the
CVD
outcome definition. We identified 12 original articles (9 cohort and 3 nested case‐control studies); participant numbers ranged from 67 to 7256. Mass spectrometry was the predominant analytical method. The number and chemical diversity of metabolites were very heterogeneous, ranging from 31 to >10 000 features. Four studies used untargeted profiling. Different types of metabolites were associated with
CVD
risk: acylcarnitines, dicarboxylacylcarnitines, and several amino acids and lipid classes. Only tiny improvements in
CVD
prediction beyond traditional risk factors were observed using these metabolites (C index improvement ranged from 0.006 to 0.05).

Conclusions

There are a limited number of longitudinal studies assessing associations between comprehensive metabolomic profiles and
CVD
risk. Quantitatively synthesizing the literature is challenging because of the widely varying analytical tools and the diversity of methodological and statistical approaches. Although some results are promising, more research is needed, notably standardization of metabolomic techniques and statistical approaches. Replication and combinations of novel and holistic methodological approaches would move the field toward the realization of its promise.
Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation
Authors: Cha Myung-Jin , Choi Eue-Keun , Han Kyung-Do , Lee So-Ryoung , Lim Woo-Hyun , Oh Seil , Lip Gregory Y.H.
Published: October 2017

Background and Purpose—

There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients.

Methods—

Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA
2
DS
2
-VASc score ≥2) between 2014 and 2015.

Results—

NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant–naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH.

Conclusions—

In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.
Safety of Pregnancy After Cerebral Venous Thrombosis
Authors: Aguiar de Sousa Diana , Canhão Patrícia , Crassard Isabelle , Coutinho Jonathan , Arauz Antonio , Conforto Adriana , Béjot Yannick , Giroud Maurice , Ferro José M. , Pinho e Melo Teresa , Pereira Liliana , Costa Elisa , Rodrigues Miguel , Viana Baptista Miguel , Carvalho Marta , Lopes Gabriela , Correia Manuel , Pinto Ana Amélia , Coelho Paulo , Cunha Luís , Veiga Andreia , Silva Mário , Costa Maria Manuela , Nzwalo Hipólito , Ferreira Fátima , Zuurbier Yvonne , Dequatre-Ponchelle Nelly , Leys Didier , Bejot Yannick , Ruiz-Sandoval José Luis , Hacke Werner , Poli Sven , Gumbinger Christoph , Nolte Christian H. , Bogdahn Ulrich , Schlachetzki Felix , Gerriets Tibo , Stolz Erwin , Bastos Vanessa , Gagliardi Rubens , Diez-Tejedor Exuperio , Fuentes Blanca , Casado-Naranjo Ignacio , Martinelli Ida , Scoditti Umberto , de Veber Gabrielle , Lanthier Sylvain
Published: October 2017

Background and Purpose—

Pregnancy is associated with increased risk of venous thrombotic events, including cerebral venous thrombosis. We aimed to study the complications and outcome of subsequent pregnancies in women with previous cerebral venous thrombosis.

Methods—

Follow-up study of women with acute cerebral venous thrombosis at childbearing age included in a previously described cohort (International Study of Cerebral Vein and Dural Sinus Thrombosis). Patients were interviewed by local neurologists to assess rate of venous thrombotic events, pregnancy outcomes, and antithrombotic prophylaxis during subsequent pregnancies.

Results—

A total of 119 women were included, with a median follow-up of 14 years. Eighty-two new pregnancies occurred in 47 women. In 83% (68 of 82), some form of antithrombotic prophylaxis was given during at least 1 trimester of pregnancy or puerperium. Venous thrombotic events occurred in 3 pregnancies, including 1 recurrent cerebral venous thrombosis. Two of the 3 women were on prophylactic low-molecular-weight heparin at the time of the event. Outcomes of pregnancies were 51 full-term newborns, 9 preterm births, 2 stillbirths, and 20 abortions (14 spontaneous).

Conclusions—

In women with prior cerebral venous thrombosis, recurrent venous thrombotic events during subsequent pregnancies are infrequent.
icsid’s Neoliberal Approach to Environmental Regulation in Developing Countries
Authors: Hippolyte Antonius R.
Published: October 2017

With the intensification of their participation in the foreign investment regime, Latin American States are finding it difficult to implement measures beneficial to protecting their environments due to their obligations to third States. This governance deficit is further compounded by the regime’s neoliberal predisposition in favour of property protection, which has penetrated the system and implicated the system of investment treaty arbitration, the regime’s primary dispute settlement mechanism. The International Centre for Settlement of Investment Disputes (icsid) has also been implicated. This is seen in the momentous diversity in investor-State disputes resolved by various icsid tribunals, which concern attempts by Latin American States to protect their physical environments such as the protection of wildlife or other matters such as the regulation of hazardous waste landfills and ensuring that citizens have access to clean water. Tribunals have approached such disputes primarily from a commercial standpoint, ignoring non-market alternatives such as environmental considerations.
Size Matters: Another Reason Why the Atlantic Is Saltier than the Pacific
Authors: Jones C. S. , Cessi Paola
Published: October 2017

The surface salinity in the North Atlantic controls the position of the sinking branch of the meridional overturning circulation (MOC); the North Atlantic has higher salinity, so deep-water formation occurs there rather than in the North Pacific. Here, it is shown that in a 3D primitive equation model of two basins of different widths connected by a reentrant channel, there is a preference for sinking in the narrow basin even under zonally uniform surface forcing. This preference is linked to the details of the velocity and salinity fields in the “sinking” basin. The southward western boundary current associated with the wind-driven subpolar gyre has higher velocity in the wide basin than in the narrow basin. It overwhelms the northward western boundary current associated with the MOC for wide-basin sinking, so freshwater is brought from the far north of the domain southward and forms a pool on the western boundary in the wide basin. The fresh pool suppresses local convection and spreads eastward, leading to low salinities in the north of the wide basin for wide-basin sinking. This pool of freshwater is much less prominent in the narrow basin for narrow-basin sinking, where the northward MOC western boundary current overcomes the southward western boundary current associated with the wind-driven subpolar gyre, bringing salty water from lower latitudes northward and enabling deep-water mass formation.
Expressing Flood Likelihood: Return Period versus Probability
Authors: Grounds Margaret A. , LeClerc Jared E. , Joslyn Susan
Published: October 2017

The likelihood of floods and other potentially destructive natural phenomena is often expressed as a return period or recurrence interval, such as a 100-yr flood. However, the expression might give users the impression that the event will occur exactly once within the described period, obscuring the intended probabilistic meaning. If so, users may think a flood is less likely when one has just occurred or more likely when it has not, leading to a “flood is due” effect. This hypothesis was tested experimentally in two studies reported here. Participants were given either a return period or a probability expression and asked to rate flood likelihood and concern. Flood recency was also manipulated. The results from both studies support a flood is due effect when the return period expression is used. In the return period condition alone, participants rated floods as more likely and expressed greater concern when no flood had occurred recently. When no likelihood information was conveyed in the control condition, the opposite effect was observed. Participants rated flood likelihood as higher and expressed greater concern when a flood had occurred recently. Participants using the percent chance expression were least affected by flood recency. This adds to the growing body of research suggesting that nonexperts can benefit from probabilistic weather forecasts.
Eustachian Tube Dysfunction–Related Symptoms in Chronic Nasal Obstruction Caused by Inferior Turbinate Enlargement
Authors: Harju Teemu , Kivekäs Ilkka , Numminen Jura , Rautiainen Markus
Published: October 2017

Objective:

The aim of this study was to evaluate the relationship between chronic nasal obstruction caused by inferior turbinate enlargement and Eustachian tube dysfunction–related symptoms using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) as an assessment method.

Methods:

A total of 80 adults were enrolled. Group 1 comprised consecutive patients with enlarged inferior turbinates and group 2 comprised healthy controls. The ETDQ-7 scores and tympanometry results of both groups were analyzed and compared.

Results:

The median total scores of the ETDQ-7 in groups 1 and 2 were 1.9 (interquartile range, 1.4-2.8) and 1.1 (interquartile range, 1.0-1.7), respectively ( P < .001). There was no significant difference in the abnormal tympanometry results between the groups. There was no significant difference in the ETDQ-7 total score between the patients with allergic sensitization and other patients in group 1.

Conclusions:

Patients with inferior turbinate enlargement have more symptoms related to Eustachian tube dysfunction than healthy controls. Most patients with Eustachian tube dysfunction had normal tympanometry and normal otoscopy, which indicates a baro-challenge-induced Eustachian tube dysfunction. Whether the patient has allergic sensitization or not does not seem to cause a difference in symptoms related to Eustachian tube dysfunction.
Defining Service and Education in Pediatrics
Authors: Boyer Debra , Gagne Josh , Kesselheim Jennifer C.
Published: October 2017

Program directors (PDs) and trainees are often queried regarding the balance of service and education during pediatric residency training. We aimed to use qualitative methods to learn how pediatric residents and PDs define service and education and to identify activities that exemplify these concepts. Focus groups of pediatric residents and PDs were performed and the data qualitatively analyzed. Thematic analysis revealed 4 themes from focus group data: (1) misalignment of the perceived definition of service; (2) agreement about the definition of education; (3) overlapping perceptions of the value of service to training; and (4) additional suggestions for improved integration of education and service. Pediatric residents hold positive definitions of service and believe that service adds value to their education. Importantly, the discovery of heterogeneous definitions of service between pediatric residents and PDs warrants further investigation and may have ramifications for Accreditation Council for Graduate Medical Education and those responsible for residency curricula.