bluuebunny/crossref_metadata_2025 huggingface dataset:
Dark matter freeze-out during matter domination
Authors: Hamdan Saleh , Unwin James
Published: September 2018

We highlight the general scenario of dark matter freeze-out while the energy density of the universe is dominated by a decoupled non-relativistic species. Decoupling during matter domination changes the freeze-out dynamics, since the Hubble rate is parametrically different for matter and radiation domination. Furthermore, for successful Big Bang Nucleosynthesis the state dominating the early universe energy density must decay, this dilutes (or repopulates) the dark matter. As a result, the masses and couplings required to reproduce the observed dark matter relic density can differ significantly from radiation-dominated freeze-out.
Armored Target Detection in Battlefield Environment Based on Top-Down Aggregation Network and Hierarchical Scale Optimization
Authors: Sun Haoze , Chang Tianqing , Zhang Lei , Yang Guozhen , Han Bin , Chen Junwei
Published: September 2018

Armored equipment plays a crucial role in the ground battlefield. The fast and accurate detection of enemy armored targets is significant to take the initiative in the battlefield. Comparing to general object detection and vehicle detection, armored target detection in battlefield environment is more challenging due to the long distance of observation and the complicated environment. In this paper, an accurate and robust automatic detection method is proposed to detect armored targets in battlefield environment. Firstly, inspired by Feature Pyramid Network (FPN), we propose a top-down aggregation (TDA) network which enhances shallow feature maps by aggregating semantic information from deeper layers. Then, using the proposed TDA network in a basic Faster R-CNN framework, we explore the further optimization of the approach for armored target detection: for the Region of Interest (RoI) Proposal Network (RPN), we propose a multi-branch RPNs framework to generate proposals that match the scale of armored targets and the specific receptive field of each aggregated layer and design hierarchical loss for the multi-branch RPNs; for RoI Classifier Network (RCN), we apply RoI pooling on the single finest scale feature map and construct a light and fast detection network. To evaluate our method, comparable experiments with state-of-art detection methods were conducted on a challenging dataset of images with armored targets. The experimental results demonstrate the effectiveness of the proposed method in terms of detection accuracy and recall rate.
Gesture Recognition Based on Kinect v2 and Leap Motion Data Fusion
Authors: Li Bo , Zhang Chao , Han Cheng , Bai Baoxing
Published: September 2018

This study proposed a method for multiple motion-sensitive devices (i.e. one Kinect v2 and two Leap Motions) to integrate gesture data in Unity. Other depth cameras could replace the Kinect. The general steps in integrating gesture data for motion-sensitive devices were introduced as follows. (1) A method was proposed to recognize the fingertip from depth images for the Kinect v2. (2) Coordinates observed by three motion-sensitive devices were aligned in space in three steps. First, preliminary coordinate conversion parameters were obtained through joint calibration of the three devices. Second, two types of devices were approached to the observed value of the standard Leap Motion by the least squares method twice (i.e. one Kinect and one Leap Motion on the first round, then two Leap Motions on the second round). (3) Data of the three devices were aligned with time by using Unity while applying the data plan. On this basis, a human hand interacted with a virtual object in Unity. Experimental results demonstrated that the proposed method had a small recognition error of hand joints and realized the natural interaction between the human hand and virtual objects.
A Robust Eigenanalysis Interference Canceler Using Sensitivity-Based Number of Sources Estimation
Authors: Qian Bingfeng , Sun Yize
Published: September 2018

When the estimation of the number of sources is inaccurate and the expected signal is mixed in the training data, the conventional eigenanalysis interference canceler (EC) will result in the expected signal cancelation, which leads the performance of adaptive beamforming to be degraded significantly. In this paper, a robust eigenanalysis interference canceler (REC) algorithm is proposed to resolve this problem by using the minimum sensitivity-based number of sources estimation. In the proposed method, the number of sources is first pre-estimated by effectively using the minimum sensitivity function. Then, based on the eigenvalue decomposition of the array covariance matrix, the expected signal in the training data is determined and eliminated, so that the corresponding impact of the adaptive weight calculation can be avoided. Finally, the adaptive weight vector is obtained by orthogonally projecting the quiescent weight vector into the interference subspace. Simulation results show that the performance of the output signal-to-interference-plus-noise ratio (SINR) of the proposed algorithm has improved significantly when compared with the conventional adaptive beamforming methods.
The redshift-dependence of radial acceleration: Modified gravity versus particle dark matter
Authors: Hossenfelder Sabine , Mistele Tobias
Published: September 2018

Modified Newtonian Dynamics has one free parameter and requires an interpolation function to recover the normal Newtonian limit. We here show that this interpolation function is unnecessary in a recently proposed covariant completion of Erik Verlinde’s emergent gravity, and that Verlinde’s approach moreover fixes the function’s one free parameter. The so-derived correlation between the observed acceleration (inferred from rotation curves) and the gravitational acceleration due to merely the baryonic matter fits well with data. We then argue that the redshift-dependence of galactic rotation curves could offer a way to tell apart different versions of modified gravity from particle dark matter.
Gravity in a warped 6D world with an extra 2D sphere
Authors: Kokado Akira , Saito Takesi
Published: September 2018

Corrections to Newton’s inverse law have been so far considered, but not clear in warped higher dimensional worlds, because of complexity of the Einstein equation. Here, we give a model of a warped 6D world with an extra 2D sphere. We take a general energy–momentum tensor, which does not depend on a special choice of bulk matter fields. The 6D Einstein equation reduces to the spheroidal differential equation, which can be easily solved. The gravitational potential in our 4D universe is calculated to be composed of infinite series of massive Yukawa potentials coming from the KK mode, together with Newton’s inverse law. The series of Yukawa type potentials converges well to behave as [Formula: see text] near [Formula: see text].
A SUBORDINATED CIR INTENSITY MODEL WITH APPLICATION TO WRONG-WAY RISK CVA
Authors: MBAYE CHEIKH , VRINS FRÉDÉRIC
Published: September 2018

Credit valuation adjustment (CVA) pricing models need to be both flexible and tractable. The survival probability has to be known in closed form (for calibration purposes), the model should be able to fit any valid credit default swap (CDS) curve, should lead to large volatilities (in line with CDS options) and finally should be able to feature significant wrong-way risk (WWR) impact. The Cox–Ingersoll–Ross (CIR) model combined with independent positive jumps and deterministic shift (JCIR[Formula: see text]) is a very good candidate : the variance (and thus covariance with exposure, i.e. WWR) can be increased with the jumps, whereas the calibration constraint is achieved via the shift. In practice however, there is a strong limit on the model parameters that can be chosen, and thus on the resulting WWR impact. This is because only non-negative shifts are allowed for consistency reasons, whereas the upwards jumps of the JCIR[Formula: see text] need to be compensated by a downward shift. To limit this problem, we consider the two-side jump model recently introduced by Mendoza-Arriaga and Linetsky, built by time-changing CIR intensities. In a multivariate setup like CVA, time-changing the intensity partly kills the potential correlation with the exposure process and destroys WWR impact. Moreover, it can introduce a forward looking effect that can lead to arbitrage opportunities. In this paper, we use the time-changed CIR process in a way that the above issues are avoided. We show that the resulting process allows to introduce a large WWR effect compared to the JCIR[Formula: see text] model. The computation cost of the resulting Monte Carlo framework is reduced by using an adaptive control variate procedure.
Braided Hopf algebras from twisting
Authors: Bochniak Arkadiusz , Sitarz Andrzej
Published: September 2018

We show that a class of braided Hopf algebras, which includes the braided [Formula: see text] of [P. Kasprzak, R. Meyer, S. Roy and S. L. Woronowicz, Braided quantum [Formula: see text] groups, J. Noncommut. Geom. 10 (2016) 1161–1125], is obtained by twisting. We show further examples and demonstrate that twisting of bicovariant differential calculi gives braided bicovariant differential calculi.
ABOUT RENEGADES AND OUTGROUP HATERS: MODELING THE LINK BETWEEN SOCIAL INFLUENCE AND INTERGROUP ATTITUDES
Authors: FLACHE ANDREAS
Published: September 2018

Polarization between groups is a major topic of contemporary societal debate and research. Formal models of opinion dynamics try to explain how intergroup polarization arises from simple first principles of social interaction. In existing models, intergroup attitudes affect social influence in the form of homophily or xenophobia, fixed tendencies of individuals to be more open to influence from ingroup members or distance themselves from attitudes of outgroup members. These models generate polarization between groups, but they neglect a central insight from empirical research. Intergroup attitudes are themselves subject to social influence in interactions with both in- and outgroup members. A model is proposed in which the attitude which is subject to social influence is also an intergroup attitude. It affects in turn the influence process itself. Furthermore, it is shown how this changes model predictions about process and conditions of polarization between groups. More complex patterns of intergroup relations emerge than in a model with fixed xenophobia. Especially, a renegade minority (‘outgroup lovers’) is found to have a key role in avoiding mutually negative intergroup relations and even elicit reversed polarization, resulting in a majority of individuals developing a negative attitude towards their ingroup and a positive one for the outgroup.
A novel SNP-set analytical method without distinguishing common variants or rare variants in genome-wide association study
Authors: Wang Xinzeng , Wang Shudong , Meng Xinzhu
Published: September 2018

Single nucleotide polymorphism (SNP)-set analysis in genome-wide association studies (GWASs) has become a hot topic. Most existing SNP-set analystic methods are designed and work well according to the different natures of common or rare variants and associated diseases. But the information that the disease associated variants are common or rare cannot be gained in advance. Therefore, in this research, we proposed a new and powerful weighted function method without distinguishing common or rare variants to select tagging SNP-set. We applied our selection method to sequence kernel association test (SKAT) and compared the power with some existing methods. The simulation results showed that our method has higher power not only than SKAT in un-weighted case, but also than SKAT in other weighted functions. Moreover, the power is improved significantly when the minor allele frequency (MAF) of causal SNP is relatively small.
Urban Vulnerability and Adaptability to Climate Change: A Case Study of Cities in the Yangtze River Delta
Authors: XIE Xinlu , ZHENG Yan , PAN Jiahua , ZHOU Hongjian
Published: September 2018

The cities of the Yangtze River Delta are densely populated with large amounts of wealth, for which reason they are faced with greater disaster risks brought by climate change. As a major research tool on climate change policies, vulnerability assessment provides reference for adaptive management. Based on literature review and case study, the paper first constructs the overall vulnerability assessment model for cities of the Yangtze River Delta by utilizing the indices of sensitivity and adaptability. Then, it assesses 16 typical cities of this region through factor analysis, an objective evaluation method, analyzes the driving factors of climate vulnerability in each city and conducts group comparisons according to their sensitivity and adaptability. Finally, it points out the importance of cities’ adaptability to climate change under multiple pressures of climate change, population growth and urbanization in the future, and gives some suggestions, such as strengthening risk assessment on climate change, including climate-proofing measures in urban development planning, protecting climatically vulnerable groups in cities, enhancing comprehensive capacities for disaster management in cities and encouraging the R&D and innovation on adaptation technologies.
Antibiotic-Induced Genetic Variation: How It Arises and How It Can Be Prevented
Authors: Blázquez Jesús , Rodríguez-Beltrán Jerónimo , Matic Ivan
Published: September 2018

By targeting essential cellular processes, antibiotics provoke metabolic perturbations and induce stress responses and genetic variation in bacteria. Here we review current knowledge of the mechanisms by which these molecules generate genetic instability. They include production of reactive oxygen species, as well as induction of the stress response regulons, which lead to enhancement of mutation and recombination rates and modulation of horizontal gene transfer. All these phenomena influence the evolution and spread of antibiotic resistance. The use of strategies to stop or decrease the generation of resistant variants is also discussed.
Transcriptional Responses to ppGpp and DksA
Authors: Gourse Richard L. , Chen Albert Y. , Gopalkrishnan Saumya , Sanchez-Vazquez Patricia , Myers Angela , Ross Wilma
Published: September 2018

The stringent response to nutrient deprivation is a stress response found throughout the bacterial domain of life. Although first described in proteobacteria for matching ribosome synthesis to the cell's translation status and for preventing formation of defective ribosomal particles, the response is actually much broader, regulating many hundreds of genes—some positively, some negatively. Utilization of the signaling molecules ppGpp and pppGpp for this purpose is ubiquitous in bacterial evolution, although the mechanisms employed vary. In proteobacteria, the signaling molecules typically bind to two sites on RNA polymerase, one at the interface of the β′ and ω subunits and one at the interface of the β′ secondary channel and the transcription factor DksA. The β′ secondary channel is targeted by other transcription regulators as well. Although studies on the transcriptional outputs of the stringent response date back at least 50 years, the mechanisms responsible are only now coming into focus.
The Novel Bromodomain and Extraterminal Domain Inhibitor INCB054329 Induces Vulnerabilities in Myeloma Cells That Inform Rational Combination Strategies
Authors: Stubbs Matthew C. , Burn Timothy C. , Sparks Richard , Maduskuie Thomas , Diamond Sharon , Rupar Mark , Wen Xiaoming , Volgina Alla , Zolotarjova Nina , Waeltz Paul , Favata Margaret , Jalluri Ravi , Liu Huiqing , Liu Xuesong Mike , Li Jun , Collins Robert , Falahatpisheh Nikoo , Polam Padmaja , DiMatteo Darlise , Feldman Patricia , Dostalik Valerie , Thekkat Pramod , Gardiner Christine , He Xin , Li Yanlong , Covington Maryanne , Wynn Richard , Ruggeri Bruce , Yeleswaram Swamy , Xue Chu-Biao , Yao Wenqing , Combs Andrew P. , Huber Reid , Hollis Gregory , Scherle Peggy , Liu Phillip C.C.
Published: September 2018

Purpose:

Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes and pathways; BET inhibitors have demonstrated activity in diverse models of hematologic and solid tumors. We report the preclinical characterization of INCB054329, a structurally distinct BET inhibitor that has been investigated in phase I clinical trials.

Experimental Design:

We used multiple myeloma models to investigate vulnerabilities created by INCB054329 treatment that could inform rational combinations.

Results:

In addition to c-MYC, INCB054329 decreased expression of oncogenes FGFR3 and NSD2/MMSET/WHSC1, which are deregulated in t(4;14)-rearranged cell lines. The profound suppression of FGFR3 sensitized the t(4;14)-positive cell line OPM-2 to combined treatment with a fibroblast growth factor receptor inhibitor in vivo. In addition, we show that BET inhibition across multiple myeloma cell lines resulted in suppressed interleukin (IL)-6 Janus kinase–signal transducers and activators of transcription (JAK–STAT) signaling. INCB054329 displaced binding of BRD4 to the promoter of IL6 receptor (IL6R) leading to reduced levels of IL6R and diminished signaling through STAT3. Combination with JAK inhibitors (ruxolitinib or itacitinib) further reduced JAK–STAT signaling and synergized to inhibit myeloma cell growth in vitro and in vivo. This combination potentiated tumor growth inhibition in vivo, even in the MM1.S model of myeloma that is not intrinsically sensitive to JAK inhibition alone.

Conclusions:

Preclinical data reveal insights into vulnerabilities created in myeloma cells by BET protein inhibition and potential strategies that can be leveraged in clinical studies to enhance the activity of INCB054329.
Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non–Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers
Authors: Peters Solange , Stahel Rolf , Bubendorf Lukas , Bonomi Philip , Villegas Augusto , Kowalski Dariusz M. , Baik Christina S. , Isla Dolores , Carpeno Javier De Castro , Garrido Pilar , Rittmeyer Achim , Tiseo Marcello , Meyenberg Christoph , de Haas Sanne , Lam Lisa H. , Lu Michael W. , Stinchcombe Thomas E.
Published: September 2018

Purpose:

HER2-targeted therapy is not standard of care for HER2-positive non–small cell lung cancer (NSCLC). This phase II study investigated efficacy and safety of the HER2-targeted antibody–drug conjugate trastuzumab emtansine (T-DM1) in patients with previously treated advanced HER2-overexpressing NSCLC.

Patients and Methods:

Eligible patients had HER2-overexpressing NSCLC (centrally tested IHC) and received previous platinum-based chemotherapy and targeted therapy in the case of EGFR mutation or ALK gene rearrangement. Patients were divided into cohorts based on HER2 IHC (2+, 3+). All patients received T-DM1 3.6 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-determined overall response rate (ORR) using RECIST v1.1.

Results:

Forty-nine patients received T-DM1 (29 IHC 2+, 20 IHC 3+). No treatment responses were observed in the IHC 2+ cohort. Four partial responses were observed in the IHC 3+ cohort (ORR, 20%; 95% confidence interval, 5.7%–43.7%). Clinical benefit rates were 7% and 30% in the IHC 2+ and 3+ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free survival and overall survival were similar between cohorts. Three of 4 responders had HER2 gene amplification. No new safety signals were observed.

Conclusions:

T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3+) advanced NSCLC. Additional investigation into HER2 pathway alterations is needed to refine the target population for T-DM1 in NSCLC; however, HER2 IHC as a single parameter was an insufficient predictive biomarker.
Effect of Chemotherapy on Removal of Indwelling Pleural Catheters in Breast Cancer Patients with Malignant Pleural Effusions
Authors: Mitchell Michael A. , Burkett Andrew , Li Pen , Zhang Tinghua , Amjadi Kayvan
Published: September 2018

Background: Indwelling pleural catheters (IPC) are commonly used in the management of malignant pleural effusions (MPE). The effect of systemic chemotherapy on IPC removal has not been reported previously. Objectives: The purpose of this study is to identify the effect of chemotherapy on the removal of IPCs in breast cancer patients with MPEs. Methods: In this retrospective cohort study at an academic tertiary-care center, patients with breast cancer and MPE who received an IPC between 2006 and 2016 were identified from a prospectively collected database. Patient chemotherapy data were obtained, as well estrogen receptor (ER) and human epidermal growth factor receptor-2 status at the time of diagnosis. Patients receiving chemotherapy while their IPC was in situ were compared to those who did not. The primary outcome was time to IPC removal. All patients were followed until IPC removal or death. Results: A total of 207 patients and 216 IPCs were included in the analysis. There was no difference in time to IPC removal between the chemotherapy and no-chemotherapy groups (HR 0.73, 95% CI 0.50–1.07, p = 0.10) or rate of IPC removal (OR 1.16, 95% CI 0.68–1.98, p = 0.59). The risk of IPC infection was not different between patients who received chemotherapy and those who did not (RR 0.57, 95% CI 0.06–5.39, p = 0.48). Conclusions: Treatment with chemotherapy with an IPC in situ was not associated with a reduced time to IPC removal in our breast cancer population. IPC insertion in patients receiving chemotherapy is safe and not associated with an increased risk of infection.
Open Spina Bifida: Why Not Fetal Surgery?
Authors: Mazzone Luca , Moehrlen Ueli , Casanova Barbara , Ryf Samira , Ochsenbein-Kölble Nicole , Zimmermann Roland , Kraehenmann Franziska , Meuli Martin
Published: September 2018

Objective: The majority of patients counseled for prenatal open spina bifida repair (SBR) do not undergo fetal surgery. The aim of this study was to analyze the reasons for this phenomenon. Materials and Methods: The data of the first 160 patients seeking counseling or referred to the Zurich Center for Fetal Diagnosis and Therapy for prenatal SBR between December 2010 and March 2017 were retrospectively analyzed. Results: A total of 104 (65%) patients did not undergo prenatal SBR. Of this subgroup, 52% met the exclusion criteria, 35% decided to terminate pregnancy, 4% chose to continue pregnancy without fetal intervention, and 3% sought care in other European centers. In 6%, data about the ensuing course of pregnancy were not recorded. The main exclusion criteria were delayed presentation (30%), absence of hindbrain herniation (28%), and concomitant spinal anomalies (17%). Conclusion: The high percentage of patients not qualifying for prenatal SBR underscores the necessity of a standard evaluation of every single patient at a qualified referral center. To allow a higher proportion of women carrying a fetus with open spina bifida to be timely and correctly informed about a potential fetal intervention, much more effort is mandatory to spawn correct, objective, and understandable information among all groups of people potentially exposed to this topic.
Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study
Authors: Tsolaki Anthoula C. , Gatzima Olympia , Daniilidou Makrina , Lazarou Eutuxia , Bamidis Panagiotis D. , Verykouki Eleni , Iakovidou-Kritsi Zafiroura , Tsolaki Magda
Published: September 2018

Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.
Prevalence of Phototherapy in the Age of Biologics
Authors: Calzavara-Pinton Piergiacomo , Zanca  Arianna , Arisi Mariachiara , Rossi Maria Teresa  , Zane Cristina , Venturini Marina , Ortel Bernhard
Published: September 2018

Background: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. Objectives: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. Methods: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. Results: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. Conclusions: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.
Evaluation of Hearing and Balance Functions of Patients with Sickle Cell Anemia
Authors: Sarac Elif Tugba , Boke Bilgehan , Okuyucu Semsettin
Published: September 2018

Introduction: Sickle cell anemia is a disease characterized by a wide vaso-occlusive incident from micro-vascular incident to muscularactivity. The cochlear function can also get affected by this vaso-occlusion. Objective: It is aimed at determining what kind of effects sickle cell anemia has on hearing and balance system. Methods: This study has been conducted on 46 patients with sickle cell anemia and 45 healthy individuals. For all participants, their pure tone hearing thresholds and videonystagmography (VNG) findings have been determined in 17 frequencies between 125–16.000 Hz. Results: All hearing thresholds between 125 and 16,000 Hz, pure tone averages of patients with sickle cell anemia have been found statistically significant to be higher than the corresponding values in the control group(p < 0.05). The normal hearing rate of patients with sickle cell anemia has been determined to be 71.1% conductive hearing loss (CHL) to be 4.4%, sensorineural hearing loss (SNHL) to be 22.2%, and mixed type hearing loss to be 2.2% in right ear; the normal hearing rate has been determined to be 71.1%, CHL to be 2.2%, SNHL to be 22.2%, and mixed type hearing loss to be 4.4% in left ear. Statistically significant difference has not been found between head shake, spontaneous nystagmus, optokinetic, tracking test batteries, static and dynamic positional tests used in VNG, saccade accuracy and saccade peak velocity, which are saccadic test findings of 2 groups. However, saccadic latency, which is a saccadic test finding, has been determined to be longer in patients with sickle cell anemia in comparison to the control group. Conclusion: While sickle cell anemia causes hearing deficits, it does not have any effect on the central or peripheral vestibular system.
Práticas de literacia familiar: uma estratégia de educação para a saúde para o desenvolvimento integral da criança
Authors: Resende Ana , Figueiredo Maria Henriqueta
Published: September 2018

Introdução: A literacia emergente ou precoce é a primeira fase de construção e desenvolvimento da literacia e deve ser vista como um processo de desenvolvimento contínuo que começa nos primeiros anos de vida e se desenvolve em contextos reais de cada pessoa. Método: Procedeu-se a uma revisão integrativa da literatura, cujo objetivo foi sistematizar o conhecimento sobre a nova abordagem da construção e apreensão da literacia. Resultados e discussão: Foram consideradas três principais áreas de apreciação: estratégias/atividades promotoras de literacia familiar, leitura partilhada de histórias (enquanto prática de literacia familiar mais conducente ao desenvolvimento da literacia emergente) e repercussões positivas da promoção precoce desta prática no desenvolvimento integral da criança. Reconhece-se, atualmente, uma nova visão da família em geral, e dos pais/figuras parentais em particular, além da própria criança, frente ao processo de literacia em si. Estes passaram a ser consi­derados como elementos-chave e sua participação nesse processo deve ser mobilizada o mais cedo possível em relação aos Cuidados de Saúde Primários.
A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation
Authors: Graves Nicholas , Venu Vivek P. , Yipp Bryan G. , Petri Björn , Hirota Simon , Gilleard John , McKay Derek M. , Lopes Fernando
Published: September 2018

It has emerged that neutrophils can play important roles in the host response following infection with helminth parasites. Mice infected with the tapeworm, Hymenolepis diminuta, are protected from some inflammatory conditions, accompanied by reduced neutrophil tissue infiltration. Thus, the ability of a phosphate-buffered saline-soluble extract of the worm (H. diminuta extract [HdE]) was tested for (1) its ability to activate murine neutrophils (Ca2+ mobilization, reactive oxygen species (ROS) and cytokine production); and (2) affect neutrophil chemotaxis in vitro to the penta-peptide, WKYMVm, the chemokine, KC, and leukotriene B4. HdE was not cytotoxic to neutrophils, elicited a Ca2+ response and ROS, but not, cytokine (KC, interleukin-10, tumour necrosis factor-α) generation. HdE is not a chemotactic stimulus for murine neutrophils. However, a heat- and trypsin-sensitive, acid-insensitive proteoglycan (sensitive to sodium metaperiodate) in the HdE significantly reduced neutrophil chemotaxis towards WKYMVm or KC, but not LTB4. The latter suggested that the HdE interfered with p38 mitogen-activated protein kinase signalling, which is important in WKYMVm chemotaxis. Corroborating this, immunoblotting revealed reduced phosphorylated p38, and the downstream signal heat-shock protein-27, in protein extracts from HdE + WkYMVm treated cells compared to those exposed to the penta-peptide only. We speculate that HdE can be used to modify the outcome of neutrophilic disease and that purification of the bioactive proteoglycan(s) from the extract could be used as a template to design immunomodulatory drugs targeting neutrophils.
Bilirubin Production Is Increased in Newborn Mice Exposed to Isoflurane
Authors: Iwatani Sota , Burgess Jordan , Kalish Flora , Wong Ronald J. , Stevenson David K.
Published: September 2018

Background: Increased bilirubin production due to hemolysis can lead to severe neonatal hyperbilirubinemia and, if left untreated, to bilirubin neurotoxicity. Post-cardiac surgery newborns have been shown to be at an increased risk for developing hyperbilirubinemia and also hemolysis. Isoflurane (ISO), a volatile anesthetic agent routinely used in newborn surgery, has been reported to upregulate heme oxygenase 1 (HO-1) expression. HO is the rate-limiting enzyme in the bilirubin production pathway. Objective: Here, we evaluated whether ISO exposure induces HO-1 and further increases bilirubin production in a hemolytic newborn mouse model. Methods: Three-day-old newborn mice were exposed to 2% ISO for 18 min or air. Liver HO activity and HO-1 protein were measured after exposure to ISO. Next, we evaluated the effect of ISO exposure on bilirubin production as indexed by the total body excretion rate of carbon monoxide following heme loading. Results: ISO significantly increased liver HO activity 120% and 116% at 24 and 48 h, respectively, after exposure. HO-1 protein levels also similarly increased after ISO exposure, but the increases were not statistically significant compared with controls. After heme loading, ISO-exposed pups had significantly higher bilirubin production rates (1.24-fold), and also peaked earlier, than age-matched nonexposed pups. Conclusions: ISO exposure can induce HO-1 expression in the liver and may explain the development of severe hyperbilirubinemia in postsurgical infants, especially in those undergoing hemolysis.
Inner Ear Damage by Firecracker Trauma
Authors: Liao Yu-Hao , Young Yi-Ho
Published: September 2018

Firecrackers are still popular among the general public of various populations worldwide. This study investigated inner ear damage in patients with firecracker trauma and analyzed noise levels in 6 kinds of commercially available firecrackers. During the past 20 years, we have experienced 30 patients with firecracker trauma. An inner ear test battery comprising audiometry, cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) tests and a caloric test was performed. The real-time noise levels were measured outdoors at a distance of 2, 4 and 6 m away from a lighting firecracker to mimic a noise event. Mean hearing levels at high frequencies (4,000 and 8,000 Hz) were significantly higher than those at the low and middle frequencies, indicating that firecrackers mostly cause high-tone hearing loss. For the vestibular damage, abnormality percentages were higher in the results of cVEMP (80%) and oVEMP (60%) tests, but not in the caloric test (8%). In conclusion, most firecrackers exhibited noise levels > 110 dB SPL even at a distance of 6 m. This blast injury simultaneously damaged the cochlea, saccule and utricle, but spared the semicircular canals, indicating that blast exposure potentiates the adverse effect of noise exposure on both cochlear and vestibular partitions.
Are mTOR and Endoplasmic Reticulum Stress Pathway Genes Associated with Oral and Bone Diseases?
Authors: Bezamat Mariana , Deeley Kathleen , Khaliq Shahryar , Letra Ariadne , Scariot Rafaela , Silva Renato M. , Weber Megan L. , Bussaneli Diego G. , Trevilatto Paula C. , Almarza Alejandro J. , Ouyang Hongjiao , Vieira Alexandre R.
Published: September 2018

The purpose of this cohort study was to identify associations between combined oral and bone disease phenotypes and genes present in cell regulatory pathways. The studied pathways play important roles in cellular growth, proliferation, differentiation, and homeostasis. DNA samples extracted from whole saliva of 3,912 individuals were genotyped and these data analyzed according to dental caries experience, periapical lesions, periodontitis, osteoporosis, or temporomandibular joint discomfort. Samples were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Twenty-seven polymorphisms in eight genes related to mTOR or endoplasmic reticulum stress pathways were selected for genotyping. Allele frequencies and Hardy-Weinberg equilibrium were calculated. Analyses were performed comparing genotypes between affected and unaffected individuals for each phenotype, as well as for the associated phenotypes combined. For all analyses, we used the software PLINK with an alpha of 0.002. Borderline associations with multiple variants of several genes were found, suggesting that both pathways may be involved in the susceptibility to multiple conditions affecting the oral cavity and bones. When combining patients that had concomitant dental caries, periodontitis, and periapical pathology, several markers in RHEB showed statistically significant association. Multiple conditions affecting bone and teeth (i.e., dental caries, periodontitis, periapical lesion formation, and osteoporosis) appear to share similar underlying genetic etiological factors, which allow us to hypothesize that instead of individually, they should be studied in conjunction in human populations.
Heart Rate Variability During Early Mobilization in Patients with Acute Ischemic Stroke
Authors: Nozoe Masafumi , Yamamoto Miho , Kobayashi Miki , Kanai Masashi , Kubo Hiroki , Shimada Shinichi , Mase Kyoshi
Published: September 2018

Autonomic dysfunction is one of the predictors of poor outcome in patients with acute ischemic stroke. We compared the heart rate variability (HRV) during early mobilization in patients with or without neurological deterioration (ND). We enrolled 7 acute ischemic patients with ND and 14 without ND and measured their HRV in the rest and mobilization by electrocardiography. There was a significant difference in sympathetic nervous activity during mobilization between the 2 groups. However, no significant differences in blood pressure, heart rate, and parasympathetic nerve activity were observed. In patients with acute ischemic stroke, it is likely that the increase in sympathetic nervous activity during mobilization is associated with ND.
Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury
Authors: Cao Mercedes , Leite Bruna N. , Ferreiro Tamara , Calvo María , Fernández Constantino , Alonso Ángel , Rodriguez Alejandro , Salvador Pilar , Seijo Rocío , Pita Salvador , Arjona Emilia , Rodríguez de Córdoba Santiago , Valdés Cañedo Francisco
Published: September 2018

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.
Safety of Carbon Dioxide Insufflation during Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma
Authors: Takada Jun , Araki Hiroshi , Mizutani Taku , Ozawa Noritaka , Sugiyama Tomohiko , Kubota Masaya , Ibuka Takashi , Shimizu Masahito
Published: September 2018

Background: Pulmonary dysfunction often accompanies esophageal squamous cell carcinoma (SCC). Aims: This study examined the use of carbon dioxide (CO2) insufflation and its safety during esophageal endoscopic submucosal dissection (ESD) while under conscious sedation. Methods: ESD using CO2 insufflation (1.4 L/min) was performed in 102 consecutive esophageal SCC patients. Patients with a forced expiratory volume of 1.0 s/forced vital capacity (FEV1.0%) < 70% or a vital capacity < 80% were defined as having pulmonary dysfunction. Transcutaneous partial pressure of CO2 (PtcCO2) was recorded before, during, and after ESD. Results: A history of smoking was found in 90 patients (88%), while 43 patients (42%) had pulmonary dysfunction. No significant differences were found between the pulmonary dysfunction and normal groups for the baseline PtcCO2 before ESD, peak PtcCO2 during ESD, and median PtcCO2 after ESD. There was a significant correlation between the PtcCO2 elevation from baseline and the ESD procedure time (r = 0.32, p < 0.01), with the correlation for the pulmonary dysfunction group much stronger (r = 0.39, p < 0.05) than that for the normal group (r = 0.30, p < 0.01). Neither of the groups exhibited any differences for either the complication incidence or the hospital stay. Conclusions: Although the use of CO2 insufflation during esophageal ESD under conscious sedation is safe with regard to the risk of complications, longer procedure times can potentially induce CO2 retention in patients with obstructive lung disease. Thus, it is necessary to both shorten the procedure times and perform CO2 monitoring.
Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice
Authors: Sugimoto Ken , Ikeya Kentaro , Kato Masaichi , Matsuura Ai , Watanabe Fumitoshi , Takano Ryosuke , Tamura Satoshi , Tani Shinya , Osawa Satoshi , Hanai Hiroyuki
Published: September 2018

Background: Although evidence for the short- to medium-term efficacy of adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited number of reports on the long-term efficacy of adalimumab. This study was to understand baseline demographic features, which potentially could be risk factors for relapse or colectomy following induction of remission by adalimumab in UC patients. Additionally, factors affecting long-term outcomes were to be identified. Methods: Twenty-one patients with UC who had been treated with adalimumab were reviewed retrospectively. Comparative analyses were undertaken by factoring steroid withdrawal versus non-withdrawal, long-term remission versus relapse following remission, and requiring surgical intervention for UC versus surgery-free. Results: Adalimumab treatment was associated with steroid tapering in steroid-dependent cases in the long term. Of the 14 patients in whom clinical remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was 43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for surgery included intolerance to salicylates (p = 0.005) and past treatment with tacrolimus (p = 0.023). Conclusions: Adalimumab treatment was associated with long-term efficacy in patients with mild UC – patients achieved a high cumulative nonoperative survival rate over a long period of time, beyond 6 years.
Medical Procedure-Related Transient Global Amnesia
Authors: Jeong Moonyoung , Kim Won Sik , Kim Ah-ran , Park Jeong Jin , Choi Dong-Hee , Kim Hahn Young
Published: September 2018

Background: Transient global amnesia (TGA) is an interesting clinical syndrome characterized by sudden memory loss for recent events and an inability to retain new memories usually lasting several hours and recovering spontaneously. We conducted a literature search of medical procedure-related TGA and its predisposing conditions. Methods: We performed PubMed searches using the keyword “transient global amnesia” combined with “procedure,” “test,” “therapy,” or various other individual medical procedures. In addition, we described 2 cases of gastroscopy-related TGA. Results: Eighty-nine patients with medical procedure-related TGA in 49 articles were summarized. The most common procedure was cerebral angiography (n = 45), followed by coronary angiography (n = 10) and general anesthesia (n = 9). After categorization, neurological procedures were most common (n = 46, 51.7%), followed by cardiac (n = 17, 19.1%), anesthetic (n = 11, 12.4%), gastrointestinal (n = 4, 4.5%), and pulmonary (n = 2, 2.2%) procedures. Conclusions: Diverse cases of medical procedure-related TGA have been reported in the literature. Valsalva-associated activities, emotional stress with anxiety, and acute pain were predisposing conditions. An understanding of medical procedure-related TGA may be important for clinicians who perform such medical procedures.
Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?
Authors: Trevisan Camila M. , Montagna Erik , de Oliveira Renato , Christofolini Denise M. , Barbosa Caio P. , Crandall Keith A. , Bianco Bianca 
Published: September 2018

Kisspeptin is involved in the control of human reproduction bridging the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone (GnRH) secretion; however, studies considering this peptide and infertility are limited. We conducted a review and critical assessment of available evidence considering kisspeptin structure, physiology, function in puberty and reproduction, its role in assisted reproduction treatments, kisspeptin dosage and the impact on KISS1 and GPR54 genes. Literature searches were conducted in PubMed using keywords related to: (i) kisspeptin or receptors, kisspeptin-1 (ii) reproduction or infertility or fertility (iii) gene and (iv) dosage or measurement or quantification or serum level, in human. Kisspeptin is a product of KISS1 gene that binds to a G-protein-coupled receptor (GPR54/KISS1R) stimulating the release of GnRH by hypothalamic neurons, leading to secretion of pituitary gonadotropins (LH and FSH) and sexual steroids, which in turn will act in the gonads to produce the gametes. Kisspeptin is being recognized as a crucial regulator of the onset of puberty, the regulation of sex hormone mediated secretion of gonadotropins, and the control of fertility. Inactivating and activating mutations in both KISS1 or GPR54 genes were associated with hypogonadotropic hypogonadism and precocious puberty. Despite this, studies considering kisspeptin and infertility are scarce. The understanding of the role of kisspeptin may lead to its use as a biomarker in infertility treatments and use in controlled ovarian hyperstimulation.