bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-Type-Specific Transcription of Innate Immune Regulators in response to HMPV Infection
Authors: Loevenich Simon , Malmo Jostein , Liberg Ann Magritt , Sherstova Tatyana , Li Youxian , Rian Kristin , Johnsen Ingvild B. , Anthonsen Marit W.
Published: October 2019

Human metapneumovirus (HMPV) may cause severe respiratory disease. The early innate immune response to viruses like HMPV is characterized by induction of antiviral interferons (IFNs) and proinflammatory immune mediators that are essential in shaping adaptive immune responses. Although innate immune responses to HMPV have been comprehensively studied in mice and murine immune cells, there is less information on these responses in human cells, comparing different cell types infected with the same HMPV strain. The aim of this study was to characterize the HMPV-induced mRNA expression of critical innate immune mediators in human primary cells relevant for airway disease. In particular, we determined type I versus type III IFN expression in human epithelial cells and monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). In epithelial cells, HMPV induced only low levels of IFN-βmRNA, while a robust mRNA expression of IFN-λs was found in epithelial cells, MDMs, and MDDCs. In addition, we determined induction of the interferon regulatory factors (IRFs) IRF1, IRF3, and IRF7 and critical inflammatory cytokines (IL-6, IP-10, and IL-1β). Interestingly, IRF1 mRNA was predominantly induced in MDMs and MDDCs. Overall, our results suggest that for HMPV infection of MDDCs, MDMs, NECs, and A549 cells (the cell types examined), cell type is a strong determinator of the ability of HMPV to induce different innate immune mediators. HMPV induces the transcription of IFN-βand IRF1 to higher extents in MDMs and MDDCs than in A549s and NECs, whereas the induction of type III IFN-λand IRF7 is considerable in MDMs, MDDCs, and A549 epithelial cells.
Estimation of Volatile Organic Compounds (VOCs) and Human Health Risk Assessment of Simulated Indoor Environment Consisting of Upholstered Furniture Made of Commercially Available Foams
Authors: Capíková Alena , Tesařová Daniela , Hlavaty Josef , Ekielski Adam , Mishra Pawan Kumar
Published: October 2019

This study was conducted for the qualitative and quantitative determination of volatile organic compounds (VOCs) and total volatile organic compounds (TVOC) from polymeric foam materials used in upholstered furniture. Six different types of foams viz. Highly elastic foam K5040, standard PU foam N5063, bonded polyurethane foam R100, viscoelastic foam V5020, self-extinguishing foam KF5560, and foam rubber were used. Short-term and long-term (24, 48, 72, 672 hours (28 day)) measurements were done to differentiate the role of primary emissions (present in new products) and secondary emissions (due to chemical reactions in material or slowly released due to the porous structure of material). The samples were collected using a small-space sampling chamber at a temperature of 23°C and a humidity of 50% depending on the aspect of time. The concentrations of VOC and TVOC were identified and quantified using a Gas chromatography–Mass spectroscopy (GC-MS) based method. Based on the VOC measurements, the standard room concentrations were simulated to estimate the human health risk assessment for all six types of foams. The results of simulations suggest no possibility of human health risk for the very long period (28 days), as the estimated values were found to be much below the prescribed limits.
Intelligent Analysis of Premature Ventricular Contraction Based on Features and Random Forest
Authors: Xie Tiantian , Li Runchuan , Shen Shengya , Zhang Xingjin , Zhou Bing , Wang Zongmin
Published: October 2019

Premature ventricular contraction (PVC) is one of the most common arrhythmias in the clinic. Due to its variability and susceptibility, patients may be at risk at any time. The rapid and accurate classification of PVC is of great significance for the treatment of diseases. Aiming at this problem, this paper proposes a method based on the combination of features and random forest to identify PVC. The RR intervals (pre_RR and post_RR), R amplitude, and QRS area are chosen as the features because they are able to identify PVC better. The experiment was validated on the MIT-BIH arrhythmia database and achieved good results. Compared with other methods, the accuracy of this method has been significantly improved.
Efficient Color Tuning of Upconversion Luminescence from Core-Shell Oxysulfide Nanoparticles
Authors: Tian Ying , Jiao Jianxin , Feng Xin , Xing Mingming , Peng Yong , Luo Xixian
Published: October 2019

The Y2O2S:Er3+@Y2O2S:Yb3+,Ho3+ core-shell up-conversion (UC) nanoparticles were successfully synthesized by the homogeneous co-precipitation method. The Y2O2S:Er3+@Y2O2S:Yb3+,Ho3+ core-shell nanoparticles exhibit bright green emissions under 980 nm excitation, while the triple-ion doped Y2O2S:Er3+,Yb3+,Ho3+ sample presents mainly red emissions. The intensity ratio of green-to-red emission of the core-shell and conventional triple-ion doped samples are 2.8 and 0.3, respectively. Investigations on the UC mechanisms show that emissions from Er3+ and Ho3+ ions are achieved simultaneously in the core-shell nanoparticles. This is due to the efficient energy transfers of Yb3+→Ho3+ within the shell layer and Yb3+→Er3+ between the shell and the core. While the triple-ion doped Y2O2S: Er3+,Yb3+,Ho3+ sample exhibits mainly the emissions of Er3+ along with weak luminescence of Ho3+ ion. Since the cross relaxation between Er3+ and Ho3+ ions in the Y2O2S:Er3+,Yb3+,Ho3+ nanoparticles can effectively suppress the emissions of Ho3+ ions. Yet, in the core-shell structure, this cross relaxation can be successfully restrained in the core-shell structure where Er3+ is in the core and Ho3+ is in the shell. Therefore, the construction of core-shell structure can improve the luminescence efficiency and provide a route for adjustment of emission color.
Improving Truncated Newton Method for the Logit‐Based Stochastic User Equilibrium Problem
Authors: Xu Min , Zhou Bojian , He Jie
Published: October 2019

This study proposes an improved truncated Newton (ITN) method for the logit‐based stochastic user equilibrium problem. The ITN method incorporates a preprocessing procedure to the traditional truncated Newton method so that a good initial point is generated, on the basis of which a useful principle is developed for the choice of the basic variables. We discuss the rationale of both improvements from a theoretical point of view and demonstrate that they can enhance the computational efficiency in the early and late iteration stages, respectively, when solving the logit‐based stochastic user equilibrium problem. The ITN method is compared with other related methods in the literature. Numerical results show that the ITN method performs favorably over these methods.
Curcumin Inhibits Proliferation of Epstein–Barr Virus-Associated Human Nasopharyngeal Carcinoma Cells by Inhibiting EBV Nuclear Antigen 1 Expression
Authors: Liu Limei , Yang Jiaomin , Ji Wuguang , Wang Chao
Published: October 2019

This investigation aims to study the effect of curcumin on the proliferation, cycle arrest, and apoptosis of Epstein–Barr virus- (EBV-) positive nasopharyngeal carcinoma (NPC) cells. EBV+ NPC cells were subjected to curcumin treatment. The cell viability was evaluated with the CCK-8. Cell cycle and apoptosis were analyzed by flow cytometry analysis. Expression (protein and mRNA) levels were detected with western blotting and quantitative real-time PCR, respectively. Curcumin efficiently reduced the viability of EBV+ NPC cells. Curcumin induced the cycle arrest of the HONE1 and HK1-EBV cells positive for EBV. Moreover, curcumin treatment promoted the NPC cell apoptosis, via the mitochondria- and death receptor-mediated pathways. Furthermore, curcumin decreased the expression of EBNA1 in the HONE1 and HK1-EBV cells and inhibited the transcriptional level of EBNA1 in the HeLa cells. Curcumin induced EBNA1 degradation via the proteasome-ubiquitin pathway. In addition, curcumin inhibited the proliferation of HONE1 and HK1-EBV cells positive for EBV, probably by decreasing the expression level of EBNA1. In both the HONE1 and HK1-EBV cells, curcumin inhibited the EBV latent and lytic replication. Curcumin could reduce the EBNA1 expression and exert antitumor effects against NPC in vitro.
Nitrate Poisoning due to Ingestion of Cabbages (Brassica oleracea var. capitata L.) (Brassicaceae) in Kitui County, Kenya
Authors: Nguta Joseph Mwanzia
Published: October 2019

Nitrate toxicosis associated with consumption of cabbages (Brassica oleracea var. capitata L.) (Brassicaceae) was diagnosed in a small herd comprising of ten goats in Matinyani ward, Kitui West sub-County of Kitui County in Kenya. The clinical signs were ataxia, ruminal tympany, bluish-brown mucous membranes, rapid and difficult breathing, incoordination, head pressing, aggressive movements, jugular distension, increased heart rates, tremors, and coma. Six goats died of intoxication. Dark brown/chocolate-colored and poorly clotted blood was the prominent necropsy finding. There was limited froth in the trachea and bronchi consistent with mild pulmonary oedema. There were liver congestion, pericarditis, and enlarged and congested kidneys with pinpoint haemorrhages. Four other affected goats were treated with intramuscular antihistamines and oral administration of ivermectin. No further mortality was observed after the treatment. Cabbages fed to goats had 6.6% nitrate on dry matter (DM) basis , while ruminal contents had 5.55% nitrate on dry matter basis (DM). Dark brown blood collected at postmortem had a methemoglobin fraction of 78%. Forage nitrate levels of 0.5% and above are potentially dangerous, with acute poisoning likely to occur if the nitrate level exceeds 1%. Death can occur when blood methemoglobin levels rise up to 67–90%. Findings from the current study are indicative of nitrate-nitrite toxidrome associated with ingestion of cabbages.
Fire Behavior of the Assembled Monolithic Hollow‐Ribbed Slabs
Authors: Li B. , Lin Y. Q. , Zhang H. L. , Ma M. J.
Published: October 2019

This paper presents the results from the furnace tests conducted on two assembled monolithic hollow‐ribbed (AMH) slabs consisting of the open box and the covered box, respectively. Detailed experimental data in the form of describing slab cracking or spalling, furnace temperatures, temperature distributions, and vertical deflections are presented. Comparison of the results from the two fire tests indicates that the covered box shows better fire resistance compared to the open box; thus, the covered box is recommended to adopt in structural fire‐resistant design. However, they are both prone to cracking or spalling at their bottom surfaces during the fire tests, so the AMH slab still needs further optimum design to meet its requirements of fire resistance and service function. In addition, the sealing quality of congruent boxes also has a great influence on the fire resistance of the AMH slab.
Antibiotic Utilization Trends in Two State Hospitals of Mongolia from 2013 to 2017
Authors: Dorj Gereltuya , Salvesen Blix Hege , Sunderland Bruce , Gankhulug Badamkhand , Tegshee Otgonbileg , Purevkhuu Mandakhnaran , Shirnen Gansaruul , Sanjjav Tsetsegmaa , Dorj Gantuya , Gendenragchaa Byambatsogt
Published: October 2019

Background. The study aimed to evaluate inpatient antibiotic use in both the State Second Hospital and State Third Hospital in Mongolia, using the WHO developed and standardized ATC/DDD methodology. Methods. Data were collected from the State Second Hospital and State Third Hospital which are major public hospitals that provide health care for approximately one fifth of the Mongolian population. Antibiotic utilization was monitored retrospectively for five years (2013–2017) using the ATC/DDD methodology and data were presented in DDD/ admission and DDD/100 bed days. Statistical analysis was performed using a Student’s t-test for parametric data. A P value of ≤0.05 was considered to be statistically significant. Results. The annual consumption rates in the State Second Hospital were stable over time while in the State Third Hospital consumption rates varied considerately between years. Overall, the total antibiotic consumption rate was very high, but has decreased in both hospitals. The rate of consumption of all antibiotics was approximately twice that in the State Third Hospital (421.7 DDD/100 bed days) between 2013 and 2017 when compared with the State Second Hospital (199.7 DDD/ 100 bed days), P<0.001). The seven most frequently used antibiotics comprised approximately 75% of all DDDs in both hospitals, in the period 2013–2017; being: amoxicillin, cefazolin, cefotaxime, ceftriaxone, clarithromycin, ciprofloxacin, and nitroxoline. However, this was not consistent when considering the individual years, since in 2015 and 2016, these seven active agents represented approximately 50%. Conclusion. This is the first hospital-based study of antibiotic consumption rates reported in Mongolia. In addition to very high consumption rates, large differences occurred between the hospitals investigated. Inappropriate and high levels of antibiotic use lead to increased costs and also increased nosocomial infection rates with potentially resistant species. The Government and health professionals need to take more active roles in improving and promoting quality antibiotic use among inpatients.
Environmental Efficiency Evaluation of Chinese Industry Systems by Using Non‐Cooperative Two‐Stage DEA Model
Authors: Shi Xiao
Published: October 2019

In evaluating the environmental efficiency analysis of Chinese industry systems, data envelopment analysis (DEA) has been a popular method. However, the production system is often treated as a black box in conventional DEA models. This study considers the internal structure of the production system to evaluate the environmental efficiency, which is characterized as a two‐stage system, i.e., production subsystem and pollutant treatment subsystem. And, in reality, some subsystems in two‐stage production systems are not equally important, and this kind of two‐stage systems usually has the feature that one subsystem dominates the other. Thus, we consider the leader and follower relationship in the environmental efficiency analysis. A new non‐cooperative two‐stage DEA model considering undesirable intermediates and undesirable outputs is proposed to calculate the environmental efficiency. The proposed method is then applied to 30 regional industry systems of China in the year 2010. Thus, each DMU’s environmental efficiencies for the overall system as well as both subsystems could be analyzed by the proposed approach. More accurate information could be provided for environmental management.
IL-37 Plays a Beneficial Role in Patients with Acute Coronary Syndrome
Authors: Mao Xiaobo , Zhu Ruirui , Zhang Fangyuan , Zhong Yucheng , Yu Kunwu , Wei Yuzhen , Sun Haitao , Xu Wenbin , Luo Quan , Wang Yue , Ding Yan , Zeng Qiutang
Published: October 2019

Background. Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated.Methods. Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested.Results. Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable.Conclusion. In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.
A Hospital-Based Study of Iodine Nutrition Status of Breastfeeding Mothers in Bangladesh
Authors: Naznin Jobaida , Fariduddin Mohammad , Hasan Mashfiqul , Atiqur-Rahman Mohammad , Sultana Nusrat , Anowar-Hossain Mohammad , Chowdhury Sharmin , Hasanat Muhammad Abul
Published: October 2019

Adequacy of iodine nutrition status in breastfeeding mothers is vital in preventing iodine deficiency disorder (IDD) in neonates and children. The aim of the study was to assess urinary iodine status in breastfeeding mothers attending Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital in Bangladesh. In this cross-sectional study carried out from January 2014 to January 2015, urinary iodine (UI;μgm/L) level of 266 mothers (age 26.6 ± 4.7 years (mean ± SD), exclusively breastfeeding: 132 and nonexclusively breastfeeding: 134), recruited on consecutive basis from BSMMU outdoor and indoor, were measured in spot urine following the wet digestion method. Median UI in the participants was 298.6 (interquartile range, IQR 206.6–454.9)μgm/L and only 6.4% lactating mother had low UI (i.e. <100 μgm/L). There was no difference of median UI in relation to exclusive or nonexclusive breast feeding, presence of goiter, parity, and age of breastfed baby (p=ns for all). But median UI was higher in older subjects (≥30 years vs. <30 years: 364.4 (228.4–529.9) vs. 283.7 (205.4–434.0); median (IQR)p=0.040)), with good socioeconomic condition (good vs. average or less: 328.2 (243.8–510.0) vs. 274.4 (200.0–433.3); median (IQR);p=0.020), and in those who are aware regarding the importance of iodine (aware vs. unaware: 316.6 (225.2–506.3) vs. 270.1 (196.0–407.2); median (IQR);p=0.018). The proportion of participants with UI < 100 μgm/L was similar in all the groups. Logistic regressions to predict deficient UI status revealed none of the variables to be an independent predictor. This study indicates that deficient iodine nutrition status in Bangladeshi breastfeeding mothers is not frequent at present.
Metformin Abrogates Age-Associated Ovarian Fibrosis
Authors: McCloskey Curtis W. , Cook David P. , Kelly Brendan S. , Azzi Feryel , Allen Christian H. , Forsyth Amanda , Upham Jeremy , Rayner Katey J. , Gray Douglas A. , Boyd Robert W. , Murugkar Sangeeta , Lo Bryan , Trudel Dominique , Senterman Mary K. , Vanderhyden Barbara C.
Published: October 2019

Purpose:

The ovarian cancer risk factors of age and ovulation are curious because ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased. To determine how age and ovulation underlie ovarian cancer risk, we assessed the effects of these risk factors on the ovarian microenvironment.

Experimental Design:

Aged C57/lcrfa mice (0–33 months old) were generated to assess the aged ovarian microenvironment. To expand our findings into human aging, we assembled a cohort of normal human ovaries (n = 18, 21–71 years old). To validate our findings, an independent cohort of normal human ovaries was assembled (n = 9, 41–82 years old).

Results:

We first validated the presence of age-associated murine ovarian fibrosis. Using interdisciplinary methodologies, we provide novel evidence that ovarian fibrosis also develops in human postmenopausal ovaries across two independent cohorts (n = 27). Fibrotic ovaries have an increased CD206+:CD68+ cell ratio, CD8+ T-cell infiltration, and profibrotic DPP4+αSMA+ fibroblasts. Metformin use was associated with attenuated CD8+ T-cell infiltration and reduced CD206+:CD68+ cell ratio.

Conclusions:

These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis.

See related commentary by Madariaga et al., p. 523
Synergy between EphA2-ILs-DTXp, a Novel EphA2-Targeted Nanoliposomal Taxane, and PD-1 Inhibitors in Preclinical Tumor Models
Authors: Kamoun Walid S. , Dugast Anne-Sophie , Suchy James J. , Grabow Stephanie , Fulton Ross B. , Sampson James F. , Luus Lia , Santiago Michael , Koshkaryev Alexander , Sun Gang , Askoxylakis Vasileios , Tam Eric , Huang Zhaohua Richard , Drummond Daryl C. , Sawyer Andrew J.
Published: October 2019

Combinations of chemotherapy with immunotherapy have seen recent clinical success, including two approvals of anti–PD-1/L1 agents in combination with taxane-based chemotherapy in non–small cell lung cancer and triple-negative breast cancer. Here, we present a study on the combination activity and mechanistic rationale of a novel EphA2-targeted liposomal taxane (EphA2-ILs-DTXp) and anti–PD-1. This combination was highly active in mouse syngeneic tumor models, with complete responses observed in 3 of 5 models. In the EMT-6 tumor model, combination of EphA2-ILs-DTXp with anti–PD-1 resulted in a 60% complete response rate, with durable responses that were resistant to rechallenge. These responses were not observed in the absence of CD8+ T cells. Characterization of the immune infiltrates in EMT-6 tumors reveals increased CD8+ T cells, increased CD8+ IFNγ+ CTLs, and an increased CD8/regulatory T-cell (Treg) ratio. These immunomodulatory effects were not observed in mice treated with a combination of docetaxel and anti–PD-1. Pharmacokinetic analysis revealed that the AUC of docetaxel was increased 15 times, from 52.1 to 785 ng/mL/hour, when delivered by EphA2-ILs-DTXp. A dose reduction study of EphA2-ILs-DTXp showed a dose–response relationship for both tumor growth inhibition and the CD8/Treg ratio. Our data indicate that synergism between docetaxel and anti–PD-1 is achievable with nanoliposomal delivery.
Unprovoked Pulmonary Embolism in Factor VII Deficiency
Authors: Singh Balraj , Modi Varun , Kaur Parminder , Guron Gunwant , Maroules Michael
Published: October 2019

Thrombotic events in bleeding disorders such as hemophilia A or B, Von Willebrand disease, afibrinogenemia, factor VII deficiency, and factor XI deficiency are rare but have been reported. These events usually occur in the presence of prothrombotic risk factors such as recent surgery, trauma, or factor replacement therapy. We present a case of a 68-year-old Hispanic female with a history of factor VII deficiency who presented with shortness of breath, chest pain, and palpitations and was found to have pulmonary embolism. Our patient did not have any of the above-mentioned thrombotic risk factors. Our case and review of the literature show that factor VII deficiency does not provide protection against thrombosis.
Dynamic Changes in Arteriovenous Malformations (AVMs): Spontaneous Growth and Resolution of AVM-Associated Aneurysms in Two Pediatric Patients
Authors: Koch Matthew J. , Mahal Brandon A. Virgil , Hadzipasic Muhamed , Fehnel Katie P. , Chapman Paul H. , Loeffler Jay S. , Orbach Daniel B. , Smith Edward R.
Published: October 2019

Arteriovenous malformations (AVMs) of the central nervous system are dynamic lesions that can change with time. One of the most clinically important concerns is the development and potential rupture of AVM-associated aneurysms. In this report, we review pediatric cases of de novo development of AVM-associated aneurysms in 2 children and present the relevant clinical and radiographic records. These 2 cases, coupled with a review of the current literature, offer insight into the risks of AVMs in children and underline the importance of timely treatment of appropriate cases.
Rheumatoid Arthritis-Associated Interstitial Lung Disease: Clinical Characteristics and Predictors of Mortality
Authors: Hyldgaard Charlotte , Ellingsen Torkell , Hilberg Ole , Bendstrup Elisabeth
Published: October 2019

Introduction: Interstitial lung disease (ILD) is a serious extraarticular manifestation of rheumatoid arthritis (RA), but no evidence-based therapy exists. Ongoing studies investigate the role of antifibrotic therapies for progressive fibrosing ILD (PF-ILD), including RA-ILD. The aim of the present study was to investigate the frequency of PF-ILD and the clinical characteristics of RA-ILD in a well-characterised, population-based cohort. Methods: We identified patients with RA-ILD diagnosed and followed at the ILD referral centre in Aarhus, Denmark, from 2004 to 2016. Adjusted hazard rate ratios for death were estimated using Cox regression models. The presence of PF-ILD was assessed using recently proposed definitions of relative forced vital capacity (FVC) decline ≥10%, relative diffusion capacity of the lung for carbon monoxide (DLco) decline ≥15% or worsening symptoms or a worsening radiological appearance accompanied by a ≥5 to <10% FVC decline. Results: We identified 102 patients with RA-ILD, and 52% had PF-ILD. Mean follow-up was 3.8 years and median survival was 7.1 years. Thirty-eight patients died during follow-up, and most deaths were from respiratory causes. Predictors of mortality in a multivariate model were DLco and high titres of IgM rheumatoid factor. Conclusion: PF RA-ILD was common and the associated mortality was high.
Excess Significance Bias in Repetitive Transcranial Magnetic Stimulation Literature for Neuropsychiatric Disorders
Authors: Amad Ali , Jardri Renaud , Rousseau Chloé , Larochelle Yann , Ioannidis John P.A. , Naudet Florian
Published: October 2019

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and promoted for use in multiple neuropsychiatric conditions, but as for many other medical devices, some gaps may exist in the literature and the evidence base for the clinical efficacy of rTMS remains under debate. Objective: We aimed to test for an excess number of statistically significant results in the literature on the therapeutic efficacy of rTMS across a wide range of meta-analyses and to characterize the power of studies included in these meta-analyses. Methods: Based on power calculations, we computed the expected number of “positive” datasets for a medium effect size (standardized mean difference, SMD = 0.30) and compared it with the number of observed “positive” datasets. Sensitivity analyses considered small (SMD = 0.20), modest (SMD = 0.50), and large (SMD = 0.80) effect sizes. Results: A total of 14 meta-analyses with 228 datasets (110 for neurological disorders and 118 for psychiatric disorders) were assessed. For SMD = 0.3, the number of observed “positive” studies (n = 94) was larger than expected (n = 35). We found evidence for an excess of significant findings overall (p < 0.0001) and in 8/14 meta-analyses. Evidence for an excess of significant findings was also observed for SMD = 0.5 for neurological disorders. Of the 228 datasets, 0 (0%), 0 (0%), 3 (1%), and 53 (23%) had a power >0.80, respectively, for SMDs of 0.30, 0.20, 0.50, and 0.80. Conclusion: Most studies in the rTMS literature are underpowered. This results in fragmentation and waste of research efforts. The somewhat high frequency of “positive” results seems spurious and may reflect bias. Caution is warranted in accepting rTMS as an established treatment for neuropsychiatric conditions.
Point-of-Care Ultrasonography for Objective Volume Management in End-Stage Renal Disease
Authors: Koratala Abhilash , Chamarthi Gajapathiraju , Kazory Amir
Published: October 2019

Focused ultrasonography or point-of-care ultrasonography (POCUS) is increasingly considered as an essential bedside diagnostic tool. In patients with end-stage renal disease (ESRD) treated with hemodialysis, it can be used as an adjunct to physical examination to objectively assess the volume status and guide the rate and amount of ultrafiltration. Herein, we describe the case of an ESRD patient presenting with hypertensive urgency where POCUS disclosed the presence of hypervolemia despite unremarkable physical examination. The sonographic findings of the inferior vena cava, heart, and lungs guided fluid extraction during hemodialysis therapy, and the actual ultrafiltration volume was significantly higher than what was anticipated based on clinical findings. This case highlights the importance of using ­POCUS as a tool for objective and precise assessment of volume status in patients with ESRD.
Spondylocostal Dysostosis Associated with Split Spinal Cord and Other Malformations
Authors: Milić Ivan , Milić Marina , Djorić Igor , Marinković Ivan , Boljanović Jelena , Marinković Slobodan
Published: October 2019

Spondylocostal dysostosis is a very rare combination of complex vertebra and rib malformations, accompanied occasionally by other disorders. A 3-year-old girl presented kyphoscoliosis, foot deformities, gate disturbance, and urinary incontinence. The CT and MRI examination revealed kyphosis and scoliosis with a double curve, some absent, broadened, bifurcating and fused ribs, hemivertebrae, butterfly and cleft vertebrae in thoracic and lumbar region, sporadic cleft or absent vertebral arches or pedicles, and hypoplastic sacrum with a cleft of the S2 vertebra. Spina bifida occulta extended from T10 to T11, and from L3 to the end of the sacrum. Two hemicords, separated by a bony septum and surrounded by their own dural tubes (type I), were present from the level of T9 to the conus medullaris. Filum terminale was thick and duplicated. Syringomyelia was present in the thoracic cord from T5 to T8. Finally, a small meningocele was seen at the T10–T11 level, and a subcutaneous lipoma in the thoracolumbar region. To our knowledge, such a combination of vertebra, rib, and cord malformations, including the mentioned additional disorders, has never been reported.
Unusual Form of Obstructive Hydrocephalus in Association with 6q Terminal Deletion Syndrome: A Case Report and Literature Review
Authors: Iwamoto Hirofumi , Muroi Ai , Sekine Tomokazu , Tsurubuchi Takao , Ishikawa Eiichi , Matsumura Akira
Published: October 2019

Introduction: Terminal deletion of chromosome 6q is a rare chromosomal abnormality associated with intellectual disabilities and various structural brain abnormalities. We present a case of 6q terminal deletion syndrome with unusual magnetic resonance imaging (MRI) findings in a neonate. Case Presentation: The neonate, who was prenatally diagnosed with dilation of both lateral ventricles, was born at 38 weeks of gestation. MRI demonstrated abnormal membranous structure continuing to the hypertrophic massa intermedia in the third ventricle that had obscured the cerebrospinal fluid pathway, causing hydrocephalus. G-band analysis revealed a terminal deletion of 6q with the karyotype 46, XY, add(6)(q25.3) or del(6)(q26). He underwent ventriculoperitoneal shunt successfully, and his head circumference has been stable. Discussion/Conclusion: 6q terminal deletion impacts the molecular pathway, which is an essential intracellular signaling cascade inducing neurological proliferation, migration, and differentiation during neuronal development. In patients with hydrocephalus in association with hypertrophy of the massa intermedia, this chromosomal abnormality should be taken into consideration. This case may offer an insight into the pathogenesis of hydrocephalus in this rare chromosomal abnormality.
Living Kidney Donation in a Type 1 Dent’s Disease Patient from His Mother
Authors: Gambaro Giovanni , Naticchia Alessandro , Ferraro Pietro Manuel , Spagnoletti Gionata , Romagnoli Jacopo , Salerno Maria Paola , Citterio Franco
Published: October 2019

Introduction: Dent’s disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease. Females are obligate carriers of the mutated gene, and some show a mild Dent’s disease phenotype. There may be reason for concern when considering a female obligate carrier (i.e., the mother) for kidney donation because of the risk of kidney function deterioration. Case Presentation: We describe the first successful kidney transplantation involving a patient with type 1 Dent’s disease and ESRD given a kidney by an obligate carrier of the gene mutation, his mother. Conclusions: After careful assessment of the female obligate carriers, intrafamilial kidney donation in Dent’s disease type 1 is feasible. No deteriorating renal function in the donor was observed.
Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation
Authors: Ramirez Rafael J. , Takemoto Yoshio , Martins Raphaël P. , Filgueiras-Rama David , Ennis Steven R. , Mironov Sergey , Bhushal Sandesh , Deo Makarand , Rajamani Sridharan , Berenfeld Omer , Belardinelli Luiz , Jalife José , Pandit Sandeep V.
Published: October 2019

Background:

Ranolazine inhibits Na
+
current (I
Na
), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF).

Methods:

PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped.

Results:

In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (
P
<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm
−2
s
−
1
(
P
<0.001) in left atrial epicardium (LA
epi
), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz;
P
<0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm
−
2
s
−
1
;
P
=ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing I
Na
decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions.

Conclusions:

PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF.
Race, Natriuretic Peptides, and High-Carbohydrate Challenge
Authors: Patel Nirav , Russell Griffin K. , Musunuru Kiran , Gutierrez Orlando M. , Halade Ganesh , Kain Vasundhara , Lv Wenjian , Prabhu Sumanth D. , Margulies Kenneth B. , Cappola Thomas P. , Arora Garima , Wang Thomas J. , Arora Pankaj
Published: October 2019

Rationale:

Lower NP (natriuretic peptide) levels may contribute to the development of cardiometabolic diseases. Blacks have lower NP levels than middle-aged and older white adults. A high-carbohydrate challenge causes an upregulation of a negative ANP regulator microRNA-425 (
miR-425
), which reduces ANP (atrial-NP) levels in whites.

Objectives:

We designed a prospective trial to study racial differences in (1) NP levels among young adults, (2) NP response to a high-carbohydrate challenge, and (3) explore underlying mechanisms for race-based differences.

Methods and Results:

Healthy self-identified blacks and whites received 3 days of study diet followed by a high-carbohydrate challenge. Gene expression from whole blood RNA was assessed in the trial participants. Additionally, atrial and ventricular tissue samples from the Myocardial Applied Genomics Network repository were examined for NP system gene expression. Among 72 healthy participants, we found that B-type-NP, NT-proBNP (N-terminal-pro-B-type NP), and MRproANP (midregional-pro-ANP) levels were 30%, 47%, and 18% lower in blacks compared with whites (
P
≤0.01), respectively. The decrease in MRproANP levels in response to a high-carbohydrate challenge differed by race (blacks 23% [95% CI, 19%–27%] versus whites 34% [95% CI, 31%–38]; P
interaction
<0.001), with no change in NT-proBNP levels. We did not observe any racial differences in expression of genes encoding for NPs (
NPPA/NPPB
) or NP signaling (
NPR1
) in atrial and ventricular tissues. NP processing (
corin
), clearance (
NPR3
), and regulation (
miR-425
) genes were ≈3.5-, ≈2.5-, and ≈2-fold higher in blacks than whites in atrial tissues, respectively. We also found a 2-and 8-fold higher whole blood RNA expression of gene encoding for Neprilysin (
MME
) and
miR-425
among blacks than whites.

Conclusions:

Racial differences in NP levels are evident in young, healthy adults suggesting a state of NP deficiency exists in blacks. Impaired NP processing and clearance may contribute to race-based NP differences. Higher miR-425 levels in blacks motivate additional studies to understand differences in NP downregulation after physiological perturbations.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov/ct2/show/NCT03072602
. Unique identifier: NCT03072602.
Renal Dysfunction and In‐Hospital Outcomes in Patients With Acute Ischemic Stroke After Intravenous Thrombolytic Therapy
Authors: Rao Zhen‐Zhen , Gu Hong‐Qiu , Wang Xian‐Wei , Xie Xue‐Wei , Yang Xin , Wang Chun‐Juan , Zhao Xingquan , Xian Ying , Wang Yi‐Long , Li Zi‐Xiao , Xiao Rui‐Ping , Wang Yong‐Jun ,   the Chinese Stroke Center Alliance investigators
Published: October 2019

Background

The impact of estimated glomerular filtration rate (
eGFR
) on clinical short‐term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial.

Methods and Results

We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between
eGFR
(<45, 45–59, 60–89, and ≥90 mL/min per 1.73 m
2
) and in‐hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an
eGFR
<45, 625 (3.4%) had an
eGFR
45 to 59, 3679 (20.1%) had an
eGFR
60 to 89, and 13 415 (73.2%) had an
eGFR
≥90. As compared with
eGFR
≥90,
eGFR
values <45 (6.7% versus 0.9%, adjusted odds ratio, 3.59; 95%
CI
, 2.18–5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95%
CI
, 1.18–3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95%
CI
, 1.20–2.34) were independently associated with increased odds of in‐hospital mortality. However, there was no statistically significant association between
eGFR
and symptomatic intracerebral hemorrhage.

Conclusions

eGFR
was associated with an increased risk of in‐hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator.
eGFR
is an important predictor of poststroke short‐term death but not of symptomatic intracerebral hemorrhage.
Contrast-Associated Acute Kidney Injury in Endovascular Thrombectomy Patients With and Without Baseline Renal Impairment
Authors: Diprose William K. , Sutherland Luke J. , Wang Michael T.M. , Barber P. Alan
Published: October 2019

Background and Purpose—

In ischemic stroke, baseline renal impairment is present in 20 to 35% of patients and may increase the risk of contrast-associated acute kidney injury (CA-AKI). We aimed to determine whether endovascular thrombectomy (EVT) patients with baseline renal impairment are at increased risk of CA-AKI.

Methods—

Consecutive EVT patients were identified from a prospective database. Patients were stratified by estimated glomerular filtration rate. The primary outcome was CA-AKI assessed at 24 to 72 hours following EVT, defined as an increase in serum creatinine of ≥26.5 µmol/L or 1.5× baseline serum creatinine. Secondary outcomes included requirement for renal replacement therapy and 3-month mortality.

Results—

Three hundred thirty-three EVT patients (201 men; mean±SD age 63.9±15.8 years) were included. The mean±SD iohexol contrast volume used in diagnostic and EVT imaging was 236±77 mL per patient. CA-AKI occurred in 11 (3.3%) patients; none required renal replacement therapy, but 4 of 11 (36.4%) had died by 3 months. Propensity score–adjusted logistic regression showed that estimated glomerular filtration rate <30 mL/(min·1.73 m
2
) was a significant predictor of CA-AKI (odds ratio, 19.93; 95% CI, 2.33–170.74;
P
=0.006). The dose of contrast was not associated with an increased risk of CA-AKI (
P
>0.05). Multiple logistic regression adjusted for potential confounders demonstrated that CA-AKI was independently associated with increased mortality (odds ratio, 4.68; 95% CI, 1.05–20.97;
P
=0.04).

Conclusions—

There is utility in obtaining baseline creatinine levels to identify patients at risk of CA-AKI and to establish a diagnosis of CA-AKI in patients with subsequent creatinine rises. However, contrast-requiring diagnostic imaging and EVT should not be delayed by waiting for the results of baseline renal function.
Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST)
Authors: Mistry Eva A. , Sucharew Heidi , Mistry Akshitkumar M. , Mehta Tapan , Arora Niraj , Starosciak Amy K. , De Los Rios La Rosa Felipe , Siegler James Ernest , Barnhill Natasha R. , Patel Kishan , Assad Salman , Tarboosh Amjad , Dakay Katarina , Salwi Sanjana , Cruz Aurora S. , Wagner Jeffrey , Fortuny Enzo , Bennett Alicia , James Robert F. , Jagadeesan Bharathi , Streib Christopher , O’Phelan Kristine , Kasner Scott E. , Weber Stewart A. , Chitale Rohan , Volpi John J. , Mayer Stephan , Yaghi Shadi , Jayaraman Mahesh V. , Khatri Pooja
Published: October 2019

Background and Purpose—

To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan.

Methods—

Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0–2 versus 3–6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression.

Results—

Among 485 enrolled patients (median age, 69 [interquartile range, 57–79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52–3.29],
P
<0.01; adjusted odds ratio, 1.29 [0.81–2.06],
P
=0.28, after adjustment for prespecified variables).

Conclusions—

A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.
Effectiveness of minimum retesting intervals in managing repetitive laboratory testing: experience from a Croatian university hospital
Authors: Lapić Ivana , Rogić Dunja , Fuček Mirjana , Galović Ružica
Published: October 2019

Introduction: Inappropriate laboratory retesting can be addressed by implementing minimum retesting intervals (MRI). The aim of our study was to assess the effectiveness of the implemented MRI protocol for inpatients. Materials and methods: Minimum retesting intervals were applied for 53 laboratory tests. The overall reduction of test requests, reduction in charges and reagent cost savings, frequency of MRI alert appearance as well as the rate of MRI acceptance and ignorance were calculated for a one-year period. Reasons for violating the MRI rule, hospital departments that contributed mostly to MRI rule violation, and the frequency of MRI violations between routine and emergency laboratory were evaluated. Results: During the one-year period, 106,780 requests violated the MRI rule, which corresponds to 14.8% of all requests received. 13,843 requests were cancelled, yielding a 1.9% reduction of requested tests. High-volume tests, namely complete blood count, C-reactive protein, alanine aminotransferase, gamma-glutamyltransferase and total bilirubin, accounted for 65% of all generated alerts and had the highest alert ignorance (>85%). The highest cancellation rate was observed for tumor markers and autoimmunity tests, for most being at least 50%. Annual charge reduction was 62,641 EUR while reagent cost savings were 11,408 EUR. Tests performed in the emergency laboratory had a higher alert appearance than the same routine tests. The most common reason for MRI violation was clinical justification based on the patient’s condition. Most frequently ignored MRI alerts were in the intensive care unit. Conclusion: MRI implementation showed limited effectiveness in reducing testing repetition and achieving financial savings, yet provided the basis for future improvements.
Clinician’s opinion about critical risk results proposed by the Croatian Chamber of Medical Biochemists
Authors: Šonjić Pavica , Nikler Ana , Vuljanić Dora , Dukić Lora , Šimundić Ana-Maria
Published: October 2019

Introduction: It has been recommended that each laboratory modify their critical result reporting practices to reflect the clinical needs of their patient populations. The aim of this survey was to assess how well critical laboratory values defined by the Croatian Chamber of Medical Biochemists (CCMB) correspond to the needs of the physicians at University hospital “Sveti Duh” (Zagreb, Croatia). Materials and methods: We conducted a survey among physicians from five departments in our hospital. Physicians were asked general questions about critical risk results (if and how they want to be informed). A list of critical risk results defined by the CCMB was offered and physicians were asked to revise the existing critical risk results and suggest adding new parameters. Obtained data were presented as numbers. Where the number of observations was low, ratios were used. Results: Survey response rate was 43% (52/121). Majority (48/52) wants to be informed of critical risk results, either personally (31/48) or through a colleague (32/48). They prefer to be informed about critical risk results of prothrombin time, platelet count, haemoglobin, glucose, creatinine, sodium and potassium. Revisions in the CCMB critical risk result list are proposed by 13 out of 48 physicians. Neonatologists approved the CCMB’s list. Conclusions: Although most critical risk results defined by the CCMB correspond well to the needs of the physicians in our hospital, some revisions are necessary to meet the particular needs of individual departments. Communication of critical risk results to those who have requested laboratory testing is highly appreciated practice.