bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Trends in Application of Stereology as a Quantitative Tool in Biomedical Research
Authors: Kipanyula Maulilio J. , Sife Alfred S.
Published: September 2018

Stereology is a quantitative and comparative method that utilizes planes, lines, and points for the estimation of three-dimensional parameters in morphological studies. It primarily focuses on geometrical features of objects such as number, density, length, area, and volume. A scientometric study was conducted to analyze global research trends in application of stereology in biomedical research. Stereology has gained wide application resulting into design-based stereological methods. Data for this study were retrieved from the SCOPUS database. At least 5,732 publications employing stereology as analytical tool were produced in a period of 50 years between 1966 and 2016. Half (2,858; 49.87%) of these publications were produced in the last 12 years from 2005 to 2016. The relative growth rate (RGR) of publications decreased from 1967 (0.69) to 2016 (0.03) whereas the doubling time (DT) increased from 1.00 to 20.56 in the same period. A great majority (5,332; 93.02%) of the publications retrieved from SCOPUS were journal articles in various biomedical fields. The Journal of Microscopy tops the list of journals with at least 205 articles. The most productive country was USA with at least 1663 (23.10%) publications and Aarhus Universitet tops the list of institutions with at least 306 publications. J.R. Nyengaard was the most prolific author who contributed at least 125 publications. The highly cited article had a total of 2,054 citations with an average of over 82 citations per year. Given the growing importance of stereology in biomedical research, it is necessary to promote its application among scholars.
Sensitivity to Damage Imperfection for Multileaf Masonry Walls Based on Vibrational Analyses
Authors: Boscato G. , Reccia E. , Baraldi D. , Cecchi A.
Published: September 2018

Damage‐imperfection indicators based on variation of dynamic parameters allow to identify the intrinsic discontinuity and the damage of structures. Here, the structural health monitoring through the vibration‐based approach has been carried out by two steps on three different multileaf masonry specimens (full infill, damaged infill, and strengthened infill) subjected to uniaxial compressive load. In the first step, the characterization of initial conditions based on the investigation of the intrinsic discontinuity and the manufacturing imperfections has been done. In this phase, the detection, localization, assessment, and prediction of damage have been given by the comparison between the experimental and numerical modal data calculated by the commercial finite element code. Subsequently, in the second step, starting from the identification of undamaged condition, the damage effects on changes of the dynamic parameters have been recorded. As well known, the incoherent response between the leaves is related to frequency values, damping ratios, and modal shapes.
Random Attractors for Stochastic Retarded 2D-Navier-Stokes Equations with Additive Noise
Authors: Jia Xiaoyao , Ding Xiaoquan
Published: September 2018

In this paper, the existence and the upper semicontinuity of a pullback attractor for stochastic retarded 2D-Navier-Stokes equation on a bounded domain are obtained. We first transform the stochastic equation into a random equation and then obtain the existence of a random attractor for random equation. Then conjugation relation between two random dynamical systems implies the existence of a random attractor for the stochastic equation. At last, we get the upper semicontinuity of random attractor.
Comparative Proteomic Analysis of Two Differently Extracted Coptis chinensis in the Treatment of Type 2 Diabetic Rats
Authors: Qiu Xin , Wei Xinyu , Guan Hongwei , Su Hao , Gong Jing , Fang Ke , Zou Xin , Dong Hui , Xu Lijun , Lu Fuer
Published: September 2018

Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese medicine due to its significant hypoglycemic and hypolipidemic effects. It was reported that CC powders are more effective than CC decoctions. In this study, a rat model of type 2 diabetes was established and treated with supercritical‐extracted CC and gastric juice extracted CC, respectively. Body weight, fasting plasma insulin, insulin resistance index, and lipid profiles were measured along with oral glucose tolerance tests (OGTTs). In addition, the levels of plasma proteins were compared between type 2 diabetic rats and CC‐treated rats using an iTRAQ‐based quantitative proteomic analysis. The results showed that the plasma levels of triglyceride (TC), total cholesterol (TG), and low‐density lipoprotein (LDL) in rats of both CC‐treated groups were significantly decreased. In addition, the proteomic analysis identified 929 proteins, while 15 proteins were selected from these 929 proteins based on their expression levels and bioinformatic results. Among these 15 proteins, 9 proteins (IGF‐1, Igfbp4, Igfbp‐6, Igfals, C2, C4, Cfi, Prdx‐2, and Prdx‐3) were upregulated in the two CC‐treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC‐1, ApoC‐3, ApoB‐100, and ApoE) were downregulated. The functions of these proteins are associated with glucose metabolism, insulin action, immunity, inflammation, lipid metabolism, oxidation, and antioxidation. The two differently extracted CC did not show significant differences in terms of their treatment efficacy. This research expanded our understanding on the therapeutic effects and mechanisms of CC in the treatment of type 2 diabetes.
A Secure Three‐Factor Multiserver Authentication Protocol against the Honest‐But‐Curious Servers
Authors: Guo Hua , Chen Chen , Gao Ya , Li Xiong , Jin Jiongchao
Published: September 2018

Three‐factor multiserver authentication protocols become a prevalence in recent years. Among these protocols, almost all of them do not involve the registration center into the authentication process. To improve the protocol’s efficiency, a common secret key is shared among all severs, which leads to a serious weakness; i.e., we find that these protocols cannot resist the passive attack from the honest‐but‐curious servers. This paper takes Wang et al.’s protocol as an example, to exhibit how an honest‐but‐curious server attacks their protocol. To remedy this weakness, a novel three‐factor multiserver authentication protocol is presented. By introducing the registration center into the authentication process, the new protocol can resist the passive attack from the honest‐but‐curious servers. Security analyses including formal and informal analyses are given, demonstrating the correctness and validity of the new protocol. Compared with related protocols, the new protocol possesses more secure properties and more practical functionalities than others at a relatively low computation cost and communication cost.
Serum Matrix Metalloproteinase 9 and Macrophage Migration Inhibitory Factor (MIF) Are Increased in Young Healthy Nonobese Subjects with Positive Family History of Type 2 Diabetes
Authors: Nikołajuk Agnieszka , Matulewicz Natalia , Stefanowicz Magdalena , Karczewska-Kupczewska Monika
Published: September 2018

Insulin resistance increases the risk for cardiovascular disease (CVD) even in the absence of classic risk factors, such as hyperglycemia, hypertension, dyslipidemia, and obesity. Low-grade chronic inflammatory state is associated both with insulin resistance and atherosclerosis. An increased circulating level of proinflammatory proatherogenic factors and biomarkers of endothelial activation was observed in diabetes and CVD. The aim of our study was to assess serum proatherogenic and proinflammatory factors in young healthy nonobese subjects with positive family history of type 2 diabetes. We studied 74 young healthy nonobese subjects with normal glucose tolerance (age < 35 years, BMI < 30 kg/m2), 29 with positive family history of type 2 diabetes (relatives, 25 males and 4 females) and 45 subjects without family history of diabetes (control group, 39 males and 6 females). Hyperinsulinemic-euglycemic clamp was performed, and serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin 18 (IL-18), macrophage inhibitory cytokine 1 (MIC-1), macrophage migration inhibitory factor (MIF), matrix metalloproteinase (MMP-9), and soluble forms of adhesion molecules were measured. Relatives had markedly lower insulin sensitivity (p=0.019) and higher serum MMP-9 (p<0.001) and MIF (p=0.006), but not other chemokines and biomarkers of endothelial function. Insulin sensitivity correlated negatively with serum MMP-9 (r=−0.23, p=0.045). Our data show that young healthy subjects with positive family history of type 2 diabetes already demonstrate an increase in some nonclassical cardiovascular risk factors.
A Mechanism for Recognizing and Suppressing the Emergent Behavior of UAV Swarm
Authors: Liu Qiang , He Ming , Xu Daqin , Ding Ning , Wang Yong
Published: September 2018

Similar to social animals in nature, UAV swarm is also a complex system that can produce emergent behavior. The emergent behavior of UAV swarm in specific airspace is undoubtedly the act that the defense side does not expect to see; therefore, recognition and suppression of the emergent behavior of UAVs swarm are needed. Based on the analysis of the UAV swarm emergent behavior mechanism, by adoptingf-divergence method, UAV swarm emergent behavior was quantified, and a rapid recognition mechanism of emergent behavior has been established, thus, making preparation for the suppression of the emergent behavior. In the academic circle, for the first time, in accordance with heuristic rules governing the algorithms of UAV swarm suppression, principle of emergent behavior suppression has been proposed, failure judgment model of UAV swarm control under interference conditions has been constructed, the stability of UAV swarm has been analyzed, and the combat command process of UAV swarm based on OODA loop has been put forward. Through the simulation, the comparison of information entropy andf-divergence based emergence measurement method has been made, andf-divergence based method has some advantages for measuring the emergence of UAV swarm. From the analysis and discussion of the inhibitory effect on swarm flocking behavior under different interference intensity and timing, conclusion has been drawn that comprehensive suppression on the premise of correct recognition of flocking behavior is the best strategy fighting against UAV swarm emergent behavior.
Major Depression in Chinese Medicine Outpatients with Stagnation Syndrome: Prevalence and the Impairments in Well‐Being
Authors: Ng Siu-Man , Leng Ling-Li
Published: September 2018

Stagnation syndrome, a diagnostic entity in traditional Chinese medicine (TCM), has been long regarded as the TCM counterpart of major depression in Western medicine. The study investigated the prevalence of major depression among stagnation syndrome patients and evaluated their well‐being and functioning outcomes. In total, 117 patients diagnosed with stagnation syndrome were measured using Stagnation Scale, the Patient Health Questionnaire‐9 (PHQ‐9), and the Body‐Mind‐Spirit Well‐Being Inventory. Results indicate major depression among stagnation syndrome patients was characterized by a high co‐occurrence rate and worse physical, mental, and functional outcomes. More than one‐quarter (26.5%) of the patients met the DSM‐V diagnostic criteria for major depression and over half (53%) exceeded the PHQ‐9 cutoff (score above 10) for moderate/severe depression symptoms. The wellness of the stagnation syndrome patients was worse (M = 298.2, SD = 66.5) than that of the general population (M = 360.9, SD = 79.9), with a large Cohen’s d value of 0.9. The “wellness outlook” of the depressed stagnation syndrome patients appeared grimmer (M = 252.3, SD = 52.2). The correlation between stagnation and depression was higher for affective symptoms than somatic symptoms. Physical distress did not mediate the relationship between stagnation and daily functioning. These might suggest that stagnation syndrome and major depression may share some similar psychological mechanisms.
Chinese Medicinal Herbs in the Treatment of Diabetic Cognitive Impairment: A Systematic Review and Meta‐Analysis
Authors: Yan Bin , Wang Jingbo , Xue Zhigang , Tian Guoqing
Published: September 2018

Background. Diabetic cognitive impairment (DCI), a serious complication of diabetes mellitus (DM), is gaining more acceptance and attention. The learning and memory function of diabetics always decreases. Traditional Chinese medicine (TCM) has been demonstrated to be effective in treating the symptoms in China, and thereinto Chinese medicinal herbs (CMH) are the most widely used. The objective of the present study was to review and analyze the existing data about reducing the symptoms in CMH treatment for DCI. Methods. Electronic literature databases (PubMed, EMBASE, CNKI, SinoMed, and Wan fang) were searched for randomized controlled trials conducted in China, comparing CMH with western medicines in the treatment of DCI, up to April 1, 2018. We applied standard meta‐analytic techniques to analyze data from papers that reached acceptable criteria. Result. Nine randomized controlled trials (n = 576) on CMH were included. We found moderate evidence that CMH used alone or in combination with western medicines was more effective than western medicines alone in reliving the symptoms for DCI (total effective rate, odds radio (OR) = 4.64 (2.60, 8.29), and 95% confidence interval, P<0.00001). Besides, CMH along or in combination with western medicines showed more beneficial effects on Montreal Cognitive Assessment (MoCA) scale (mean difference (MD) = 1.31(0.75, 1.87), P<0.00001), Mini‐Mental State Examination (MMSE) scale (MD = 2.07 (0.86, 3.28), P<0.00001, and TCM symptom score (TCMSS) (MD = ‐4.89 (‐8.44, ‐1.34), P = 0.007). Most of the included studies showed that there was not a significant difference in the adverse events. Conclusions. These findings demonstrated that CMH used alone or in combination with western medicines were apparently better than western medicines alone in the treatment of DCI. Because of the poor quality of the studies that were available for the present meta‐analysis, further researches are still needed to support these early findings.
Temporary CBD Stenting with a Nelaton Tube Is a More Practical and Safer Option Than T-Tube Drainage after Conventional CBD Exploration for Choledocholithiasis
Authors: Abdelkader Ashraf M. , Zidan Ahmed M. , Younis Mohamed T.
Published: September 2018

Objective. We are trying to investigate the possibility, safety, and benefits of replacing the role of T-tube by another more safe and effective procedure for biliary decompression in the case of common bile duct (CBD) exploration. Methods. Our present study includes fifty consecutive patients who underwent a traditional CBD exploration due to choledocholithiasis. Patients were divided into 2 equal groups. In the 1st group, a spontaneously expelled Nelaton tube is placed in the CBD to aid in bile drainage to the duodenum, while in the 2nd group, a conventional T-tube is placed to decompress the CBD in the early postoperative (PO) days to a drainage bag. Operative and PO data as well as PO hospital stay time were recorded. All data were collected and statistically analyzed. Results. The mean operative time and PO hospital stay days were significantly low (p value < 0.05) in the Nelaton tube drainage group compared with the T-tube drainage group. On the other hand, the mean time needed for the abdominal drain removal was significantly higher in the T-tube drainage group (p value < 0.05). Conclusion. Nelaton tube with internal biliary drainage is effective and safer than T-tube drainage and it helps in reduction of the PO hospital stay time. In addition, it avoids all short-term complications of T-tube.
The Impact of Scientific and Technical Training on Improving Routine Collection of Antenatal Care Data for Maternal and Foetal Risk Assessment: A Case Study in the Province of South Kalimantan, Indonesia
Authors: Anggraini Dewi , Abdollahian Mali , Marion Kaye , Nuryani Supri , Ramadhan Fadly , Rahayu Rezky Putri , Rachman Irfan Rizki , Wurianto Widya
Published: September 2018

Objectives. First, to assess the impact of scientific and technical training on midwives’ abilities in collecting and recording the results of routine antenatal care examinations. Second, to explore midwives’ views with regard to factors affecting their abilities to successfully complete the data documentation tasks. Methods. The study was conducted in South Kalimantan, Indonesia (April 2016-October 2017). Nineteen urban and rural midwives were selected. Access to antenatal care information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study) was granted. A descriptive and exploratory design was used to describe midwives’ abilities and challenges pertaining to timely collection and recording of results concerning antenatal care examinations. Results. Scientific and technical training has significantly improved the average amount of recorded antenatal care data (from 17.5% to 62.1%, p-value < 0.0005). Lack of awareness, high workload, and insufficient skills and facilities are the main reasons for the database gaps. Conclusions. The training has equipped midwives with scientific knowledge and technical abilities to allow routine collection of antenatal care data. Provision and adequate use of this information during different stages of pregnancy is crucial as an evidence-based guideline to assess maternal and foetal risk factors to ending preventable mortality.
Breakage in Two Points of a Short and Undersized “Affixus” Cephalomedullary Nail in a Very Active Elderly Female: A Case Report and Review of the Literature
Authors: Rollo Giuseppe , Rinonapoli Giuseppe , Pichierri Paolo , Bisaccia Michele , Caraffa Auro , Meccariello Luigi
Published: September 2018

Introduction. Trochanteric fractures of the femur are common in elderly individuals with osteoporosis. The use of cephalomedullary nails is increasing, and they are now the most commonly used fixation devices, especially for the treatment of unstable trochanteric fractures. The nail breakage is not the most common complication of intramedullary nailing. Many scientific papers report nail breakage in a specific location: through the lag screw hole, the nail shaft, or the distal locking hole. Materials and Methods. We present a case of an 84-year-old patient treated with modular revision hip arthroplasty due to the breakage in two points of a cephalomedullary nail implanted 3 years earlier for a subtrochanteric fracture. Results. After modular revision hip arthroplasty, the functional results and quality of life have been excellent. Conclusions. As far as we could determine, this appears to be the first case of a breakage of a cephalomedullary nail in two points after nonunion in a very active elderly female.
The Contact Mechanics of Novikov’s Surface-Hardened Gearing during Running-in Process
Authors: Beskopylny Alexey , Onishkov Nikolay , Korotkin Viktor
Published: September 2018

The article is devoted to the analysis of the state of the contact surfaces of the higher kinematic pair in the general case of relative motion, that is, in the presence of rolling, sliding, and twisting, which is characteristic of Novikov’s circular-screw gears. The purpose of the work is to assess the impact of friction forces, the state of contact surfaces after tool processing, and the localization of the instantaneous contact spot on the level of contact—fatigue durability of gears. Power contact in the presence of geometric slippage of the mating surfaces leads to a significant change in the initial geometry and the mechanical properties of surface layers. In the existing methods of calculations of contact strength, the effect of running-in is investigated insufficiently, which leads to an incorrect result, especially for gear with high hardness of the teeth. In this work, the conditions of contact interaction close to the real requirements are studied on the basis of experimental material, numerical solution of the contact problem, determination of the terms of the contact areas of slip, and adhesion within the instantaneous spot. The shape of the instant contact spot has asymmetry and can be approximated by an ellipse with the introduction of a correction factor. The running-in period is of a plastic nature with cold deformation and reduction of the roughness of surfaces. As a result of the run-in period, the area of actual contact (tooth height) is increased by 2 or more times. It is not desirable to spread the area of contact at the area of adhesion that initiates the formation of pitting. The presence of defective surface area on the level of contact strength does not have significant influence, because of the running-in period, but increases the risk of spalling and brittle fracture.
The Effects of Construction Techniques and Geometrical Properties on the Dynamic Behavior of Historic Timber Minarets in Sakarya, Turkey
Authors: Bağbancı M. Bilal , Köprülü Bağbancı Özlem
Published: September 2018

Sakarya City, as the host of many civilizations, has many historic monuments. The city is in the most active earthquake zone in the region. The minarets of mosques are the most important structures because they are slender. Therefore, they are sensitive to lateral loads, and earthquakes and strong winds may cause damage to these structures. The highest number of mosque minarets partly or totally collapsed in the 1999 Kocaeli and Düzce earthquakes that occurred in Turkey. The region is rich in trees, so timber has been used in the construction of different structures in Sakarya City and the vicinity for many years. In this study, five historic timber minarets in Sakarya City were experimentally and computationally examined to determine the effects of the construction techniques and geometrical properties on the dynamic behavior of the minarets. Ambient vibration tests of timber minarets were performed, and the construction techniques and geometrical features were examined; the results of these are discussed below. It was determined that the outer wall construction technique, body height, slenderness, and cross‐sectional area play important roles in the dynamic behavior of timber minarets. Finally, an empirical formula was derived from the relationships for rapid estimation of the fundamental period of timber minarets.
Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Søegaard Signe Holst , Rostgaard Klaus , Skogstrand Kristin , Wiemels Joseph Leo , Schmiegelow Kjeld , Hjalgrim Henrik
Published: September 2018

It has been proposed that children with acute lymphoblastic leukemia (ALL) are born with a dysregulated immune function that together with postnatal environmental exposures causes childhood ALL. Despite its importance for the understanding of ALL etiology, this hypothesis has been inadequately explored. In a population-based case–control study, we measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with Danish nationwide registers, we also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL. Children who developed B-cell precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6 receptor (sIL6R) α, TGFβ1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared with matched controls. Concentrations of IL10 were below the detection level for both patients and controls. Birth order (IL18 and CRP), gestational age (sIL6Rα, TGFβ1, and CRP), and sex (sIL6Rα, IL8, and CRP), but not maternal age, infections during pregnancy, birth weight nor mode of delivery were significantly associated with the neonatal concentrations of inflammatory markers. Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function.

Significance: Children who develop acute lymphoblastic leukemia are immunologically distinct at birth and could potentially react abnormally to infections in early childhood. Cancer Res; 78(18); 5458–63. ©2018 AACR.
An Interleukin-1 Signature in Breast Cancer Treated with Interleukin-1 Receptor Blockade: Implications for Treating Cytokine Release Syndrome of Checkpoint Inhibitors
Authors: Dinarello Charles Anthony
Published: September 2018

In this issue of Cancer Research, Wu and colleagues show that IL1b orchestrates tumor-promoting inflammation in breast cancer and can be targeted in patients using an IL1 receptor antagonist. Cancer Res; 78(18); 5200–2. ©2018 AACR.

See related article by Wu et al., p. 5243
Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids
Authors: Hill Sarah J. , Decker Brennan , Roberts Emma A. , Horowitz Neil S. , Muto Michael G. , Worley Michael J. , Feltmate Colleen M. , Nucci Marisa R. , Swisher Elizabeth M. , Nguyen Huy , Yang Chunyu , Morizane Ryuji , Kochupurakkal Bose S. , Do Khanh T. , Konstantinopoulos Panagiotis A. , Liu Joyce F. , Bonventre Joseph V. , Matulonis Ursula A. , Shapiro Geoffrey I. , Berkowitz Ross S. , Crum Christopher P. , D'Andrea Alan D.
Published: September 2018

Based on genomic analysis, 50% of high-grade serous ovarian cancers (HGSC) are predicted to have DNA repair defects. Whether this substantial subset of HGSCs actually have functional repair defects remains unknown. Here, we devise a platform for functional profiling of DNA repair in short-term patient-derived HGSC organoids. We tested 33 organoid cultures derived from 22 patients with HGSC for defects in homologous recombination (HR) and replication fork protection. Regardless of DNA repair gene mutational status, a functional defect in HR in the organoids correlated with PARP inhibitor sensitivity. A functional defect in replication fork protection correlated with carboplatin and CHK1 and ATR inhibitor sensitivity. Our results indicate that a combination of genomic analysis and functional testing of organoids allows for the identification of targetable DNA damage repair defects. Larger numbers of patient-derived organoids must be analyzed to determine whether these assays can reproducibly predict patient response in the clinic.

Significance: Patient-derived ovarian tumor organoids grow rapidly and match the tumors from which they are derived, both genetically and functionally. These organoids can be used for DNA repair profiling and therapeutic sensitivity testing and provide a rapid means of assessing targetable defects in the parent tumor, offering more suitable treatment options. Cancer Discov; 8(11); 1404–21. ©2018 AACR.

This article is highlighted in the In This Issue feature, p. 1333
Malignant Eyelid Tumors in India: A Study of 536 Asian Indian Patients
Authors: Kaliki Swathi , Bothra Nandini , Bejjanki Kavya Madhuri  , Nayak Arpita , Ramappa George , Mohamed Ashik , Dave Tarjani Vivek , Ali Mohammad Javed , Naik Milind N.
Published: September 2018

Purpose: To study the proportion of eyelid malignant tumors in an Asian Indian population and to review their clinical features and outcomes. Methods: This is a retrospective study of 536 patients. Results: The mean age at presentation with eyelid malignancy was 58 years. Histopathology-proven diagnoses of these patients included sebaceous gland carcinoma (SGC) (n = 285, 53%), basal cell carcinoma (BCC) (n = 128, 24%), squamous cell carcinoma (SCC) (n = 99, 18%), and miscellaneous tumors (n = 24, 4%). The statistically significant differences between eyelid malignant tumors included age at presentation, tumor location, and tumor extent. The clinicopathological correlation of SGC, BCC, SCC, and miscellaneous tumors was 91, 86, 46, and 38% (p = 0.001), respectively. Comparing SGC with BCC, SCC, and miscellaneous tumors, SGC was more commonly associated with tumor recurrence (21 vs. 3, 8, and 13%; p = 0.001), systemic metastasis (13 vs. 0, 4, and 13%; p = 0.001), and death (9 vs. 0, 4, and 0%; p = 0.004). Compared to SGC, BCC, and SCC, locoregional lymph node metastasis was more common with miscellaneous tumors (26 vs. 16, < 1, and 8%; p = 0.001) over a mean follow-up period of 19 months. Conclusion: In Asian Indians, SGC is twice as common as BCC and 3 times more common than SCC. SGC is associated with poorer prognosis compared to other eyelid malignant tumors.
Prognostic Significance of the Neutrophil/Lymphocyte Ratio in Patients with Non-Human Papilloma Virus-Related Oropharyngeal Cancer: A Retrospective Cohort Study
Authors: De Felice Francesca , Tombolini Mario , Abate Gessica , Salerno Francesca , Bulzonetti Nadia , Tombolini Vincenzo , Musio Daniela
Published: September 2018

Purpose: To investigate the effects of the pretreatment neutrophil-to-lymphocyte ratio (N/L) on non-human papilloma virus (HPV)-related oropharyngeal cancer. Materials and Methods: N/L was calculated by dividing the neutrophil count by the lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of N/L and other clinical factors on survival outcomes. High/low N/L groups were defined as > 4.7 and ≤4.7, respectively. Results: Data of 57 consecutive patients with non-HPV-related oropharyngeal cancer were analyzed. The 3-year disease-free survival was 79 versus 36.9% in favor of the low N/L group (p = 0.04). The 5-year overall survival was 71.6 versus 53.3% in the low N/L and high N/L group, respectively (p = 0.07). Conclusion: N/L could play an important role in non-HPV-related oropharyngeal cancer progression and indicate prognosis.
Total Flavonoids from Leaves of Carya Cathayensis Ameliorate Renal Fibrosis via the miR-21/Smad7 Signaling Pathway
Authors: Wu Xiaoli , Ding Xiaoqiang , Ding Zhishan , Jia Ping 
Published: September 2018

Background/Aims: Renal tubulointerstitial fibrosis is the most common pathway of progressive kidney injury, leading to end-stage renal disease. At present, no effective prophylactic treatment method is available. This study investigated the anti-fibrotic effects of total flavonoids (TFs) extracted from leaves of Carya Cathayensis in vivo and in vitro, and explored the underlying mechanisms. Methods: Anti-fibrotic effects of TFs were measured using a mouse model of unilateral ureteral obstruction (UUO) and in transforming growth factor-β1 (TGF-β1)-treated mouse tubular epithelial cells (mTECs). mRNA expression and protein levels of Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also tested by real-time reverse transcription PCR and western blot analysis. To elucidate the underlying mechanisms, expression of miR-21 was examined in mTECs treated with TFs using miR-21 mimics transfected into mTECs before TGF-β1 and TFs treatment. Regulation of mothers against decapentaplegic homolog (Smad) signaling by miR-21 was subsequently validated via overexpression and deletion of miR-21 followed by a luciferase assay. Results: TFs treatment attenuated renal fibrosis, and inhibited expression of collagens and α-SMA in the kidneys of mice subjected to UUO. In vitro, the TFs significantly decreased expression of fibrotic markers in TGF-β1-treated mTECs. Moreover, TFs reduced miR-21 expression in a time- and dose-dependent manner in mTECs, increased expression of Smad7, and decreased phosphorylation of Smad3. Treatment with miR-21 mimics abolished the anti-fibrotic effects of the TFs on the TGF-β1-treated mTECs. In addition, genetic deletion of miR-21 upregulated expression of Smad7 and suppressed phosphorylation of Smad3, attenuating renal fibrosis in mice. Bioinformatics predictions revealed the potential binding site of miR-21 in the 3′-untranslated region of Smad7, and this was further confirmed by the luciferase assay. Conclusion: TFs ameliorate renal fibrosis via a miR-21/Smad7 signaling pathway, indicating a potential therapy for the prevention of renal fibrosis.
As várias maneiras filosóficas de recorrer ao senso comum nas Luzes britânicas
Authors: Jaffro Laurent
Published: September 2018

O artigo analisa os usos e figuras do senso comum na filosofia britânica do século XVIII, de Shaftesbury a Reid. Essa noção, longe de exprimir uma recusa da filosofia, serve para definir o estatuto dos argumentos e conceitos que compõem o discurso filosófico.
Notas sobre o método crítico de Gilda de Mello e Souza
Authors: Arantes Otília Beatriz Fiori
Published: September 2018

Aliando a própria experiência perceptiva à arqueologia visual dos mestres da escola de Warburg, à prática indiciária dos connaisseurs e, principalmente, do mais conhecido deles, o médico italiano do século XIX, Giovanni Morelli - junto com um pouco de psicanálise e a técnica dos romances policiais -, Gilda de Mello e Souxa desenvolveu um "método" crítico inteiramente livre e original, que rendeu enormes frutos. Entre outras tantas coisas, foi ela a primeira a compreender o "caipirismo imanente" ou, mais exatamente, "a verdade dos gestos da nossa gente".
Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association
Authors: Johnson Rachel K. , Lichtenstein Alice H. , Anderson Cheryl A.M. , Carson Jo Ann , Després Jean-Pierre , Hu Frank B. , Kris-Etherton Penny M. , Otten Jennifer J. , Towfighi Amytis , Wylie-Rosett Judith ,   On behalf of the American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Quality of Care and Outcomes Research; and Stroke Council
Published: September 2018

In the United States, 32% of beverages consumed by adults and 19% of beverages consumed by children in 2007 to 2010 contained low-calorie sweeteners (LCSs). Among all foods and beverages containing LCSs, beverages represent the largest proportion of LCS consumption worldwide. The term LCS includes the 6 high-intensity sweeteners currently approved by the US Food and Drug Administration and 2 additional high-intensity sweeteners for which the US Food and Drug Administration has issued no objection letters. Because of a lack of data on specific LCSs, this advisory does not distinguish among these LCSs. Furthermore, the advisory does not address foods sweetened with LCSs. This advisory reviews evidence from observational studies and clinical trials assessing the cardiometabolic outcomes of LCS beverages. It summarizes the positions of government agencies and other health organizations on LCS beverages and identifies research needs on the effects of LCS beverages on energy balance and cardiometabolic health. The use of LCS beverages may be an effective strategy to help control energy intake and promote weight loss. Nonetheless, there is a dearth of evidence on the potential adverse effects of LCS beverages relative to potential benefits. On the basis of the available evidence, the writing group concluded that, at this time, it is prudent to advise against prolonged consumption of LCS beverages by children. (Although water is the optimal beverage choice, children with diabetes mellitus who consume a balanced diet and closely monitor their blood glucose may be able to prevent excessive glucose excursions by substituting LCS beverages for sugar-sweetened beverages [SSBs] when needed.) For adults who are habitually high consumers of SSBs, the writing group concluded that LCS beverages may be a useful replacement strategy to reduce intake of SSBs. This approach may be particularly helpful for persons who are habituated to a sweet-tasting beverage and for whom water, at least initially, is an undesirable option. Encouragingly, self-reported consumption of both SSBs and LCS beverages has been declining in the United States, suggesting that it is feasible to reduce SSB intake without necessarily substituting LCS beverages for SSBs. Thus, the use of other alternatives to SSBs, with a focus on water (plain, carbonated, and unsweetened flavored), should be encouraged.
Efficacy of Endocardial Ablation of Drug-Resistant Ventricular Fibrillation in Brugada Syndrome
Authors: Talib Ahmed Karim , Takagi Masahiko , Shimane Akira , Nakano Makoto , Hayashi Tatsuya , Okajima Katsunori , Kentaro Minami , Fukada Koji , Kowase Shinya , Kurosaki Kenji , Nitta Junichi , Nishizaki Mitsushiro , Yui Yoshiaki , Talib Ali , Sato Nobuyuki , Kawamura Yuichiro , Hasebe Naoyuki , Aita Satoshi , Sai Eikou , Komatsu Yuki , Kuroki Kenji , Kaneshiro Takashi , Dongzu Xu , Tajiri Kazuko , Igarashi Miyako , Yamasaki Hiro , Murakoshi Nobuyuki , Kumagai Koji , Sekiguchi Yukio , Nogami Akihiko , Aonuma Kazutaka
Published: September 2018

Background

Both endocardial trigger elimination and epicardial substrate modification are effective in treating ventricular fibrillation (VF) in Brugada syndrome. However, the primary approach and the characteristics of patients who respond to endocardial ablation remain unknown.

Methods

Among 123 symptomatic Brugada syndrome patients (VF, 63%; syncope, 37%), ablation was performed in 21 VF/electrical storm patients, the majority of whom were resistant to antiarrhythmic drugs.

Results

Careful endocardial mapping revealed that 81% of the patients had no specific findings, whereas 19% of the patients, who experienced the most frequent VF episodes with notching of the QRS in lead V
1
, had delayed low-voltage fractionated endocardial electrograms. Ablation of VF triggers followed by endocardial substrate modification was performed in the right ventricular outflow tract in 85% of the cases and in the right ventricle in 15%. VF triggers could not be completely eliminated in 1 patient and VF became noninducible in 14 (88%) patients among 16 patients who underwent VF induction with normalization of Brugada-type ECG in 3. During follow-up (56.14±36.95 months), VF recurrence was observed in 7 patients. Importantly, all patients who had nothing of QRS in lead V
1
did not respond to endocardial ablation despite presence of VF-triggering ectopic beats during ablation.

Conclusions

With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome, whereas presence of QRS notching in lead V
1
was associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach.
Outcome of Cardiac Sarcoidosis Presenting With High-Grade Atrioventricular Block
Authors: Nordenswan Hanna-Kaisa , Lehtonen Jukka , Ekström Kaj , Kandolin Riina , Simonen Piia , Mäyränpää Mikko , Vihinen Tapani , Miettinen Heikki , Kaikkonen Kari , Haataja Petri , Kerola Tuomas , Rissanen Tuomas T. , Kokkonen Jorma , Alatalo Aleksi , Pietilä-Effati Päivi , Utriainen Seppo , Kupari Markku
Published: September 2018

Background:

Symptomatic high-grade atrioventricular block (AVB) is the most common and often the only presenting manifestation (lone AVB) of cardiac sarcoidosis. Implantation of an intracardiac cardioverter defibrillator instead of a pacemaker is recommended, but the true risk of fatal arrhythmia, one incident to lone AVB in particular, remains poorly known.

Methods:

We used Myocardial Inflammatory Diseases in Finland Study Group Registry to analyze the presentations, left ventricular (LV) function, pacemaker therapy, and ventricular arrhythmias in cardiac sarcoidosis. From year 1988 to 2015, altogether 325 cases of cardiac sarcoidosis were diagnosed in Finland. Of them, 143 patients (112 women, mean age 52 years) presented with Mobitz II second degree or third degree AVB in the absence of other explanatory cardiac disease.

Results:

Concomitant with AVB at presentation, 20 patients had either ventricular tachycardia or severe LV dysfunction with ejection fraction <35% and 29 patients had nonsevere LV dysfunction (ejection fraction, 35%–50%) while 90 patients presented with AVB alone. During a median of 2.8 years’ follow-up, 23 sudden cardiac deaths (fatal or aborted) and 19 ventricular tachycardias were recorded as arrhythmic end point events. Their composite 5-year incidence (95% confidence interval) was 56% (36%–88%) in the AVB subgroup with ventricular tachycardia or severe LV dysfunction versus 24% (12%–49%) in the subgroup with nonsevere LV dysfunction and 24% (15%–38%) with lone AVB (
P
=0.019). The 5-year incidence of sudden cardiac death was 34% (16%–71%), 14% (6%–35%), and 9% (4%–22%) in the respective subgroups (
P
=0.060).

Conclusions:

The risk of sudden cardiac death is significant in cardiac sarcoidosis presenting with high-grade AVB with or without ventricular tachycardia or LV dysfunction. The consensus recommendation to implant an intracardiac cardioverter defibrillator whenever permanent pacing is needed seems well-founded.
Home-Delivered Meals Postdischarge From Heart Failure Hospitalization
Authors: Hummel Scott L. , Karmally Wahida , Gillespie Brenda W. , Helmke Stephen , Teruya Sergio , Wells Joanna , Trumble Erika , Jimenez Omar , Marolt Cara , Wessler Jeffrey D. , Cornellier Maria L. , Maurer Mathew S.
Published: September 2018

Background

In patients with heart failure (HF), malnutrition and dietary sodium excess are common and may worsen outcomes. No prior studies have provided low-sodium, nutritionally complete meals following HF hospitalization.

Methods and Results

The GOURMET-HF study (Geriatric Out-of-Hospital Randomized Meal Trial in Heart Failure) randomized patients discharged from HF hospitalization to 4 weeks of home-delivered sodium-restricted Dietary Approaches to Stop Hypertension meals (DASH/SRD; 1500 mg sodium/d) versus usual care. The primary outcome was the between-group change in the Kansas City Cardiomyopathy Questionnaire summary score from discharge to 4 weeks postdischarge. Additional outcomes included changes in the Kansas City Cardiomyopathy Questionnaire clinical summary score and cardiac biomarkers. All patients were followed 12 weeks for death/all-cause readmission and potential diet-related adverse events (symptomatic hypotension, hyperkalemia, acute kidney injury). Sixty-six patients were randomized 1:1 at discharge to DASH/SRD versus usual care (age, 71±8 years; 30% female; ejection fraction, 39±18%). The Kansas City Cardiomyopathy Questionnaire summary score increased similarly between groups (DASH/SRD 46±23–59±20 versus usual care 43±19–53±24;
P
=0.38), but the Kansas City Cardiomyopathy Questionnaire clinical summary score increase tended to be greater in DASH/SRD participants (47±22–65±19 versus 45±20–55±26;
P
=0.053). Potentially diet-related adverse events were uncommon; 30-day HF readmissions (11% versus 27%;
P
=0.06) and days rehospitalized within that timeframe (17 versus 55;
P
=0.055) trended lower in DASH/SRD participants.

Conclusions

Home-delivered DASH/SRD after HF hospitalization appeared safe in selected patients and had directionally favorable effects on HF clinical status and 30-day readmissions. Larger studies are warranted to clarify the effects of postdischarge nutritional support in patients with HF.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02148679.
Chronotropic Incompetence in Chronic Heart Failure
Authors: Zweerink Alwin , van der Lingen Anne-Lotte C.J. , Handoko M. Louis , van Rossum Albert C. , Allaart Cornelis P.
Published: September 2018

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.
Impact of Epicardial Adipose Tissue, Left Ventricular Myocardial Fat Content, and Interstitial Fibrosis on Myocardial Contractile Function
Authors: Ng Arnold C.T. , Strudwick Mark , van der Geest Rob J. , Ng Austin C.C. , Gillinder Lisa , Goo Shi Yi , Cowin Gary , Delgado Victoria , Wang William Y.S. , Bax Jeroen J.
Published: September 2018

Background

Current understanding of metabolic heart disease consists of a myriad of different pathophysiological mechanisms. Epicardial adipose tissue (EAT) is increasingly recognized as metabolically active and associated with adverse cardiovascular outcomes. The present study aimed to investigate the effect of increased EAT volume index on left ventricular (LV) myocardial fat content and burden of interstitial myocardial fibrosis and their subsequent effects on LV myocardial contractile function.

Methods and Results

A total of 40 volunteers (mean age, 35±10 years; 26 males) of varying body mass index (25.0±4.1 kg/m
2
; range, 19.3–36.3 kg/m
2
) and without diabetes mellitus or hypertension were prospectively recruited. EAT volume index, LV myocardial fat content, and extracellular volume were quantified by magnetic resonance imaging. LV myocardial contractile function was quantified by speckle tracking echocardiography global longitudinal strain on the same day as magnetic resonance imaging examination. Mean total EAT volume index, LV myocardial fat content, and extracellular volume were 30.0±19.6 cm
3
/m
2
, 5.06%±1.18%, and 27.5%±0.5%, respectively. On multivariable analyses, increased EAT volume index and insulin resistance were independently associated with both increased LV myocardial fat content content and higher burden of interstitial myocardial fibrosis. Furthermore, increased EAT volume index was independently associated with LV global longitudinal strain.

Conclusions

Increased EAT volume index and insulin resistance were independently associated with increased myocardial fat accumulation and interstitial myocardial fibrosis. Increased EAT volume index was associated with detrimental effects on myocardial contractile function as evidenced by a reduction in LV global longitudinal strain.