bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative and Natural Therapies for Acute Lung Injury and Acute Respiratory Distress Syndrome
Authors: Patel Vipul J. , Biswas Roy Sreeja , Mehta Hiren J. , Joo Myungsoo , Sadikot Ruxana T.
Published: May 2018

Introduction. Acute respiratory distress syndrome (ARDS) is a complex clinical syndrome characterized by acute inflammation, microvascular damage, and increased pulmonary vascular and epithelial permeability, frequently resulting in acute respiratory failure and death. Current best practice for ARDS involves “lung-protective ventilation,” which entails low tidal volumes and limiting the plateau pressures in mechanically ventilated patients. Although considerable progress has been made in understanding the pathogenesis of ARDS, little progress has been made in the development of specific therapies to combat injury and inflammation. Areas Covered. In recent years, several natural products have been studied in experimental models and have been shown to inhibit multiple inflammatory pathways associated with acute lung injury and ARDS at a molecular level. Because of the pleiotropic effects of these agents, many of them also activate antioxidant pathways through nuclear factor erythroid-related factor 2, thereby targeting multiple pathways. Several of these agents are prescribed for treatment of inflammatory conditions in the Asian subcontinent and have shown to be relatively safe. Expert Commentary. Here we review natural remedies shown to attenuate lung injury and inflammation in experimental models. Translational human studies in patients with ARDS may facilitate treatment of this devastating disease.
Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury
Authors: Li Haixia , Wang Jingtao , Wang Pengqian , Zhang Yingying , Liu Jun , Yu Yanan , Li Bing , Wang Zhong
Published: May 2018

Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA’s dose-dependent pharmacological mechanism from a system’s perspective. The top 10 enriched pathways in the 2·JA condition were mainly involved in neuroprotection (70% of the pathways), apoptosis and survival (40%), and anti-inflammation (20%), while JA induced pathways were mainly involved in apoptosis and survival (60%), anti-inflammation (20%), and lipid metabolism (20%). Regarding shared pathways and processes, 3, 1, and 3 pathways overlapped between the Vehicle and JA, Vehicle and 2·JA, and JA and 2·JA conditions, respectively; for the top ten overlapped processes these numbers were 3, 0, and 4, respectively. The common pathways and processes in the 2·JA condition included differentially expressed genes significantly different from those in JA. Seven representative pathways were only activated by 2·JA, such asGamma-Secretase regulation of neuronal cell development.Process network comparison indicated that significant nodes, such asalpha-MSH,ACTH,PKR1, andWNT, were involved in the pharmacological mechanism of 2·JA. Function distribution was different between JA and 2·JA groups, indicating a dosage additive mechanism in cerebral ischemia treatment. Such systemic approach based on whole-genome multiple pathways and networks may provide an effective and alternative approach to identify alterations underlining dosage-dependent therapeutic benefits of pharmacological compounds on complex disease processes.
The Impact of Quality of Life on the Health of Older People from a Multidimensional Perspective
Authors: Rondón García Luis Miguel , Ramírez Navarrro Jose Manuel
Published: May 2018

Background. This research analyzes the impact of quality of life as a metavariable that conditions the health and social welfare of the elderly. The sample of this study is composed of 500 people, randomly selected from the major day centers for the elderly in the province of Granada (Spain).Method. For the inferential analysis, we used the CUBRECAVI questionnaire, which is a multidimensional scale of health and quality of life, along with the Katz and García measure questionnaires, which are also applied to quality of life. Through the technique of the interview, we have distributed the participants into two groups: experimental and control.Results and Conclusions. Once the tests have been completed, we have concluded from the meta-analysis and validation tests that the participants have a good perception of their quality of life, considering health, leisure, environmental quality, functional capacity, level of satisfaction, social support, social networks, and positive social interactions as the determinants of their well-being, although social contact reduces as the age advances. We conclude that multidimensional evaluation is an effective tool to evaluate the quality of life and the objective and subjective health of the elderly. These variables can be related to the improvement of health and well-being.
Sociodemographic Characteristics and Health Profile of the Elderly Seeking Health Care in Kampala, Uganda
Authors: Nawagi Faith , Söderberg Martin , Berggren Vanja , Midlöv Patrik , Ajambo Aidah , Nakasujja Noeline
Published: May 2018

Aging entails health challenges globally, but pertinent data from low-income countries like Uganda remains scarce. A cross-sectional study was carried out at Mulago National Referral Hospital in Kampala, among 134 patients (38% men and 62% women) aged ≥60 years. Data was collected on sociodemographic characteristics, medical disorders, cognitive function, hearing handicap, and functional status, that is, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL). The participants had high independency in BADL (89%) and IADL (75%). The most common medical conditions were bone/joint pain (35%), hypertension (24%), and visual problems (20%). More women (54%) than men (37%) reported bone and joint pain. The majority (80%) of the participants did not report any hearing handicap, and half (54%) did not have any cognitive impairment. Dependency in IADL was associated with advanced age, being female, and being financially dependent, and the risk of having a hearing handicap was higher among those above the median age (68 years). In adjusted models, the effects remained similar although statistical significance was only achieved for advanced age versus dependency in IADL (RR: 2.38, 95% CI: 1.12–5.08) and hearing handicap (RR: 2.67, 95% CI: 1.17–6.12). Thus, socioeconomic status and gender are relevant aspects when attempting to understand the health profile of the elderly in Kampala, Uganda.
Superposition Coded Modulation Based Faster‐Than‐Nyquist Signaling
Authors: Li Shuangyang , Bai Baoming , Zhou Jing , He Qingli , Li Qian
Published: May 2018

A structure of faster‐than‐Nyquist (FTN) signaling combined with superposition coded modulation (SCM) is considered. The so‐called FTN‐SCM structure is able to achieve the constrained capacity of FTN signaling and only requires a low detection complexity. By deriving a new observation model suitable for FTN‐SCM, we offer the power allocation based on a proper detection method. Simulation results show that, at any given spectral efficiency, the bit error rate (BER) curve of FTN‐SCM lies clearly outside the minimum signal‐to‐noise ratio (SNR) boundary of orthogonal signaling with a larger alphabet. The achieved data rates are also close to the maximum data rates of the certain shaping pulse.
The Influence of the Crown-Implant Ratio on the Crestal Bone Level and Implant Secondary Stability: 36-Month Clinical Study
Authors: Hadzik Jakub , Krawiec Maciej , Sławecki Konstanty , Kunert-Keil Christiane , Dominiak Marzena , Gedrange Tomasz
Published: May 2018

Introduction. When the era of dental implantology began, the pioneers defined some gold standards used in dental prosthetics treatment for implant-supported restorations. Referring to traditional prosthetics, it was taken for granted that the length of an implant placed in the alveolar bone (the equivalent of the root) should exceed the length of the superstructure. Aim of the Study. The aim of the study was to determine whether implant length and the crown-to-implant (C/I) ratio influence implant stability and the loss of the surrounding marginal bone and whether short implants can be used instead of sinus augmentation procedures. Material and Methods. The patients participating in the study (n=30) had one single tooth implant, a short (OsseoSpeed™ L6 Ø4 mm, Implants) or a regular implant (OsseoSpeed L11 and L13 Ø4 mm, DENTSPLY Implants), placed in the maxilla. The evaluation was based on clinical and radiological examination. The crown-to-implant ratio was determined by dividing the length of the crown together with the abutment by the length of the implant placed crestally. Mean crown-to-implant ratios were calculated separately for each group and its correlation with the MBL (marginal bone loss) and stability was assessed. The authors compared the correlation between the C/I ratio values, MBL, and secondary implant stability. Results. Positive results in terms of primary and secondary stability were achieved with both (short and conventional) implants. The MBL was low for short and conventional implants being 0.34±0.24 mm and 0.22±0.46 mm, respectively. No significant correlation was found between the C/I ratio and secondary stability as well as the C/I ratio and the marginal bone loss. Conclusions. Short implants can be successfully used to support single crowns. The study has revealed no significant differences in the clinical performance of prosthetic restorations supported by short implants. Clinical trial registration number is NCT03471000.
Design and Profit Allocation in Two-Echelon Heterogeneous Cooperative Logistics Network Optimization
Authors: Wang Yong , Yuan Yingying , Assogba Kevin , Gong Ke , Wang Haizhong , Xu Maozeng , Wang Yinhai
Published: May 2018

In modern supply chain, logistics companies usually operate individually and optimization researches often concentrate on solving problems related to separate networks. Consequences like the complexity of urban transportation networks and long distance deliveries or pickups and pollution are leading problems to more expenses and more complaints from environment protection organizations. A solution approach to these issues is proposed in this article and consists in the adoption of two-echelon heterogeneous cooperative logistics networks (THCLN). The optimization methodology includes the formation of cooperative coalitions, the reallocation of customers to appropriate logistics facilities, and the determination of the best profit allocation scheme. First, a mixed integer linear programing model is introduced to minimize the total operating cost of nonempty coalitions. Thus, the Genetic Algorithm (GA) and the Particle Swarm Optimization (PSO) algorithm are hybridized to propose GA-PSO heuristics. GA-PSO is employed to provide good solutions to customer clustering units’ reallocation problem. In addition, a negotiation process is established based on logistics centers as coordinators. The case study of Chongqing city is conducted to verify the feasibility of THCLN in practice. The grand coalition and two heterogeneous subcoalitions are designed, and the collective profit is distributed based on cooperative game theory. The Minimum Cost Remaining Savings (MCRS) model is used to determine good allocation schemes and strictly monotonic path principles are considered to evaluate and decide the most appropriate coalition sequence. Comparisons proved the combination of GA-PSO and MCRS better as results are found closest to the core center. Therefore, the proposed approach can be implemented in real world environment, increase the reliability of urban logistics network, and allow decision makers to improve service efficiency.
Association of Poor Social Support and Financial Insecurity with Psychological Distress of Chronic Kidney Disease Patients Attending National Nephrology Unit in Sri Lanka
Authors: Hettiarachchi Ramya , Abeysena Chrishantha
Published: May 2018

Background. Chronic kidney disease (CKD) is associated with high morbidity and mortality. Hence, CKD patients are often in chronic psychological distress. The objective of the study was to describe factors associated with psychological distress of CKD patients attending National Nephrology Unit. Methods. A descriptive cross-sectional study was conducted among 382 CKD patients above 18 years of age applying systematic sampling. The data was collected using self-administered questionnaires to assess the psychological distress (GHQ-12), social support (SSQ6), coping strategies (BRIEFCOPE), pain (0 to 10 numeric pain rating scale), and physical role limitation due to ill health (SF36QOL). Sociodemographic and disease-related data were collected using an interviewer administered questionnaire and a data extraction sheet. Multiple logistic regression was applied for determining the associated factors. The results were expressed as adjusted odds ratio (AOR) and 95% confidence intervals (95% CI). Results. Percentage of psychological distress was 55.2% (95% CI: 48.4% to 62%). Poor social support (AOR = 1.81, 95% CI: 1.14–2.88), low satisfaction with the social support received (AOR = 4.14, 95% CI: 1.59–10.78), stages IV and V of CKD (AOR = 2.67, 95% CI: 1.65–4.20), presence of comorbidities (AOR = 2.38, 95% CI: 1.21–4.67), within one year of diagnosis (AOR = 2.23, 95% CI: 1.36–3.67), low monthly income (AOR = 2.26, CI: 1.26–4.06), higher out-of-pocket expenditure per month (AOR = 1.75, 95% CI: 1.75–1.99), and being a female (AOR = 2.95, 95% CI: 1.79–4.9) were significantly associated with psychological distress. Conclusions. More than half of the CKD patients were psychologically distressed. Factors such as financial and social support will be worth considering early because of their modifiability.
Adaptive Diffeomorphic Multiresolution Demons and Their Application to Same Modality Medical Image Registration with Large Deformation
Authors: Wang Chang , Ren Qiongqiong , Qin Xin , Yu Yi
Published: May 2018

Diffeomorphic demons can guarantee smooth and reversible deformation and avoid unreasonable deformation. However, the number of iterations needs to be set manually, and this greatly influences the registration result. In order to solve this problem, we proposed adaptive diffeomorphic multiresolution demons in this paper. We used an optimized framework with nonrigid registration and diffeomorphism strategy, designed a similarity energy function based on grey value, and stopped iterations adaptively. This method was tested by synthetic image and same modality medical image. Large deformation was simulated by rotational distortion and extrusion transform, medical image registration with large deformation was performed, and quantitative analyses were conducted using the registration evaluation indexes, and the influence of different driving forces and parameters on the registration result was analyzed. The registration results of same modality medical images were compared with those obtained using active demons, additive demons, and diffeomorphic demons. Quantitative analyses showed that the proposed method’s normalized cross-correlation coefficient and structural similarity were the highest and mean square error was the lowest. Medical image registration with large deformation could be performed successfully; evaluation indexes remained stable with an increase in deformation strength. The proposed method is effective and robust, and it can be applied to nonrigid registration of same modality medical images with large deformation.
A Rare Case of Erdheim-Chester Disease (Non-Langerhans Cell Histiocytosis) with Concurrent Langerhans Cell Histiocytosis: A Diagnostic and Therapeutic Challenge
Authors: Hashmi Hamza , Murray Drew , Greenwell John , Shaikh Marwan , Basu Soumit , Krem Maxwell
Published: May 2018

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocyte disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD can be difficult to diagnose since it is a very rare disease that can affect many organ systems. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Patients who have the BRAF V600E mutation are treated first line with vemurafenib. For those without the mutation with symptomatic ECD, conventional or PEGylated interferon alpha is recommended. For patients who are either intolerant or nonresponsive to interferon alpha, systemic chemotherapy with or without corticosteroids can be used. We present a rare case of Erdheim-Chester disease with concurrent Langerhans cell histiocytosis which occurs in only one fifth of the cases and often presents as a diagnostic and therapeutic challenge.
Research on Aerodynamic Characteristics of Straight-Bladed Vertical Axis Wind Turbine with S Series Airfoils
Authors: Feng Fang , Zhao Shouyang , Qu Chunming , Bai Yuedi , Zhang Yuliang , Li Yan
Published: May 2018

Background. In order to investigate the effect of aerodynamic characteristics of S series airfoils on the straight-bladed vertical axis wind turbine (SB-VAWT), numerical simulations and wind tunnel experiments were carried out using a small SB-VAWT model with three kinds of blade airfoils, which are asymmetric airfoil S809, symmetric airfoil S1046, and NACA0018 used for performance comparison among S series. The aerodynamics characteristics researched in this study included static torque coefficient, out power coefficient, and rotational speed performance. The flow fields of these three kinds of blade under static and dynamic conditions were also simulated and analyzed to explain the mechanism effect of aerodynamic performance. According to the results, the SB-VAWT with airfoil S1046 has better dynamic aerodynamic characteristics than other two airfoils, while the SB-VAWT with airfoil S809 is better in terms of the static characteristics. As the most suitable airfoil for SB-VAWT, the S series airfoil is worth researching deeply.
Mass and Heat Transport Models for Analysis of the Drying Process in Porous Media: A Review and Numerical Implementation
Authors: Vu Hong Thai , Tsotsas Evangelos
Published: May 2018

The modeling and numerical simulation of drying in porous media is discussed in this work by revisiting the different models of moisture migration during the drying process of porous media as well as their restrictions and applications. Among the models and theories, we consider those are ranging from simple ones like the diffusion theory to more complex ones like the receding front theory, the model of Philip and de Vries, Luikov’s theory, Krischer’s theory, and finally Whitaker’s model, in which all mass, heat transport, and phase change (evaporation) are taken into account. The review of drying models as such serves as the basis for the development of a framework for numerical simulation. In order to demonstrate this, the system of equations governing the drying process in porous media resulting from Whitaker’s model is presented and used in our numerical implementation. A numerical simulation of drying is presented and discussed to show the capability of the implementation.
Mathematical Modeling Predicts Response to Chemotherapy and Drug Combinations in Ovarian Cancer
Authors: Kozłowska Emilia , Färkkilä Anniina , Vallius Tuulia , Carpén Olli , Kemppainen Jukka , Grénman Seija , Lehtonen Rainer , Hynninen Johanna , Hietanen Sakari , Hautaniemi Sampsa
Published: May 2018

Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of patients with cancer. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and posttreatment clinical data, including 18F-FDG-PET/CT images, to reliably estimate the model parameters and simulate “virtual patients with HGSOC.” Treatment responses of the virtual patients generated by our mathematical model were indistinguishable from real-life patients with HGSOC. We demonstrated the utility of our approach by evaluating the survival benefit of combination therapies that contain up to six drugs targeting platinum resistance mechanisms. Several resistance mechanisms were already active at diagnosis, but combining SOC with a drug that targets the most dominant resistance subpopulation resulted in a significant survival benefit. This work provides a theoretical basis for a cancer treatment paradigm in which maximizing platinum's killing effect on cancer cells requires overcoming resistance mechanisms with targeted drugs. This freely available mathematical model and simulation framework enable rapid and rigorous evaluation of the benefit of a targeted drug or combination therapy in virtual patients before clinical trials, which facilitates translating preclinical findings into clinical practice.

Significance: These findings present a comprehensive mathematical model for platinum resistance and standard-of-care therapy in a solid cancer, allowing virtual evaluation of novel therapy regimens. Cancer Res; 78(14); 4036–44. ©2018 AACR.
Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells
Authors: Liu Shengzhi , Fan Yao , Chen Andy , Jalali Aydin , Minami Kazumasa , Ogawa Kazuhiko , Nakshatri Harikrishna , Li Bai-Yan , Yokota Hiroki
Published: May 2018

While bone is a frequent target of breast cancer–associated metastasis, little is known about the effects of tumor–bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, fluphenazine and trifluoperazine, on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1). Three-dimensional spheroid formation assays revealed that tumor cells have high affinity to osteocytes and type I collagen, and interactions with osteocytes as well as administration of fluphenazine and trifluoperazine downregulated Snail and suppressed migratory behaviors. Unlike the inhibitory action of fluphenazine and trifluoperazine on tumor growth, tumor–osteocyte interactions stimulated tumor proliferation by upregulating NFκB and Akt. In the bone microenvironment, osteocytes downregulated Snail and acted as an attractant as well as a stimulant to mammary tumor cells. These results demonstrate that tumor–osteocyte interactions strengthen dopamine receptor–mediated suppression of tumor migration but weaken its inhibition of tumor proliferation in the osteocyte-rich bone microenvironment.

Significance: These findings provide novel insight into the cellular cross-talk in the bone microevironment and the effects of dopamine modulators on mammary tumor cells and osteocytes. Cancer Res; 78(14); 3865–76. ©2018 AACR.
Chemopreventive Efficacy of the Cyclooxygenase-2 (Cox-2) Inhibitor, Celecoxib, Is Predicted by Adenoma Expression of Cox-2 and 15-PGDH
Authors: Wang Jiping , Cho Nancy L. , Zauber Ann G. , Hsu Meier , Dawson Dawn , Srivastava Amitabh , Mitchell-Richards Kisha A. , Markowitz Sanford D. , Bertagnolli Monica M.
Published: May 2018

Background: The Adenoma Prevention with Celecoxib (APC) Trial showed that cyclooxygenase-2 (Cox-2) inhibitor, celecoxib, decreased adenoma development in patients at high risk for colorectal cancer. A prospectively planned analysis of the APC Trial tested the hypothesis that expression of target enzymes in adenomas removed before beginning study treatment would identify individuals at high risk of adenoma development, and/or predict response to Cox-2 inhibition.

Methods: Pre-treatment adenomas were examined using immunohistochemistry to assess expression of Cox-2 (high vs. low) and 15-prostaglandin dehydrogenase (15-PGDH, presence vs. loss). The Mantel–Cox test evaluated whether these markers predicted benefit from celecoxib for reduction of adenoma detection.

Results: Patients whose pre-treatment adenomas demonstrated elevated Cox-2 achieved the greatest adenoma reduction with celecoxib treatment [RR, 0.37; 95% confidence interval (CI), 0.22–0.61; P = 0.0001]. This reduction was less in the low Cox-2 category (RR, 0.64; 95% CI, 0.56–0.73). Patients whose pre-treatment adenomas showed 15-PGDH loss had a similar treatment-associated reduction in adenoma detection (RR, 0.60; 95% CI, 0.52–0.69; P < 0.0001). In contrast, patients with intact tumor 15-PGDH expression did not significantly benefit from celecoxib (RR, 0.73; 95% CI, 0.47–1.12; P = 0.15). However, subset analysis suggested that this lack of response to celecoxib was confined to those patients with 15-PGDH intact tumors who were also using cardioprotective aspirin.

Conclusions: The expression of Cox-2 and 15-PGDH in pre-treatment adenomas provides predictive information in patients treated with celecoxib for prevention of colorectal adenomas.

Impact: The results of this study show that Cox-2 and 15-PGDH are characteristics of colorectal adenomas that may be used to predict nonsteroidal anti-inflammatory drug chemoprevention efficacy. Cancer Epidemiol Biomarkers Prev; 27(7); 728–36. ©2018 AACR.
Time-to-Event Bayesian Optimal Interval Design to Accelerate Phase I Trials
Authors: Yuan Ying , Lin Ruitao , Li Daniel , Nie Lei , Warren Katherine E.
Published: May 2018

Late-onset toxicity is common for novel molecularly targeted agents and immunotherapy. It causes major logistic difficulty for existing adaptive phase I trial designs, which require the observance of toxicity early enough to apply dose-escalation rules for new patients. The same logistic difficulty arises when the accrual is rapid. We propose the time-to-event Bayesian optimal interval (TITE-BOIN) design to accelerate phase I trials by allowing for real-time dose assignment decisions for new patients while some enrolled patients’ toxicity data are still pending. Similar to the rolling six design, the TITE-BOIN dose-escalation/deescalation rule can be tabulated before the trial begins, making it transparent and simple to implement, but is more flexible in choosing the target dose-limiting toxicity (DLT) rate and has higher accuracy to identify the MTD. Compared with the more complicated model-based time-to-event continuous reassessment method (TITE-CRM), the TITE-BOIN has comparable accuracy to identify the MTD but is simpler to implement with substantially better overdose control. As the TITE-CRM is more aggressive in dose escalation, it is less likely to underdose patients. When there are no pending data, the TITE-BOIN seamlessly reduces to the BOIN design. Numerical studies show that the TITE-BOIN design supports continuous accrual without sacrificing patient safety or the accuracy of identifying the MTD, and therefore has great potential to accelerate early-phase drug development. Clin Cancer Res; 24(20); 4921–30. ©2018 AACR.
Spindle Assembly Disruption and Cancer Cell Apoptosis with a CLTC-Binding Compound
Authors: Bond Michael J. , Bleiler Marina , Harrison Lauren E. , Scocchera Eric W. , Nakanishi Masako , G-Dayanan Narendran , Keshipeddy Santosh , Rosenberg Daniel W. , Wright Dennis L. , Giardina Charles
Published: May 2018

AK3 compounds are mitotic arrest agents that induce high levels of γH2AX during mitosis and apoptosis following release from arrest. We synthesized a potent AK3 derivative, AK306, that induced arrest and apoptosis of the HCT116 colon cancer cell line with an EC50 of approximately 50 nmol/L. AK306 was active on a broad spectrum of cancer cell lines with total growth inhibition values ranging from approximately 25 nmol/L to 25 μmol/L. Using biotin and BODIPY-linked derivatives of AK306, binding to clathrin heavy chain (CLTC/CHC) was observed, a protein with roles in endocytosis and mitosis. AK306 inhibited mitosis and endocytosis, while disrupting CHC cellular localization. Cells arrested in mitosis by AK306 showed the formation of multiple microtubule-organizing centers consisting of pericentrin, γ-tubulin, and Aurora A foci, without apparent centrosome amplification. Cells released from AK306 arrest were unable to form bipolar spindles, unlike nocodazole-released cells that reformed spindles and completed division. Like AK306, CHC siRNA knockdown disrupted spindle formation and activated p53. A short-term (3-day) treatment of tumor-bearing APC-mutant mice with AK306 increased apoptosis in tumors, but not normal mucosa. These findings indicate that targeting the mitotic CHC complex can selectively induce apoptosis and may have therapeutic value.

Implication: Disruption of clathrin with a small-molecule inhibitor, AK306, selectively induces apoptosis in cancer cells by disrupting bipolar spindle formation. Mol Cancer Res; 16(9); 1361–72. ©2018 AACR.
A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma
Authors: Chan Wing Keung , Kang Siwen , Youssef Youssef , Glankler Erin N. , Barrett Emma R. , Carter Alex M. , Ahmed Elshafa H. , Prasad Aman , Chen Luxi , Zhang Jianying , Benson Don M. , Caligiuri Michael A. , Yu Jianhua
Published: May 2018

Multiple myeloma (MM) is an incurable hematologic malignancy of plasma cells, with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single-chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb). Although NKG2D is a potent activation receptor ubiquitously expressed on mostly cytolytic immune cells including NK cells, CD8+ T cells, γδ T cells, and NKT cells, the CS1 tumor-associated antigen on MM represents a promising target. CS1-NKG2D biAb engaged human MM cell lines and NKG2D+ immune cells, forming immune synapses. In effector cells, CS1-NKG2D biAb triggered the phosphorylation of AKT, a downstream protein kinase of the activated NKG2D–DAP10 complex. The EC50 values of CS1-NKG2D biAb for CS1high and for CS1low MM cell lines with effector PBMCs were 10−12 and 10−9 mol/L, respectively. CS1-NKG2D biAb acted through multiple types of immune cells, and this induced cytotoxicity was both CS1- and NKG2D-specific. In vivo, survival was significantly prolonged using CS1-NKG2D biAb in a xenograft NOD-SCIDIL2γc−/− (NSG) mouse model engrafted with both human PBMCs and MM cell lines. Collectively, we demonstrated that the CS1-NKG2D biAb facilitated an enhanced immune synapse between CS1+ MM cells and NKG2D+ cytolytic innate and antigen-specific effector cells, which, in turn, activated these immune cells for improved clearance of MM. Cancer Immunol Res; 6(7); 776–87. ©2018 AACR.
Ultrasound Cyclo-Plasty in Patients with Glaucoma: 1-Year Results from a Multicentre Prospective Study
Authors: Giannaccare Giuseppe , Vagge Aldo , Sebastiani Stefano , Urbini Lara E. , Corazza Paolo , Pellegrini Marco , Carmassi Luciana , Bergamini Fulvio , Traverso Carlo E. , Campos Emilio C.
Published: May 2018

Purpose: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma. Methods: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications. Results: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%). Conclusions: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety.
Neuroimaging Characteristics of Small-Vessel Disease in Older Adults with Normal Cognition, Mild Cognitive Impairment, and Alzheimer Disease
Authors: Mimenza-Alvarado Alberto , Aguilar-Navarro Sara G. , Yeverino-Castro Sara , Mendoza-Franco César , Ávila-Funes José Alberto , Román Gustavo C.
Published: May 2018

Introduction: Cerebral small-vessel disease (SVD) represents the most frequent type of vascular brain lesions, often coexisting with Alzheimer disease (AD). By quantifying white matter hyperintensities (WMH) and hippocampal and parietal atrophy, we aimed to describe the prevalence and severity of SVD among older adults with normal cognition (NC), mild cognitive impairment (MCI), and probable AD and to describe associated risk factors. Methods: This study included 105 older adults evaluated with magnetic resonance imaging and clinical and neuropsychological tests. We used the Fazekas scale (FS) for quantification of WMH, the Scheltens scale (SS) for hippocampal atrophy, and the Koedam scale (KS) for parietal atrophy. Logistic regression models were performed to determine the association between FS, SS, and KS scores and the presence of NC, MCI, or probable AD. Results: Compared to NC subjects, SVD was more prevalent in MCI and probable AD subjects. After adjusting for confounding factors, logistic regression showed a positive association between higher scores on the FS and probable AD (OR = 7.6, 95% CI 2.7–20, p < 0.001). With the use of the SS and KS (OR = 4.5, 95% CI 3.5–58, p = 0.003 and OR = 8.9, 95% CI 1–72, p = 0.04, respectively), the risk also remained significant for probable AD. Conclusions: These results suggest an association between severity of vascular brain lesions and neurodegeneration.
The Brief Sexual Symptom Checklist as a Screening Tool for Sex-Related Problems in the Primary Care Setting: Focus on Erectile Dysfunction
Authors: Romero Otero Javier , García Gómez Borja , Medina Polo José , García Rojo Esther , García Cruz Eduardo , Peinado Francois , Sopeña Sutil Raquel , Bozzini Giorgio , Rodríguez Antolín Alfredo
Published: May 2018

Purpose: To assess the performance of the Brief Sexual Symptom Checklist for men (BSSC-M) questionnaire in General Practitioner’s (GP) consults in Spain. Methods: Multicenter, cross-sectional study conducted in Spain among men ≥50 years, visiting a GP for any reason, and being able to answer self-administered questionnaires. Patients receiving medicines for erectile dysfunction (ED) and those with poor functional status were excluded. Sexual satisfaction was assessed by the BSSC-M, ED by the Sexual Health Inventory for Men (SHIM), and quality of life (QoL) using a 5-point Likert scale. Results: In all, 770 men met all the selection criteria and 556 patients (72.2%) reported sexually related problems, ED being the most frequent (n = 427; 55.5%). The SHIM score decreased progressively with the number of causes of sexual dissatisfaction. Prevalence of ED (SHIM ≤21) was greater in patients who referred problems with erection in the BSSC-M questionnaire (76 vs. 14%; p < 0.001). Multivariate analysis for ED prediction revealed that sexual dissatisfaction, QoL (average or low/very low), and the presence of 3 or more comorbidities significantly influenced the chances of having ED. Conclusions: Our results encourage the use of the BSSC-M for identifying suspicion of ED and other sexual problems in patients > 50 who visit their GP for a routine follow-up.
An Introduction to the Studies of Strabo’s Geography
Authors: Silva Bruno Dos Santos
Published: May 2018

Este artigo visa a oferecer um sumário de tudo quanto se produziu a respeito de um dos mais completos documentos escritos que a Antiguidade nos legou, a Geografia, de Estrabão. O objetivo é apresentar determinadas informações importantes sobre esta fonte, tais como história dos manuscritos, edições existentes e traduções disponíveis. Além disso, apresentarei alguns dos estudos que pesquisadores de várias nacionalidades têm realizado, especialmente no Brasil. Para finalizar, apontarei de forma sucinta a proposta de trabalho que deverá resultar em minha Dissertação de Mestrado, a qual envolve Estrabão e sua relação com a península Ibérica.
The Public Bbaths Phenomena and the Pompeian Cases
Authors: Antonio Victor Sá Ramalho
Published: May 2018

Este artigo busca prover subsídios para o estudo dos banhos públicos romanos no contexto de seus desenvolvimentos iniciais na Campânia romana. Na tentativa de executar tal proposta, este pequeno trabalho consiste em um estudo comparativo de três banhos públicos encontrados em Pompeia em seu ano final, 79 D.C.: as Termas de Stabia, as Termas do Foro e as Termas Centrais. O Foco aqui está na discussão das identidades romanas associadas a esta s construções, dentro de um debate mais amplo sobre a romanização da Campânia e os problemas deste conceito.
The Foreigner and the Autochthonous: Dionysius in the Mediterranean
Authors: Barbosa Leandro Mendonça
Published: May 2018

Tratar da questão mítica do nascimento e da vida do deus Dioniso é o que propõe este artigo. A intenção é trabalhar os conceitos de estrangeiro e autóctone em uma mesma unidade, na tentativa de construir um panorama, de como o culto e a própria imagem de Dioniso difundiu-se nos ambientes mediterrânicos Grécia e Ásia Menor.
The Mediterranean and Ancient History
Authors: Harris William V.
Published: May 2018

O objetivo deste artigo é lidar com duas questões bastante difíceis que podem ser esquematizadas de modo um tanto simples. Como deve ser escrita a história do Mediterrâneo antigo – se é que ela deve ser escrita? E seria o mediterranismo de muita utilidade para o historiador da antiguidade, ou, diferentemente disso, ele é algo perigoso (e, na verdade, um primo do orientalismo)?
Introdução ao Dossiê "História Antiga no Brasil: Ensino e Pesquisa": Uma Antiguidade Fora do Lugar?
Authors: Silva Uiran Gebara da
Published: May 2018

Introdução ao Dossiê "História Antiga no Brasil: Ensino e Pesquisa": Uma Antiguidade Fora do Lugar?
O Ensino e a Pesquisa em História Antiga no Brasil: Reflexões a partir dos Dados da Plataforma Lattes
Authors: Santos Dominique , Kolv Graziele , Nazário Juliano João
Published: May 2018

A área de História Antiga se desenvolveu muito nas últimas décadas no Brasil, o que pode ser percebido tanto pela quantidade de pesquisadores dedicados aos estudos deste período histórico específico quanto pela qualidade das reflexões produzidas sobre ele. O objetivo deste artigo é realizar uma análise sistemática desta produção acadêmica a partir dos dados fornecidos pela Plataforma Lattes, o que nos permitirá compreender algumas questões importantes para a área, como, por exemplo, o que tem sido pesquisado sobre História Antiga no país recentemente.
Ensino de História, reformas do ensino e percepções da Antiguidade: apontamentos a partir da atual conjuntura brasileira
Authors: Leite Priscilla Gontijo
Published: May 2018

artigo tem como principal objetivo refletir sobre o ensino da História Antiga, bem como sobre a divulgação e a percepção desse conhecimento na sociedade brasileira, principalmente na esfera política. Para tanto, nosso ponto de partida será a conjuntura brasileira que perpassa por um modelo de reforma no ensino que irá impactar diretamente o ensino a respeito da Antiguidade na Educação Básica. Iremos demonstrar a importância do ensino de História Antiga no processo educativo e suas potencialidades para o exercício de uma educação que priorize os valores ligados a autonomia do sujeito e a cidadania.
O Lugar da História Antiga no Brasil
Authors: Francisco Gilberto Da Silva
Published: May 2018

Este texto apresenta uma discussão sobre o lugar da História Antiga no Brasil. Não do ponto de vista da produção acadêmica, nem do ensino formal, disciplinar. Trata-se de um debate amplo sobre História Antiga e memória social. Para pensar a História Antiga no Brasil, foi necessário considerar a noção de história e de antiguidade atrelada a ela, bem como as críticas que começam a aparecer mais recentemente ao caráter universalista e civilizatório que destacava a História Antiga em narrativas históricas variadas. Com isso, a discussão sobre a especificidade do lugar da História Antiga no Brasil é apresentado em diálogo com um contexto de crítica do campo que é mais amplo, internacionalmente articulado, e as especificidades próprias da sociedade brasileira.
Multivessel Occlusion in Patients Subjected to Thrombectomy
Authors: Kaesmacher Johannes , Mosimann Pascal J. , Giarrusso Mattia , El-Koussy Marwan , Zibold Felix , Piechowiak Eike , Dobrocky Tomas , Meier Raphael , Jung Simon , Bellwald Sebastian , Arnold Marcel , Mordasini Pasquale , Fischer Urs , Gralla Jan
Published: May 2018

Background and Purpose—

Patients with embolic large-vessel occlusion may present with additional coincidental acute occlusions within or distant from the involved territory, referred to as multivessel occlusion (MVO). Purpose of this study was to assess prevalence of MVO, associated factors, and clinical relevance in patients undergoing endovascular stroke treatment.

Methods—

Image data of consecutive endovascular candidates (n=720) with direct access to angiography were extracted from a prospective registry. Prevalence of MVO was assessed with multimodal magnetic resonance imaging/computed tomography and confirmed by intra-arterial angiography. Explorative analysis of associated factors and clinical relevance was evaluated using multivariable logistic regression including variables with
P
<0.15 in univariate comparison. Good functional outcome was defined as modified Rankin Scale score ≤2 at day 90.

Results—

MVO was present in 10.7% of patients (95% confidence interval [CI], 6.4%–13.0%). Two, 3, and 4 concomitant occlusions were found in 80.5%, 16.9%, and 2.6% of MVO cases, respectively. Detection rate on initial radiological report was 54.5%. Downstream MVO was present in around one third of MVO (n=27/77, 35.1%), whereas all other MVO (n=50/77, 64.9%) occurred in different territories. Independent factors related to MVO were statin treatment (adjusted odds ratio [aOR], 0.477; 95% CI, 0.276–0.827), higher systolic blood pressure (aOR per mm Hg increase, 1.014; 95% CI, 1.005–1.023), and primary occlusion site M2 (aOR, 1.870; 95% CI, 1.103–3.170). MVO was related to lower rates of successful reperfusion (aOR, 0.549; 95% CI, 0.316–0.953) and lower rates of good functional outcome (aOR, 0.437; 95% CI, 0.207–0.923).

Conclusions—

Every tenth patient subjected to angiography for endovascular stroke treatment experienced MVO in our series, and only half were prospectively identified on preinterventional diagnostic imaging. Patients with MVO had higher baseline systolic blood pressure and were less often medicated with statins, an observation that warrants external validation and evaluation regarding causality. Occurrence of MVO has implication for treatment decisions, negatively affects endovascular treatment success, and is predictive of worse clinical outcome.
Pupal stages of three species of the phytophagous genus Merodon Meigen (Diptera: Syrphidae)
Authors: PRERADOVIĆ JELENA , ANDRIĆ ANDRIJANA , RADENKOVIĆ SNEŽANA , ZORIĆ LJILJANA ŠAŠIĆ , PÉREZ-BAÑÓN CELESTE , CAMPOY ANDRÉS , VUJIĆ ANTE
Published: May 2018

plants, are mostly unknown. All known immature stages of Merodon feed on underground storage organs (bulbs, rhizomes and corms) of geophytes of the families Asparagaceae, Iridaceae and Amaryllidaceae. Of 160 known Merodon species, to date, the pupal stages have been described for only four: M. equestris (Fabricius), M. bombiformis Hull, M. luteihumerus Marcos-García, Vujić & Mengual, and M. geniculatus Strobl. During field investigations in Đerdap National Park, Serbia, Merodon puparia were found in the ground near the bulbs of Ornithogalum umbellatum L. (Asparagaceae). DNA barcoding revealed that they belonged to the species M. aureus Fabricius and M. avidus (Rossi). Analysis of museum material from the Bavarian State Collection of Zoology in Germany revealed the puparium of an additional species, M. rufus Meigen. In our study we provide for the first time descriptions of the puparia of these three Merodon species. The main diagnostic morphological characters of the pupal spiracles and posterior respiratory processes are described using scanning electron microscopy, and cephalopharyngeal skeletons using binocular microscopy. In addition, puparium morphology of M. aureus, M. avidus and M. rufus is compared with known puparia of four other Merodon species and with the third larval stage of M. hurkmansi Marcos-García, Vujić & Mengual.
Haptic Foot Pedal: Influence of Shoe Type, Age, and Gender on Subjective Pulse Perception
Authors: Geitner Claudia , Birrell Stewart , Krehl Claudia , Jennings Paul
Published: May 2018

Objective:

This study investigates the influence of shoe type (sneakers and safety boots), age, and gender on the perception of haptic pulse feedback provided by a prototype accelerator pedal in a running stationary vehicle.

Background:

Haptic feedback can be a less distracting alternative to traditionally visual and auditory in-vehicle feedback. However, to be effective, the device delivering the haptic feedback needs to be in contact with the person. Factors such as shoe type vary naturally over the season and could render feedback that is perceived well in one situation, unnoticeable in another. In this study, we evaluate factors that can influence the subjective perception of haptic feedback in a stationary but running car: shoe type, age, and gender.

Method:

Thirty-six drivers within three age groups (≤39, 40–59, and ≥60) took part. For each haptic feedback, participants rated intensity, urgency, and comfort via a questionnaire.

Results:

The perception of the haptic feedback is significantly influenced by the interaction between the pulse’s duration and force amplitude and the participant’s age and gender but not shoe type.

Conclusion:

The results indicate that it is important to consider different age groups and gender in the evaluation of haptic feedback. Future research might also look into approaches to adapt haptic feedback to the individual driver’s preferences.

Application:

Findings from this study can be applied to the design of an accelerator pedal in a car, for example, for a nonvisual in-vehicle warning, but also to plan user studies with a haptic pedal in general.