bluuebunny/crossref_metadata_2025 huggingface dataset:
Bushehr Elderly Health (BEH) Programme, phase I (cardiovascular system)
Authors: Ostovar Afshin , Nabipour Iraj , Larijani Bagher , Heshmat Ramin , Darabi Hossein , Vahdat Katayoun , Ravanipour Maryam , Mehrdad Neda , Raeisi Alireza , Heidari Gholamreza , Shafiee Gita , Haeri Mohammadjavad , Pourbehi Mohammadreza , Sharifi Farshad , Noroozi Azita , Tahmasebi Rahim , Aghaei Meybodi Hamidreza , Assadi Majid , Farrokhi Shokrollah , Nemati Reza , Amini Mohammad Reza , Barekat Maryam , Amini Abdullatif , Salimipour Houman , Dobaradaran Sina , Moshtaghi Darab
Published: December 2015

Purpose

The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events.

Participants

Between March 2013 and October 2014, a total of 3000 men and women aged ≥60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%).

Findings to date

Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at –80°C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men.

Future plans

Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration.
Ultrasound‐guided sciatic and femoral nerve blocks for metatarsal fracture stabilisation in a two‐day‐old neonatal calf
Authors: Viscasillas Jaime , Drozdzynska Maja Justyna , McSloy Alex
Published: December 2015

A two‐day‐old heifer calf presented with a non‐weight bearing right hindlimb lameness following a traumatic event. A closed, complete, overriding, displaced fracture of the distal right metatarsal diaphysis was diagnosed and closed reduction and cast placement was elected as treatment. The calf was sedated intravenously with a combination of diazepam and ketamine. With the calf in lateral recumbency, sciatic and femoral nerve blocks were performed using procaine to provide analgesia and muscle relaxation for the procedure. The procedure was performed with the patient sedated and no further anaesthetics or analgesics were needed. This report is the first describing the use of sciatic and femoral nerve blocks as analgesia for a young calf. The success of the technique allowed a decrease in the dosage of other systemic drugs. This is an important factor in decreasing potential complications related to anaesthesia in these patients.
Whole-body fat oxidation increases more by prior exercise than overnight fasting in elite endurance athletes
Authors: Andersson Hall Ulrika , Edin Fredrik , Pedersen Anders , Madsen Klavs
Published: December 2015

The purpose of this study was to compare whole-body fat oxidation kinetics after prior exercise with overnight fasting in elite endurance athletes. Thirteen highly trained athletes (9 men and 4 women; maximal oxygen uptake: 66 ± 1 mL·min−1·kg−1) performed 3 identical submaximal incremental tests on a cycle ergometer using a cross-over design. A control test (CON) was performed 3 h after a standardized breakfast, a fasting test (FAST) 12 h after a standardized evening meal, and a postexercise test (EXER) after standardized breakfast, endurance exercise, and 2 h fasting recovery. The test consisted of 3 min each at 30%, 40%, 50%, 60%, 70%, and 80% of maximal oxygen uptake and fat oxidation rates were measured through indirect calorimetry. During CON, maximal fat oxidation rate was 0.51 ± 0.04 g·min−1 compared with 0.69 ± 0.04 g·min−1 in FAST (P < 0.01), and 0.89 ± 0.05 g·min−1 in EXER (P < 0.01). Across all intensities, EXER was significantly higher than FAST and FAST was higher than CON (P < 0.01). Blood insulin levels were lower and free fatty acid and cortisol levels were higher at the start of EXER compared with CON and FAST (P < 0.05). Plasma nuclear magnetic resonance-metabolomics showed similar changes in both EXER and FAST, including increased levels of fatty acids and succinate. In conclusion, prior exercise significantly increases whole-body fat oxidation during submaximal exercise compared with overnight fasting. Already high rates of maximal fat oxidation in elite endurance athletes were increased by approximately 75% after prior exercise and fasting recovery.
Synthesis and evaluation of original bioisosteres of bacterial type IIA topoisomerases inhibitors
Authors: Petrella Stéphanie , Aubry Alexandra , Janvier Geneviève , Coutant Eloi P. , Cartier Alex , Dao Thuy-Ha , Bonhomme Frédéric J. , Motreff Laurence , Pissis Cédric , Bizet Chantal , Clermont Dominique , Begaud Evelyne , Retailleau Pascal , Munier-Lehmann Hélène , Capton Estelle , Mayer Claudine , Janin Yves L.
Published: December 2015

A recently discovered series of inhibitors of the ATPase function of bacterial type IIA topoisomerases featuring a carboxypyrrole component led us to attempt to replace this group with a potentially bioisosteric carboxypyrazole. Accordingly, synthetic pathways to 2-(4-(1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids or 2-(4-(N-methyl-1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids featuring an array of substituents on the pyrazole ring were explored. Unfortunately, none of the analogues made were effective on the ATPase function of Mycobacterium tuberculosis gyrase as well on the DNA supercoiling activity of the whole gyrase of M. tuberculosis and Escherichia coli. However, this work is still providing original insights in chemistry as well as in the structure–activity relationships of this series of inhibitors.
Finite gravitational time dilation in black holes using dynamic Newtonian advanced gravity (DNAg)
Authors: Worsley Andrew , Worsley Joseph
Published: December 2015

In this paper we use a dynamic form of modified Newtonian gravity to reformulate the equations for gravitational time dilation. Here we introduce the generic equations for gravitational time dilation. It is shown that these equations agree exactly with gravitational time dilation in satellite navigation systems. The equations are also in agreement with a reanalysis of observations of gravitational red shifts in black hole accretion discs. Using these equations, we translate the time dilation into a finite value at the black hole event horizon. Thus this reformulation resolves the difficulties of the existence of black hole singularities. Importantly these dynamic gravitational equations provide testable predictions in the vicinity of black holes.
First-principles study of structural, elastic and thermodynamic properties of AuIn2
Authors: Wu Hai Ying , Chen Ya Hong , Deng Chen Rong , Yin Peng Fei , Cao Hong
Published: December 2015

The structural, elastic and thermodynamic properties of [Formula: see text] in the [Formula: see text] structure under pressure have been investigated using ab initio plane wave pseudopotential method within the generalized gradient approximation. The calculated structural parameters and equation of state are in excellent agreement with the available experimental and theoretical results. The elastic constants of [Formula: see text] at ambient condition are calculated, and the bulk modulus obtained from these calculated elastic constants agrees well with the experimental data. The pressure dependence of the elastic constants, bulk modulus, shear modulus and Young’s modulus has also been investigated. The Debye temperature presents a slight increase with pressure. [Formula: see text] exhibits ductibility and low hardness characteristics, the ductibility increases while the hardness decreases with the increasing of pressure. The pressure effect on the heat capacity and thermal expansion coefficient for [Formula: see text] is much larger.
Higher order multi-dimensional extensions of Cesàro theorem
Authors: Accardi Luigi , Ji Un Cig , Saitô Kimiaki
Published: December 2015

The Cesàro theorem is extended to the cases: (1) higher order Cesàro mean for sequence (discrete case); and (2) higher order, multi-dimensional and continuous Cesàro mean for functions. Also, we study the Cesàro theorem for the case of positive-order.
Do technical studies reduce subsurface risk in hydrocarbon exploration: and if not, how do they add value?
Authors: Peel Frank J. , White Jonathan
Published: December 2015

The title ‘The Value of Outcrop Studies in Reducing Subsurface Uncertainty and Risk’ might suggest that we expect new information to improve prospect risk, but this is not correct. Gaining new information generally does change our estimate of prospect risk: the change may be up or down, and the average of all possibilities is zero change. You cannot acquire data for the purpose of increasing the probability of success. We should expect that: (a) the expected value of the risk of a single prospect, post-data, is equal to the prior (pre-data) value; and (b) risk should become worse for the majority of prospects. New information adds value, not from changing pre-drill risk, but from decisions made as a consequence. The main value added is from identifying prospects not to drill, thereby saving the cost of likely dry holes, and by choosing the ones to test first, accelerating revenue from a successful outcome. Further value is added if the new information leads to the identification of new prospects or new plays, or suggests follow-on potential elsewhere in the region. Value may also be added if the new information is negative for a whole region, enabling us to focus our attention elsewhere.
Human cervical spinal cord circuitry activated by tonic input can generate rhythmic arm movements
Authors: Solopova I. A. , Selionov V. A. , Zhvansky D. S. , Gurfinkel V. S. , Ivanenko Y.
Published: December 2015

The coordination between arms and legs during human locomotion shares many features with that in quadrupeds, yet there is limited evidence for the central pattern generator for the upper limbs in humans. Here we investigated whether different types of tonic stimulation, previously used for eliciting stepping-like leg movements, may evoke nonvoluntary rhythmic arm movements. Twenty healthy subjects participated in this study. The subject was lying on the side, the trunk was fixed, and all four limbs were suspended in a gravity neutral position, allowing unrestricted low-friction limb movements in the horizontal plane. The results showed that peripheral sensory stimulation (continuous muscle vibration) and central tonic activation (postcontraction state of neuronal networks following a long-lasting isometric voluntary effort, Kohnstamm phenomenon) could evoke nonvoluntary rhythmic arm movements in most subjects. In ∼40% of subjects, tonic stimulation elicited nonvoluntary rhythmic arm movements together with rhythmic movements of suspended legs. The fact that not all participants exhibited nonvoluntary limb oscillations may reflect interindividual differences in responsiveness of spinal pattern generation circuitry to its activation. The occurrence and the characteristics of induced movements highlight the rhythmogenesis capacity of cervical neuronal circuitries, complementing the growing body of work on the quadrupedal nature of human gait.
Perinodal glial swelling mitigates axonal degradation in a model of axonal injury
Authors: Volman Vladislav , Ng Laurel J.
Published: December 2015

Mild traumatic brain injury (mTBI) has been associated with the damage to myelinated axons in white matter tracts. Animal models and in vitro studies suggest that axonal degradation develops during a latent period following a traumatic event. This delay has been attributed to slowly developing axonal membrane depolarization that is initiated by injury-induced ionic imbalance and in turn, leads to the activation of Ca2+ proteases via pathological accumulation of Ca2+. However, the mechanisms mitigating the transition to axonal degradation after injury remain elusive. We addressed this question in a detailed biophysical model of axonal injury that incorporated ion exchange and glial swelling mechanisms. We show that glial swelling, which often co-occurs with mTBI, promotes axonal survival by regulating extracellular K+ dynamics, extending the range of injury parameters in which axons exhibit stable membrane potential postinjury. In addition, glial swelling was instrumental in reducing axonal sensitivity to repetitive stretch injury that occurred several minutes following the first one. Results of this study suggest that acute post-traumatic swelling of perinodal astrocytes helps prevent or postpone axonal degradation by maintaining physiologically relevant levels of extracellular K+.
Single-subject prediction of response inhibition behavior by event-related potentials
Authors: Stock Ann-Kathrin , Popescu Florin , Neuhaus Andres H. , Beste Christian
Published: December 2015

Much research has been devoted to investigating response inhibition and the neuronal processes constituting this essential cognitive faculty. However, the nexus between cognitive subprocesses, behavior, and electrophysiological processes remains associative in nature. We therefore investigated whether neurophysiological correlates of inhibition subprocesses merely correlate with behavioral performance or actually provide information expedient to the prediction of behavior on a single-subject level. Tackling this question, we used different data-driven classification approaches in a sample of n = 262 healthy young subjects who completed a standard Go/Nogo task while an EEG was recorded. On the basis of median-split response inhibition performance, subjects were classified as “accurate/slow” and “less accurate/fast.” Even though these behavioral group differences were associated with significant amplitude variations in classical electrophysiological correlates of response inhibition (i.e., N2 and P3), they were not predictive for group membership on a single-subject level. Instead, amplitude differences in the Go-P2 originating in the precuneus (BA7) were shown to predict group membership on a single-subject level with up to 64% accuracy. These findings strongly suggest that the behavioral outcome of response inhibition greatly depends on the amount of cognitive resources allocated to early stages of stimulus-response activation during responding. This suggests that research should focus more on early processing steps during responding when trying to understand the origin of interindividual differences in response inhibition processes.
Periosteal Pedicle Flap Harvested during Vestibular Extension for Root Coverage
Authors: Kumar Shubham , Gupta Krishna Kumar , Agrawal Rahul , Srivastava Pratima , Soni Shalabh
Published: December 2015

Root exposure along with inadequate vestibular depth is a common clinical finding. Treatment option includes many techniques to treat such defects for obtaining predictable root coverage. Normally, the vestibular depth is increased first followed by a second surgery for root coverage. The present case report describes a single-stage technique for vestibular extension and root coverage in a single tooth by using thePeriosteal Pedicle Flap (PPF). This technique involves no donor site morbidity and allows for reflection of sufficient amount of periosteal flap tissue with its own blood supply at the surgical site, thus increasing the chances of success of root coverage with simultaneous increase in vestibular depth.
Terrain Adaptability Mechanism of Large Ruminants’ Feet on the Kinematics View
Authors: Zhang Qun , Ding Xilun , Xu Kun
Published: December 2015

Ruminants live in various parts of land. Similar cloven hooves assist ruminants in adapting to different ground environment during locomotion. This paper analyzes the general terrain adaptability of the feet of ruminants using kinematics of the equivalent mechanism model based on screw theory. Cloven hooves could adjust attitude by changing relative positions between two digits in swing phase. This function helps to choose better landing orientation. “Grasping” or “holding” a rock or other object on the ground passively provides extra adhesion force in stance phase. Ruminants could adjust the position of the metacarpophalangeal joint or metatarsophalangeal joint (MTP or MCP) with no relative motion between the tip of feet and the ground, which ensures the adhesion and dexterity in stance phase. These functions are derived from an example from chamois’ feet and several assumptions, which are believed to demonstrate the foundation of adaptation of ruminants and ensure a stable and continuous movement.
Recognition Algorithm of Acoustic Emission Signals Based on Conditional Random Field Model in Storage Tank Floor Inspection Using Inner Detector
Authors: Li Yibo , Zhang Yuxiang , Zhu Huiyu , Yan Rongxin , Liu Yuanyuan , Sun Liying , Zeng Zhoumo
Published: December 2015

Acoustic emission (AE) technique is often used to detect inaccessible area of large storage tank floor with AE sensors placed outside the tank. For tanks with fixed roofs, the drop-back signals caused by condensation mix with corrosion signals from the tank floor and interfere with the online AE inspection. The drop-back signals are very difficult to filter out using conventional methods. To solve this problem, a novel AE inner detector, which works inside the storage tank, is adopted and a pattern recognition algorithm based on CRF (Conditional Random Field) model is presented. The algorithm is applied to differentiate the corrosion signals from interference signals, especially drop-back signals caused by condensation. Q235 steel corrosion signals and drop-signals were collected both in laboratory and in field site, and seven typical AE features based on hits and frequency are extracted and selected by mRMR (Minimum Redundancy Maximum Relevance) for pattern recognition. To validate the effectiveness of the proposed algorithm, the recognition result of CRF model was compared with BP (Back Propagation), SVM (Support Vector Machine), and HMM (Hidden Markov Model). The results show that training speed, accuracy, and ROC (Receiver Operating Characteristic) results of the CRF model outperform other methods.
An Investigation into the Impact of Reaction Temperature on Various Parameters during Torrefaction of Sugarcane Bagasse Relevant to Gasification
Authors: Anukam Anthony , Mamphweli Sampson , Reddy Prashant , Okoh Omobola , Meyer Edson
Published: December 2015

Torrefaction of sugarcane bagasse was conducted in an electric muffle furnace at 200, 250, and 300°C in order to establish the impact of heat treatment temperature on various parameters and as a method to improve sugarcane bagasse characteristics for the purpose of gasification. The results show that weight loss of bagasse reduced as temperature of torrefaction increased due to excessive devolatilization. A reduced moisture and volatile matter content as well as improved calorific value were also achieved with increasing temperature of torrefaction. The torrefaction progress was again followed by elemental analysis of the material which showed the presence of C, H, and O in varying proportions depending on torrefaction temperature. The decrease in the weight percentages of O2and H2as torrefaction reaction temperature increased resulted in the accumulation of C in the solid product. The thermogravimetric analysis conducted established the maximum reactivity temperature of the torrefied material and revealed that the degradation of torrefied sugarcane bagasse was accelerated by thermal treatment of the material prior to analysis. Finally, the study established that torrefaction at 300°C led to a much more degraded material compared to the lower torrefaction reaction temperatures of 200 and 250°C, respectively.
Removal of Refractory Organics from Biologically Treated Landfill Leachate by Microwave Discharge Electrodeless Lamp Assisted Fenton Process
Authors: Li Jiuyi , Qin Lele , Zhao Lei , Wang Aimin , Chen Yong , Meng Liao , Zhang Zhongguo , Tian Xiujun , Zhou Yanmei
Published: December 2015

Biologically treated leachate usually contains considerable amount of refractory organics and trace concentrations of xenobiotic pollutants. Removal of refractory organics from biologically treated landfill leachate by a novel microwave discharge electrodeless lamp (MDEL) assisted Fenton process was investigated in the present study in comparison to conventional Fenton and ultraviolet Fenton processes. Conventional Fenton and ultraviolet Fenton processes could substantially remove up to 70% of the refractory organics in a membrane bioreactor treated leachate. MDEL assisted Fenton process achieved excellent removal performance of the refractory components, and the effluent chemical oxygen demand concentration was lower than 100 mg L−1. Most organic matters were transformed into smaller compounds with molecular weights less than 1000 Da. Ten different polycyclic aromatic hydrocarbons were detected in the biologically treated leachate, most of which were effectively removed by MDEL-Fenton treatment. MDEL-Fenton process provides powerful capability in degradation of refractory and xenobiotic organic pollutants in landfill leachate and could be adopted as a single-stage polishing process for biologically treated landfill leachate to meet the stringent discharge limit.
Addressing “Nature-Deficit Disorder”: A Mixed Methods Pilot Study of Young Adults Attending a Wilderness Camp
Authors: Warber Sara L. , DeHudy Ashley A. , Bialko Matthew F. , Marselle Melissa R. , Irvine Katherine N.
Published: December 2015

Background and Objectives. Rapid urbanization raises concern about chronic human health issues along with less frequent interaction with the natural world. “Nature-deficit disorder,” a nonclinical term, describes this potential impact on the well-being of youth. We conducted a mixed methods pilot study of young adults attending a four-week wilderness camp to investigate whether nature-based camp experiences would increase connection to nature and promote multiple dimensions of well-being.Methods. Participants completed precamp (n= 46) and postcamp (n= 36) online questionnaires including nature-related and holistic well-being measures. Differences were investigated using pairedt-tests. Interviews (n= 16) explored camp experiences and social relations.Results. All nature-related measures—exposure, knowledge, skills, willingness to lead, perceived safety, sense of place, and nature connection—significantly increased. Well-being outcomes also significantly improved, including perceived stress, relaxation, positive and negative emotions, sense of wholeness, and transcendence. Physical activity and psychological measures showed no change. Interviews described how the wilderness environment facilitated social connections.Conclusion. Findings illustrate the change in nature relations and well-being that wilderness camp experiences can provide. Results can guide future research agendas and suggest that nature immersion experiences could address the risk of “nature-deficit disorder,” improve health, and prepare future environmental leaders.
Particle Dynamics around Weakly Magnetized Reissner-Nordström Black Hole
Authors: Majeed Bushra , Jamil Mubasher , Hussain Saqib
Published: December 2015

Considering the geometry of Reissner-Nordström (RN) black hole immersed in magnetic field, we have studied the dynamics of neutral and charged particles. A collision of particles in the inner stable circular orbit is considered and the conditions for the escape of colliding particles from the vicinity of black hole are given. The trajectories of the escaping particle are discussed. Also, the velocity required for this escape is calculated. It is observed that there is more than one stable region if magnetic field is present in the accretion disk of black hole, so the stability of ISCO increases in the presence of magnetic field. Effect of magnetic field on the angular motion of neutral and charged particles is observed graphically.
Percutaneous Ultrasound-Guided Laser Ablation with Contrast-Enhanced Ultrasonography for Hyperfunctioning Parathyroid Adenoma: A Preliminary Case Series
Authors: Jiang Tianan , Chen Fen , Zhou Xiang , Hu Ying , Zhao Qiyu
Published: December 2015

The study was to evaluate the safety and effectiveness of ultrasound-guided percutaneous laser ablation (pLA) as a nonsurgical treatment for primary parathyroid adenoma. Surgery was contraindicated in, or refused by, the included patients. No lesion enhancement on contrast-enhanced ultrasound immediately after pLA was considered “complete ablation.” Nodule size, serum calcium, and parathyroid hormone level were compared before and after pLA. Complete ablation was achieved in all 21 patients with 1 (n=20) or 2 (n=1) sessions. Nodule volume decreased from0.93±0.58 mL at baseline to0.53±0.38and0.48±0.34 mL at 6 and 12 months after pLA (P<0.05). At 1 day, 6 months, and 12 months after pLA, serum PTH decreased from15.23±3.00 pmol/L at baseline to7.41±2.79,6.95±1.78, and6.90±1.46 pmol/L, serum calcium decreased from3.77±0.77 mmol/L at baseline to2.50±0.72,2.41±0.37, and2.28±0.26 mmol/L, respectively (P<0.05). At 12 months, treatment success (normalization of PTH and serum calcium) was achieved in 81%. No serious complications were observed. Ultrasound-guided pLA with contrast-enhanced ultrasound is a viable alternative to surgery for primary parathyroid adenoma.
Transmit TACAN Bearing Information with a Circular Array
Authors: Dorsey W. Mark , Coleman Jeffrey O. , Pickles William R.
Published: December 2015

Using TACAN and array fundamentals, we derive an architecture for transmitting TACAN bearing information from a circular array with time-varying weights. We evaluate performance for a simulated example array of Vivaldi elements.
Chemical Components and Cardiovascular Activities ofValerianaspp.
Authors: Chen Heng-Wen , Wei Ben-Jun , He Xuan-Hui , Liu Yan , Wang Jie
Published: December 2015

Valerianaspp. is a flowering plant that is well known for its essential oils, iridoid compounds such as monoterpenes and sesquiterpenes, flavonoids, alkaloids, amino acids, and lignanoids.Valerianaspp. exhibits a wide range of biological activities such as lowering blood pressure and heart rate, antimyocardial ischemia reperfusion injury, antiarrhythmia, and regulation of blood lipid levels. This review focuses on the chemical constituents and cardiovascular activities ofValerianaspp.
Parkinsonian Rigidity Depends on the Velocity of Passive Joint Movement
Authors: Endo Takuyuki , Yoshikawa Naoya , Fujimura Harutoshi , Sakoda Saburo
Published: December 2015

Background.It has been long believed that Parkinsonian rigidity is not velocity-dependent based on the neurological examination. However, this has not been verified scientifically.Methods.The elbow joints of 20 Parkinson’s disease patients were passively flexed and extended, and two characteristic values, the elastic coefficient (elasticity) and the difference in bias (difference in torque measurements for extension and flexion), were identified from a plot of the angle and torque characteristics. Flexion and extension were done at two different velocities, 60°/s and 120°/s, and a statistical analysis was performed to determine whether the changes in these characteristic values were velocity-dependent.Results.The elastic coefficient was not velocity-dependent, but the difference in bias increased in a velocity-dependent manner (P=0.0017).Conclusions.The features of rigidity may differ from the conventional definition, which states that they are not dependent on the velocity of joint movement.
Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity
Authors: Kim Dong Joon , Roh Eunmiri , Lee Mee-Hyun , Oi Naomi , Lim Do Young , Kim Myoung Ok , Cho Yong-Yeon , Pugliese Angelo , Shim Jung-Hyun , Chen Hanyong , Cho Eun Jin , Kim Jong-Eun , Kang Sun Chul , Paul Souren , Kang Hee Eun , Jung Ji Won , Lee Sung-Young , Kim Sung-Hyun , Reddy Kanamata , Yeom Young Il , Bode Ann M. , Dong Zigang
Published: December 2015

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC. Using computer docking simulation and an in vitro ODC enzyme assay, we identified herbacetin, a natural compound found in flax and other plants, as a novel ODC inhibitor. Mechanistic investigations defined aspartate 44 in ODC as critical for binding. Herbacetin exhibited potent anticancer activity in colon cancer cell lines expressing high levels of ODC. Intraperitoneal or oral administration of herbacetin effectively suppressed HCT116 xenograft tumor growth and also reduced the number and size of polyps in a mouse model of APC-driven colon cancer (ApcMin/+). Unlike the well-established ODC inhibitor DFMO, herbacetin treatment was not associated with hearing loss. Taken together, our findings defined the natural product herbacetin as an allosteric inhibitor of ODC with chemopreventive and antitumor activity in preclinical models of colon cancer, prompting its further investigation in clinical trials. Cancer Res; 76(5); 1146–57. ©2015 AACR.
Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling
Authors: Catalano Veronica , Dentice Monica , Ambrosio Raffaele , Luongo Cristina , Carollo Rosachiara , Benfante Antonina , Todaro Matilde , Stassi Giorgio , Salvatore Domenico
Published: December 2015

Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2–D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that drug-induced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. Cancer Res; 76(5); 1237–44. ©2015 AACR.
Targeting the WASF3–CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion
Authors: Teng Yong , Bahassan Abdulaziz , Dong Dayong , Hanold Laura E. , Ren Xiaoou , Kennedy Eileen J. , Cowell John K.
Published: December 2015

Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function. Here, we show that genetic knockdown of CYFIP1 in cancer cells led to the destabilization of the WASF3 complex, loss of WASF3 function, and suppressed invasion. Based on existing crystallographic data, we developed stapled peptides, referred to as WASF Helix Mimics (WAHM), that target an α-helical interface between WASF3 and CYFIP1. Treatment of highly invasive breast and prostate cancer cells with WAHM inhibitor peptides significantly reduced motility and invasion in vitro. Mechanistic investigations revealed that these inhibitors suppressed the interaction between Rac and the WASF3 complex, which has been shown to promote cell migration. Furthermore, peptide-mediated inhibition of WASF3 also resulted in the dysregulation of known downstream targets such as MMP-9 and KISS1. Finally, we demonstrate that this invasive phenotype is specific to WASF3 as depletion of WASF1 and WASF2, which can also bind to CYFIP1, did not affect invasion. Collectively, our findings suggest that targeting WASF3 function with WAHM peptides could represent a promising therapeutic strategy for preventing tumor invasion and metastasis. Cancer Res; 76(4); 965–73. ©2015 AACR.
Myc Induces miRNA-Mediated Apoptosis in Response to HDAC Inhibition in Hematologic Malignancies
Authors: Adams Clare M. , Hiebert Scott W. , Eischen Christine M.
Published: December 2015

Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc-driven B-cell lymphoma and five other hematopoietic malignancies. We determined that Myc-mediated transcriptional repression of the miR-15 and let-7 families in malignant cells was relieved upon HDACi, and Myc was required for their upregulation. The miR-15 and let-7 families then targeted and downregulated the antiapoptotic genes Bcl-2 and Bcl-xL, respectively, to induce HDACi-mediated apoptosis. Notably, Myc also transcriptionally upregulated these miRNA in untransformed cells, indicating that this Myc-induced miRNA-mediated apoptotic pathway is suppressed in malignant cells, but becomes reactivated upon HDACi. Taken together, our results reveal a previously unknown mechanism by which Myc induces apoptosis independent of the p53 pathway and as a response to HDACi in malignant hematopoietic cells. Cancer Res; 76(3); 736–48. ©2015 AACR.
Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study
Authors: Markt Sarah C. , Flynn-Evans Erin E. , Valdimarsdottir Unnur A. , Sigurdardottir Lara G. , Tamimi Rulla M. , Batista Julie L. , Haneuse Sebastien , Lockley Steven W. , Stampfer Meir , Wilson Kathryn M. , Czeisler Charles A. , Rider Jennifer R. , Mucci Lorelei A.
Published: December 2015

Background: Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer.

Methods: We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer.

Results: In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15–8.10).

Conclusions: We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes.

Impact: We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men. Cancer Epidemiol Biomarkers Prev; 25(2); 302–8. ©2015 AACR.
Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity
Authors: Jansen Rick J. , Argos Maria , Tong Lin , Li Jiabei , Rakibuz-Zaman Muhammad , Islam Md. Tariqul , Slavkovich Vesna , Ahmed Alauddin , Navas-Acien Ana , Parvez Faruque , Chen Yu , Gamble Mary V. , Graziano Joseph H. , Pierce Brandon L. , Ahsan Habibul
Published: December 2015

Background: Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity.

Methods: The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species.

Results: Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations.

Conclusions: Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions.

Impact: This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles. Cancer Epidemiol Biomarkers Prev; 25(2); 381–90. ©2015 AACR.
Polymorphisms of a Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 and Aflatoxin B1–Related Hepatocellular Carcinoma
Authors: Huang Xiao-Ying , Yao Jin-Guang , Huang Bing-Chen , Ma Yun , Xia Qiang , Long Xi-Dai
Published: December 2015

Background: Altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is observed in hepatocellular carcinoma. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)–related hepatocellular carcinoma have not yet been elucidated.

Methods: We conducted a hospital-based case–control study, including 1,706 hepatocellular carcinoma cases and 2,270 controls without any liver diseases or tumors, to assess the association between 74 polymorphisms in ADAMTS5 and AFB1-related hepatocellular carcinoma risk and prognosis. Genotype, mRNA levels, and TP53 gene mutation (TP53M) related to AFB1 exposure were tested using TaqMan-PCR or sequencing technique. ADAMTS5 protein level and microvessel density were analyzed by IHC.

Results: Among these 74 polymorphisms, only rs2830581 affected hepatocellular carcinoma risk. Compared with the homozygote of rs2830581 G alleles (rs2830581-GG), the genotypes of rs2830581 A alleles (rs2830581-GA or -AA) increased hepatocellular carcinoma risk (OR: 1.85 and 4.40; 95% CI: 1.57–2.19 and 3.43–5.64, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Furthermore, the rs2830581 polymorphism modified the tumor recurrence-free survival and overall survival of patients. This polymorphism not only affected pathologic features of hepatocellular carcinoma such as tumor dedifferentiation and microvessel density, but also modified ADAMTS5 expression and the effects of transarterial chemoembolization treatment on hepatocellular carcinoma.

Conclusions: These results suggest ADAMTS5 polymorphisms may be risk and prognostic biomarkers of AFB1-related hepatocellular carcinoma, and rs2830581 is a potential candidate.

Impact: Our findings support the hypothesis that ADAMTS5 rs2830581 polymorphism modifies AFB1-related hepatocellular carcinoma risk and prognosis. Cancer Epidemiol Biomarkers Prev; 25(2); 334–43. ©2015 AACR.
Occipitocervical Fetus in Fetu with Extracalvarial Extension: A Case Report
Authors: Padwal Amit Dattatraya , Devi Bhagvatula Indira , Ramachandran Sudheesh , Bhat Dhananjaya Ishwar , Shukla Dhaval , Ramu Rajalakshmi
Published: December 2015

Fetus in fetu (FIF) is an extremely rare congenital anomaly in the pediatric age group. It is defined by the presence of an axial skeleton and well-formed internal organs in a fetiform mass. Only about 15 cases of intracranial FIF have been reported in the literature worldwide. We report a case of temporo-occipitocervical FIF. This 7-month-old female child presented to us with occipital swelling that she had had since birth. A soft swelling was palpable in the retroauricular region with extension into the neck. A few bony parts were palpable in the swelling. Imaging was suggestive of a multiseptate mass lesion in the right occipital region with intracranial, intraspinal and extracranial components. The patient underwent exploration and excision of the extracranial mass and retromastoid suboccipital craniectomy and decompression of the intracranial component. Different parts, such as a terminal ileum, cecum, appendix, femur, humerus and vertebral body, were identified within the mass. This case meets Willis' criteria as well as 4/5 criteria stated by Spencer for the diagnosis of this condition. To the best of our knowledge, this is the first reported case of temporo-occipitocervical FIF with a well-defined embryological spectrum. This also supports Spencer's hypothesis of abnormal twinning.
Outcome of Multifetal Pregnancy Reduction in Women with a Dichorionic Triamniotic Triplet Pregnancy to a Singleton Pregnancy: A Retrospective Nationwide Cohort Study
Authors: van de Mheen L. , Everwijn S.M.P. , Haak M.C. , Manten G.T.R. , Zondervan H.A. , Knapen M.F.C.M. , Engels M.A.J. , Erwich J.J.H.M. , Coumans A.B. , van Vugt J.M.G. , Bilardo C.M. , van Pampus M.G. , de Groot C.J.M. , Mol B.W.J. , Pajkrt E.
Published: December 2015

Objective: To study the pregnancy outcomes of women with a dichorionic triamniotic triplet pregnancy that was reduced to a singleton pregnancy and to review the literature. Methods: We performed a nationwide retrospective cohort study. We compared time to delivery and perinatal mortality in dichorionic triplet pregnancies reduced to singletons with ongoing dichorionic triplet pregnancies and primary singleton pregnancies. Additionally, we reviewed the literature on the subject. Results: We studied 46 women with a reduced dichorionic triplet pregnancy and 42 women with an ongoing dichorionic triplet pregnancy. Median gestational age at delivery was 38.7 vs. 32.8 weeks, respectively (p < 0.001). Delivery <24 weeks occurred in 9 (19.6%) women with a reduced triplet pregnancy and 4 (9.5%) with an ongoing triplet pregnancy (p = 0.19). Perinatal survival rates between the reduced group and the ongoing triplet group were not significantly different. Conclusion: Multifetal pregnancy reduction in women with a dichorionic triplet pregnancy to a singleton pregnancy prolongs median gestational age at birth. No statistically significant association was found with miscarriage and perinatal survival rates.
Effects of Different Blood Glucose Levels on Critically Ill Patients in an Intensive Care Unit
Authors: Kang Li , Han Juan , Yang Qun-Cao , Huang Hui-Lin , Hao Nan
Published: December 2015

Aims: We explore the infection incidence and possible prognostic outcome relevance for patients with different blood glucose levels in an intensive care unit (ICU). Methods: A total of 98 cases were enrolled and divided into three groups based on average fasting blood glucose levels (group A: ≤6.1 mmol/l; group B: 6.1-10 mmol/l; group C: ≥10 mmol/l). Results: There were no statistical differences in the time to ICU admission, the indwelling durations of gastric tubes, urinary or deep vein catheters, tracheal intubations and tracheotomies, or the length of ventilator use (all p > 0.05). No evident difference in the multiple organ dysfunction syndrome rate was found between the three groups (p = 0.226). The infection and mortality rates between the groups showed significant differences (all p < 0.05). Furthermore, the difference of respiratory system infections was statistically significant among the three groups (p = 0.008), yet no such statistical difference was observed among groups regarding nonrespiratory system infections (p = 0.227). Conclusions: Critically ill patients with a high blood glucose level were positively correlated with a relatively high APACHE II score and more serious degree of disease, as well as a higher incidence of respiratory infection during their ICU stay than those with lower blood glucose levels (<10 mmol/l).