bluuebunny/crossref_metadata_2025 huggingface dataset:
A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?
Authors: Lim Roxanne , Choudry Hassan , Conner Kim , Karnsakul Wikrom
Published: November 2014

Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.
Association of TNF-αwith Impaired Migration Capacity of Mesenchymal Stem Cells in Patients with Systemic Lupus Erythematosus
Authors: Geng Linyu , Li Xia , Feng Xuebing , Zhang Jiyun , Wang Dandan , Chen Jinyun , Liu Rui , Chen Haifeng , Sun Lingyun
Published: November 2014

Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of proliferation, differentiation, and immune modulation. Considering that migration capacity is important for the exertion of BMSCs functions, the defects in migration might contribute to BMSCs dysfunction in SLE patients. In this study, we showed that the migration capacity of SLE BMSCs was remarkably impaired in comparison with those of healthy controls. Increased tumor necrosis factorα(TNF-α) in SLE serum significantly inhibited the migration capacity andin vivohoming capacity of SLE BMSCs via a specific TNF receptor I (TNFRI) manner, in which decreased HGF mRNA production caused by the activation of I kappa B kinase beta (IKK-β) pathway is partially involved. To our knowledge, this is the first report to discuss the possible mechanisms for impaired migration of BMSCs in SLE patients. Our results suggest that inhibition of TNF-αpathway might be helpful for accelerating BMSCs migration to the inflammatory microenvironment in SLE patients, thereby having a potential role in SLE treatment.
High SHIP2 Expression Indicates Poor Survival in Colorectal Cancer
Authors: Yang Ju , Fu Maoying , Ding Yaoguang , Weng Yajing , Fan Weifei , Pu Xiaolin , Ge Zhijun , Zhan Feng , Ni Huihui , Zhang Wei , Jin Feng , Xu Ning , Li Jiang , Qiu Liang , Wang Jun , Gu Xuefeng
Published: November 2014

SH2-containing inositol 5′-phosphatase 2 (SHIP2), which generally regulates insulin signaling, cytoskeleton remodeling, and receptor endocytosis, has been suggested to play a significant role in tumor development and progression. However, the associations between SHIP2 expression and the clinical features to evaluate its clinicopathologic significance in colorectal cancer (CRC) have not been determined yet. In the present study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with CRC tissue microarrays (TMA) were employed to evaluate the mRNA and protein expression of SHIP2 in CRC. The results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in CRC tissues than that in corresponding noncancerous tissues (bothP<0.05). The expression of SHIP2 protein in CRC was related to lymph node metastasis(P=0.036), distant metastasis(P=0.001), and overall survival(P=0.009). Kaplan-Meier method and Cox multifactor analysis suggested that high SHIP2 protein level(P=0.040)and positive distant metastasis(P=0.048)were critically associated with the unfavorable survival of CRC patients. The findings suggested that SHIP2 may be identified as a useful prognostic marker in CRC and targeting CRC may provide novel strategy for CRC treatment.
Motor Activity in Aging: An Integrated Approach for Better Quality of Life
Authors: Pratali Lorenza , Mastorci Francesca , Vitiello Nicola , Sironi Annamaria , Gastaldelli Amalia , Gemignani Angelo
Published: November 2014

Old age is normally associated with stereotypical structural and physiological changes in the brain that are caused by deterioration in elementary cognitive, sensory, and sensorimotor functions as well as increased susceptibility to stress. These changes are connected with gait impairment and falls, especially among patients with common neurological diseases. Even in the absence of history of falling or when there is no physical injury after a fall, many older people develop a fear of falling that leads to restricted mobility, reduced activity, depression, social isolation, worsened metabolic disease, and increasing risk of cardiovascular morbidity and mortality. Although links between cognitive decline and age-associated brain changes have been clarified, relationships between gait disorders and psychophysiological alterations in aging are less well understood. This review focuses on two crucial elements of aged individuals with gait disorders: characteristic comorbidities in the elderly and the psychophysiological effects of physical exercise in the elderly with gait disorder. We propose an integrated approach to studying elderly subjects with gait disorder before starting a program of motor rehabilitation with wearable robotic devices, in order to investigate the effectiveness and safety of the ambulatory training.
Vaginal Treatment of Vaginal Cuff Dehiscence with Visceral Loop Prolapse: A New Challenge in Reparative Vaginal Surgery?
Authors: Mastrolia Salvatore Andrea , Di Naro Edoardo , Schonauer Luca Maria , Loverro Maria Teresa , Indellicati Beatrice , Barnaba Mario , Loverro Giuseppe
Published: November 2014

Vaginal cuff dehiscence is a rare, but potentially morbid, complication of total hysterectomy and refers to separation of the vaginal cuff closure. The term vaginal cuff dehiscence is frequently interchanged with the terms of cuff separation or cuff rupture. All denote the separation of a vaginal incision that was previously closed at time of total hysterectomy. After dehiscence of the vaginal cuff, abdominal or pelvic contents may prolapse through the vaginal opening. Bowel evisceration, outside the vulvar introitus, can lead to serious sequelae, including peritonitis, bowel injury and necrosis, or sepsis. Therefore, although prompt surgical and medical intervention is required to replace prolapsed structures, the main problem remains the reconstruction of vaginal vault. In case of recent hysterectomy, vaginal reparation only requires the approximation of vaginal walls, including their fascia, while if dehiscence occurs after a long time from hysterectomy, the adequate suspension of the vaginal vault has to be taken into consideration. In this report we describe the case of a postmenopausal patient, undergoing surgical emergency because of the evisceration of an intestinal loop through a dehiscence of vaginal vault, after numerous reconstructive vaginal surgeries for vaginal prolapse. This paper analyzes clinical circumstances, risk factors, comorbidity, and clinical and surgical management of this complication.
Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin
Authors: Marcondes Maria Cecilia Garibaldi , Ojakian Ryan , Bortell Nikki , Flynn Claudia , Conti Bruno , Fox Howard S.
Published: November 2014

Upregulation of osteopontin (OPN) is a characteristic of central nervous system pathologies. However, the role of OPN in inflammation is still controversial, since it can both prevent cell death and induce the migration of potentially damaging inflammatory cells. To understand the role of OPN in inflammation and cell survival, we expressed OPN, utilizing an adenoviral vector, in the caudoputamen of mice deficient in OPN, using beta-galactosidase- (β-gal-) expressing vector as control. The tissue pathology and the expression of proinflammatory genes were compared in both treatments. Interestingly, inflammatory infiltrate was only found when the OPN-vector was combined with a peripheral treatment with pertussis toxin (Ptx), which activated peripheral cells to express the OPN receptor CD44v6. Relative toβ-gal, OPN increased the levels of inflammatory markers, including IL13Rα1, CXCR3, and CD40L. In Ptx-treated OPN KOs, apoptotic TUNEL+ cells surrounding the OPN expression site increased, compared toβ-gal. Together, these results show that local OPN expression combined with a peripheral inflammatory stimulus, such as Ptx, may be implicated in the development of brain inflammation and induction of cell death, by driving a molecular pattern characteristic of cytotoxicity. These are characteristics of inflammatory pathologies of the CNS in which OPN upregulation is a hallmark.
Incidence of Radix Entomolaris in Mandibular First Molars in Palestinian Population: A Clinical Investigation
Authors: Mukhaimer Raed , Azizi Zafer
Published: November 2014

Purpose. The aim of this investigation was to evaluate clinically the percentage of permanent mandibular first molar teeth with three roots amongst Palestinian population. Patients and Methods. Three hundred twenty-two mandibular first molars from 185 females and 137 males scheduled for root canal treatment at the Dental Center of the Arab American University were examined over a 2-year period. The incidence of a third root revealed by periapical radiographs and the comparison of the occurrence between males and females and between the right and left sides of the mandible were recorded. Statistical Analysis. It was performed using the chi-square test with a significant level set at P<0.05%. Results. Of the 322 treated mandibular first molars, twelve teeth were found to have a third root with an overall incidence being 3.73%. More teeth with a third root were treated on the right side of the mandible compared to the left side. Conclusion. The incidence of a third root in Palestinian population was within the range of previous reports from the Middle East but considerably lower than the percentage from the Far East.
Adverse Reactions to Antituberculosis Drugs in Iranian Tuberculosis Patients
Authors: Farazi Aliasghar , Sofian Masoomeh , Jabbariasl Mansoureh , Keshavarz Sara
Published: November 2014

Background. Antituberculosis multidrug regimens have been associated with increased incidence of adverse drug reactions (ADRs). This study aimed to determine the incidence and associated factors of ADRs due to antituberculosis therapy.Methods. This is a retrospective cross-sectional study on tuberculosis patients who were treated in tuberculosis clinics in Markazi province in Iran. The information contained in the medical files was extracted and entered into the questionnaire. Data was descriptively analyzed by using statistical package for social sciences (SPSS 18).Results. A total of 940 TB patients of 1240 patients’ medical records available in 10 medical offices were included in this study. Of the 563 ADRs found in this study, 82.4% were considered minor reactions and 17.6% were major reactions. No death from antituberculosis ADR was observed. We found that the risk of major ADRs was higher in females (P  value=0.0241), age >50 y (P  value=0.0223), coinfection with HIV (P  value=0.0323), smoking (P  value=0.002), retreatment TB (P  value=0.0203), and comorbidities (P  value=0.0005).Conclusions. This study showed that severe side effects of anti-TB drugs are common in patients who have risk factors of ADRs and they should be followed up by close monitoring.
Suicidal Ideation and Associated Factors among Adolescents in Northeastern Brazil
Authors: Silva Roberto Jerônimo dos Santos , Santos Fabio Alexandre Lima dos , Soares Nara Michelle Moura , Pardono Emerson
Published: November 2014

This study aimed to identify the prevalence and factors associated with suicidal ideation among Brazilian adolescents. The instrument designed for the research was used considering three models with outcomes that identified the following: (a) adolescent had considered suicide, (b) adolescents have planned suicide, and (c) adolescents have attempted suicide. Logistic Regression was used in all models with significance level of 5%. An association between being female and suicidal ideation(OR=2.18, CI 95% 1.60 to 2.97), suicide planning(OR=1.80, CI 95% = 1.26–2.56), and suicide attempt(OR=2.91, CI 95% 1.79 to 4.75) was found. Violent behavior/involvement in fights was associated with thinking about suicide(OR=2.00, CI 95% = 1.43 to 2.81), suicide planning(OR=1.65, CI 95% = 1.10–2.46), and suicide attempt(OR=2.35, CI 95% = 1.49 to 3.70). For cigarette consumption, association was found with suicide ideation(OR=1.62, CI 95% 1.03 to 2.55), planning(OR=1.88, CI 95% = 1.15 to 3.08), and attempt(OR=2.35, CI 95% 1.37 to 4.03). For alcohol consumption, association was found with suicide ideation(OR=1.93, CI 95% 1.47 to 2.54), planning(OR=2.22, CI 95% 1.61 to 3.08), and attempt(OR=1.73, CI 95% 1.15 to 2.59). It was concluded that suicidal ideation was associated with female sex, involvement in fights, and illicit drug use.
Interocular Symmetry in Macular Choroidal Thickness in Children
Authors: Al-Haddad Christiane , El Chaar Lama , Antonios Rafic , El-Dairi Mays , Noureddin Baha’
Published: November 2014

Objective.To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT) and correlate findings with biometric data.Methods.This observational cross-sectional study included 91 (182 eyes) healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed.Results.Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers’ measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender.Conclusion.Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction.
Temporal Bacteriostatic Effect and Growth Factor Loss in Equine Platelet Components and Plasma Cultured with Methicillin-Sensitive and Methicillin-ResistantStaphylococcus aureus: A ComparativeIn VitroStudy
Authors: López Catalina , Álvarez María E. , Carmona Jorge U.
Published: November 2014

The aims were (1) to evaluate the bacteriostatic effect of platelet-rich plasma (PRP), platelet-rich gel (PRG), leukocyte-poor plasma (LPP), leukocyte-poor gel (LPG), plasma, and heat-inactivated plasma (IP) on both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) over a period of 24 h; (2) to determine and to compare the concentrations and degradation over time of platelet factor 4 (PF-4), transforming growth factor beta 1 (TGF-β1), and platelet-derived growth factor isoform BB (PDGF-BB); and (3) to identify any correlations between MSSA and MRSA growth and either the cellular, PF-4, TGF-β1, or PDGF-BB concentrations in the blood components. PRP and its byproducts from 18 horses were obtained by the tube method. All blood components were cultured with either MSSA or MRSA. Bacterial growth, PF-4, TGF-β1, and PDGF-BB were determined at 6 h and 24 h. At six hours, bacterial growth was significantly inhibited by all blood components, with the exception of IP. MSSA was more sensitive to the treatments than MRSA. At 24 hours, bacterial growth was significantly higher in IP. MRSA bacterial growth was significantly higher in PRP, LPP, and plasma when compared to MSSA. Growth factor concentrations were not significantly affected by bacteria.
3D Dynamic Culture of Rabbit Articular Chondrocytes Encapsulated in Alginate Gel Beads Using Spinner Flasks for Cartilage Tissue Regeneration
Authors: Xu Feiyue , Xu Lei , Wang Qi , Ye Zhaoyang , Zhou Yan , Tan Wen-Song
Published: November 2014

Cell-based therapy using chondrocytes for cartilage repair suffers from chondrocyte dedifferentiation. In the present study, the effects of an integrated three-dimensional and dynamic culture on rabbit articular chondrocytes were investigated. Cells (passages 1 and 4) were encapsulated in alginate gel beads and cultured in spinner flasks in chondrogenic and chondrocyte growth media. Subcutaneous implantation of the cell-laden beads was performed to evaluate the ectopic chondrogenesis. It was found that cells remained viable after 35 days in the three-dimensional dynamic culture. Passage 1 cells demonstrated a proliferative growth in both media. Passage 4 cells showed a gradual reduction in DNA content in growth medium, which was attenuated in chondrogenic medium. Deposition of glycosaminoglycans (GAG) was found in all cultures. While passage 1 cells generally produced higher amounts of GAG than passage 4 cells, GAG/DNA became similar on day 35 for both cells in growth media. Interestingly, GAG/DNA in growth medium was greater than that in chondrogenic medium for both cells. Based on GAG quantification and gene expression analysis, encapsulated passage 1 cells cultured in growth medium displayed the best ectopic chondrogenesis. Taken together, the three-dimensional and dynamic culture for chondrocytes holds great potential in cartilage regeneration.
Perihelion Precession and Deflection of Light in the General Spherically Symmetric Spacetime
Authors: Hu Ya-Peng , Zhang Hongsheng , Hou Jun-Peng , Tang Liang-Zun
Published: November 2014

The perihelion precession and deflection of light have been investigated in the 4-dimensional general spherically symmetric spacetime, and the master equation is obtained. As the application of this master equation, the Reissner-Nordstorm-AdS solution and Clifton-Barrow solution inf(R)gravity have been taken as examples. We find that both the electric charge andf(R)gravity can affect the perihelion precession and deflection of light, while the cosmological constant can only effect the perihelion precession. Moreover, we clarify a subtlety in the deflection of light in the solar system that the possible sun’s electric charge is usually used to interpret the gap between the experiment data and theoretical result. However, after also considering the effect from the sun’s same electric charge on the perihelion precession of Mercury, we can find that it is not the truth.
Multiple Adaptive Fading Schmidt‐Kalman Filter for Unknown Bias
Authors: Lou Tai-Shan , Wang Zhi-Hua , Xiao Meng-Li , Fu Hui-Min
Published: November 2014

Unknown biases in dynamic and measurement models of the dynamic systems can bring greatly negative effects to the state estimates when using a conventional Kalman filter algorithm. Schmidt introduces the “consider” analysis to account for errors in both the dynamic and measurement models due to the unknown biases. Although the Schmidt‐Kalman filter “considers” the biases, the uncertain initial values and incorrect covariance matrices of the unknown biases still are not considered. To solve this problem, a multiple adaptive fading Schmidt‐Kalman filter (MAFSKF) is designed by using the proposed multiple adaptive fading Kalman filter to mitigate the negative effects of the unknown biases in dynamic or measurement model. The performance of the MAFSKF algorithm is verified by simulation.
Bayesian Inference of a Multivariate Regression Model
Authors: Sinay Marick S. , Hsu John S. J.
Published: November 2014

We explore Bayesian inference of a multivariate linear regression model with use of a flexible prior for the covariance structure. The commonly adopted Bayesian setup involves the conjugate prior, multivariate normal distribution for the regression coefficients and inverse Wishart specification for the covariance matrix. Here we depart from this approach and propose a novel Bayesian estimator for the covariance. A multivariate normal prior for the unique elements of the matrix logarithm of the covariance matrix is considered. Such structure allows for a richer class of prior distributions for the covariance, with respect to strength of beliefs in prior location hyperparameters, as well as the added ability, to model potential correlation amongst the covariance structure. The posterior moments of all relevant parameters of interest are calculated based upon numerical results via a Markov chain Monte Carlo procedure. The Metropolis-Hastings-within-Gibbs algorithm is invoked to account for the construction of a proposal density that closely matches the shape of the target posterior distribution. As an application of the proposed technique, we investigate a multiple regression based upon the 1980 High School and Beyond Survey.
Intraoperative Neuromonitoring of the External Branch of the Superior Laryngeal Nerve during Thyroidectomy: The Need for Evidence-Based Data and Perioperative Technical/Technological Standardization
Authors: Mangano Alberto , Lianos Georgios D. , Boni Luigi , Kim Hoon Yub , Roukos Dimitrios H. , Dionigi Gianlorenzo
Published: November 2014

The external branch of the superior laryngeal nerve (EBSLN) is surgically relevant since its close anatomical proximity to the superior thyroid vessels. There is heterogeneity in the EBSLN anatomy and EBSLN damage produces changes in voice that are very heterogenous and difficult to diagnose. The reported prevalence of EBSLN injury widely ranges. EBSLN iatrogenic injury is considered the most commonly underestimated complication in endocrine surgery because vocal assessment underestimates such event and laryngoscopic postsurgical evaluation does not show standardized findings. In order to decrease the risk for EBSLN injury, multiple surgical approaches have been described so far. IONM provides multiple advantages in the EBSLN surgical approach. In this review, we discuss the current state of the art of the monitored approach to the EBSLN. In particular, we summarize, providing our additional remarks, the most relevant aspects of the standardized technique brilliantly described by the INMSG (International Neuromonitoring Study Group). In conclusion, in our opinion, there is currently the need for more prospective randomized trials investigating the electrophysiological and pathological aspects of the EBSLN for a better understanding of the role of IONM in the EBSLN surgery.
Interactive Digital Serious Games for the Assessment, Rehabilitation, and Prediction of Dementia
Authors: Kazmi Sayed , Ugail Hassan , Lesk Valerie , Palmer Ian
Published: November 2014

Dementia is a serious, progressive, and often debilitating illness with no known cure, having a severe adverse effect on memory, behaviour, reasoning, and communication. A comprehensive review of current refereed research material in the use of games in this area is scarce and suffers from being orientated towards commercially available games or derivatives such as “Dr. Kawashima’s brain training.” There is much lesser concern for bespoke research grade alternatives. This review will attempt to assess the current state of the art in research orientated games for dementia, importantly identifying systems capable of prediction before the onset of the disease. It can be ascertained from the literature reviewed that there are clearly a large number of interactive computer game based mechanisms used for dementia. However, these are each highly intrusive in terms of affecting normal living and the patient is aware of being tested; furthermore their long-term or real benefits are unknown as is their effect over conventional tests. It is important to predict cognitive impairment at a stage early enough to maximise benefit from treatment and therapeutic intervention. Considering the availability, use, and increasing power of modern mobile smartphones, it is logically plausible to explore this platform for dementia healthcare.
Immediate Return to Ambulation and Improved Functional Capacity for Rehabilitation in Complex Regional Pain Syndrome following Early Implantation of a Spinal Cord Stimulation System
Authors: Goff Brandon Jesse , Naber Jeremy Wingseng , McCallin John Patrick , Lopez Edward Michael , Guthmiller Kevin Brant , Lautenschlager Karl Alan , Lai Tristan Toll , Hommer Dean Harry , Marin Gonzalez Raul
Published: November 2014

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is characterized by vasomotor, sensory, sudomotor, and motor symptoms. Spinal cord stimulation (SCS) has been successfully utilized for the treatment of pain refractory to conventional therapies. We present a case of a previously highly functioning 54-year-old female who developed a rarely reported case of idiopathic CRPS of the right ankle which spontaneously occurred four months after an uncomplicated anterior cervical disc fusion. This condition resulted in severe pain and functional impairment that was unresponsive to pharmacological management. The patient’s rehabilitation was severely stymied by her excruciating pain. However, with the initiation of spinal cord stimulation, her pain was adequately controlled allowing for progression to full unassisted ambulation, advancing functional capacity, and improving quality of life. This case report supports the concept that rapid progression to neuromodulation, rather than delays that occur due to attempts at serial sympathetic blocks, may better control symptoms leading allowing for a more meaningful recovery.
Malignant Granular Cell Tumor of the Back: A Case Report and Review of the Literature
Authors: McGuire Laura Stone , Yakoub Danny , Möller Mecker G. , Rosenberg Andrew , Livingstone Alan
Published: November 2014

Malignant granular cell tumors are rare, intensely aggressive entities. This paper presents a case of a large rapidly recurrent malignant granular cell tumor with regional and distal metastases on the back of a 54-year-old Cuban man. The primary tumor recurred within six months of the original wide local excision and with satellite lesions apparent at twelve months, and the mass was diagnosed using the histological criteria established by Fanburg-Smith et al. for malignant granular cell tumors. By fifteen months, right axillary lymphadenopathy, multiple satellite lesions, pulmonary nodules, and distant metastasis in the right thigh were present. At sixteen months, wide local excision of recurrent mass and local satellite masses along with right axillary dissection and placement of Integra with subsequent split-thickness skin graft were performed by surgical oncology and plastic surgery teams. The surgical specimen measured 32.0 × 13.5 × 5.5 cm, containing multiple homogeneous masses with the largest mass 22.0 × 9.0 × 4.6 cm. Following surgery, patient was started on Pazopanib 800 mg/day based on phase III randomized trial data in the treatment of soft tissue sarcomas showing this as a potential novel therapy for malignant granular cell tumors.
Novel Harmonic Regularization Approach for Variable Selection in Cox’s Proportional Hazards Model
Authors: Chu Ge-Jin , Liang Yong , Wang Jia-Xuan
Published: November 2014

Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvexLq  (1/2<q<1)regularizations, to select key risk factors in the Cox’s proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods.
Modeling and Performance Analysis for Cell Access and Handoff Schemes in Two‐Tier Cellular Networks
Authors: Jun Kyungkoo , Kim Sijung
Published: November 2014

We investigate the effects of handoff on system performance in two‐tier cellular networks. Two of the main performance metrics are new call blocking probability and handoff drop rate. We develop analytical models to evaluate the performance of two different handoff schemes. One scheme considers only femto‐to‐macrocell handoff while the other is bidirectional including macro‐to‐femtocell handoff. Our model is more elaborate than existing ones which have not considered the mobility of mobile stations. Numerical results show that the bidirectional scheme performs better than the femto‐to‐macrocell handoff as it achieves lower blocking probability and drop rate.
Geographical Differences in the Population-Based Cross-Sectional Growth Curve and Age at Peak Height Velocity with respect to the Prevalence Rate of Overweight in Japanese Children
Authors: Yokoya Masana , Higuchi Yukito
Published: November 2014

The School Health Examination Survey is a nationwide examination carried out annually in Japan, and the results are entered into a prefectural-level physical measurement database. We used this database to determine the geographical differences in a population-based cross-sectional growth curve and investigated the association between age at peak height velocity (PHV) and the prevalence rate of overweight in children among Japanese prefectures. Mean prefectural-level age at PHV was estimated by the cubic spline-fitting procedure using cross-sectional whole-year prefectural mean height data (5–17 years, 2006–2013), and 8-year (2006–2013) means of the standardized prevalence rates of overweight children and other anatomical data (8-year standardized weight and height) were recalculated. Mean prefectural age at PHV was more strongly correlated with the mean prefectural prevalence rate of overweight (age 5–8 years) than with other weights or heights in both sexes. On the basis of these findings and their confirmation by multiple regression analysis, the prevalence rate of overweight was selected as a primary factor to explain the geographical difference in age at PHV. These findings suggest that childhood overweight is a dominant factor responsible for the observed geographical differences in onset of puberty in Japan.
Automatic Gauge Control in Rolling Process Based on Multiple Smith Predictor Models
Authors: Li Jiangyun , Wang Kang , Li Yang
Published: November 2014

Automatic rolling process is a high-speed system which always requires high-speed control and communication capabilities. Meanwhile, it is also a typical complex electromechanical system; distributed control has become the mainstream of computer control system for rolling mill. Generally, the control system adopts the 2-level control structure—basic automation (Level 1) and process control (Level 2)—to achieve the automatic gauge control. In Level 1, there is always a certain distance between the roll gap of each stand and the thickness testing point, leading to the time delay of gauge control. Smith predictor is a method to cope with time-delay system, but the practical feedback control based on traditional Smith predictor cannot get the ideal control result, because the time delay is hard to be measured precisely and in some situations it may vary in a certain range. In this paper, based on adaptive Smith predictor, we employ multiple models to cover the uncertainties of time delay. The optimal model will be selected by the proposed switch mechanism. Simulations show that the proposed multiple Smith model method exhibits excellent performance in improving the control result even for system with jumping time delay.
Effects of the Distance between Small Intramural Uterine Fibroids and the Endometrium on the Pregnancy Outcomes of in Vitro Fertilization-Embryo Transfer
Authors: Lu Na , Wang Yang , Su Ying-chun , Sun Ying-pu , Guo Yi-hong
Published: November 2014

Aim: To explore the effects of the distance between small intramural uterine fibroids (≤4 cm) and the endometrium on the outcomes of in vitro fertilization-embryo transfer (IVF-ET). Methods: We prospectively analyzed pregnancy outcomes in 117 infertile women with small intramural uterine fibroids and 117 infertile women without uterine fibroids who all underwent IVF-ET. The size and number of small intramural uterine fibroids and the shortest distance between the small intramural uterine fibroids and the endometrium were measured by transvaginal three-dimensional ultrasound. The endometrial and subendometrial blood flow parameters, implantation rate, clinical pregnancy rate, abortion rate and live birth rate were compared between the women with and without small uterine fibroids and among the different shortest distances (≤1, 1-3 and >3 mm). The effects of the size and number of small intramural uterine fibroids on IVF-ET outcomes were observed. Results: The endometrial volume on ET day, the implantation rate and the live birth rate were significantly lower, but the abortion rate was significantly higher, in the women with small intramural uterine fibroids than in those without uterine fibroids (p < 0.05). The endometrial flow index was higher in the shortest distance ≤1-mm group than in the groups with 1-3 and >3 mm, and the implantation rate was higher in ≤1-mm group than in the >3-mm group (p < 0.05). There were no significant differences in clinical outcomes between different sizes and numbers of small intramural uterine fibroids. Conclusion: Small intramural uterine fibroids can affect IVF-ET outcomes. Compared with other shortest distances (1-3 and >3 mm), the shortest distance of ≤1 mm has a higher implantation rate.
Age and Sex as Moderators of the Placebo Response - An Evaluation of Systematic Reviews and Meta-Analyses across Medicine
Authors: Weimer Katja , Colloca Luana , Enck Paul
Published: November 2014

Predictors of the placebo response (PR) in randomized controlled trials (RCT) have been searched for ever since RCT have become the standard for testing novel therapies and age and gender are routinely documented data in all trials irrespective of the drug tested, its indication, and the primary and secondary end points chosen. To evaluate whether age and gender have been found to be reliable predictors of the PR across medical subspecialties, we extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine) known for high PR rates. The literature database used contains approximately 2,500 papers on various aspects of the genuine PR. These ‘meta-analyses' were screened for statistical predictors of the PR across multiple RCT, including age and gender, but also other patient-based and design-based predictors of higher PR rates. Retrieved papers were sorted for areas and disease categories. Only 15 of the 75 analyses noted an effect of younger age to be associated with higher PR, and this was predominantly in psychiatric conditions but not in depression, and internal medicine but not in gastroenterology. Female gender was associated with higher PR in only 3 analyses. Among the patient-based predictors, the most frequently noted factor was lower symptom severity at baseline, and among the design-based factors, it was a randomization ratio that selected more patients to drugs than to placebo, more frequent study visits, and more recent trials that were associated with higher PR rates. While younger age may contribute to the PR in some conditions, sex does not. There is currently no evidence that the PR is different in the elderly. PR are, however, markedly influenced by the symptom severity at baseline, and by the likelihood of receiving active treatment in placebo-controlled trials.
Ontogeny of the Electric Organs in the Electric Eel, Electrophorus electricus: Physiological, Histological, and Fine Structural Investigations
Authors: Schwassmann Horst O. , Assunção M. Ivaneide S. , Kirschbaum Frank
Published: November 2014

This study attempts to clarify the controversy regarding the ontogenetic origin of the main organ electrocytes in the electric eel, Electrophorus electricus. The dispute was between an earlier claimed origin from a skeletal muscle precursor [Fritsch, 1881], or from a distinct electrocyte-generating matrix, or germinative zone [Keynes, 1961]. We demonstrate electrocyte formation from a metamerically organized group of pre-electroblasts, splitting off the ventralmost tip of the embryonic trunk mesoderm at the moment of hatching from the egg. We show details of successive stages in the development of rows of electric plates, the electrocytes, by means of conventional histology and electron microscopy. The membrane-bound pre-electroblasts multiply rapidly and then undergo a specific mitosis where they lose their membranes and begin extensive cytoplasm production as electroblasts. Electrical activity, consisting of single and multiple pulses, was noticed in seven-day-old larvae that began to exhibit swimming movements. A separation of discharges into single pulses and trains of higher voltage pulses was seen first in 45-mm-long larvae. A lateralis imus muscle and anal fin ray muscles, implicated by earlier investigators in the formation of electrocytes, begin developing at a time in larval life when eight columns of electrocytes are already present. Axonal innervation is seen very early during electrocyte formation.
Surveillance and Diagnostic Algorithm for Hepatocellular Carcinoma Proposed by the Liver Cancer Study Group of Japan: 2014 Update
Authors: Kudo Masatoshi , Matsui Osamu , Izumi Namiki , Iijima Hiroko , Kadoya Masumi , Imai Yasuharu ,   on behalf of the Liver Cancer Study Group of Japan
Published: November 2014

Surveillance and diagnostic algorithms for hepatocellular carcinoma (HCC) have already been described in guidelines published by the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver and the European Organisation for Research and Treatment of Cancer (EASL-EORTC), and the Japan Society of Hepatology (JSH), but the content of these algorithms differs slightly. The JSH algorithm mainly differs from the other two algorithms in that it is highly sophisticated and considers the functional imaging techniques of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) and Sonazoid contrast-enhanced ultrasound (CEUS) to be very important diagnostic modalities. In contrast, the AASLD and EASL-EORTC algorithms are less advanced and suggest that a diagnosis be made based solely on hemodynamic findings using dynamic CT/MRI and biopsy findings. A consensus meeting regarding the JSH surveillance and diagnostic algorithm was held at the 50th Liver Cancer Study Group of Japan Congress, and a 2014 update of the algorithm was completed. The new algorithm reaffirms the very important role of EOB-MRI and Sonazoid CEUS in the surveillance and diagnosis of liver cancer and is more sophisticated than those currently used in the United States and Europe. This is now an optimized algorithm that can be used to diagnose early-stage to classical HCC easily and highly accurately.
Transarterial Chemoembolization Failure/Refractoriness: JSH-LCSGJ Criteria 2014 Update
Authors: Kudo Masatoshi , Matsui Osamu , Izumi Namiki , Kadoya Masumi , Okusaka Takuji , Miyayama Shiro , Yamakado Koichiro , Tsuchiya Kaoru , Ueshima Kazuomi , Hiraoka Atsushi , Ikeda Masafumi , Ogasawara Sadahisa , Yamashita Tatsuya , Minami Tetsuya ,   on behalf of the Liver Cancer Study Group of Japan
Published: November 2014

In the 2010 version of the Japan Society of Hepatology (JSH) consensus-based treatment algorithm for the management of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) failure/refractoriness was defined assuming the use of superselective lipiodol TACE, which has been widely used worldwide and particularly in Japan, and areas with lipiodol deposition were considered to be necrotic. However, this concept is not well accepted internationally. Furthermore, following the approval of microspheres, an embolic material that does not use lipiodol, in February 2014 in Japan, the phrase ‘lipiodol deposition' needed to be changed to ‘necrotic lesion or viable lesion'. Accordingly, the respective section in the JSH guidelines was revised to define TACE failure as an insufficient response after ≥2 consecutive TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, even after chemotherapeutic agents have been changed and/or the feeding artery has been reanalyzed. In addition, the appearance of a higher number of lesions in the liver than that recorded at the previous TACE procedure (other than the nodule being treated) was added to the definition of TACE failure/refractoriness. Following the discussion of other issues concerning the continuous elevation of tumor markers, vascular invasion, and extrahepatic spread, descriptions similar to those in the previous version were approved. The revision of these TACE failure definitions was approved by over 85% of HCC experts. © 2014 S. Karger AG, Basel
Validation of the Criteria of Transcatheter Arterial Chemoembolization Failure or Refractoriness in Patients with Advanced Hepatocellular Carcinoma Proposed by the LCSGJ
Authors: Arizumi Tadaaki , Ueshima Kazuomi , Chishina Hirokazu , Kono Masashi , Takita Masahiro , Kitai Satoshi , Inoue Tatsuo , Yada Norihisa , Hagiwara Satoru , Minami Yasunori , Sakurai Toshiharu , Nishida Naoshi , Kudo Masatoshi
Published: November 2014

Background: Transcatheter arterial chemoembolization (TACE) failure or refractoriness is an indication for sorafenib therapy in patients with advanced hepatocellular carcinoma. The study evaluated the validity of the definition of TACE failure or refractoriness as proposed by the Liver Cancer Study Group of Japan (LCSGJ) through a retrospective analysis of sorafenib treatment. Methods: Out of 265 patients with advanced hepatocellular carcinoma who were treated with sorafenib at our hospital, 45 experienced TACE failure or refractoriness and were included in this study and retrospectively analyzed. Results: Multivariate analysis only identified the number of ineffective TACE procedures performed before starting sorafenib treatment as significant factors. Overall survival (OS) after starting sorafenib was statistically longer in patients treated with ≤2 consecutive ineffective TACE procedures before sorafenib administration than in patients treated with ≥3 consecutive ineffective TACE procedures (p < 0.005). This result matched the LCSGJ criteria. Conclusion: In patients treated with sorafenib, OS was extended with ≤2 consecutive ineffective TACE procedures compared to that with ≥3 consecutive ineffective TACE procedures. Thus, if tumors are uncontrolled, TACE should not be repeated. The result of this study supports the definition of TACE failure or refractoriness proposed by the LCSGJ.
Pathological Diagnosis of Benign Hepatocellular Nodular Lesions Based on the New World Health Organization Classification
Authors: Kondo Fukuo , Fukusato Toshio , Kudo Masatoshi
Published: November 2014

There are various types of benign hepatocellular nodular lesions, and their diagnostic criteria were formulated in detail. However, in 2010, the new World Health Organization (WHO) classification introduced immunohistochemical diagnostic criteria for hepatocellular adenoma (HCA) reflecting molecular pathological properties, and HCA was classified into 4 subtypes. These criteria were useful for its differential diagnosis from focal nodular hyperplasia (FNH). They were also useful for the diagnosis of HCA, its subtyping, and differentiation from FNH in Japan. However, the new WHO classification is based on principles that differ from those of conventional definitions of disease concepts and methods for the differential diagnosis. Therefore, it has caused disagreements in the diagnosis in some cases. Based on this background, we present a new perspective on the diagnosis of benign hepatocellular nodular lesions.
Treatment Strategies of Intermediate-Stage Hepatocellular Carcinomas in Japan (Barcelona Clinic Liver Cancer Stage B)
Authors: Yamakado Koichiro , Kudo Masatoshi
Published: November 2014

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and it shows increasing incidence worldwide. The Barcelona Clinic Liver Cancer (BCLC) staging system has become widely accepted in clinical practice, but in Japan, two clinical practice guidelines have been used for HCC: the Evidence-Based Clinical Practice Guidelines and the Consensus-Based Clinical Practice Guidelines. Although, in Japan, chemoembolization is the first-line treatment of intermediate-stage (stage B) HCC patients in the BCLC staging system, along with chemoembolization, locoregional treatments, such as resection and radiofrequency ablation, and hepatic arterial infusion chemotherapy are incorporated into the treatment algorithm based on the tumor number and size as well as on the liver profile.
Multimodality Treatment with Radiotherapy for Huge Hepatocellular Carcinoma
Authors: Han Hee Ji , Kim Mi Sun , Cha Jihye , Choi Jin Sub , Han Kwang Hyub , Seong Jinsil
Published: November 2014

Background: For huge hepatocellular carcinoma (HCC), therapeutic decisions have varied from local therapy to systemic therapy, with radiotherapy (RT) playing only a palliative role. In this study, we investigated whether multimodality treatment involving RT could be effective in huge HCC. Results: This study was performed in 116 patients with HCC >10 cm. The number of patients in stage II, III and IV was 12, 54 and 50, respectively. RT was given as a combined modality in most patients. The median dose was 45 Gy, with 1.8 Gy per fraction. The median overall survival (OS) and progression-free survival (PFS) were 14.8 and 6.5 months, respectively. The median infield PFS was not reached. Infield failure, outfield intrahepatic and extrahepatic failure were observed in 8.6, 18.1, and 12.1% of patients, respectively. For OS and PFS, number of tumors, initial alpha-fetoprotein (AFP) level, treatment response, percent AFP decrement, and hepatic resection were significant prognostic factors. Tumor characteristics and treatment response were significantly different between long-term survivors and the other patients. Conclusion: Although huge HCC presents an aggressive clinical course, multimodality approaches involving RT can offer an opportunity for prolonged survival.