bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral spondyloarthritis: no association with clinical response to treatment or with disease relapse upon treatment discontinuation
Authors: Paramarta Jacqueline E , Baeten Dominique L 
Published: July 2014

Abstract
Introduction
In this study, we evaluated the clinical relevance of serum drug levels and antidrug antibodies (ADAbs) with regard to response to treatment, as well as to relapse upon treatment discontinuation, in peripheral spondyloarthritis (pSpA) patients treated with adalimumab.

Methods
The study included 26 pSpA patients treated with adalimumab for either 12 weeks (n = 12) or 24 weeks (n = 14) in a randomized controlled trial. Patients achieving inactive disease measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) at the end of the treatment period were classified as responders. Clinical characteristics, serum trough adalimumab levels and ADAbs were assessed at the end of the treatment period and at follow-up (upon relapse or, in absence of relapse, at 16 weeks after discontinuation).

Results
Serum adalimumab levels measured 2 weeks after the last adalimumab administration ranged from <0.002 to 23.0 μg/ml, with a median of 11.5 μg/ml. These levels were associated with neither response to treatment or disease activity measurements at the end of treatment nor with the occurrence of relapse and time to relapse after discontinuation of treatment. Antiadalimumab ADAbs were present in 23% of the patients at end of treatment and in 35% at follow-up after treatment discontinuation, indicating that ADAbs were masked by the presence of the drug in some patients. However, ADAbs at the end of treatment and at follow-up were not different between responders and nonresponders and were not associated with relapse upon discontinuation of treatment.

Conclusions
There is no clear association between adalimumab serum levels or antiadalimumab ADAbs with clinical response to treatment or with relapse upon treatment discontinuation in pSpA.

Trial registration
Netherlands Trial Register ID:NTR1806 (registered 7 May 2009)
Emergence of New ALK Mutations at Relapse of Neuroblastoma
Authors: Schleiermacher Gudrun , Javanmardi Niloufar , Bernard Virginie , Leroy Quentin , Cappo Julie , Rio Frio Thomas , Pierron Gaelle , Lapouble Eve , Combaret Valérie , Speleman Frank , de Wilde Bram , Djos Anna , Øra Ingrid , Hedborg Fredrik , Träger Catarina , Holmqvist Britt-Marie , Abrahamsson Jonas , Peuchmaur Michel , Michon Jean , Janoueix-Lerosey Isabelle , Kogner Per , Delattre Olivier , Martinsson Tommy 
Published: July 2014

Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. Methods We analyzed ALK mutations in 54 paired diagnosis–relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000× deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. Results All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). Conclusion In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199
Authors: Adams Sylvia , Gray Robert J. , Demaria Sandra , Goldstein Lori , Perez Edith A. , Shulman Lawrence N. , Martino Silvana , Wang Molin , Jones Vicky E. , Saphner Thomas J. , Wolff Antonio C. , Wood William C. , Davidson Nancy E. , Sledge George W. , Sparano Joseph A. , Badve Sunil S. 
Published: July 2014

Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
Surgical Considerations in Older Adults With Cancer
Authors: Korc-Grodzicki Beatriz , Downey Robert J. , Shahrokni Armin , Kingham T. Peter , Patel Snehal G. , Audisio Riccardo A. 
Published: July 2014

Purpose The aging of the population is a real concern for surgical oncologists, who are increasingly being asked to treat patients who would not have been considered for surgery in the past. In many cases, decisions are made with relatively little evidence, most of which was derived from trials in which older age was a limiting factor for recruitment. Methods This review focuses on risk assessment and perioperative management. It describes the relationship between age and outcomes for colon, lung, hepatobiliary, and head and neck cancer, which are predominantly diseases of the elderly and are a major cause of morbidity and mortality. Results Effective surgery requires safe performance as well as reasonable postoperative life expectancy and maintenance of quality of life. Treatment decisions for potentially vulnerable elderly patients should take into account data obtained from the evaluation of geriatric syndromes, such as frailty, functional and cognitive limitations, malnutrition, comorbidities, and polypharmacy, as well as social support. Postoperative care should include prevention and treatment of complications seen more frequently in the elderly, including postoperative delirium, functional decline, and the need for institutionalization. Conclusion Surgery remains the best modality for treatment of solid tumors, and chronologic age alone should not be a determinant for treatment decisions. With adequate perioperative risk stratification, functional assessment, and oncologic prognostication, elderly patients with cancer can do as well in terms of morbidity and mortality as their younger counterparts. If surgery is determined to be the appropriate treatment modality, patients should not be denied this option because of their age.
Supportive Care Considerations for Older Adults With Cancer
Authors: Naeim Arash , Aapro Matti , Subbarao Rashmi , Balducci Lodovico 
Published: July 2014

The treatment of cancer presents specific concerns that are unique to the growing demographic of elderly patients. Because the incidence of cancer is strongly correlated with aging, the expansion of supportive care and other age-appropriate therapies will be of great importance as the population of elderly patients with cancer increases in the coming years. Elderly patients are especially likely to experience febrile neutropenia, complications from chemotherapy-induced nausea, anemia, osteoporosis (especially in patients diagnosed with breast or prostate cancer), depression, insomnia, and fatigue. These issues are often complicated by other chronic conditions related to age, such as diabetes and cardiac disease. For many patients, symptoms may be addressed both through lifestyle management and pharmaceutical approaches. Therefore, the key to improving quality of life for the elderly patient with cancer is an awareness of their specific needs and a familiarity with emergent treatment options.
Scientific Publications in the Journal
Authors: Девисилов  , Devisilov Vladimir 
Published: July 2014

Summing up eight years of publishing the journal, analyzing issued articles and journal topic, studying manuscript
preparation and publication. Laying out editors’ and publishers’ requirements to submitted manuscripts. Offering
recommendations on article writing and design, approximate and recommended manuscript writing schedules and
schemes, and technical standards for reference lists that are obligatory for every article. Informing on transliteration rules
for reference lists in Russian, the journal’s web-sites, and Agreement between authors and editors.
Spectral Clarity Modified Method in Ecological Safety Monitoring of Dust-trapping and Gas-cleaning Units
Authors: Дьяченко  , Dyachenko Vladimir , Роговский  , Rogovskiy Viktor , Чартий  , Chartiy Pavel 
Published: July 2014

The article develops a new approach to the enhancement of ecological safety and productivity of dust-trapping and gascleaning
units; technique is based on modified spectral clarity method. Dusted airflow was studied on special dust-test bed
with modified spectral clarity method. Research is based on implementing three-wavelength lasers for discovering not only
mass concentration of dust, but its size-consist determination. It allows constructing a sensor able to detect faults of sock
filters in real-time on early stages.
Lasers and Safety. Yesterday, Today, Tomorrow. Part 1
Authors: Пальцев  , Paltsev Yuriy , Кибовский  , Kibovskiy V. , Рахманов  , Rakhmanov Boris , Девисилов  , Devisilov Vladimir 
Published: July 2014

The article surveys evolutionary issues of military and civil laser technology, as well as historic aspects of formation and
contemporary state of laser safety in Russia and abroad. Biological impact of laser emission and the principles of rulemaking
are considered. Major regulatory documents for laser safety and laser dosimetry are reviewed. The study grounds
the necessity of enhancement of state regulation methods for laser safety.
Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB
Authors: Polito Vinicia A , Li Hongmei , Martini‐Stoica Heidi , Wang Baiping , Yang Li , Xu Yin , Swartzlander Daniel B , Palmieri Michela , di Ronza Alberto , Lee Virginia M‐Y , Sardiello Marco , Ballabio Andrea , Zheng Hui 
Published: July 2014

AbstractAccumulating evidence implicates impairment of the autophagy‐lysosome pathway in Alzheimer's disease (AD). Recently discovered, transcription factor EB (TFEB) is a molecule shown to play central roles in cellular degradative processes. Here we investigate the role of TFEB in AD mouse models. In this study, we demonstrate that TFEB effectively reduces neurofibrillary tangle pathology and rescues behavioral and synaptic deficits and neurodegeneration in the rTg4510 mouse model of tauopathy with no detectable adverse effects when expressed in wild‐type mice. TFEB specifically targets hyperphosphorylated and misfolded Tau species present in both soluble and aggregated fractions while leaving normal Tau intact. We provide in vitro evidence that this effect requires lysosomal activity and we identify phosphatase and tensin homolog (PTEN) as a direct target of TFEB that is required for TFEB‐dependent aberrant Tau clearance. The specificity and efficacy of TFEB in mediating the clearance of toxic Tau species makes it an attractive therapeutic target for treating diseases of tauopathy including AD.
Growth After Adenotonsillectomy for Obstructive Sleep Apnea: An RCT
Authors: Katz Eliot S. , Moore Renee H. , Rosen Carol L. , Mitchell Ron B. , Amin Raouf , Arens Raanan , Muzumdar Hiren , Chervin Ronald D. , Marcus Carole L. , Paruthi Shalini , Willging Paul , Redline Susan 
Published: July 2014

BACKGROUND AND OBJECTIVES:
Adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) may lead to weight gain, which can have deleterious health effects when leading to obesity. However, previous data have been from nonrandomized uncontrolled studies, limiting inferences. This study examined the anthropometric changes over a 7-month interval in a randomized controlled trial of adenotonsillectomy for OSAS, the Childhood Adenotonsillectomy Trial.

METHODS:
A total of 464 children who had OSAS (average apnea/hypopnea index [AHI] 5.1/hour), aged 5 to 9.9 years, were randomized to Early Adenotonsillectomy (eAT) or Watchful Waiting and Supportive Care (WWSC). Polysomnography and anthropometry were performed at baseline and 7-month follow-up. Multivariable regression modeling was used to predict the change in weight and growth indices.

RESULTS:
Interval increases in the BMI z score (0.13 vs 0.31) was observed in both the WWSC and eAT intervention arms, respectively, but were greater with eAT (P &lt; .0001). Statistical modeling showed that BMI z score increased significantly more in association with eAT after considering the influences of baseline weight and AHI. A greater proportion of overweight children randomized to eAT compared with WWSC developed obesity over the 7-month interval (52% vs 21%; P &lt; .05). Race, gender, and follow-up AHI were not significantly associated with BMI z score change.

CONCLUSIONS:
eAT for OSAS in children results in clinically significant greater than expected weight gain, even in children overweight at baseline. The increase in adiposity in overweight children places them at further risk for OSAS and the adverse consequences of obesity. Monitoring weight, nutritional counseling, and encouragement of physical activity should be considered after eAT for OSAS.
Numerical Simulations of Capacitive Resistivity Imaging (CRI) Measurements
Authors: Uhlemann Sebastian , Kuras Oliver 
Published: July 2014

ABSTRACTElectrical resistivity tomography (ERT) is a well‐developed geophysical technique that is used to study a variety of geoscientific problems. In recent years it has been applied to the study of permafrost processes at both field and laboratory scale. However, highly resistive surface conditions limit its applicability due to high and variable contact resistances. The use of capacitively coupled sensors is expected to overcome this problem by providing a steady contact impedance regime. Although the theory of capacitive resistivity imaging (CRI) is well understood, a point‐pole approximation of the sensors is typically used to show the similarity between CRI and ERT. Due to their nature, capacitive sensors cannot be designed as point‐poles as they require a finite extent. This paper assesses the effects the finite size of sensors has on the applicability of CRI theory and aims to provide an improved understanding of the measured data. We employ finite‐element numerical modelling to simulate CRI measurements over a homogeneous halfspace and on a finite rock sample. The results of a parameter study over a homogeneous halfspace are compared to an analytical solution. Observed discrepancies between the two solutions clearly indicate that large sensor sizes and small sensor separations violate the point‐pole assumption of the analytical solution. In terms of data interpretation, this dictates that sensor separations smaller than twice the sensor size have to be avoided in order to remain below a generic error threshold of 5%. We show that sensor elevation, halfspace resistivity, halfspace permittivity, and measurement frequency have only minor effects on the discrepancy between simulation and analytical solution. The simulation of sequential CRI measurements on a finite rock sample suggests that, in line with expectations, the measured signals lie mainly in the 4th quadrant of the complex plane. However, we can also observe data with negative geometric factors, which are related to uncommon array. A comparison between simulated and measured data showed very good agreement; it validated the simulations and explained the measured data acquired using a prototype multisensor CRI system. We show that a comparison of simulated and measured imaginary parts of the transfer impedance can be used to assess CRI measurement errors. Our work demonstrates that finite‐element numerical modelling of CRI measurements is a valuable tool with which to define limitations on array design and to assess data quality.
Calibration of frequency‐domain electromagnetic devices used in near‐surface surveying
Authors: Thiesson Julien , Kessouri Pauline , Schamper Cyril , Tabbagh Alain 
Published: July 2014

ABSTRACTFor the past forty years electromagnetic prospecting instruments have played a growing role in the mapping of soil EM properties in the very low‐frequency (VLF) range for a large variety of applica tions and they are now beginning to be applied in the medium‐frequency range. Measurement interpretations, however, necessitate expressing the results in terms of physical properties. This step allows not only comparisons and joint interpretation with data generated by different electromag netic induction (EMI) instruments but also with other types of field measurements e.g., vertical electrical sounding (VES) or electrical resistivity tomography (ERT) or laboratory tests on samples.The calibration process here proposed is based on comparisons between the instrument respons es and: (1) an exact 1D multi‐layer analytical modelling that takes the three EM properties into account, i.e., the electrical conductivity, the complex magnetic susceptibility and the complex die lectric permittivity when the instrument is elevated above a layered ground; (2) the response to purely conductive metallic spheres, which only depends on the diameter of the spheres. It is applied to two instrument prototypes: one in the VLF frequency range and the other in the medium‐frequency (MF) range.
Specific Increase in Potency via Structure-Based Design of a TCR
Authors: Malecek Karolina , Grigoryan Arsen , Zhong Shi , Gu Wei Jun , Johnson Laura A. , Rosenberg Steven A. , Cardozo Timothy , Krogsgaard Michelle 
Published: July 2014

Abstract
Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive “self” proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo. Although encouraging, the limited clinical responses underscore the need for enrichment of T cells with desirable antitumor capabilities prior to patient transfer. In this study, we used structure-based design to predict point mutations of a TCR (DMF5) that enhance its binding affinity for an agonist tumor Ag–MHC (peptide–MHC [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger immune responses. We analyzed the effects of selected TCR point mutations on T cell activation potency and analyzed cross-reactivity with related Ags. Our results showed that the mutated TCRs had improved T cell activation potency while retaining a high degree of specificity. Such affinity-optimized TCRs have demonstrated to be very specific for Mart-1 (27L), the epitope for which they were structurally designed. Although of somewhat limited clinical relevance, these studies open the possibility for future structural-based studies that could potentially be used in adoptive immunotherapy to treat melanoma while avoiding adverse autoimmunity-derived effects.
CaMKIV-Dependent Preservation of mTOR Expression Is Required for Autophagy during Lipopolysaccharide-Induced Inflammation and Acute Kidney Injury
Authors: Zhang Xianghong , Howell Gina M. , Guo Lanping , Collage Richard D. , Loughran Patricia A. , Zuckerbraun Brian S. , Rosengart Matthew R. 
Published: July 2014

Abstract
Autophagy, an evolutionarily conserved homeostasis process regulating biomass quantity and quality, plays a critical role in the host response to sepsis. Recent studies show its calcium dependence, but the calcium-sensitive regulatory cascades have not been defined. In this study, we describe a novel mechanism in which calcium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory serine phosphorylation of GSK-3β and inhibition of FBXW7 recruitment, prevents ubiquitin proteosomal degradation of mammalian target of rapamycin (mTOR) and thereby augments autophagy in both the macrophage and the kidney. Under the conditions of sepsis studied, mTOR expression and activity were requisite for autophagy, a paradigm countering the current perspective that prototypically, mTOR inhibition induces autophagy. CaMKIV–mTOR-dependent autophagy was fundamentally important for IL-6 production in vitro and in vivo. Similar mechanisms were operant in the kidney during endotoxemia and served a cytoprotective role in mitigating acute kidney injury. Thus, CaMKIV–mTOR-dependent autophagy is conserved in both immune and nonimmune/parenchymal cells and is fundamental for the respective functional and adaptive responses to septic insult.