bluuebunny/crossref_metadata_2025 huggingface dataset:
Valorization of agroindustrial wastes: Identification by LC‐MS and NMR of benzylglucosinolate from papaya (Carica papaya L.) seeds, a protective agent against lipid oxidation in edible oils
Authors: Castro‐Vargas Henry I. , Baumann Wolfram , Parada‐Alfonso Fabián
Published: January 2016

In the present study we report the characterization of benzylglucosinolate (BG) isolated from papaya (Carica papaya L.) seeds. A methanolic extract was fractionated and further purified by solid phase extraction (SPE). It was analyzed by liquid chromatography‐electrospray ionization‐mass spectrometry (LC‐ESI‐MS), and nuclear magnetic resonance spectroscopy (1H and 13C‐NMR) as well, and the target compound BG was identified by these two techniques. The effect of BG on lipid oxidation in edible vegetable oil (EO) was shown by observing some lipid oxidation products (linoleic acid hydroperoxides, LHP; hexanal, HEX; nonanal, NON; thiobarbituric acid reactives species, TBARS). BG reduced lipid oxidation production in EO by over 80%, as compared to a control sample and in this way has proved to be a useful antioxidant, even more effective than some antioxidants used by food industry.
Interactions of metal-based engineered nanoparticles with aquatic higher plants: A review of the state of current knowledge
Authors: Thwala Melusi , Klaine Stephen J. , Musee Ndeke
Published: January 2016

The rising potential for the release of engineered nanoparticles (ENPs) into aquatic environments requires evaluation of risks to protect ecological health. The present review examines knowledge pertaining to the interactions of metal-based ENPs with aquatic higher plants, identifies information gaps, and raises considerations for future research to advance knowledge on the subject. The discussion focuses on ENPs' bioaccessibility; uptake, adsorption, translocation, and bioaccumulation; and toxicity effects on aquatic higher plants. An information deficit surrounds the uptake of ENPs and associated dynamics, because the influence of ENP characteristics and water quality conditions has not been well documented. Dissolution appears to be a key mechanism driving bioaccumulation of ENPs, whereas nanoparticulates often adsorb to plant surfaces with minimal internalization. However, few reports document the internalization of ENPs by plants; thus, the role of nanoparticulates' internalization in bioaccumulation and toxicity remains unclear, requiring further investigation. The toxicities of metal-based ENPs mainly have been associated with dissolution as a predominant mechanism, although nano toxicity has also been reported. To advance knowledge in this domain, future investigations need to integrate the influence of ENP characteristics and water physicochemical parameters, as their interplay determines ENP bioaccessibility and influences their risk to health of aquatic higher plants. Furthermore, harmonization of test protocols is recommended for fast tracking the generation of comparable data. Environ Toxicol Chem 2016;35:1677–1694. © 2016 SETAC
Behavioural and neurofunctional impact of transcranial direct current stimulation on somatosensory learning
Authors: Hilgenstock Raphael , Weiss Thomas , Huonker Ralph , Witte Otto W.
Published: January 2016

We investigated the effect of repeated delivery of anodal transcranial direct current stimulation (tDCS) on somatosensory performance and long‐term learning. Over the course of five days, tDCS was applied to the primary somatosensory cortex (S1) by means of neuronavigation employing magnetencephalography (MEG). Compared to its sham application, tDCS promoted tactile learning by reducing the two‐point discrimination threshold assessed by the grating orientation task (GOT) primarily by affecting intersessional changes in performance. These results were accompanied by alterations in the neurofunctional organization of the brain, as revealed by functional magnetic resonance imaging conducted prior to the study, at the fifth day of tDCS delivery and four weeks after the last application of tDCS. A decrease in activation at the primary site of anodal tDCS delivery in the left S1 along retention of superior tactile acuity was observed at follow‐up four weeks after the application of tDCS. Thus, we demonstrate long‐term effects that repeated tDCS imposes on somatosensory functioning. This is the first study to provide insight into the mode of operation of tDCS on the brain's response to long‐term perceptual learning, adding an important piece of evidence from the domain of non‐invasive brain stimulation to show that functional changes detectable by fMRI in primary sensory cortices participate in perceptual learning. Hum Brain Mapp 37:1277‐1295, 2016. © 2016 Wiley Periodicals, Inc.
Automated segmentation of chronic stroke lesions using LINDA: Lesion identification with neighborhood data analysis
Authors: Pustina Dorian , Coslett H. Branch , Turkeltaub Peter E. , Tustison Nicholas , Schwartz Myrna F. , Avants Brian
Published: January 2016

The gold standard for identifying stroke lesions is manual tracing, a method that is known to be observer dependent and time consuming, thus impractical for big data studies. We propose LINDA (Lesion Identification with Neighborhood Data Analysis), an automated segmentation algorithm capable of learning the relationship between existing manual segmentations and a single T1‐weighted MRI. A dataset of 60 left hemispheric chronic stroke patients is used to build the method and test it with k‐fold and leave‐one‐out procedures. With respect to manual tracings, predicted lesion maps showed a mean dice overlap of 0.696 ± 0.16, Hausdorff distance of 17.9 ± 9.8 mm, and average displacement of 2.54 ± 1.38 mm. The manual and predicted lesion volumes correlated at r = 0.961. An additional dataset of 45 patients was utilized to test LINDA with independent data, achieving high accuracy rates and confirming its cross‐institutional applicability. To investigate the cost of moving from manual tracings to automated segmentation, we performed comparative lesion‐to‐symptom mapping (LSM) on five behavioral scores. Predicted and manual lesions produced similar neuro‐cognitive maps, albeit with some discussed discrepancies. Of note, region‐wise LSM was more robust to the prediction error than voxel‐wise LSM. Our results show that, while several limitations exist, our current results compete with or exceed the state‐of‐the‐art, producing consistent predictions, very low failure rates, and transferable knowledge between labs. This work also establishes a new viewpoint on evaluating automated methods not only with segmentation accuracy but also with brain–behavior relationships. LINDA is made available online with trained models from over 100 patients. Hum Brain Mapp 37:1405‐1421, 2016. © 2016 Wiley Periodicals, Inc.
miR‐28‐5p‐IL‐34‐macrophage feedback loop modulates hepatocellular carcinoma metastasis
Authors: Zhou Shao‐Lai , Hu Zhi‐Qiang , Zhou Zheng‐Jun , Dai Zhi , Wang Zheng , Cao Ya , Fan Jia , Huang Xiao‐Wu , Zhou Jian
Published: January 2016

MicroRNAs (miRNAs) play a critical role in regulation of tumor metastasis. However, the role of these molecules in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we employed miRNA‐sequencing and identified 22 miRNAs involved in HCC metastasis. One of these, miR‐28‐5p, was down‐regulated in HCCs. This down‐regulation correlated with tumor metastasis, recurrence, and poor survival. Biofunctional investigations revealed that miR‐28‐5p deficiency promoted tumor growth and metastasis in nude mice without altering the in vitro biological characteristics of HCC cells. Through gene expression profiles and bioinformatics analysis, we identified interleukin‐34 (IL‐34) as a direct target of miR‐28‐5p, and the effects of miR‐28‐5p deficiency on HCC growth and metastasis was dependent on IL‐34‐mediated tumor‐associated macrophage (TAM) infiltration. Moreover, we found that TAMs induced by miR‐28‐5p‐IL‐34 signaling inhibit miR‐28‐5p expression on HCC cells by transforming growth factor beta 1, resulting in an miR‐28‐5p‐IL‐34‐macrophage‐positive feedback loop. In clinical HCC samples, miR‐28‐5p levels were inversely correlated with IL‐34 expression and the number of TAMs. Patients with low miR‐28‐5p expression, high IL‐34 levels, and high numbers of TAMs had a poor prognosis with shorter overall survival and time to recurrence. Conclusion: A miR‐28‐5p‐IL‐34‐macrophage feedback loop modulates HCC metastasis and serves as a novel prognostic factor as well as a therapeutic target for HCC. (Hepatology 2016;63:1560‐1575)
Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post‐liver transplantation recurrence
Authors: Poordad Fred , Schiff Eugene R. , Vierling John M. , Landis Charles , Fontana Robert J. , Yang Rong , McPhee Fiona , Hughes Eric A. , Noviello Stephanie , Swenson Eugene S.
Published: January 2016

Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post‐liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open‐label ALLY‐1 study assessed the safety and efficacy of a 60‐mg once‐daily dosage of daclatasvir (pan‐genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24‐week follow‐up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on‐treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child‐Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%‐92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child‐Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%‐99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment‐related serious adverse events. Conclusion: The pan‐genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post‐liver transplantation recurrence or advanced cirrhosis. (Hepatology 2016;63:1493‐1505)
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha
Authors: Desai Seema S. , Tung Jason C. , Zhou Vivian X. , Grenert James P. , Malato Yann , Rezvani Milad , Español‐Suñer Regina , Willenbring Holger , Weaver Valerie M. , Chang Tammy T.
Published: January 2016

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver‐specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1‐6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte‐specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho‐associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion: Fibrotic levels of matrix stiffness significantly inhibit hepatocyte‐specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho‐associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261–275)
Effects of methylphenidate on body index and physical fitness in Korean children with attention deficit hyperactivity disorder
Authors: Kang Kyoung Doo , Yun Sin Weon , Chung Unsun , Kim Tae Ho , Park Jeong Ha , Park In Hui , Han Doug Hyun
Published: January 2016

Objective

The side effects of methylphenidate (MPH) on growth remain a controversial concern. This study aimed to investigate the effect of MPH on clinical symptoms, growth, and physical fitness in Korean children.

Methods

Fifty male children with attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (MPH‐ADHD), 69 MPH‐naïve male children with ADHD (Naïve‐ADHD), and 60 age‐matched and sex‐matched healthy control subjects were recruited. Intelligence quotient (IQ), clinical symptoms of ADHD, body index (height, weight, and body mass index [BMI]), and physical fitness (muscular strength, endurance, flexibility, agility, speed, and balance) were assessed.

Results

Total IQ and performance IQ scores were significantly different among the three groups, as were mean Korean Attention Deficit Hyperactivity Disorder (K‐ARS)‐total, K‐ARS‐inattention, and K‐ARS‐hyperactivity scores. There was no significant difference in height, weight, or BMI among the three groups. There were significant differences in skill‐related fitness scores for balance (healthy controls > MPH‐ADHD > Naïve‐ADHD) and agility shuttle test time (healthy controls < MPH‐ADHD < Naïve‐ADHD).

Conclusions

Our findings support the effectiveness of MPH treatment for improving IQ, attention, and balance and agility measures of skill‐related fitness in Korean children with ADHD. MPH was not associated with growth delays in height, weight, and BMI. Copyright © 2016 John Wiley & Sons, Ltd.
Shiyang River streamflow since AD 1765, reconstructed by tree rings, contains far‐reaching hydro‐climatic signals over and beyond the mid‐latitude Asian continent
Authors: Chen Feng , Yuan Yu‐jiang , Zhang Rui‐bo , Wang Hui‐qin , Shang Hua‐ming , Zhang Tong‐wen , Qin Li , Fan Zi‐ang
Published: January 2016

In this study, the regional tree‐ring chronology of Picea crassifolia was used to estimate annual (September to August) streamflow of the Shiyang River for the period from AD 1765 to 2010. The linear regression model was stable and could explain 41.5% of the variance for the calibration period of 1955–2005. According to the streamflow reconstruction, dry periods with below average streamflow occurred in AD 1775–1804, 1814–1823, 1831–1856, 1862–1867, 1877–1885, 1905–1910, 1926–1932, 1948–1951, 1960–1963 and 1989–2002. Periods of relatively wet years are identified for AD 1765–1774, 1805–1813, 1824–1830, 1857–1861, 1868–1876, 1886–1904, 1911–1925, 1933–1947, 1952–1959, 1964–1988 and 2003–2010. Comparisons with the precipitation reconstructions from surrounding areas supplied a high degree of confidence in our reconstruction. Our reconstructed streamflow is significantly correlated with sea surface temperature in the eastern equatorial Pacific Ocean and the North Atlantic Ocean. The Multitaper spectral and correlation analyses also suggested that the reconstructed streamflow variation in the Shiyang River could be associated with large‐scale atmospheric‐oceanic variability, such as El Niño‐Southern Oscillation (ENSO). The linkages among the streamflow reconstruction, NAO and ENSO suggest the connection of regional streamflow variations to the Asian monsoon and westerlies circulations. Copyright © 2016 John Wiley & Sons, Ltd.
Adipose‐derived mesenchymal stem cells modulate the immune response in chronic experimental autoimmune encephalomyelitis model
Authors: Shalaby Sally M. , Sabbah Norhan A. , Saber Taisir , Abdel Hamid Reda A.
Published: January 2016

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system (CNS) that disrupts the myelin sheath, leading to dysfunction of the brain and spinal cord. No curative treatment is known for MS. Mesenchymal stem cells, through their immunomodulatory effects, represent a promising therapeutic approach for MS. The aim of this article is to explore the impact of human adipose‐derived mesenchymal stem cells (ASCs) on chronic experimental autoimmune encephalomyelitis (EAE) model of MS when injected after a disease entered an irreversible clinical course. Forty‐one female albino rats were classified into the following groups: I: control, II: EAE‐untreated, III and IV: EAE treated with PBS at 15 and 25 days postimmunization (dpi), respectively, V and VI: EAE treated with ASCs at 15 and 25 dpi, respectively. Intravenous administration of ASCs at 15 or 25 dpi significantly ameliorates the disease course and decreases the immune cell infiltration, vascular congestion and axonal loss of the gray and white matters of cerebral cortex. ASCs treatment induced a Th2 shift of the immune response and downregulation of IL‐17 levels. We also found an engraftment of the ASCs into the lymph nodes and the brains up to 25 days after injection. The important finding was that human HLA‐G gene was significantly expressed in lymph nodes and brains of rats treated with ASCs. Transplantation of human ASCs has demonstrated striking therapeutic effects and unique immunomodulatory capacities when delivered at the peak or later in the course of the disease in EAE rats. Interestingly, ASCs injection at the peak of EAE had better effects than those injected after disease stabilization. We first determined that the immunomodulatory properties of ASCs in the brain are explained, at least in part, by the ability of ASCs to express HLA‐G. © 2016 IUBMB Life, 68(2):106–115, 2016
Design, Synthesis, Characterization, and Antimicrobial Screening of Novel Indazole Bearing Oxadiazole Derivatives
Authors: Ghelani Satish M. , Khunt Hasmukh R. , Naliapara Yogesh T.
Published: January 2016

Ethyl 2‐(2,6‐dioxocyclohexyl)‐2‐oxoacetate was prepared by reacting cyclohexane‐1,3‐dione (1) and diethyl oxalate (2) with the help of sodium ethoxide in ethanol at 0–5°C. Subsequent treatment of ethyl 2‐(2,6‐dioxocyclohexyl)‐2‐oxoacetate with hydrazine hydrate in ethanol resulted into ethyl 4‐oxo‐4,5,6,7‐tetrahydro‐2H‐indazole‐3‐carboxylate while without solvent in excess hydrazine hydrate on reflux resulted into 4‐oxo‐4,5,6,7‐tetrahydro‐2H‐indazole‐3‐carbohydrazide (3). The synthesis of novel indazole bearing oxadiazole derivatives (ODZ 01 to 16) has been achieved by the reaction of hydrazide of 2H‐indazole (3) with acid (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p) in the presence of POCl3, and the antimicrobial activity of synthesized novel compounds has been studied.
GetReal in network meta‐analysis: a review of the methodology
Authors: Efthimiou Orestis , Debray Thomas P. A. , van Valkenhoef Gert , Trelle Sven , Panayidou Klea , Moons Karel G. M. , Reitsma Johannes B. , Shang Aijing , Salanti Georgia ,   on behalf of GetReal Methods Review Group
Published: January 2016

Pairwise meta‐analysis is an established statistical tool for synthesizing evidence from multiple trials, but it is informative only about the relative efficacy of two specific interventions. The usefulness of pairwise meta‐analysis is thus limited in real‐life medical practice, where many competing interventions may be available for a certain condition and studies informing some of the pairwise comparisons may be lacking. This commonly encountered scenario has led to the development of network meta‐analysis (NMA). In the last decade, several applications, methodological developments, and empirical studies in NMA have been published, and the area is thriving as its relevance to public health is increasingly recognized. This article presents a review of the relevant literature on NMA methodology aiming to pinpoint the developments that have appeared in the field. Copyright © 2016 John Wiley & Sons, Ltd.
Expression of the potential cancer stem cell markers CD133 and CD44 in medullary thyroid carcinoma: A ten‐year follow‐up and prognostic analysis
Authors: Bi Yalan , Meng Yunxiao , Wu Huanwen , Cui Quancai , Luo Yufeng , Xue Xiaowei
Published: January 2016

Background and Objectives

To investigate the expression profiles of cancer stem cells (CSCs) markers CD133 and CD44 in a cohort of medullary thyroid carcinoma (MTC) patients, and their prognostic values during 10‐year follow‐up.

Methods

MTC samples were obtained for H&E and immunohistochemical analysis. Survival analysis was performed using Kaplan–Meier method and log‐rank test.

Results

Both the CD133 and CD44 positives were higher in MTC than control. High expression of CD133 and CD44 was positively correlated with capsule invasion and each other, and their co‐expression was significantly correlated with capsule invasion, tissue invasion, and metastases at surgery. Tumor size, capsular invasion, tissue invasion, metastases at surgery, surgical plan, lymph node metastases, TNM stage, CD133, and CD44 were prognostic factors for overall survival (OS) and/or disease free survival (DFS). Both the CD133 and CD44 were unfavorable prognostic predictors for OS (P = 0.046,P = 0.03), while only CD44 was a significant predictor for DFS (P = 0.017). OS rate in CD133/CD44 co‐expression group was significantly lower than that in non‐co‐expression group (χ2 = 8.44,P = 0.004).

Conclusion

Our study suggested the high expression of CD133 and CD44 in the MTC, and CD133 and CD44 expressions were correlated with capsule invasion and with OS. CD133 and/or CD44 may be prognostic factors for OS and/or DFS in our MTC patients.J. Surg. Oncol. 2016;113:144–151. © 2016 Wiley Periodicals, Inc
Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: The French Sentimag feasibility trial
Authors: Houpeau Jean‐Louis , Chauvet Marie‐Pierre , Guillemin François , Bendavid‐Athias Cécile , Charitansky Hélène , Kramar Andrew , Giard Sylvia
Published: January 2016

Background and Objectives

The French Sentimag feasibility trial evaluated a new method for the localization of breast cancer sentinel lymph node (SLN) using Sienna+®, superparamagnetic iron oxide particles, and Sentimag® detection in comparison to the standard technique (isotopes ± blue dye).

Methods

We conducted a prospective multicentric paired comparison trial on 115 patients. SLN localization was performed using both the magnetic technique and the standard method. Detection rate and concordance between magnetic and standard tracers were calculated. Post‐operative complications were assessed after 30 days.

Results

Results are based on 108 patients. SLN identification rate was 98.1% [93.5–99.8] for both methods, 97.2% [92.1–99.4] for Sienna+® and 95.4% [89.5–98.5] for standard technique. A mean of 2.1 SLNs per patient was removed. The concordance rate was 99.0% [94.7–100.0%] per patient and 97.4% [94.1–99.2] per node. Forty‐six patients (43.4%) had nodal involvement. Among involved SLNs, concordance rate was 97.7% [88.0–99.9] per patient and 98.1% [90.1–100.0] per node.

Conclusions

This new magnetic tracer is a feasible method and a promising alternative to the isotope. It could offer benefits for ambulatory surgery or sites without nuclear medicine departments. J. Surg. Oncol. 2016;113:501–507. © 2016 Wiley Periodicals, Inc.
Multicenter clinical trial of the Nucleus Hybrid S8 cochlear implant: Final outcomes
Authors: Gantz Bruce J. , Dunn Camille , Oleson Jacob , Hansen Marlan , Parkinson Aaron , Turner Christopher
Published: January 2016

Objectives/Hypothesis

The concept of expanding electrical speech processing to those with more residual acoustic hearing with a less‐invasive shorter cochlear implant (CI) has been ongoing since 1999. A multicenter study of the Nucleus Hybrid S8 CI took place between 2002 and 2011. This report describes the final outcomes of this clinical trial.

Study Design

Multicenter, longitudinal, single‐subject design.

Methods

Eighty‐seven subjects received a Nucleus Hybrid S8 CI in their poorer ear. Speech perception in quiet (Consonant‐Nucleus‐Consonant [CNC] words) and in noise (Bamford‐Kowal‐Bench Sentences‐In‐Noise [BKB‐SIN]) were collected pre‐ and postoperatively at 3, 6, and 12 months. Subjective questionnaire data using the Abbreviated Profile for Hearing Aid Benefit (APHAB) were also collected.

Results

Some level of hearing preservation was accomplished in 98% subjects, with 90% maintaining a functional low‐frequency pure‐tone average (LFPTA) at initial activation. By 12 months, five subjects had total hearing loss, and 80% of subjects maintained functional hearing. CNC words demonstrated that 82.5% and 87.5% of subjects had significant improvements in the hybrid and combined conditions, respectively. The majority had improvements with BKB‐SIN. Results also indicated that as long as subjects maintained at least a severe LFPTA, there was significant improvement in speech understanding. Furthermore, all subjects reported positive improvements in hearing in three of the four subscales of the APHAB.

Conclusions

The concept of hybrid speech processing has significant advantages for subjects with residual low‐frequency hearing. In this study, the Nucleus Hybrid S8 provided improved word understanding in quiet and noise. Additionally, there appears to be stability of the residual hearing after initial activation of the device.

Level of Evidence

2c Laryngoscope, 126:962–973, 2016
Microwave preservation method for DMSP, DMSO, and acrylate in unfiltered seawater and phytoplankton culture samples
Authors: Kinsey Joanna D. , Kieber David J.
Published: January 2016

A microwave‐preservation method was developed to quantify total dimethylsulfoniopropionate (DMSPT), dimethylsulfoxide (DMSOT), and acrylate (acrylateT) concentrations in unfiltered samples to alleviate problems associated with the acidification method when applied to samples containing Phaeocystis. Microwave‐ and acid‐preservation methods were compared using batch cultures of Phaeocystis antarctica and 11 other marine phytoplankton species for DMSPT, batch P. antarctica cultures for DMSOT and acrylateT, and unfiltered Delaware Estuary water samples for DMSPT to demonstrate the general applicability of this method. Acidification of P. antarctica culture samples resulted in the underestimation of DMSPT (42–69%) and overestimation of dimethylsulfide (DMS) (2156–3819%), DMSOT (9–101%), and acrylateT (71–249%). By comparison, DMSPT concentrations in microwaved samples agreed with non‐microwaved, non‐acidified controls. In contrast to P. antarctica results, the microwave‐ and acid‐preservation methods yielded DMSPT concentrations that were statistically indistinguishable for 11 other marine phytoplankton species and Delaware Estuary samples. Unfiltered samples stored frozen following microwave treatment or stored at room temperature if acidified after the microwaving step, resulted in no change in DMSPT or acrylateT; DMSOT concentrations increased slightly (∼ 15%) when they were not sparged to remove DMS prior to acidification and room temperature storage. Based on these findings, we propose microwaving small sample volumes (≤ 7 mL) of unfiltered seawater or culture samples as a general approach to preserve samples for subsequent DMSPT, DMSOT, and acrylateT analyses, especially when the phytoplankton composition of the samples is unknown.
Dentinal tubule penetration of AH Plus, iRoot SP, MTA fillapex, and guttaflow bioseal root canal sealers after different final irrigation procedures: A confocal microscopic study
Authors: Akcay Merve , Arslan Hakan , Durmus Nazli , Mese Merve , Capar Ismail Davut
Published: January 2016

Background and Objective

Varied physical and chemical characteristic of root canal sealers and different irrigant agitation systems can influence the depth of penetration. The aim of this in vitro study was to use a laser scanning confocal microscope in order to assess the dentinal tubules penetration of various sealers after the application of different final irrigation techniques.

Study Design/Materials and Methods

A total of 156 single‐rooted extracted mandibular premolars were prepared up to size 40 and randomly distributed into four groups according to the sealer type (n = 39): AH Plus, iRoot SP, MTA Fillapex, and GF Bioseal. Each group was randomly subdivided into three groups according to the final irrigation protocol (n = 13): conventional needle irrigation (CI), photon‐induced‐photoacoustic streaming activation (PIPS), and passive ultrasonic irrigation (PUI). After the final irrigation procedures, the root canals were obturated with single gutta‐percha and labeled sealer mixed with 0.1% fluorescent rhodamine B isothiocyanate. Specimens were sectioned at 2, 5, and 8 mm from the apex, and all the sections were examined under confocal microscope to calculate the dentinal tubule penetration area. Data were analyzed using three‐way analysis of variance and Tukey's post hoc tests (P = 0.05).

Results

iRoot SP exhibited a significantly higher penetration area than the other groups (P < 0.001), although there were no statistically significant differences between AH Plus, MTA Fillapex, and GF Bioseal (P > 0.05). Er:YAG laser activation with PIPS and PUI had significantly higher penetration than CI (P < 0.001). Statistically significant differences were also determined at each root canal third (coronal > middle > apical; P < 0.001).

Conclusions

The dentinal tubule penetration area was significantly affected by the selection of root canal sealer, final irrigation procedure, and root canal third. Use of iRoot with PIPS tip or PUI seems advantageous in dentinal tubule penetration. Lasers Surg. Med. 48:70–76, 2016. © 2016 Wiley Periodicals, Inc.
Transcranial laser stimulation improves human cerebral oxygenation
Authors: Tian Fenghua , Hase Snehal N. , Gonzalez‐Lima F. , Liu Hanli
Published: January 2016

Background and Objective

Transcranial laser stimulation of the brain with near‐infrared light is a novel form of non‐invasive photobiomodulation or low‐level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near‐infrared spectroscopy (fNIRS).

Materials and Methods

Two separate experiments were conducted in which 1,064‐nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2, corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18–40 years old were included in each experiment.

Results

In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Δ[HbO2]) and a decrease of deoxygenated hemoglobin concentration (Δ[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Δ[HbD] = Δ[HbO2] − Δ[Hb]). These effects increased in a dose‐dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Δ[HbT] = Δ[HbO2] + Δ[Hb]) remained nearly unchanged in most cases.

Conclusion

Near‐infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans. Lasers Surg. Med. 48:343–349, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Targeting c‐MET by LY2801653 for treatment of cholangiocarcinoma
Authors: Barat Samarpita , Bozko Przemyslaw , Chen Xi , Scholta Tim , Hanert Franziska , Götze Julian , Malek Nisar P. , Wilkens Ludwig , Plentz Ruben R.
Published: January 2016

Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c‐MET has been shown to be deregulated in many cancers, but the role of c‐MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression and also to investigate the role of c‐MET and its effective inhibition for the treatment of CCC. In this study we investigated the effects of LY2801653, a small‐molecule inhibitor with potent activity against MET kinase, in human CCC cell lines and in vivo using a xenograft mouse model. We have investigated the role of c‐MET and its inhibitory effects on migration, invasion, colony formation, MET downstream targets, and CCC tumor growth. We also analyzed the role of apoptosis and senescence as well as the influence of hypoxia in this context. c‐MET and p‐MET were expressed in 72% and 12.5% of human CCC tissues and in TFK‐1, SZ‐1 cell lines. MET inhibition was achieved by blocking phosphorylation of MET with LY2801653 and subsequent down regulation of c‐MET downstream targets. Treatment showed in a xenograft model potent anti‐tumor activity. LY2801653 is an effective inhibitor and suppress the proliferation of CCC cells as well as the growth of xenograft tumors. Therefore, inhibition of c‐MET could be a possible alternative approach for the treatment of human CCC. © 2016 Wiley Periodicals, Inc.
High expression of long non‐coding RNA AFAP1‐AS1 predicts chemoradioresistance and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy
Authors: Zhou Xi‐Lei , Wang Wan‐Wei , Zhu Wei‐Guo , Yu Chang‐Hua , Tao Guang‐Zhou , Wu Qing‐Quan , Song Ya‐Qi , Pan Peng , Tong Yu‐Suo
Published: January 2016

To evaluate the clinical significance of lncRNAs in the resistance to cisplatin‐based chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). We focused on lncRNAs which were frequently reported in ESCC or were involved in chemoradiotherapy resistance. LncRNA expressions were examined in paired cisplatin‐resistant and parental ESCC cell lines. Dysregulated lncRNAs were further measured in 162 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (dCRT). Then the correlations between lncRNA expression and response to dCRT and prognosis were analyzed. Three lncRNAs (AFAP1‐AS1, UCA1, HOTAIR) were found to be deregulated in cisplatin‐resistant cells compared with their parent cells. AFAP1‐AS1 was significantly up‐regulated in tumor tissues compared with adjacent normal tissues (P = 0.006). Furthermore, overexpression of AFAP1‐AS1 was closely associated with lymph node metastasis (P < 0.001), distant metastasis (P = 0.016), advanced clinical stage (P = 0.002), and response to dCRT (P < 0.001). Kaplan–Meier survival analysis revealed that high expression of AFAP1‐AS1 was significantly associated with shorter progression free survival (PFS) (median, 15 months vs. 27 months, P < 0.001) and overall survival (OS) (median, 29 months vs. 42 months, P < 0.001). In the multivariate analysis, high expression of AFAP1‐AS1 was found to be an independent risk factor to predict poor PFS (HR, 1.626; P = 0.027) and OS (HR, 1.888; P = 0.004). Thus, high expression of AFAP1‐AS1 could serve as a potential biomarker to predict tumor response and survival. Determination of this lncRNA expression might be useful for selection ESCC patients for dCRT. © 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.
Development of a double cap on the humidity sensor in radiosondes for improving ventilation
Authors: Lee Sang‐Wook , Kim Jong Chul , Choi Byung Il , Woo Sang‐Bong , So Jae Won , Yang Seung Gu , Kim Yong‐Gyoo
Published: January 2016

Although a protective cap on the humidity sensor of radiosondes is an effective tool to prevent the sensor from wetting by rain and/or clouds, the cap is thought to be responsible for poor ventilation and thereby induces a time delay in the measurement of relative humidity in upper air. In the present study, a new type of the protective cap having a double cap configuration has been developed for improving the ventilation of air. The double cap consists of an outer cap and an inner cap with holes and windows on the top and sides of each cap, respectively, that are designed not to face each other, between two caps for blocking the penetration of water droplets. The wetting of the double cap was tested by artificial water droplets as well as during flying tests on rainy days and the humidity sensor in a double cap was not wet in both cases. In addition, the response of sensors to indoor humidity changes as well as during balloon‐borne measurements was found to be faster in the case of double caps than conventional closed caps, suggesting the enhancement of ventilation when using the double cap. The present study provides an efficient way to improve the performance of humidity sensors of radiosondes by simply modifying the design of protective caps.
Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations
Authors: Sjursen Wenche , McPhillips Mary , Scott Rodney J. , Talseth‐Palmer Bente A.
Published: January 2016

Background

Lynch syndrome, the most frequent hereditary colorectal cancer syndrome, is caused by defects in mismatch repair genes. Genetic testing is important in order to identify mutation carriers who can benefit from intensive surveillance programs. One of the challenges with genetic testing is the interpretation of pathogenicity of detected DNA variants. The aim of this study was to investigate all putative pathogenic variants tested for at the Division of Molecular Medicine, Pathology North, in Newcastle, Australia, to establish whether previous variant classification is in accordance with that recently performed in the InSiGHT collaboration.

Methods

Prediction programs and available literature were used to classify new variants or variants without classification.

Results

We identified 333 mutation positive families, in which 211 different putative pathogenic mismatch repair mutations were found. Most variants with an InSiGHT classification (141 out of 146) were in accordance with our classification. Five variants were discordant, of which one can definitively be reclassified according to the InSiGHT scheme as class 5. Sixty‐four variants had not been classified by InSiGHT, of whom 55 have not been previously reported.

Conclusion

In conclusion, we found that our classifications were mostly in accordance with the InSiGHT scheme. In addition to already known MMR mutations, we have also presented 55 novel pathogenic or putative pathogenic mutations.
CNS Multiparameter Optimization Approach: Is it in Accordance with Occam’s Razor Principle?
Authors: Raevsky Oleg A.
Published: January 2016

A detailed analysis of the possibility of using the Multiparameter Optimization approach (MPO) for CNS/non‐CNS classification of drugs was carried out. This work has shown that MPO descriptors are able to describe only part of chemical transport in the CNS connected with transmembrane diffusion. Hence the “intuitive” CNS MPO approach with arbitrary selection of descriptors and calculations of score functions, search of thresholds of classification, and absence of any chemometric procedures, leads to rather modest accuracy of CNS/non‐CNS classification models.
Analysengerät Mobiltelefon
Authors: Ehrensberger Christian
Published: January 2016

Das Smartphone ist zur Plattform geworden: Es erkennt Sprache, macht Fotos, zeichnet bewegte Bilder auf und bietet Informationsaustausch jeglicher Art – nun wird es auch zum Messsystem für chemische Analytik, insbesondere in der medizinischen Diagnostik.
Polymere auf Schwefelbasis: Vulkanisation andersherum
Authors: Hoefling Alexander , Theato Patrick
Published: January 2016

Die inverse Vulkanisation stellt aus elementarem Schwefel und organischen Molekülen funktionalisierte Polymere her. Die Produkte sind prozessierbare Materialien, die Forscher als Kathodenmaterial in Batterien, als Infrarotlinsen oder als Halbleiter für die Photovoltaik nutzen.
Öffentlichkeitsarbeit für die Katalyse
Authors: Penno Martin
Published: January 2016

Die Pressestelle einer Forschungsinstitution wie des Exzellenzclusters Unicat in Berlin versteht sich als Schnittstelle zwischen den Wissenschaftlern und Laien und möchte die Forschung einem breiteren Publikum näher bringen.
Reference values for frequency volume chart and uroflowmetry parameters in adolescent and adult enuresis patients
Authors: Hofmeester Ilse , Brinker Astrid E. , Steffens Martijn G. , Mulder Zwaan , van Capelle Jan Willem , Feitz Wout F.J. , Blanker Marco H.
Published: January 2016

Aims

Reference values of Frequency Volume Chart (FVC) and uroflowmetry parameters for adolescent and adult enuresis patients are lacking. In this study, we aim to describe those parameters, in order to interpret findings from FVCs and uroflowmetries in those patients.

Methods

Retrospective, descriptive cohort study, concerning 907 patients aged 11 years and older, suffering from enuresis of at least one wet night per fortnight, treated in a secondary/tertiary centre, between 2003 and 2013. The main FVC parameters of interest were: maximum voided volume (MVV), 24 hr urine production and nocturnal urine volume (NUV) including first morning void (FMV). Nocturnal polyuria (NP) was defined based on both International Children's Continence Society (ICCS, 2014) and International Continence Society (ICS, 2002) definitions. Data of all patients were collected from the medical files.

Results

Age had an impact on diurnal and nocturnal FVC parameters. Median MVV excluding FMV was 250 ml in the youngest, 11‐year‐old males and 363 ml in the eldest, ≥18‐yr‐old males. For females, these values were 230 ml and 310 ml. Median 24 hr urine production increased from 1,025 ml to 1,502 ml (males) and from 1,007 ml to 1,557 ml (females). Median NUV showed an increase from 387 ml to 519 ml (males) and from 393 ml to 525 (females). Forty‐two percent of men and 30% of women had a small MVV (for age). Prevalence of NP differed when assessed by the ICS or the ICCS definition: following ICS guidelines, NP was present in 96% of our male and 93% of our female population, compared to 27% and 41%, respectively, following ICCS guidelines.

Conclusions

Both small MVV and NP were found frequently in our adolescent and adult enuresis patients, which is in line with the current thoughts on causal factors. NP prevalence is quite different when using ICS or ICCS definitions, respectively. We would like to encourage the development of an unambiguous definition of NP to use both in pediatric and adult urology. Neurourol. Urodynam. 36:463–468, 2017. © 2016 Wiley Periodicals, Inc.
Use of a Fitness Tracker to Promote Physical Activity in Children With Acute Lymphoblastic Leukemia
Authors: Hooke Mary C. , Gilchrist Laura , Tanner Lynn , Hart Nicole , Withycombe Janice S.
Published: January 2016

Background

Children with cancer identify fatigue as a pervasive symptom, which increases during the corticosteroid pulse in acute lymphoblastic leukemia (ALL) maintenance. The FitBit® is a fitness tracker that downloads activity measurements to the Internet in real time. In this feasibility study, we explored if children who received daily FitBit® coaching for 2 weeks before a maintenance steroid pulse had an increase in steps per day and determined the relationship between steps per day prepulse and fatigue postpulse.

Procedure

Seventeen children in ALL maintenance, aged 6–15, wore the FitBit® for 3 days to establish a baseline. A tailored weekly step goal was then set with the child and parent. Daily emails with feedback and FitBit® screenshots were sent over the 2‐week intervention. Self‐report of fatigue was measured at baseline, after 2 weeks (i.e. before the steroid pulse), and after 5 days of steroids.

Results

There was a trend toward increased steps per day from weeks 1–2 (P = 0.079); fatigue was low and did not increase during the corticosteroid pulse. A significant correlation (r = −0.66, P = 0.005) was found between the steps per day during week 2 and fatigue after the steroid pulse with higher steps associated with lower fatigue.

Conclusions

The intervention was feasible in this small sample. The average steps each time period (week 1, week 2, and during steroids) was over 10,000, demonstrating that children with ALL can be active during treatment. Physical activity may be protective of fatigue during a corticosteroid pulse.
Histology, Fusion Status, and Outcome in Alveolar Rhabdomyosarcoma With Low‐Risk Clinical Features: A Report From the Children's Oncology Group
Authors: Arnold Michael A. , Anderson James R. , Gastier‐Foster Julie M. , Barr Frederic G. , Skapek Stephen X. , Hawkins Douglas S. , Raney R. Beverly , Parham David M. , Teot Lisa A. , Rudzinski Erin R. , Walterhouse David O.
Published: January 2016

Background

Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) is of prognostic and therapeutic importance. Criteria for classifying these entities evolved significantly from 1995 to 2013. ARMS is associated with inferior outcome; therefore, patients with alveolar histology have generally been excluded from low‐risk therapy. However, patients with ARMS and low‐risk stage and group (Stage 1, Group I/II/orbit III; or Stage 2/3, Group I/II) were eligible for the Children's Oncology Group (COG) low‐risk rhabdomyosarcoma (RMS) study D9602 from 1997 to 1999. The characteristics and outcomes of these patients have not been previously reported, and the histology of these cases has not been reviewed using current criteria.

Procedure

We re‐reviewed cases that were classified as ARMS on D9602 using current histologic criteria, determined PAX3/PAX7‐FOXO1 fusion status, and compared these data with outcome for this unique group of patients.

Results

Thirty‐eight patients with ARMS were enrolled onto D9602. Only one‐third of cases with slides available for re‐review (11/33) remained classified as ARMS by current histologic criteria. Most cases were reclassified as ERMS (17/33, 51.5%). Cases that remained classified as ARMS were typically fusion‐positive (8/11, 73%), therefore current classification results in a similar rate of fusion‐positive ARMS for all clinical risk groups. In conjunction with data from COG intermediate‐risk treatment protocol D9803, our data demonstrate excellent outcomes for fusion‐negative ARMS with otherwise low‐risk clinical features.

Conclusions

Patients with fusion‐positive RMS with low‐risk clinical features should be classified and treated as intermediate risk, while patients with fusion‐negative ARMS could be appropriately treated with reduced intensity therapy.