bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoskeleton and ECM tumor mutant peptides: Increased protease sensitivities and potential consequences for the HLA class I mutant epitope reservoir
Authors: Callahan Blake M. , Patel Jay S. , Fawcett Timothy J. , Blanck George
Published: October 2017

Cytoskeleton and extracellular matrix‐related proteins (CECMPs) represent the most common class of cancer mutants, owing to the large size of their coding regions and the randomness of mutagenesis. We used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to proteases relevant to melanoma and on the binding affinities for HLA class I. CECMP peptides with AA substitutions overwhelmingly reflect increased sensitivity to proteases implicated in melanoma development (MME, CTSS, MMP2, CTSD, CTSL) in comparison to the wild‐type peptide sequences. Furthermore, peptides with AA substitutions representing increased peptide protease sensitivity also represented relatively high binding affinities for HLA class I allelic variants. These analyses raise the question of whether increased protease sensitivity, of mutant cancer peptides represents a significant increase in the availability of cancer mutant, HLA class I epitopes and a hitherto unappreciated aspect of cancer cell immunogenicity, particularly in the case of melanoma?
In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene‐based MR imaging
Authors: Cao Minghui , Mao Jiaji , Duan Xiaohui , Lu Liejing , Zhang Fang , Lin Bingling , Chen Meiwei , Zheng Chushan , Zhang Xiang , Shen Jun
Published: October 2017

Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell‐based gene therapies for tumors. In this study, we used ferritin gene‐based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and enhanced green fluorescent protein (eGFP). Intra‐arterial, intravenous and intertumoral injections of these FTH transgenic MSCs (FTH‐MSCs) were performed in rats bearing intracranial orthotopic C6 gliomas. The FTH‐MSCs were detected as hypointense signals on T2‐ and T2*‐weighted images on a 3.0 T clinical MRI. After intra‐arterial injection, 17% of FTH‐MSCs migrated toward the tumor and gradually diffused throughout the orthotopic glioma. This dynamic process could be tracked in vivo by MRI up to 10 days of follow‐up, as confirmed by histology. Moreover, the tumor tropism of MSCs showed no appreciable impact on the progression of the tumor. These results suggest that FTH reporter gene‐based MRI can be used to reliably track the tropism and fate of MSCs after their systemic transplantation in orthotopic gliomas. This real‐time in vivo tracking system will facilitate the future development of stem cell‐based therapies for malignant gliomas.
Relevance of liver‐limited disease in metastatic colorectal cancer: Subgroup findings of the FIRE‐3/AIO KRK0306 trial
Authors: Holch Julian Walter , Ricard Ingrid , Stintzing Sebastian , Fischer von Weikersthal Ludwig , Decker Thomas , Kiani Alexander , Vehling‐Kaiser Ursula , Al‐Batran Salah‐Eddin , Heintges Tobias , Lerchenmüller Christian , Kahl Christoph , Kullmann Frank , Scheithauer Werner , Scholz Michael , Müller Sebastian , Link Hartmut , Rost Andreas , Höffkes Heinz‐Gert , Moehler Markus , Lindig Reinhard Udo , Miller‐Phillips Lisa , Kirchner Thomas , Jung Andreas , von Einem Jobst Christian , Modest Dominik Paul , Heinemann Volker
Published: October 2017

In metastatic colorectal cancer (mCRC), liver‐limited disease (LLD) is associated with a higher chance of metastectomy leading to long‐term survival. However, limited data describes the prognostic and predictive relevance of initially unresectable LLD with regard to targeted first‐line therapy. The present analysis investigated the relevance of initially unresectable LLD in mCRC patients treated with targeted therapy against either the epidermal growth factor receptor (EGFR) or vascular epithelial growth factor (VEGF). The analysis was performed based on FIRE‐3, a randomized phase III trial comparing first‐line chemotherapy with FOLFIRI plus either cetuximab (anti‐EGFR) or bevacizumab (anti‐VEGF) in RAS wild‐type (WT) mCRC. Of 400 patients, 133 (33.3%) had LLD and 267 (66.8%) had non‐LLD. Median overall survival (OS) was significantly longer in LLD compared to non‐LLD patients (36.0 vs. 25.4 months; hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.51–0.87; p = 0.002). In a multivariate analysis also including secondary hepatic resection as time‐dependent variable, LLD status was independently prognostic for OS (HR = 0.67; 95% CI: 0.50–0.91; p = 0.01). As assessed by interaction tests, treatment benefit from FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab was independent of LLD status with regard to objective response rate (ORR), early tumour shrinkage ≥20% (ETS), depth of response (DpR) and OS (all p > 0.05). In conclusion, LLD could be identified as a prognostic factor in RAS‐WT mCRC, which was independent of hepatic resection in patients treated with targeted therapy. LLD had no predictive relevance since benefit from FOLFIRI plus cetuximab over bevacizumab was independent of LLD status.
γ‐Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma
Authors: Mao Liang , Zhao Zhi‐Li , Yu Guang‐Tao , Wu Lei , Deng Wei‐Wei , Li Yi‐Cun , Liu Jian‐Feng , Bu Lin‐Lin , Liu Bing , Kulkarni Ashok B. , Zhang Wen‐Feng , Zhang Lu , Sun Zhi‐Jun
Published: October 2017

Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/Pten‐knockout HNSCC mouse model. Notch signaling inhibition using a γ‐secretase inhibitor (GSI‐IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub‐population of myeloid‐derived suppressor cells (MDSCs), tumour‐associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC.
Maduramicin induces apoptosis and necrosis, and blocks autophagic flux in myocardial H9c2 cells
Authors: Chen Xin , Chen Long , Jiang Shanxiang , Huang Shile
Published: October 2017

Maduramicin, a polyether ionophore antibiotic, is widely used as an anticoccidial agent in the poultry industry. It has been reported that maduramicin may cause heart and skeletal muscle cell damage, resulting in heart failure, skeletal muscle degeneration and even death in animals and humans, if improperly used. However, the molecular mechanism behind its capability to cause death of cardiac cells is not known. Here, we show that maduramicin induced apoptosis and necrosis in rat myocardial cells (H9c2). Maduramicin did not apparently upregulate the expression of pro‐apoptotic proteins (e.g., BAD, BAK and BAX) or downregulate the expression of anti‐apoptotic proteins (e.g. Bcl‐2, Bcl‐xL, Mcl‐1 and survivin). Interestingly, maduramicin increased the expression of DR4 and TRAIL, activating caspases 8/3 and triggering cleavage of poly ADP ribose polymerase (PARP). In addition, maduramicin induced nuclear translocation of apoptosis inducing factor. Furthermore, maduramicin blocked autophagic flux, as evidenced by inducing accumulation of both LC3‐II and p62/SQSTM1. Taken together, the above results suggest that maduramicin executes its toxicity in the myocardial cells at least by inducing caspase‐dependent cell death through TRAIL/DR4‐mediated extrinsic pathway and caspase‐independent cell death by inducing apoptosis inducing factor nuclear translocation and blocking autophagic flux. Our findings provide a new insight into the molecular mechanism of maduramicin's toxicity in myocardial cells.
Accuracy of fetal sex determination in the first trimester of pregnancy using 3D virtual reality ultrasound
Authors: Bogers Hein , Rifouna Maria S. , Koning Anton H. J. , Husen‐Ebbinge Margreet , Go Attie T. J. I. , van der Spek Peter J. , Steegers‐Theunissen Régine P. M. , Steegers Eric A. P. , Exalto Niek
Published: October 2017

Purpose

Early detection of fetal sex is becoming more popular. The aim of this study was to evaluate the accuracy of fetal sex determination in the first trimester, using 3D virtual reality.

Methods

Three‐dimensional (3D) US volumes were obtained in 112 pregnancies between 9 and 13 weeks of gestational age. They were offline projected as a hologram in the BARCO I‐Space and subsequently the genital tubercle angle was measured. Separately, the 3D US aspect of the genitalia was examined for having a male or female appearance.

Results

Although a significant difference in genital tubercle angles was found between male and female fetuses, it did not result in a reliable prediction of fetal gender. Correct sex prediction based on first trimester genital appearance was at best 56%.

Conclusion

Our results indicate that accurate determination of the fetal sex in the first trimester of pregnancy is not possible, even using an advanced 3D US technique.
Predictive value of the 8th edition American Joint Commission Cancer (AJCC) nodal staging system for patients with cutaneous squamous cell carcinoma of the head and neck
Authors: Liu Jessica , Ebrahimi Ardalan , Low Tsu‐Hui (Hubert) , Gao Kan , Palme Carsten E. , Sydney Ch'ng , Ashford Bruce G. , Iyer N. Gopalakrishna , Clark Jonathan R. , Gupta Ruta
Published: October 2017

Background

The 8th edition American Joint Committee on Cancer (AJCC8) provides the same nodal staging system for mucosal and cutaneous squamous cell carcinoma of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an adverse prognostic criterion. This study evaluates the prognostic efficacy of the AJCC8 pathologic nodal staging system (pN) for HNcSCC.

Methods

Univariate analysis of 382 patients with metastatic HNcSCC staged according to both the 7th (AJCC7) and the 8th edition staging systems.

Results

The AJCC7 pN3 category was associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83‐16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54‐7.58; P = 0.002) as compared with pN1. However, no difference was observed between pN1, pN2, and pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34‐1.67; P = 0.478) or OS (HR 0.88; 95% CI: 0.51‐1.51; P = 0.648).

Conclusion

The AJCC8 performed poorly as a prognostic indicator for patients with metastatic HNcSCC in this cohort. HNcSCC would benefit from a staging system that accounts for its unique biologic characteristics distinct from mucosal SCC.
Vasa Previa: Prenatal Diagnosis and Outcomes: Thirty‐five Cases From a Single Maternal‐Fetal Medicine Practice
Authors: Kulkarni Ankita , Powel Jennifer , Aziz Michael , Shah Leena , Lashley Susan , Benito Carlos , Oyelese Yinka
Published: October 2017

Objectives

To assess the accuracy and effectiveness of routine screening for vasa previa, to describe our experience, and to assess factors that contribute to missed cases of vasa previa.

Methods

A retrospective descriptive study of all cases of vasa previa from a single maternal‐fetal medicine service between 2009 and 2017 was performed. Ultrasound findings and obstetric and neonatal outcomes were reviewed and analyzed.

Results

Thirty‐five cases of vasa previa were identified. Most cases (33 of 35 [94.3%]) were diagnosed antenatally. All 33 cases that followed our screening protocol were diagnosed antenatally and had favorable outcomes. Two cases that did not follow our protocol were not diagnosed antenatally and were delivered emergently. The mean gestational age ± SD at delivery of antenatally diagnosed cases was 34.9 ± 1.69 weeks. All neonates survived.

Conclusions

Routine ultrasound screening for vasa previa using American Institute of Ultrasound in Medicine criteria will almost universally lead to good outcomes and prevent perinatal mortality.
On improving the formability of AA6061/SiCp composite synthesized using friction stir processing
Authors: Puviyarasan M. , Kumar V.S. Senthil , Viswanathan D. , Padmanabhan K.A.
Published: October 2017

Friction stir process is a potentially useful method for producing composites of enhanced surface properties. In this work, an AA6061/SiCp composite, synthesized using friction stir processing, was tested in three‐point bending and uniaxial hot tensile and bi‐axial stressing to assess its formability. Bending test results reveal an increased bending strength in the composite compared with the AA6061 alloy, subjected to friction stir processing, but without the addition of the silicon carbide particles. Based on the hot tensile tests, the biaxial stressing temperatures were fixed as 623 K and 673 K. Bi‐axial stressing reveals that a maximum bulge height of 18 mm could be obtained by forming into a cavity of 59 mm diameter at a pressure of 0.2 MPa. Based on the results, process parameters such as formed bulge height, forming time, strain rate and strain rate sensitivity index were determined. In the present experiments, the strain rate sensitivity index increased with increasing forming pressure and reached a maximum value of 0.40 at a forming pressure of 0.25, as the latter variable was increased from 0.20 MPa to 0.25 MPa. The present findings can pave the way for the commercial exploitation of friction stir process‐technology‐based, efficient processing of the AA6061/SiCp composite.
Optimal bed net use for a dengue disease model with mosquito seasonal pattern
Authors: Buonomo Bruno , Della Marca Rossella
Published: October 2017

Controversial results concerning the effectiveness of bed net in reducing dengue fever transmission make further research necessary in this direction. At this aim, we consider a mathematical model of dengue transmission where the use by individuals of insecticide‐treated bed nets is taken into account, combined or not with insecticide spraying. Furthermore, as climatic factors play a key role in mosquito‐borne diseases, we model the effect of seasonality through a periodic mosquito birth rate. We numerically investigate some specific scenarios according to different rainfall and mean temperature values. We set an optimal control problem to minimize the number of human infections and the cost of efforts placed into bed net adoption and maintenance and insecticide spraying. To assess the most appropriate strategy to eliminate dengue with minimum costs, we perform a comparative cost‐effectiveness analysis, which also shows how the cost‐benefit of intervention efforts is affected by changes in the amplitude of seasonal variation. One general result is that in any case the combination of bed net use and insecticide spraying produces the highest ratio of infections averted, whereas in terms of cost‐benefit only spraying campaigns should be implemented in control programs for regions with no large seasonality.
On application of matrix summability to Fourier series
Authors: Yildiz Sebnem
Published: October 2017

Bor has recently obtained a main theorem dealing with absolute weighted mean summability of Fourier series. In this paper, we generalized that theorem forsummability method. Also, some new and known results are obtained dealing with some basic summability methods.
Lifespan for a semilinear pseudo‐parabolic equation
Authors: Xu Guangyu , Zhou Jun
Published: October 2017

This paper deals with the blow‐up solution to the following semilinear pseudo‐parabolic equation

urn:x-wiley:mma:media:mma4639:mma4639-math-0001
in a bounded domain
, which was studied by Luo (Math Method Appl Sci 38(12):2636‐2641, 2015) with the following assumptions on p:

urn:x-wiley:mma:media:mma4639:mma4639-math-0003
and the lifespan for the initial energy J(u0)<0 is considered. This paper generalizes the above results on the following two aspects:

a new blow‐up condition is given, which holds for all p> 1;

a new lifespan is given, which holds for all p> 1 and possible J(u0)≥0.

Moreover, as a byproduct, we refine the lifespan when J(u0)<0.
A table‐top PXI based low‐field spectrometer for solution dynamic nuclear polarization
Authors: Biller Joshua R. , Stupic Karl F. , Moreland J.
Published: October 2017

We present the development of a portable dynamic nuclear polarization (DNP) instrument based on the PCI eXtensions for Instrumentation platform. The main purpose of the instrument is for study of 1H polarization enhancements in solution through the Overhauser mechanism at low magnetic fields. A DNP probe set was constructed for use at 6.7 mT, using a modified Alderman–Grant resonator at 241 MHz for saturation of the electron transition. The solenoid for detection of the enhanced 1H signal at 288 kHz was constructed with Litz wire. The largest observed 1H enhancements (ε) at 6.7 mT for 14N‐CTPO radical in air saturated aqueous solution was ε~65. A concentration dependence of the enhancement is observed, with maximum ε at 5.5 mM. A low resonator efficiency for saturation of the electron paramagnetic resonance transition results in a decrease in ε for the 10.3 mM sample. At high incident powers (42 W) and long pump times, capacitor heating effects can also decrease the enhancement. The core unit and program described here could be easily adopted for multi‐frequency DNP work, depending on available main magnets and selection of the “plug and play” arbitrary waveform generator, digitizer, and radiofrequency synthesizer PCI eXtensions for Instrumentatione cards.
Improved rotational hardening rule for cohesive soils and definition of inherent anisotropy
Authors: Nieto Leal Andrés , Kaliakin Victor N. , Mashayekhi Meysam
Published: October 2017

Improved, microfabric‐inspired rotational hardening rules for the plastic potential and bounding surfaces associated with the generalized bounding surface model for cohesive soils are presented. These hardening rules include 2 new functions, fη and
, that improve the simulation of anisotropically consolidated cohesive soils. Three model parameters are associated with the improved hardening rules. A detailed procedure for obtaining suitable values for these parameters is presented. The first 2 parameters affect the simulation of constant stress ratio loading where, because of the presence of fη, the third parameter is inactive. The second new function,
, accelerates the rotation of the plastic potential and bounding surfaces during shearing, which is particularly important for overconsolidated soils tested in extension. This paper also describes the proper manner in which to define the inherent anisotropy. This seemingly straightforward test has rarely been discussed in sufficient detail.
Long‐term occurrence of secondary compartment pelvic organ prolapse after open mesh sacrocolpopexy for symptomatic prolapse
Authors: Wang Connie , Christie Alana L. , Zimmern Philippe E.
Published: October 2017

Aims

To report on the long‐term occurrence of secondary compartment pelvic organ prolapse (POP) after open mesh sacrocolpopexy (MSC).

Methods

A prospectively maintained, IRB‐approved database of non‐neurogenic women with symptomatic triple compartment POP who underwent open MSC between 1999 and 2011 and had a 1‐year minimum follow‐up was reviewed. Length of follow‐up was categorized as: intermediate (1‐3 yr), late (3‐5 yr), and very late (>5 yr). Demographic data, history of POP repairs, exam with Baden‐Walker grading, validated questionnaires (Urogenital Distress Inventory short form [UDI‐6], QoL), and outcomes at each follow‐up visit were recorded. Failure was defined by either secondary compartment prolapse recurrence (BW > 2) on examination at the last visit or re‐operation for POP.

Results

Out of sixty‐eight, sixty‐one women met study criteria. Mean age was 66 ± 11, mean BMI 26.1 ± 4.5, mean parity 2.8 ± 1.4 and cohort was mostly Caucasian. ­­Eighty seven percent had prior hysterectomy and 72% had prior POP repair. Mean follow‐up was 6.8 ± 3.9 years with over 75% in the late or very late categories. There were 4/61 (7%) clinical failures, 3 of which underwent surgical repair (2 anterior and 1 posterior compartment repair) at 2‐12 year interval post‐MSC. Mean changes between baseline and last visit UDI‐6, QoL, and BW prolapse grade trended favorably.

Conclusions

Following open MSC, the rate of secondary prolapse compartment failure was found low at very long‐term follow‐up.
Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type interstitial cystitis
Authors: Niimi Aya , Igawa Yasuhiko , Aizawa Naoki , Honma Toshiki , Nomiya Akira , Akiyama Yoshiyuki , Kamei Jun , Fujimura Tetsuya , Fukuhara Hiroshi , Homma Yukio
Published: October 2017

Aim

To investigate the feasibility of chemokines and cytokines potentially elevated in the bladder tissue of Hunner type interstitial cystitis (HIC) as urinary markers for distinguishing HIC from non‐Hunner type interstitial cystitis (NHIC)

Methods

Urine specimens were collected from 41 HIC patients, 25 NHIC patients, and 31 healthy volunteers (control). The supernatants of urine specimens were subjected to ELISA kits for measurements of 10 cytokines and chemokines, whose gene expression was known to be elevated in HIC bladder tissue. Urinary levels normalized by urinary creatinine (Cr) concentration were compared among three groups. Efficiency in differentiating IC and IC subtypes was explored by ROC analysis. The correlation of marker levels with symptom severity, assessed by O'Leary‐Sant's symptom index (OSSI) and problem index (OSPI), was examined.

Results

The urinary levels of CXCL10 and NGF were significantly higher in HIC than NHIC. CXCL10 and NGF differentiated HIC against NHIC with AUC of 0.78 and 0.68, respectively. Combination of CXCL10 and NGF levels yielded an AUS of 0.81. The CXCL10 cut‐off of 53.2 pg/mg Cr had sensitivity of 46.1%, specificity of 93.7%, positive predictive value of 97.7%, and negative predictive value of 60.0%. The urinary level of other cytokines showed no significant difference between HIC and NHIC. Significant correlation with symptoms was detected for CXCL10 alone.

Conclusion

The results suggested that increased urinary level of CXCL10 combined with or without high NGF level could be a promising supplementary biomarker for differentiating HIC from NHIC with modest sensitivity and high specificity.
A Novel Home‐Based Intervention for Child and Adolescent Obesity: The Results of the Whānau Pakari Randomized Controlled Trial
Authors: Anderson Yvonne C. , Wynter Lisa E. , Grant Cameron C. , Cave Tami L. , Derraik José G. B. , Cutfield Wayne S. , Hofman Paul L.
Published: October 2017

Objective

To report 12‐month outcomes from a multidisciplinary child obesity intervention program, targeting high‐risk groups.

Methods

In this unblinded randomized controlled trial, participants (recruited January 2012‐August 2014) were aged 5 to 16 years, resided in Taranaki, Aotearoa/New Zealand, and had BMI ≥ 98th percentile or BMI > 91st percentile with weight‐related comorbidities. Randomization was by minimization (age and ethnicity), with participants assigned to an intense intervention group (home‐based assessments at 6‐month intervals and a 12‐month multidisciplinary program with weekly group sessions) or to a minimal‐intensity control group with home‐based assessments and advice at each 6‐month follow‐up. The primary outcome was the change in BMI standard deviation score (SDS) at 12 months from baseline. A mixed model analysis was undertaken, incorporating all 6‐ and 12‐month data.

Results

Two hundred and three children were randomly assigned (47% Māori, 43% New Zealand European, 53% female, 28% from the most deprived quintile, mean age 10.7 years, mean BMI SDS 3.12). Both groups displayed a change in BMI SDS at 12 months from baseline (−0.12 control, −0.10 intervention), improvements in cardiovascular fitness (P < 0.0001), and improvements in quality of life (P < 0.001). Achieving ≥ 70% attendance in the intense intervention group resulted in a change in BMI SDS of −0.22.

Conclusions

This program achieved a high recruitment of target groups and a high rate of BMI SDS reduction, irrespective of intervention intensity. If retention is optimized, the intensive program doubles its effect.
Primary mediastinal large B‐cell lymphoma: Outcome of a series of pediatric patients treated with high‐dose methotrexate and cytarabine plus anti‐CD20
Authors: Pillon Marta , Carraro E. , Mussolin L. , Conter V. , Tondo A. , Aricò M. , Mura R. , Sala A. , Vinti L. , Buffardi S. , Pierani P. , d'Amore E. S. G. , Basso G.
Published: October 2017

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B‐cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH‐97 protocol based on high‐dose methotrexate, anthracyclines, and addition of anti‐CD20. Ten patients achieved a continuous complete remission with front‐line therapy. The overall 5‐year survival was 91.7%, and event‐free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti‐CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.
Local therapy to distant metastatic sites in stage IV rhabdomyosarcoma
Authors: Mohan Arvind C. , Venkatramani Rajkumar , Okcu M. Fatih , Nuchtern Jed G. , Vasudevan Sanjeev A. , Mahajan Anita , Rainusso Nino C. , Allen‐Rhoades Wendy , Chintagumpala Murali , Paulino Arnold C.
Published: October 2017

Purpose

To determine the impact of surgery and/or radiation therapy on distant metastatic sites (DMS) in children with stage IV rhabdomyosarcoma (RMS).

Methods

A retrospective chart review was conducted on all patients with stage IV RMS at Texas Children's Hospital from 1992 to 2012. Data analyzed included age, gender, primary site, histologic subtype, number and sites of metastases, treatment including local therapy to DMS, and Oberlin score.

Results

The 5‐year progression‐free survival (PFS) and overall survival (OS) rates were 20% and 25%. The 5‐year PFS in patients receiving local therapy to all DMS (n = 16) and to less than all DMS (n = 19) was 31.3% versus 0% (P = 0.002), whereas the 5‐year OS was 37.3% versus 0% (P < 0.001), respectively. The 5‐year PFS in patients with isolated lung metastasis versus other types of metastasis was 29% versus 7% (P = n.s.), whereas the 5‐year OS was 43% versus 10% (P = 0.01). The 5‐year pulmonary local control was improved by the use of whole lung irradiation (WLI; 56% vs. 10%, P = 0.03).

Conclusions

Local treatment to all metastatic sites was associated with improved PFS and OS at 5 years. The use of WLI improved pulmonary control in patients with lung metastasis. We recommend an aggressive approach including local therapy to DMS in children with stage IV RMS.
Parental experiences of prenatal whole exome sequencing (WES) in cases of ultrasound diagnosed fetal structural anomaly
Authors: Quinlan‐Jones Elizabeth , Hillman Sarah C. , Kilby Mark D. , Greenfield Sheila M.
Published: October 2017

Objective

To explore parental experiences of whole exome sequencing (WES) for prenatal diagnosis and ascertain what influenced their decision‐making to undergo testing.

Method

Twelve women comprised a purposeful sample in a series of semistructured interviews. All had received a fetal anomaly diagnosis on ultrasound. A topic guide was used, and transcripts were thematically analyzed to elicit key themes.

Results

Five main themes (parental experiences of prenatal WES, need for information, consent/reasons for prenatal WES, sources of support for prenatal WES, and return of WES findings to families) emerged, some with multiple subthemes.

Conclusions

Parents desired as much information as possible and appreciated information being repeated and provided in various formats. Many struggled with clinical uncertainty relating to the cause and prognosis following a fetal anomaly diagnosis and found it difficult to balance the risks of invasive testing against their need for more definitive information. Parents trusted their clinicians and valued their support with decisions in pregnancy. Testing was sometimes pursued to reassure parents that their baby was “normal” rather than to confirm an underlying genetic problem. Parents were motivated to undergo WES for personal and altruistic reasons but disliked waiting times for results and were uncertain about what findings might be returned.
Locus of control, optimism, and recollections of depression and self‐reported cognitive functioning following treatment for colorectal cancer
Authors: Wilson Carlene , Giles Kristy , Nettelbeck Ted , Hutchinson Amanda
Published: October 2017

Objective

To investigate the effects of disposition (locus of control, optimism, and depression) on recollections of cognitive functioning following cancer treatment.

Methods

Participants were survivors of colorectal cancer (n = 88) and their spouses (n = 40). Survivors retrospectively rated their cognitive functioning and depression, as experienced following treatment and currently rated their dispositions for optimism and locus of control. Survivors' spouses likewise provided their recollections of survivors' cognitive functioning and depression at time following treatment.

Results

Correlations between survivors' and spouses' ratings for cognitive functioning were statistically significant but not for depression. Results supported validity of survivors' longer term retrospective reports. Although internal locus of control correlated positively with retrospectively self‐reported cognitive functioning, and negatively with retrospectively self‐reported depression, moderated hierarchical multiple regression found independent contribution of internal locus of control was limited to predicting quality of life; and that, among variables tested, depression correlated strongest with cognitive functioning.

Conclusions

Neither internal locus of control nor optimism in colorectal cancer survivors influences correlation between cognition and depression. Health care providers should note individual differences in responses to treatment and be alert to the impact of depression on perceived everyday functioning.
Fluoropolymer coated alanine films treated by atmospheric pressure plasmas − In comparison with gamma irradiation
Authors: Kusano Yukihiro , Bardenshtein Alexander , Morgen Per
Published: October 2017

Fluoropolymer coated alanine films are treated by a dielectric barrier discharge and a gliding arc at atmospheric pressure as well as with gamma irradiation. The film surfaces and the underlying bulk materials are characterized before and after each treatment. The fluorine content decreases and the oxygen content increases at the fluoropolymer surfaces, while deposition of specific plasma energies in the alanine films is detected by electron paramagnetic resonance spectroscopy, indicating that not only the fluoropolymer surfaces but also the bulk alanine materials are modified. Differences of surface and bulk modification effects between the two plasma treatments are discussed in detail.
Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions
Authors: Ali Muhammad , Khan Tariq , Fatima Kaneez , Ali Qurat ul Ain , Ovais Muhammad , Khalil Ali Talha , Ullah Ikram , Raza Abida , Shinwari Zabta Khan , Idrees Muhammad
Published: October 2017

Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol‐induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta‐1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.
Acid digestion on river influenced shelf sediment organic matter: Carbon and nitrogen contents and isotopic ratios
Authors: Pasquier Virgil , Sansjofre Pierre , Lebeau Oanez , Liorzou Celine , Rabineau Marina
Published: October 2017

Rationale

Natural stable isotope ratios (δ13Corg and δ15N values) and associated elemental concentrations (i.e. total organic carbon and total nitrogen contents) preserved in marine sediments are frequently used for the determination of paleo‐environmental processes such as the origin of organic matter. Previous studies highlighted biases in the determination of such geochemical proxies due to pre‐analysis acid treatment methods. This study is the first systematic comparison of the effect of acid treatment methods on bulk organic matter using a unique sedimentary system, under two contrasting climatic contexts (i.e. glacial vs interglacial).

Methods

We used the most common method for pre‐treatment analysis, which consists of the acidification of bulk sediments followed by several rinses with deionised water. We investigated the effect of acid type (hydrochloric and acetic acid), and also acid strength (from 0.2 to 10 mol.L−1) on the δ13Corg, δ15N, TOC, TN and C/N values of three samples from the Gulf of Lion. Two of them (S.304 and S.102) were deposited during glacial maxima (i.e. high sedimentation rate, low porosity and high terrestrial inputs) whereas S.157 characterizes interglacial conditions (high porosity, high foraminifera content, low sedimentation rates and low terrestrial inputs).

Results

For all three samples the δ13Corg values are between −21.7 and −24.4‰ with the TOC varying from 0.56 to 0.84 %wt/wt. The δ15N values are more stable with an average value of 3.0 ± 0.1‰ with a TN average of 0.08 ± 0.002 %wt/wt.

Conclusions

We show that acid type did not significantly affect results. We also find that (i) glacial and interglacial samples do not react similarly to acid pre‐treatment, (ii) high acid strength (>1.5 mol.L−1) induces significant bias on δ13Corg and TOC values, and therefore on C/N ratios; (iii) 25% of an isotopically distinct pool of organic carbon was lost when using acid concentrations of 0.2–1.5 mol.L−1, affecting δ13Corg values by more than 1.5‰; and (iv) geochemical evidence indicates that the leachable organic carbon pool is preferentially composed of terrestrial organic matter. These findings call for precautions when using C/N ratios and associated δ13Corg values for paleo‐environmental and climate reconstructions.
Rotavirus virus‐like particles (RV‐VLPs) vaccines: An update
Authors: Changotra Harish , Vij Avni
Published: October 2017

Rotaviruses (RVs) cause over 0.2 million deaths annually and are reported to be the foremost cause of gastroenteritis in infants and children worldwide. Vaccination against RVs is the most successful and unsurpassed strategy to combat infection to date. Although the 2 current vaccines, Rotarix and RotaTeq, have dramatically reduced the disease burden, still there is a need for new vaccines. In this context, RV virus‐like particles (RV‐VLPs) represent potential vaccine candidates as they are noninfectious and effective nonreplicating immunogens that may reduce the risk of side effects related to the conventional vaccines. VLPs being conformationally similar to the parent virus are highly immunogenic and hence provide enhanced protection and better serotype coverage. In this review, we have highlighted the various advantages and the implications of RV‐VLPs, discussed the general strategies employed for their production, and talked about the recent developments made in this regard. Overall, the review emphasizes the probable utility of RV‐VLPs in eradicating the highly widespread RVs.
Uncertainty of a detected spatial cluster in 1D: quantification and visualization
Authors: Lee Junho , Gangnon Ronald E. , Zhu Jun , Liang Jingjing
Published: October 2017

Spatial cluster detection is an important problem in a variety of scientific disciplines such as environmental sciences, epidemiology and sociology. However, there appears to be very limited statistical methodology for quantifying the uncertainty of a detected cluster. In this paper, we develop a new method for the quantification and visualization of uncertainty associated with a detected cluster. Our approach is defining a confidence set for the true cluster and visualizing the confidence set, based on the maximum likelihood, in time or in one‐dimensional space. We evaluate the pivotal property of the statistic used to construct the confidence set and the coverage rate for the true cluster via empirical distributions. For illustration, our methodology is applied to both simulated data and an Alaska boreal forest dataset. Copyright © 2017 John Wiley & Sons, Ltd.
Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells
Authors: Veltri Anthony , Lang Christopher , Lien Wen-Hui
Published: October 2017

Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF. Epidermal development and SC behavior are mainly regulated by various extrinsic cues, among which Wnt-dependent signaling pathways play crucial roles. This review not only summarizes the current knowledge of Wnt signaling pathways in the regulation of skin development and governance of SCs during tissue homeostasis, but also discusses the potential crosstalk of Wnt signaling with other pathways involved in these processes.
Amyloid β synaptotoxicity is Wnt‐PCP dependent and blocked by fasudil
Authors: Sellers Katherine J. , Elliott Christina , Jackson Joshua , Ghosh Anshua , Ribe Elena , Rojo Ana I. , Jarosz‐Griffiths Heledd H. , Watson Iain A. , Xia Weiming , Semenov Mikhail , Morin Peter , Hooper Nigel M. , Porter Rod , Preston Jane , Al‐Shawi Raya , Baillie George , Lovestone Simon , Cuadrado Antonio , Harte Michael , Simons Paul , Srivastava Deepak P. , Killick Richard
Published: October 2017

Introduction

Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf‐1 (Dkk1), which in turn activates the Wnt–planar cell polarity (Wnt‐PCP) pathway to drive tau pathology and neuronal death.

Methods

We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt‐PCP pathway.

Results

We demonstrate that Aβ synaptotoxicity is also Dkk1 and Wnt‐PCP dependent, mediated by the arm of Wnt‐PCP regulating actin cytoskeletal dynamics via Daam1, RhoA and ROCK, and can be blocked by the drug fasudil.

Discussion

Our data add to the importance of aberrant Wnt signaling in Alzheimer's disease neuropathology and indicate that fasudil could be repurposed as a treatment for the disease.
Traumatic exposures, posttraumatic stress disorder, and cognitive functioning in World Trade Center responders
Authors: Clouston Sean A.P. , Pietrzak Robert H. , Kotov Roman , Richards Marcus , Spiro Avron , Scott Stacey B. , Deri Yael , Mukherjee Soumyadeep , Stewart Candace , Bromet Evelyn J. , Luft Benjamin J.
Published: October 2017

Introduction

This study examined whether World Trade Center (WTC)‐related exposures and posttraumatic stress disorder (PTSD) were associated with cognitive function and whether WTC responders' cognition differed from normative data.

Methods

A computer‐assisted neuropsychological battery was administered to a prospective cohort study of 1193 WTC responders with no history of stroke or WTC‐related head injuries. Data were linked to information collected prospectively since 2002. Sample averages were compared to published norms.

Results

Approximately 14.8% of sampled responders had cognitive dysfunction. WTC responders had worse cognitive function compared to normative data. PTSD symptom severity and working >5 weeks on‐site was associated with cognitive dysfunction.

Discussion

Results from this sample highlight the potential for WTC responders to be experiencing an increased burden of cognitive dysfunction and linked lowered cognitive functioning to physical exposures and to PTSD. Future research is warranted to understand the extent to which cognitive dysfunction is evident in neural dysfunction.
BIBLE TRANSLATION AND THE FORMATION OF CORPORATE IDENTITY IN UGANDA AND CONGO 1900–40
Authors: WILD-WOOD EMMA
Published: October 2017

Engaging debates around ethnic nationhood and knowledge production, this article examines the influence of Bible translation on corporate identity formation in Toro and Ituri (1900–40). It studies translations instigated by one individual to investigate textual agency wherever it leads. The translator Apolo Kivebulaya promoted adherence to Christianity as an inclusive and linguistically-plural global community. His translation for the Mbuti, which had limited circulation among its intended audience, shows an aspect of this global community at work, remaking the international image of the Mbuti. His earlier Runyoro-Rutoro translation, however, encouraged a local and political form of corporate identity in which translation and Old Testament stories helped to form an ethnic moral economy. In focusing upon Bible translation among the Toro and the Mbuti, the article moves from the politically influential Ganda, the focus of much historiography of Christianity in East Africa, and explains the roots of later revivalism and patriotism.
BRINGING HISTORY BACK IN: PAST, PRESENT, AND CONFLICT IN RWANDA AND THE EASTERN DEMOCRATIC REPUBLIC OF CONGO
Authors: MATHYS GILLIAN
Published: October 2017

This article argues that on the borderland between eastern DRC and Rwanda, the past and its representations have been constantly manipulated. The cataclysmic events in both Rwanda and Congo since the 1990s have widened the gap between partial and politicized historical discourse and careful historical analysis. The failure to pay attention to the multiple layers in the production of historical narratives risks reproducing a politicized social present that ‘naturalizes’ differences and antagonisms between different groups by giving them more time-depth. This is a danger both for insiders and outsiders looking in. The answer is to focus on the historical trajectories that shape historical narratives, and to ‘bring history back in’.
Effects of entrenchment and preemption in second language learners’ acceptance of English denominal verbs
Authors: ZHANG XIAOPENG , MAI CHUNPING
Published: October 2017

Entrenchment and preemption are theorized to constrain the novel use of well-attested constructions. This study tested the effects of these two mechanisms in second language (L2) learners’ acceptance of English denominal verbs (DVs). Two groups of Chinese English-L2 speakers (fourth-year English major students and teachers of English) judged the acceptability of English locatum (e.g.,Lucywateredthe rose) and location (e.g.,Lisaboxedthe apples) DVs. Results based on both corpus and introspective frequencies show that the fourth-year learners’ judgments on the acceptability of all DVs were significantly negatively influenced by the frequency of nominal forms of the DVs, suggesting that entrenchment constrains L2 learners from accepting English DVs. Results based on introspective frequency demonstrate that the teachers’ judgments on the acceptability of all DVs were significantly negatively affected by the frequency of alternative verbs, demonstrating that preemption has a role to play in restricting L2 learners’ acceptance of English DVs. Moreover, the obtained DV frequency based on both corpus and learners’ introspection is a significant factor that helps all the participants’ acceptance of the English DVs, suggesting that the more frequently a DV is used, the more likely L2 learners are to judge it as acceptable.
Culture-Based Emotional Working Models of Attachment, Western-Based Attachment, and Psychosocial Functioning of Chinese Young Adults
Authors: Sun Qi-Wu , Wang Chiachih D. C. , Jiang Guang-Rong
Published: October 2017

The aim of these 2 studies is to address the applicability of adult attachment theory to Chinese populations. Guided by the emic principle, the first study used a bottom-up, locally normed approach to develop a culture-based adult attachment scale, named Feelings in Significant Relationships Scale (FSRS) that focused on the emotional components of internal working models (IWMs) experienced by Chinese individuals. Results of Study 1 provided initial evidence for the preliminary psychometric properties of the FSRS. Study 2 examined the unique and joint effects of the emotional components of IWMs, Western-based adult attachment, and parental attachment on 3 psychosocial variables: depression, loneliness, and interpersonal problems. Results indicated that parental and adult attachment variables significantly predicted all 3 dependent variables reported by Chinese participants. In addition, the FSRS was found to predict a significant amount of variance in all dependent variables above and beyond what was accounted for by the existing attachment scales. An important implication of the findings is that the inclusion of the emotional components of IWMs, as measured by the emic-based FSRS, provides a more comprehensive understanding of attachment impacts on Chinese adults’ psychosocial functioning.