bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Genetic Approach Identifies MET, HER3, IGF1R, INSR Pathways as Determinants of Lapatinib Unresponsiveness in HER2-Positive Gastric Cancer
Authors: Zhang Zhe , Wang Jiping , Ji Dongmei , Wang Chenchen , Liu Rujiao , Wu Zheng , Liu Lian , Zhu Dan , Chang Jinjia , Geng Ruixuan , Xiong Lei , Fang Qiangyi , Li Jin 
Published: June 2014

Abstract
Purpose: Targeting human epidermal growth factor receptor 2 (HER2) therapy is currently considered as the standard treatment for HER2-positive (HER2+) advanced gastric cancer. However, as seen in recent clinical trials, most of HER2+ gastric cancer are actually unresponsive to HER2-targeted agents, including lapatinib. The aim of this study is to identify the responsible receptor tyrosine kinases (RTK) potentially conferring lapatinib unresponsiveness in HER2+ gastric cancer and elucidate the molecular mechanism underlying this RTKs-induced resistance.
Experimental Design: A functional RNAi screen targeting human RTKs and related growth factors was used to identify candidate RTKs conferring lapatinib unresponsiveness in HER2+ gastric cancer cells. Independent siRNAs transfection and corresponding ligands supplement were performed to validate the effects of candidate RTKs on lapatinib sensitivity. Cross-talks of pathways involved were analyzed via Western blot analysis. Cell apoptosis and cell motility were detected using FACS system and Transwell assay. Immunohistochemistry was used to analyze protein expression in clinical samples.
Results: MET, HER3, insulin-like growth factor (IGF)-1R, and INSR were identified to mediate lapatinib unresponsiveness in HER2+ gastric cancer cells. Activation of these bypass RTKs attenuated lapatinib-induced apoptosis and suppression of cell motility, mechanistically because of restimulating the shared downstream AKT or ERK signaling, as well as restimulating WNT signaling and epithelial-to-mesenchymal transition (EMT)–like process. Patients' specimens revealed that these unresponsiveness-conferring RTKs were particularly enriched in the majority of patients with HER2+ gastric cancer.
Conclusions: MET, HER3, IGF1R, and INSR pathways activation represent novel mechanism underlying lapatinib unresponsiveness in HER2+ gastric cancer. Combination strategy may be recommended in treating patients with HER2+ gastric cancer with these pathways activation. Clin Cancer Res; 20(17); 4559–73. ©2014 AACR.
Effects of Vowel Auditory Training on Concurrent Speech Segregation in Hearing Impaired Children
Authors: Talebi Hossein , Moossavi Abdollah , Lotfi Yones , Faghihzadeh Soghrat 
Published: June 2014

Objective: This clinical trial investigated the ability of concurrent speech segregation in hearing impaired children. The auditory behavioral responses and auditory late responses (ALRs) were compared between test and control groups prior to vowel auditory training and after 3 and 6 months of vowel auditory training to find the effects of bottom-up training on concurrent speech segregation in hearing impaired children. Methods: Auditory behavioral responses for 5 vowels and ALRs for double synthetic vowels, with special physical properties, were recorded in a timetable in 30 hearing impaired children (test group = 15 and control group = 15). Results: Identification score and reaction time data showed that the test group was approximately proficient for some vowels ( P < .05 for vowels /æ/, /e/, and /u:/) and took less time to process after 6 months of training. N1-P2 amplitude indexing of the vowel change detection and reflecting central auditory speech representation without active client participation has been increased in the test group ( P < .05). Conclusion: The present study showed training-related improvements in concurrent speech segregation. This information provided evidence for bottom-up training based on F0, its differences in auditory scene analysis, and neural underpinnings.
A meta-analysis of fMRI studies in healthy relatives of patients with schizophrenia
Authors: Scognamiglio Claire , Houenou Josselin 
Published: June 2014

Objective: Genetically at-risk yet healthy relatives of patients with schizophrenia, sharing an important part of the genetic susceptibility to the disease, allow the study of neuroimaging endophenotypes. The aim of our study was to perform a meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies that compared adult healthy relatives of patients with schizophrenia and controls. Methods: Twenty-one whole-brain fMRI studies were included (17 using cognitive tasks and four using emotional tasks), published between 2003 and 2013. These studies included 467 healthy relatives of patients with schizophrenia and 768 controls. To conduct the statistical analysis, we used the effect-size signed differential mapping software, a voxel-based meta-analytic approach. Results: In healthy relatives of patients with schizophrenia, we observed a general pattern of overactivation across the 21 fMRI studies in right-sided frontal, parietal and temporal regions compared to controls. This pattern was accompanied by an underactivation in the cingulate gyrus. Our analyses showed a very similar pattern during purely cognitive tasks; during emotional tasks, healthy relatives additionally overactivated the left parahippocampal gyrus. Conclusions: This fMRI pattern of prefrontal overactivation and hypoactivation of the cingulate gyrus may represent a candidate endophenotype for schizophrenia.
Coping strategies and self-stigma among adolescents discharged from psychiatric hospitalization: A 6-month follow-up study
Authors: Moses Tally 
Published: June 2014

Background: The effects of mental illness stigma on adolescents receiving psychiatric treatment may largely be determined by their coping strategies. Yet, little is known about adolescents’ use of stigma-coping strategies, or how helpful these are for addressing stigma-related stress. Aims: This study explores how adolescents discharged from psychiatric hospitalization anticipate coping with a hypothetical social stigma event related to hospitalization. We examine how well anticipated coping strategies predict adolescents’ self-stigma ratings following 6 months. To evaluate the direction of causality, the reverse order of effects, the influence of self-stigma on coping strategies, is also assessed. Methods: A voluntary sample of 80 adolescents participated in two face-to-face interviews that assessed coping and self-stigma. Anticipated (baseline) and actual (follow-up) coping strategies were measured with a modified Response to Stress Questionnaire (primary and secondary control engagement coping, disengagement) and two stigma-specific strategies developed for this study (disconfirming stereotypes and aggression/confrontation). Relationships between anticipated coping strategies and self-stigma were assessed with ordinary least squares (OLS) regression; multivariate general linear modeling (GLM) and structural equation modeling (SEM) explored the reverse associations. Results: Youth reporting higher self-stigma ratings at follow-up anticipated using more disengagement and effort to disconfirm stereotypes and less secondary control engagement coping at baseline. Anticipated use of secondary control engagement coping was uniquely significant in predicting participants’ self-stigma when controlling for baseline self-stigma. At the same time, higher baseline self-stigma ratings predicted less adaptive coping (disengagement and effort to disconfirm stereotypes) at follow-up. Conclusions: The results point to the particular importance of secondary control engagement coping for helping to mitigate the impact of peer prejudice or discrimination on self-stigma among youth receiving psychiatric services. At the same time, higher initial levels of self-stigma likely drive less adaptive coping with peer stigma. These bidirectional influences point to a vicious cycle between internalizing negative stereotypes and coping in ways that perpetuate negative outcomes.
What helps or undermines adolescents’ anticipated capacity to cope with mental illness stigma following psychiatric hospitalization
Authors: Moses Tally 
Published: June 2014

Background: Better understanding of the individual and environmental factors that promote adolescents’ use of more or less adaptive coping strategies with mental illness stigma would inform interventions designed to bolster youth resilience. Aims: This cross-sectional study draws on data from research on adolescents’ well-being after discharge from a first psychiatric hospitalization to explore the relationships between anticipated coping in reaction to a hypothetical social stigma scenario, and various factors conceptualized as ‘coping resource’ and ‘coping vulnerability’ factors. Focusing on coping strategies also identified in the companion article, we hypothesize that primary and secondary control engagement coping would relate to more coping resource and less coping vulnerability factors, and the opposite would be true for disengagement, aggression/confrontation and efforts to disconfirm stereotypes. Methods: Data were elicited from interviews with 102 adolescents within 7 days of discharge. Hypothesized coping resource factors included social resources, optimistic illness perceptions, better hospital experiences and higher self-esteem. Vulnerability factors included more previous stigma experiences, desire for concealment of treatment, more contingent self-worth, higher symptom levels and higher anticipated stress. Multivariate ordinary least squares (OLS) regression was used to analyze associations between coping strategy endorsement and correlates. Results: Although some coping correlates ‘behaved’ contrary to expectations, for the most part, our hypotheses were confirmed. As expected, youth anticipating reacting to the stigmatizing situation with greater disengagement, aggression/confrontation or efforts to disconfirm stenotypes rated significantly lower on ‘coping resources’ such as self-esteem and higher on vulnerability factors such as symptom severity. The opposite was true for youth who anticipated exercising more primary and secondary control engagement coping. Conclusions: This study begins to identify factors that promote more and less adaptive coping strategies among youth at high risk for social stigma. Some factors that can be modified in the shorter term point to useful directions for clinical interventions.
Identifying the socio-demographic and clinical determinants of family functioning in Greek patients with psychosis
Authors: Koutra Katerina , Triliva Sofia , Roumeliotaki Theano , Lionis Christos , Vgontzas Alexandros N 
Published: June 2014

Background: Studies on determinants affecting family functioning of patients with psychosis are still limited in Greece. Aim: The aim of this study was to describe the socio-demographic and clinical characteristics associated with family functioning in patients with schizophrenia and bipolar disorder in Crete, Greece. Methods: A total of 100 patients and their caregivers agreed to participate in the study. Family functioning was assessed in terms of cohesion, adaptability, communication and satisfaction dimensions (Family Adaptability and Cohesion Evaluation Scale IV Package), expressed emotion (Family Questionnaire), family burden (Family Burden Scale) and caregivers’ psychological distress (General Health Questionnaire-28). Multivariate linear regression models were implemented to examine the associations between each one of the family measures and different social and clinical characteristics. Results: With regard to the caregivers’ characteristics, gender, employment status, origin, residence, financial status, relation to the patient, contact with the patient and family structure were among the most significant determinants of family functioning. Also, patients’ socio-demographic characteristics, including age, education, origin, residence and employment status, as well as illness-related factors, such as onset of mental illness, number of hospitalisations, last hospitalisation, longer hospitalisation and clinical diagnosis impacted intrafamilial relationships. Conclusion: The results of this study suggest that a number of social and clinical factors contributed to the family environment of patients with psychosis. Identifying the determinants of family functioning in psychosis is instrumental in developing understandings regarding the factors which may contribute to the rehabilitation or relapse of the patient and the support required to strengthen positive family interactions.
Fibroblasts Regulate Variable Aggressiveness of Syndromic Keratocystic and Non-syndromic Odontogenic Tumors
Authors: Hong Y.-Y. , Yu F.-Y. , Qu J.-F. , Chen F. , Li T.-J. 
Published: June 2014

Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor–kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype. Abbreviations: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase.
A fast model for identifying multiple indoor contaminant sources by considering sensor threshold and measurement error
Authors: Cai Hao , Li Xianting , Chen Zhilong , Wang Mingyang 
Published: June 2014

In an emergency where a hazardous contaminant is abruptly released into indoor air, identifying the characteristics of contaminant source promptly and accurately is very important to eliminate source, control contamination and protect people. An identification model is presented in this study for quickly identifying the exact locations and emissions rates of multiple indoor contaminant sources with constant emissions rates and known release time, by considering sensor thresholds and measurement errors. Through case studies in a three-dimensional room, the model was numerically demonstrated and validated, and thorough analyses were made on the effects of the sensor threshold and measurement error on model performance. The results suggest that the model has the potential to obtain accurate results in real-time allowing for high levels of sensor data loss and measurement error. Practical application: The presented identification model is applicable to a wide variety of indoor environments involving multiple continuous contaminant sources, such as the emission of volatile compounds from building materials or furniture, the leakage of toxic or inflammable gases from pipeline or vessels in trace amount. This study will hopefully contribute to developing more realistic source identification techniques with unknown release time and real sensor use.
Medical and Surgical Management of Congenital Laryngomalacia: A Case‐control Study
Authors: Faria John , Behar Philomena 
Published: June 2014

ObjectiveTo compare the growth of infants with moderate to severe laryngomalacia who underwent supraglottoplasty to the growth of those treated with medical therapy alone.Study DesignCase‐control study of patients treated between 2008 and 2013.SettingTertiary care pediatric otolaryngology practice.Subjects and MethodsFifty‐one infants newly diagnosed with moderate to severe congenital laryngomalacia. Seventeen infants underwent supraglottoplasty and 34 matched controls had medical management, which included acid suppression therapy, speech and swallowing therapy, and/or high‐calorie formula. The primary outcome measure was weight percentile recorded at the second clinic visit and at the last available follow‐up. The secondary outcomes were the need for primary or revision supraglottoplasty, tracheostomy or gastrostromy, or the development of or persistence of failure to thrive.ResultsThere was no difference in the mean weight percentile between the surgical and nonsurgical groups at the time of last follow‐up (P =. 89). The mean change in weight percentile during the study period was 32% (95% CI, 15%‐48%) in the supraglottoplasty group and 31% (95% CI, 22%‐40%) in the medical group (P =. 97). Five of 5 (100%) patients with failure to thrive managed surgically and 10 of 10 (100%) managed medically were above the fifth percentile at the end of the follow‐up period. One (3%) patient in the medical management group required tracheostomy and gastrostomy tube placement.ConclusionsMedical management and close observation of infants with moderate to severe congenital laryngomalacia may be a viable alternative to supraglottoplasty in appropriately selected infants.
Ultrastructure of internal jugular vein defective valves
Authors: Zamboni P , Tisato V , Menegatti E , Mascoli F , Gianesini S , Salvi F , Secchiero P 
Published: June 2014

Objectives To study the ultrastructure of intraluminal defects found in the internal jugular vein by using a scanning electron microscopy. Methods Using a scanning electron microscopy, intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein of seven patients were studied together with the adjacent wall and compared with control specimen. Results The internal jugular veins’ wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina. Conclusions Although the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/inflammatory remodelling.
CT urography and hematuria: a retrospective analysis of 771 patients undergoing CT urography over a 1-year period
Authors: Bretlau Thomas , Hansen Rasmus H , Thomsen Henrik S 
Published: June 2014

Background Computed tomography (CT) urography is now used in the work-up of patients with hematuria. The dose of contrast medium and radiation varies considerably between the different CT protocols. Purpose To study the disease prevalence in a consecutive group of patients with hematuria undergoing CT urography with a low dose of contrast medium and radiation. Material and Methods From 1 April 2007 to 31 March 2008, using the Radiological Information System (RIS) as well as electronic patient records, demographic data, reason for referral, and diagnosis were obtained for all patients undergoing CT urography due to hematuria. The patients were followed for 3 years. Results A total of 771 patients had hematuria diagnosed at the time of referral. In 137 patients (18%), a tumor and / or a complex cyst was found in the urinary tract (renal, ureteral, or bladder), in 68 (9%) a calculi, in 118 (15%) other disease (i.e. infection or anomaly) was found. No abnormalities were found at CT urography in 455 (58%) of the patients with hematuria. Lesions were found more frequently in patients with visible hematuria than in patients with non-visible hematuria (48% vs. 29%). No malignant tumor or complex cyst was found in the kidneys or the ureters in patients with nonvisible hematuria. Conclusion CT urography with its low dose of contrast medium and radiation is a useful diagnostic imaging test for investigating patients with hematuria.
Pre-treatment staging of multiple myeloma patients: comparison of whole-body diffusion weighted imaging with whole-body T1-weighted contrast-enhanced imaging
Authors: Squillaci Ettore , Bolacchi Francesca , Altobelli Simone , Franceschini Luca , Bergamini Alberto , Cantonetti Maria , Simonetti Giovanni 
Published: June 2014

Background Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells. Accurate staging is of pivotal importance in the management of MM. Advanced imaging techniques, such as magnetic resonance imaging (MRI), are increasingly used for the initial diagnosis and staging of MM. Purpose To compare whole-body (WB) MR diffusion-weighted imaging with background body signal suppression (DWIBS) with (WB) MR fat-suppressed T1-weighted contrast-enhanced imaging (T1-CE) in the pre-treatment staging evaluation of multiple myeloma (MM) patients. Material and Methods Thirty-six patients with MM were included in the study. T1-CE and DWIBS were performed using a 3 T scanner. The Durie-Salmon plus staging system was used. Kappa statistics was used to assess agreement. Results For all MM stages good to very good agreement was found for both T1-CE and DWIBS. The unweighted kappa statistic indicated a moderate, good and very good agreement between T1-CE and DWIBS for stages I, II, and III, respectively. In particular, in 67% of patients the MM staging according to T1-CE was not different from DWIBS. In the remaining 33% of patients, the MM stage obtained with T1-CE was lower than that provided by DWIBS. Conclusion DWIBS and T1-CE were concordant in the majority of patients. In a minority of cases DWIBS evidenced areas of water restriction that did not correspond to contrast enhancement areas. Studies monitoring therapeutic response in relation to tumour burden and aggressiveness should be performed to assess the clinical relevance of DWIBS findings.