bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETV6/RUNX1‐like acute lymphoblastic leukemia: A novel B‐cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype
Authors: Zaliova Marketa , Kotrova Michaela , Bresolin Silvia , Stuchly Jan , Stary Jan , Hrusak Ondrej , te Kronnie Geertruy , Trka Jan , Zuna Jan , Vaskova Martina 
Published: April 2017

AbstractWe have shown previously that ETV6/RUNX1‐positive acute lymphoblastic leukemia (ALL) is distinguishable from other ALL subtypes by CD27pos/CD44low‐neg immunophenotype. During diagnostic immunophenotyping of 573 childhood B‐cell precursor ALL (BCP‐ALL), we identified eight cases with this immunophenotype among “B‐other ALL” (BCP‐ALL cases negative for routinely tested chromosomal/genetic aberrations). We aimed to elucidate whether these cases belong to the recently described ETV6/RUNX1‐like ALL defined by the ETV6/RUNX1‐specific gene expression profile (GEP), harboring concurrent ETV6 and IKZF1 lesions. We performed comprehensive genomic analysis using single nucleotide polymorphism arrays, whole exome and transcriptome sequencing and GEP on microarrays. In unsupervised hierarchical clustering based on GEP, five out of seven analyzed CD27pos/CD44low‐neg B‐other cases clustered with ETV6/RUNX1‐positive ALL and were thus classified as ETV6/RUNX1‐like ALL. The two cases clustering outside ETV6/RUNX1‐positive ALL harbored a P2RY8/CRLF2 fusion with activating JAK2 mutations and a TCF3/ZNF384 fusion, respectively, assigning them to other ALL subtypes. All five ETV6/RUNX1‐like cases harbored ETV6 deletions; uniform intragenic ARPP21 deletions and various IKZF1 lesions were each found in three ETV6/RUNX1‐like cases. The frequency of ETV6 and ARPP21 deletions was significantly higher in ETV6/RUNX1‐like ALL compared with a reference cohort of 42 B‐other ALL. In conclusion, we show that ETV6/RUNX1‐like ALL is associated with CD27pos/CD44low‐neg immunophenotype and identify ARPP21 deletions to contribute to its specific genomic profile enriched for ETV6 and IKZF1 lesions. In conjunction with previously published data, our study identifies the ETV6 lesion as the only common genetic aberration and thus the most likely key driver of ETV6/RUNX1‐like ALL.
Abdominal obesity and white matter microstructure in midlife
Authors: Birdsill Alex Cole , Oleson Stephanie , Kaur Sonya , Pasha Evan , Ireton Adele , Tanaka Hirofumi , Haley Andreana 
Published: April 2017

AbstractThe aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion‐tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40–62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full‐tensor, high‐dimension normalization, and tract‐based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL‐cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337–3344, 2017. © 2017 Wiley Periodicals, Inc.
White matter developmental trajectories associated with persistence and recovery of childhood stuttering
Authors: Chow Ho Ming , Chang Soo‐Eun 
Published: April 2017

AbstractStuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual's psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering has been reported. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3 and 12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel‐wise to examine group and age‐related differences using a linear mixed‐effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum was found, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering. Hum Brain Mapp 38:3345–3359, 2017. © 2017 Wiley Periodicals, Inc.
Toward an electrophysiological “sweet spot” for deep brain stimulation in the subthalamic nucleus
Authors: Horn Andreas , Neumann Wolf‐Julian , Degen Katharina , Schneider Gerd‐Helge , Kühn Andrea A. 
Published: April 2017

AbstractEnhanced beta‐band activity recorded in patients suffering from Parkinson‘s Disease (PD) has been described as a potential physiomarker for disease severity. Beta power is suppressed by Levodopa intake and STN deep brain stimulation (DBS) and correlates with disease severity across patients. The aim of the present study was to explore the promising signature of the physiomarker in the spatial domain. Based on local field potential data acquired from 54 patients undergoing STN‐DBS, power values within alpha, beta, low beta, and high beta bands were calculated. Values were projected into common stereotactic space after DBS lead localization. Recorded beta power values were significantly higher at posterior and dorsal lead positions, as well as in active compared with inactive pairs. The peak of activity in the beta band was situated within the sensorimotor functional zone of the nucleus. In contrast, higher alpha activity was found in a more ventromedial region, potentially corresponding to associative or premotor functional zones of the STN. Beta‐ and alpha‐power peaks were then used as seeds in a fiber tracking experiment. Here, the beta‐site received more input from primary motor cortex whereas the alpha‐site was more strongly connected to premotor and prefrontal areas. The results summarize predominant spatial locations of frequency signatures recorded in STN‐DBS patients in a probabilistic fashion. The site of predominant beta‐activity may serve as an electrophysiologically determined target for optimal outcome in STN‐DBS for PD in the future. Hum Brain Mapp 38:3377–3390, 2017. © 2017 Wiley Periodicals, Inc.
Brain structure and verbal function across adulthood while controlling for cerebrovascular risks
Authors: Sanfratello L. , Lundy S.L. , Qualls C. , Knoefel J.E. , Adair J.C. , Caprihan A. , Stephen J.M. , Aine C.J. 
Published: April 2017

AbstractThe development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age‐related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle‐aged group (MC: 35–45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18–25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age‐related cognitive decline.Hum Brain Mapp 38:3472–3490, 2017. ©2017 Wiley Periodicals, Inc.
Default mode and task‐positive networks connectivity during the N‐Back task in remitted depressed patients with or without emotional residual symptoms
Authors: Delaveau Pauline , Arruda Sanchez Tiago , Steffen Ricardo , Deschet Karine , Jabourian Maritza , Perlbarg Vincent , Gasparetto Emerson Leandro , Dubal Stéphanie , Costa e Silva Jorge , Fossati Philippe 
Published: April 2017

AbstractClinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N‐Back task. Twenty‐six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N‐Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N‐Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N‐Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3‐Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491–3501, 2017. © 2017 Wiley Periodicals, Inc.
Role of the Lysosomal Membrane Protein, CLN3, in the Regulation of Cathepsin D Activity
Authors: Cárcel‐Trullols Jaime , Kovács Attila D. , Pearce David A. 
Published: April 2017

ABSTRACTAmong Neuronal Ceroid Lipofuscinoses (NCLs), which are childhood fatal neurodegenerative disorders, the juvenile onset form (JNCL) is the most common. JNCL is caused by recessive mutations in the CLN3 gene. CLN3 encodes a lysosomal/endosomal transmembrane protein but its precise function is not completely known. We have previously reported that in baby hamster kidney (BHK) cells stably expressing myc‐tagged human CLN3 (myc‐CLN3), hyperosmotic conditions drastically increased myc‐CLN3 mRNA and protein expression. In the present study, we analyzed the consequences of hyperosmolarity, and increased CLN3 expression on cathepsin D (CTSD) activity and prosaposin processing using BHK cells transiently or stably expressing myc‐CLN3. We found that hyperosmolarity increased lysotracker staining of lysosomes, and elevated the levels of myc‐CLN3 and lysosome‐associated membrane protein‐1 (LAMP1). Hyperosmolarity, independently of the expression level of myc‐CLN3, decreased the levels of PSAP and saposin D, which are protein cofactors in sphingolipid metabolism. The lysosomal enzyme cathepsin D (CTSD) mediates the proteolytic cleavage of PSAP precursor into saposins A‐D. Myc‐CLN3 colocalized with CTSD and activity of CTSD decreased as myc‐CLN3 expression increased, and clearly decreased under hyperosmotic conditions. Nevertheless, levels of CTSD measured by Western blotting were not altered under any studied condition. Our results suggest a direct involvement of CLN3 in the regulation of CTSD activity. J. Cell. Biochem. 118: 3883–3890, 2017. © 2017 Wiley Periodicals, Inc.
Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy
Authors: Xiao Yang , Yang Zheng , Wu Qing‐Qing , Jiang Xiao‐Han , Yuan Yuan , Chang Wei , Bian Zhou Yan , Zhu Jin Xiu , Tang Qi‐Zhu 
Published: April 2017

ABSTRACTLack of effective anti‐cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti‐hypertrophy and anti‐fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti‐hypertrophy and ‐fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross‐sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B‐mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3‐MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B‐mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899–3910, 2017. © 2017 Wiley Periodicals, Inc.
Molecular Imaging and Oral Cancer Diagnosis and Therapy
Authors: Keshavarzi Maryam , Darijani Mansoreh , Momeni Fatemeh , Moradi Pouya , Ebrahimnejad Hamed , Masoudifar Aria , Mirzaei Hamed 
Published: April 2017

ABSTRACTOral cancer is known as one of relatively common type of cancer worldwide. Despite the easy access of the oral cavity to examination, oral tumors are diagnosed in more advanced stages of the disease. Imaging techniques have been recently emerged as non‐invasive approaches to detect molecular and cellular changes in living cells and organisms. These techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) could help physicians to screen patients with oral tumors particularly oral squamous cell carcinoma (OSCC) in early stage of the disease. In this review, we discuss that early detection and diagnosis of oral tumors through using more robust and precise imaging techniques and a variety of cellular/molecular biomarkers not only could lead to more effective and less aggressive form of treatment for the disease but also could improve survival rates and lower treatment costs. J. Cell. Biochem. 118: 3055–3060, 2017. © 2017 Wiley Periodicals, Inc.
Exploring the Influence of Attitude and Stigma on Participation of African American and Latino Populations in Mental Health Services
Authors: Fripp Jessica A. , Carlson Ryan G. 
Published: April 2017

Various factors, including mistrust and disparities, prevent people of color from taking advantage of mental health services. Previous research has focused on mistrust, disparities, and stigma. However, little is understood about how one's attitude affects participation in mental health. The authors surveyed 129 African American and Latino community participants to examine the relationships among attitudes, stigma, and help‐seeking behavior. Linear regression analyses revealed that attitude is a unique predictor in one's decision to seek counseling and is influenced by the presence of stigma.Varios factores, entre los que se incluyen la falta de confianza y las disparidades, impiden que las personas de color aprovechen los servicios de salud mental. Las investigaciones hasta ahora se han centrado en la falta de confianza, las disparidades y los estigmas. Sin embargo, falta mucho para comprender cómo la actitud de una persona afecta a su participación en la salud mental. Los autores entrevistaron a 129 participantes de comunidades afroamericanas y latinas para examinar las relaciones entre actitudes, estigmas y la búsqueda de ayuda. Los análisis de regresión lineal revelaron que la actitud es un indicador único en la decisión de un individuo de buscar servicios de consejería, y está influida por la presencia de estigmas.
Efficacy and safety of nucleoside‐sparing regimen based on raltegravir and ritonavir‐boosted darunavir in HIV‐1‐infected treatment‐experienced patients
Authors: Jabłonowska Elżbieta , Pulik Piotr , Kalinowska Anna , Gąsiorowski Jacek , Parczewski Miłosz , Bociąga‐Jasik Monika , Pulik Łukasz , Siwak Ewa , Wójcik Kamila 
Published: April 2017

AimTo assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV‐1‐infected treatment‐experienced patients.MethodRetrospective analysis of 81 HIV‐1‐infected treatment‐experienced patients (56 male and 25 female, 5 Polish centers) who switched to RAL/DRV/r.ResultsThe main reasons for the introduction of dual therapy were renal dysfunction (16/81 patients—19.8%) and virologic failure on previous regimens (15/81 patients—18.5%). At 48 weeks the treatment was continued in 58/81 (71.6% of patients). In three patients the therapy was discontinued because of virologic failure. However, no mutations to DRV or integrase inhibitors (InI) were detected. At 48 weeks of treatment CD4+ lymphocyte count increased statistically significantly (median 121 cells/μL) P < 0.005. The main reasons for the discontinuation of therapy were treatment simplification (11/23—47.8% patients), adverse events (7/23 patients 30.4%), virologic failure (3/23 patients 13.0%). All patients who switched to RAL/DRV/r therapy because of prior renal impairment were maintained on the treatment for 48 weeks. In this group, before the introduction of dual therapy eGFR (estimated glomerular filtration rate) <60 mL/min/1.72 m2 was reported in nine patients and after 48 weeks in four patients (56.3% vs 25%) (P > 0.05). We found a statistically significant decrease in the prevalence of proteinuria or eGFR <60 mL/min/1.72 m2 (93.8% vs 37.5%; P = 0.004 before and after the introduction of dual therapy, respectively).ConclusionsDual therapy was effective and safe for the vast majority of antiretroviral‐experienced subjects. Such therapy can be recommended especially for patients with renal impairment or NRTIs intolerance.
Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma‐induced heterotopic ossification
Authors: Seavey Jonathan G. , Wheatley Benjamin M. , Pavey Gabriel J. , Tomasino Allison M. , Hanson Margaret A. , Sanders Erin M. , Dey Devaveena , Moss Kaitlyn L. , Potter Benjamin K. , Forsberg Jonathan A. , Qureshi Ammar T. , Davis Thomas A. 
Published: April 2017

ABSTRACTHeterotopic ossification (HO) is a debilitating sequela of high‐energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat‐injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast‐related, post‐traumatic HO. Male Sprague‐Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin‐resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD‐0, n = 34) or on postoperative day‐3 (POD‐3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12‐weeks post‐injury by micro‐CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post‐injury. Vancomycin treatment on POD‐0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro‐inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397–2406, 2017.