bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide RNAi Screening Identifies RFC4 as a Factor That Mediates Radioresistance in Colorectal Cancer by Facilitating Nonhomologous End Joining Repair
Authors: Wang Xue-Cen , Yue Xin , Zhang Rong-Xin , Liu Ting-Yu , Pan Zhi-Zhong , Yang Meng-Jie , Lu Zhen-Hai , Wang Zi-Yang , Peng Jian-Hong , Le Li-Yuan , Wang Gao-Yuan , Peng Qi-Hua , Meng Yuan , Huang Wenlin , Liu Ran-Yi 
Published: April 2019

Abstract

Purpose:
Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms.

Experimental Design:
A genome-wide RNAi screen was used to search for candidate radioresistance genes. After RFC4 knockdown or overexpression, colorectal cancer cells exposed to X-rays both in vitro and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated in vitro. Finally, the relationships between RFC4 expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT.

Results:
RFC4, NCAPH, SYNE3, LDLRAD2, NHP2, and FICD were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-ray–induced DNA damage and apoptosis in vitro and in vivo. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/Ku80 but did not affect homologous recombination–mediated repair. Higher RFC4 expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance.

Conclusions:
RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.
Precision Targeting with EZH2 and HDAC Inhibitors in Epigenetically Dysregulated Lymphomas
Authors: Lue Jennifer K. , Prabhu Sathyen A. , Liu Yuxuan , Gonzalez Yulissa , Verma Akanksha , Mundi Prabhjot S. , Abshiru Nebiyu , Camarillo Jeannie M. , Mehta Swasti , Chen Emily I. , Qiao Changhong , Nandakumar Renu , Cremers Serge , Kelleher Neil L. , Elemento Olivier , Amengual Jennifer E. 
Published: April 2019

Abstract

Purpose:
Both gain-of-function enhancer of zeste homolog 2 (EZH2) mutations and inactivating histone acetyltransferases mutations, such as CREBBP and EP300, have been implicated in the pathogenesis of germinal center (GC)–derived lymphomas. We hypothesized that direct inhibition of EZH2 and histone deacetyltransferase (HDAC) would be synergistic in GC-derived lymphomas.

Experimental Design:
Lymphoma cell lines (n = 21) were exposed to GSK126, an EZH2 inhibitor, and romidepsin, a pan-HDAC inhibitor. Synergy was assessed by excess over bliss. Western blot, mass spectrometry, and coimmunoprecipitation were performed. A SU-DHL-10 xenograft model was utilized to validate in vitro findings. Pretreatment RNA-sequencing of cell lines was performed. MetaVIPER analysis was used to infer protein activity.

Results:
Exposure to GSK126 and romidepsin demonstrated potent synergy in lymphoma cell lines with EZH2 dysregulation. Combination of romidepsin with other EZH2 inhibitors also demonstrated synergy suggesting a class effect of EZH2 inhibition with romidepsin. Dual inhibition of EZH2 and HDAC led to modulation of acetylation and methylation of H3K27. The synergistic effects of the combination were due to disruption of the PRC2 complex secondary to acetylation of RbAP 46/48. A common basal gene signature was shared among synergistic lymphoma cell lines and was characterized by upregulation in chromatin remodeling genes and transcriptional regulators. This finding was supported by metaVIPER analysis which also revealed that HDAC 1/2 and DNA methyltransferase were associated with EZH2 activation.

Conclusions:
Inhibition of EZH2 and HDAC is synergistic and leads to the dissociation of PRC2 complex. Our findings support the clinical translation of the combination of EZH2 and HDAC inhibition in EZH2 dysregulated lymphomas.
Left Ventricular Twist Mechanics to Identify Left Ventricular Noncompaction in Childhood
Authors: Sabatino Jolanda , Di Salvo Giovanni , Krupickova Sylvia , Fraisse Alain , Prota Costantina , Bucciarelli Valentina , Josen Manjit , Paredes Josefa , Sirico Domenico , Voges Inga , Indolfi Ciro , Prasad Sanjay , Daubeney Piers 
Published: April 2019

Background:
Left ventricular noncompaction cardiomyopathy (LVNC) is associated with poor clinical outcome in childhood. Standard diagnostic criteria are still controversial, especially in young patients. Recent studies in adults demonstrated that left ventricular (LV) twist is abnormal in LVNC, but it has not been investigated in pediatric patients to date. Our aim was to assess LV cardiac mechanics, LV twist, and the prevalence of rigid body rotation, using 2-dimensional speckle tracking echocardiography, in young patients with LVNC and LV hypertrabeculation.

Methods:
Forty-seven children (age range: 0–18 years) were assessed for suspected LVNC. All patients underwent 2-dimensional speckle tracking echocardiography and cardiovascular magnetic resonance imaging at 1.5 Tesla (T). Twenty-three patients fulfilled the cardiovascular magnetic resonance imaging diagnostic criteria for LVNC (LVNC group), while the remaining 24 did not and were included in the LV hypertrabeculation group. Forty-seven age- and sex-matched healthy volunteers were used as controls.

Results:

The average LV twist was significantly reduced in LVNC compared with control and LV hypertrabeculation. Rigid body rotation was recognized in 13 (56%) children with LVNC and in 1 (4%) child with LV hypertrabeculation and a strong family history for LVNC. Multivariable analysis demonstrated that LV twist is an independent predictor of LVNC (
P
=0.006; coefficient=0.462). The receiver operating characteristics curve showed that LV twist had optimal predictive value to discriminate patients with LVNC (cutoff value <5.8°; sensitivity, 82%; specificity, 92%; area under the curve=0.914).

Conclusions:
LV twist has good predictive value in diagnosing LVNC in young patients. Our findings strongly support the routine use of 2-dimensional speckle tracking echocardiography in the evaluation of young patients with suspected LVNC.
A Numerical Study of “Hijikawa-Arashi”: A Thermally Driven Gap Wind Visualized by Nocturnal Fog
Authors: Ito Junshi , Nagoshi Toshiyuki , Niino Hiroshi 
Published: April 2019

AbstractA renowned local wind in Japan, “Hijikawa-Arashi,” is a thermally driven nocturnal gap wind accompanied by fog. The wind is visually identified by the fog along the valley of the Hijikawa River between the Ozu basin and the Seto Inland Sea during the early morning in autumn and winter. A fine-resolution numerical model is employed to reproduce the main observed features of Hijikawa-Arashi. A vertical resolution of 10 m or less at the lowest level is required to express the nocturnal radiative cooling of the land that is required for fog formation in the basin, and fine horizontal resolution is necessary to express a realistic valley through which the fog is advected to the sea. Multiple hydraulic jumps accompanied by supercritical flow occur because of the complex topography. Both moisture transport by the sea breeze during the daytime and evaporation from the land surface are important for accumulating moisture to produce the fog.
A Global Analysis of Land Surface Temperature Diurnal Cycle Using MODIS Observations
Authors: Sharifnezhadazizi Zahra , Norouzi Hamid , Prakash Satya , Beale Christopher , Khanbilvardi Reza 
Published: April 2019

AbstractDiurnal variations of land surface temperature (LST) play a vital role in a wide range of applications such as climate change assessment, land–atmosphere interactions, and heat-related health issues in urban regions. This study uses 15 years (2003–17) of daily observations of LST Collection 6 from the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on board the Aqua and the Terra satellites. A spline interpolation method is used to estimate half-hourly global LST from the MODIS measurements. A preliminary assessment of interpolated LST with hourly ground-based observations over selected stations of North America shows bias and an error of less than 1 K. Results suggest that the present interpolation method is capable of capturing the diurnal variations of LST reasonably well for different land-cover types. The diurnal cycle of LST and time of occurrence of maximum temperature are computed from the spatially and temporally consistent interpolated diurnal LST data at a global scale. Regions with higher variability in the timing of maximum LST hours and diurnal amplitude are identified in this study. The global desert regions show generally small variability of the monthly mean diurnal LST range, whereas larger areas of the global land exhibit rather higher variability in the diurnal LST range during the study period. Moreover, the changes in diurnal temperature range for the study period are examined for distinct land-cover types. Analysis of the 15-yr time series of the diurnal LST record shows an overall decrease of 0.5 K in amplitude over the Northern Hemisphere. However, the diurnal LST range shows variant changes in the Southern Hemisphere.
Effective Self-Determination Practices for Students with Disabilities: Implications for Students with Visual Impairments
Authors: Cmar Jennifer L. 
Published: April 2019

Introduction: Given the lack of self-determination research and curricula focusing on children and youths with visual impairments (i.e., those who are blind or have low vision), the purpose of this article was to review the literature on effective self-determination practices for students with other disabilities for applicability to students with visual impairments. Method: A narrative review was conducted that focused on six self-determination practices for students with disabilities. Studies of the effectiveness of these practices that were published in the year 2000 or later were included in the review. Results: A total of 14 articles were identified that focused on the following interventions: Self-Determined Learning Model of Instruction, Whose Future Is It Anyway?, Check and Connect, Self-Advocacy Strategy, Self-Directed Individualized Education Program, and Computer-Assisted Instruction. The levels of evidence supporting each intervention varied from potential to moderate, with none falling into the strong category. Discussion: Although several studies included at least one student with visual impairment, their results were not disaggregated by disability category. As a result, the existing literature does not allow for any specific conclusions to be made about the effects of these interventions on students with visual impairments. Additional research that evaluates self-determination interventions among this population is warranted. Implications for practitioners: By providing descriptions of six self-determination interventions and research evidence (including contextual information) supporting each one, this study serves as a starting point for practitioners to identify curricula that may be used to promote self-determination among their students. For students with visual impairments to fully benefit from these interventions, preteaching and accommodations by teachers of students with visual impairments or orientation and mobility specialists is necessary.
Foreign Body Aspiration in Infants and Older Children: A Comparative Study
Authors: Na’ara Shorook , Vainer Igor , Amit Moran , Gordin Arie 
Published: April 2019

Background: Foreign body aspiration (FBA) is a major cause of morbidity and mortality in children. It is a preventable event that predominates in preschool age. The signs and symptoms mimic respiratory diseases common in the same age-group. We compared FBA in infants to FBA in older children. Methods: Retrospective analysis of all the cases of suspected FBA of children under the age of 18 years hospitalized at one medical center during 2002 to 2016. We analyzed the data according to age: up to 1 year (infants) and 1 to 18 years. Results: One hundred seventy-five children with suspected FBA were admitted; of whom, 27 (15%) were infants and 148 (85%) were older children (age 1-18 years). For the 2 age groups, adults witnessed 85% and 73%, respectively, of the incidents ( P = .4). In the neonate group, 48% presented with normal X-ray findings compared to only 20% in the older group; 15% of the older group had a positive chest X-ray for a foreign body, while none had such in the infants’ group ( P = .01). For the 2 age groups, the majority of the FBs found were from organic origin. About half of the patients were diagnosed and managed within 24 hours of the aspiration event. In 10%, repeated bronchoscopy was performed due to a retained FB remnant. In a multivariate analysis, signs and symptoms ( P < .05), location of the FB ( P < .001), and witnessed aspiration ( P < .001) were independent prognostic factors for the length of hospitalization. Conclusion: Foreign body aspiration is not uncommon in young infants; the management is challenging due to small airways, the need to use smaller bronchoscopes, and the lack of working channel forces in pediatric bronchoscopes.
Minimally invasive versus conventional extracorporeal circulation circuits in patients undergoing coronary artery bypass surgery: a propensity-matched analysis
Authors: Saha Shekhar , Varghese Sam , Herr Mike , Leistner Marcus , Ulrich Christian , Niehaus Heidi , Ahmad Ammar Al , Baraki Hassina , Kutschka Ingo 
Published: April 2019

Objectives: Minimally invasive extracorporeal circulation circuits provide several advantages compared to conventional extracorporeal circulation circuits. We compared the results of a minimally invasive extracorporeal circulation system with those of conventional extracorporeal circulation system, in patients undergoing isolated coronary artery bypass grafting. Methods: We identified 753 consecutive patients who underwent coronary artery bypass grafting at our centre between October 2014 and September 2016. These patients were divided into two groups: a minimally invasive extracorporeal circulation group (M, n = 229) and a conventional extracorporeal circulation group (C, n = 524). Baseline parameters, details of cardiac surgery as well as postoperative complications and outcomes were compared by means of a propensity-matched analysis of 180 matched pairs. Results: The median EuroSCORE II was 1.3%. Transfusion requirement of packed red blood cells (p = 0.002) was lower in Group M compared to conventional extracorporeal circulation systems. There were no differences in hospital mortality or in rates of adverse events between the matched groups. Total in-hospital mortality of the cohort was 1.7%. Conclusion: The use of minimally invasive extracorporeal circulation is associated with a significantly lower use of blood products after isolated coronary revascularisation. There were no differences concerning duration of surgery, complication rates and mortality between the groups. Therefore, the application of minimally invasive extracorporeal circulation systems should be considered as preferred technique in isolated coronary artery bypass grafting procedures.
Standard early rehabilitation and lower limb transcutaneous nerve or neuromuscular electrical stimulation in acute stroke patients: a randomized controlled pilot study
Authors: Yen Hsiao-Ching , Chen Wen-Shiang , Jeng Jiann-Shing , Luh Jer-Junn , Lee Ya-Yun , Pan Guan-Shuo 
Published: April 2019

Objective: We investigated adding lower limb transcutaneous nerve stimulation or neuromuscular electrical stimulation to standard early rehabilitation in acute stroke patients. Design: An assessor-blinded, randomized controlled pilot study. Setting: A medical stroke center. Subjects: First-stroke patients aged 20–80 years admitted to the stroke center within 24 hours post stroke. Interventions: A total of 42 participants were randomly assigned to groups: transcutaneous nerve stimulation + standard early rehabilitation, neuromuscular electrical stimulation + standard early rehabilitation, or standard early rehabilitation-only. Transcutaneous nerve or neuromuscular electrical stimulation was delivered to the affected tibialis anterior and quadriceps muscles for 30 minutes a day, five days per week for two weeks. Main measures: The Postural Assessment Scale for Stroke Patients, the Functional Independence Measure, and three mobility milestones, namely, sitting for >five minutes, standing for >one minute, and walking ⩾50 m, were evaluated, respectively, at baseline, at the two-week post-intervention, and at two-week follow-up. Results: Significant differences existed in the Postural Assessment Scale for Stroke Patients scores between the transcutaneous nerve stimulation and standard early rehabilitation-only groups measured at two-weeks post-intervention (mean (SD) = 31.38 (5.39) and 18.00 (8.65), respectively) and at the two-week follow-up (34.08 (2.69) and 26.14 (7.77), respectively). A higher proportion of participants could walk ⩾50 m independently in the transcutaneous nerve stimulation group than in the standard early rehabilitation-only group at the two-week post-intervention ( P = 0.013) and two-week follow-up ( P = 0.01) marks. Conclusion: Two weeks of transcutaneous nerve stimulation added to standard early rehabilitation improved postural stability and walking in acute stroke patients.
The Italian Spine Youth Quality of Life questionnaire measures health-related quality of life of adolescents with spinal deformities better than the reference standard, the Scoliosis Research Society 22 questionnaire
Authors: Caronni Antonio , Donzelli Sabrina , Zaina Fabio , Negrini Stefano 
Published: April 2019

Objective: To compare the validity of the Italian Spine Youth Quality of Life (ISYQOL) questionnaire with that of the Scoliosis Research Society 22 (SRS22) questionnaire, the criterion standard for health-related quality of life (HRQOL) measurement in adolescents with spinal deformities. Design: Cross-sectional study. Setting: Outpatient clinic. Subjects: Consecutive adolescents (10–18 years; 541 wearing brace) affected by idiopathic scoliosis (642 females, 100 males) or hyperkyphosis (87 females, 109 males). Interventions: NA. Main measures: The Spearman’s correlation coefficient (rho) between ISYQOL and SRS22 was used to assess ISYQOL concurrent validity. Sex, age, severity, bracing, trunk appearance and deformity type were assessed for known-groups validity. Cohen’s d quantified between-groups differences. Multiple linear regression exploring the effect of sex, age, body mass index (BMI), severity, bone age, trunk appearance, physiotherapy, bracing and sport on HRQOL of scoliosis patients was used to assess concurrent validity further. Results: Satisfactory correlations were found between ISYQOL and SRS22 (scoliosis, rho = 0.71; kyphosis, rho = 0.56). Known-groups validity analysis showed that ISYQOL detects all the between-groups differences detected by SRS22 and a males-females difference undetected by SRS22. ISYQOL Cohen’s d was larger than SRS22 Cohen’s d in three between-groups comparisons and similar in the others. Brace, sport and scoliosis severity were independently related to ISYQOL (linear regression: R2 = 0.23; p < 0.001). Brace, sport and physiotherapy were related to SRS22 ( R2 = 0.17). Conclusions: ISYQOL showed high validity when used to measure HRQOL in adolescents with spinal deformities. Moreover, ISYQOL performs better than SRS22, having better known-groups validity and (contrary to SRS22) detecting the impact of disease severity on HRQOL.
Barriers and Facilitators to Fruit and Vegetable Consumption Among Rural Indian Women of Reproductive Age
Authors: Kehoe Sarah H. , Dhurde Varsha , Bhaise Shilpa , Kale Rashmi , Kumaran Kalyanaraman , Gelli Aulo , Rengalakshmi R. , Lawrence Wendy , Bloom Ilse , Sahariah Sirazul A. , Potdar Ramesh D. , Fall Caroline H. D. 
Published: April 2019

Background: Micronutrient deficiencies have been a serious public health problem among women of reproductive age in low- and middle-income countries including India, adversely affecting maternal and child health and human capital outcomes. Fruit and vegetables are important sources of micronutrients, and consumption of these foods is less than recommendations. Objective: The objective of this study was to identify perceived barriers and facilitators to fruit and vegetable consumption among women of reproductive age living in rural communities in the State of Maharashtra, India. Methods: Women aged 18 to 40 years were recruited from 8 villages surrounding the city of Wardha, Maharashtra, India. We used qualitative methods and held 9 focus group discussions and 12 one-to-one interviews. The data collection was stopped when no new information emerged. We used inductive thematic coding to analyze the data. Results: Women knew that fruit and vegetables were beneficial to health and expressed that they wanted to increase the intake of these foods for themselves and their children. Seven main themes were identified as being barriers or facilitators to fruit and vegetable consumption: (1) personal factors, (2) household dynamics, (3) social and cultural norms, (4) workload, (5) time pressures, (6) environmental factors, and (7) cost. Conclusions: Rural Indian women consumed fruit and vegetables infrequently and said they would like to consume more. Several potentially modifiable factors affecting the intake of fruit and vegetables were identified. Value chain analyses of fruit and vegetables in these communities will be important to identify opportunities to intervene and increase consumption.
Six-Month Prevalence of Mental Disorders and Service Contacts among Children and Youth in Ontario: Evidence from the 2014 Ontario Child Health Study
Authors: Georgiades Katholiki , Duncan Laura , Wang Li , Comeau Jinette , Boyle Michael H. ,   2014 Ontario Child Health Study Team
Published: April 2019

Objectives: To present the 6-month prevalence and sociodemographic correlates of mental disorders and mental health–related service contacts in a sample of children (4 to 11 years) and youth (12 to 17 years) in Ontario. Methods: The 2014 Ontario Child Health Study is a provincially representative survey of 6537 families with children aged 4 to 17 years in Ontario. DSM-IV-TR mental disorders were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and included mood (major depressive episode), anxiety (generalized anxiety, separation anxiety, social phobia, specific phobia), and behaviour disorders (attention-deficit/hyperactivity disorder, oppositional-defiant disorder, conduct disorder).The MINI-KID was administered independently to the primary caregiver and youth aged 12 to 17 years in the family’s home. Results: Past 6-month prevalence of any mental disorder ranged from 18.2% to 21.8% depending on age and informant. Behaviour disorders were the most common among children, and anxiety disorders were the most common among youth. Among children and youth with a parent-identified mental disorder, 25.6% of children and 33.7% of youth had contact with a mental health provider. However, 60% had contact with one or more of the providers or service settings assessed, most often through schools. Conclusions: Between 18% and 22% of children and youth in Ontario met criteria for a mental disorder but less than one-third had contact with a mental health provider. These findings provide support for strengthening prevention and early intervention efforts and enhancing service capacity to meet the mental health needs of children and youth in Ontario.