bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Computational Modeling Approach for Deriving Biomarkers to Predict Cancer Risk in Premalignant Disease
Authors: Dhawan Andrew , Graham Trevor A. , Fletcher Alexander G. 
Published: February 2016

Abstract
The lack of effective biomarkers for predicting cancer risk in premalignant disease is a major clinical problem. There is a near-limitless list of candidate biomarkers, and it remains unclear how best to sample the tissue in space and time. Practical constraints mean that only a few of these candidate biomarker strategies can be evaluated empirically, and there is no framework to determine which of the plethora of possibilities is the most promising. Here, we have sought to solve this problem by developing a theoretical platform for in silico biomarker development. We construct a simple computational model of carcinogenesis in premalignant disease and use the model to evaluate an extensive list of tissue sampling strategies and different molecular measures of these samples. Our model predicts that (i) taking more biopsies improves prognostication, but with diminishing returns for each additional biopsy; (ii) longitudinally collected biopsies provide slightly more prognostic information than a single biopsy collected at the latest possible time point; (iii) measurements of clonal diversity are more prognostic than measurements of the presence or absence of a particular abnormality and are particularly robust to confounding by tissue sampling; and (iv) the spatial pattern of clonal expansions is a particularly prognostic measure. This study demonstrates how the use of a mechanistic framework provided by computational modeling can diminish empirical constraints on biomarker development. Cancer Prev Res; 9(4); 283–95. ©2016 AACR.
Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines
Authors: Jin Ke , Su Kun-kai , Li Tong , Zhu Xia-qing , Wang Qi , Ge Ren-shan , Pan Zong-fu , Wu Bo-wen , Ge Li-jun , Zhang Yi-han , Wang Yi-fan , Shen Guo-fang , Zhu Dan-yan , Xiang Chun-sheng , Li Lan-juan , Lou Yi-jia 
Published: February 2016

Abstract
Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR-23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-κB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis. Cancer Prev Res; 9(4); 324–34. ©2016 AACR.
Characterizing the Molecular Pathology of Arrhythmogenic Cardiomyopathy in Patient Buccal Mucosa Cells
Authors: Asimaki Angeliki , Protonotarios Alexandros , James Cynthia A. , Chelko Stephen P. , Tichnell Crystal , Murray Brittney , Tsatsopoulou Adalena , Anastasakis Aris , te Riele Anneline , Kléber André G. , Judge Daniel P. , Calkins Hugh , Saffitz Jeffrey E. 
Published: February 2016

Background—
Analysis of myocardium has revealed mechanistic insights into arrhythmogenic cardiomyopathy but cardiac samples are difficult to obtain from probands and especially from family members. To identify a potential surrogate tissue, we characterized buccal mucosa cells.

Methods and Results—

Buccal cells from patients, mutation carriers, and controls were immunostained and analyzed in a blinded fashion. In additional studies, buccal cells were grown in vitro and incubated with SB216763. Immunoreactive signals for the desmosomal protein plakoglobin and the major cardiac gap junction protein Cx43 were markedly diminished in buccal mucosa cells from arrhythmogenic cardiomyopathy patients with known desmosomal mutations when compared with controls. Plakoglobin and Cx43 signals were also reduced in most family members who carried disease alleles but showed no evidence of heart disease. Signal for the desmosomal protein plakophilin-1 was reduced in buccal mucosa cells in patients with
PKP2
mutations but not in those with mutations in other desmosomal genes. Signal for the desmosomal protein desmoplakin was reduced in buccal mucosa cells from patients with mutations in
DSP
,
DSG2
, or
DSC2
but not in
PKP2
or
JUP
. Abnormal protein distributions were reversed in cultured cells incubated with SB216763, a small molecule that rescues the disease phenotype in cardiac myocytes.

Conclusions—
Buccal mucosa cells from arrhythmogenic cardiomyopathy patients exhibit changes in the distribution of cell junction proteins similar to those seen in the heart. These cells may prove useful in future studies of disease mechanisms and drug screens for effective therapies in arrhythmogenic cardiomyopathy.
Spectrum of Wave Forcing Associated with the Annual Cycle of Upwelling at the Tropical Tropopause
Authors: Kim Joowan , Randel William J. , Birner Thomas , Abalos Marta 
Published: February 2016

Abstract
The zonal wavenumber spectrum of atmospheric wave forcing in the lower stratosphere is examined to understand the annual cycle of upwelling at the tropical tropopause. Tropopause upwelling is derived based on the wave forcing computed from ERA-Interim using the momentum and mass conservation equations in the transformed Eulerian-mean framework. The calculated upwelling agrees well with other upwelling estimates and successfully captures the annual cycle, with a maximum during Northern Hemisphere (NH) winter. The spectrum of wave forcing reveals that the zonal wavenumber-3 component drives a large portion of the annual cycle in upwelling. The wave activity flux (Eliassen–Palm flux) shows that the associated waves originate from the NH extratropics and the Southern Hemisphere tropics during December–February, with both regions contributing significant wavenumber-3 fluxes. These wave fluxes are nearly absent during June–August. Wavenumbers 1 and 2 and synoptic-scale waves have a notable contribution to tropopause upwelling but have little influence on the annual cycle, except the wavenumber-4 component. The quasigeostrophic refractive index suggests that the NH extratropical wavenumber-3 component can enhance tropopause upwelling because these planetary-scale waves are largely trapped in the vertical, while being refracted toward the subtropical upper troposphere and lower stratosphere. Regression analysis based on interannual variability suggests that the wavenumber-3 waves are related to tropical convection and wave breaking along the subtropical jet in the NH extratropics.
State-Society Dynamics in Contemporary Brazilian Land Reform
Authors: Wolford Wendy 
Published: February 2016

Over the past 15 years, land reform has returned from the “dustbin of history” to serve again as a viable policy option. Much has been written about its resurgence, with the research tending to focus narrowly on the role of prices, policies, and politics in shaping the design and outcome of distribution. While these are necessary elements to understand, their reification neglects the critical element of process. Land reform programs are implemented by an array of government actors and negotiated on the ground by beneficiaries, social movement activists, large farmers, and the general public. A messy assemblage of actors and interests shapes both the design and the outcome of distribution. Qualitative analysis of the federal agency in charge of land reform in Brazil, the Instituto Nacional de Colonização e Reforma Agrária (National Institute of Colonization and Agrarian Reform—INCRA), reveals that, in the context of increased citizen participation and reduced funding, the agency must work together with social movement activists to perform its task. The analysis suggests that the study of state-society relations today requires a new vocabulary that highlights substance and process rather than form. Nos últimos 15 anos, a reforma agrária foi resgatada do arquivo histórico para servir como opção políticamente viável. Muito se tem escrito sobre essa restauração. Pesquisas têm concentrado atenção no papel de preços, legislação e política no desenho e resultado da distribuição. Ainda que seja necessário entender esses elementos, sua ratificação ignora os elementos críticos do processo. Programas de reforma agrária são implementados por uma variedade de atores governamentais e negociados por beneficiários, ativistas de movimentos sociais, grandes agricultores e pelo público em geral. Um mosaico desengonçado de atores e interesses dão forma tanto ao desenho quanto ao resultado da distribuição. Análise qualitativa da agência federal responsável pela reforma agrária no Brasil, o Instituto Nacional de Colonização e Reforma Agrária (INCRA), revela que, no contexto de maior participação de cidadãos e de recursos reduzidos, é importante que a agência atue coordenadamente com ativistas de movimentos sociais para desempenhar seu papel. A análise sugere que o estudo das relações entre sociedade e Estado hoje exige um novo vocabulário que acentue mais a importância de substância e processo do que da forma.
Educational Needs and Technological Preferences of Fathers of Youth With Type 1 Diabetes
Authors: Albanese-O’Neill Anastasia , Schatz Desmond A. , Bernhardt Jay M. , Elder Jennifer H. 
Published: February 2016

Purpose The purpose of this study was to identify the educational needs and technological preferences of fathers of youth aged 6 to 17 years with type 1 diabetes (T1DM). Methods Participants completed 2 surveys and 1 in-person semistructured interview. Survey data were collected via Qualtrics; interviews were recorded and transcribed. The quantitative data were analyzed with SPSS 22. Results Thirty fathers/stepfathers of youth 6 to 17 years old with T1DM participated in the study. Participants reported high levels of unmet diabetes-related educational needs, including needs in fundamental areas of diabetes management such as treatment of hyperglycemia, hypoglycemia, and calculating and adjusting insulin doses. A majority of participants identified educational needs in more nuanced aspects of diabetes management, indicating a need for more information about insulin pumps and continuous glucose monitors, managing diabetes at school, and finding help for diabetes challenges. All participants used smartphone technology, and most expressed interest in receiving diabetes education via mobile technology. Conclusions The findings contribute to our understanding of the educational needs of fathers of children with T1DM and provide preliminary support for the acceptability of delivering diabetes education via mobile technology. The incorporation of patient and caregiver perspectives into the development of mHealth diabetes education applications may increase engagement and improve health outcomes.
Testing for Response Shift Bias in Evaluations of School Antibullying Programs
Authors: Shaw Thérèse , Cross Donna , Zubrick Stephen R. 
Published: February 2016

Background: Involvement in bullying at school is detrimental to students’ mental and physical health; however, school antibullying programs have not been found to be uniformly successful. Self-reported frequency of involvement in bullying victimization and perpetration, often used as outcome measures in intervention impact evaluation studies, may be subject to response shift, particularly in intervention conditions. Such differential shifts could lead to biased estimates of intervention effects. Objectives: This study investigated the presence of reconceptualization, reprioritization, and recalibration response shift, resulting from intervention implementation. Method: The study subjects were Grade 8 students ( n = 3,382, 53% female) in the 35 schools participating in the Cyber Friendly Schools Project, a longitudinal group-randomized intervention trial. Response shift was assessed by comparing traditional and retrospective pretest measures of bullying involvement, as well as testing for measurement invariance over time in the Forms of Bullying Scale (FBS) using confirmatory factor analyses. Results: No evidence of response shift was found, indicating students’ understandings of bullying behavior remained stable over time. These findings also demonstrate the applicability of the FBS in longitudinal studies involving adolescents. Conclusion: While response shift was not present in our study, researchers conducting program evaluations in other contexts are advised to consider testing for this potential source of bias in their studies.
A new pretest probability score for diagnosis of lower limb deep vein thrombosis in unselected population of outpatients and inpatients
Authors: Sermsathanasawadi Nuttawut , Chaivanit Trakarn , Suparatchatpun Pinyo , Chinsakchai Khamin , Wongwanit Chumpol , Ruangsetakit Chanean , Mutirangura Pramook 
Published: February 2016

Objective To develop a new pretest probability score for deep vein thrombosis (DVT) in unselected population of outpatients and inpatients. Methods The new score was developed using independent factors from 500 patients clinically suspected of leg DVT. The new score was validated in a second group of 315 patients. Results The score consists of four components: unilateral leg pain, confinement to bed, calf enlargement >3 cm compared with the other side, and previous venous thromboembolism. A score ≥2 indicated a high probability while a score <2 indicated low probability. The sensitivity and specificity of the new score were 71.60% and 79.49%, respectively. The area under the receiver operating characteristic curve for the new score was 0.79. The combination of a new score <2 and D-dimer level <500 µg/L had a negative predictive value of 96.43%. Conclusions Our new score was valid in an unselected population of outpatients and inpatients.
Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later
Authors: Villain Marie , Sibon Igor , Renou Pauline , Poli Mathilde , Swendsen Joel 
Published: February 2016

Objective: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. Design: Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. Setting: A university hospital acute stroke unit. Subjects: Thirty-four mild ischemic stroke patients. Interventions: None. Main measures: One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. Results: The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. Conclusions: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.
Stability of the Glenohumeral Joint With Combined Humeral Head and Glenoid Defects
Authors: Gottschalk Lionel J. , Walia Piyush , Patel Ronak M. , Kuklis Matthew , Jones Morgan H. , Fening Stephen D. , Miniaci Anthony 
Published: February 2016

Background: Shoulders with recurrent anterior instability often have combined bony defects of the humeral head and glenoid. Previous studies have looked at only isolated humeral head or glenoid defects. Purpose/Hypothesis: The aim of this study was to define the relationship of combined humeral head and glenoid defects on anterior shoulder instability. Combined bony defects will lead to increased instability compared with an isolated defect, and the “critical” size of humeral head and glenoid defects that need to be addressed to restore stability will be smaller when combined rather than isolated. Study Design: Controlled laboratory study. Methods: Eighteen shoulder specimens were tested at 60° of glenohumeral abduction and 80° of glenohumeral external rotation. Humeral head defect sizes included 6%, 19%, 31%, and 44% of the humeral head diameter. Glenoid defect sizes included 10%, 20%, and 30% of the glenoid width. Outcome measures included percentage of intact stability ratio (%ISR; the stability ratio for a given trial divided by the stability ratio in the intact state for that specimen) and percentage of intact translation (%IT; the distance to dislocation for a given trial divided by the distance to dislocation in the intact state for that specimen). Results: The decrease in %ISR reached statistical significance for humeral head defects of 44%, for glenoid defects of 30%, and for a combined 19% humeral head defect with a 20% glenoid defect (65% mean %ISR). The decrease in %IT reached statistical significance for humeral head defects ≥31%, for glenoid defects ≥20%, and for a combined 19% humeral head defect with a 10% glenoid defect (69% mean %IT). Conclusion: In shoulders with combined humeral head and glenoid defects, bony reconstruction may be indicated for humeral head defects as small as 19% of the humeral head diameter and glenoid defects as small as 10% to 20% of the glenoid width, especially if the glenoid defect produces a significant loss of glenoid concavity depth. Clinical Relevance: In shoulders with combined humeral head and glenoid defects, bony reconstruction may be indicated for defect sizes smaller than would be indicated for either defect found in isolation.
Recovery of Muscle Strength After Intact Arthroscopic Rotator Cuff Repair According to Preoperative Rotator Cuff Tear Size
Authors: Shin Sang-Jin , Chung Jaeyoon , Lee Juyeob , Ko Young-Won 
Published: February 2016

Background: The recovery of muscle strength after arthroscopic rotator cuff repair based on the preoperative tear size has not yet been well described. Purpose/Hypothesis: The purpose of this study was to evaluate the recovery period of muscle strength by a serial assessment of isometric strength after arthroscopic rotator cuff repair based on the preoperative tear size. The hypothesis was that muscle strength in patients with small and medium tears would recover faster than that in those with large-to-massive tears. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 164 patients who underwent arthroscopic rotator cuff repair were included. Isometric strength in forward flexion (FF), internal rotation (IR), and external rotation (ER) was evaluated preoperatively and at 6, 12, 18, and 24 months after surgery. Preoperative magnetic resonance imaging scans were assessed to evaluate the quality of the rotator cuff muscle, including fatty infiltration, occupation ratio, and tangent sign. Patient satisfaction as well as visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES), and Constant scores were assessed at every follow-up. Results: Muscle strength demonstrated the slowest recovery in pain relief and the restoration of shoulder function. To reach the strength of the uninjured contralateral shoulder in all 3 planes of motion, recovery took 6 months in patients with small tears and 18 months in patients with medium tears. Patients with large-to-massive tears showed continuous improvement in strength up to 18 months; however, they did not reach the strength of the contralateral shoulder at final follow-up. At final follow-up, mean strength in FF, IR, and ER was 113.0%, 118.0%, and 112.6% of the contralateral shoulder in patients with small tears, respectively; 105.0%, 112.1%, and 102.6% in patients with medium tears, respectively; and 87.6%, 89.5%, and 85.2% in patients with large-to-massive tears, respectively. Muscle strength in any direction did not significantly correlate with postoperative patient satisfaction ( P = .374, .515, and .692 for FF, IR, and ER, respectively), whereas it highly correlated with preoperative quality of the muscle. Conclusion: The recovery of muscle strength after arthroscopic repair was poorly correlated with patient satisfaction. This study recommends that regardless of pain relief and improved shoulder function, patients with larger than medium tears should be encouraged to continue with rehabilitation for the maximal restoration of muscle strength beyond 1 year postoperatively.
Outcomes of Combined Bone Marrow Stimulation and Patch Augmentation for Massive Rotator Cuff Tears
Authors: Yoon Jong Pil , Chung Seok Won , Kim Jae Yoon , Lee Byung Joo , Kim Hyung-Sub , Kim Ju Eun , Cho Jung Hyun 
Published: February 2016

Background: The high failure rate after surgical repair of massive rotator cuff tears is a consistent problem. Purpose: To evaluate the clinical and radiological outcomes of arthroscopic rotator cuff repair with bone marrow stimulation and patch augmentation in patients with massive rotator cuff tears. Study Design: Cohort study; Level of evidence, 3. Methods: This study included 21 patients who underwent bone marrow stimulation and patch augmentation (group 1) and 54 patients who underwent conventional repair (group 2) for massive rotator cuff tears. Postoperative clinical outcomes were evaluated based on visual analog scale (VAS) for pain, simple shoulder test (SST), University of California, Los Angeles (UCLA), Constant, and American Shoulder and Elbow Surgeons (ASES) scores at baseline, 1 year postoperatively, and final follow-up. Anatomic outcomes were evaluated by using postoperative magnetic resonance imaging at 1 year after surgery. Results: No significant differences in demographic characteristics and baseline data were observed between groups 1 and 2. Clinical symptoms were significantly improved at the final follow-up in both groups ( P < .001). At the final follow-up, no significant differences were found in VAS pain ( P = .676), SST ( P = .598), UCLA ( P = .100), Constant ( P = .469), or ASES ( P = .880) scores. However, the retear rate was lower in group 1 (4/21, 19.0%) than in group 2 (25/54, 46.3%) ( P = .036), and the medial-row failure rate (type 2 retears) was much lower in group 1 (0/4, 0%) than in group 2 (18/25, 72.0%) ( P = .014). Conclusion: Concomitant bone marrow stimulation and patch augmentation significantly reduced retear and medial-row failure rates in the arthroscopic repair of massive rotator cuff tears.