bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA14: Functional genomics to identify cancer targets and resistance
Authors: Hahn William C. 
Published: March 2013

Abstract
Recent advances in genomics now make it possible to consider enumerating all of the genetic lesions in specific cancers. While these approaches will yield critical information regarding the identity, number, and types of alterations found in human tumors, a complementary approach to decipher the molecular basis of malignant transformation depends upon the application of genome scale tools to annotate the function of genes involved in cancer initiation and progression. Over the past several years, we have developed genome scale RNAi libraries and open reading frame expression libraries that permit a systematic evaluation of genes involved in cancer initiation and maintenance. Using these libraries, we have now performed screens in a panel of human cancer cell lines to systematically identify cancer vulnerabilities. By combining these functional approaches with information derived from mapping the structural abnormalities present in cancer genomes, we have identified several new oncogenes that contribute to cancer development. In pilot studies, we have identified several genes that act as synthetic lethal partners to known oncogenes or mediate resistance to targeted therapies. In recent work, we have expanded the scale of these experiments to genome scale in more than 100 cell lines, which has permitted greater expansion and deeper investigation into genes that program the malignant state. Together, these studies suggest that combining forward and reverse genetic approaches with information derived from the cancer genome characterization projects will yield a comprehensive list of cancer vulnerabilities and establish a general approach for the rational identification of oncogenic and codependent pathways in cancer.
Abstract IA2: Mechanisms of resistance to anti EGFR therapies in colorectal cancers
Authors: Bardelli Alberto 
Published: March 2013

Abstract
Personalized cancer medicine based on the genetic milieu of individual colorectal tumors has long been postulated but until recently this concept was not supported by clinical evidence. The advent of the EGFR-targeted monoclonal antibodies cetuximab and panitumumab has paved the way to the individualized treatment of metastatic colorectal cancer (mCRC). There is clear evidence that mCRCs respond differently to EGFR-targeted agents and that the tumor specific response has a genetic basis. From the initial observation that cetuximab or panitumumab as monotherapy are effective only in 10–20%, of mCRCs, knowledge has being gained on the molecular mechanisms underlying primary resistance to these agents. The role of oncogenic activation of EGFR downstream effectors such as KRAS, BRAF, PIK3CA and PTEN on response to therapy will be discussed. The rapid and effective translation of these findings into predictive biomarkers to couple EGFR-targeted antibodies to the patients that benefit from them will be presented as a paradigm of modern clinical oncology. Unresolved questions such as understanding the molecular basis of response as well the mechanisms of secondary resistance will be discussed as the future fundamental goals in this research field.
Abstract IA8: BRAF and MEK resistance in melanoma
Authors: Herlyn Meenhard , Villanueva Jessie 
Published: March 2013

Abstract
The melanoma field has had a long history of frustrating experiences in clinical trials. Most of these were in immunotherapy, although all approaches in biotherapy, chemotherapy and radiation therapy have been similarly unsuccessful for the past 30 years with unchanged five-year survival rates of 15% for advanced disease. The therapy arena is dramatically changing with a new generation of BRAF inhibitors. Particularly those with high specificity for the mutant kinase are effective in killing cells carrying the BRAFV600E mutation. Two BRAF inhibitors have increased progression-free survival and overall survival from the disease. Considering the poor success rate from previous trials, the currently accumulated data are dramatic and exciting. However, there are no cures and all treated patients recur due to the development of resistance. In treated melanoma cells with BRAFV600E there are no new mutations, except the appearances of splice variants and mutations in NRAS in some tumors. Instead, cells learn to signal around inhibited BRAF through CRAF or ARAF to activate MEK and ERK. At the same time compensatory signaling activates receptor tyrosine kinases such as IGFR1 and PDGFR, leading to activation of the PI3K pathway. Potentially, additional pathways can be activated likely requiring an individual assessment of the mechanisms of resistance. Inhibition of the newly activated pathways can prevent progression in experimental systems but has not yet been validated in patients. In contrast to inhibitors of BRAF, inhibitors for MEK appear to induce mutations in either MEK 1 or MEK 2. It is not yet clear whether the mutations occur at multiple or unique sites. Likely, similar mutational events as in MEK will occur when inhibitors of ERK are given to cells over prolonged time periods. In summary, the MAPK pathway has emerged as a major driver for melanoma cells. However, when the malignant cells are treated with inhibitors for BRAF/MEK/ERK they develop secondary resistance. Why do some cells survive the drug insult? This question is particularly pertinent for inhibitors of mutant BRAF because all cells invariably contain the mutations. The reasons for this intrinsic or primary resistance are not clear and will require a major investigational effort in future years. Experimental studies in immunodeficient mice have shown that single melanoma cells are sufficient to induce a tumor, thus, the goal has to be the elimination of all cells and not just the majority of cells. Strategies to achieve this goal will in part depend on the mechanisms of survival of a sub-population of malignant cells. It is most likely that non-genetic events are responsible for the survival and they will be discussed.
Prevalence, Awareness, Treatment, and Control of Hypertension Among Residents in Guangdong Province, China, 2004 to 2007
Authors: Xu Bayi , Xu Zhixia , Xu Xiaojun , Cai Qiumao , Xu Yanjun 
Published: March 2013

Background—
As a result of the large variation in geographic, demographic, and socioeconomic characteristics in different regions of China, the prevalence and treatment of hypertension in different regions differ widely. However, little is known about the recent trends of hypertension in Guangdong Province in southern China. We assessed the trends in prevalence, awareness, treatment, and control of hypertension in Guangdong Province between 2004 and 2007.

Methods and Results—

The Guangdong Provincial Chronic Disease Risk Factor Surveillance, modeled on the national Chronic Disease Risk Factor Surveillance, was conducted every 3 years beginning in 2004 with a representative sample of Guangdong Province residents ≥18 years of age. Data from the Guangdong Provincial Chronic Disease Risk Factor Surveillance I (2004; n=7633) and II (2007; n=6447) were used to describe the trends in the prevalence of hypertension among Guangdong Province adults. Hypertension outcomes were examined with interview and examination data. From 2004 to 2007, the age-standardized prevalence rate of hypertension in Guangdong Province residents increased from 12.2% to 15.4% (
P
<0.001), with the largest increases among rural women (from 9.3% to 19.1%;
P
<0.001). Among hypertensive people, there was no improvement in awareness and treatment between 2004 and 2007; the control rates decreased from 7.1% in 2004 to 4.5% in 2007 (
P
<0.01).

Conclusions—
One in 7 Guangdong Province adults is hypertensive, but only one quarter are aware of the condition. About 22% of hypertensive patients receive treatment, and few have their hypertension effectively controlled. Hypertension has become a major public health problem in southern China. Comprehensive public health measures need to be taken to decrease the incidence of hypertension and to prevent the progression of hypertension to cardiovascular disease.
Lost Childhoods in a New China: Child-Citizen-Workers at War, 1937–1945
Authors: Plum M. Colette 
Published: March 2013

This article examines the emerging discourse of child-citizen-workers in wartime China and demonstrates how this concept of children’s citizenship was put into practice in work training programs within wartime children’s homes. This article argues that the idea of child-citizen-workers grew from three pre-war antecedents that converged and were greatly accelerated by China’s war with Japan: the new idea of an autonomous sphere of childhood articulated during the early Republican period; a progressive education movement to introduce labor training and experiential learning as essential elements of modern education; and Nationalist state-building and activist efforts at family reform, which viewed traditional parents with distrust and increasingly intervened in family life.
The second half of the article focuses particularly on orphans, who were considered potentially unstable social elements due to their position outside the control of families, and whose lack of parental protection made them available for appropriation. This article demonstrates that the war opened up a space in which Guomindang state-builders, working with educators and childcare workers, attempted to restructure orphans lives within wartime child welfare institutions to realize a vision for China’s future: the ideal of child-citizen-workers habituated toward sacrifice for the nation.
Integration of a Road Surface Model into NWS Operations
Authors: Rutz Jonathan J. , Gibson Chris V. 
Published: March 2013

Today's winter weather headlines are based on the meteorological strength of an event with the assumption that stronger events produce larger public impacts. In reality, public impacts involve many factors, such as whether or not snow will accumulate on roads and affect traffic. Along with numerous environmental factors, decisions are further complicated by societal factors (e.g., timing of the commute).
The National Weather Service (NWS) Strategic Plan calls for increased emphasis on decision support services (DSS) to our partners, especially during high-impact events. However, determining when events will produce high-impact conditions often remains a challenge. While forecasters should be aware of the relevant societal factors, they also need objective tools capable of integrating over the wide range of environmental factors that intersect in producing high-impact weather. This is particularly true in the case of road surface conditions, where complex interactions between temperature, moisture, and the road surface play a key role in determining what hazards might develop during wintry weather.
Initial verification suggests that output from the Model of the Environment and Temperature of Roads (METRo) can provide useful information with regard to the timing and severity of hazardous road surface conditions, allowing NWS forecasters to more effectively highlight the impacts associated with impending meteorological events. This information enhances the DSS that the NWS is able to provide to government partners, local emergency management, and the public during high-impact winter weather events.
Analysis of WRF Model Wind Estimate Sensitivity to Physics Parameterization Choice and Terrain Representation in Andalusia (Southern Spain)
Authors: Santos-Alamillos F. J. , Pozo-Vázquez D. , Ruiz-Arias J. A. , Lara-Fanego V. , Tovar-Pescador J. 
Published: March 2013

AbstractThis paper reports on an evaluation of the relative roles of choice of parameterization scheme and terrain representation in the Weather Research and Forecasting (WRF) mesoscale model, in the context of a regional wind resource assessment. As a first step, 32 configurations using two different schemes for microphysics, cumulus, planetary boundary layer (PBL), or shortwave and longwave radiation were evaluated. In a second step, wind estimates that were obtained from various experiments with different spatial resolution (1, 3, and 9 km) were assessed. Estimates were tested against data from four stations, located in southern Spain, that provided hourly wind speed and direction data at 40 m above ground level. Results from the first analysis showed that wind speed standard deviation (STD) and bias values were mainly sensitive to the PBL parameterization selection, with STD differences up to 10% and bias differences between −15% and 10%. The second analysis showed a weak influence of spatial resolution on the STD values. On the other hand, the bias was found to be highly sensitive to model spatial resolution. The sign of the bias depended on terrain morphology and the spatial resolution, but absolute values tended to be much higher with coarser spatial resolution. Physical configuration was found to have little impact on wind direction distribution estimates. In addition, these estimates proved to be more sensitive to the ability of WRF to represent the terrain morphology around the station than to the model spatial resolution itself.
A recovery journey for people with personality disorder
Authors: Castillo Heather , Ramon Shulamit , Morant Nicola 
Published: March 2013

Background: The study investigates the process of recovery for people diagnosed with personality disorder, a client group that suffers significant social exclusion known to impact on demand for health and other public services. It aims to examine efforts that attempt to reverse this social exclusion as an aspect of the recovery process. Aim and Method: The following study aims to (1) explore what recovery means to people with personality disorder; (2) develop a conceptual model of recovery in personality disorder; and (3) evaluate the contribution of the setting (The Haven) to recovery practice. The study uses a Participatory Action Research (PAR) design. Data was collected from 66 participants by focus groups and individual interviews. Findings: A map based on thematic analysis of data collected during the study is proposed of the recovery journey for people with this diagnosis, shown as a pyramid that represents a hierarchy of progress, from building trust through stages of recovery to social inclusion. Conclusion: The findings offer contributions to knowledge in terms of the service design and propose a new model of recovery in personality disorder. This is defined as a journey of small steps highlighting recovery as a process rather than a goal, leading to the emergence of the new concept of transitional recovery.
The utility and prognostic value of dipyridamole technetium-99m sestamibi myocardial perfusion imaging SPECT in predicting perioperative cardiac events following non-cardiac surgery
Authors: Asli IN , Shahoseini R , Azizmohammadi Z , Javadi H , Assadi M 
Published: March 2013

Objective: A perioperative cardiac events is one of the most important medical concerns for both surgeons and patients. The purpose of the current study was to determine the prognostic value of myocardial perfusion imaging (MPI), using dipyridamole 99m Tc-MIBI, for the prediction of perioperative cardiac events. Materials and methods: This study included 253 patients who were candidates for non-cardiac elective surgery and underwent scanning with dipyridamole 99m Tc-MIBI. Based on normal or abnormal MPI, patients were divided into two groups and all preoperative cardiac events were recorded. Risk factors, including diabetes mellitus, dyslipidemia, hypertension, smoking and age ≥70 years, were compared between patients with normal and abnormal MPI and, also, in patients with or without cardiac events. Results: There were 197 patients with normal and 56 patients with abnormal MPI. In total, 14 patients had perioperative cardiac events, which included myocardial infarction (MI), hypotension, arrhythmia and death; of the 14 patients with perioperative cardiac events, 12 had abnormal and two had normal MPI. There were statistically meaningful differences between the two groups (p<0.001). Based on these findings, we determined that MPI had a sensitivity of 85.7%, a specificity of 81.6%, an accuracy of 81.8%, a positive predictive value of 21.4 % and a negative predictive value of 98.9%. Conclusion: The incidence of perioperative cardiac events is higher in patients with abnormal MPI. Dipyridamole 99m Tc-MIBI myocardial perfusion imaging can accurately detect the preoperative cardiac risk of patients undergoing major non-cardiac surgery. Based on these findings, the occurrence of perioperative cardiac events in patients with abnormal MPI should be considered, especially in the older age population (age ≥70).
Rigid Spinal Muscular Dystrophy and Rigid Spine Syndrome
Authors: Koul Roshan , Al-Yarubi Saif , Al-Kindy Hussein , Al-Futaisi Amna , Al-Thihli Khalid , Chacko Poovathoor Alexander , Sankhla Dilip 
Published: March 2013

Seven children (5 male, 2 female) were seen over the last 16 years with rigid spine syndrome. Six children had rigid spinal muscular dystrophy (selenoprotein N1–related myopathy [SEPN1RM]) and 1 had myopathy associated with rigid spine. The main presenting complaint in all was difficulty in bending the spine. The diagnosis was made on clinical features and imaging of the paraspinal muscles. Muscle histopathology revealed minimal myopathic changes to severe muscle degeneration. Genetic testing, which was only available for the last case, for selenoprotein was negative.
Demographic and health factors associated with enrollment in posttrial studies: The women’s health initiative hormone therapy trials
Authors: Espeland Mark A , Pettinger Mary , Falkner Karen L , Shumaker Sally A , Limacher Marian , Thomas Fridtjof , Weaver Kathryn E , Stefanick Marcia L , McQuellon Cynthia , Hunt Julie R , Johnson Karen C 
Published: March 2013

Background After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants’ decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied. Purpose We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women’s Health Initiative (WHI) Hormone Therapy clinical trials. Methods We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees. Results The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76). Limitations We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. Conclusions Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.
Update on Banned Substances 2013
Authors: Barnes Kenneth P. , Rainbow Catherine R. 
Published: March 2013

Context: Doping has been pervasive throughout the history of athletic competitions and has only recently been regulated by organizations such as the World Anti-Doping Agency (WADA), US Anti-Doping Agency (USADA), and the National Collegiate Athletic Association (NCAA). These regulatory bodies were created to preserve fair play and maintain the safety of the participants. Their updated 2013 lists of banned substances and practices include a variety of drugs and practices that could cause harm to an athlete or give one an unfair competitive advantage. Evidence Acquisition: Published websites for the WADA, USADA, and NCAA were investigated. These governing bodies update and publish their lists annually. Results: The WADA, USADA, and NCAA monitor anabolic steroids, hormones, growth factors, β-agonists, hormone and metabolic modulators, masking agents, street drugs, manipulation of blood and blood components, chemical and physical manipulation, gene doping, stimulants, narcotics, glucocorticosteroids, and β-blockers. Some substances may be used by athletes but require formal exemption. The WADA has also recently created a category of nonapproved substances that have yet to be identified to curb athletes from experimenting with new doping agents. Conclusion: The lists of banned substances and practices per the WADA, USADA, and NCAA are in place to ensure the integrity of sports and maintain safe competition. Health care providers who work with athletes under the jurisdiction of these organizations should review updated lists of banned substances when prescribing medications.
Patellar Tendinopathy
Authors: Beebe Justin A. , Cross Patrick S. 
Published: March 2013

Background: Calcific deposits (CaDs) may be related to chronic postoperative pain and may affect function after patellar tendon surgery. Study Design: Cross-sectional. Hypothesis: We hypothesized that patients with CaDs (+CaDs) would rate lower than those without (−CaDs) on measures of knee function and quality of life. Methods: Patients completed the Tegner Lysholm Knee Scoring Scale (Lysholm), Knee Injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee Subjective Knee Form (IKDC), and the Tegner Activity Level Scale. Sixteen postsurgical and 16 age-matched controls were tested. Patients +CaDs were 5.6 years older than those patients −CaDs and had 4.2 years of longer elapse since surgery. Bilateral patellar tendons were examined for CaDs with musculoskeletal ultrasound imaging. One-way analysis of variance was used to determine if differences existed among patients +CaDs and −CaDs and healthy controls. Hierarchical logistic regressions were used to determine which variables best predicted the presence of CaDs. Results: CaDs were found in 44% (7 of 16) of postsurgical patients, who scored lower than controls on all dimensions of the Lysholm, KOOS, and IKDC. Patients +CaD had lower KOOS scores than controls (symptoms, activities of daily living, and quality of life). Age and time since surgery were both moderately related to the presence of CaDs, and both correctly predicted 71% of patients +CaDs. Conclusion: Calcific deposits were found in the patellar tendon of 44% of postsurgical patients, who rated themselves lower on all subjective measures of knee function and quality of life following surgery. Age is an important factor for developing CaDs postsurgery. Clinical Relevance: Calcific deposits may be present in patellar tendons following surgery, but their direct role in functional or clinical limitations remains unknown.
Functional Performance Testing for Power and Return to Sports
Authors: Manske Robert , Reiman Michael 
Published: March 2013

Context: Functional performance testing of athletes can determine physical limitations that may affect sporting activities. Optimal functional performance testing simulates the athlete’s activity. Evidence Acquisition: A Medline search from 1960 to 2012 was implemented with the keywords functional testing, functional impairment testing, and functional performance testing in the English language. Each author also undertook independent searches of article references. Conclusion: Functional performance tests can bridge the gap between general physical tests and full, unrestricted athletic activity.