bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA4 Blockade Induces Frequent Tumor Infiltration by Activated Lymphocytes Regardless of Clinical Responses in Humans
Authors: Huang Rong Rong , Jalil Jason , Economou James S. , Chmielowski Bartosz , Koya Richard C. , Mok Stephen , Sazegar Hooman , Seja Elizabeth , Villanueva Arturo , Gomez-Navarro Jesus , Glaspy John A. , Cochran Alistair J. , Ribas Antoni 
Published: May 2011

Abstract
Background: CTLA4 blocking monoclonal antibodies provide durable clinical benefit in a subset of patients with advanced melanoma mediated by intratumoral lymphocytic infiltrates. A key question is defining whether the intratumoral infiltration (ITI) is a differentiating factor between patients with and without tumor responses.
Methods: Paired baseline and postdosing tumor biopsy specimens were prospectively collected from 19 patients with metastatic melanoma, including 3 patients with an objective tumor response, receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8+ cytotoxic T-lymphocyte (CTL) infiltration in tumors. Samples were analyzed for cell density by automated imaging capture and further characterized for functional lymphocyte properties by assessing the cell activation markers HLA-DR and CD45RO, the cell proliferation marker Ki67, and the regulatory T-cell marker FOXP3.
Results: There was a highly significant increase in ITI by CD8+ cells in biopsy samples taken after tremelimumab treatment. This included increases between 1-fold and 100-fold changes in 14 of 18 evaluable cases regardless of clinical tumor response or progression. There was no difference between the absolute number, location, or cell density of infiltrating cells between clinical responders and patients with nonresponding lesions that showed acquired intratumoral infiltrates. There were similar levels of expression of T-cell activation markers (CD45RO, HLA-DR) in both groups and no difference in markers for cell replication (Ki67) or the suppressor cell marker FOXP3.
Conclusion: CTLA4 blockade induces frequent increases in ITI by T cells despite which only a minority of patients have objective tumor responses. Clin Cancer Res; 17(12); 4101–9. ©2011 AACR.
Distinguishing Inflammation from Tumor and Peritumoral Edema by Myeloperoxidase Magnetic Resonance Imaging
Authors: Kleijn Anne , Chen John W. , Buhrman Jason S. , Wojtkiewicz Gregory R. , Iwamoto Yoshiko , Lamfers Martine L. , Stemmer-Rachamimov Anat O. , Rabkin Samuel D. , Weissleder Ralph , Martuza Robert L. , Fulci Giulia 
Published: May 2011

AbstractPurpose: Inflammation occurs routinely when managing gliomas and is not easily distinguishable from tumor regrowth by current MRI methods. The lack of noninvasive technologies that monitor inflammation prevents us to understand whether it is beneficial or detrimental for the patient, and current therapies do not take this host response in consideration. We aim to establish whether a gadolinium (Gd)-based agent targeting the inflammatory enzyme myeloperoxidase (MPO) can selectively detect intra- and peritumoral inflammation as well as glioma response to treatment by MRI.Methods: We carried out serial Gd-bis-5-HT-DTPA (MPO-Gd) MRI before and after treating rodent gliomas with different doses of oncolytic virus (OV) and analyzed animal survival. The imaging results were compared with histopathologic and molecular analyses of the tumors for macrophage/microglia infiltration, virus persistence, and MPO levels.Results: Elevated MPO activity was observed by MRI inside the tumor and in the peritumoral cerebrum at day 1 post–OV injection, which corresponded with activation/infiltration of myeloid cells inhibiting OV intratumoral persistence. MPO activity decreased, whereas tumor size increased, as the virus and the immune cells were cleared (days 1–7 post–OV injection). A 10-fold increase in viral dose temporally decreased tumor size, but augmented MPO activity, thus preventing extension of viral intratumoral persistence.Conclusions: MPO-Gd MRI can distinguish enhancement patterns that reflect treatment-induced spatiotemporal changes of intratumoral and intracerebral inflammation from those indicating tumor and peritumoral edema. This technology improves the posttreatment diagnosis of gliomas and will increase our understanding of the role of inflammation in cancer therapy. Clin Cancer Res; 17(13); 4484–93. ©2011 AACR.
NID2 and HOXA9 Promoter Hypermethylation as Biomarkers for Prevention and Early Detection in Oral Cavity Squamous Cell Carcinoma Tissues and Saliva
Authors: Guerrero-Preston R. , Soudry E. , Acero J. , Orera M. , Moreno-López L. , Macía-Colón G. , Jaffe A. , Berdasco M. , Ili-Gangas C. , Brebi-Mieville P. , Fu Y. , Engstrom C. , Irizarry R.A. , Esteller M. , Westra W. , Koch W. , Califano J. , Sidransky D. 
Published: May 2011

AbstractDifferentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles.To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles.A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma.Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC.This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. Cancer Prev Res; 4(7); 1061–72. ©2011 AACR.
Is the ACT two minutes after heparin injection reliable?
Authors: Bellaiche AL , Nielsen PF , Kirkegaard H. 
Published: May 2011

Background: Blood for activated clotting time (ACT) measurement to verify the effect of the initial dose of heparin before cannulation in heart surgery has traditionally been drawn 5 minutes (min) after injection of the heparin. However, there has been an increasing demand to reduce the waiting time. The aim of this study was to investigate if ACT measured 1, 2, 3 and 4 min after heparin injection is as reliable as ACT measured 5 min after heparin injection. Materials and methods: Fifty adult patients undergoing routine cardiac surgery with a heart-lung machine. Heparinization was obtained with unfractioned porcine heparin. The ACT was measured with 5 Hemochron® Jr. machines 1, 2, 3, 4 and 5 min after the heparin injection. Full heparinization was defined as an ACT >400 seconds. Results: At 1 and 2 min, 94% (n=47) of the ACTs were > 400. All ACTs >400 seconds after 2 min remained >400 seconds at 3, 4 and 5 min. Mean values declined from 533 to 498. ANOVA analysis showed statistically significantly higher values at 1, 2 and 3 min, compared to 5 min, but not at 4 min. However, the estimated differences were small: 3.7-36 seconds. There was no significant difference between variances for the five sample times. Standard deviation declined from 123 to 100. Values at 2 min correlated as well as those at 5 min with mean 1-5 min values. Conclusion: The range of the ACT values tends to diminish over time and, consequently, the reliability of the results increases. However, the difference is small and has little or no clinical relevance. Giving time for the circulation to distribute the heparin in the bloodstream, we recommend measuring the ACT two min after heparin administration.
Recognition of persistent left superior vena cava in non-congenital patients undergoing cardiac surgery
Authors: Lentini S. , Recupero A. 
Published: May 2011

Persistent left superior vena cava (PLSVC) represents the most frequent congenital malformation of the thoracic venous drainage system. In adults referred to surgery for an acquired cardiac disease, abnormal venous drainage may be missed if not carefully researched. Discovering a previously undiagnosed PLSVC during cardiopulmonary bypass (CPB) may present some inconvenience for both the perfusionist and the surgeon, especially during a minimally invasive approach. The authors believe PLSVC probably may represent an under-reported condition. A careful screening of patients undergoing cardiac surgery may prove helpful. In particular, a complete echocardiographic study may help to better diagnose this condition before surgery. Different signs may raise the suspicion of PLSVC and should be carefully researched during preoperative patient work-up.
First application of a new portable, miniaturized system for extracorporeal membrane oxygenation
Authors: Müller T. , Philipp A. , Lubnow M. , Weingart C. , Pfeifer M. , Riegger GAJ , Schmid C. 
Published: May 2011

Extracorporeal assist systems for respiratory and circulatory failure are increasingly used in intensive care medicine. Important technical innovations over the past years have resulted in improved biocompatibility and, consequently, reduced complication rates. Extracorporeal membrane oxygenation (ECMO) technology experienced a surge of use during the influenza A (H1N1) pandemic, but transport of unstable patients with life-threatening ARDS is still hazardous. We describe the first successful application of a newly developed, compact and easily portable ECMO device in a patient with severe ARDS due to influenza A (H1N1). Support with the miniaturized ECMO resulted in immediate improvement of gas exchange and a highly protective ventilation. Inspiratory pressure was decreased from 40 to 29 cmH2O and tidal volume per kilogram of predicted bodyweight could be reduced from 6.5 to 3.3 mL. Small and efficient heart-lung assist systems will become a tool of growing importance in intensive care medicine, both for profound respiratory and cardiac failure in the future. The reduced weight and compact design of the device greatly facilitates transport and handling of unstable patients on ECMO.
Total testosterone in young men is more closely associated than free testosterone with prostate cancer disparities
Authors: Alvarado Louis Calistro 
Published: May 2011

Introduction: Early adulthood has been suggested as the most relevant time to determine the influence of testosterone on prostate carcinogenesis. For a more detailed assessment of this hypothesis, the present study examined whether serum total or free testosterone in young men was more closely associated with prostate cancer disparities. Methods: A literature search was conducted for studies that reported both total and free testosterone levels for population samples of young men, along with prostate cancer incidences for the populations from which study populations were sampled. A previously developed analytical method was used to standardize the hormone levels of 19 population samples gathered from nine studies, and these standardized values were compared with disparities in prostate cancer incidence. Results: Population differences in total testosterone levels were significantly associated with prostate cancer disparities, r = 0.833, p = 0.001, as were population differences in free testosterone, r = 0.661, p = 0.027. After controlling for age differences, total and free testosterone remained associated with prostate cancer disparities, partial r = 0.888, p < 0.001, and partial r = 0.657, p = 0.039, respectively. A marginally significant difference existed in the strength of relationships between total and free testosterone with respect to prostate cancer disparities, with total testosterone exhibiting a stronger association, T2 = 1.573, p = 0.077. Conclusions: Across analyses, total testosterone demonstrated a more robust relationship than free testosterone with cancer disparities, which may suggest that total testosterone is the more sensitive biomarker for evaluating androgenic stimulation of the prostate gland.
Implementing public health in secondary care: A Rotherham perspective on strategy development and implementation
Authors: Al-alawy Khamis , Roche Teresa , Alwali Walid 
Published: May 2011

Aims: This paper reports an approach to develop and implement a public health strategy in secondary care and uses smoking cessation as a means for measuring success. Methods: Rotherham Foundation Hospital Trust recognized its unique role to promote, prevent and protect health and well-being in Rotherham. Following consultation across key departments, the trust developed a public health strategy encompassing five priorities. Results: We report ongoing commitment and engagement following the launch of the public health strategy. Over a period of one year (April 2008 to March 2009) 269 front-line staff were trained on smoking cessation brief interventions. We report 890 referrals to smoking cessation, resulting in 414 setting a quit date and 143 four-week quitters (35% conversion rate). Despite progress in implementing smoking cessation, more communication is required to ensure that GPs and hospital staff continue to maximize patient outcomes through brief interventions. Conclusions: The paper provides an approach to implement public health in secondary care. The Commissioning for Quality and Innovation (CQUIN) payment framework would be a useful tool to ensure key public health areas such as smoking cessation are systemized in secondary care.
GP consortia: Navigating ambiguity to produce greater public value?
Authors: Holbeche Linda 
Published: May 2011

The UK’s NHS is about to be significantly remodelled according to a white paper published in July 20101 that outlines the devolution of commissioning responsibilities away from strategic health authorities and primary care trusts to consortia of GPs, which are to be established at local level. Details of how the new GP consortia will operate are as yet unclear, but in essence they will be strategic alliances and it is likely that they will develop more or less formal arrangements between consortia partners, such as those of a commercial joint venture. This article draws on primary research into strategic alliances between organizations in all sectors. It suggests that there can be significant challenges for those working within strategic alliances, given that these tend to be beset by ambiguity and political tensions. In a context of ever greater transparency and accountability, it will be crucial to attend to the human aspects of strategic alliances since these represent significant risk if neglected. Conversely, alliances also offer the opportunity to develop the synergy of people, organizations and communities to deliver greater public value. Successful collaborations need to get three things right: governance, operations and behaviours. Relationships between consortia partners have a significant bearing on their ability to deliver desired outcomes. They must be able to build and maintain trust. Consortia partners will need sophisticated negotiating and stakeholder management skills and must be able to engage the public in setting the strategic goals for which they will be accountable. They also need strategic and operational management skills and must be able to cope with ambiguity and manage complexity. This paper argues that specific forms of leadership are needed in collaborative arrangements to mobilize people for positive action. People must work together by willingly and effectively pooling their initiative and expertise, and create a product or energy that is greater than the sum of their parts. The nature of leadership required to produce such high performance outcomes is likely to supersede leadership that is the result of structural relationships or of individual action. In particular, distributed leadership is likely to be relevant.
Implementation of force distribution analysis for molecular dynamics simulations
Authors: Stacklies Wolfram , Seifert Christian , Graeter Frauke 
Published: May 2011

Abstract

Background
The way mechanical stress is distributed inside and propagated by proteins and other biopolymers largely defines their function. Yet, determining the network of interactions propagating internal strain remains a challenge for both, experiment and theory. Based on molecular dynamics simulations, we developed force distribution analysis (FDA), a method that allows visualizing strain propagation in macromolecules.

Results
To be immediately applicable to a wide range of systems, FDA was implemented as an extension to Gromacs, a commonly used package for molecular simulations. The FDA code comes with an easy-to-use command line interface and can directly be applied to every system built using Gromacs. We provide an additional R-package providing functions for advanced statistical analysis and presentation of the FDA data.

Conclusions
Using FDA, we were able to explain the origin of mechanical robustness in immunoglobulin domains and silk fibers. By elucidating propagation of internal strain upon ligand binding, we previously also successfully revealed the functionality of a stiff allosteric protein. FDA thus has the potential to be a valuable tool in the investigation and rational design of mechanical properties in proteins and nano-materials.
Analysis of Gene expression in soybean (Glycine max) roots in response to the root knot nematode Meloidogyne incognita using microarrays and KEGG pathways
Authors: Ibrahim Heba MM , Hosseini Parsa , Alkharouf Nadim W , Hussein Ebtissam HA , Gamal El-Din Abd El Kader Y , Aly Mohammed AM , Matthews Benjamin F 
Published: May 2011

Abstract

Background
Root-knot nematodes are sedentary endoparasites that can infect more than 3000 plant species. Root-knot nematodes cause an estimated $100 billion annual loss worldwide. For successful establishment of the root-knot nematode in its host plant, it causes dramatic morphological and physiological changes in plant cells. The expression of some plant genes is altered by the nematode as it establishes its feeding site.

Results
We examined the expression of soybean (Glycine max) genes in galls formed in roots by the root-knot nematode, Meloidogyne incognita, 12 days and 10 weeks after infection to understand the effects of infection of roots by M. incognita. Gene expression was monitored using the Affymetrix Soybean GeneChip containing 37,500 G. max probe sets. Gene expression patterns were integrated with biochemical pathways from the Kyoto Encyclopedia of Genes and Genomes using PAICE software. Genes encoding enzymes involved in carbohydrate and cell wall metabolism, cell cycle control and plant defense were altered.

Conclusions
A number of different soybean genes were identified that were differentially expressed which provided insights into the interaction between M. incognita and soybean and into the formation and maintenance of giant cells. Some of these genes may be candidates for broadening plants resistance to root-knot nematode through over-expression or silencing and require further examination.
Long-term follow-up of nonspecific small bowel ulcers with a benign course and no requirement for surgery: is this a distinct group?
Authors: Wang Weifeng , Wang Zhanbo , Yang Yunsheng , Linghu Enqiang , Lu Zhongsheng 
Published: May 2011

Abstract

Background
Nonspecific small bowel ulcers are rare and surgical intervention is often believed to be elective. Since the extensive investigation of the small bowel in the 1990s, there have been limited reports of these ulcers and the updates have been unsatisfactory. The aim of this study was to explore the clinical features and natural histories of nonspecific small bowel ulcers through prospective observational study.

Methods
We reviewed the medical records of all patients who had undergone ileocolonoscopy or enteroscopy between 2000 and 2005 in a tertiary referral hospital. Seven patients with small bowel ulcers of unknown cause were identified. These patients were prospectively followed in a prolonged observation until March 2010.

Results
All seven patients (mean age: 54.7 years) presented with mild gastrointestinal symptoms, including chronic diarrhea and/or abdominal pain/discomfort, except for one who was asymptomatic when surveyed for colon polyps. Most patients were suspected of having functional bowel disorders for a long time (4.4 years) before small bowel ulcers were demonstrated on ileoscopy. The ulcers were characteristically multiple, superficial, and small (3-6 mm), locating at the terminal ileum and/or ileocecal valve. Various empirical treatments were applied, and most patients felt partly improved, even relieved. However the gastrointestinal symptoms did not always correlate with the presence of ulcers, and the ulcers tended to be either persistent (4 patients) or recurrent (1 patient). Ileocolonoscopy was repeated 4.1 times during follow-up, even after the lesions had healed. The characteristics of the ulcers, if still present during follow-up, were similar to their earlier characteristics. No patient experienced exacerbation or complications, such as intestinal obstruction, perforation, or bleeding. All patient survived and no surgical intervention was involved during the prolonged follow-up (7.0 years).

Conclusion
The reported patients with nonspecific small bowel ulcers experienced benign courses, inconsistent with previous reports. Without extensive investigation, this disease can be confused with functional bowel disorders.
A cross-sectional study of HIV and syphilis infections among male students who have sex with men (MSM) in northeast China: implications for implementing HIV screening and intervention programs
Authors: Xu Jun-Jie , Reilly Kathleen Heather , Lu Chun-Ming , Ma Ning , Zhang Min , Chu Zhen-Xing , Wang Jun-Jie , Yun Ke , Shang Hong 
Published: May 2011

Abstract

Background
China has 76.2 million high school and college students, in which the number of reported HIV/AIDS cases is increasing rapidly. Most of these cases are attributed to male-to-male sexual contact. Few studies have explored HIV prevalence and behavioural characteristics of Chinese male students who have sex with men (MSM).

Methods
A cross-sectional study of MSM high school and college students in Liaoning Province was conducted. Data were collected through face-to-face interviews and blood specimens were obtained and tested for HIV and syphilis.

Results
There were 436 eligible participants. HIV and syphilis prevalence was 3.0% and 5.0%, respectively. In multivariate analysis, sexual orientation known by family members (OR: 7.3; 95% CI: 1.5-34.6), HIV/AIDS information obtained from clinical doctors (OR: 6.7; 95% CI: 1.7-25.9), HIV/AIDS information obtained through free educational services and materials such as voluntary counseling and testing (VCT) and condom distribution services (OR: 0.2; 95% CI: 0.4-1.0), inconsistent condom use (OR: 5.7; 95%: 1.3-25.3), sexual partner experienced anal bleeding after insertive anal intercourse (OR: 6.8; 95% CI: 1.6-28.4), and history of illegal drug use (OR: 18.9; 95% CI: 2.2-165.3) were found to be significantly associated with HIV infection.

Conclusions
Greater effort should be made towards stemming the HIV and syphilis epidemics among Chinese student MSM. Immediate screening and comprehensive interventions towards student MSM should be implemented in order to curb the spread of HIV. Family and school-based interventions should be considered to target this educated, yet vulnerable, population.