bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building tobacco control research in Thailand: meeting the need for innovative change in Asia
Authors: Hamann Stephen L , Mock Jeremiah , Hense Sibasis , Charoenca Naowarut , Kungskulniti Nipapun 
Published: January 2012

Abstract

Introduction
In low- and middle-income countries (LMICs) over the past two decades locally relevant tobacco control research has been scant. Experience shows that tobacco control measures should be based on sound research findings to ensure that measures are appropriate for local conditions and that they are likely to have an impact. Research should also be integrated within tobacco control measures to ensure ongoing learning and the production of knowledge. Thailand, a middle-income country, has a public health community with a record of successful tobacco control and a longstanding commitment to research. Thailand's comprehensive approach includes taxation; bans on tobacco advertising, sponsorship and promotion; smoke-free areas; graphic cigarette pack warnings; social marketing campaigns; cessation counseling; and an established tobacco control research program. The purpose of this study was to document and analyze the development of tobacco control research capacity in Thailand and the impact of research on Thai tobacco control measures.

Method
We used mixed methods including review of historical documentation and policy reports, qualitative interviews with key members of Thailand's tobacco control community, and an analysis of research productivity.

Findings
In Thailand, tobacco control research has evolved through three phases: (1) discovery of the value of research in the policymaking arena, (2) development of a structure to support research capacity building through international collaborations supported by foreign funding agencies, and (3) delivery of locally relevant research made possible largely through substantial stable funding from a domestic health promotion foundation. Over two decades, Thai tobacco control advocates have constructed five steppingstones to success: (1) adapting foreign research to inform policymaking and lobbying for more support for domestic research; (2) attracting foreign funding agencies to support small-scale research and capacity building; (3) participating in multi-country research and capacity building programs; (4) using collaborative experiences to demonstrate the need for domestic support of locally relevant research; and (5) maintaining an unwavering commitment to research while being vigilant to ensure continued research support.

Conclusion
The evolution of tobacco control research in Thailand provides examples of steppingstones that LMICs may be able to use to construct their own tobacco control research pathways.
A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions
Authors: Raheem Omer , Kulidjian Anna A , Wu Christina , Jeong Young B , Yamaguchi Tomonori , Smith Kristen M , Goff Daniel , Leu Heather , Morris Sheldon R , Cacalano Nicholas A , Masuda Koichi , Jamieson Catriona HM , Kane Christopher J , Jamieson Christina AM 
Published: January 2012

AbstractProstate cancer metastasizes to bone in the majority of patients with advanced disease leading to painfully debilitating fractures, spinal compression and rapid decline. In addition, prostate cancer bone metastases often become resistant to standard therapies including androgen deprivation, radiation and chemotherapy. There are currently few models to elucidate mechanisms of interaction between the bone microenvironment and prostate cancer. It is, thus, essential to develop new patient-derived, orthotopic models. Here we report the development and characterization of PCSD1 (Prostate Cancer San Diego 1), a novel patient-derived intra-femoral xenograft model of prostate bone metastatic cancer that recapitulates mixed osteolytic and osteoblastic lesions.MethodsA femoral bone metastasis of prostate cancer was removed during hemiarthroplasty and transplanted intoRag2-/-;γc-/-mice either intra-femorally or sub-cutaneously. Xenograft tumors that developed were analyzed for prostate cancer biomarker expression using RT-PCR and immunohistochemistry. Osteoblastic, osteolytic and mixed lesion formation was measured using micro-computed tomography (microCT).ResultsPCSD1 cells isolated directly from the patient formed tumors in all mice that were transplanted intra-femorally or sub-cutaneously intoRag2-/-;γc-/-mice. Xenograft tumors expressed human prostate specific antigen (PSA) in RT-PCR and immunohistochemical analyses. PCSD1 tumors also expressed AR, NKX3.1, Keratins 8 and 18, and AMACR. Histologic and microCT analyses revealed that intra-femoral PCSD1 xenograft tumors formed mixed osteolytic and osteoblastic lesions. PCSD1 tumors have been serially passaged in mice as xenografts intra-femorally or sub-cutaneously as well as grown in culture.ConclusionsPCSD1 xenografts tumors were characterized as advanced, luminal epithelial prostate cancer from a bone metastasis using RT-PCR and immunohistochemical biomarker analyses. PCSD1 intra-femoral xenografts formed mixed osteoblastic/osteolytic lesions that closely resembled the bone lesions in the patient. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study metastatic disease in the bone and to develop novel therapies for inhibiting prostate cancer growth in the bone-niche.
A functional variant in promoter region of platelet-derived growth factor-D is probably associated with intracerebral hemorrhage
Authors: Bai Yongyi , Chen Jingzhou , Sun Kai , Wang Yibo , Hui Rutai 
Published: January 2012

Abstract

Background
Platelet-derived growth factor D (PDGF-D) plays an important role in angiogenesis, vessel remodeling, inflammation and repair in response to injury. We hypothesized that genetic variation in PDGFD gene might alter the susceptibility to stroke.

Findings
We determined the genotypes of a single nucleotide polymorphism (SNP) (-858A/C, rs3809021) in 1484 patients with stroke (654 cerebral thrombosis, 419 lacunar infarction, 411 intracerebral hemorrhage [ICH]) and 1528 control subjects from an unrelated Chinese Han population and followed the stroke patients up for a median of 4.5 years.
The -858AA genotype showed significantly increased risk of ICH (dominant model: odds ratio [OR] 1.29, 95% confidence interval [CI] 1.00-1.68, P = 0.05; additive model: OR 1.24, 95% CI 1.01-1.52, P = 0.04) than wild-type genotype. Further analyses showed that -858AA genotype conferred about 2-fold increase in risk of non-hypertensive ICH (dominant model: OR 2.1, 95%CI 1.34-3.29, P = 0.001; additive model: OR 1.75, 95% CI 1.24-2.46, P = 0.001). After a median follow-up of 4.5 years, -858AA genotype was associated with a reduced risk of ICH recurrence (dominant model: adjusted hazard ratio [HR] 0.09, 95%CI 0.01-0.74, P = 0.025; additive model: HR 0.21, 95% CI 0.04-1.16, P = 0.073) in non-hypertensive patients.

Conclusions
The -858AA genotype is probably associated with risk for non-hypertensive ICH. Further studies should be conducted to reveal the role of PDGF-D at various stages of ICH development--beneficial, or deleterious.
Binding of more than one Tva800 molecule is required for ASLV-A entry
Authors: Gray Eleanor R , Illingworth Christopher JR , Coffin John M , Stoye Jonathan P 
Published: January 2012

AbstractBackgroundUnderstanding the mechanism by which viruses enter their target cell is an essential part of understanding their infectious cycle. Previous studies have focussed on the multiplicity of viral envelope proteins that need to bind to their cognate receptor to initiate entry. Avian sarcoma and leukosis virus Envelope protein (ASLV Env) mediates entry via a receptor, Tva, which can be attached to the cell surface either by a phospholipid anchor (Tva800) or a transmembrane domain (Tva950). In these studies, we have now investigated the number of target receptors necessary for entry of ASLV Env-pseudotyped virions.ResultsUsing titration and modelling experiments we provide evidence that binding of more than one receptor, probably two, is needed for entry of virions via Tva800. However, binding of just one Tva950 receptor is sufficient for successful entry.ConclusionsThe different modes of attachment of Tva800 and Tva950 to the cell membrane have important implications for the utilisation of these proteins as receptors for viral binding and/or uptake.
Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals
Authors: Luzna Pavla , Gregar Jan , Uberall Ivo , Radova Lenka , Prochazka Vlastimil , Ehrmann Jiri 
Published: January 2012

Abstract

Background
Barrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops.

Methods
71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out.

Results
We demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals.

Conclusions
We hypothetize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals.
Use of combined maximum and minimum intensity projections to determine internal target volume in 4-dimensional CT scans for hepatic malignancies
Authors: Liu Jin , Wang Jia-Zhou , Zhao Jian-Dong , Xu Zhi-Yong , Jiang Guo-Liang 
Published: January 2012

Abstract

Background
To evaluate the accuracy of the combined maximum and minimum intensity projection-based internal target volume (ITV) delineation in 4-dimensional (4D) CT scans for liver malignancies.

Methods
4D CT with synchronized IV contrast data were acquired from 15 liver cancer patients (4 hepatocellular carcinomas; 11 hepatic metastases). We used five approaches to determine ITVs: (1). ITVAllPhases: contouring gross tumor volume (GTV) on each of 10 respiratory phases of 4D CT data set and combining these GTVs; (2). ITV2Phase: contouring GTV on CT of the peak inhale phase (0% phase) and the peak exhale phase (50%) and then combining the two; (3). ITVMIP: contouring GTV on MIP with modifications based on physician's visual verification of contours in each respiratory phase; (4). ITVMinIP: contouring GTV on MinIP with modification by physician; (5). ITV2M: combining ITVMIP and ITVMinIP. ITVAllPhases was taken as the reference ITV, and the metrics used for comparison were: matching index (MI), under- and over-estimated volume (Vunder and Vover).

Results
4D CT images were successfully acquired from 15 patients and tumor margins were clearly discernable in all patients. There were 9 cases of low density and 6, mixed on CT images. After comparisons of metrics, the tool of ITV2M was the most appropriate to contour ITV for liver malignancies with the highest MI of 0.93 ± 0.04 and the lowest proportion of Vunder (0.07 ± 0.04). Moreover, tumor volume, target motion three-dimensionally and ratio of tumor vertical diameter over tumor motion magnitude in cranio-caudal direction did not significantly influence the values of MI and proportion of Vunder.

Conclusion
The tool of ITV2M is recommended as a reliable method for generating ITVs from 4D CT data sets in liver cancer.
Bilateral enucleation alters gene expression and intraneocortical connections in the mouse
Authors: Dye Catherine A , Abbott Charles W , Huffman Kelly J 
Published: January 2012

Abstract

Background
Anatomically and functionally distinct sensory and motor neocortical areas form during mammalian development through a process called arealization. This process is believed to be reliant on both activity-dependent and activity-independent mechanisms. Although both mechanisms are thought to function concurrently during arealization, the nature of their interaction is not understood. To examine the potential interplay of extrinsic activity-dependent mechanisms, such as sensory input, and intrinsic activity-independent mechanisms, including gene expression in mouse neocortical development, we performed bilateral enucleations in newborn mice and conducted anatomical and molecular analyses 10 days later. In this study, by surgically removing the eyes of the newborn mouse, we examined whether early enucleation would impact normal gene expression and the development of basic anatomical features such as intraneocortical connections and cortical area boundaries in the first 10 days of life, before natural eye opening. We examined the acute effects of bilateral enucleation on the lateral geniculate nucleus of the thalamus and the neocortical somatosensory-visual area boundary through detailed analyses of intraneocortical connections and gene expression of six developmentally regulated genes at postnatal day 10.

Results
Our results demonstrate short-term plasticity on postnatal day 10 resulting from the removal of the eyes at birth, with changes in nuclear size and gene expression within the lateral geniculate nucleus as well as a shift in intraneocortical connections and ephrin A5 expression at the somatosensory-visual boundary. In this report, we highlight the correlation between positional shifts in ephrin A5 expression and improper refinement of intraneocortical connections observed at the somatosensory-visual boundary in enucleates on postnatal day 10.

Conclusions
Bilateral enucleation induces a positional shift of both ephrin A5 expression and intraneocortical projections at the somatosensory-visual border in only 10 days. These changes occur prior to natural eye opening, suggesting a possible role of spontaneous retinal activity in area border formation within the neocortex. Through these analyses, we gain a deeper understanding of how extrinsic activity-dependent mechanisms, particularly input from sensory organs, are integrated with intrinsic activity-independent mechanisms to regulate neocortical arealization and plasticity.
Predicting outcomes of steady-state 13C isotope tracing experiments using Monte Carlo sampling
Authors: Schellenberger Jan , Zielinski Daniel C , Choi Wing , Madireddi Sunthosh , Portnoy Vasiliy , Scott David A , Reed Jennifer L , Osterman Andrei L , Palsson Bernhard ∅ 
Published: January 2012

Abstract

Background
Carbon-13 (13C) analysis is a commonly used method for estimating reaction rates in biochemical networks. The choice of carbon labeling pattern is an important consideration when designing these experiments. We present a novel Monte Carlo algorithm for finding the optimal substrate input label for a particular experimental objective (flux or flux ratio). Unlike previous work, this method does not require assumption of the flux distribution beforehand.

Results
Using a large E. coli isotopomer model, different commercially available substrate labeling patterns were tested computationally for their ability to determine reaction fluxes. The choice of optimal labeled substrate was found to be dependent upon the desired experimental objective. Many commercially available labels are predicted to be outperformed by complex labeling patterns. Based on Monte Carlo Sampling, the dimensionality of experimental data was found to be considerably less than anticipated, suggesting that effectiveness of 13C experiments for determining reaction fluxes across a large-scale metabolic network is less than previously believed.

Conclusions
While 13C analysis is a useful tool in systems biology, high redundancy in measurements limits the information that can be obtained from each experiment. It is however possible to compute potential limitations before an experiment is run and predict whether, and to what degree, the rate of each reaction can be resolved.
Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples
Authors: de la Blétière Diane Raingeard , Blanchet Odile , Cornillet-Lefèbvre Pascale , Coutolleau Anne , Baranger Laurence , Geneviève Franck , Luquet Isabelle , Hunault-Berger Mathilde , Beucher Annaelle , Schmidt-Tanguy Aline , Zandecki Marc , Delneste Yves , Ifrah Norbert , Guardiola Philippe 
Published: January 2012

Abstract

Background
Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified.

Methods
Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n = 101) and/or poor quality control criteria (n = 10) (test set).

Results
With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load.

Conclusion
Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist - neurokinin 1 receptor antagonist chimera
Authors: Guillemyn Karel , Kleczkowska Patrycja , Novoa Alexandre , Vandormael Bart , Van den Eynde Isabelle , Kosson Piotr , Asim Muhammad Faheem , Schiller Peter W , Spetea Mariana , Lipkowski Andrzej W , Tourwé Dirk , Ballet Steven 
Published: January 2012

Abstract

Background
An important limiting factor in the development of centrally acting pharmaceuticals is the blood-brain barrier (BBB). Transport of therapeutic peptides through this highly protective physiological barrier remains a challenge for peptide drug delivery into the central nervous system (CNS). Because the most common strategy to treat moderate to severe pain consists of the activation of opioid receptors in the brain, the development of active opioid peptide analogues as potential analgesics requires compounds with a high resistance to enzymatic degradation and an ability to cross the BBB.

Results
Herein we report that tetrapeptide analogues of the type H-Dmt1-Xxx2-Yyy3-Gly4-NH2 are transported into the brain after intravenous and subcutaneous administration and are able to activate the μ- and δ opioid receptors more efficiently and over longer periods of time than morphine. Using the hot water tail flick test as the animal model for antinociception, a comparison in potency is presented between a side chain conformationally constrained analogue containing the benzazepine ring (BVD03, Yyy3: Aba), and a "ring opened" analogue (BVD02, Yyy3: Phe). The results show that in addition to the increased lipophilicity through amide bond N-methylation, the conformational constraint introduced at the level of the Phe3 side chain causes a prolonged antinociception. Further replacement of NMe-D-Ala2 by D-Arg2 in the tetrapeptide sequence led to an improved potency as demonstrated by a higher and maintained antinociception for AN81 (Xxx2: D-Arg) vs. BVD03 (Xxx2: NMe-D-Ala). A daily injection of the studied opioid ligands over a time period of 5 days did however result in a substantial decrease in antinociception on the fifth day of the experiment. The compact opioid agonist - NK1 antagonist hybrid SBCHM01 could not circumvent opioid induced tolerance.

Conclusions
We demonstrated that the introduction of a conformational constraint has an important impact on opioid receptor activation and subsequent antinociception in vivo. Further amino acid substitution allowed to identify AN81 as an opioid ligand able to access the CNS and induce antinociception at very low doses (0.1 mg/kg) over a time period up to 7 hours. However, tolerance became apparent after repetitive i.v. administration of the investigated tetrapeptides. This side effect was also observed with the dual opioid agonist-NK1 receptor antagonist SBCHM01.
Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database
Authors: Lim Poh‐Lian , Zhou Jialun , Ditangco Rossana A , Law Matthew G , Sirisanthana Thira , Kumarasamy Nagalingeswaran , Chen Yi‐Ming A , Phanuphak Praphan , Lee Christopher KC , Saphonn Vonthanak , Oka Shinichi , Zhang Fujie , Choi Jun Y , Pujari Sanjay , Kamarulzaman Adeeba , Li Patrick CK , Merati Tuti P , Yunihastuti Evy , Messerschmidt Liesl , Sungkanuparph Somnuek ,   the TREAT Asia HIV Observational Database
Published: January 2012

BackgroundPneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.MethodsTAHOD patients with prospective follow up had data extracted for prophylaxis using co‐trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random‐effect Poisson regression models.ResultsThere were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co‐trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person‐years) and 169 died from all causes (1.36/100 person‐years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person‐years.ConclusionsApproximately two‐thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under‐diagnosed, these data suggest that prophylaxis is associated with important survival benefits.