bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome Profile of Human Colorectal Adenomas
Authors: Sabates-Bellver Jacob , Van der Flier Laurens G. , de Palo Mariagrazia , Cattaneo Elisa , Maake Caroline , Rehrauer Hubert , Laczko Endre , Kurowski Michal A. , Bujnicki Janusz M. , Menigatti Mirco , Luz Judith , Ranalli Teresa V. , Gomes Vito , Pastorelli Alfredo , Faggiani Roberto , Anti Marcello , Jiricny Josef , Clevers Hans , Marra Giancarlo 
Published: January 2008

Abstract
Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the β-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation. (Mol Cancer Res 2007;5(12):1263–75)
Basal Caspase Activity Promotes Migration and Invasiveness in Glioblastoma Cells
Authors: Gdynia Georg , Grund Kerstin , Eckert Anika , Böck Barbara C. , Funke Benjamin , Macher-Goeppinger Stephan , Sieber Sebastian , Herold-Mende Christel , Wiestler Benedict , Wiestler Otmar D. , Roth Wilfried 
Published: January 2008

Abstract
Glioblastomas, the most malignant of all brain tumors, are characterized by cellular resistance to apoptosis and a highly invasive growth pattern. These factors contribute to the poor response of glioblastomas to radiochemotherapy and prevent their complete neurosurgical resection. However, the driving force behind the distinct motility of glioma cells is only partly understood. Here, we report that in the absence of cellular stress and proapoptotic stimuli, human glioblastoma cells exhibit a constitutive activation of caspases in vivo and in vitro. The inhibition of caspases by various peptide inhibitors decreases the migration of cells in scrape motility assays and the invasiveness of cells in spheroid assays. Similarly, specific small interfering RNA– or antisense-mediated down-regulation of caspase-3 and caspase-8 results in an inhibition of the migratory potential of glioma cells. The constitutive caspase-dependent motility of glioblastoma cells is independent of CD95 activation and it is not mediated by mitogen-activated protein/extracellular signal-regulated kinase kinase signaling. The basal caspase activity is accompanied by a constant cleavage of the motility-associated gelsolin protein, which may contribute to the caspase-mediated promotion of migration and invasiveness in glioblastoma cells. Our results suggest that the administration of low doses of caspase inhibitors that block glioma cell motility without affecting the execution of apoptotic cell death may be exploited as a novel strategy for the treatment of glioblastomas. (Mol Cancer Res 2007;5(12):1232–40)
The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo
Authors: Hutt Karla J , Shi Zhanquan , Albertini David F , Petroff Brian K 
Published: January 2008

Abstract

Background
Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation.

Results
We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts.

Conclusion
We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.
Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host
Authors: Xi Zhiyong , Gavotte Laurent , Xie Yan , Dobson Stephen L 
Published: January 2008

Abstract

Background
Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown.

Results
Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism.

Conclusion

Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.
A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population
Authors: Zeng Zheng , Guan Li , An Ping , Sun Shan , O'Brien Stephen J , Winkler Cheryl A ,   the HBV study consortium
Published: January 2008

Abstract

Background
Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5–6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options.

Methods/Design
This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases.

Conclusion
This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development.
Participatory design in the development of the wheelchair convoy system
Authors: Sharma Vinod , Simpson Richard C , LoPresti Edmund F , Mostowy Casimir , Olson Joseph , Puhlman Jeremy , Hayashi Steve , Cooper Rory A , Konarski Ed , Kerley Barry 
Published: January 2008

Abstract

Background
In long-term care environments, residents who have severe mobility deficits are typically transported by having another person push the individual in a manual wheelchair. This practice is inefficient and encourages staff to hurry to complete the process, thereby setting the stage for unsafe practices. Furthermore, the time involved in assembling multiple individuals with disabilities often deters their participation in group activities.

Methods
The Wheelchair Convoy System (WCS) is being developed to allow a single caregiver to move multiple individuals without removing them from their wheelchairs. The WCS will consist of a processor, and a flexible cord linking each wheelchair to the wheelchair in front of it. A Participatory Design approach – in which several iterations of design, fabrication and evaluation are used to elicit feedback from users – was used.

Results
An iterative cycle of development and evaluation was followed through five prototypes of the device. The third and fourth prototypes were evaluated in unmanned field trials at J. Iverson Riddle Development Center. The prototypes were used to form a convoy of three wheelchairs that successfully completed a series of navigation tasks.

Conclusion
A Participatory Design approach to the project allowed the design of the WCS to quickly evolve towards a viable solution. The design that emerged by the end of the fifth development cycle bore little resemblance to the initial design, but successfully met the project's design criteria. Additional development and testing is planned to further refine the system.
SCREENING NEWBORNS FOR SICKLE CELL DISEASE IN GHANA
Authors: Ohene-Frempong Kwaku , Oduro Joseph , Tetteh Hannah , Nkrumah Francis 
Published: January 2008

INTRODUCTION: Screening of newborns for sickle cell disease (SCD) allows early initiation of prophylactic therapy, parental education, and comprehensive management, which results in reduced mortality. Since April 1993, a demonstration project to develop and implement a program of newborn screening for SCD has been conducted in Kumasi, Ghana, by the Comprehensive Sickle Cell Center at the Children's Hospital of Philadelphia in collaboration with the Ministry of Health and other institutions in Ghana.
OBJECTIVE: Our goal was to assess the program of screening and follow-up of children with SCD in Ghana.
METHODS: Infants are screened at birth or at well-infant visits within days or a few weeks after birth. Mothers are asked to come for results within 4 weeks, and failing that, an extensive tracking system is used to deliver results to the homes of families with infants with possible SCD. Tracking relies solely on information obtained from mothers at the time of screening. The goal is to enroll infants with possible SCD into the sickle cell clinic by 8 weeks of age. Pregnant women, parents with children, and the general public are educated regularly about the screening program. Children with SCD receive comprehensive care through the Sickle Cell Clinic at Komfo Anokye Teaching Hospital (Kumasi, Ghana).
RESULTS: From February 13, 1995 (when newborn testing was started), to December 31, 2005, a total of 202 244 infants were screened through 8 public health institutions and 14 private clinics in Kumasi and 1 private maternity center and 1 public health Center in Tikrom, a nearby, rural community. A total of 3745 (1.9%) infants were identified as having possible SCD with the following hemoglobin phenotypes according to isoelectric focusing: 2047 (1.04%) fetal sickle cell hemoglobin; 1684 (0.83%) fetal SC hemoglobin; and, 14 (0.003%) fetal SA hemoglobin (Table 1).
CONCLUSIONS: Screening and follow-up of newborns for SCD is feasible in a developing country in Africa. Extra effort in tracking is necessary to ensure that infants with disease are found early and referred for medical management.
TABLE 1.Screening and Tracking Results: February 1995 to December 2005No.%Total No. of infants screened202 244100.0Infants with possible SCD37451.9 (of infants screened)Under active tracking (newly diagnosed)(125)3.3 (of infants with possible SCD; excluded)Total possible SCD accounted for362096.7 (of infants with possible SCD; reported)Lost to follow-up/never found(494)13.6 (of infants with possible SCD; reported)Dead before contact made(34)0.9 (of infants with possible SCD; reported)No. contacted with results (eligible for enrollment)309285.4 (of infants with possible SCD; reported)    Came for results65121.0 (of those contacted)    Through home visiting244179.0 (of those contacted)Eligible but not enrolled after contact47715.4 (of those eligible)Enrolled in clinic261584.6 (of those eligible)Known deaths after enrollment1094.2 (of those enrolled)
To Pay or Not to Pay: Examining Underlying Principles in the Debate on Financial Support for Family Caregivers
Authors: Keefe Janice , Rajnovich Beth 
Published: January 2008

ABSTRACTIn many countries one approach to supporting family-and-friend caregivers is direct financial or monetary support. Debates about the benefits and consequences of such policies pervade the literature. Building on the premise that values underlie public policy, the paper examines four policy paradoxes in the literature and uses selected examples from an international policy analysis to illustrate the underlying objectives and values upon which many of the policies were developed. These include the responsibility to care, economic or social objectives, gender equity, and the autonomy of care receivers. The authors conclude that policy makers need to be cautious about the unintended effects of financial support policy and develop a menu of policies and services to support caregivers. Future policy development in Canada must enable legitimate choice across the life course and ensure that neither the caregiver nor the care receiver will experience short- or long-term financial consequences of his or her choice.
Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain
Authors: Hlatky Roman , Valadka Alex B. , Gopinath Shankar P. , Robertson Claudia S. 
Published: January 2008

Object
Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia.

Methods
The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon–enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 × 100/change in PaO2.

Results
The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11–15, 16–20, 21–40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min.

Conclusions
Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.
Combined internal uncusectomy and decompressive craniectomy for the treatment of severe closed head injury: experience with 80 cases
Authors: Chibbaro Salvatore , Marsella Marco , Romano Antonio , Ippolito Salvatore , Benericetti Eugenio 
Published: January 2008

Object
Transtentorial brain herniation is a major cause of morbidity and death following severe closed head injury. The purpose of this study was to evaluate the efficacy of selective uncoparahippocampectomy and tentorial splitting as an adjuvant method of treating otherwise uncontrollable elevated intracranial pressure (ICP) while attempting to prevent or minimize the devastating consequences caused by transtentorial herniation.

Methods
The authors retrospectively reviewed data from a series of 80 consecutive cases of severe closed head injury (Glasgow Coma Scale [GCS] score <8) treated in their neurosurgical unit. All patients had elevated ICP and downward tentorial herniation, as documented with ICP monitoring, and clinical examination and computed tomography, respectively. Given the evidence of acute and ongoing neurological deterioration, all patients were treated with selective uncoparahippocampectomy and tentorial edge incision followed by wide decompressive craniectomy and duraplasty.

Results
All injuries were caused by blunt trauma with signs of acute and/or progressive increased ICP causing downward transtentorial herniation. Fifty-eight patients were male and 22 were female with a mean age of 35 years and a mean preoperative GCS score of 5. Based on the current American Association of Neurological Surgeons guidelines for head trauma, an intraparenchymal ICP device (Camino, Integra) was placed in all patients who had a GCS score <8, and ICP was consistently >20 cm H2O. Whenever possible, risks and benefits were explained to family members, and then surgery was performed within 3–16 hours (median 6 hours). At a mean follow-up of 30 months, the outcome was favorable (Glasgow Outcome Scale [GOS] score of 4 or 5) in 60 patients (75%) and unfavorable (GOS score of 3) in 8 (10%), whereas the remaining 12 patients (15%) died at some point during the postoperative course. There was no survivor patient in a vegetative state. A younger age had a significant effect on positive outcome (p < 0.0005), as did an earlier operation (p < 0.04). The preoperative neurological status as assessed using the GCS as well as pupillary reactivity had no significant effect on outcome (p = 0.054 and p > 0.05, respectively).

Conclusions
A selective uncoparahippocampectomy with a tentorial edge incision and a wide decompressive craniectomy with duraplasty can be an effective adjuvant form of aggressive treatment to improve outcome in patients with severe closed head injury, especially in those who are younger if they are treated promptly.
Dose–response relationship of mannitol and intracranial pressure: a metaanalysis
Authors: Sorani Marco D. , Manley Geoffrey T. 
Published: January 2008

Object
Brain edema can increase intracranial pressure (ICP), potentially leading to ischemia, herniation, and death. Edema and elevated ICP are often treated with osmotic agents to remove water from brain tissue. Mannitol is the osmotic diuretic most commonly used in the intensive care unit; however, despite its clinical importance, treatment protocols vary from center to center, and the dose–response relationship is not understood. The goal of this metaanalysis was to aggregate and analyze data from studies in which authors have described the dose–response relationship between mannitol and ICP.

Methods
The authors identified 18 studies that quantitatively characterized the dose–response relationship of mannitol and ICP. We also examined study designs and mannitol administration protocols.

Results
Meta-regression found a weak linear relationship between change in ICP (ΔICP) and dose (ΔICP = 6.6 × dose − 1.1; p = 0.27, R2 = 0.05). The lack of statistical significance could reflect the variation in protocols among studies and the variation in patients both within and among studies. However, the authors found a highly significant difference (p < 0.001) in decrease in ICP when the initial ICP was higher or lower than 30 mm Hg. Nonlinear regression suggested that ICP decrease is greatest shortly after mannitol is given (R2 = 0.63). Finally, the authors found that recent studies tend to include fewer patients and set a lower ICP threshold for mannitol administration but report more parameters of interest; the duration of mannitol's effect was the most frequently unreported parameter.

Conclusions
Despite its clinical importance, the determination of the mannitol dose–response curve continues to be challenging for many reasons. This metaanalysis highlights the need for a consensus of methods and results required to determine this important relationship.