bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel semi-automatic image processing approach to determine Plasmodium falciparum parasitemia in Giemsa-stained thin blood smears
Authors: Le Minh-Tam , Bretschneider Timo R , Kuss Claudia , Preiser Peter R 
Published: March 2008

Abstract

Background
Malaria parasitemia is commonly used as a measurement of the amount of parasites in the patient's blood and a crucial indicator for the degree of infection. Manual evaluation of Giemsa-stained thin blood smears under the microscope is onerous, time consuming and subject to human error. Although automatic assessments can overcome some of these problems the available methods are currently limited by their inability to evaluate cases that deviate from a chosen "standard" model.

Results
In this study reliable parasitemia counts were achieved even for sub-standard smear and image quality. The outcome was assessed through comparisons with manual evaluations of more than 200 sample smears and related to the complexity of cell overlaps. On average an estimation error of less than 1% with respect to the average of manually obtained parasitemia counts was achieved. In particular the results from the proposed approach are generally within one standard deviation of the counts provided by a comparison group of malariologists yielding a correlation of 0.97. Variations occur mainly for blurred out-of-focus imagery exhibiting larger degrees of cell overlaps in clusters of erythrocytes.
The assessment was also carried out in terms of precision and recall and combined in the F-measure providing results generally in the range of 92% to 97% for a variety of smears. In this context the observed trade-off relation between precision and recall guaranteed stable results. Finally, relating the F-measure with the degree of cell overlaps, showed that up to 50% total cell overlap can be tolerated if the smear image is well-focused and the smear itself adequately stained.

Conclusion
The automatic analysis has proven to be comparable with manual evaluations in terms of accuracy. Moreover, the test results have shown that the proposed comparison-based approach, by exploiting the interrelation between different images and color channels, has successfully overcome most of the inherent limitations possibly occurring during the sample preparation and image acquisition phase. Eventually, this can be seen as an opportunity for developing low-cost solutions for mass screening.
The backbone structure of the thermophilic Thermoanaerobacter tengcongensis ribose binding protein is essentially identical to its mesophilic E. coli homolog
Authors: Cuneo Matthew J , Tian Yaji , Allert Malin , Hellinga Homme W 
Published: March 2008

Abstract

Background
Comparison of experimentally determined mesophilic and thermophilic homologous protein structures is an important tool for understanding the mechanisms that contribute to thermal stability. Of particular interest are pairs of homologous structures that are structurally very similar, but differ significantly in thermal stability.

Results
We report the X-ray crystal structure of a Thermoanaerobacter tengcongensis ribose binding protein (tteRBP) determined to 1.9 Å resolution. We find that tteRBP is significantly more stable (
app

T

m
value ~102°C) than the mesophilic Escherichia coli ribose binding protein (ecRBP) (
app

T

m
value ~56°C). The tteRBP has essentially the identical backbone conformation (0.41 Å RMSD of 235/271 Cα positions and 0.65 Å RMSD of 270/271 Cα positions) as ecRBP. Classification of the amino acid substitutions as a function of structure therefore allows the identification of amino acids which potentially contribute to the observed thermal stability of tteRBP in the absence of large structural heterogeneities.

Conclusion
The near identity of backbone structures of this pair of proteins entails that the significant differences in their thermal stabilities are encoded exclusively by the identity of the amino acid side-chains. Furthermore, the degree of sequence divergence is strongly correlated with structure; with a high degree of conservation in the core progressing to increased diversity in the boundary and surface regions. Different factors that may possibly contribute to thermal stability appear to be differentially encoded in each of these regions of the protein. The tteRBP/ecRBP pair therefore offers an opportunity to dissect contributions to thermal stability by side-chains alone in the absence of large structural differences.
Unreported births and deaths, a severe obstacle for improved neonatal survival in low-income countries; a population based study
Authors: Målqvist Mats , Eriksson Leif , Nga Nguyen Thu , Fagerland Linn Irene , Hoa Dinh Phuong , Wallin Lars , Ewald Uwe , Persson Lars-Åke 
Published: March 2008

Abstract

Background
In order to improve child survival there is a need to target neonatal mortality. In this pursuit, valid local and national statistics on child health are essential. We analyze to what extent births and neonatal deaths are unreported in a low-income country and discuss the consequences at local and international levels for efforts to save newborn lives.

Methods
Information on all births and neonatal deaths in Quang Ninh province in Northern Vietnam in 2005 was ascertained by systematic inventory through group interviews with key informants, questionnaires and examination of health facility records. Health care staff at 187 Community Health Centers (CHC) and 18 hospitals, in addition to 1372 Village Health Workers (VHW), were included in the study. Results were compared with the official reports of the Provincial Health Bureau.

Results
The neonatal mortality rate (NMR) was 16/1000 (284 neonatal deaths/17 519 births), as compared to the official rate of 4.2/1000. The NMR varied between 44/1000 and 10/1000 in the different districts of the province. The under-reporting was mainly attributable to a dysfunctional reporting system and the fact that families, not the health system, were made responsible to register births and deaths. This under-reporting has severe consequences at local, national and international levels. At a local level, it results in a lack of awareness of the magnitude and differentials in NMR, leading to an indifference towards the problem. At a national and international level the perceived low mortality rate is manifested in a lack of investments in perinatal health programs.

Conclusion
This example of a faulty health information system is reportedly not unique in low and middle income countries where needs for neonatal health reforms are greatest. Improving reporting systems on births and neonatal deaths is a matter of human rights and a prerequisite for reducing neonatal mortality in order to reach the fourth millennium goal.
The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome
Authors: Butt Alison J , Sergio C Marcelo , Inman Claire K , Anderson Luke R , McNeil Catriona M , Russell Amanda J , Nousch Marco , Preiss Thomas , Biankin Andrew V , Sutherland Robert L , Musgrove Elizabeth A 
Published: March 2008

Abstract
Introduction
Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced mitogenesis and endocrine resistance.

Methods
We used a transcript profiling approach to identify targets of estrogen and c-Myc in breast cancer cells. One previously uncharacterized gene, namely HBV pre-S2 trans-regulated protein 3 (HSPC111), was acutely upregulated after estrogen treatment or inducible expression of c-Myc, and was selected for further functional analysis using over-expression and knock-down strategies. HSPC111 expression was also analyzed in relation to MYC expression and outcome in primary breast carcinomas and published gene expression datasets.

Results
Pretreatment of cells with c-Myc small interfering RNA abrogated estrogen induction of HSPC111, identifying HSPC111 as a potential c-Myc target gene. This was confirmed by the demonstration of two functional E-box motifs upstream of the transcription start site. HSPC111 mRNA and protein were over-expressed in breast cancer cell lines and primary breast carcinomas, and this was positively correlated with MYC mRNA levels. HSPC111 is present in a large, RNA-dependent nucleolar complex, suggesting a possible role in ribosomal biosynthesis. Neither over-expression or small interfering RNA knock-down of HSPC111 affected cell proliferation rates or sensitivity to estrogen/antiestrogen treatment. However, high expression of HSPC111 mRNA was associated with adverse patient outcome in published gene expression datasets.

Conclusion
These data identify HSPC111 as an estrogen and c-Myc target gene that is over-expressed in breast cancer and is associated with an adverse patient outcome.
Clinical Classification ofBRCA1andBRCA2DNA Sequence Variants: The Value of Cytokeratin Profiles and Evolutionary Analysis—A Report From the kConFab Investigators
Authors: Spurdle Amanda B. , Lakhani Sunil R. , Healey Sue , Parry Suzanne , Da Silva Leonard M. , Brinkworth Ross , Hopper John L. , Brown Melissa A. , Babikyan Davit , Chenevix-Trench Georgia , Tavtigian Sean V. , Goldgar David E. 
Published: March 2008

PurposeRare missense substitutions and in-frame deletions of BRCA1 and BRCA2 genes present a challenge for genetic counseling of individuals carrying such unclassified variants. We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants.Patients and MethodsWe studied 10 BRCA1 and 12 BRCA2 variants identified in Australian families with breast cancer. Analyses assumed a prior probability based on revised cross-species sequence alignment methods assessing amino acid evolutionary conservation and position, combined with likelihoods from data on co-occurrence with pathogenic mutations in the same gene, segregation analysis, and immunohistochemistry. We specifically explored the value of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 as tumor markers of BRCA1 mutation status.ResultsPosterior probabilities classified 72% of variants. BRCA1 variants IVS18+1 G>T (del exon 18) and 5632 T >A (V1838E) were classified as pathogenic, with >99% posterior probability of being deleterious, and tumor histopathology was particularly important for their classification. BRCA2 variant classification was improved over previous studies, largely by incorporating the prior probability of pathogenicity based on amino acid cross-species sequence alignments.ConclusionVariant classification was considerably improved by analysis of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumor expression, and use of updated methods estimating the clinical relevance of amino acid evolutionary conservation and position. These methodologies may assist genetic counseling of individuals with unclassified sequence variants.
Physician-Identified Factors Affecting Patient Participation in Reaching Treatment Decisions
Authors: Shepherd Heather L. , Tattersall Martin H.N. , Butow Phyllis N. 
Published: March 2008

Purpose Cancer physicians report high comfort with shared decision making but a lower frequency of using this approach in practice. Information regarding physicians’ perceptions of what helps and what hinders patient involvement in decision making may facilitate understanding of this discrepancy. Methods We surveyed 604 Australian cancer physicians treating breast, colorectal, gynecologic, hematologic, or urologic cancer to investigate barriers and facilitators to reaching treatment decisions with their patients and their support of strategies to encourage patient involvement and reflection on treatment options. Factor analysis and regression analyses were used to investigate relationships between variables and identify predictors of greater reporting of barriers to sharing treatment decisions with patients. Results Insufficient information at the first consultation (28.9%) and insufficient time (28.4%) were the most frequently reported barriers to reaching treatment decisions with patients. Multivariate analysis revealed that less experienced physicians more commonly reported system barriers (P = .00). Patients trusting their physician and being accompanied at the consultation were most helpful to reaching a treatment decision. Providing written information about treatment options, making a further appointment to reach a decision, encouraging the patient to speak with their family physician and treatment team, and the presence of a third person during the consultation were felt to encourage involvement and reflection on treatment decisions. Conclusion Cancer physicians experience difficulties when reaching treatment decisions with their patients. Interventions and strategies that physicians support are required to enhance patient involvement in reaching a treatment decision.
Complete Pathologic Response After Preoperative Chemotherapy for Colorectal Liver Metastases: Myth or Reality?
Authors: Adam René , Wicherts Dennis A. , de Haas Robbert J. , Aloia Thomas , Lévi Francis , Paule Bernard , Guettier Catherine , Kunstlinger Francis , Delvart Valérie , Azoulay Daniel , Castaing Denis 
Published: March 2008

Purpose Complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy is of limited predictive value for complete pathologic response (CPR) and cure of the disease. The objective of this study was to determine predictive factors of CPR as well as its impact on survival. Patients and Methods From January 1985 to July 2006, 767 consecutive patients with CLM underwent liver resection after systemic chemotherapy. Patients with CPR were compared with patients without CPR. Results Twenty-nine of 767 (4%) patients had CPR, and none of these 29 patients had CCR. Patients with CPR (mean age, 54 years) had a mean number of 3.3 metastases at diagnosis (mean size, 29.3 mm). Objective response and stable disease were observed in 79% and 21% of cases, respectively. Postoperative mortality rate was 0%. After a median follow-up of 52.2 months (range, 1.1 to 193.0 months), overall 5-year survival was 76% for patients with CPR compared with 45% for patients without CPR (P = .004). Independent predictive factors for CPR were: age ≤ 60 years, size of metastases ≤ 3 cm at diagnosis, carcinoembryonic antigen (CEA) level at diagnosis ≤ 30 ng/mL, and objective response following chemotherapy. The probability of CPR ranged from 0.2% when all factors were absent to 30.9% when all were present. Conclusion CPR was observed in 4% of patients with CLM treated with preoperative chemotherapy. However, CPR may occur in almost one-third of objective responders age ≤ 60 years with metastases ≤ 3 cm and low CEA values. CPR is associated with uncommon high survival rates.
Easing of Suffering in Children With Cancer at the End of Life: Is Care Changing?
Authors: Wolfe Joanne , Hammel Jim F. , Edwards Kelly E. , Duncan Janet , Comeau Michael , Breyer Joanna , Aldridge Sarah A. , Grier Holcombe E. , Berde Charles , Dussel Veronica , Weeks Jane C. 
Published: March 2008

Purpose In the past decade studies have documented substantial suffering among children dying of cancer, prompting national attention on the quality of end-of-life care and the development of a palliative care service in our institutions. We sought to determine whether national and local efforts have led to changes in patterns of care, advanced care planning, and symptom control among children with cancer at the end of life. Methods Retrospective cohort study from a US tertiary level pediatric institution. Parent survey and chart review data from 119 children who died between 1997 and 2004 (follow-up cohort) were compared with 102 children who died between 1990 and 1997 (baseline cohort). Results In the follow-up cohort, hospice discussions occurred more often (76% v 54%; adjusted risk difference [RD], 22%; P < .001) and earlier (adjusted geometric mean 52 days v 28 days before death; P = .002) compared with the baseline cohort. Do-not-resuscitate orders were also documented earlier (18 v 12 days; P = .031). Deaths in the intensive care unit or other hospitals decreased significantly (RD, 16%; P = .024). Parents reported less child suffering from pain (RD, 19%; P = .018) and dyspnea (RD, 21%; P = .020). A larger proportion of parents felt more prepared during the child's last month of life (RD, 29%; P < .001) and at the time of death (RD, 24%; P = .002). Conclusion Children dying of cancer are currently receiving care that is more consistent with optimal palliative care and according to parents, are experiencing less suffering. With ongoing growth of the field of hospice and palliative medicine, further advancements are likely.
Automated visual tracking for studying the ontogeny of zebrafish swimming
Authors: Fontaine Ebraheem , Lentink David , Kranenbarg Sander , Müller Ulrike K. , van Leeuwen Johan L. , Barr Alan H. , Burdick Joel W. 
Published: March 2008

SUMMARY
The zebrafish Danio rerio is a widely used model organism in studies of genetics, developmental biology, and recently, biomechanics. In order to quantify changes in swimming during all stages of development, we have developed a visual tracking system that estimates the posture of fish. Our current approach assumes planar motion of the fish, given image sequences taken from a top view. An accurate geometric fish model is automatically designed and fit to the images at each time frame. Our approach works across a range of fish shapes and sizes and is therefore well suited for studying the ontogeny of fish swimming, while also being robust to common environmental occlusions. Our current analysis focuses on measuring the influence of vertebra development on the swimming capabilities of zebrafish. We examine wild-type zebrafish and mutants with stiff vertebrae (stocksteif) and quantify their body kinematics as a function of their development from larvae to adult (mutants made available by the Hubrecht laboratory, The Netherlands). By tracking the fish, we are able to measure the curvature and net acceleration along the body that result from the fish's body wave. Here, we demonstrate the capabilities of the tracking system for the escape response of wild-type zebrafish and stocksteif mutant zebrafish. The response was filmed with a digital high-speed camera at 1500 frames s–1. Our approach enables biomechanists and ethologists to process much larger datasets than possible at present. Our automated tracking scheme can therefore accelerate insight in the swimming behavior of many species of (developing)fish.
Three-dimensional flow structures and evolution of the leading-edge vortices on a flapping wing
Authors: Lu Yuan , Shen Gong Xin 
Published: March 2008

SUMMARYFollowing the identification and confirmation of the substructures of the leading-edge vortex (LEV) system on flapping wings, it is apparent that the actual LEV structures could be more complex than had been estimated in previous investigations. In this experimental study, we reveal for the first time the detailed three-dimensional (3-D) flow structures and evolution of the LEVs on a flapping wing in the hovering condition at high Reynolds number(Re=1624). This was accomplished by utilizing an electromechanical model dragonfly wing flapping in a water tank (mid-stroke angle of attack=60°) and applying phase-lock based multi-slice digital stereoscopic particle image velocimetry (DSPIV) to measure the target flow fields at three typical stroke phases: at 0.125T (T=stroke period), when the wing was accelerating; at 0.25T, when the wing had maximum speed; and at 0.375T, when the wing was decelerating. The result shows that the LEV system is a collection of four vortical elements: one primary vortex and three minor vortices, instead of a single conical or tube-like vortex as reported or hypothesized in previous studies. These vortical elements are highly time-dependent in structure and show distinct `stay properties' at different spanwise sections. The spanwise flows are also time-dependent, not only in the velocity magnitude but also in direction.
Visual sensitivity to a conspicuous male cue varies by reproductive state inPhysalaemus pustulosusfemales
Authors: Cummings Molly E. , Bernal Ximena E. , Reynaga Roberto , Rand A. Stanley , Ryan Michael J. 
Published: March 2008

SUMMARYThe vocal sac is a visually conspicuous attribute of most male frogs, but its role in visual communication has only been demonstrated recently in diurnally displaying frogs. Here we characterized the spectral properties of the inflated vocal sac of male túngara frogs (Physalaemus pustulosus), a nocturnal species, and túngara visual sensitivity to this cue across reproductive state and sex. We measured the spectral and total reflectance of different male body regions, including inflated and non-inflated vocal sacs, along with samples of the visual background against which males are perceived. Inflated vocal sacs were the most reflective of all body parts, being one log unit more reflective than background materials. We utilized an optomotor drum with black stripes and stripes that mimicked the spectral reflectance of the inflated vocal sacs with various nocturnal light intensities to measure the visual sensitivity thresholds of males,non-reproductive females and reproductive females. All three groups exhibited visual sensitivities corresponding to intensities below moonless conditions in open habitats or at the edge of secondary tropical forests. Reproductive females exhibited the greatest visual sensitivity of all groups, and were significantly more sensitive than non-reproductive females. Though the mechanism for this physiological difference between reproductive and non-reproductive females is unknown, it is consistent with previously observed patterns of light-dependent phonotaxic behavior in túngaras. We suggest that the visual ecology of the vocal sac, especially in nocturnal frogs,offers a rich source for investigations of visual ecology and physiological regulation of vision.
Cold induced changes of adenosine levels in common eelpout (Zoarces viviparus): a role in modulating cytochromecoxidase expression
Authors: Eckerle L. G. , Lucassen M. , Hirse T. , Pörtner H. O. 
Published: March 2008

SUMMARYExposure of ectothermic organisms to variations in temperatures causes a transient mismatch between energy supply and demand, which needs to be compensated for during acclimation. Adenosine accumulation from ATP breakdown indicates such an imbalance and its reversal reflects a restoration of energy status. We monitored adenosine levels in blood serum and liver of common eelpout (Zoarces viviparus) during cold exposure in vivo. Furthermore, we tested its effect on the pattern of thermal acclimation in hepatocytes isolated from cold- (4°C) versus warm- (11°C) exposed fish. Adenosine levels increased during cold exposure in vivo and reached a transient maximum after 24 h in serum, but remained permanently elevated in liver. Whole animal cold acclimation induced a rise of liver citrate synthase activity by 44±15%, but left cytochrome c oxidase activity (COX) and RNA expression of the respective genes unchanged. Cold incubation of hepatocytes from warm-acclimated fish failed to cause an increase of mitochondrial enzyme activities despite increased COX4 mRNA levels. Conversely, warm acclimation of hepatocytes from cold-acclimated fish reduced both enzyme activities and COX2 and COX4 mRNA levels by 26–37%. Adenosine treatment of both warm- and cold-acclimated hepatocytes suppressed COX activities but activated COX mRNA expression. These effects were not receptor mediated. The present findings indicate that adenosine has the potential to regulate mitochondrial functioning in vivo, albeit the pathways resulting in the contrasting effects on expression and activity need to be identified.