bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis
Authors: Murray Fiona , Darzentas Nikos , Hadzidimitriou Anastasia , Tobin Gerard , Boudjogra Myriam , Scielzo Cristina , Laoutaris Nikolaos , Karlsson Karin , Baran-Marzsak Fanny , Tsaftaris Athanasios , Moreno Carol , Anagnostopoulos Achilles , Caligaris-Cappio Federico , Vaur Dominique , Ouzounis Christos , Belessi Chrysoula , Ghia Paolo , Davi Fred , Rosenquist Richard , Stamatopoulos Kostas 
Published: October 2007

AbstractSomatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, “stereotyped” amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are underrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).
Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7− lympho-myeloid thymic progenitors
Authors: Hao Qian-Lin , George Aswathi A. , Zhu Judy , Barsky Lora , Zielinska Ewa , Wang Xiuli , Price Mary , Ge Shundi , Crooks Gay M. 
Published: October 2007

AbstractThe identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34+lin− thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1% to 2% of progenitors are CD7−. CD34+lin− thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid, and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, that is, the CD7hi fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7int (CD10+) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7− fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34+lin−CD7− thymocytes also expressed early T lymphoid genes Tdt, pTα, and IL-7Rα and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated on arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7− lympho-myeloid thymic progenitor.
Cost-effectiveness analysis of guidelines for antihypertensive care in Finland
Authors: Booth Neill , Jula Antti , Aronen Pasi , Kaila Minna , Klaukka Timo , Kukkonen-Harjula Katriina , Reunanen Antti , Rissanen Pekka , Sintonen Harri , Mäkelä Marjukka 
Published: October 2007

AbstractBackgroundHypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).MethodsA decision analytic model compares the ACCG and PCP scenarios using information synthesised from a set of national registers covering prescription drug reimbursements, morbidity, and mortality with data from two national surveys concerning health and functional capacity. Statistical methods are used to estimate model parameters from Finnish data. We model the potential impact of the different treatment strategies under the ACCG and PCP scenarios, such as lifestyle counselling and drug therapy, for subgroups stratified by age, gender, and blood pressure. The model provides estimates of the differences in major health-related outcomes in the form of life-years and costs as calculated from a 'public health care system' perspective. Cost-effectiveness analysis results are presented for subgroups and for the target population as a whole.ResultsThe impact of the use of the ACCG scenario in subgroups (aged 40–80) without concomitant cardiovascular and related diseases is mainly positive. Generally, costs and life-years decrease in unison in the lowest blood pressure group, while in the highest blood pressure group costs and life-years increase together and in the other groups the ACCG scenario is less expensive and produces more life-years. When the costs and effects for subgroups are combined using standard decision analytic aggregation methods, the ACCG scenario is cost-saving and more effective.ConclusionThe ACCG scenario is likely to reduce costs and increase life-years compared to the PCP scenario in many subgroups. If the estimated trade-offs between the subgroups in terms of outcomes and costs are acceptable to decision-makers, then widespread implementation of the ACCG scenario is expected to reduce overall costs and be accompanied by positive outcomes overall.
The implementation of the Medical Regulation Office and Mobile Emergency Attendance System and its impact on the gravity profile of non-traumatic afflictions treated in a University Hospital: a research study
Authors: Lopes Sérgio LB , dos Santos José Sebastião , Scarpelini Sandro 
Published: October 2007

Abstract
Background
The public health system of Brazil is structured by a network of increasing complexity, but the low resolution of emergency care at pre-hospital units and the lack of organization of patient flow overloaded the hospitals, mainly the ones of higher complexity. The knowledge of this phenomenon induced Ribeirão Preto to implement the Medical Regulation Office and the Mobile Emergency Attendance System. The objective of this study was to analyze the impact of these services on the gravity profile of non-traumatic afflictions in a University Hospital.

Methods
The study conducted a retrospective analysis of the medical records of 906 patients older than 13 years of age who entered the Emergency Care Unit of the Hospital of the University of São Paulo School of Medicine at Ribeirão Preto. All presented acute non-traumatic afflictions and were admitted to the Internal Medicine, Surgery or Neurology Departments during two study periods: May 1996 (prior to) and May 2001 (after the implementation of the Medical Regulation Office and Mobile Emergency Attendance System). Demographics and mortality risk levels calculated by Acute Physiology and Chronic Health Evaluation II (APACHE II) were determined.

Results
From 1996 to 2001, the mean age increased from 49 ± 0.9 to 52 ± 0.9 (P = 0.021), as did the percentage of co-morbidities, from 66.6 to 77.0 (P = 0.0001), the number of in-hospital complications from 260 to 284 (P = 0.0001), the mean calculated APACHE II mortality risk increased from 12.0 ± 0.5 to 14.8 ± 0.6 (P = 0.0008) and mortality rate from 6.1 to 12.2 (P = 0.002). The differences were more significant for patients admitted to the Internal Medicine Department.

Conclusion
The implementation of the Medical Regulation and Mobile Emergency Attendance System contributed to directing patients with higher gravity scores to the Emergency Care Unit, demonstrating the potential of these services for hierarchical structuring of pre-hospital networks and referrals.
Diabetes and pre-diabetes are associated with cardiovascular risk factors and carotid/femoral intima-media thickness independently of markers of insulin resistance and adiposity
Authors: Faeh David , William Julita , Yerly Patrick , Paccaud Fred , Bovet Pascal 
Published: October 2007

Abstract

Background
Impaired glucose regulation (IGR) is associated with detrimental cardiovascular outcomes such as cardiovascular disease risk factors (CVD risk factors) or intima-media thickness (IMT). Our aim was to examine whether these associations are mediated by body mass index (BMI), waist circumference (waist) or fasting serum insulin (insulin) in a population in the African region.

Methods
Major CVD risk factors (systolic blood pressure, smoking, LDL-cholesterol, HDL-cholesterol,) were measured in a random sample of adults aged 25–64 in the Seychelles (n = 1255, participation rate: 80.2%).
According to the criteria of the American Diabetes Association, IGR was divided in four ordered categories: 1) normal fasting glucose (NFG), 2) impaired fasting glucose (IFG) and normal glucose tolerance (IFG/NGT), 3) IFG and impaired glucose tolerance (IFG/IGT), and 4) diabetes mellitus (DM). Carotid and femoral IMT was assessed by ultrasound (n = 496).

Results
Age-adjusted levels of the major CVD risk factors worsened gradually across IGR categories (NFG < IFG/NGT < IFG/IGT < DM), particularly HDL-cholesterol and blood pressure (p for trend < 0.001). These relationships were marginally attenuated upon further adjustment for waist, BMI or insulin (whether considered alone or combined) and most of these relationships remained significant. With regards to IMT, the association was null with IFG/NGT, weak with IFG/IGT and stronger with DM (all more markedly at femoral than carotid levels). The associations between IMT and IFG/IGT or DM (adjusted by age and major CVD risk factors) decreased only marginally upon further adjustment for BMI, waist or insulin. Further adjustment for family history of diabetes did not alter the results.

Conclusion
We found graded relationships between IGR categories and both major CVD risk factors and carotid/femoral IMT. These relationships were only partly accounted for by BMI, waist and insulin. This suggests that increased CVD-risk associated with IGR is also mediated by factors other than the considered markers of adiposity and insulin resistance. The results also imply that IGR and associated major CVD risk factors should be systematically screened and appropriately managed.
Mannitol as adjunct therapy for childhood cerebral malaria in Uganda: A randomized clinical trial
Authors: Namutangula Beatrice , Ndeezi Grace , Byarugaba Justus S , Tumwine James K 
Published: October 2007

Abstract

Background
Several reports have suggested that raised intracranial pressure (ICP) is a major contributor to death among children with cerebral malaria. Mannitol, an osmotic diuretic, effectively lowers ICP and is used to treat post-traumatic raised ICP. It is not clear whether intravenous mannitol given to children with cerebral malaria improves clinical outcome. The objective of this study was to determine the effect of mannitol as adjunct therapy on the clinical outcome of children with cerebral malaria.

Methods
This randomized double-blind placebo controlled clinical trial was carried out at the Emergency Paediatric ward of Mulago Hospital, Uganda's national referral and teaching hospital. One hundred and fifty six children aged 6 to 60 months with cerebral malaria were randomized to either one dose of mannitol 1 g/kg or placebo, in addition to intravenous quinine. Main outcome measures included coma recovery time; time to sit unsupported, begin oral intake; duration of hospitalization; death and adverse effects.

Results
Time to regain consciousness (p = 0.11), sit unsupported (p = 0.81), time to start oral intake (p = 0.13) and total coma duration (p = 0.07) were similar in both groups. There was no significant difference in the mortality between the placebo (13/80 or 16.3%) and mannitol (10/76 or 13.2%) groups: RR = 1.2 (CI 0.5–2.7). No adverse effects were observed after administration of mannitol.

Conclusion
Mannitol had no significant impact on clinical outcome of cerebral malaria. It is difficult to recommend intravenous mannitol as adjunct therapy for childhood cerebral malaria.

Clinical registration number
ClinicalTrials.gov ID: NCT00113854
Poor follow-up rates at a self-pay northern Indian tertiary AIDS clinic
Authors: Maru Duncan Smith-Rohrberg , Khakha Deepika C , Tahir Mohammad , Basu Sanjay , Sharma Surendra K 
Published: October 2007

Abstract

Background
In many developing countries, out-of-pocket payment remains a primary mechanism by which patients infected with HIV access treatment. In India, this has been changing as the National AIDS Control Organization (NACO) has been rolling out free antiretroviral therapy throughout the country since 2004. The vast majority of patients, however, remain without access to free medicines.

Methods
A retrospective chart review was performed on data obtained from a registry of ninety-three (93) patients attending a self-pay clinic at the All India Institute of Medical Sciences in Delhi, India. Multivariable Cox proportional hazard and logistic regression models were explored to assess the relationship between lost-to-follow-up status and the predictor variables: age, sex, household income, baseline CD4 count, and distance from clinic.

Results
Lost-to-follow-up rates were very high; 68% (63/93) were lost-to-follow-up till the time of chart review, including 59% (55/93) who were lost within one year. In both regression models, younger age, low baseline CD4 counts, and low income level were significantly associated with increased risk of lost-to-follow-up. Additionally, there was a significant interaction between income and CD4 counts. The patients with both low CD4 counts and low income level were more likely to be lost-to-follow-up than would be predicted by each covariable alone.

Conclusion
In this small cohort of AIDS patients attending a self-pay antiretroviral clinic at a large tertiary care center in Delhi, India, follow-up rates were quite poor. Poorer patients tended to present to clinic with more depressed CD4 counts and were less likely to be retained in care. These findings indicate that greater strides must be taken to improve the recruitment and retention of poor patients. The expansion of free antiretrovirals is one step among many necessary to achieve this objective.
Hepatitis B virus and hepatitis C virus in pregnant Sudanese women
Authors: Elsheikh Rasha M , Daak Ahmed A , Elsheikh Mohamed A , Karsany Mubarak S , Adam Ishag 
Published: October 2007

AbstractBackgroundThe epidemiology of viral hepatitis during pregnancy is essential for health planners and programme managers. While much data exist concerning viral hepatitis during pregnancy in many African countries, no proper published data are available in Sudan.AimThe study aimed to investigate the sero-prevalance and the possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) among antenatal care attendants in central Sudan.MethodsDuring 3 months from March–June 2006, sera were collected from pregnant women at Umdurman Maternity Hospital in Sudan, and they were tested for markers of hepatitis B virus (HBVsAg) and HCV.ResultsHBVsAg was detected in 41 (5.6%) out 728 women, Anti-HCV was detected in 3 (0.6%) out of 423 women, all of them were not aware of their condition. Age, parity, gestational age, residence, history of blood transfusion, dental manipulations, tattooing and circumcision did not contribute significantly to increased HBVsAg sero-positivity.ConclusionThus 5.6% of pregnant women were positive for HBVsAg irrespective of their age, parity and socio-demographic characteristics. There was low prevalence of Anti-HCV.
Nucleocapsid formation and RNA synthesis of Marburg virus is dependent on two coiled coil motifs in the nucleoprotein
Authors: DiCarlo Andrea , Möller Peggy , Lander Angelika , Kolesnikova Larissa , Becker Stephan 
Published: October 2007

Abstract
The nucleoprotein (NP) of Marburg virus (MARV) is responsible for the encapsidation of viral genomic RNA and the formation of the helical nucleocapsid precursors that accumulate in intracellular inclusions in infected cells. To form the large helical MARV nucleocapsid, NP needs to interact with itself and the viral proteins VP30, VP35 and L, which are also part of the MARV nucleocapsid. In the present study, a conserved coiled coil motif in the central part of MARV NP was shown to be an important element for the interactions of NP with itself and VP35, the viral polymerase cofactor. Additionally, the coiled coil motif was essential for the formation of NP-induced intracellular inclusions and for the function of NP in the process of transcription and replication of viral RNA in a minigenome system. Transfer of the coiled coil motif to a reporter protein was sufficient to mediate interaction of the constructed fusion protein with the N-terminus of NP. The coiled coil motif is bipartite, constituted by two coiled coils which are separated by a flexible linker.
Phylogenetic simulation of promoter evolution: estimation and modeling of binding site turnover events and assessment of their impact on alignment tools
Authors: Huang Weichun , Nevins Joseph R , Ohler Uwe 
Published: October 2007

Abstract
Background
The phenomenon of functional site turnover has important implications for the study of regulatory region evolution, such as for promoter sequence alignments and transcription factor binding site (TFBS) identification. At present, it remains difficult to estimate TFBS turnover rates on real genomic sequences, as reliable mappings of functional sites across related species are often not available. As an alternative, we introduce a flexible new simulation system, Phylogenetic Simulation of Promoter Evolution (PSPE), designed to study functional site turnovers in regulatory sequences.

Results
Using PSPE, we study replacement turnover rates of different individual TFBSs and simple modules of two sites under neutral evolutionary functional constraints. We find that TFBS replacement turnover can happen rapidly in promoters, and turnover rates vary significantly among different TFBSs and modules. We assess the influence of different constraints such as insertion/deletion rate and translocation distances. Complementing the simulations, we give simple but effective mathematical models for TFBS turnover rate prediction. As one important application of PSPE, we also present a first systematic evaluation of multiple sequence aligners regarding their capability of detecting TFBSs in promoters with site turnovers.

Conclusion
PSPE allows researchers for the first time to investigate TFBS replacement turnovers in promoters systematically. The assessment of alignment tools points out the limitations of current approaches to identify TFBSs in non-coding sequences, where turnover events of functional sites may happen frequently, and where we are interested in assessing the similarity on the functional level. PSPE is freely available at the authors' website.
Quality of Life in Cured Patients with Differentiated Thyroid Carcinoma
Authors: Hoftijzer Hendrieke C. , Heemstra Karen A. , Corssmit Eleonora P. M. , van der Klaauw Agatha A. , Romijn Johannes A. , Smit Johannes W. A. 
Published: October 2007

Abstract
Objective: This study was performed to evaluate the impact of cured differentiated thyroid carcinoma (DTC) on quality of life. Previous studies on quality of life in patients with DTC were hampered by small patient numbers or limited quality-of-life parameters or were uncontrolled.
Design: This was a cross-sectional case-control study.
Method: We assessed quality of life in 153 cured DTC patients with a median duration of cure of 6.34 yr (range 0.3–41.8) and studied the contribution of disease-specific, biochemical, and social variables, focusing on the degree of TSH suppression. Four validated health-related questionnaires were used (Short Form-36, Multidimensional Fatigue Index-20, Hospital Anxiety and Depression Scale, and Somatoform Disorder Questionnaire), including multiple aspects of physical, psychological, and social functioning. Patients were compared with 113 controls selected by patients themselves (control group I) and 336 pooled age- and gender-matched controls from other Leiden quality-of-life studies (control group II).
Results: Patients had significantly decreased quality of life in 11 of 16 subscales when compared with control group I. In comparison with control group II, decreased scores in 13 of 16 items were observed. An important independent predictor for quality of life was duration of cure. Quality-of-life parameters were not influenced by serum TSH levels both measured at the time of quality-of-life assessment and measured over time since initial therapy.
Conclusions: Patients cured for DTC have impaired quality of life, independently of TSH level. Quality-of-life parameters were inversely affected by duration of cure and consequently may be restored after prolonged follow-up.
Differences in Free Estradiol and Sex Hormone-Binding Globulin in Women with and without Premenstrual Dysphoric Disorder
Authors: Thys-Jacobs Susan , McMahon Don , Bilezikian John P. 
Published: October 2007

Abstract
Context: Over the years, different hypotheses involving the ovarian steroid hormones have been proposed to explain the luteal phase occurrence of severe premenstrual syndrome symptoms. Although it had been strongly suspected that differences in the concentrations of the ovarian steroids may underlie the mood and psychological imbalance of this disorder, the evidence for this hypothesis has been inconsistent and remains controversial.
Objective: Our objective was to measure the ovarian steroid hormones across the menstrual cycle in women with and without luteal phase symptoms consistent with premenstrual dysphoric disorder (PMDD).
Design: We measured estradiol (E2), progesterone, and SHBG in women with and without PMDD using a cross-sectional and prospective experimental design. Participating women underwent 2-month self-assessment symptom screening and 1-month hormonal evaluation.
Results: Overall means for LH, progesterone, E2, peak E2, and free E2 were not different between groups. Across the menstrual cycle, overall percent free E2 was significantly lower and SHBG significantly greater in the PMDD group compared with controls (1.39 ± 0.26 vs. 1.50 ± 0.28, P = 0.03; 61.4 ± 25.1 vs. 52.4 ± 21.3 nmol/liter, P = 0.046, respectively). During the luteal phase, free E2 was significantly lower in the PMDD group compared with controls (PMDD 7.6 ± 7.0 vs. controls 8.9 ± 8.4 pmol/liter; P = 0.032). For both follicular and luteal phases, SHBG was significantly higher in the PMDD group (follicular phase 60.5 ± 31.7 vs. 51.4 ± 38.2 nmol/liter, P = 0.047; luteal phase 65.1 ± 32.3 vs. 55.1 ± 38.9 nmol/liter, P =0.03). In both groups, SHBG significantly increased from the follicular to luteal phase.
Conclusion: Luteal phase concentrations of free E2, percent free E2, and SHBG differ significantly between women with and without PMDD.