bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteolytic Activation of the 1918 Influenza Virus Hemagglutinin
Authors: Chaipan Chawaree , Kobasa Darwyn , Bertram Stephanie , Glowacka Ilona , Steffen Imke , Solomon Tsegaye Theodros , Takeda Makoto , Bugge Thomas H. , Kim Semi , Park Youngwoo , Marzi Andrea , Pöhlmann Stefan 
Published: January 2009

ABSTRACT
Proteolytic activation of the hemagglutinin (HA) protein is indispensable for influenza virus infectivity, and the tissue expression of the responsible cellular proteases impacts viral tropism and pathogenicity. The HA protein critically contributes to the exceptionally high pathogenicity of the 1918 influenza virus, but the mechanisms underlying cleavage activation of the 1918 HA have not been characterized. The neuraminidase (NA) protein of the 1918 influenza virus allows trypsin-independent growth in canine kidney cells (MDCK). However, it is at present unknown if the 1918 NA, like the NA of the closely related strain A/WSN/33, facilitates HA cleavage activation by recruiting the proprotease plasminogen. Moreover, it is not known which pulmonary proteases activate the 1918 HA. We provide evidence that NA-dependent, trypsin-independent cleavage activation of the 1918 HA is cell line dependent and most likely plasminogen independent since the 1918 NA failed to recruit plasminogen and neither exogenous plasminogen nor the presence of the A/WSN/33 NA promoted efficient cleavage of the 1918 HA. The transmembrane serine protease TMPRSS4 was found to be expressed in lung tissue and was shown to cleave the 1918 HA. Accordingly, coexpression of the 1918 HA with TMPRSS4 or the previously identified HA-processing protease TMPRSS2 allowed trypsin-independent infection by pseuodotypes bearing the 1918 HA, indicating that these proteases might support 1918 influenza virus spread in the lung. In summary, we show that the previously reported 1918 NA-dependent spread of the 1918 influenza virus is a cell line-dependent phenomenon and is not due to plasminogen recruitment by the 1918 NA. Moreover, we provide evidence that TMPRSS2 and TMPRSS4 activate the 1918 HA by cleavage and therefore may promote viral spread in lung tissue.
UNIVERSAL LOW/MEDIUM SPEED I2C-SLAVE TRANSCEIVER: A DETAILED FPGA IMPLEMENTATION
Authors: OUDJIDA A. K. , LIACHA A. , BENAMROUCHE D. , GOUDJIL M. , TIAR R. , OUCHABANE A. 
Published: January 2009

Based on a recent market study of an important number of I2C devices, all fully compliant with the Philips I2C-bus specification, version 2.1, release January 2000, this paper introduces a detailed I2C-slave VLSI-architecture that incorporates all necessary features required by modern ASIC/SoC applications, except high speed mode. The design is a general purpose solution offering viable ways to controlling I2C-bus and highly flexible to suit any particular needs. The purpose of this paper is to provide a full description of an up-to-date I2C-slave FPGA implementation. All related issues, starting from the elaboration of initial specifications, till the final verifications and synthesis, are comprehensively discussed and justified. This includes all issues from basic architectural operations to final software drivers and application. The whole design code, either for synthesis or verification, is implemented in Verilog 2001 (IEEE 1365). The synthesis design code is technology independent and was simulated at both RTL and gate level with timing back annotation using ModelSim SE 5.8e and synthesized using both Leonardo Spectrum V2001_1d.45 and Xilinx's XST 6.1i.
Pedometer step counts in individuals with neurological conditions
Authors: Elsworth Charlotte , Dawes Helen , Winward Charlotte , Howells Ken , Collett Johnny , Dennis Andrea , Sackley Catherine , Wade Derick 
Published: January 2009

Objective: To examine the accuracy of measuring step counts using a pedometer in participants with neurological conditions and healthy volunteers in relation to a manual step count tally. Setting: Oxford Centre for Enablement, Nuffield Orthopaedic Centre NHS Trust, Oxford, UK. Subjects: Healthy adults (n = 13, age: mean 29, SD = 12) and adults with neurological conditions (n=20 stroke, n=16 multiple sclerosis, n=5 muscular dystrophy, n=1 spinal cord injury, n=1 traumatic brain injury; age: mean 54, SD=13). Main measures: Individuals walked for 2 minutes at self-selected walking speeds (SSWS) wearing a pedometer. Healthy individuals were then asked to walk at slow walking speeds (SWS). Step counts were recorded manually and using a pedometer. Results: In healthy individuals there was no difference between manually measured and pedometer counts during walking (P>0.05). In adults with neurological conditions the pedometers undercounted (P = 0.003); bias (random error): 27 (111); percentage variability 30% and intraclass correlation coefficient (ICC) 0.66. In neurological adults, from regression analysis the relationship between error and walking speed was cubic, with walking speed accounting for 29% of pedometer error. Healthy individuals showed greater variability and undercounting at SWS bias (random error): 10 (31), percentage variability 8% and ICC 0.73, compared with SSWS bias (random error): —3 (13), percentage variability 3% and ICC 0.84. Conclusions: Pedometers may undercount when used for people with neurological conditions. There may be variability in pedometer accuracy but this was not strongly related to walking speed. The suitability of pedometer use for exercise monitoring should be individually determined.
Large-scale inference of the point mutational spectrum in human segmental duplications
Authors: Nakken Sigve , Rødland Einar A , Rognes Torbjørn , Hovig Eivind 
Published: January 2009

Abstract

Background
Recent segmental duplications are relatively large (≥ 1 kb) genomic regions of high sequence identity (≥ 90%). They cover approximately 4–5% of the human genome and play important roles in gene evolution and genomic disease. The DNA sequence differences between copies of a segmental duplication represent the result of various mutational events over time, since any two duplication copies originated from the same ancestral DNA sequence. Based on this fact, we have developed a computational scheme for inference of point mutational events in human segmental duplications, which we collectively term duplication-inferred mutations (DIMs). We have characterized these nucleotide substitutions by comparing them with high-quality SNPs from dbSNP, both in terms of sequence context and frequency of substitution types.

Results
Overall, DIMs show a lower ratio of transitions relative to transversions than SNPs, although this ratio approaches that of SNPs when considering DIMs within most recent duplications. Our findings indicate that DIMs and SNPs in general are caused by similar mutational mechanisms, with some deviances at the CpG dinucleotide. Furthermore, we discover a large number of reference SNPs that coincide with computationally inferred DIMs. The latter reflects how sequence variation in duplicated sequences can be misinterpreted as ordinary allelic variation.

Conclusion
In summary, we show how DNA sequence analysis of segmental duplications can provide a genome-wide mutational spectrum that mirrors recent genome evolution. The inferred set of nucleotide substitutions represents a valuable complement to SNPs for the analysis of genetic variation and point mutagenesis.
Delayed transfer of care from NHS secondary care to primary care in England: its determinants, effect on hospital bed days, prevalence of acute medical conditions and deaths during delay, in older adults aged 65 years and over
Authors: Jasinarachchi Krishantha H , Ibrahim Ibrahim R , Keegan Breffni C , Mathialagan Rajaratnam , McGourty John C , Phillips James RN , Myint Phyo K 
Published: January 2009

Abstract

Background
The delay in discharge or transfer of care back to the community following an acute admission to the hospital in older adults has long been a recognized challenge in the UK. We examined the determinants and outcomes of delayed transfer of care in older adults.

Methods
A prospective observational study was conducted in a district general hospital with a catchment population of 250,000 in England, UK. Those >= 65 years admitted to two care of the elderly wards during February 2007 were identified and prospectively followed-up till their discharge. Data was presented descriptively.

Results
36.7% (58/158) of patients had a delay in transfer of care. They tended to be older, had poorer pre-morbid mobility, and were more likely to be confused at the time of admission. Compared to the 2003 National Audit Report, a significantly higher percentage (29.3%vs.17%) awaited therapist assessments or (27.6%vs.9%) domiciliary care, with a lower percentage (< 1%vs.14%) awaiting further NHS care. Of 18 in-patient deaths, five occurred during the delay. Seven patients developed medical conditions during the delay making them unfit for discharge. The number of extra bed days attributable to delayed discharges in this study was 682 (mean = 4.8) days.

Conclusion
Awaiting therapy and domiciliary care input were significant contributing factors in delayed transfer of care. Similar local assessments could provide valuable information in identifying areas for improvement. Based on available current evidence, efficacy driven changes to the organisation and provision of support, for example rapid response delayed discharge services at the time of "fit to discharge" may help to improve the situation.
A genome-wide genetic signature of Jewish ancestry perfectly separates individuals with and without full Jewish ancestry in a large random sample of European Americans
Authors: Need Anna C , Kasperavičiūtė Dalia , Cirulli Elizabeth T , Goldstein David B 
Published: January 2009

Abstract
Background
It was recently shown that the genetic distinction between self-identified Ashkenazi Jewish and non-Jewish individuals is a prominent component of genome-wide patterns of genetic variation in European Americans. No study however has yet assessed how accurately self-identified (Ashkenazi) Jewish ancestry can be inferred from genomic information, nor whether the degree of Jewish ancestry can be inferred among individuals with fewer than four Jewish grandparents.

Results
Using a principal components analysis, we found that the individuals with full Jewish ancestry formed a clearly distinct cluster from those individuals with no Jewish ancestry. Using the position on the first principal component axis, every single individual with self-reported full Jewish ancestry had a higher score than any individual with no Jewish ancestry.

Conclusions
Here we show that within Americans of European ancestry there is a perfect genetic corollary of Jewish ancestry which, in principle, would permit near perfect genetic inference of Ashkenazi Jewish ancestry. In fact, even subjects with a single Jewish grandparent can be statistically distinguished from those without Jewish ancestry. We also found that subjects with Jewish ancestry were slightly more heterozygous than the subjects with no Jewish ancestry, suggesting that the genetic distinction between Jews and non-Jews may be more attributable to a Near-Eastern origin for Jewish populations than to population bottlenecks.
Crucial implication of protein kinase C (PKC)-δ, PKC-ζ, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils
Authors: Langlois Anick , Chouinard Francois , Flamand Nicolas , Ferland Claudine , Rola-Pleszczynski Marek , Laviolette Michel 
Published: January 2009

AbstractAsthma is associated with an eosinophil infiltration into the bronchial mucosa. 5-Oxo-6,8,11,14(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemotactic factor, activates cell motility, adherence, and proteolysis, notably, by promoting CD11b expression, matrix metalloproteinase (MMP)-9 secretion, and plasmin generation. We investigated the intracellular signaling pathways implicated in these various steps by using different, selective inhibitors. Human eosinophil migration through a reconstituted basement membrane in response to 5-oxo-ETE was greatly inhibited (≥72%) by the protein kinase C (PKC)-δ, PKC-ζ, ERK-1/2, and p38 inhibitors. Our findings indicate that PKC-δ mediates cell motility, CD11b expression, and MMP-9 granule release. PKC-ζ is also largely involved in eosinophil migration, although its specific targets remain undefined. ERK-1/2 and p38 modulate CD11b expression; ERK-1/2 is also involved in long-term MMP-9 secretion and p38 in the plasmin activation system. We demonstrated the crucial implication of PKC-δ, PKC-ζ, ERK-1/2, and p38 in human blood eosinophil migration through extracellular matrix components. Targeting specific pathways may have therapeutic potential for the treatment of allergic airway inflammation.
The mechanism involved in the repression of the μ opioid receptor gene expression in CEM ×174 cells infected by simian immunodeficiency virus
Authors: Liu Han , Li Hui , Guo Liyuan , Li Chaoying , Li Mengsen , Jiang Wei , Liu Xinhua , McNutt Michael A , Li Gang 
Published: January 2009

AbstractMorphine can promote the pathogenesis of human acquired immunodeficiency syndrome through binding to the μ opioid receptor (MOR) in immune cells. Previous investigation has suggested that expression of the MOR gene in lymphocytes is triggered by cooperative interaction between transcription factors, specificity protein 1 (Sp1) and Ying Yang 1 (YY1), in the promoter region. However, the specific molecular mechanism by which immunodeficiency virus infection impacts regulation of the MOR gene expression in lymphocytes is still unclear. In this study, it was demonstrated that SIV (SIVmac239) infection may result in gradual reduction of the MOR gene expression and Sp1 during a period of 48 h postinfection by analysis of quantitative real-time RT-PCR and Western blotting. The results of methylation-specific PCR showed that two of 14 CpG islands adjacent to the Sp1 and YY1 elements in the promoter region were methylated, which together with reduced Sp1, contributed to the failure of interaction of Sp1 with YY1 and their binding to the elements, as determined by coimmunoprecipitation, chromatin immunoprecipitation-real-time PCR, and EMSAs. The repression of the MOR gene secondary to SIVmac239 infection could be abolished by the demethylating agent 5-aza-2′-deoxycytidine. Transfection with Sp1-expressing vector (PN3-Sp1) was also able to enhance the activity of the promoter in SIVmac239-infected cells. We therefore concluded that aberrant methylation of the promoter and reduction of Sp1 resulting from SIVmac239 infection led to the silencing of the MOR gene. This finding will be helpful in understanding the synergistic mechanism of HIV infection and morphine addiction in the pathogenesis of AIDS.
Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan
Authors: Bibeau Frédéric , Lopez-Crapez Evelyne , Di Fiore Frédéric , Thezenas Simon , Ychou Marc , Blanchard France , Lamy Aude , Penault-Llorca Frédérique , Frébourg Thierry , Michel Pierre , Sabourin Jean-Christophe , Boissière-Michot Florence 
Published: January 2009

Purpose The antiepidermal growth factor receptor antibody cetuximab shows activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in wild-type KRAS tumors. Cetuximab may also exert antitumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion interacts with Fc receptors (FcγRs) expressed by immune cells. ADCC is influenced by FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms that are clinically relevant in follicular lymphoma and metastatic breast cancer treated with rituximab and trastuzumab, respectively. We investigated the association of FcγR polymorphisms and KRAS mutation with the outcome of irinotecan-refractory mCRC patients treated with cetuximab plus irinotecan. Patients and Methods Tumor and normal tissues from 69 patients were screened for KRAS mutations using a sensitive multiplex assay and genotyped for FcγRIIa and FcγRIIIa polymorphisms by direct sequencing and multiplex allele-specific polymerase chain reaction, respectively. The results were correlated with response and progression-free survival (PFS). Results KRAS mutations were associated with lower response rate (4% v 27% in nonmutated patients; P = .021) and shorter PFS (3.0 v 5.3 months; P = .021). Patients with FcγRIIa-131H/H and/or FcγIIIa-158V/V genotypes had longer PFS than 131R and 158F carriers (5.5 v 3.0 months; P = .005). The difference remained significant for mutated-KRAS patients. By multivariate analysis, KRAS mutation and FcγR combined status were independent risk factors for PFS. Conclusion Combined FcγRIIa/FcγRIIIa polymorphisms are prognostic factors for disease progression in mCRC patients treated with cetuximab plus irinotecan. As these polymorphisms are also clinically relevant in mutated-KRAS mCRC, an important role of ADCC in cetuximab efficacy is presumed.
Evaluation of Screening Instruments for Cancer-Related Fatigue Syndrome in Breast Cancer Survivors
Authors: Alexander Susanna , Minton Ollie , Stone Patrick C. 
Published: January 2009

Purpose Cases of cancer-related fatigue syndrome (CRFS) can be reliably indentified using a diagnostic interview combined with a structured psychiatric interview. However, these interviews are time consuming to conduct, require specialist training, and are not suitable for routine clinical use. The purpose of this study was to identify whether a screening questionnaire could identify patients at high risk of clinically significant fatigue who should be considered for a suitable intervention. Patients and Methods The diagnostic interview for CRFS and the structured clinical interview for the diagnostic and statistical manual of mental disorders were used in order to identify breast cancer survivors who fulfilled the criteria for CRFS. Two fatigue questionnaires (the Bidimensional Fatigue Scale [BFS] and the Functional Assessment of Cancer Therapy-Fatigue subscale [FACT-F]) were administered in order to determine their screening properties. Results Two hundred women were interviewed and 60 women fulfilled the criteria for CRFS. The BFS cutoff score of 11 had a sensitivity of 92%, a specificity of 53%, a positive predictive value (PPV) of 46%, and a negative predictive value (NPV) of 94%. The FACT-F cutoff score of 36 had a sensitivity of 80%, a specificity of 71%, a PPV of 55%, and a NPV of 89%. Conclusion The BFS and FACT-F cutoff scores can be used to identify breast cancer survivors at higher risk of clinically significant ongoing post treatment fatigue. Neither scale can be used as a diagnostic instrument for CRFS.
Phase II Study of Capecitabine and Oxaliplatin for Advanced Adenocarcinoma of the Small Bowel and Ampulla of Vater
Authors: Overman Michael J. , Varadhachary Gauri R. , Kopetz Scott , Adinin Rosni , Lin E. , Morris Jeffrey S. , Eng Cathy , Abbruzzese James L. , Wolff Robert A. 
Published: January 2009

Purpose Adenocarcinomas of the small bowel and ampulla of Vater represent rare cancers that have limited data regarding first-line therapy. We conducted a phase II trial to evaluate the benefit of capecitabine in combination with oxaliplatin (CAPOX) in patients with advanced adenocarcinoma of small bowel or ampullary origin. Patients and Methods Eligible patients with metastatic or unresectable tumors and no prior systemic chemotherapy for advanced disease participated in this phase II trial. CAPOX was administered as a 21-day cycle with oxaliplatin 130 mg/m2 on day 1 and capecitabine 750 mg/m2 twice a day on days 1 through 14. The primary end point was overall response rate as assessed by Response Evaluation Criteria in Solid Tumors. Results Thirty-one patients were enrolled onto the study, and 30 patients received study treatment. The confirmed overall response rate was 50%; three patients with metastatic disease achieved complete responses. The median time to progression (TTP) was 11.3 months, and the median overall survival (OS) was 20.4 months. Subset analysis of patients with metastatic disease only (n = 25) revealed a median TTP of 9.4 months and median OS of 15.5 months. The most common grades 3 or 4 toxicities included fatigue (30%), peripheral neuropathy (10%), vomiting (10%), diarrhea (10%), and neutropenia (10%). Conclusion When administered to patients with good performance status, CAPOX is well tolerated and produces a superior response rate and longer OS compared with other regimens in the literature. CAPOX should be considered a new standard regimen for advanced small bowel and ampullary adenocarcinomas.
Symptoms of depression in non‐routine caregivers: The role of caregiver strain and burden
Authors: Phillips Anna C. , Gallagher Stephen , Hunt Kate , Der Geoff , Carroll Douglas 
Published: January 2009

Objectives. The origins and persistence of psychological morbidity in caregivers are not fully understood. The present analysis examined the relationship between the strain and burden of caregiving and depression and anxiety in a large community sample. Social support and sleep quality were investigated as potential mediators.Design. Cross‐sectional and prospective observational study.Method. Individuals caring for someone other than their own child (N=393) were identified from a population of 2,079. Caregiving strain and burden, social support, and sleep quality were assessed. Participants completed the hospital anxiety and depression scale at the same time and 5 years later.Results. Caregiving strain and burden were associated with depression and anxiety symptoms cross‐sectionally, and with a worsening of symptoms 5 years later. Sleep quality appeared to mediate the cross‐sectional relationships.Conclusions. The demands of caregiving and associated sleep disruption contribute to symptoms of depression and anxiety in caregivers.