bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemoglobinopathies: genetic and clinical aspects with an impact on blood transfusion
Authors: Politis C. 
Published: May 2013

The haemoglobinopathies are autosomal recessive genetic disorders resulting in qualitative or quantitative change in the haemoglobin (Hb) molecule. HbS, the most widespread structural haemoglobin variant, hinders microcirculation by causing a sickle shape of red cells. In sickle cell disease, blood transfusion should be done only for strict indications. In thalassaemias, Hb synthesis is impeded by defective production of globin chains. The commonest types of clinical importance are α‐, βδ‐ and β‐thalassaemia. Compound heterozygotes for thalassaemia and Hb variants may have varying clinical impact.Morbidity is related to the anaemia, complications of blood transfusions including iron overload and transfusion transmissible infections, and splenectomy.Treatment of homozygous β‐thalassaemia is based on regular blood transfusion from early childhood, placing a major workload for blood transfusion services. Stringent quality measures are necessary to ensure that the transfused product meets requirements.Greece's national registry records 4,506 thalassaemia major and intermedia, “Η” haemoglobinopathy and sickle cell disease patients. Thalassaemia patients consume 18% of total RBC supply. Incidence of transfusion associated adverse reactions is 250:100 000 units of RBCs. Allergic (87.6:100 000) and NHFTR (89.9:100 000) are most common. One sickle thalassaemia patient died of hyperhaemolysis syndrome. Eight patients died of HCV hepatocellular carcinoma. HIV was transmitted to one patient during the window period.
Draft Genome Sequence of the Deep-Sea Bacterium Shewanella benthica Strain KT99
Authors: Lauro F. M. , Chastain R. A. , Ferriera S. , Johnson J. , Yayanos A. A. , Bartlett D. H. 
Published: May 2013

ABSTRACT

We report the draft genome sequence of the obligately piezophilic
Shewanella benthica
strain KT99 isolated from the abyssal South Pacific Ocean. Strain KT99 is the first piezophilic isolate from the Tonga-Kermadec trench, and its genome provides many clues on high-pressure adaptation and the evolution of deep-sea piezophilic bacteria.
Identification of Starling Circovirus in an Estuarine Mollusc (
Amphibola crenata
) in New Zealand Using Metagenomic Approaches
Authors: Dayaram Anisha , Goldstien Sharyn , Zawar-Reza Peyman , Gomez Christopher , Harding Jon S. , Varsani Arvind 
Published: May 2013

ABSTRACT

Two complete genomes of starling circovirus (StCV) were recovered from
Amphibola crenata
, an estuarine New Zealand mollusc. This is the first report of StCV outside Europe. The viral genomes were recovered from rolling circle-amplified enriched circular DNA followed by back-to-back primers and specific primer PCR amplification.
Genome Sequence of the Polycyclic Aromatic Hydrocarbon-Degrading Bacterium Strain
Marinobacter nanhaiticus
D15-8W
T
Authors: Cui Zhisong , Gao Wei , Li Qian , Xu Guangsu , Zheng Li 
Published: May 2013

ABSTRACT

Marinobacter nanhaiticus
strain D15-8W
T
was isolated from a phenanthrene-degrading consortium, enriched from sediment of the South China Sea. Here, we present the draft genome of strain D15-8W
T
, which contains 5,358,309 bp with a G+C content of 58.53% and contains 4,829 protein-coding genes and 47 tRNA genes.
Complete Genome Sequence of the Deep-Sea Bacterium
Psychromonas
Strain CNPT3
Authors: Lauro F. M. , Stratton T. K. , Chastain R. A. , Ferriera S. , Johnson J. , Goldberg S. M. D. , Yayanos A. A. , Bartlett D. H. 
Published: May 2013

ABSTRACT

Members of the genus
Psychromonas
are commonly found in polar and deep-sea environments. Here we present the genome of
Psychromonas
strain CNPT3. Historically, it was the first bacterium shown to piezoregulate the composition of its membrane lipids and to have a higher growth rate at 57 megapascals (MPa) than at 0.1 MPa.
Whole-Genome Draft Sequences of Three Multidrug-Resistant Klebsiella pneumoniae Strains Available from the American Type Culture Collection
Authors: Broberg Christopher A. , Palacios Michelle , Miller Virginia L. 
Published: May 2013

ABSTRACT

Infection with multidrug-resistant
Klebsiella pneumoniae
is a significant problem worldwide, requiring a better understanding of how various strains are able to defeat current antibiotic therapies and cause disease. Here, we report the draft genome sequences of three
K. pneumoniae
strains harboring the SHV-18, KPC-2, or NDM-1 β-lactamases.
Acupuncture for Treatment of Arthralgia Secondary to Aromatase Inhibitor Therapy in Women with Early Breast Cancer: Pilot Study
Authors: Oh B , Kimble B , Costa D S J , Davis E , McLean A , Orme K , Beith J 
Published: May 2013

Background Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain. Objective A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia. Methods A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6 weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6 weeks and 12 weeks, except for blood samples at baseline and 6 weeks only. Results No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA. Conclusions Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed.
Extracellular DNA in Pancreatic Cancer Promotes Cell Invasion and Metastasis
Authors: Wen Fushi , Shen Alex , Choi Andrew , Gerner Eugene W. , Shi Jiaqi 
Published: May 2013

Abstract
Aggressive metastasis is the chief cause of the high morbidity and mortality associated with pancreatic cancer, yet the basis for its aggressive behavior remains elusive. Extracellular DNA (exDNA) is a recently discovered component of inflammatory tissue states. Here, we report that exDNA is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. exDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells but absent from normal pancreas cells. Strikingly, treatment of cancer cell cultures with DNase I to degrade DNA nonspecifically reduced metastatic characters associated with matrix attachment, migration, and invasion. We further assessed the role of exDNA in pancreatic cancer metastasis in vivo using an orthotopic xenograft model established by implantation of pancreatic cancer cells expressing firefly luciferase. Noninvasive bioluminescent imaging confirmed that DNase I treatment was sufficient to suppress tumor metastasis. Mechanistic investigations suggested the existence of a positive feedback loop in which exDNA promotes expression of the inflammatory chemokine CXCL8, which leads to higher production of exDNA by pancreatic cancer cells, with a significant reduction in CXCL8 levels achieved by DNase I treatment. Taken together, our results strongly suggest that exDNA contributes to the highly invasive and metastatic character of pancreatic cancer. Cancer Res; 73(14); 4256–66. ©2013 AACR.
4-Hydroxytamoxifen Induces Autophagic Death through K-Ras Degradation
Authors: Kohli Latika , Kaza Niroop , Coric Tatjana , Byer Stephanie J. , Brossier Nicole M. , Klocke Barbara J. , Bjornsti Mary-Ann , Carroll Steven L. , Roth Kevin A. 
Published: May 2013

Abstract
Tamoxifen is widely used to treat estrogen receptor–positive breast cancer. Recent findings that tamoxifen and its derivative 4-hydroxytamoxifen (OHT) can exert estrogen receptor–independent cytotoxic effects have prompted the initiation of clinical trials to evaluate its use in estrogen receptor–negative malignancies. For example, tamoxifen and OHT exert cytotoxic effects in malignant peripheral nerve sheath tumors (MPNST) where estrogen is not involved. In this study, we gained insights into the estrogen receptor–independent cytotoxic effects of OHT by studying how it kills MPNST cells. Although caspases were activated following OHT treatment, caspase inhibition provided no protection from OHT-induced death. Rather, OHT-induced death in MPNST cells was associated with autophagic induction and attenuated by genetic inhibition of autophagic vacuole formation. Mechanistic investigations revealed that OHT stimulated autophagic degradation of K-Ras, which is critical for survival of MPNST cells. Similarly, we found that OHT induced K-Ras degradation in breast, colon, glioma, and pancreatic cancer cells. Our findings describe a novel mechanism of autophagic death triggered by OHT in tumor cells that may be more broadly useful clinically in cancer treatment. Cancer Res; 73(14); 4395–405. ©2013 AACR.
Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor Suppressor Mutations
Authors: Price Richard L. , Song Jieun , Bingmer Katherine , Kim Tae Hyong , Yi Ji-Yeun , Nowicki Michal O. , Mo Xiaokui , Hollon Todd , Murnan Eric , Alvarez-Breckenridge Christopher , Fernandez Soledad , Kaur Balveen , Rivera Andreana , Oglesbee Michael , Cook Charles , Chiocca E. Antonio , Kwon Chang-Hyuk 
Published: May 2013

Abstract
To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1loxP/+; Trp53−/+ genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans. Cancer Res; 73(11); 3441–50. ©2013 AACR.
Vinblastine Rapidly Induces NOXA and Acutely Sensitizes Primary Chronic Lymphocytic Leukemia Cells to ABT-737
Authors: Bates Darcy J.P. , Danilov Alexey V. , Lowrey Christopher H. , Eastman Alan 
Published: May 2013

Abstract
Proteins of the BCL2 family provide a survival mechanism in many human malignancies, including chronic lymphocytic leukemia (CLL). The BCL2 inhibitor ABT-263 (navitoclax) is active in clinical trials for lymphoid malignancies, yet resistance is expected on the basis of preclinical models. We recently showed that vinblastine can dramatically sensitize several leukemia cell lines to ABT-737 (the experimental congener of ABT-263). The goal of these experiments was to determine the impact of vinblastine on ABT-737 sensitivity in CLL cells isolated from peripheral blood and to define the underlying mechanism. Freshly isolated CLL cells from 35 patients, as well as normal lymphocytes and platelets, were incubated with various microtubule-disrupting agents plus ABT-737 to assess sensitivity to the single agents and the combination. ABT-737 and vinblastine displayed a range of sensitivity as single agents, and vinblastine markedly sensitized all CLL samples to ABT-737 within six hours. Vinblastine potently induced the proapoptotic protein PMAIP1 (NOXA) in both time- and dose-dependent manner and this was required for the observed apoptosis. Combretastatin A4, which dissociates microtubules by binding to a different site, had the same effect, confirming that interaction of these agents with microtubules is the initial target. Similarly, vincristine and vinorelbine induced NOXA and enhanced CLL sensitivity to ABT-737. Furthermore, vinblastine plus ABT-737 overcame stroma-mediated resistance to ABT-737 alone. Apoptosis was induced with clinically achievable concentrations with no additional toxicity to normal lymphocytes or platelets. These results suggest that vinca alkaloids may improve the clinical efficacy of ABT-263 in patients with CLL. Mol Cancer Ther; 12(8); 1504–14. ©2013 AACR.
Histone and DNA Methylation–Mediated Epigenetic Downregulation of Endothelial Kruppel-Like Factor 2 by Low-Density Lipoprotein Cholesterol
Authors: Kumar Ajay , Kumar Santosh , Vikram Ajit , Hoffman Timothy A. , Naqvi Asma , Lewarchik Christopher M. , Kim Young-Rae , Irani Kaikobad 
Published: May 2013

Objective—
Low-density lipoprotein (LDL) cholesterol induces endothelial dysfunction and is a major modifiable risk factor for coronary heart disease. Endothelial Kruppel-like Factor 2 (KLF2) is a transcription factor that is vital to endothelium-dependent vascular homeostasis. The purpose of this study is to determine whether and how LDL affects endothelial KLF2 expression.

Approach and Results—
LDL downregulates KLF2 expression and promoter activity in endothelial cells. LDL-induced decrease in KLF2 parallels changes in endothelial KLF2 target genes thrombomodulin, endothelial NO synthase, and plasminogen activator inhibitor-1. Pharmacological inhibition of DNA methyltransferases or knockdown of DNA methyltransferase 1 prevents downregulation of endothelial KLF2 by LDL. LDL induces endothelial DNA methyltransferase 1 expression and DNA methyltransferase activity. LDL stimulates binding of the DNA methyl-CpG–binding protein-2 and histone methyltransferase enhancer of zeste homolog 2, whereas decreases binding of the KLF2 transcriptional activator myocyte enhancing factor-2, to the KLF2 promoter in endothelial cells. Knockdown of myocyte enhancing factor-2, or mutation of the myocyte enhancing factor-2 site in the KLF2 promoter, abrogates LDL-induced downregulation of endothelial KLF2 and thrombomodulin, and KLF2 promoter activity. Similarly, knockdown of enhancer of zeste homolog 2 negates LDL-induced downregulation of KLF2 and thrombomodulin in endothelial cells. Finally, overexpression of KLF2 rescues LDL-induced clotting of platelet-rich plasma on endothelial cells.

Conclusions—
LDL represses endothelial KLF2 expression via DNA and histone methylation. Downregulation of KLF2 by LDL leads to a dysfunctional, hypercoagulable endothelium.
A Case-Controlled Comparison of Thrombolysis Outcomes Between Wake-Up and Known Time of Onset Ischemic Stroke Patients
Authors: Manawadu Dulka , Bodla Shankaranand , Jarosz Jozef , Keep Jeff , Kalra Lalit 
Published: May 2013

Background and Purpose—
Wake-up ischemic stroke (WUIS) patients are not thrombolysed even if they meet other criteria for treatment. We hypothesized that patients with WUIS showing no or early ischemic changes on brain imaging will have thrombolysis outcomes comparable with those with known time of symptom onset.

Methods—
Consecutive sampling of a prospective registry of patients with stroke between January 2009 and December 2010 identified 394 thrombolysed patients meeting predefined inclusion criteria, 326 presenting within 0 to 4.5 hours of symptom onset (Reference Group) and 68 WUIS patients. Inclusion criteria were last seen normal <12 hours or >4.5 hours (WUIS) or presented <4.5 hours (Reference Group), had National Institutes of Health Stroke Scale score ≥5, and no or early ischemic changes on imaging at presentation. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days measured by trained assessors blinded to patient grouping. Other outcome measures were symptomatic intracerebral hemorrhage, modified Rankin Scale 0 to 1, and mortality at 90 days.

Results—

The groups were comparable for mean age (72.8 versus 73.9 years;
P
=0.58) and baseline median National Institutes of Health Stroke Scale score (median 13 versus 12;
P
=0.34). The proportions of patients with modified Rankin Scale 0 to 2 (38% versus 37%;
P
=0.89) and modified Rankin Scale 0 to 1 (24% versus 16%;
P
=0.18) at 90 days, any ICH (20% versus 22%;
P
=0.42) and symptomatic intracerebral hemorrhage (3.4% versus 2.9%;
P
=1.0) were comparable after adjusting for age, stroke severity, and imaging changes. Only 9/394 (2%) patients were lost to follow-up.

Conclusions—
Thrombolysis in selected patients with WUIS is feasible, and its outcomes are comparable with those thrombolysed with 0 to 4.5 hours.
Very Low Cerebral Blood Volume Predicts Parenchymal Hematoma in Acute Ischemic Stroke
Authors: Hermitte Laure , Cho Tae-Hee , Ozenne Brice , Nighoghossian Norbert , Mikkelsen Irene Klærke , Ribe Lars , Baron Jean-Claude , Østergaard Leif , Derex Laurent , Hjort Niels , Fiehler Jens , Pedraza Salvador , Hermier Marc , Maucort-Boulch Delphine , Berthezène Yves 
Published: May 2013

Background and Purpose—
Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization.

Methods—
The volume of cerebral tissue with CBV ≤2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI.

Results—

Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score (
P
=0.002), acute diffusion-weighted imaging lesion volume (
P
=0.02), and thrombolysis (
P
=0.03), but not very low CBV (
P
=0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH (
P
=0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH.

Conclusion—
Very low CBV was the only independent predictor of PH in patients with acute stroke.
Comparison of Flow Diversion and Coiling in Large Unruptured Intracranial Saccular Aneurysms
Authors: Chalouhi Nohra , Tjoumakaris Stavropoula , Starke Robert M. , Gonzalez L. Fernando , Randazzo Ciro , Hasan David , McMahon Jeffrey F. , Singhal Saurabh , Moukarzel Lea A. , Dumont Aaron S. , Rosenwasser Robert , Jabbour Pascal 
Published: May 2013

Background and Purpose—
Flow diversion has emerged as an important tool for the management of intracranial aneurysms. The purpose of this study was to compare flow diversion and traditional embolization strategies in terms of safety, efficacy, and clinical outcomes in patients with unruptured, large saccular aneurysms (≥10 mm).

Methods—
Forty patients treated with the Pipeline Embolization Device (PED) were matched in a 1:3 fashion with 120 patients treated with coiling based on patient age and aneurysm size. Fusiform and anterior communicating artery aneurysms were eliminated from the analysis. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.

Results—

There were no differences between the 2 groups in terms of patient age, sex, aneurysm size, and aneurysm location. The rate of procedure-related complications did not differ between the PED (7.5%) and the coil group (7.5%;
P
=1). At the latest follow-up, a significantly higher proportion of aneurysms treated with PED (86%) achieved complete obliteration compared with coiled aneurysms (41%;
P
<0.001). In multivariable analysis, coiling was an independent predictor of nonocclusion. Retreatment was necessary in fewer patients in the PED group (2.8%) than the coil group (37%;
P
<0.001). A similar proportion of patients attained a favorable outcome (modified Rankin Scale, 0–2) in the PED group (92%) and in the coil group (94%;
P
=0.8).

Conclusions—
The PED provides higher aneurysm occlusion rates than coiling, with no additional morbidity and similar clinical outcomes. These findings suggest that the PED might be a preferred treatment option for large unruptured saccular aneurysms.
The Chinese Army in the First Burma Campaign
Authors: Chen Li 
Published: May 2013

Abstract
The article analyzes the performance of the Chinese Nationalist army in the First Burma Campaign in 1942. This combat demonstrated new challenges that faced the Chinese army. After more than four years of fighting, a weakened Chinese army struggled to open a new front in the remote southwestern border area and Burma. The Chinese forces deployed in Burma included some of the best Chinese divisions, but the rest were ordinary or even weak formations. Hence their performance in Burma was no better than those back in China. Their doctrine of defense in depth (and their tactics) did not suit warfare in Burma. Although they succeeded in defending Toungoo for ten days, in other engagements the Chinese units failed to halt the Japanese. They suffered further losses during the retreat since they were not familiar with jungle warfare. In addition, the Chinese troops did not handle their relations with the British forces and local Burmese population well. These failures contributed to the collapse of the front.
The (Bio)Technological Sublime
Authors: de Mul Jos 
Published: May 2013

AbstractThe notion of the sublime, which since the nineteenth century is one of the dominant aesthetic categories, is strongly connected with (the artistic representation of) overwhelming nature. In this article it is argued that in the course of the 20th century the sublime increasingly becomes entangled with the experience of technology. However, in the age of biotechnologies, such as genetic modification and synthetic biology, the sublime regains a natural dimension. Taking Eduard Kac’s Alba fluo rabbit (a ‘transgenic’ bunny, that resulted from the injection of green fluorescent protein of a Pacific jellyfish into the egg of an Albino rabbit) as an example, it will be argued that in the age of biotechnology the difference between nature, technology and art will gradually vanish, and new dimensions of the sublime will become manifest.