bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol Outlet Availability and Excessive Alcohol Consumption in Breast Cancer Survivors
Authors: Schootman Mario , Deshpande Anjali D. , Lynskey Michael T. , Pruitt Sandi L. , Lian Min , Jeffe Donna B. 
Published: April 2012

Background: Breast cancer survivors who consume alcohol excessively are at increased risk of recurrence and have worse prognosis. Because the environments in which people live shape many health behaviors, there has been increased attention to how neighborhood environments (eg, alcohol outlet availability) may influence alcohol consumption. The authors hypothesized that proximity to alcohol outlets increases the likelihood of excessive consumption (ie, more than 1 drink/day) among breast cancer survivors independent of their personal or neighborhood characteristics. Methods: With the Missouri Cancer Registry, the authors conducted a cross-sectional study of 1047 female breast cancer survivors (aged 27-96 years) 1 year after diagnosis. Using telephone interviews, the authors obtained data regarding survivors’ alcohol consumption during the past 30 days and several covariates of alcohol use. They also obtained street addresses of all licensed alcohol outlets in Missouri and calculated the road network distance between a participant’s address of residence and the nearest alcohol outlet, using a geographic information system. Logistic regression was used to determine if distance was independently associated with excessive alcohol consumption. Results: Eighteen percent of participants reported consuming more than 1 drink on average per day. Women who lived within 3 miles of the nearest outlet were more likely to report excessive alcohol consumption (odds ratio: 2.09; 95% confidence interval: 1.08, 4.05) than women who lived at least 3 miles from the nearest outlet in adjusted analysis. Discussion: Opportunities exist to reduce excessive alcohol use among breast cancer survivors through policy (eg, restricting number of alcohol outlets) and behavioral (eg, counseling) interventions.
Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia
Authors: Jácomo Rafael H. , Santana-Lemos Barbara A. , Lima Ana Silvia G. , Assis Patricia A. , Lange Ana Paula A. , Figueiredo-Pontes Lorena L. , Oliveira Luciana O. , Bassi Sarah C. , Benício Mariana T. L. , Baggio Márcia S. , Garcia Aglair B. , Falcão Roberto P. , Rego Eduardo M. 
Published: April 2012

AbstractIncreased fibrinolysis is an important component of acute promyelocytic leukemia (APL) bleeding diathesis. APL blasts overexpress annexin II (ANXII), a receptor for tissue plasminogen activator (tPA), and plasminogen, thereby increasing plasmin generation. Previous studies suggested that ANXII plays a pivotal role in APL coagulopathy. ANXII binding to tPA can be inhibited by homocysteine and hyperhomocysteinemia can be induced by L-methionine supplementation. In the present study, we used an APL mouse model to study ANXII function and the effects of hyperhomocysteinemia in vivo. Leukemic cells expressed higher ANXII and tPA plasma levels (11.95 ng/mL in leukemic vs 10.74 ng/mL in wild-type; P = .004). In leukemic mice, administration of L-methionine significantly increased homocysteine levels (49.0 μmol/mL and < 6.0 μmol/mL in the treated and nontreated groups, respectively) and reduced tPA levels to baseline concentrations. The latter were also decreased after infusion of the LCKLSL peptide, a competitor for the ANXII tPA–binding site (11.07 ng/mL; P = .001). We also expressed and purified the p36 component of ANXII in Pichia methanolica. The infusion of p36 in wild-type mice increased tPA and thrombin-antithrombin levels, and the latter was reversed by L-methionine administration. The results of the present study demonstrate the relevance of ANXII in vivo and suggest that methionine-induced hyperhomocysteinemia may reverse hyperfibrinolysis in APL.
How I treat acquired aplastic anemia
Authors: Scheinberg Phillip , Young Neal S. 
Published: April 2012

AbstractSurvival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive biologics and drugs, and supportive care. However, management of SAA patients remains challenging, both acutely in addressing the immediate consequences of pancytopenia and in the long term because of the disease's natural history and the consequences of therapy. Recent insights into pathophysiology have practical implications. We review key aspects of differential diagnosis, considerations in the choice of first- and second-line therapies, and the management of patients after immunosuppression, based on both a critical review of the recent literature and our large personal and research protocol experience of bone marrow failure in the Hematology Branch of the National Heart, Lung, and Blood Institute.
A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis
Authors: Kastritis Efstathios , Terpos Evangelos , Roussou Maria , Gavriatopoulou Maria , Pamboukas Constantinos , Boletis Ioannis , Marinaki Smaragda , Apostolou Theofanis , Nikitas Nikitas , Gkortzolidis Georgios , Michalis Eurydiki , Delimpasi Sossana , Dimopoulos Meletios A. 
Published: April 2012

Abstract
In this phase 1/2 study, we explored the feasibility and activity of an oral regimen of lenalidomide with low-dose dexamethasone and low-dose oral cyclophosphamide (RdC) in patients with primary systemic light chain amyloidosis. RdC was given for up to 12 cycles in prespecified cohorts at escalated doses: 13 patients were treated in phase 1 and 24 in phase 2; 65% were previously untreated, and most had renal and/or cardiac involvement and elevated cardiac biomarkers. Lenalidomide 15 mg/d and cyclophosphamide 100 mg/d were further evaluated in phase 2. On intention to treat, 20 (55%) patients achieved a hematologic response, including 3 (8%) complete remissions. Hematologic responses were seen at all dose levels and in 4 of 5 patients who had received bortezomib previously. An organ response was recorded in 22% of patients on intention-to-treat and in 40% of patients who survived at least 6 months. The median time to progression was 10 months and the 2-year survival was 41%. Fatigue, nonneutropenic infections, and rash were the most common toxicities. The results of the present study show that RdC is an oral regimen with activity in primary systemic light chain amyloidosis and may be an additional treatment option, especially for patients with preserved organ function or for patients who cannot receive or who relapse after bortezomib. This study is registered at www.clinicaltrials.gov as NCT00981708.
Non–cell-autonomous hedgehog signaling promotes murine B lymphopoiesis from hematopoietic progenitors
Authors: Cooper Christopher L. , Hardy Richard R. , Reth Michael , Desiderio Stephen 
Published: April 2012

AbstractThe role of hedgehog (Hh) signaling in B lymphopoiesis has remained unclear. We observed that the proliferation of pro-B cells in stromal cocultures was impaired by interruption of Hh signaling, prompting us to investigate whether the target of Hh antagonism was intrinsic or extrinsic to the B-lymphoid compartment. In the present study, using conditional deletion of the pathway activator gene Smo, we found that cell-autonomous Hh signaling is dispensable for B-cell development, B-lymphoid repopulation of the BM, and humoral immune function. In contrast, depletion of the Smo protein from stromal cells was associated with impaired generation of B-lymphoid cells from hematopoietic stem progenitor cells, whereas reciprocal removal of Smo from these cells had no effect on the production of B-cell progenitors. Depletion of Smo from stromal cells was associated with coordinate down-regulation of genes for which expression is associated with osteoblastoid identity and B-lymphopoietic activity. The results of the present study suggest that activity of the Hh pathway within stromal cells promotes B lymphopoiesis in a non–cell-autonomous fashion.
Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma
Authors: Cubedo Elena , Gentles Andrew J. , Huang Chuanxin , Natkunam Yasodha , Bhatt Shruti , Lu Xiaoqing , Jiang Xiaoyu , Romero-Camarero Isabel , Freud Aharon , Zhao Shuchun , Bacchi Carlos E. , Martínez-Climent Jose A. , Sánchez-García Isidro , Melnick Ari , Lossos Izidore S. 
Published: April 2012

Abstract
LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis.
Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia
Authors: Leung Wing , Pui Ching-Hon , Coustan-Smith Elaine , Yang Jie , Pei Deqing , Gan Kwan , Srinivasan Ashok , Hartford Christine , Triplett Brandon M. , Dallas Mari , Pillai Asha , Shook David , Rubnitz Jeffrey E. , Sandlund John T. , Jeha Sima , Inaba Hiroto , Ribeiro Raul C. , Handgretinger Rupert , Laver Joseph H. , Campana Dario 
Published: April 2012

AbstractIn patients with acute leukemia, detection of minimal residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) correlates with risk of relapse. However, the level of MRD that is most likely to preclude cure by HCT is unclear, and the benefit of further chemotherapy to reduce MRD before HCT is unknown. In 122 children with very-high-risk acute lymphoblastic leukemia (ALL; n = 64) or acute myeloid leukemia (AML, n = 58), higher MRD levels at the time of HCT predicted a poorer survival after HCT (P = .0019); MRD was an independent prognostic factor in a multivariate analysis (P = .0035). However, the increase in risk of death associated with a similar increment of MRD was greater in ALL than in AML, suggesting that a pretransplantation reduction of leukemia burden would have a higher impact in ALL. At any given MRD level, survival rates were higher for patients treated in recent protocols: the 5-year overall survival for patients with ALL was 49% if MRD was detectable and 88% if it was not and the corresponding rates for patients with AML were 67% and 80%, respectively. Although MRD before HCT is a strong prognostic factor, its impact has diminished and should not be regarded as a contraindication for HCT.
O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions
Authors: Nowak Agata A. , Canis Kevin , Riddell Anne , Laffan Michael A. , McKinnon Thomas A. J. 
Published: April 2012

AbstractWe have examined the effect of the O-linked glycan (OLG) structures of VWF on its interaction with the platelet receptor glycoprotein Ibα. The 10 OLGs were mutated individually and as clusters (Clus) on either and both sides of the A1 domain: Clus1 (N-terminal side), Clus2 (C-terminal side), and double cluster (DC), in both full-length-VWF and in a VWF construct spanning D′ to A3 domains. Mutations did not alter VWF secretion by HEK293T cells, multimeric structure, or static collagen binding. The T1255A, Clus1, and DC variants caused increased ristocetin-mediated GPIbα binding to VWF. Platelet translocation rate on OLG mutants was increased because of reduced numbers of GPIbα binding sites but without effect on bond lifetime. In contrast, OLG mutants mediated increased platelet capture on collagen under high shear stress that was associated with increased adhesion of these variants to the collagen under flow. These findings suggest that removal of OLGs increases the flexibility of the hinge linker region between the D3 and A1 domain, facilitating VWF unfolding by shear stress, thereby enhancing its ability to bind collagen and capture platelets. These data demonstrate an important functional role of VWF OLGs under shear stress conditions.
A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages
Authors: Tibúrcio Marta , Niang Makhtar , Deplaine Guillaume , Perrot Sylvie , Bischoff Emmanuel , Ndour Papa Alioune , Silvestrini Francesco , Khattab Ayman , Milon Geneviève , David Peter H. , Hardeman Max , Vernick Kenneth D. , Sauerwein Robert W. , Preiser Peter R. , Mercereau-Puijalon Odile , Buffet Pierre , Alano Pietro , Lavazec Catherine 
Published: April 2012

AbstractAchievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-infected erythrocytes (GIEs) sequester in host tissues. Only mature stage GIEs circulate in the peripheral blood, available to uptake by the Anopheles vector. Mechanisms underlying GIE sequestration and release in circulation are virtually unknown. We show here that mature GIEs are more deformable than immature stages using ektacytometry and microsphiltration methods, and that a switch in cellular deformability in the transition from immature to mature gametocytes is accompanied by the deassociation of parasite-derived STEVOR proteins from the infected erythrocyte membrane. We hypothesize that mechanical retention contributes to sequestration of immature GIEs and that regained deformability of mature gametocytes is associated with their release in the bloodstream and ability to circulate. These processes are proposed to play a key role in P falciparum gametocyte development in the host and to represent novel and unconventional targets for interfering with parasite transmission.
Heritability of cortisol response to confinement stress in European sea bass dicentrarchus labrax
Authors: Volckaert Filip AM , Hellemans Bart , Batargias Costas , Louro Bruno , Massault Cécile , Van Houdt Jeroen K J , Haley Chris , de Koning Dirk-Jan , Canario Adelino VM 
Published: April 2012

AbstractBackgroundIn fish, the most studied production traits in terms of heritability are body weight or growth, stress or disease resistance, while heritability of cortisol levels, widely used as a measure of response to stress, is less studied. In this study, we have estimated heritabilities of two growth traits (body weight and length) and of cortisol response to confinement stress in the European sea bass.FindingsThe F1 progeny analysed (n = 922) belonged to a small effective breeding population with contributions from an unbalanced family structure of just 10 males and 2 females. Heritability values ranged from 0.54 (±0.21) for body weight to 0.65 (±0.22) for standard body length and were low for cortisol response i.e. 0.08 (±0.06). Genetic correlations were positive (0.94) between standard body length and body weight and negative between cortisol and body weight and between cortisol and standard body length (−0.60 and −0.55, respectively).ConclusionThis study confirms that in European sea bass, heritability of growth-related traits is high and that selection on such traits has potential. However, heritability of cortisol response to stress is low in European sea bass and since it is known to vary greatly among species, further studies are necessary to understand the reasons for these differences.
BB0324 and BB0028 are constituents of the Borrelia burgdorferi β-barrel assembly machine (BAM) complex
Authors: Lenhart Tiffany R , Kenedy Melisha R , Yang Xiuli , Pal Utpal , Akins Darrin R 
Published: April 2012

Abstract

Background
Similar to Gram-negative bacteria, the outer membrane (OM) of the pathogenic spirochete, Borrelia burgdorferi, contains integral OM-spanning proteins (OMPs), as well as membrane-anchored lipoproteins. Although the mechanism of OMP biogenesis is still not well-understood, recent studies have indicated that a heterooligomeric OM protein complex, known as BAM (β-barrel assembly machine) is required for proper assembly of OMPs into the bacterial OM. We previously identified and characterized the essential β-barrel OMP component of this complex in B. burgdorferi, which we determined to be a functional BamA ortholog.

Results
In the current study, we report on the identification of two additional protein components of the B. burgdorferi BAM complex, which were identified as putative lipoproteins encoded by ORFs BB0324 and BB0028. Biochemical assays with a BamA-depleted B. burgdorferi strain indicate that BB0324 and BB0028 do not readily interact with the BAM complex without the presence of BamA, suggesting that the individual B. burgdorferi BAM components may associate only when forming a functional BAM complex. Cellular localization assays indicate that BB0324 and BB0028 are OM-associated subsurface lipoproteins, and in silico analyses indicate that BB0324 is a putative BamD ortholog.

Conclusions
The combined data suggest that the BAM complex of B. burgdorferi contains unique protein constituents which differ from those found in other proteobacterial BAM complexes. The novel findings now allow for the B. burgdorferi BAM complex to be further studied as a model system to better our understanding of spirochetal OM biogenesis in general.
Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan
Authors: Huang Shiou-Huei , Hsu Chien-Ning , Yu Shu-Hui , Cham Thau-Ming 
Published: April 2012

Abstract

Background
A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication.

Methods
Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed.

Results
The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001).

Conclusions
Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.
In vitro antiplasmodial, antileishmanial and antitrypanosomal activities of selected medicinal plants used in the traditional Arabian Peninsular region
Authors: Al-Musayeib Nawal M , Mothana Ramzi A , Matheeussen An , Cos Paul , Maes Louis 
Published: April 2012

Abstract

Background
Worldwide particularly in developing countries, a large proportion of the population is at risk for tropical parasitic diseases. Several medicinal plants are still used traditionally against protozoal infections in Yemen and Saudi Arabia. Thus the present study investigated the in vitro antiprotozoal activity of twenty-five plants collected from the Arabian Peninsula.

Methods
Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC50 < 10 μg/ml (<5 μg/ml for T. brucei) and selectivity index of >4.

Results
Antiplasmodial activity was found in the extracts of Chrozophora oblongifolia, Ficus ingens, Lavandula dentata and Plectranthus barbatus. Amastigotes of T. cruzi were affected by Grewia erythraea, L. dentata, Tagetes minuta and Vernonia leopoldii. Activity against T. brucei was obtained in G. erythraea, L. dentata, P. barbatus and T. minuta. No relevant activity was found against L. infantum. High levels of cytotoxicity (MRC-5 IC50 < 10 μg/ml) and hence non-specific activities were noted in Cupressus sempervirens, Kanahia laniflora and Kniphofia sumarae.

Conclusion
The results endorse that medicinal plants can be promising sources of natural products with antiprotozoal activity potential. The results support to some extent the traditional uses of some plants for the treatment of parasitic protozoal diseases.
Intraduodenal sarcoma recurrence of retroperitoneal origin: an unusual cause for a duodenal obstruction
Authors: Bao Jean J , Mansour John C , Timmerman Robert D , Kirane Amanda , Ewing Gene E , Schwarz Roderich E 
Published: April 2012

Abstract
Soft tissue sarcomas are uncommon tumors, and intraduodenal soft tissue sarcoma manifestation is even more rare. Only three cases of intraduodenal sarcomas have been reported in the literature thus far. Here, we report a case of an intraduodenal recurrence of a retroperitoneal sarcoma causing bowel obstruction. This unusual recurrence pattern likely relates to the patient’s previous resection and radiation treatment, and highlights the benefits, limitations and follow-up strategies after multimodality treatment.