bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Factors of Arthroscopic Pull-out Repair for a Posterior Root Tear of the Medial Meniscus
Authors: Moon Hong-Kyo , Koh Yong-Gon , Kim Yong-Chan , Park Young-Sik , Jo Seung-Bae , Kwon Sae-Kwang 
Published: February 2012

Background: Repair of a posterior root tear of the medial meniscus (MRT) decreases peak contact pressure by restoring hoop tension and is expected to prevent progression to osteoarthritis. Purpose: The purposes of this study were (1) to report the clinical and magnetic resonance imaging (MRI) results of arthroscopic pull-out repair of the MRT and (2) to identify prognostic factors of poor outcome. Study Design: Case series; Level of evidence, 4. Methods: Fifty-one patients (47 women, 4 men) who underwent arthroscopic pull-out repair of the MRT by a single surgeon were enrolled. Mean follow-up after surgery was 33 months (range, 24-44 months). To identify factors affecting final outcome, patient-specific factors, such as gender, age, body mass index, meniscus extrusion, extrusion increase, subchondral edema, degree of varus alignment (<5° or >5°), and cartilage status in the medial compartment (Outerbridge grade 1 or 2 lesion vs grade 3 or 4 lesion), were investigated. Final clinical outcomes were determined using a visual analog scale (VAS) for pain and patient satisfaction scores, American Knee Society (AKS) scores, and Lysholm scores, and MRI outcomes were determined by evaluating meniscus extrusion and articular cartilage status. Multiple regression analysis was performed to identify variables that independently affected clinical and MRI-determined outcomes. Results: All clinical outcome measures significantly improved after surgery. Patients with Outerbridge grade 3 or 4 chondral lesions had poorer results than those with grade 1 or 2 lesions in terms of AKS function and Lysholm scores. Patients with varus alignment of >5° had poorer results than those with varus alignment of <5° in terms of VAS satisfaction, AKS function, and Lysholm scores. Mean meniscus extrusion increased from 3.6 mm preoperatively to 5.0 mm postoperatively. Chondral lesions progressed in 3 (9.7%) of 31 patients. Preoperative meniscus extrusion was found to be positively correlated with final extrusion. Conclusion: At a mean follow-up of 33 months after pull-out repair, extrusion of the meniscus was found to have progressed. Nevertheless, this technique provided patients with a clinical benefit. Outerbridge grade 3 or 4 chondral lesions and varus alignment of >5° were found to independently predict an inferior clinical outcome.
Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia
Authors: Zhao Li-Juan , Wang Yue-Ying , Li Guo , Ma Li-Yuan , Xiong Shu-Min , Weng Xiang-Qin , Zhang Wei-Na , Wu Bo , Chen Zhu , Chen Sai-Juan 
Published: February 2012

AbstractThe BCR-ABL fusion protein generated by t(9;22)(q34;q11) in chronic myeloid leukemia (CML) plays an essential role in the pathogenesis of the myeloproliferative disorder status at the chronic phase of the disease, but progression from the chronic phase to blast crisis (BC) is believed to require additional mutations. To explore the underlying mechanisms for BC, which is characterized by a blockage of blood cell differentiation, we screened several genes crucial to hematopoiesis and identified 10 types of mutations in RUNX1 among 11 of 85 (12.9%) patients with acute transformation of CML. Most of the mutations occurred in the runt homology domain, including H78Q, W79C, R139G, D171G, R174Q, L71fs-ter94, and V91fs-ter94. Further studies indicated that RUNX1 mutants not only exhibited decreased transactivation activity but also had an inhibitory effect on the WT RUNX1. To investigate the leukemogenic effect of mutated RUNX1, H78Q and V91fs-ter94 were transduced into 32D cells or BCR-ABL–harboring murine cells, respectively. Consistent with the myeloblastic features of advanced CML patients with RUNX1 mutations, H78Q and V91fs-ter94 disturbed myeloid differentiation and induced a BC or accelerated phase–like phenotype in mice. These results suggest that RUNX1 abnormalities may promote acute myeloid leukemic transformation in a subset of CML patients.
TCR affinity and specificity requirements for human regulatory T-cell function
Authors: Plesa Gabriela , Zheng Lingjie , Medvec Andrew , Wilson Caleph B. , Robles-Oteiza Camila , Liddy Nathaniel , Bennett Alan D. , Gavarret Jessie , Vuidepot Annelise , Zhao Yangbing , Blazar Bruce R. , Jakobsen Bent K. , Riley James L. 
Published: February 2012

AbstractWe investigated whether TCRs restricted to the more ubiquitously expressed MHC class I molecules could be used to redirect human regulatory T cells (Tregs). Using a series of HLA-A2–restricted TCRs that recognize the same peptide-MHC class I complex (pMHC) with affinities varying up to 3500 fold, we observed that TCR affinity had no effect on the ability of the introduced TCRs to confer potent Ag-specific suppressive activity. Surprisingly, we found a naturally occurring, low-affinity MHC class I–restricted TCR specific for an NY-ESO-1 epitope that was unable to redirect a functional CD4 T-effector cell response could confer potent antigen-specific suppressive activity when expressed in Tregs and severely impair the expansion of highly functional HIV-1GAG–specific CD8 T cells expressing a high-affinity TCR. This suppressive activity was only observed when both Ags were presented by the same cell, and no suppression was observed when the target Ags were put in distinct cells. These studies underscore the clinical utility of using MHC class I–restricted TCRs to endow Tregs with specificity to control autoimmune disease and highlight the conditions in which this approach would have most therapeutic benefit.
Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica
Authors: Enose-Akahata Yoshimi , Abrams Anna , Johnson Kory R. , Maloney Elizabeth M. , Jacobson Steven 
Published: February 2012

AbstractAdult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLV-I–seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I–infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio = 14.12) and from ATL patients (odds ratio = 7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLV-I–infected groups may be a useful diagnostic tool in the future.
Evolution of the intercontinental disjunctions in six continents in the Ampelopsis clade of the grape family (Vitaceae)
Authors: Nie Ze-Long , Sun Hang , Manchester Steven R , Meng Ying , Luke Quentin , Wen Jun 
Published: February 2012

AbstractBackgroundTheAmpelopsisclade (Ampelopsisand its close allies) of the grape family Vitaceae contains ca. 43 species disjunctly distributed in Asia, Europe, North America, South America, Africa, and Australia, and is a rare example to study both the Northern and the Southern Hemisphere intercontinental disjunctions. We reconstruct the temporal and spatial diversification of theAmpelopsisclade to explore the evolutionary processes that have resulted in their intercontinental disjunctions in six continents.ResultsThe Bayesian molecular clock dating and the likelihood ancestral area analyses suggest that theAmpelopsisclade most likely originated in North America with its crown group dated at 41.2 Ma (95% HPD 23.4 - 61.0 Ma) in the middle Eocene. Two independent Laurasian migrations into Eurasia are inferred to have occurred in the early Miocene via the North Atlantic land bridges. The ancestor of the Southern Hemisphere lineage migrated from North America to South America in the early Oligocene. The Gondwanan-like pattern of intercontinental disjunction is best explained by two long-distance dispersals: once from South America to Africa estimated at 30.5 Ma (95% HPD 16.9 - 45.9 Ma), and the other from South America to Australia dated to 19.2 Ma (95% HPD 6.7 - 22.3 Ma).ConclusionsThe global disjunctions in theAmpelopsisclade are best explained by a diversification model of North American origin, two Laurasian migrations, one migration into South America, and two post-Gondwanan long-distance dispersals. These findings highlight the importance of both vicariance and long distance dispersal in shaping intercontinental disjunctions of flowering plants.
Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer's disease in Germany using discrete event simulation
Authors: Hartz Susanne , Getsios Denis , Tao Sunning , Blume Steve , Maclaine Grant 
Published: February 2012

Abstract

Background
Previous cost-effectiveness studies of cholinesterase inhibitors have modeled Alzheimer's disease (AD) progression and treatment effects through single or global severity measures, or progression to "Full Time Care". This analysis evaluates the cost-effectiveness of donepezil versus memantine or no treatment in Germany by considering correlated changes in cognition, behavior and function.

Methods
Rates of change were modeled using trial and registry-based patient level data. A discrete event simulation projected outcomes for three identical patient groups: donepezil 10 mg, memantine 20 mg and no therapy. Patient mix, mortality and costs were developed using Germany-specific sources.

Results
Treatment of patients with mild to moderately severe AD with donepezil compared to no treatment was associated with 0.13 QALYs gained per patient, and 0.01 QALYs gained per caregiver and resulted in average savings of €7,007 and €9,893 per patient from the healthcare system and societal perspectives, respectively. In patients with moderate to moderately-severe AD, donepezil compared to memantine resulted in QALY gains averaging 0.01 per patient, and savings averaging €1,960 and €2,825 from the healthcare system and societal perspective, respectively.
In probabilistic sensitivity analyses, donepezil dominated no treatment in most replications and memantine in over 70% of the replications. Donepezil leads to savings in 95% of replications versus memantine.

Conclusions
Donepezil is highly cost-effective in patients with AD in Germany, leading to improvements in health outcomes and substantial savings compared to no treatment. This holds across a variety of sensitivity analyses.
Effects of partner proteins on BCA2 RING ligase activity
Authors: Bacopulos Stephanie , Amemiya Yutaka , Yang Wenyi , Zubovits Judit , Burger Angelika , Yaffe Martin , Seth Arun K 
Published: February 2012

Abstract

Background
BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2.

Methods
Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays.

Results
Ten unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = < 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways.

Conclusions
The interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression.
Construction of a cellulase hyper-expression system in Trichoderma reesei by promoter and enzyme engineering
Authors: Zou Gen , Shi Shaohua , Jiang Yanping , van den Brink Joost , de Vries Ronald P , Chen Ling , Zhang Jun , Ma Liang , Wang Chengshu , Zhou Zhihua 
Published: February 2012

Abstract

Background

Trichoderma reesei is the preferred organism for producing industrial cellulases. However, a more efficient heterologous expression system for enzymes from different organism is needed to further improve its cellulase mixture. The strong cbh1 promoter of T. reesei is frequently used in heterologous expression, however, the carbon catabolite repressor CREI may reduce its strength by binding to the cbh1 promoter at several binding sites. Another crucial point to enhance the production of heterologous enzymes is the stability of recombinant mRNA and the prevention of protein degradation within the endoplasmic reticulum, especially for the bacteria originated enzymes.
In this study, the CREI binding sites within the cbh1 promoter were replaced with the binding sites of transcription activator ACEII and the HAP2/3/5 complex to improve the promoter efficiency. To further improve heterologous expression efficiency of bacterial genes within T. reesei, a flexible polyglycine linker and a rigid α-helix linker were tested in the construction of fusion genes between cbh1 from T. reesei and e1, encoding an endoglucanase from Acidothermus cellulolyticus.

Results
The modified promoter resulted in an increased expression level of the green fluorescent protein reporter by 5.5-fold in inducing culture medium and 7.4-fold in repressing culture medium. The fusion genes of cbh1 and e1 were successfully expressed in T. reesei under the control of promoter pcbh1m2. The higher enzyme activities and thermostability of the fusion protein with rigid linker indicated that the rigid linker might be more suitable for the heterologous expression system in T. reesei. Compared to the parent strain RC30-8, the FPase and CMCase activities of the secreted enzyme mixture from the corresponding transformant R1 with the rigid linker increased by 39% and 30% at 60°C, respectively, and the reduced sugar concentration in the hydrolysate of pretreated corn stover (PCS) was dramatically increased by 40% at 55°C and 169% at 60°C when its enzyme mixture was used in the hydrolysis.

Conclusions
This study shows that optimizations of the promoter and linker for hybrid genes can dramatically improve the efficiency of heterologous expression of cellulase genes in T. reesei.
The magnitude and trend of artemether-lumefantrine stock-outs at public health facilities in Kenya
Authors: Sudoi Raymond K , Githinji Sophie , Nyandigisi Andrew , Muturi Alex , Snow Robert W , Zurovac Dejan 
Published: February 2012

Abstract

Background
Health facility stock-outs of artemether-lumefantrine (AL), the common first-line therapy for uncomplicated malaria across Africa, adversely affect effective malaria case-management. They have been previously reported on various scales in time and space, however the magnitude of the problem and trends over time are less clear. Here, 2010-2011 data are reported from public facilities in Kenya where alarming stock-outs were revealed in 2008.

Methods
Data were collected between January 2010 and June 2011 as part of 18 monthly cross-sectional surveys undertaken at nationally representative samples of public health facilities. The primary monitoring indicator was total stock-out of all four weight-specific AL packs. The secondary indicators were stock-outs of at least one AL pack and individual stock-outs for each AL pack. Monthly proportions and summary means of the proportions over the monitoring period were measured for each indicator. Stock-out trends were assessed using linear regression.

Results
The number of surveyed facilities across 18 time points ranged between 162 and 176 facilities. The stock-out means of the proportion of health facilities were 11.6% for total AL stock-out, 40.6% for stock-out of at least one AL pack, and between 20.5% and 27.4% for stock-outs of individual AL packs. Monthly decrease of the total AL stock-out was 0.005% (95% CI: -0.5 to +0.5; p = 0.983). Monthly decrease in the stock-out of at least one AL pack was 0.7% (95% CI: -1.5 to +0.3; p = 0.058) while stock-outs of individual AL packs decreased monthly between 0.2% for AL 24-pack and 0.7% for AL six-pack without statistical significance for any of the weight-specific packs.

Conclusions
Despite lower levels of AL stock-outs compared to the reports in 2008, the stock-outs at Kenyan facilities during 2010-2011 are still substantial and of particular worry for the most detrimental:- simultaneous absence of any AL pack. Only minor decrease was observed in the stock-outs of individual AL packs. Recently launched interventions to eliminate AL stock-outs in Kenya are fully justified.
High IFN-gamma and TNF production by peripheral NK cells of Colombian patients with different clinical presentation of Plasmodium falciparum
Authors: Agudelo Olga , Bueno Julio , Villa Andres , Maestre Amanda 
Published: February 2012

Abstract

Background
In Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored.

Methods
Seventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNγ and TNF production by NK cells in the different patient groups.

Results
The total mean CD56+/CD3- NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56dim, 2.01%CD56bright) and 19.62% (16.05%CD56dim, 3.58%CD56bright), respectively, in contrast to healthy controls from endemic (total mean CD56+/CD3-1.2%) and non-endemic area (total mean CD56+/CD3- 0.67%). Analysis of basal IFNγ and TNF levels confirmed the CD56bright NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56dim NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group.

Conclusions
The results confirm the important role of not only CD56bright but also of CD56dim NK cell populations as producers of the two cytokines in malaria patients in Colombia.
Effect of H2S on the circadian rhythm of mouse hepatocytes
Authors: Shang Zhanxian , Lu Chao , Chen Sifeng , Hua Luchun , Qian Ruizhe 
Published: February 2012

Abstract

Background
Dysregulation of circadian rhythms can contribute to diseases of lipid metabolism. NAD-dependent deacetylase sirtuin-1(SIRT1) is an important hub which links lipid metabolism with circadian clock by its deacetylation activity depends on intracellular NAD+/NADH content ratio. Hydrogen sulfide (H2S) is an endogenous reductant which can affect the intracellular redox state. Therefore, we hypothesized that exogenous H2S can affect the expression of circadian clock genes mediated by sirt1 thereby affecting body's lipid metabolism. And also because the liver is a typical peripheral circadian clock oscillator that is intimately linked to lipid metabolism. Thus the effect of H2S were observed on 24-hour dynamic expression of 4 central circadian clock genes and sirt1gene in primary cultured hepatocytes.

Results
We established a hepatocyte model that showed a circadian rhythm by serum shock method. And detected that the expression level and the peak of circadian clock genes decreased gradually and H2S could maintain the expression and amplitude of circadian clock genes such as Clock, Per2, Bmal1 and Rev-erbαwithin a certain period time. Accordingly the expression level of sirt1 in H2S group was significantly higher than that in the control group.

Conclusion
Exogenous reductant H2S maintain the circadian rhythm of clock gene in isolated liver cells. We speculated that H2S has changed NAD+/NADH content ratio in hepatocytes and enhanced the activity of SIRT1 protein directly or indirectly, so as to maintain the rhythm of expression of circadian clock genes, they play a role in the prevention and treatment of lipid metabolism-related disease caused by the biological clock disorders.
Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode
Authors: Liang Qiong-Lin , Liang Xiao-Ping , Wang Yi-Ming , Xie Yuan-Yuan , Zhang Rong-Li , Chen Xi , Gao Rong , Cheng Yi-Jun , Wu Jun , Xu Qing-Bo , Xiao Qing-Zhong , Li Xue , Lv Shu-Feng , Fan Xue-Mei , Zhang Hong-Yang , Zhang Qing-Li , Luo Guo-An 
Published: February 2012

Abstract

Background

Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF.

Method
In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI.

Results
Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage.

Conclusions
The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.