bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoprenoid Precursor Biosynthesis Is the Essential Metabolic Role of the Apicoplast during Gametocytogenesis in Plasmodium falciparum
Authors: Wiley Jessica D. , Merino Emilio F. , Krai Priscilla M. , McLean Kyle J. , Tripathi Abhai K. , Vega-Rodríguez Joel , Jacobs-Lorena Marcelo , Klemba Michael , Cassera Maria B. 
Published: December 2014

ABSTRACT
The malaria parasite harbors a relict plastid called the apicoplast and its discovery opened a new avenue for drug discovery and development due to its unusual, nonmammalian metabolism. The apicoplast is essential during the asexual intraerythrocytic and hepatic stages of the parasite, and there is strong evidence supporting its essential metabolic role during the mosquito stages of the parasite. Supply of the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast during the asexual intraerythrocytic stages. However, the metabolic role of the apicoplast during gametocyte development, the malaria stages transmitted to the mosquito, remains unknown. In this study, we showed that production of IPP for isoprenoid biosynthesis is the essential metabolic function of the apicoplast during gametocytogenesis, by obtaining normal gametocytes lacking the apicoplast when supplemented with IPP. When IPP supplementation was removed early in gametocytogenesis, developmental defects were observed, supporting the essential role of isoprenoids for normal gametocytogenesis. Furthermore, mosquitoes infected with gametocytes lacking the apicoplast developed fewer and smaller oocysts that failed to produce sporozoites. This finding further supports the essential role of the apicoplast in establishing a successful infection in the mosquito vector. Our study supports isoprenoid biosynthesis as a valid drug target for development of malaria transmission-blocking inhibitors.
Two novel type 2 diabetes loci revealed through integration of TCF7L2 DNA occupancy and SNP association data
Authors: Johnson Matthew E , Zhao Jianhua , Schug Jonathan , Deliard Sandra , Xia Qianghua , Guy Vanessa C , Sainz Jesus , Kaestner Klaus H , Wells Andrew D , Grant Struan F A 
Published: December 2014

BackgroundThe transcription factor 7-like 2 (TCF7L2) locus is strongly implicated in the pathogenesis of type 2 diabetes (T2D). We previously mapped the genomic regions bound by TCF7L2 using ChIP (chromatin immunoprecipitation)-seq in the colorectal carcinoma cell line, HCT116, revealing an unexpected highly significant over-representation of genome-wide association studies (GWAS) loci associated primarily with endocrine (in particular T2D) and cardiovascular traits.MethodsIn order to further explore if this observed phenomenon occurs in other cell lines, we carried out ChIP-seq in HepG2 cells and leveraged ENCODE data for five additional cell lines. Given that only a minority of the predicted genetic component to most complex traits has been identified to date, plus our GWAS-related observations with respect to TCF7L2 occupancy, we investigated if restricting association analyses to the genes yielded from this approach, in order to reduce the constraints of multiple testing, could reveal novel T2D loci.ResultsWe found strong evidence for the continued enrichment of endocrine and cardiovascular GWAS categories, with additional support for cancer. When investigating all the known GWAS loci bound by TCF7L2 in the shortest gene list, derived from HCT116, the coronary artery disease-associated variant, rs46522 at theUBE2Z-GIP-ATP5G1-SNF8locus, yielded significant association with T2D within DIAGRAM. Furthermore, when we analyzed tag-SNPs (single nucleotide polymorphisms) in genes not previously implicated by GWAS but bound by TCF7L2 within 5 kb, we observed a significant association of rs4780476 withinCPPED1in DIAGRAM.ConclusionsChIP-seq data generated with this GWAS-implicated transcription factor provided a biologically plausible method to limit multiple testing in the assessment of genome-wide genotyping data to uncover two novel T2D-associated loci.
A new oxygen prescription produces real improvements in therapeutic oxygen use
Authors: Rudge James , Odedra Sunita , Harrison Danielle 
Published: December 2014

AbstractIn the UK, safe use and administration of oxygen therapy was unsatisfactory prior to the implementation of national guidelines in 2008. Each year since then the British Thoracic Society (BTS) has conducted a national audit that has demonstrated a slow but steady improvement in oxygen use across four key standards. Sandwell and West Birmingham NHS Hospitals Trust has participated in this audit process but has failed to show consistent improvements. The aim of this quality improvement project was to produce meaningful and sustained improvements in oxygen use across each of the four standards.Four interventions were developed over three PDSA cycles and included: 1. a new oxygen prescription chart, 2. oxygen ‘alert’ stickers for use on drug and MEWS charts, 3. point of care resources, and 4. senior led educational sessions for healthcare staff. Each intervention was tested on the Acute Medical Unit over seven days and data collected using the BTS data collection form.The QIP improved oxygen use across each of the standards: baseline measurement for standard one demonstrated that 55% of patients using oxygen had a valid oxygen prescription, improving to 94% after PDSA cycle three. For standard two, baseline measurement demonstrated that 50% of patients had a documented oxygen target saturation range, improving to 94% after PDSA cycle three. For standard three, baseline measurement demonstrated that 84% patients using oxygen had saturations documented on the MEWS chart, improving to 100% after PDSA cycle three. Finally, baseline measurement of standard four demonstrated that 0% patients with a valid oxygen prescription had it signed for at drugs rounds, improving to 18% after PDSA cycle three.Oxygen use was substantially improved during the QIP. Following engagement with stakeholders a new oxygen prescription will be rolled out within the Trust with projected annual savings of £30,400.
Serum free light chains in patients with HIV infection: their association with markers of disease severity and antiretroviral use
Authors: Zemlin Annalise E , Ipp Hayley , Rensburg Megan A , Germishuys Jurie J , Esser Monika M , Olivier Madeleen , Erasmus Rajiv T 
Published: December 2014

AimSerum free light chain measurements are used to follow-up and manage patients with monoclonal gammopathies, and abnormal ratios are associated with risk of progression in certain diseases. B cell dysfunction is well described in HIV and patients are at risk of developing B cell lymphomas. This study investigated whether HIV is associated with abnormal free light chain levels and the impact of antiretroviral treatment (ART) on these.Methodsκ And λ free light chain concentrations and ratios, serum albumin and immunoglobulin G (IgG) were measured in 366 HIV positive subjects and correlated with CD4+ counts, viral loads, IgG, albumin and ART use.Results66% were women and most were black Africans (66%), 26% were of mixed ethnicity and 8% were Caucasian or of unknown or other race. 89% were on ART. κ Free light chain values ranged from 5.59 to 357.0 mg/L (median 19.6 mg/L) and λ free light chain values ranged from 9.28 to 286 mg/L (median 22.3 mg/L). Both correlated positively with viral load and IgG and negatively with CD4+ counts and albumin concentrations. The ratio only correlated with IgG concentrations. Patients on ART had significantly lower free light chain concentrations, but the ratio was not significantly affected.ConclusionsThis study demonstrated that free light chain concentrations were significantly correlated with markers of HIV disease severity, suggesting ongoing B cell dysfunction despite ART use. Free light chain ratio was not significantly affected.
The world's most isolated vet?
Authors: Hollins Joe 
Published: December 2014

In the remote tropical waters of the mid‐South Atlantic stands a vast and ancient volcano some 5000 metres high. Only the tip, worn over 14 million years into an 830 metre craggy pimple, rises out of the ocean, violently eroded into dinosaur‐back peaks and vertiginous gullies, and surrounded by near impregnable sea cliffs of red cinder and blue‐grey magma. The nearest landfall 1200 miles to the east is Angola, and 2000 miles to the west, Brazil. This is Joe Hollins’ patch – 47 square miles of convulsed igneous rock: the island of St Helena
Spot
Authors: Bocchino Robert L. , Gamble Edward , Gostelow Kim P. , Some Raphael R. 
Published: December 2014

The C programming language is widely used for programming space flight software and other safety-critical real time systems. C, however, is far from ideal for this purpose: as is well known, it is both low-level and unsafe. This paper describes Spot, a language derived from C for programming space flight systems. Spot aims to maintain compatibility with existing C code while improving the language and supporting verification with the SPIN model checker. The major features of Spot include actor-based concurrency, distributed state with message passing and transactional updates, and annotations for testing and verification. Spot also supports domain-specific annotations for managing spacecraft state, e.g., communicating telemetry information to the ground.
We describe the motivation and design rationale for Spot, give an overview of the design, provide examples of Spot's capabilities, and discuss the current status of the implementation.
The Aramaic Component and Aramaisms in the Arabic Column of Ms. BL OR7562
Authors: Zewi Tamar 
Published: December 2014

The article analyzes the Aramaic component and Aramaisms embedded in the first hand’s stage of the Arabic column of Ms. BL OR7562 (c. 1300),1 which mainly conveys a Samaritan version of Saadya Gaon’s translation of the Pentateuch. While Aramaic words are known to feature in all versions of Saadya’s Tafsīr, Ms. BL OR7562 evinces examples of Aramaic loan words and various kinds of Aramaisms that are found neither in other versions of Saadya’s Tafsīr, nor in the other two main Samaritan Arabic versions, namely the early Samaritan Arabic translation and its later revision.
A Second-Order Exact Ensemble Square Root Filter for Nonlinear Data Assimilation
Authors: Tödter Julian , Ahrens Bodo 
Published: December 2014

AbstractThe ensemble Kalman filter (EnKF) and its deterministic variants, mostly square root filters such as the ensemble transform Kalman filter (ETKF), represent a popular alternative to variational data assimilation schemes and are applied in a wide range of operational and research activities. Their forecast step employs an ensemble integration that fully respects the nonlinear nature of the analyzed system. In the analysis step, they implicitly assume the prior state and observation errors to be Gaussian. Consequently, in nonlinear systems, the analysis mean and covariance are biased, and these filters remain suboptimal. In contrast, the fully nonlinear, non-Gaussian particle filter (PF) only relies on Bayes’s theorem, which guarantees an exact asymptotic behavior, but because of the so-called curse of dimensionality it is exposed to weight collapse. Here, it is shown how to obtain a new analysis ensemble whose mean and covariance exactly match the Bayesian estimates. This is achieved by a deterministic matrix square root transformation of the forecast ensemble, and subsequently a suitable random rotation that significantly contributes to filter stability while preserving the required second-order statistics. The properties and performance of the proposed algorithm are further investigated via a set of experiments. They indicate that such a filter formulation can increase the analysis quality, even for relatively small ensemble sizes, compared to other ensemble filters in nonlinear, non-Gaussian scenarios. Localization enhances the potential applicability of this PF-inspired scheme in larger-dimensional systems. The proposed algorithm, which is fairly easy to implement and computationally efficient, is referred to as the nonlinear ensemble transform filter (NETF).
Early mobilization of patients who have had a hip or knee joint replacement reduces length of stay in hospital: a systematic review
Authors: Guerra Mark L , Singh Parminder J , Taylor Nicholas F 
Published: December 2014

Objective: To systematically review the effect of early mobilization after hip or knee joint replacement surgery on length of stay in an acute hospital. Methods: Randomized controlled trials were selected from electronic databases based on inclusion criterion requiring an experimental group mobilizing (sitting out of bed/walking) earlier than a comparison group post joint replacement surgery of the hip or knee in an acute hospital. Clinically homogeneous data were analyzed with meta-analysis. Results: Five randomized controlled trials (totaling 622 participants) were included for review. A meta-analysis of 5 trials found a reduced length of stay of 1.8 days (95% confidence interval 1.1 to 2.6) in favor of the experimental group. In 4 of the 5 trials the experimental group first sat out of bed within 24 hours post operatively. In 4 of the 5 trials the experimental group first walked within 48 hours post operatively. Individual trials reported benefits in range of motion, muscle strength and health-related quality of life in favor of the experimental group. There were no differences in discharge destinations, incidence of negative outcomes or adverse events attributable to early mobilization when compared to the comparison groups. Conclusion: Early mobilization post hip or knee joint replacement surgery can result in a reduced length of stay of about 1.8 days. Trials that reported these positive results showed that early mobilization can be achieved within 24 hours of operation. This positive gain was achieved without an increase in negative outcomes.
The Effect of Autologous Platelet Rich Plasma in the Treatment of Achilles Tendon Ruptures
Authors: Şen Baran , Güler Serkan , Çeçen Berivan , Kumtepe Erdem , Bağrıyanık Alper , Özkal Sermin , Özcan M. Ali , Özsan Hayri , Şanlı Namık , Tatari Mehmet Hasan 
Published: December 2014

Objectives: The aim of this study was to determine the effect of autologous platelet rich plasma (PRP) in the treatment of Achilles tendon ruptures in rabbits. Methods: The study included 14 New Zealand albino rabbits that were divided randomly into 2 groups, A and B, each containing seven rabbits. On day zero, all 28 Achilles tendons were tenotomized and repaired. In group A, the tendons were injected with PRP post surgery whereas those in group B were left untreated. On day 28, the right tendons in both groups were examined histopathologically via both light and electron microscopy, and the left tendons were subjected to biomechanical testing. Results: The histological and biomechanical findings in group A were better than those in group B, but the difference was not significant. Conclusion: PRP had no effect on the healing process 28 days post Achilles tendon rupture.
The Comparison of Results of Early and Late Rehabilitation Following Arthroscopic Bankart Repair with Knotless Anchor in Recurrent Traumatic Anterior Shoulder Dislocation
Authors: Kütahya Harun , Yel Mustafa , Bilge Onur , Güleç Ali , Kaçıra Burkay Kutluhan , Toker Serdar 
Published: December 2014

Objectives: The aim of this study was to compare the clinical and functional results of early and late rehabilitation of patients who had undergone arthroscopic Bankart repair with knotless anchor for recurrent shoulder dislocation and to define the most appropriate rehabilitation time and the effect of this on recurrence. Methods: 34 patients (32 male and 2 female) were included in this study. The patients were diagnosed with recurrent anterior shoulder dislocation with Bankart lesion in our institution. The exclusion criteria in this study were multi-directional shoulder instability, wide osseous Bankart lesion, wide Hill-Sachs lesion or rotator cuff tear. All patients underwent arthroscopic Bankart repair. Knotless anchor was used in all patients. The patients were grouped into 2 groups postoperatively according to the immobilization period and rehabilitation regimen. Both groups equally consisted of 17 patients. (Group 1; early rehabilitation group, Group 2; late rehabilitation group) All patients were examined retrospectively. Gender, age, dislocated side, dominant hand, recurrence, presence of additional pathologies, time of first and last dislocations preoperatively and numbers of dislocations were the demographic data recorded. At the final follow-up; the restriction in external rotation was measured by comparative goniometry and clinical evaluation was made using the Constant and Rowe scores. One-sample T-test, Mann-Whitney U Test, Crosstabs Chi Square Test and Shapiro-Wilk Tests used for statistical analysis. Results: The mean age of the patients in Group 1 was found to be 25.1 ± 6.5 ( 17-43) years and in Group 2, 30.8 ± 6.8 (21-46) years. After a mean follow-up period of 14.7 months, no patients in Group 1 experienced a recurrence, whereas in Group 2 over the mean follow-up period of 38.5 months, there was dislocation, following episodes of subluxation, in only 1 patient (5.8%). When the parameters of first dislocation, last dislocation and number of dislocations were evaluated separately in two groups, no statistical difference was observed between the groups in the relevant parameters (n.s.). A statistically significant difference was determined between the groups in respect to the restriction in external rotation (p<0.05). There was no statistically significant difference between the groups in respect to the Constant and Rowe scores (n.s.). Conclusion: The most important result of this study was that the early beginning of rehabilitation yielded less external rotation restriction than late beginning of rehabilitation. The absence of recurrence in the group of early beginning of rehabilitation reminds the question “does early rehabilitation reduce recurrence rates?” The findings in this study should be confirmed with further prospective, randomized and longer follow-up studies.
Comparison of Mesenchymal Stem Cell Versus Bone Marrow Treatment to Enhance Tendon to Bone Healing in an Animal Model
Authors: Aktaş Erdem , Lu Jun , Chamberlain Connie , Saether Erin , Lee Jae Sung , Vanderby Ray 
Published: December 2014

Objectives: Although anterior cruciate ligament reconstruction is one of the most common procedures in the field of sports medicine, less than 50% can return to previous activity level partially due to poor biological incorporation of tendon to bone. The aim of the study is to investigate the biological and mechanical effects of Mesenchymal Stem Cell (MSC) and Bone Marrow (BM) treatment for early tendon graft healing in a bone tunnel. Methods: 60 Wistar Albino rats were enrolled in the study and divided in 3 groups equal in number. In all animals a bilateral 1.2 mm bone tunnel was created in proximal tibia. 15 mm Digital Flexor tendons were harvested from each lower extremity and passed from each tunnel. Medial ends of the graft was secured to bone using a custom made endobutton while lateral portion was sutured to periosteum. 100μl whole Bone marrow was aspirated from group 1 animals and injected into the tunnel after tendon transfer while 106 MSCs in 50μl HBSS was injected in the tunnel in group 2. Group 3 was taken as control. Tendon to bone healing was evaluated via immunohistochemistry and mechanical testing at 2 and 6 weeks. Results: At 2 weeks the tendon to bone interface tissue was found to be stronger in the BM treatment group whereas there was no difference in stiffness between group 1 and 2. Interface tissue width was found to be significantly decreased in the BM group compared to control and MSC treatment groups (p=0.0012, p=0.0001). At 2 weeks the number of M1 macrophages at the interface tissue was found to be significantly low in the BM group while M2 macrophages were highest in the MSC group. Cellularity was observed significantly high in the MSC group while tissue density was lowest in the BM group due to accelerated graft degradation at 2 weeks. Conclusion: Although both Bone Marrow and Mesenchymal Stem Cell treatments enhance tendon to bone healing by accelerating the remodeling process, Bone Marrow treatment reveals a more anti-inflammatory healing with improved mechanical properties.
How Consistent are the MRI Findings and the Clinical Outcomes after Meniscus Repair?
Authors: Bombaci Hasan , Cetinkaya Fatih , Meric Kaan 
Published: December 2014

Objectives: The meniscal repair is a preferred treatment whenever possible after meniscus tear. There are reports in the literature that MRI assessment is not useful to evaluate healing of the meniscus after repair. However, we have not found any study which compares the clinical outcomes of meniscus repair according to the MRI findings. The purpose of this study was to compare the MRI features and the clinical outcomes after meniscus repair. Methods: 32 patients underwent meniscus repair between January 2011 and June 2013. Twenty three of them accepted a control MRI examination at last follow-up visit. One patient was more than 130 kg in weight so it was not possible to perform MRI examination in our institution. Therefore, twenty-two patients (17 male, 5 female) were included in this study. The mean age was 31.81 (18-48). Preoperative clinical and radiological findings were obtained from the hospital registry. At last follow-up, the clinical examination and MRI assessment were performed. The results were compared statistically with the ANOVA method. Results: MRI assessment, obtained at the last follow-up, was performed blindly by the radiology specialist and senior surgeon and any conflicts between the two assessments were settled by using the preoperative MRI findings. In 10 patients (45.45%), the MRI examination revealed normal/nearly normal meniscal signal alteration, in three (13.64%), incomplete tear and in nine (40.91%), a vertical/complex tear signal located in the previously torn meniscus area. Post-operatively the mean Lysholm score was 91.40±10.57 and Tegner activity score, 4.59±1.62. Also, the Lysholm score (91.5±12.44, 94.33±5.50 and 90.33±10.34, respectively) and Tegner activity score (4.2±1.87, 6±1.00 and 4.5±1.33, respectively) were evaluated in each group separately, however the difference was not statistically significant (p>0.05). Conclusion: In the present study, there was no correlation between the MRI signals and clinical outcomes. The Lysholm score was found to be over 90 in 20 of the 22 knees in this series. In conclusion, the findings reveal that the meniscus fulfills its function as normal or nearly normal even though the MRI findings fail to prove healing, in the mean 19. 5 months’ period postoperatively.