bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sentry
Authors: Shriraman Arrvindh , Dwarkadas Sandhya 
Published: October 2012

Light-weight, flexible access control, which allows software to regulate reads and writes to any granularity of memory region, can help improve the reliability of today's multi-module multi-programmer applications, as well as the efficiency of software debugging tools. Unfortunately, access control in today's processors is tied to support for virtual memory, making its use both heavy weight and coarse grain. In this paper, we propose Sentry, an auxiliary level of virtual memory tagging that is entirely subordinate to existing virtual memory-based protection mechanisms and can be manipulated at the user level. We implement these tags in a complexity-effective manner using an M-cache (metadata cache) structure that only intervenes on L1 misses, thereby minimizing changes to the processor core. Existing cache coherence states are repurposed to implicitly validate permissions for L1 hits. Sentry achieves its goal of flexible and light-weight access control without disrupting existing inter-application protection, sidestepping the challenges associated with adding a new protection framework to an existing operating system.
We illustrate the benefits of our design point using 1) an Apache-based web server that uses the M-cache to enforce protection boundaries among its modules and 2) a watchpoint-based tool to demonstrate low-overhead debugging. Protection is achieved with very few changes to the source code, no changes to the programming model, minimal modifications to the operating system, and with low overhead incurred only when accessing memory regions for which the additional level of access control is enabled.
Dual Systemic Tumor Targeting with Ligand-Directed Phage and Grp78 Promoter Induces Tumor Regression
Authors: Kia Azadeh , Przystal Justyna M. , Nianiaris Nastasia , Mazarakis Nicholas D. , Mintz Paul J. , Hajitou Amin 
Published: October 2012

Abstract
The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications. Mol Cancer Ther; 11(12); 2566–77. ©2012 AACR.
Three-Grade Classification of Photoplethysmography for Evaluating the Effects of Treatment in Raynaud Phenomenon
Authors: Yang Shin-Seok , Park Keun-Myoung , Kim Young-Wook , Kim Dong-Ik 
Published: October 2012

We assessed the utility of a 3-grade classification of photoplethysmography (PPG) with cold water provocation test in Raynaud phenomenon (RP). A total of 35 patients with RP and 38 healthy volunteers were recruited. In healthy volunteers, PPG was measured twice at intervals of 30 minutes for evaluating reproducibility of test. Percentage variation of the PPG amplitude in post- versus precold provocation was expressed on a 3-grade scale at 1, 3, and 5 minutes (reflection index: RI) in patients with RP. The improvement pattern of the PPG (IPPPG) was evaluated by summing the score differences from RI1 min to RI3 min and RI5 min. After a therapeutic period of 8 weeks with nifedipine, the decreases in posttherapeutic RI3 min and RI5 min were statistically significant ( P < .05). Subgroup analysis of IPPPG showed statistical significance in patients with negative fluorescent antinuclear antibody ( P < .05). The analysis of cold-provoked PPG waves demonstrated and quantified improvements in peripheral arterial circulation in RP.
Return to High-Level Throwing After Combination Infraspinatus Repair, SLAP Repair, and Release of Glenohumeral Internal Rotation Deficit
Authors: Van Kleunen Jonathan P. , Tucker Scott A. , Field Larry D. , Savoie Felix H. 
Published: October 2012

Background: The overhead-throwing athlete is a unique patient, requiring an elite, precise functional ability. Superior labral tears are quite common, and the percentage of athletes who return to play after superior labrum anterior-posterior (SLAP) repair has been variable. A tear of the infraspinatus caused by either internal impingement or tension overload may compromise this return. Hypothesis: The rate of return to a level of play similar to or greater than the preinjury level after repair of combined SLAP and infraspinatus injuries will be lower than in previous reports of SLAP repair alone. Study Design: Case series; Level of evidence, 4. Methods: In the current study, we examined a series of overhead-throwing athletes with diagnoses of both a SLAP tear and a significant (>50%) tear of the infraspinatus tendon who underwent surgical repair of both injuries. We identified 17 high-level baseball players younger than 25 years who underwent simultaneous arthroscopic repairs of a SLAP tear with a standard suture anchor technique and of an infraspinatus tear with either a free polydioxanone (PDS) suture or suture anchor between 2005 and 2008. The postoperative records of all patients were reviewed to determine their ability to return to play and their postoperative level of performance. All patients were then contacted to determine their Kerlan-Jobe Orthopaedic Clinic Overhead Athlete Shoulder and Elbow score and their current sport participation level. Results: All 17 patients in the series attempted to return to their prior sport after completion of postoperative rehabilitation. Only 6 patients (35%) were able to return to the same or a superior preinjury level of performance. Five of the remaining 11 patients returned to play at a lower level, either playing the same position or else forced to switch to another position of play because of a decline in throwing velocity. Six patients were unable to return to play. No complications or reoperations occurred in any of the patients following surgery. Conclusion: A significant (>50%) tear of the infraspinatus in combination with glenohumeral internal rotation deficit (GIRD) and SLAP tears in the throwing athlete results in a guarded prognosis in return to play at the same level. While the rates of return to play in overhead-throwing athletes with an isolated SLAP tear have historically been encouraging, the prognosis for an athlete with both a SLAP and infraspinatus tear is more guarded. These patients are not likely to return to their preinjury level of play.
Level of Evidence in Anterior Cruciate Ligament Reconstruction Research
Authors: Samuelsson Kristian , Desai Neel , McNair Erik , van Eck Carola F. , Petzold Max , Fu Freddie H. , Bhandari Mohit , Karlsson Jón 
Published: October 2012

Background: There have been numerous studies on anterior cruciate ligament (ACL) reconstruction. Considering the vast number of studies, a quick assessment reveals rather few with a high level of evidence. Purpose: The primary aim was to categorize the study type and level of evidence of studies on primary ACL reconstruction by applying the level of evidence rating system proposed by the Oxford Centre for Evidence-Based Medicine. The secondary aims were to correlate the level of evidence with the impact factor of the journal, to evaluate the level of evidence over time, and to evaluate the geographic distribution of the included studies. Study Design: Systematic review. Methods: An electronic search was performed using the databases PubMed, EMBASE, and Cochrane Library. Studies published from January 1995 to August 2011 were included. Therapeutic studies written in English that report on isolated primary ACL reconstruction with clinical outcome measurements related to the reconstruction were included. Categorization and implementation of the level of evidence were performed. Correlation between the level of evidence and the impact factor of the journal was analyzed together with linear regression models to reveal any significant trends over time. Results: A total of 7154 studies were analyzed, of which 1510 were included. Analysis of the study types revealed that case series (n = 494; 32.7%) was the most frequent study type. Randomized controlled trials represented 9.2% (n = 139) of the sample, whereas meta-analyses were rare. Single-bundle studies were the most common studies (n = 1333; 88.3%), followed by double-bundle (n = 98; 6.5%) and single- versus double-bundle (n = 79; 5.2%). The journals Arthroscopy, Knee Surgery Sports Traumatology Arthroscopy (KSSTA), and American Journal of Sports Medicine (AJSM) represented 43.5% (n = 657) of the included studies. Arthroscopy had the highest number of publications in general and in level 4 and 5 studies, whereas AJSM had the lowest number of the 3. AJSM had the highest number of level 1 and 2 studies in general. The mean level of evidence calculated without level 5 studies was 3.15 for Arthroscopy, 3.20 for KSSTA, and 2.9 for AJSM. There was a significant correlation ( P < .05) between the impact factor of the journal and mean level of evidence of the journal and the proportion high level of evidence studies (levels 1 and 2). There was a significant ( P < .05) trend toward higher mean level of evidence over time. Conclusion: Most therapeutic studies on primary ACL reconstruction were of low level of evidence, and there was a positive correlation between the journal’s impact factor and the mean level of evidence and the proportion of high level of evidence studies. There was significant trend toward higher mean level of evidence over time.
Fixation of Ankle Syndesmotic Injuries
Authors: Naqvi Gohar A. , Cunningham Patricia , Lynch Bernadette , Galvin Rose , Awan Nasir 
Published: October 2012

Background: Ankle syndesmotic injuries are complex and require anatomic reduction and fixation to restore the normal biomechanics of the ankle joint and prevent long-term complications. Purpose: The aim of this study is to compare the accuracy and maintenance of syndesmotic reduction using TightRope versus syndesmotic screw fixation. Study Design: Cohort study; Level of evidence, 2. Methods: This cohort study included consecutive patients treated for ankle syndesmotic diastases between July 2007 and June 2009. Single slice axial computed tomography (CT) scans of both the ankles together were performed at the level of syndesmosis, 1 cm above the tibial plafond. A greater than 2-mm widening of syndesmosis compared with the untreated contralateral ankle was considered significant malreduction. Clinical outcomes were measured using the American Orthopaedics Foot and Ankle Society (AOFAS) and Foot and Ankle Disability Index (FADI) scores. Results: Forty-six of 55 eligible patients participated in the study; 23 patients were in the TightRope group and 23 in the syndesmotic screw group. The average age was 42 years in the TightRope and 40 years in the syndesmotic screw group, and the mean follow-up time was 2.5 years (range, 1.5-3.5 years). The average width of normal syndesmosis was 4.03 ± 0.89 mm. In the TightRope group, the mean width of syndesmosis was 4.37 mm (SD, ±1.12 mm) ( P = .30, t test) compared with 5.16 mm (SD, ±1.92 mm) in the syndesmotic screw group ( P = .01, t test). Five of 23 ankles (21.7%) in the syndesmotic screw group had syndesmotic malreduction, whereas none of the TightRope group showed malreduction on CT scans ( P = .04, Fisher exact test). Average time to full weightbearing was 8 weeks in the TightRope group and 9.1 weeks in the syndesmotic screw group. There was no significant difference between the TightRope and syndesmotic screw groups in mean postoperative AOFAS score (89.56 and 86.52, respectively) or FADI score (82.42 and 81.22, respectively). Regression analysis confirmed malreduction of syndesmosis as the only independent variable that affected the clinical outcome (regression coefficient, −12.39; t = −2.43; P = .02). Conclusion: The results of this study indicate that fixation with TightRope provides a more accurate method of syndesmotic stabilization compared with screw fixation. Syndesmotic malreduction is the most important independent predictor of clinical outcomes; therefore, care should be taken to reduce the syndesmosis accurately.
Coagulanolide modulates hepatic glucose metabolism in C57BL/KsJ-db/db mice
Authors: Singh AB , Singh N , Akanksha  , Jayendra  , Maurya R , Srivastava AK 
Published: October 2012

Increased hepatic glucose output is one of the major causes of fasting hyperglycemia in diabetic patients. In this study, we investigated the mechanism of action of coagulanolide on hepatic glucose, regulating enzymes in type 2 diabetic C57BL/KsJ- db/db ( db/db) mice. Coagulanolide is an active component of Withania coagulans fruit. Oral administration of coagulanolide for 3 weeks decreases fasting blood glucose and plasma insulin significantly, and it improves glucose tolerance in the db/db mice group. The enzyme activity and protein expression of glucokinase and pyruvate kinase was significantly enhanced in coagulanolide-treated db/db group when compared with untreated one. On the other hand, activities and protein expression of fructose-1,6-bisphosphatase, glucose 6-phosphatase, phosphoenolpyruvate carboxykinase, and glycogen phosphorylase enzymes were significantly lowered in treated group. The treatment with coagulanolide also normalizes the concentrations of plasma cholesterol, triglyceride, free fatty acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the db/db mice. These findings suggested that the coagulanolide is useful in the control of fasting hyperglycemia in type 2 diabetes by regulating the production of hepatic glucose.
Posttraumatic Stress Disorder and Traumatic Brain Injury in Current Military Populations
Authors: Wall Pamela L. (Herbig) 
Published: October 2012

Background: The use of unconventional weaponry combined with decreased mortality rates and servicemembers being exposed to intense ground combat during multiple deployments has increased the risk of servicemembers living with the consequences of traumatic brain injuries (TBI) and combat operational stress. Objective: The purpose of this article is to perform a critical analysis of the literature to identify current rates of comorbid posttraumatic stress disorder (PTSD) and TBI in military and veteran populations who have served in Iraq or Afghanistan and their combined effects on persistent postconcussive symptoms. Design: A search of the literature with military and veteran populations published after 2001 in Pubmed, OVID/Medline, Cochran Database, Embase, Scopus, CINAHL, and PsychInfo was conducted using keywords. Results: Twenty studies met inclusion criteria. The literature search yielded mixed results for rates of PTSD, TBI, and comorbid conditions. Conclusions: There is some evidence that comorbid PTSD and TBI result in greater reports of postconcussive symptomology than either condition alone. Limitations include lack of consistency of measurements, sampling biases, and lack of experimental design, and these warrant further exploration. Future research is needed to decrease variability in study findings and elucidate relationships between these disorders and their effects on persistent postconcussive symptomology.
Increasing trial efficiency by early reallocation of placebo nonresponders in sequential parallel comparison designs: Application to antidepressant trials
Authors: Boessen Ruud , Knol Mirjam J , Groenwold Rolf HH , Grobbee Diederick E , Roes Kit CB 
Published: October 2012

Background The sequential parallel comparison (SPC) design was proposed to improve the efficiency of psychiatric clinical trials by reducing the impact of placebo response. It consists of two consecutive placebo-controlled comparisons of which the second is only entered by placebo nonresponders from the first. Previous studies suggest that in antidepressant trials, nonresponse to placebo can already be predicted after 2 weeks of follow-up. This would allow to reduce the first phase of the SPC design to further increase its efficiency. Purpose To compare the sample size requirements of an 8-week randomized controlled trial (RCT8) and alternative SPC designs with equal or longer total follow-up duration (SPC2+6, SPC4+4, and SPC6+6). Methods Scenarios for response and dropout rates were defined. Sample sizes to achieve 80% power were determined for the various designs. Three treatment functions assumed either a smaller, equal, or larger effect at the early stage of the trial as compared with that at the end. Two dropout models described either predominantly early or linearly increasing dropout, and dropout was considered as nonresponse. The relative efficiency of the different designs was evaluated across these scenarios and for a specific scenario based on empirical antidepressant trial data. Results The different SPC designs (i.e., SPC2+6, SPC4+4, and SPC6+6) were generally more efficient than the RCT8 design when the treatment effect at the early stage of the trial was equal or larger than the effect at the end. In this case, the advantage of the SPC designs increased in the presence of dropout. The SPC2+6 design was usually more efficient than the SPC4+4 design and was relatively less affected by dropout when it occurred predominantly early. For the scenario that was based on antidepressant trial data, the SPC2+6 and SPC4+4 designs required 51% and 53% fewer patients than the RCT8 design. Limitations A limited variety of scenarios was evaluated. Parameter values resembled those observed in antidepressant trials. Conclusions This study suggests that SPC designs are highly efficient alternatives to a conventional RCT in indications where placebo response is high and substantial treatment effects are established after a relatively short follow-up period (i.e., after the first SPC design phase). We conclude that SPC designs can reduce sample size requirements and increase success rates of antidepressant trials.
Convergent differentiation: myeloid and lymphoid pathways to murine plasmacytoid dendritic cells
Authors: Sathe Priyanka , Vremec David , Wu Li , Corcoran Lynn , Shortman Ken 
Published: October 2012

Abstract
The developmental origin of IFN-producing plasmacytoid dendritic cells (pDCs) has been uncertain. In the present study, we tracked the development of pDCs in cultures of BM precursors stimulated with Flt3 ligand. Common myeloid precursors (CMPs) produced both conventional DCs (cDCs) and pDCs via the DC-restricted common DC precursor. Common lymphoid precursors (CLPs) produced only a few cDCs with variable efficiency, but produced pDCs via a transient intermediate precursor with B-cell potential. The pDCs of both origins produced IFN-α when stimulated with CpG oligonucleotides. The pDCs of CLP origin showed evidence of past RAG1 expression and had D-J rearrangements in IgH genes. Most pDCs and all cDCs of CMP origin lacked these signs of a lymphoid past. However, in these cultures, some pDCs of CMP origin showed evidence of past RAG1 expression and had D-J IgH gene rearrangements; most of these derived from a subset of CMPs already expressing RAG1.
Genotyping of B. licheniformisbased on a novel multi-locus sequence typing (MLST) scheme
Authors: Madslien Elisabeth H , Olsen Jaran S , Granum Per E , Blatny Janet M 
Published: October 2012

Abstract

Background

Bacillus licheniformis has for many years been used in the industrial production of enzymes, antibiotics and detergents. However, as a producer of dormant heat-resistant endospores B. licheniformis might contaminate semi-preserved foods. The aim of this study was to establish a robust and novel genotyping scheme for B. licheniformis in order to reveal the evolutionary history of 53 strains of this species. Furthermore, the genotyping scheme was also investigated for its use to detect food-contaminating strains.

Results
A multi-locus sequence typing (MLST) scheme, based on the sequence of six house-keeping genes (adk, ccpA, recF, rpoB, spo0A and sucC) of 53 B. licheniformis strains from different sources was established. The result of the MLST analysis supported previous findings of two different subgroups (lineages) within this species, named “A” and “B” Statistical analysis of the MLST data indicated a higher rate of recombination within group “A”. Food isolates were widely dispersed in the MLST tree and could not be distinguished from the other strains. However, the food contaminating strain B. licheniformis NVH1032, represented by a unique sequence type (ST8), was distantly related to all other strains.

Conclusions
In this study, a novel and robust genotyping scheme for B. licheniformis was established, separating the species into two subgroups. This scheme could be used for further studies of evolution and population genetics in B. licheniformis.