bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Specialized Transduction Using Recombineering in Mycobacterium tuberculosis
Authors: Tufariello JoAnn M. , Malek Adel A. , Vilchèze Catherine , Cole Laura E. , Ratner Hannah K. , González Pablo A. , Jain Paras , Hatfull Graham F. , Larsen Michelle H. , Jacobs William R. 
Published: May 2014

ABSTRACT

G
enetic engineering has contributed greatly to our understanding of
Mycobacterium tuberculosis
biology and has facilitated antimycobacterial and vaccine development. However, methods to generate
M. tuberculosis
deletion mutants remain labor-intensive and relatively inefficient. Here, methods are described that significantly enhance the efficiency (greater than 100-fold) of recovering deletion mutants by the expression of mycobacteriophage recombineering functions during the course of infection with specialized transducing phages delivering allelic exchange substrates. This system has been successfully applied to the CDC1551 strain of
M. tuberculosis
, as well as to a Δ
recD
mutant generated in the CDC1551 parental strain. The latter studies were undertaken as there were precedents in both the
Escherichia coli
literature and mycobacterial literature for enhancement of homologous recombination in strains lacking RecD. In combination, these measures yielded a dramatic increase in the recovery of deletion mutants and are expected to facilitate construction of a comprehensive library of mutants with every nonessential gene of
M. tuberculosis
deleted. The findings also open up the potential for sophisticated genetic screens, such as synthetic lethal analyses, which have so far not been feasible for the slow-growing mycobacteria.

IMPORTANCE
Genetic manipulation of
M. tuberculosis
is hampered by laborious and relatively inefficient methods for generating deletion mutant strains. The combined use of phage-based transduction and recombineering methods greatly enhances the efficiency by which knockout strains can be generated. The additional elimination of
recD
further enhances this efficiency. The methods described herein will facilitate the construction of comprehensive gene knockout libraries and expedite the isolation of previously difficult to recover mutants, promoting antimicrobial and vaccine development.
A 5-year-old boy with miliary and osteoarticular tuberculosis
Authors: Washington Charles Henry , Oberdorfer Peninnah 
Published: May 2014

SummaryOsteoarticular involvement is one manifestation of extrapulmonary tuberculosis (TB). We present a 5-year-old Burmese boy with 10 months of right hip pain and decreased range of motion. The patient also had low-grade fever, cough and decreased appetite. The patient was undocumented and had recently moved from Myanmar. He was thin, in moderate distress with bilateral lung rhonchi, mild subcostal retractions, low back pain, right hip tenderness and painful and limited right range of motion. The patient's chest and pelvis radiographs showed a miliary pattern and right acetabulum osteolytic lesions, respectively. He was started on anti-TB medication and cefotaxime. Ofloxacin was added because of the concern of drug-resistant TB. The patient underwent a right hip debridement. His symptoms improved markedly, with improved mobility. TB is a challenging infection to diagnose, which can cause significant delays in management.
Klein's paradox and quantum Hamiltonian dynamics in complex spacetime
Authors: Payandeh Farrin 
Published: May 2014

In this paper, along with previous investigation in Payandeh et al., Chin. Phys. C 37, 113103 (2013), we will use the full set of free Dirac's solutions to remove the Klein's paradox. However, we choose a different approach, namely the relativistic quantum Hamilton–Jacobi equations and the resultant quantum states. We show that this full set of solutions can also be retained as a single wave function, and also possess the potential of removing Klein's paradox.
Mechanism and Efficacy of Sub–50-nm Tenfibgen Nanocapsules for Cancer Cell–Directed Delivery of Anti-CK2 RNAi to Primary and Metastatic Squamous Cell Carcinoma
Authors: Unger Gretchen M. , Kren Betsy T. , Korman Vicci L. , Kimbrough Tyler G. , Vogel Rachel I. , Ondrey Frank G. , Trembley Janeen H. , Ahmed Khalil 
Published: May 2014

Abstract
Improved survival for patients with head and neck cancers (HNC) with recurrent and metastatic disease warrants that cancer therapy is specific, with protected delivery of the therapeutic agent to primary and metastatic cancer cells. A further objective should be that downregulation of the intracellular therapy target leads to cell death without compensation by an alternate pathway. To address these goals, we report the utilization of a sub–50-nm tenfibgen (s50-TBG) nanocapsule that delivers RNAi oligonucleotides directed against the essential survival signal protein kinase CK2 (RNAi-CK2) in a cancer cell–specific manner. We have evaluated mechanism and efficacy of using s50-TBG-RNAi-CK2 nanocapsules for therapy of primary and metastatic head and neck squamous cell carcinoma (HNSCC). s50-TBG nanocapsules enter cancer cells via the lipid raft/caveolar pathway and deliver their cargo (RNAi-CK2) preferentially to malignant but not normal tissues in mice. Our data suggest that RNAi-CK2, a unique single-stranded oligonucleotide, co-opts the argonaute 2/RNA-induced silencing complex pathway to target the CK2αα′ mRNAs. s50-TBG-RNAi-CK2 inhibited cell growth corresponding with reduced CK2 expression in targeted tumor cells. Treatment of three xenograft HNSCC models showed that primary tumors and metastases responded to s50-TBG-RNAi-CK2 therapy, with tumor shrinkage and 6-month host survival that was achieved at relatively low doses of the therapeutic agent without any adverse toxic effect in normal tissues in the mice. We suggest that our nanocapsule technology and anti-CK2 targeting combine into a therapeutic modality with a potential of significant translational promise. Mol Cancer Ther; 13(8); 2018–29. ©2014 AACR.
Myeloid Lineage–Specific Deletion of Antioxidant System Enhances Tumor Metastasis
Authors: Hiramoto Keiichiro , Satoh Hironori , Suzuki Takafumi , Moriguchi Takashi , Pi Jingbo , Shimosegawa Tooru , Yamamoto Masayuki 
Published: May 2014

Abstract
Oxidative stress accelerates the pathogenesis of a number of chronic diseases including cancer growth and its metastasis. Transcription factor NF-E2–related factor-2 (Nrf2), which regulates the cellular defense system against oxidative stress, elicits essential protection against chemical-induced carcinogenic insults. We recently demonstrate that the systemic deletion of Nrf2 leads to an increased susceptibility to cancer metastasis, which is associated with aberrant reactive oxygen species (ROS) accumulation in myeloid-derived suppressor cells (MDSC). However, it remains elusive whether cellular antioxidant defense system in the myeloid lineage cells plays indispensable roles for metastatic cancer progression. We herein found that myeloid lineage–specific Nrf2-deficient mice exhibited an increased susceptibility to pulmonary metastasis of the mouse Lewis lung carcinoma cells, and ROS level was more highly elevated in MDSCs of cancer-bearing Nrf2-deficient mice. Similarly, myeloid lineage–specific deletion of selenocysteine-tRNA gene (Trsp), which is essential for synthesis of antioxidant selenoenzymes, resulted in increased number of metastatic nodules along with ROS accumulation in MDSCs of cancer-bearing mice. These results thus indicate that the antioxidant systems directed by Nrf2 and selenoenzymes contribute to the clearance of ROS in MDSCs, efficiently preventing cancer cell metastasis. Consistent with this notion, a synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im), a potent Nrf2 inducer, attenuated the ROS production in MDSCs, and thereafter reduced metastatic nodules. Taken together, this study provides compelling lines of evidence that Nrf2 inducer retains therapeutic efficacy against cancer cell metastasis. Cancer Prev Res; 7(8); 835–44. ©2014 AACR.
Optimization in Stent Implantation by Manual Thrombus Aspiration in ST-Segment–Elevation Myocardial Infarction
Authors: Fernández-Rodríguez Diego , Regueiro Ander , Brugaletta Salvatore , Martín-Yuste Victoria , Masotti Mónica , Cequier Angel , Iñíguez Andrés , Serra Antonio , Hernández-Antolín Rosana , Mainar Vicente , Valgimigli Marco , Tespili Maurizio , den Heijer Pieter , Bethencourt Armando , Vázquez Nicolás , Serruys Patrick W. , Sabaté Manel 
Published: May 2014

Background—
Manual thrombus aspiration (TA) is effective to reduce the thrombus burden during primary percutaneous coronary intervention for ST-elevation myocardial infarction. The objective of this study is to assess the impact of manual TA on stent implantation during primary percutaneous coronary intervention.

Methods and Results—

Population of the EXAMINATION trial (n=1498) was divided into 2 groups according to the use of TA. Immediate angiographic results, primary patient-oriented end point (combination of all-cause death, myocardial infarction, and any revascularization) and secondary device-oriented end point (combination of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization), definite/probable stent thrombosis, and major/minor bleeding were evaluated at 2 years. A total of 976 (65.2%) patients were classified into TA group and 522 (34.8%) patients into nonthrombus aspiration group. Manual TA was most frequently used in patients with worse initial thrombolysis in myocardial infarction flow. The TA group received less number of stents implanted (1.35±0.62 versus 1.45±0.71,
P
=0.005) with bigger size (3.25±0.44 versus 3.11±0.46 mm,
P
<0.001) compared with the nonthrombus aspiration group. A higher rate of direct stenting (69.2% versus 43.3%,
P
<0.001) with lower rate of postdilatation (13.0% versus 18.0%,
P
<0.009) was also present in the TA group compared with the nonthrombus aspiration group. At 2-year follow-up, no differences in clinical end point were observed between groups.

Conclusions—
Manual TA during primary percutaneous coronary intervention is associated with a higher rate of direct stenting, a lower rate of postdilatation, and larger and less stents in comparison with conventional primary percutaneous coronary intervention. Conversely, manual TA had no apparent impact on clinical outcomes at long-term follow-up.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00828087.
Is More Better? Using Metadata to Explore Dose–Response Relationships in Stroke Rehabilitation
Authors: Lohse Keith R. , Lang Catherine E. , Boyd Lara A. 
Published: May 2014

Background and Purpose—
Neurophysiological models of rehabilitation and recovery suggest that a large volume of specific practice is required to induce the neuroplastic changes that underlie behavioral recovery. The primary objective of this meta-analysis was to explore the relationship between time scheduled for therapy and improvement in motor therapy for adults after stroke by (1) comparing high doses to low doses and (2) using metaregression to quantify the dose–response relationship further.

Methods—
Databases were searched to find randomized controlled trials that were not dosage matched for total time scheduled for therapy. Regression models were used to predict improvement during therapy as a function of total time scheduled for therapy and years after stroke.

Results—

Overall, treatment groups receiving more therapy improved beyond control groups that received less (
g
=0.35; 95% confidence interval, 0.26–0.45). Furthermore, increased time scheduled for therapy was a significant predictor of increased improvement by itself and when controlling for linear and quadratic effects of time after stroke.

Conclusions—
There is a positive relationship between the time scheduled for therapy and therapy outcomes. These data suggest that large doses of therapy lead to clinically meaningful improvements, controlling for time after stroke. Currently, trials report time scheduled for therapy as a measure of therapy dose. Preferable measures of dose would be active time in therapy or repetitions of an exercise.
A Sociotechnical Model of the Flight Crew Task
Authors: Cahill Joan , McDonald Nick , Losa Captain Gabriel 
Published: May 2014

Objective: The objective of this research was to advance an improved model of Flight Crew task performance. Background: Existing task models present a “local” description of Flight Crew task performance. Method: Process mapping workshops, interviews, and observations were conducted with both pilots and flight operations personnel from five airlines, as part of the Human Integration into the Lifecycle of Aviation Systems (HILAS) project. Results: The functional logic of the process dictates Flight Crew task requirements and specific task workflows. The Flight Crew task involves managing different levels of operational and environmental complexity, associated with the particular flight context. In so doing, the Flight Crew act as a coordinating interface between different human agents involved in the Active Flight Operations process and other processes that interface with this process. Conclusion: This article presents a new sociotechnical model of the Flight Crew task. The proposed model reflects a shift from a local explanation of Flight Crew task activity to a broader process-centric explanation. In so doing, it illuminates the complex role of procedures in commercial operations. Application: The task model suggests specific requirements for pilot task support tools, procedures design, performance evaluation and crew resource management (CRM) training. Also, this model might be used to assess future operational concepts and associated technology requirements. Lastly, this model provides the basis for the operational validation of both existing and future cockpit technologies.
“We Are All Gonna Get Diabetic These Days”
Authors: Pyatak Elizabeth A. , Florindez Daniella , Peters Anne L. , Weigensberg Marc J. 
Published: May 2014

Purpose The purpose of this study was to investigate how an intergenerational legacy of type 2 diabetes affected the knowledge, attitudes, and treatment strategies of Hispanic young adults with diabetes. Methods Eight Hispanic young adults (ages 18-30 years) participated in a series of in-home longitudinal qualitative interviews, and 11 of their family members completed single in-home interviews, regarding their diabetes management practices. Interview transcripts were analyzed thematically by a team of researchers. Results Five themes emerged that characterized the influence of an intergenerational legacy of diabetes on young adults: food and family (how meal preparation and eating are shared within families), doing together (activity participation is contingent on others’ participation), knowledge and expectations (expectations for the future and understandings of diabetes are shaped by family members), miscarried helping (well-intentioned actions have negative consequences), and reciprocal support (children and parents support each other’s diabetes care). Conclusions Hispanic young adults’ knowledge, attitudes, and self-care practices related to diabetes are strongly influenced by the diabetes management practices of family members with diabetes, which often depart from current standards of diabetes care. Care providers should consider family members as a potentially significant influence, either positive or negative, on the diabetes self-care practices of this population.
The Ophthalmology Microscalpel versus Standard Scalpels and Wound Healing in a Rat Model
Authors: Pearce Elizabeth C. , Hall Joseph E. , Boyd Kelli L. , Rousseau Bernard , Ries W. Russell 
Published: May 2014

ObjectiveWe tested the hypothesis that the ophthalmology microscalpel, compared to standard incisional instruments, causes less trauma during incisions resulting in decreased inflammation and greater tensile strength of wounds.Study DesignProspective animal study.SettingAnimal laboratory.Subjects and MethodsThirty‐four Sprague‐Dawley rats received dorsum skin incisions with the microscalpel, electrosurgical device, 11 blade scalpel, and 15 blade scalpel. Wounds were harvested at 1 week, 2 weeks, 3 weeks, and 6 weeks, then analyzed histologically in a blinded manner for inflammation markers and tested for tensile strength.ResultsThe microscalpel wounds had significantly higher tensile strength compared to the 15 blade (P =. 045) and electrocautery device (P =. 000) but equivocal strength to the 11 blade (P =. 457). The electrocautery wounds were weaker than all 3 steel blades. No significant difference was found between the microscalpel, 11 blade, and 15 blade incisions for the 5 markers of inflammation. Electrocautery wounds had significantly worse inflammatory scores, specifically, higher angiogenesis and larger wound gap compared to the microscalpel (P =. 004, P =. 002), 11 blade (P =. 007, P =. 023), and 15 blade (P =. 010, P =. 003), respectively.ConclusionMicroscalpel incisions result in less inflammation and increased tensile strength compared with electrocautery and higher tensile strength compared to the 15 blade in the rat model. Inflammation scores were equivocal between the microscalpel, 11 blade, and 15 blade. Our findings support the use of the microscalpel blade for facial plastic and reconstructive procedures. Prospective, randomized human studies are warranted.
Chondroprotection and the Prevention of Osteoarthritis Progression of the Knee
Authors: Gallagher Brian , Tjoumakaris Fotios P. , Harwood Marc I. , Good Robert P. , Ciccotti Michael G. , Freedman Kevin B. 
Published: May 2014

Background: Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP). Purpose: To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis. Study Design: Systematic review; Level of evidence, 2. Methods: A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using “treatment,” “osteoarthritis,” and “knee” as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures. Results: A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP. Conclusion: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection.
In the United States, a Mother’s Plans for Infant Feeding Are Associated with Her Plans for Employment
Authors: Mirkovic Kelsey R. , Perrine Cria G. , Scanlon Kelley S. , Grummer-Strawn Laurence M. 
Published: May 2014

Background: The American Academy of Pediatrics recommends 6 months of exclusive breastfeeding, however, only 16% of US infants meet this recommendation. Shorter exclusive/predominant breastfeeding durations have been observed from women who return to work early and/or full-time. Objective: We assessed the relationship between prenatal plans for maternity leave duration and return to full-time/part-time status and plans for exclusive breastfeeding. Methods: This study included 2348 prenatally employed women from the Infant Feeding Practices Study II (2005-2007) who planned to return to work in the first year postpartum. Bivariate analysis and logistic regression were used to describe the association of maternity leave duration and return status with plans for infant feeding. Results: Overall, 59.5% of mothers planned to exclusively breastfeed in the first few weeks. Mothers planning to return to work within 6 weeks had 0.60 times the odds (95% confidence interval [CI], 0.46-0.77) and mothers planning to return between 7 and 12 weeks had 0.72 times the odds (95% CI, 0.56-0.92) of planning to exclusively breastfeed compared with mothers who were planning to return after 12 weeks. Prenatal plans to return full-time (≥ 30 hours/week vs part-time) were also associated with lower odds of planning to exclusively breastfeed (adjusted odds ratio = 0.61; 95% CI, 0.51-0.77). Conclusion: Mothers planning to return to work before 12 weeks and/or full-time were less likely to plan to exclusively breastfeed. Longer maternity leave and/or part-time return schedules may increase the proportion of mothers who plan to exclusively breastfeed.
Open reduction and fixation of displaced lateral clavicle fractures using the Minimally Invasive Acromioclavicular Joint Reconstruction (MINAR®) technique: a case series review
Authors: Kenyon Peter , Morgan Barnes William , Webb Mark , Ebreo Darren , Wheelton Andrew , Ravenscroft Matt John 
Published: May 2014

Background Lateral end of clavicle fractures can be a challenge, with a 20% to 30% non-union rate if treated non-operatively. Several operative options exist, each having their own merits and some having potential disadvantages. The Minimally Invasive Acromioclavicular Joint Reconstruction (MINAR®) (Storz, Tutlingen, Germany) set uses an Orthocord (Depuy Synthes Mitek, Leeds, UK) suture and two Flip Tacks (Storz) via a transclavicular-coracoid approach to reconstruct the coracoclavicular ligaments. Methods Referrals were made to two senior surgeons at separate institutions regarding Robinson Type 3 fractures of the lateral end of the clavicle. All patients were treated with MINAR implant via a minimally invasive approach. Two-year follow-up was obtained using the Oxford Shoulder Score (OSS) and the Quick DASH (Disability of the Arm Shoulder and Hand) score. Results Sixteen cases of acute fractures of the lateral end of the clavicle were included in this series. At final follow-up, the mean OSS was 44.75 (range 35 to 48) and the median Quick DASH score was 2.3 (range 0 to 35.9). Fifteen patients achieved bony union (one asymptomatic non-union) and there were no complications or re-operations. Conclusions The MINAR is reproducible and safe when treating lateral end of clavicle fractures. We consider that, over the short- to mid-term, it achieves results equivalent to those for other implants.