bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triple-acting Lytic Enzyme Treatment of Drug-Resistant and Intracellular Staphylococcus aureus
Authors: Becker Stephen C. , Roach Dwayne R. , Chauhan Vinita S. , Shen Yang , Foster-Frey Juli , Powell Anne M. , Bauchan Gary , Lease Richard A. , Mohammadi Homan , Harty William J. , Simmons Chad , Schmelcher Mathias , Camp Mary , Dong Shengli , Baker John R. , Sheen Tamsin R. , Doran Kelly S. , Pritchard David G. , Almeida Raul A. , Nelson Daniel C. , Marriott Ian , Lee Jean C. , Donovan David M. 
Published: April 2016

AbstractMulti-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique antimicrobial activities from two parental proteins are combined into a single fusion protein. This effectively reduces the incidence of resistant strain development. The fusion protein reduced colonization by Staphylococcus aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of a triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular S. aureus as demonstrated in cultured mammary epithelial cells and in a mouse model of staphylococcal mastitis. Interestingly, the protein transduction domain was not necessary for reducing the intracellular pathogens in cultured osteoblasts or in two mouse models of osteomyelitis, highlighting the vagaries of exactly how protein transduction domains facilitate protein uptake. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics.
Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury
Authors: Zhang Yali , Wu Jianzhang , Ying Shilong , Chen Gaozhi , Wu Beibei , Xu Tingting , Liu Zhiguo , Liu Xing , Huang Lehao , Shan Xiaoou , Dai Yuanrong , Liang Guang 
Published: April 2016

AbstractAcute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases.
FET proteins regulate lifespan and neuronal integrity
Authors: Therrien Martine , Rouleau Guy A. , Dion Patrick A. , Parker J. Alex 
Published: April 2016

AbstractThe FET protein family includes FUS, EWS and TAF15 proteins, all of which have been linked to amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motor neurons. Here, we show that a reduction of FET proteins in the nematode Caenorhabditis elegans causes synaptic dysfunction accompanied by impaired motor phenotypes. FET proteins are also involved in the regulation of lifespan and stress resistance, acting partially through the insulin/IGF-signalling pathway. We propose that FET proteins are involved in the maintenance of lifespan, cellular stress resistance and neuronal integrity.
Zn/Cd ratios and cadmium isotope evidence for the classification of lead-zinc deposits
Authors: Wen Hanjie , Zhu Chuanwei , Zhang Yuxu , Cloquet Christophe , Fan Haifeng , Fu Shaohong 
Published: April 2016

AbstractLead-zinc deposits are often difficult to classify because clear criteria are lacking. In recent years, new tools, such as Cd and Zn isotopes, have been used to better understand the ore-formation processes and to classify Pb-Zn deposits. Herein, we investigate Cd concentrations, Cd isotope systematics and Zn/Cd ratios in sphalerite from nine Pb-Zn deposits divided into high-temperature systems (e.g., porphyry), low-temperature systems (e.g., Mississippi Valley type [MVT]) and exhalative systems (e.g., sedimentary exhalative [SEDEX]). Our results showed little evidence of fractionation in the high-temperature systems. In the low-temperature systems, Cd concentrations were the highest, but were also highly variable, a result consistent with the higher fractionation of Cd at low temperatures. The δ114/110Cd values in low-temperature systems were enriched in heavier isotopes (mean of 0.32 ± 0.31‰). Exhalative systems had the lowest Cd concentrations, with a mean δ114/110Cd value of 0.12 ± 0.50‰. We thus conclude that different ore-formation systems result in different characteristic Cd concentrations and fraction levels and that low-temperature processes lead to the most significant fractionation of Cd. Therefore, Cd distribution and isotopic studies can support better understanding of the geochemistry of ore-formation processes and the classification of Pb-Zn deposits.
A Comparison of Magnetic Resonance Imaging Muscle Fat Content in the Lumbar Paraspinal Muscles with Patient-Reported Outcome Measures in Patients with Lumbar Degenerative Disk Disease and Focal Disk Prolapse
Authors: Bhadresha Ashwin , Lawrence Owen John , McCarthy Michael J. H. 
Published: April 2016

Study Design Retrospective study. Objectives To assess the fatty atrophy of the lumbar paraspinal muscles (LPMs) as determined using magnetic resonance imaging in patients with lumbar degenerative disk disease (DDD) and focal disk herniation and to determine if fatty atrophy is associated with patient-reported outcome measures (PROMS). Methods One hundred sixty-five patients with lumbar DDD were identified from a PROMS database of >1,500 patients. These patients were divided into two study groups: DDD alone ( n= 58) and DDD with disk herniation ( n= 107). A grid was randomly applied to the axial scans at the L3–L4, L4–L5, and L5–S1 levels. The muscle-to-fat ratio of the LPMs was recorded and compared with PROMS data. Subcutaneous fat thickness at each level was also measured. Results This study found no difference in the muscle-to-fat ratio between the DDD and disk herniation groups. There was no association between the muscle-to-fat ratio and PROMS data in either group. There was significantly more subcutaneous fat at all levels in the DDD group as compared with the disk prolapse group. In DDD and disk prolapses, subcutaneous fat was thicker in women ( p = 0.013 and 0.001). In patients with DDD, more subcutaneous fat was associated with disability ( p < 0.001). Muscle content of erector spinae and multifidus negatively correlated with increasing age in both groups at the L3–L4 level. Conclusions Muscle fat content in the LPM does not appear to relate to PROMS. Muscle content decreases with age. Those with low back pain (DDD) have greater subcutaneous fat thickness.
10 Best resources on… intersectionality with an emphasis on low- and middle-income countries
Authors: Larson Elizabeth , George Asha , Morgan Rosemary , Poteat Tonia 
Published: April 2016

Abstract
Intersectionality has emerged as an important framework for understanding and responding to health inequities by making visible the fluid and interconnected structures of power that create them. It promotes an understanding of the dynamic nature of the privileges and disadvantages that permeate health systems and affect health. It considers the interaction of different social stratifiers (e.g. ‘race’/ethnicity, indigeneity, gender, class, sexuality, geography, age, disability/ability, migration status, religion) and the power structures that underpin them at multiple levels. In doing so, it is a departure from previous health inequalities research that looked at these forms of social stratification in isolation from one another or in an additive manner. Despite its potential use and long history in other disciplines, intersectionality is uncommonly used in health systems research in low- and middle-income countries (LMICs). To orient readers to intersectionality theory and research, we first define intersectionality and describe its role in public health, and then we review resources on intersectionality. We found that applications in public health mostly increased after 2009, with only 14 out of 86 articles focused on LMICs. To arrive at 10 best resources, we selected articles based on the proportion of the article that was devoted to intersectionality, the strength of the intersectionality analysis, and its relevance to LMICs. The first four resources explain intersectionality as a methodology. The subsequent six articles apply intersectionality to research in LMIC with quantitative and qualitative analysis. We provide examples from India, Swaziland, Uganda and Mexico. Topics for the studies range from HIV, violence and sexual abuse to immunization and the use of health entitlements. Through these 10 resources, we hope to spark interest and open a needed conversation on the importance and use of intersectional analysis in LMICs as part of understanding people-centred health systems.
Clinician–Educators as Dual Professionals: A Contemporary Reappraisal
Authors: Stoddard Hugh A. , Brownfield Erica D. 
Published: April 2016

Physicians who teach face unique responsibilities and expectations because they must educate learners while simultaneously caring for patients. Recently this has become even more difficult as the environment for clinician–educators has been undermined by public antipathy toward both the education profession and the medicine profession.
Erosion of public confidence in both professions is evidenced by three trends. First, the democratizing nature of the Internet and the availability of technical knowledge to laypeople have encroached on the domain of professional knowledge. Second, the responsibility of a professional to make decisions has been undercut by legal interpretations regarding how physicians are paid for patient care and how teachers are evaluated on performance. And finally, altruistic motivations in both professions have been called into question by external forces promoting “accountability” rather than trusting professionals to act for the best interest of their patients or students.
In this climate of increasing accountability and decreasing trust for professionals, clinician–educators can best serve patients and learners through transdisciplinary collaboration with professional educators. Clinician–educators should rely on professional educators for judgment and specialized knowledge in the field of education rather than embodying both professions by themselves. Health care practice has become more team oriented; health care education should do likewise to counteract the social and political trends eroding public confidence in medicine and education. Relying on collaboration with education professionals constitutes a substantial change to how clinician–educators define themselves, but it holds the best promise for medical training in the current social milieu.
Comparison of the yield from two faecal immunochemical tests at identical cutoff concentrations – a randomized trial in Latvia
Authors: Santare Daiga , Kojalo Ilona , Liepniece-Karele Inta , Kikuste Ilze , Tolmanis Ivars , Polaka Inese , Vikmanis Uldis , Boka Viesturs , Leja Marcis 
Published: April 2016

Objective
We have compared the performance of two faecal immunochemical tests (FIT) in an average-risk population.

Materials and methods
Altogether, 10 000 individuals aged 50–74 were selected randomly from the population of Latvia in 2011 and assigned randomly either to OC-Sensor or to FOB Gold single-time testing. Positivity of the test, frequency of colonic lesions, number needed to screen (NNscreen) and scope for the detection of an advanced neoplasm (cancer and advanced adenoma) were compared between the tests using the same cutoff concentrations in µg/g faeces. Confidence intervals (CIs) at 95% were calculated.

Results
Positivity with the cutoff set at 10 µg/g faeces was 12.8% (95% CI: 11.4–14.2) for FOB Gold and 8.3% (95% CI: 7.2–9.4) for OC-Sensor (P<0.001). Positivity was higher in men and the older age groups. Colonoscopy compliance was 55.5%. There was no significant difference between the two tests at comparable cutoff concentrations in µg/g, colonoscopy attendance rate or colonoscopy results. For advanced neoplasm detection, there was no significant difference in number needed to scope and NNscreen at a cutoff of 10 µg/g faeces; however, lower NNscreen was required to detect advanced neoplasms with the FOB Gold test at increased cutoff concentrations.

Conclusion
Different quantitative FIT systems may report different positivity rate at identical cutoff concentrations, which has to be considered when implementing the use of FIT in national screening programmes.
Psychological Strains and Suicidal Intent
Authors: Sun Long , Zhang Jie 
Published: April 2016

Abstract
Psychological strains are hypothesized to precede a suicidal intent that may lead to suicide, where psychological strains can be considered a function of social structure embedded with negative life events. This study aimed to test the potential relationship between psychological strains and suicidal intent in Chinese rural suicide attempters. Data regarding medically serious suicide attempters (N = 791) were gathered from county-level emergency rooms in randomly selected counties in rural China (15–54 years of age). Face-to-face interview data were obtained with semistructured instruments. Results showed that the strain variables interacted with gender in predicting degree of suicide intent in Chinese rural suicide attempters. Specifically, aspiration strain and coping strain were associated with suicide intent in Chinese male suicide attempters, whereas value strain was associated with suicide intent in Chinese female suicide attempters. This study supported the strain hypothesis in Chinese rural suicide attempters.
Development of a Prediction Model of Early Acute Kidney Injury in Critically Ill Children Using Electronic Health Record Data
Authors: Sanchez-Pinto L. Nelson , Khemani Robinder G. 
Published: April 2016

Objective:
Acute kidney injury is independently associated with poor outcomes in critically ill children. However, the main biomarker of acute kidney injury, serum creatinine, is a late marker of injury and can cause a delay in diagnosis. Our goal was to develop and validate a data-driven multivariable clinical prediction model of acute kidney injury in a general PICU using electronic health record data.

Design:
Derivation and validation of a prediction model using retrospective data.

Patients:
All patients 1 month to 21 years old admitted between May 2003 and March 2015 without acute kidney injury at admission and alive and in the ICU for at least 24 hours.

Setting:
A multidisciplinary, tertiary PICU.

Intervention:
The primary outcome was early acute kidney injury, which was defined as new acute kidney injury developed in the ICU within 72 hours of admission. Multivariable logistic regression was performed to derive the Pediatric Early AKI Risk Score using electronic health record data from the first 12 hours of ICU stay.

Measurements and Main Results:
A total of 9,396 patients were included in the analysis, of whom 4% had early acute kidney injury, and these had significantly higher mortality than those without early acute kidney injury (26% vs 3.3%; p < 0.001). Thirty-three candidate variables were tested. The final model had seven predictors and had good discrimination (area under the curve 0.84) and appropriate calibration. The model was validated in two validation sets and maintained good discrimination (area under the curves, 0.81 and 0.86).

Conclusion:
We developed and validated the Pediatric Early AKI Risk Score, a data-driven acute kidney injury clinical prediction model that has good discrimination and calibration in a general PICU population using only electronic health record data that is objective, available in real time during the first 12 hours of ICU care and generalizable across PICUs. This prediction model was designed to be implemented in the form of an automated clinical decision support system and could be used to guide preventive, therapeutic, and research strategies.
Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder
Authors: VINCENZI BRENDA , GREENE CLAIRE M. , ULLOA MELISSA , PARNAROUSKIS LINDSEY , JACKSON JOHN W. , HENDERSON DAVID C. 
Published: April 2016

Objective:
People with schizophrenia are at greater risk for cardiovascular disease and their overall mortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote.

Methods:
Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis.

Results:
No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance.

Conclusions:
These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.
Age at the Time of Surgery and Maintenance of Head Size in Nonsyndromic Sagittal Craniosynostosis
Authors: Bergquist Curtis S. , Nauta Allison C. , Selden Nathan R. , Kuang Anna A. 
Published: April 2016

Background:
Repair of nonsyndromic sagittal craniosynostosis should durably improve intracranial volume and cranial index. The optimal timing of surgery is not known. The authors previously reported reoperation in patients aged younger than 6 months at primary repair.

Methods:
Patients undergoing primary reconstruction for sagittal craniosynostosis before age 1 year between 2005 and 2013 at Oregon Health & Science University underwent retrospective computed tomographic determination of cranial index and intracranial volume preoperatively and 2 years postoperatively and head circumference measurements until age 6 years.

Results:
Fifty-six patients undergoing operation before their first birthday were studied in two groups: those younger than 6 months [34 (61 percent)] and those aged 6 months or older at the time of operation. Head circumference percentile increased immediately after surgery but decreased at 1 and 2 years after surgery, significantly more so in patients younger than 6 months (p < 0.015 at 1 year; p < 0.011 at 2-year follow-up). Mean 2-year postoperative cranial index was significantly increased in both groups (p < 0.001), which did not differ preoperatively (younger than 6 months, 76.5; 6 months or older, 78.0) or 2 years postoperatively (younger than 6 months, 88.4; 6 months or older, 87.1; p = not significant). Intracranial volume increased in all patients from before surgery to 2 years postoperatively and was higher in the patients aged 6 months or older (p < 0.001).

Conclusion:
Cranial reconstruction for nonsyndromic sagittal craniosynostosis improved cranial index equally in all patients but increased head circumference and intracranial volume significantly more in patients who underwent surgical reconstruction at age 6 months or older.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Dual-Pedicle Flap for Unilateral Autologous Breast Reconstruction Revisited: Evolution and Optimization of Flap Design over 15 Years
Authors: Chang Edward I. , Kronowitz Steven J. 
Published: April 2016

Background:
In thin patients or when a significant amount of skin is needed, use of the entire abdomen to reconstruct a single breast may be necessary. In this article, the authors present their 15-year experience in dual-pedicle flap evolution and optimization of flap design.

Methods:
A retrospective review was conducted of all bipedicle flaps performed from 2000 to 2015.

Results:
Overall, 57 patients (mean age, 49.2 years; mean body mass index, 26.2 kg/m2) underwent dual-pedicle flap reconstruction of a unilateral mastectomy defect. Thirteen patients had a history of smoking, 30 patients had previously undergone irradiation, and 21 patients underwent immediate reconstruction. Eleven bipedicle flaps were performed with a pedicle transverse rectus abdominis musculocutaneous (TRAM) flap coupled to a free TRAM (n = 4), muscle-sparing TRAM (n = 4), or deep inferior epigastric artery perforator (DIEP) (n = 3) flap, and all were performed from 2000 to 2007. The thoracodorsal vessels (n = 8) were used more frequently earlier in the study period with the internal mammary vessels, whereas the antegrade/retrograde internal mammary vessels were used in the remaining patients, except for three patients in whom the internal mammary vessels and an internal mammary vessel perforator were used. Over the study period, there was an increase in the use of DIEP and superficial inferior epigastric artery flaps and the internal mammary vessels as recipients. Complications included delayed wound healing (n = 6), abdominal bulge (n = 2), cellulitis (n = 4), seroma (n = 3), and fat necrosis (n = 4). There was one partial flap loss where the superficial inferior epigastric artery portion of the dual-pedicle flap was lost.

Conclusions:
Dual-pedicle free flaps can be performed safely and reliably. Use of DIEP flaps maximizes pedicle length, and the internal mammary vessels can be used reliably in an antegrade and retrograde fashion to perfuse both components of the dual-pedicle flap.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.