bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties
Authors: Sekula Bartosz , Ciesielska Anna , Rytczak Przemyslaw , Koziołkiewicz Maria , Bujacz Anna 
Published: April 2016

Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signalling molecules, which are involved in several pathological states, such as cancer, diabetes or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein–serum albumin. Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids (LPLs). Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer (PC) cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC50 value of 29.0 μM after 24 h incubation, which is almost 30% lower than IC50 of single substituted phosphorothioate cPA. Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this LPL analogue. HSA binds three molecules of Myr-2S-cPA, whereas ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins.
Racial Differences and the Role of Neighborhood in the Sequencing of Marijuana and Tobacco Initiation among Urban Youth
Authors: Green Kerry M. , Johnson Renee M. , Milam Adam J. , Furr-Holden Debra , Ialongo Nicholas S. , Reboussin Beth A. 
Published: April 2016

Background: With patterns of initiation of tobacco and marijuana changing, there is increasing evidence that marijuana use may serve as an antecedent to tobacco use among adolescents. However, studies have not fully characterized the prevalence of these patterns among vulnerable youth and have rarely examined the factors that predict the sequencing of onset of tobacco and marijuana use. Methods: Utilizing longitudinal data from a sample of urban youth followed from age 6 to age 18, the authors identify the sequencing of initiation of tobacco and marijuana and test whether race and 5 neighborhood factors (i.e., perceived disorder, drug activity, drug access, exposure to violence, and exposure to violent victimization) predict onset sequencing. Results: Various sequencing patterns were observed, with 12.4% of the sample initiating marijuana use before tobacco use was initiated. In adjusted logistic regression models, black youth were 2.66 times as likely as whites to initiate marijuana before tobacco compared with initiating tobacco before marijuana ( P = .032). Youth with greater exposure to violent victimization were 3.89 times as likely to initiate marijuana first than initiate tobacco first ( P = .002). Other neighborhood factors were not statistically significantly associated with sequencing. Conclusions: Black youth and youth with greater exposure to victimization had an increased risk of initiating marijuana before tobacco, which suggests that this pattern may be rooted in specific risk factors. Substance use prevention efforts should consider taking into account that marijuana use may put certain youth at risk of initiating tobacco. Future research needs to monitor sequencing, as well as risk factors for and consequences of the various patterns, particularly since marijuana use and the mixing of tobacco and marijuana use are gaining acceptability in general populations.
Intoxication and Binge and High-Intensity Drinking among US Young Adults in their Mid-20s
Authors: Terry-McElrath Yvonne M. , Patrick Megan E. 
Published: April 2016

Background: Alcohol use is a key risk factor for young adult mortality and disease, but limited research has focused on high-risk alcohol use among individuals moving from early young adulthood into building and maintaining an initial structure of adult life. This study estimated the prevalence of a range of alcohol use behaviors among US young adults aged 25/26, examined evidence for historical change in prevalence rates, and estimated associations between alcohol use and key demographic, substance use, and adult social role characteristics. Methods: Data were obtained from 3542 individuals selected for follow-up from the nationally representative 12th-grade student Monitoring the Future study. Respondents self-reported alcohol use behaviors at age 25/26 during calendar years 2005–2014. Results: Two fifths (39.9%) of young adults aged 25/26 reported being intoxicated at least once in the past 30 days; 25.6% reported usually experiencing a sustained high of 3 or more hours when drinking alcohol. Past-2-week binge drinking (5+ drinks in a row) was reported by 36.3% of respondents. Past-2-week high-intensity drinking (10+ drinks in a row) was reported by 12.4%. These age 25/26 alcohol use prevalence rates remained stable over the 10 years of data examined, in contrast to significant declines over historical time in alcohol prevalence rates among these same individuals at age 18. High-risk drinking was particularly associated with being male, white, unmarried, employed, a nonparent, and an alcohol user before finishing high school. Conclusions: Among US young adults in their mid-20s, alcohol use was highly normative and frequently included participation in high-risk drinking behaviors. High-risk alcohol use prevention approaches developed specifically to reach young adults in their mid-20s are needed, as well as efforts to increase proactive clinician screening to identify young adults participating in high-risk alcohol use.
Digital resource developments for mathematics education involving homework across formal, non‐formal and informal settings
Authors: Radović Slaviša , Passey Don 
Published: April 2016

ABSTRACTThe aim of this paper is to explore further an under‐developed area – how drivers of curriculum, pedagogy and assessment conceptions and practices shape the creation and uses of technologically based resources to support mathematics learning across informal, non‐formal and formal learning environments. The paper considers: the importance of mathematics learning in informal and non‐formal as well as formal settings; how curriculum focuses on pedagogy supporting these needs, contrasting this focus in England and Serbia; and in these contexts, the roles of homework, the potential of technologies and the roles of the teacher. Technological developments to support mathematics learning for 11‐ to 14‐year‐old pupils in the two countries are explored and contrasted, and ways that recent developments inform our understandings of formal, informal and non‐formal learning through learning activities, learning support and settings are modelled. The conception of ‘extended pedagogies’ is introduced; implications are outlined.
Genomic architecture of phenotypic divergence between two hybridizing plant species along an elevational gradient
Authors: Brennan Adrian C. , Hiscock Simon J. , Abbott Richard J. 
Published: April 2016

Abstract
Knowledge of the genetic basis of phenotypic divergence between species and how such divergence is caused and maintained is crucial to an understanding of speciation and the generation of biodiversity. The hybrid zone between Senecio aethnensis and S. chrysanthemifolius on Mount Etna, Sicily, provides a well-studied example of species divergence in response to conditions at different elevations, despite hybridization and gene flow. Here, we investigate the genetic architecture of divergence between these two species using a combination of quantitative trait locus (QTL) mapping and genetic differentiation measures based on genetic marker analysis. A QTL architecture characterized by physical QTL clustering, epistatic interactions between QTLs, and pleiotropy was identified, and is consistent with the presence of divergent QTL complexes resistant to gene flow. A role for divergent selection between species was indicated by significant negative associations between levels of interspecific genetic differentiation at mapped marker gene loci and map distance from QTLs and hybrid incompatibility loci. Within-species selection contributing to interspecific differentiation was evidenced by negative associations between interspecific genetic differentiation and genetic diversity within species. These results show that the two Senecio species, while subject to gene flow, maintain divergent genomic regions consistent with local selection within species and selection against hybrids between species which, in turn, contribute to the maintenance of their distinct phenotypic differences.
Accounting for correlated observations in an age-based state-space stock assessment model
Authors: Berg Casper W. , Nielsen Anders 
Published: April 2016

Abstract
Fish stock assessment models often rely on size- or age-specific observations that are assumed to be statistically independent of each other. In reality, these observations are not raw observations, but rather they are estimates from a catch-standardization model or similar summary statistics based on observations from many fishing hauls and subsamples of the size and age composition of the data. Although aggregation mitigates the strong intra-haul correlation between sizes/ages that is usually found in haul-by-haul data, violations of the independence assumption can have a large impact on the results and specifically on reported confidence bounds. A state-space assessment model that allows for correlations between age groups within years in the observation model for catches and surveys is presented and applied to data on several North Sea fish stocks using various correlation structures. In all cases the independence assumption is rejected. Less fluctuating estimates of the fishing mortality is obtained due to a reduced process error. The improved model does not suffer from correlated residuals unlike the independent model, and the variance of forecasts is decreased.
Tetratricopeptide repeat factor XAB2 mediates the end resection step of homologous recombination
Authors: Onyango David O , Howard Sean M , Neherin Kashfia , Yanez Diana A , Stark Jeremy M 
Published: April 2016

Abstract
We examined the influence of the tetratricopeptide repeat factor XAB2 on chromosomal break repair, and found that XAB2 promotes end resection that generates the 3′ ssDNA intermediate for homologous recombination (HR). Namely, XAB2 is important for chromosomal double-strand break (DSB) repair via two pathways of HR that require end resection as an intermediate step, end resection of camptothecin (Cpt)-induced DNA damage, and RAD51 recruitment to ionizing radiation induced foci (IRIF), which requires end resection. Furthermore, XAB2 mediates specific aspects of the DNA damage response associated with end resection proficiency: CtIP hyperphosphorylation induced by Cpt and BRCA1 IRIF. XAB2 also promotes histone acetylation events linked to HR proficiency. From truncation mutation analysis, the capacity for XAB2 to promote HR correlates with its ability to form a complex with ISY1 and PRP19, which show a similar influence as XAB2 on HR. This XAB2 complex localizes to punctate structures consistent with interchromatin granules that show a striking adjacent-localization to the DSB marker γH2AX. In summary, we suggest that the XAB2 complex mediates DNA damage response events important for the end resection step of HR, and speculate that its adjacent-localization relative to DSBs marked by γH2AX is important for this function.
Characteristics and Distribution of Graduate Medical Education Training Sites: Are We Missing Opportunities to Meet U.S. Health Workforce Needs?
Authors: Blanchard Janice , Petterson Stephen , Bazemore Andrew , Watkins Kayla , Mullan Fitzhugh 
Published: April 2016

Purpose
Shortages of generalist physicians in primary care and surgery have been projected. Residency programs that expose trainees to community-based health clinics and rural settings have a greater likelihood of producing physicians who later practice in these environments. The objective of this study was to characterize the distribution of residency training sites in different settings for three high-need specialties—family medicine, internal medicine, and general surgery.

Method
The authors merged 2012 data from the Accreditation Council for Graduate Medical Education Accreditation Data System and 2010 data from the Centers for Medicare and Medicaid Services hospital cost report to match training sites with descriptive data about those locations. They used chi-square tests to compare the characteristics and distribution of residency programs and training sites in family medicine, internal medicine, and general surgery.

Results
The authors identified 1,095 residency programs and 3,373 training sites. The majority of training occurred in private, not-for-profit hospitals. Only 48 (of 1,390; 4%) family medicine training sites and 43 (of 936; 5%) internal medicine training sites were community-based health clinics. Seventy-eight (6%) family medicine sites, 8 (1%) internal medicine sites, and 16 (2%) general surgery sites were located in rural settings. One hundred thirty (14%) internal medicine sites were Department of Veterans Affairs medical facilities compared with 78 (6%) family medicine sites and 94 (9%) general surgery sites (P < .001).

Conclusions
Relatively little training occurs in rural or community-based settings. Expanding training opportunities in these low-access areas could improve physician supply there.
The Prevalence of Congenital Hand and Upper Extremity Anomalies Based Upon the New York Congenital Malformations Registry
Authors: Goldfarb Charles A. , Shaw Neil , Steffen Jennifer A. , Wall Lindley B. 
Published: April 2016

Background:
There have been few publications regarding the prevalence of congenital upper extremity anomalies and no recent reports from the United States. The purpose of this investigation was to examine the prevalence of congenital upper extremity anomalies in the total birth population of New York State over a 19-year period utilizing the New York Congenital Malformations Registry (NYCMR) database.

Methods:
The NYCMR includes children with at least 1 birth anomaly diagnosed by 2 years of age and listed by diagnosis code. We scrutinized these codes for specific upper extremity anomalies, including polydactyly, syndactyly, reduction defects, clubhand malformations, and syndromes with upper limb anomalies. We included children born between 1992 and 2010.

Results:
There were a total of 4,883,072 live births in New York State during the study period. The overall prevalence of congenital upper extremity anomalies was 27.2 cases per 10,000 live births. Polydactyly was most common with 12,418 cases and a prevalence rate of 23.4 per 10,000 live births. The next most common anomalies included syndactyly with 627 cases affecting the hands (1498 total) and reduction defects (1111 cases). Specific syndromes were quite rare and were noted in a total of 215 live births. The prevalence of anomalies was higher in New York City compared with New York State populations at 33.0 and 21.9 per 10,000 live births, respectively.

Conclusions:
The NYCMR data demonstrate that congenital upper extremity anomalies are more common than previously reported. This is in large part due to the high prevalence of polydactyly. Although registries are imperfect, such data are helpful in monitoring prevalence rates over time, identifying potential causes or associations, and guiding health care planning and future research.

Level of Evidence:
Level I—diagnostic.
Comparison Between Doppler-Echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study*
Authors: Scolletta Sabino , Franchi Federico , Romagnoli Stefano , Carlà Rossella , Donati Abele , Fabbri Lea P. , Forfori Francesco , Alonso-Iñigo José M. , Laviola Silvia , Mangani Valerio , Maj Giulia , Martinelli Giampaolo , Mirabella Lucia , Morelli Andrea , Persona Paolo , Payen Didier 
Published: April 2016

Objectives:
Echocardiography and pulse contour methods allow, respectively, noninvasive and less invasive cardiac output estimation. The aim of the present study was to compare Doppler echocardiography with the pulse contour method MostCare for cardiac output estimation in a large and nonselected critically ill population.

Design:
A prospective multicenter observational comparison study.

Setting:
The study was conducted in 15 European medicosurgical ICUs.

Patients:
We assessed cardiac output in 400 patients in whom an echocardiographic evaluation was performed as a routine need or for cardiocirculatory assessment.

Interventions:
None.

Measurements and Main Results:
One echocardiographic cardiac output measurement was compared with the corresponding MostCare cardiac output value per patient, considering different ICU admission categories and clinical conditions. For statistical analysis, we used Bland-Altman and linear regression analyses. To assess heterogeneity in results of individual centers, Cochran Q, and the I
2 statistics were applied. A total of 400 paired echocardiographic cardiac output and MostCare cardiac output measures were compared. MostCare cardiac output values ranged from 1.95 to 9.90 L/min, and echocardiographic cardiac output ranged from 1.82 to 9.75 L/min. A significant correlation was found between echocardiographic cardiac output and MostCare cardiac output (r = 0.85; p < 0.0001). Among the different ICUs, the mean bias between echocardiographic cardiac output and MostCare cardiac output ranged from –0.40 to 0.45 L/min, and the percentage error ranged from 13.2% to 47.2%. Overall, the mean bias was –0.03 L/min, with 95% limits of agreement of –1.54 to 1.47 L/min and a relative percentage error of 30.1%. The percentage error was 24% in the sepsis category, 26% in the trauma category, 30% in the surgical category, and 33% in the medical admission category. The final overall percentage error was 27.3% with a 95% CI of 22.2–32.4%.

Conclusions:
Our results suggest that MostCare could be an alternative to echocardiography to assess cardiac output in ICU patients with a large spectrum of clinical conditions.
Development of Novel Criteria of the “Lethal Triad” as an Indicator of Decision Making in Current Trauma Care: A Retrospective Multicenter Observational Study in Japan
Authors: Endo Akira , Shiraishi Atsushi , Otomo Yasuhiro , Kushimoto Shigeki , Saitoh Daizoh , Hayakawa Mineji , Ogura Hiroshi , Murata Kiyoshi , Hagiwara Akiyoshi , Sasaki Junichi , Matsuoka Tetsuya , Uejima Toshifumi , Morimura Naoto , Ishikura Hiroyasu , Takeda Munekazu , Kaneko Naoyuki , Kato Hiroshi , Kudo Daisuke , Kanemura Takashi , Shibusawa Takayuki , Hagiwara Yasushi , Furugori Shintaro , Nakamura Yoshihiko , Maekawa Kunihiko , Mayama Gou , Yaguchi Arino , Kim Shiei , Takasu Osamu , Nishiyama Kazutaka 
Published: April 2016

Objectives:
To evaluate the utility of the conventional lethal triad in current trauma care practice and to develop novel criteria as indicators of treatment strategy.

Design:
Retrospective observational study.

Settings:
Fifteen acute critical care medical centers in Japan.

Patients:
In total, 796 consecutive trauma patients who were admitted to emergency departments with an injury severity score of greater than or equal to 16 from January 2012 to December 2012.

Interventions:
None.

Measurements and Main Results:
All data were retrospectively collected, including laboratory data on arrival. Sensitivities to predict trauma death within 28 days of prothrombin time international normalized ratio greater than 1.50, pH less than 7.2, and body temperature less than 35°C were 15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and base excess (the cutoff values were 88.8 µg/mL and –3.05 mmol/L). The optimal cutoff value of hypothermia was 36.0°C. The impact of the fibrin/fibrinogen degradation product and base excess abnormality on the outcome were approximately three- and two-folds compared with those of hypothermia. Using these variables, if the patient had a hemostatic disorder alone or a combined disorder with acidosis and hypothermia, the sensitivity and specificity were 80.7% and 66.8%.

Conclusions:
Because of the low sensitivity and high specificity, conventional criteria were unsuitable as prognostic indicators. Our revised criteria are assumed to be useful for predicting trauma death and have the potential to be the objective indicators for activating the damage control strategy in early trauma care.
Combined Neprilysin and RAS Inhibition in Cardiovascular Diseases: A Review of Clinical Studies
Authors: Tummala Ramyashree , Bhadra Rajarshi , Gupta Anjan , Ghosh Raktim K. 
Published: April 2016

Abstract:
The aim of this comprehensive review article is to emphasize on the possible exploration of a new therapeutic approach in the management of heart failure (HF) and other cardiovascular diseases: the renin–angiotensin–aldosterone system–neprilysin combination inhibitors, also called angiotensin receptor neprilysin inhibitor, valsartan/sacubitril (LCZ696). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides such as atrial natriuretic peptide and brain natriuretic peptide. Valsartan is an angiotensin receptor blocker which is usually used in hypertension. Although HF has been a global health burden, for decades there has been lack of novel therapeutic options as many trials failed due to potential side effects. With the published results of the landmark trial Prospective comparison of ARNI with ACEI to Determine the Impact on Global Mortality and morbidity in HF (PARADIGM-HF), a new direction in the treatment of HF is anticipated. This trial showed that LCZ696 was able to reduce the primary composite end point of cardiovascular death or HF hospitalization, and similar reduction was observed for cardiovascular death. This review article also highlights the results of 4 published trials of LCZ696 in both HTN and HF. After the results of PARADIGM-HF trial, the major challenge will be outcome in regular clinical practice, as subjects in the trial were mostly stable New York Heart Association class II patients with no comorbidities. In addition, many trials are simultaneously in progress regarding the use of LCZ696 in patients with diabetes, renal failure, and hepatic impairment. To conclude, sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HF, but it will need meticulous attention when used in real outpatient practice.