bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac MR Characterization of left ventricular remodeling in a swine model of infarct followed by reperfusion
Authors: Whitaker John , Tschabrunn Cory M. , Jang Jihye , Leshem Eran , O'Neill Mark , Manning Warren J. , Anter Elad , Nezafat Reza 
Published: March 2018

BackgroundMyocardial infarction (MI) survivors are at risk of complications including heart failure and malignant arrhythmias.PurposeWe undertook serial imaging of swine following MI with the aim of characterizing the longitudinal left ventricular (LV) remodeling in a translational model of ischemia‐reperfusion‐mediated MI.Animal ModelEight Yorkshire swine underwent mid left anterior descending coronary artery balloon occlusion to create an ischemia‐reperfusion experimental model of MI.Field Strength/Sequences1.5T Philips Achieva scanner. Serial cardiac MRI was performed at 16, 33, and 62 days post‐MI, including cine imaging, native and postcontrast T1, T2 and dark‐blood late gadolinium enhanced (DB‐LGE) scar imaging.AssessmentRegions of interest were selected on the parametric maps to assess native T1 and T2 in the infarct and in remote tissue. Volume of enhanced tissue, nonenhanced tissue, and gray zone were assessed from DB‐LGE imaging. Volumes, cardiac function, and strain were calculated from cine imaging.Statistical TestsParameters estimated at more than two timepoints were compared with a one‐way repeated measures analysis of variance. Parametric mapping data were analyzed using a generalized linear mixed model corrected for multiple observations. A result was considered statistically significant at P < 0.05.ResultsAll animals developed anteroseptal akinesia and hyperenhancement on DB‐LGE with a central core of nonenhancing tissue. Mean hyperenhancement volume did not change during the observation period, while the central core contracted from 2.2 ± 1.8 ml at 16 days to 0.08 ± 0.19 ml at 62 days (P = 0.008). Native T1 of ischemic myocardium increased from 1173 ± 93 msec at 16 days to 1309 ± 97 msec at 62 days (P < 0.001). Mean radial and circumferential strain rate magnitude in remote myocardium increased with time from the infarct (P < 0.05).Date ConclusionIn this swine model of MI, serial quantitative cardiac MR exams allow characterization of LV remodeling and scar formation.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:808–817.
Pharmacists’ perceptions of career opportunities in Australia
Authors: Taylor Hayley , Kyle Greg , Cheong Lynn 
Published: March 2018

AbstractBackgroundAnecdotal reports of an oversupply of pharmacy graduates are a growing concern for Australian pharmacists. However, limited data exists regarding pharmacists’ employment experiences and perceptions of current career opportunities in Australia.AimTo understand Australian pharmacists’ and pharmacy interns’ employment experiences by exploring their satisfaction and perspectives on current employment opportunities.MethodAn electronic survey was distributed to pharmacists and pharmacy interns across Australia between March and June 2016. National professional organisations for pharmacists assisted with the distribution of the survey. Follow‐up interviews were conducted to further explore survey findings.ResultsA total of 306 individuals completed the survey (83% pharmacists; 17% interns). The majority of pharmacists and interns reported high satisfaction with current employment and professional practice opportunities; however, there is a misalignment between their rated satisfaction and their perspectives on future employment prospects. Key themes that emerged included personal networks for employment, salary and location, and concerns for the future of the profession. The results suggested a confused workforce that are glad to have jobs, but not confident that they could move to other positions if required, or further, that there will be even fewer jobs available in the future.ConclusionThis study provided valuable insight to the Australian Pharmacist workforce, by improving our understanding of pharmacists’ employment experiences and perspectives. Further exploration of themes identified in this study is required to better inform the future of pharmacy professional practice and employment.
Teach the teacher: Training otolaryngology fellows to become academic educators
Authors: Cramer John D. , Chi David H. , Schaitkin Barry M. , Eibling David E. , Johnson Jonas T. 
Published: March 2018

Objectives/HypothesisFellowship is the capstone of academic training and serves as preparation for an academic career. Fellows are expected to educate medical students and residents during and long after fellowship. However, little time is typically spent teaching fellows to become effective educators. We investigate a formal curriculum addressing teaching skills among fellows in otolaryngology–head and neck surgery (OHNS).Study DesignE‐mail survey.MethodsWe developed and implemented an educational program called Teach the Teacher to build skills as educators for fellows in OHNS. We conducted a survey of fellows from 2014 to 2017 in OHNS who participated in the course. The survey evaluated demographics, teaching experiences, and teaching limitations structured as yes/no and Likert‐style questions (1 = strongly disagree, 5 = strongly agree).ResultsThirty fellows were surveyed with a response rate was 80%. Fellowship was rated highly as an experience that will make fellows a better academic educator (mean ± standard deviation: 4.54 ± 0.64). The most important components of teaching during fellowship were role modeling (4.67 ± 0.62), followed by teaching psychomotor skills in the operating room (4.29 ± 0.89), diagnostic reasoning (4.25 ± 0.66), and evidence‐based medicine (4.25 ± 0.83). The Teach the Teacher course specifically was rated as a helpful experience (4.00 ± 0.90). The primary limitations to developing teaching skills during fellowship identified were lack of time, patient safety, and inexperience with hospital culture.ConclusionsFellowship is a key time to improve skills as academic educators. Fellows value formal efforts to teach academic skills.Level of EvidenceNA. Laryngoscope, 128:2034–2048, 2018
Chemical Synthesis of Rare Natural Bile Acids: 11α‐Hydroxy Derivatives of Lithocholic and Chenodeoxycholic Acids
Authors: Namegawa Kazunari , Iida Kyoko , Omura Kaoru , Ogawa Shoujiro , Hofmann Alan F. , Iida Takashi 
Published: March 2018

AbstractA method for the preparation of 11α‐hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α‐mesyloxy group of the methyl esters of 3α‐acetate‐12α‐mesylate and 3α,7α‐diacetate‐12α‐mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △11‐3α‐acetoxy and △11‐3α,7α‐diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α‐hydroxylation of the △11‐3α,24‐diol and △11‐3α,7α,24‐triol intermediates with B2H6/tetrahydrofuran (THF); and (4) selective oxidation at C‐24 of the resulting 3α,11α,24‐triol and 3α,7α,11α,24‐tetrol to the corresponding C‐24 carboxylic acids with NaClO2 catalyzed by 2,2,6,6‐tetramethylpiperidine 1‐oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α‐dihydroxy‐5β‐cholan‐24‐oic acid and 3α,7α,11α‐trihydroxy‐5β‐cholan‐24‐oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis.
Decreasing ALT donor site morbidity with the keystone flap
Authors: Turin Sergey Y. , Spitz Jamie A. , Alexander Karina , Ellis Marco F. 
Published: March 2018

BackgroundThe anterolateral thigh (ALT) flap is a workhorse flap for a variety of wounds. The primary disadvantage of ALT flaps is donor site morbidity associated with large skin paddle defects. We present a strategy of managing the donor site with the Keystone flap to avoid skin grafts in cases where primary closure is not possible.MethodsA retrospective, multi‐institutional review from December 2015 to March 2017 based on a single surgeon's experience was performed. Inclusion criteria were harvest of an ALT flap and closure of the thigh donor site with a keystone flap.ResultsSix patients underwent reconstruction of the ALT donor site with a keystone flap. The average width of the ALT skin paddle was 7.8 cm (range 7–8 cm) and the defects could not be closed primarily or with wide undermining. Surface area of the ALT flaps averaged 96.8 cm2 (range 64–152 cm2). Mean patient BMI was 24.6 (range 16–37). Keystone flap dimensions averaged 9.5 × 17.8 cm. There were no major donor or recipient site complications, and one ×minor complication of delayed wound healing. No patients exhibited decreased range of motion at the hip or knee.ConclusionsPrimary closure of the ALT donor site is preferred, but becomes difficult as skin paddle width approaches 8 cm. Managing the ALT flap donor site with a keystone flap is safe, does not appear to have significant morbidity, and can allow the surgeon to avoid the morbidity and secondary donor site associated with skin grafting.
Porphyrin–peptide conjugates in biomedical applications
Authors: Biscaglia Francesca , Gobbo Marina 
Published: March 2018

AbstractThe conjugation of peptides to porphyrins and related tetrapyrrole based macrocycles have extended their applications in biological systems, where the photophysical properties of these molecules and their ability to coordinate metals can be exploited for detecting and opposing to the onset of important diseases. This review presents a survey of the published literature over last years on biomedical applications of these hybrid compounds, mostly in the field of photodynamic therapy (PDT), but also in sensing key metabolites and peculiar structures of biomolecules in living systems. Peptides based strategies to improve the efficacy of the photosensitizer (PS) in PDT will be discussed, as well as solutions to overcome some limitations recently emerged in the use of peptides as delivery vehicles. An overview on possible application of porphyrin–peptide conjugates in detection of biomarkers of physiological and pathological states will be also presented.
Site‐Specific Systematic Analysis of Lysine Modification Crosstalk
Authors: Xu Hao‐Dong , Wang Li‐Na , Wen Ping‐Ping , Shi Shao‐Ping , Qiu Jian‐Ding 
Published: March 2018

AbstractResearch has revealed that post‐translational modifications (PTMs) that occur at lysine (PLMs) can cooperatively regulate various biological processes by crosstalk. However, the trend of the crosstalk between multiple PLMs and the properties of PLM crosstalk require additional investigation. Here, the crosstalk among acetylation, succinylation, and SUMOylation is systematically studied in a site‐specific waz. First, crosstalk between SUMOylation is detected and succinylation is found to be underexpressed, whereas succinylation tends to crosstalk with acetylation and SUMOylation on the same lysine residue while PLM crosstalk is tissue‐specific across different species. Further analysis reveals that different PLMs tend to occur crosstalk at diverse subcellular compartments and structural regions, and they participate in distinct biological processes and functions. Additionally, short‐term evolutionary analysis shows that there is no additional evolutionary pressure on PLMs crosstalk sites, as found by comparison with singly modified sites. Finally, phylogenetic classification reveals that genes with co‐occupied lysine crosstalk are more likely to have higher evolutionary similarity and possess a tendency to cluster in the specific branch. The integrated approach reported here has the potential for large‐scale prioritization of in situ crosstalk of PLM candidates and provides a profound understanding of the underlying relationship between different lysine modifications.
A Deep Proteomics Perspective Into Grape Berry Quality Traits During Ripening
Authors: Martínez‐Esteso María José , Bru Martínez Roque 
Published: March 2018

AbstractDiscovery‐based proteomics studies have an important role in the understanding of the biochemical processes that occur during grape berry ripening. The ripening process is relevant in determining grape berry quality. For a proteome analysis of grape berry ripening, Kambiranda et al. (2018) applied a label‐free mass spectrometry–based quantitative approach. The authors reported the identification of proteins associated with the production flavor, aroma and ethylene production. Despite the valuable contribution of discovery‐based proteomics studies, the picture is still incomplete. Future efforts in gaining proteome coverage would benefit the identification of proteins associated with grape berry quality traits.
Aromaticity in heterocyclic analogues of benzene: Dissected NICS and current density analysis
Authors: Báez‐Grez R. , Rabanal‐León Walter A. , Alvarez‐Thon Luis , Ruiz Lina , Tiznado W. , Pino‐Rios R. 
Published: March 2018

AbstractThe magnetic aromaticity of 6‐membered monoheterocycles containing Group 13 to 16 elements (C5H5X, where X = SiH, GeH, N, P, As, O+, S+, Se+) was assessed by using 2 magnetic descriptors: the π‐electron contribution to the out‐of‐plane component of the nucleus‐independent chemical shifts (NICSzz,π) and ring current strength. The results show that both descriptors lead to the same conclusion regarding magnetic aromaticity. However, they do not agree with the predictions obtained by isotropic NICS, which is a most commonly used method. Ring current strength and NICSπ predict that benzene is the most aromatic molecule of the series, with an only slightly less aromatic pyridine. Additionally, aromaticity decreases when going down in the same group of the periodic system. The only exception is the pyrylium cation, which is predicted as the least aromatic species of this series.
Behavioral symptoms and psychiatric disorders in child and adolescent long‐term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only
Authors: Liu Wei , Cheung Yin Ting , Brinkman Tara M. , Banerjee Pia , Srivastava Deokumar , Nolan Vikki G. , Zhang Hongmei , Gurney James G. , Pui Ching‐Hon , Robison Leslie L. , Hudson Melissa M. , Krull Kevin R. 
Published: March 2018

AbstractBackgroundPrevalence of emotional, behavioral, and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia treated on a chemotherapy‐only protocol were not well defined.MethodsSelf‐ and parent‐reported emotional and behavioral symptoms were assessed for 161 survivors of childhood acute lymphoblastic leukemia (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post‐diagnosis). Age‐ and sex‐adjusted scores were calculated for standardized measures and compared with 90th percentile of norms. Frequencies of survivor psychiatric disorders from structured diagnostic interviews with parents were compared with the general population. Parent emotional distress and post‐traumatic stress symptoms were assessed. Associations between child symptoms/disorders and parent distress were examined with log‐binomial models, adjusting for highest parent education.ResultsCompared with population expectations (10%), more survivors self‐reported symptoms of inattention (27.9; 95% CI, 21.0%‐35.7%), hyperactivity/impulsivity (26.0%; CI, 19.2%‐33.6%), and oppositional‐defiant behavior (20.1%; CI, 14.1%‐27.3%). Parents reported survivors with more symptoms of inattention (23.6%; CI, 17.2%‐31.0%), higher frequencies of obsessive‐compulsive disorder (10.3% vs 2%) and oppositional defiant disorder (16.0% vs 9.5%), but not attention‐deficit/hyperactivity disorder (7.1% vs 7.8%) or generalized anxiety disorder (3.2% vs 4.1%), compared with national norms. Parent‐report of child anxiety disorders was associated with parent self‐reported emotional distress but not survivor self‐report of anxiety.ConclusionA significant minority of survivors have long‐term psychiatric morbidity, multi‐informant assessment is important to understand these symptom profiles and to inform selection of appropriate interventions. Interventions targeting inattention and oppositional behavior in children and emotional distress in parents are warranted in families with survivors who display behavioral problems.
Fused dimerization increases expression, solubility, and activity of bacterial dehydratase enzymes
Authors: Rullán‐Lind Carlos , Pietri Ruth B. , Vázquez‐Cintrón Melvin , Baerga‐Ortiz Abel 
Published: March 2018

AbstractFabA and FabZ are the two dehydratase enzymes in Escherichia coli that catalyze the dehydration of acyl intermediates in the biosynthesis of fatty acids. Both enzymes form obligate dimers in which the active site contains key amino acids from both subunits. While FabA is a soluble protein that has been relatively straightforward to express and to purify from cultured E. coli, FabZ has shown to be mostly insoluble and only partially active. In an effort to increase the solubility and activity of both dehydratases, we made constructs consisting of two identical subunits of FabA or FabZ fused with a naturally occurring peptide linker, so as to force their dimerization. The fused dimer of FabZ (FabZ‐FabZ) was expressed as a soluble enzyme with an ninefold higher activity in vitro than the unfused FabZ. This construct exemplifies a strategy for the improvement of enzymes from the fatty acid biosynthesis pathways, many of which function as dimers, catalyzing critical steps for the production of fatty acids.
PBOV1 as a potential biomarker for more advanced prostate cancer based on protein and digital histomorphometric analysis
Authors: Carleton Neil M. , Zhu Guangjing , Gorbounov Mikhail , Miller M. Craig , Pienta Kenneth J. , Resar Linda M. S. , Veltri Robert W. 
Published: March 2018

BackgroundThere are few tissue‐based biomarkers that can accurately predict prostate cancer (PCa) progression and aggressiveness. We sought to evaluate the clinical utility of prostate and breast overexpressed 1 (PBOV1) as a potential PCa biomarker.MethodsPatient tumor samples were designated by Grade Groups using the 2014 Gleason grading system. Primary radical prostatectomy tumors were obtained from 48 patients and evaluated for PBOV1 levels using Western blot analysis in matched cancer and benign cancer‐adjacent regions. Immunohistochemical evaluation of PBOV1 was subsequently performed in 80 cancer and 80 benign cancer‐adjacent patient samples across two tissue microarrays (TMAs) to verify protein levels in epithelial tissue and to assess correlation between PBOV1 proteins and nuclear architectural changes in PCa cells. Digital histomorphometric analysis was used to track 22 parameters that characterized nuclear changes in PBOV1‐stained cells. Using a training and test set for validation, multivariate logistic regression (MLR) models were used to identify significant nuclear parameters that distinguish Grade Group 3 and above PCa from Grade Group 1 and 2 PCa regions.ResultsPBOV1 protein levels were increased in tumors from Grade Group 3 and above (GS 4 + 3 and ≥ 8) regions versus Grade Groups 1 and 2 (GS 3 + 3 and 3 + 4) regions (P = 0.005) as assessed by densitometry of immunoblots. Additionally, by immunoblotting, PBOV1 protein levels differed significantly between Grade Group 2 (GS 3 + 4) and Grade Group 3 (GS 4 + 3) PCa samples (P = 0.028). In the immunohistochemical analysis, measures of PBOV1 staining intensity strongly correlated with nuclear alterations in cancer cells. An MLR model retaining eight parameters describing PBOV1 staining intensity and nuclear architecture discriminated Grade Group 3 and above PCa from Grade Group 1 and 2 PCa and benign cancer‐adjacent regions with a ROC‐AUC of 0.90 and 0.80, respectively, in training and test sets.ConclusionsOur study demonstrates that the PBOV1 protein could be used to discriminate Grade Group 3 and above PCa. Additionally, the PBOV1 protein could be involved in modulating changes to the nuclear architecture of PCa cells. Confirmatory studies are warranted in an independent population for further validation.
The composition of prostate core matrisome in vivo and in vitro unveiled by mass spectrometric analysis
Authors: Ojalill Marjaana , Rappu Pekka , Siljamäki Elina , Taimen Pekka , Boström Peter , Heino Jyrki 
Published: March 2018

BackgroundThe composition and organization of extracellular matrix (ECM) are important regulators of cell behavior. In particular in the prostate, this central role of the ECM is further stressed by the fact that several potential markers of prostate stem cells are matrix receptors.MethodsWe established 12 fibroblastic cell lines from cancerous and non‐cancerous areas of six prostates and allowed the cells to produce ECM under cell culture conditions. We also performed a proteome wide analysis of the ECM components by mass spectrometry. To study the in vitro activation of fibroblastic cells we compared the differences between the ECM produced in cell culture by six non‐cancerous‐tissue‐derived fibroblasts and the in vivo matrisome from the corresponding non‐cancerous tissue of prostate.ResultsOur results suggest that at tissue level the ECM is mainly produced by fibroblastic cells and that it contains standard collagen I fibrils and fibril‐associated proteins. Beaded‐filament forming collagen VI is also abundant and basement membranes potentially contain five laminin subtypes and collagens XV and XVIII. As the main finding, we also detected differences when in vivo and in vitro matrisomes were compared. Only 65 out of 206 proteins were found to be common for both in vivo and in vitro samples. Majority of the 55 proteins, which were solely detected in in vivo samples, were considered to be plasma derived. Eighty‐six proteins were solely found from in vitro fibroblast‐derived ECM, and most of them were related to matrix remodeling or growth factor action, proposing that the activation of fibroblasts in cell culture may remarkably modify their gene expression profile. Finally, in comparison to traditional 2D in vitro cell culture, the ECM composition of 3D spheroid culture was analyzed. The matrisome in spheroid culture did not resemble the in vivo ECM more closely than in monolayer culture.ConclusionsArtificial activation of ECM remodeling seems to be a distinctive feature in in vitro models. In conclusion the constitution of ECM produced by prostate derived fibroblasts in vitro is similar, but not identical to the prostate ECM in vivo as shown here by mass spectrometric analysis.