bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Continuum of Innovation: Curricular Renewal Strategies in Undergraduate Medical Education, 2010–2018
Authors: Novak Daniel A. , Hallowell Ronan , Ben-Ari Ron , Elliott Donna 
Published: July 2019

Purpose
Since 2010, medical schools across the United States have engaged in a new cycle of curricular revision and renewal for their undergraduate medical curricula. But what structures, features, and trends have emerged in U.S. medical schools as a result of deliberate curricular redesign efforts? An analysis of the ways that medical schools have approached the reorganization of their curricula to prepare their students for the growing complexity of medical practice is presented.

Method
This study drew a total pool of 40 U.S. MD-granting programs, of which 25 met the inclusion criteria for the study. The authors used a qualitative coding approach to materials from the undergraduate medical education (UME) program websites to identify 4 dimensions of strategies that these programs used to renew their curricula.

Results
The analysis of the curricular maps and website content of the UME programs provided evidence for a continuum approach to the description of innovation strategies: 96% of schools employed a cohort-based linear pathway, 80% of schools used thematic basic science blocks, 47% placed their Step 1 exams outside of the second year, and 68% moved their clerkships to the second year.

Conclusions
The Continuum of Innovation strategies will enable programs to renew their curricula in ways that promote deliberate curricular changes that are consistent with emerging needs in the field. This study and future research may be useful for UME programs with limited resources by providing consensus practices that enable them to plan curricular changes in ways that best serve their institutions.
Technological Pedagogical Content Knowledge Among Medical Educators: What Is Our Readiness to Teach With Technology?
Authors: Youm Julie , Corral Janet 
Published: July 2019

Purpose
This study aimed to empirically assess medical educator knowledge of pedagogy and technology to inform the direction of faculty development efforts.

Method
The technological pedagogical content knowledge (TPACK) framework survey is a validated instrument for understanding educators’ knowledge of content (CK), pedagogy (PK), and technology (TK) in teaching. A modified version of the TPACK was administered to medical educators (N = 76) at 2 public institutions: University of California, Irvine School of Medicine (UC Irvine); and University of Colorado School of Medicine (CU).

Results
An independent-samples t test compared TK with PK and CK within each institution. The means of TK (UC Irvine: 3.4; CU: 3.4) and both PK for didactic sessions (UC Irvine: 3.9; CU: 4.4) and PK for clinical settings (UC Irvine: 4.0; CU: 4.4) were compared using a t test and statistically different, P < .01. Similarly, the means of TK and CK (UC Irvine: 4.5; CU: 4.7) were statistically different, P < .01. A Wilcoxon rank sum test indicated that the CU PK for a didactic session (mean: 4.4) was greater than the UC Irvine PK for a didactic session (mean: 3.9), P < .01. Similarly, the CU PK for a clinical setting (mean: 4.4) was greater than the UC Irvine PK for a clinical setting (mean: 4.0), P < .01.

Conclusions
There is a clear need for faculty development programs for medical educators to focus on how to teach with technology if medical schools continue to adopt technology within their curricula.
Learning Conversations: An Analysis of the Theoretical Roots and Their Manifestations of Feedback and Debriefing in Medical Education
Authors: Tavares Walter , Eppich Walter , Cheng Adam , Miller Stephen , Teunissen Pim W. , Watling Christopher J. , Sargeant Joan 
Published: July 2019

Feedback and debriefing are experience-informed dialogues upon which experiential models of learning often depend. Efforts to understand each have largely been independent of each other, thus splitting them into potentially problematic and less productive factions. Given their shared purpose of improving future performance, the authors asked whether efforts to understand these dialogues are, for theoretical and pragmatic reasons, best advanced by keeping these concepts unique or whether some unifying conceptual framework could better support educational contributions and advancements in medical education.
The authors identified seminal works and foundational concepts to formulate a purposeful review and analysis exploring these dialogues’ theoretical roots and their manifestations. They considered conceptual and theoretical details within and across feedback and debriefing literatures and traced developmental paths to discover underlying and foundational conceptual approaches and theoretical similarities and differences.
Findings suggest that each of these strategies was derived from distinct theoretical roots, leading to variations in how they have been studied, advanced, and enacted; both now draw on multiple (often similar) educational theories, also positioning themselves as ways of operationalizing similar educational frameworks. Considerable commonality now exists; those studying and advancing feedback and debriefing are leveraging similar cognitive and social theories to refine and structure their approaches. As such, there may be room to merge these educational strategies as learning conversations because of their conceptual and theoretical consistency. Future scholarly work should further delineate the theoretical, educational, and practical relevance of integrating feedback and debriefing.
Safety of 6-week Neonatal Triple-combination Antiretroviral Postexposure Prophylaxis in High-risk HIV-exposed Infants
Authors: Anugulruengkitt Suvaporn , Suntarattiwong Piyarat , Ounchanum Pradthana , Srirompotong Ussanee , Jantarabenjakul Watsamon , Sophonphan Jiratchaya , Punnahitanon Sunti , Pancharoen Chitsanu , Cressey Tim R. , Chokephaibulkit Kulkanya , Puthanakit Thanyawee 
Published: July 2019

Background:
Combination antiretroviral drug regimens are increasingly preferred for neonatal postexposure prophylaxis (PEP) among HIV-exposed infants with high-risk of transmission. We evaluated the adverse events associated with the use of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) for neonatal PEP during the first 6 weeks of life.

Methods:
A prospective cohort of non-breast-fed HIV-exposed infants was conducted at 5 clinical sites in Thailand. Study population included 100 high-risk HIV-exposed infants (maternal HIV RNA > 50 copies/mL prior to delivery or received antiretroviral therapy less than 12 weeks) and 100 low-risk HIV-exposed neonates. High-risk infants received ZDV/3TC/NVP for 6 weeks whereas low-risk HIV-exposed neonates received a 4-week regimen of ZDV. Complete blood count, aspartate transaminase and alanine transaminase were assessed at birth, 1, 2 and 4 months of life.

Results:
From October 2015 to November 2017, 200 infants were enrolled, of which 18.5% had low birth weight < 2500 g. The proportion of infants with anemia grade 2 or higher at 1 and 2 months of life between ZDV/3TC/NVP and ZDV prophylaxis was 48.5% vs 32.3% (P=0.02); nevertheless, severe anemia (grade 3) was not significantly different; 9.2% vs 10.2% (P=0.81), respectively. At 1 month old, infants on ZDV/3TC/NVP prophylaxis had significantly higher grade 2 anemia versus infants on ZDV alone (33.0% vs 13.4%; P=0.001); however, no difference was observed at 2 months old. No differences in neutropenia or hepatotoxicity between infant prophylactic regimens were observed.

Conclusions:
Triple antiretroviral neonatal PEP with ZDV/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with ZDV-monotherapy prophylaxis.
A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy
Authors: Gaifullina Aisylu S. , Lazniewska Joanna , Gerasimova Elena V. , Burkhanova Gulshat F. , Rzhepetskyy Yuriy , Tomin Andriy , Rivas-Ramirez Paula , Huang Junting , Cmarko Leos , Zamponi Gerald W. , Sitdikova Guzel F. , Weiss Norbert 
Published: July 2019

Abstract
Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C–dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.
Texture Analysis of Magnetic Resonance Enterography Contrast Enhancement Can Detect Fibrosis in Crohn Disease Strictures
Authors: Tabari Azadeh , Kilcoyne Aoife , Jeck William R. , Mino‐Kenudson Mari , Gee Michael S. 
Published: July 2019

ABSTRACTObjective:The aim of the study was to investigate if texture analysis of contrast‐enhanced magnetic resonance enterography (MRE) images can determine Crohn disease (CD) stricture histologic type.Materials and Methods:A radiology report database query identified 25 pediatric patients with established CD who underwent MRE followed by bowel resection within 30 days. MRE images were reviewed to identify strictures on enteric phase T1‐weighted fat‐suppressed images, that were matched with sites of histologic sectioning. Regions of interest were drawn over the bowel wall and texture analysis was performed using TexRAD software (Cambridge, UK), with skewness, mean, entropy and standard deviation parameters assessed. A pathologist reviewed all stricture histology specimens to assess for active mucosal inflammation and mural fibrosis. Multivariate logistic regression and analysis of variance were performed to identify texture features associated with stricture fibrosis.Results:Sixty‐four bowel segments from 25 patients (mean age 16 ± 2 years) with imaging‐histologic correlation were included. Of note, all strictures included had undergone surgical resection with MRE imaging available within 30 days. The histologic distribution of these bowel segments included 9 segments that showed active inflammation without fibrosis, 23 segments that showed only fibrosis, and 32 mixed segments with concomitant active inflammation and fibrosis. Bivariate regression analysis demonstrated that skewness, standard deviation, entropy, and mean texture analysis features are independently associated with stricture fibrosis. Stepwise logistic regression showed that the combination of mean, skewness, and entropy texture predicted stricture fibrosis with a goodness‐of‐fit value of 0.995. A combination of threshold values for these 3 texture analysis parameters was able to correctly classify 100% of the strictures in the study cohort for presence (55/55) and absence (9/9) of fibrosis.Conclusions:MRE texture analysis (MRE‐TA) texture features can differentiate CD stricture types and accurately detect fibrosis.
Time‐to‐reach Target Calprotectin Level in Newly Diagnosed Patients With Inflammatory Bowel Disease
Authors: Haisma Sjoukje‐Marije , Verkade Henkjan J. , Scheenstra Rene , van der Doef Hubert P.J. , Bodewes Frank A.J.A. , van Rheenen Patrick F. 
Published: July 2019

ABSTRACTObjectives:Treatment targets in inflammatory bowel disease (IBD) move away from controlling symptoms towards complete recovery of the intestinal mucosa. Currently, the most frequently used noninvasive surrogate marker of mucosal healing is a faecal calprotectin concentration in the target range. This study tested if there was a relation between time‐to‐reach target calprotectin and first flare.Methods:We prospectively included new‐onset IBD patients ages 17 and younger in a cloud‐based registry (FastForwardCare) and followed them for at least 52 weeks. They were treated according to Dutch national guidelines that advocate a step‐up approach. Time‐to‐reach target was defined as the first calprotectin measurement below 250 μg/g after the start of induction therapy. Time‐to‐first flare was the time from the first calprotectin measurement below 250 μg/g until reappearance of symptoms with calprotectin values above 250 μg/g.Results:We included 76 patients (luminal Crohn disease [CD] 43); ulcerative colitis [UC] 33). Median age at diagnosis was, respectively 14.5 and 14.1 years. Median time‐to‐reach target calprotectin was 37 weeks in CD and 11 weeks in UC patients (Log‐rank test, P = 0.001). Once the calprotectin target was reached, time‐to‐first flare was significantly longer in CD than in UC patients (Log‐rank test, P = 0.001). CD patients with time‐to‐reach target calprotectin ≤12 weeks after conventional induction therapy (ie, exclusive enteral nutrition or steroids) had a more favorable disease course in the first year than those with time‐to‐reach target calprotectin >12 weeks (Log‐rank test, P = 0.057). In UC patients, time‐to‐reach target calprotectin ≤12 weeks is not associated with a favorable disease course in the first year.Conclusions:The findings of this prospective registry suggest that a quick response to conventional therapy predicts a favorable disease course in new‐onset paediatric CD, but not in UC. The concept “time‐to‐reach target calprotectin level” rationalizes the indefinite term “response to treatment” and is well suited for studying treatment effectiveness in real‐world practices.
Cough, an unresolved problem in interstitial lung diseases
Authors: van Manen Mirjam J.G. , Wijsenbeek Marlies S. 
Published: July 2019

Purpose of review
Many patients with interstitial lung diseases (ILDs), especially fibrotic ILDs, experience chronic cough. Cough has a major impact on wellbeing, affecting both physical and psychological aspects of life. The pathophysiology of cough in ILDs is poorly understood and currently no good antitussive therapy exists.

Recent findings
Research on cough in ILDs is increasing. A recent proof-of-concept study with nebulized sodium cromoglycate for patients with idiopathic pulmonary fibrosis (IPF)-related cough showed a promising effect on cough. Observational data suggest that antifibrotic pirfenidone might reduce cough in IPF. Studies on the effect of acid inhibition on cough in ILDs show contradicting results.

Summary
The first steps in analyzing new treatment options for chronic cough in patients with ILDs, especially in IPF, have been taken, but an effective treatment is still lacking.
Heterogeneity of Human Pancreatic Islet Isolation Around Europe: Results of a Survey Study
Authors: Nano Rita , Kerr-Conte Julie A. , Scholz Hanne , Engelse Marten , Karlsson Marie , Saudek Frantisek , Bosco Domenico , Antonioli Barbara , Bertuzzi Federico , Johnson Paul R.V. , Ludwing Barbara , Ling Zhidong , De Paep Diedert L. , Keymeulen Bart , Pattou François , Berney Thierry , Korsgren Olle , de Koning Eelco , Piemonti Lorenzo 
Published: July 2019

Background.
Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries.

Methods.
A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan.

Results.
Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities.

Conclusions.
The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.
Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition
Authors: Nosrati Meisam , Dey Debayan , Mehrani Atousa , Strassler Sarah E. , Zelinskaya Natalia , Hoffer Eric D. , Stagg Scott M. , Dunham Christine M. , Conn Graeme L. 
Published: July 2019

ABSTRACTMethylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (m7G1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.14 Å resolution, here we report a structure-guided functional study of 30S substrate recognition by the aminoglycoside resistance–associated 16S rRNA (m7G1405) methyltransferases. We found that the binding site for these enzymes in the 30S subunit directly overlaps with that of a second family of aminoglycoside resistance–associated 16S rRNA (m1A1408) methyltransferases, suggesting both groups of enzymes may exploit the same conserved rRNA tertiary surface for docking to the 30S. Within RmtC, we defined an N-terminal domain surface, comprising basic residues from both the N1 and N2 subdomains, that directly contributes to 30S-binding affinity. In contrast, additional residues lining a contiguous adjacent surface on the C-terminal domain were critical for 16S rRNA modification, but did not directly contribute to the binding affinity. The results from our experiments define the critical features of m7G1405 methyltransferase–substrate recognition and distinguish at least two distinct, functionally critical contributions of the tested enzyme residues: 30S-binding affinity and stabilizing a binding-induced 16S rRNA conformation necessary for G1405 modification. Our study sets the scene for future high-resolution structural studies of the 30S–methyltransferase complex and for potential exploitation of unique aspects of substrate recognition in future therapeutic strategies.
Cross-species transcriptomic and epigenomic analysis reveals key regulators of injury response and neuronal regeneration in vertebrate retinas
Authors: Hoang Thanh , Wang Jie , Boyd Patrick , Wang Fang , Santiago Clayton , Jiang Lizhi , Lahne Manuela , Yoo Sooyeon , Todd Levi J. , Saez Cristian , Keuthan Casey , Palazzo Isabella , Squires Natalie , Campbell Warren A. , Jia Meng , Rajaii Fatemeh , Parayil Trisha , Trinh Vickie , Kim Dong Won , Wang Guohua , Ash John , Fischer Andy J. , Hyde David R. , Qian Jiang , Blackshaw Seth 
Published: July 2019

AbstractInjury induces retinal Müller glia of cold-blooded, but not mammalian, vertebrates to regenerate neurons. To identify gene regulatory networks that control neuronal reprogramming in retinal glia, we comprehensively profiled injury-dependent changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick and mice using bulk RNA-Seq and ATAC-Seq, as well as single-cell RNA-Seq. Cross-species integrative analysis of these data, together with functional validation, identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, gliosis and neurogenesis. In zebrafish and chick, transition from the resting state to gliosis is essential for initiation of retinal regeneration, while in mice a dedicated network suppresses neurogenic competence and restores quiescence. Selective disruption of NFI family transcription factors, which maintain and restore quiescence, enables Müller glia to proliferate and generate neurons in adult mice following retinal injury. These findings may aid in the design of cell-based therapies aimed at restoring retinal neurons lost to degenerative disease.Summary sentenceThis study identifies gene regulatory networks controlling proliferative and neurogenic competence in retinal Müller glia.
Genome wide analysis inDrosophilareveals diet by gene interactions and uncovers diet-responsive genes
Authors: Francis Deanne , Ghazanfar Shila , Havula Essi , Krycer James R. , Senior Alistair , Minard Annabel Y. , Geddes Thomas , Weiss Fiona , Stöckli Jacqueline , Yang Jean Y.H. , James David E. 
Published: July 2019

AbstractGenetic and environmental factors play a major role in metabolic health. However, they do not act in isolation, as a change in an environmental factor such as diet may exert different effects based on an individual’s genotype. Here, we sought to understand how such gene-diet interactions influenced nutrient storage and utilisation, a major determinant of metabolic disease. We subjected the Drosophila Genetic Reference Panel (DGRP), comprising 200 genetically divergent inbred fly strains, to diets varying in sugar, fat and protein. We assessed starvation resistance, a holistic phenotype of nutrient storage and utilisation that can be robustly measured. Diet influenced the starvation resistance of each strain, but this effect varied markedly between strains. This demonstrates that genetics plays a major role in the response to diet. Furthermore, heritability analysis revealed that the greatest variability arose from diets either high in sugar or high in protein. To uncover the genetic underpinnings of this variation, we mapped 1,239 diet-responsive SNPs in 534 genes, 325 of which have human orthologues. Using whole-body knockdown, we confirmed that 30 candidate genes were required for glucose tolerance, storage and utilization. In particular, we characterised CG4607, a GLUT6/GLUT8 homolog, as a key protein involved in sugar tolerance. Overall, this provides strong evidence that genetics is a major contributor to how individuals respond to diets of varying nutrient composition. It is likely that a similar principle may be applied to metabolic disease in higher organisms thus supporting the case for nutrigenomics as an important health strategy.