bluuebunny/crossref_metadata_2025_split huggingface dataset:
eMolTox: prediction of molecular toxicity with confidence
Authors: Ji Changge , Svensson Fredrik , Zoufir Azedine , Bender Andreas 
Published: March 2018

Abstract

Summary
In this work, we present eMolTox, a web server for the prediction of potential toxicity associated with a given molecule. A total of 174 toxicology-related in vitro/vivo experimental datasets were used for model construction and Mondrian conformal prediction was used to estimate the confidence of the resulting predictions. Toxic substructure analysis is also implemented in eMolTox. eMolTox predicts and displays a wealth of information of potential molecular toxicities for safety analysis in drug development.

Availability and implementation
The eMolTox Server is freely available for use on the web at http://xundrug.cn/moltox.

Supplementary information
Supplementary data are available at Bioinformatics online.
Purpose in Life Among Centenarian Offspring
Authors: Marone Sarah , Bloore Katherine , Sebastiani Paola , Flynn Christopher , Leonard Brittany , Whitaker Kelsey , Mostowy Marilyn , Perls Thomas T , Andersen Stacy L 
Published: March 2018

Abstract

Objectives
Purpose in life (PIL), a feeling of meaning and direction in life, is associated with favorable health outcomes including lower mortality and reduced risk of disease, disability, and cognitive impairment. Since centenarian offspring have been shown to have long health spans we sought to examine whether they have higher PIL than individuals without familial longevity.

Method
We compared PIL scores from the Ryff Scales of Psychological Well-Being in centenarian offspring from the New England Centenarian Study (N = 361, mean age = 82.0 years) with 3 referent groups: spouses, birth cohort-matched referents, and Health and Retirement Study (HRS) participants.

Results
Logistic regression analyses adjusted for age, sex, education, and marital status indicated greater odds of high PIL among centenarian offspring compared with spouse (adjusted odds ratio [aOR] = 1.92, 95% confidence interval [CI] = 1.002–3.68, p = .049) and birth cohort referents (aOR = 2.64, 95% CI = 1.36–5.14, p = .004). Offspring had an almost 3 times greater odds of having high PIL than HRS participants (odds ratio [OR] = 2.93, 95% CI = 2.17–3.96, p &lt; .0001).

Discussion
Higher PIL is associated with being an offspring of a long-lived parent and may play a role in the ability to delay age-associated illnesses and functional decline. Increasing purposefulness may be a target for interventions to promote healthy aging.
Chemical pre-processing of cluster galaxies over the past 10 billion years in the IllustrisTNG simulations
Authors: Gupta Anshu , Yuan Tiantian , Torrey Paul , Vogelsberger Mark , Martizzi Davide , Tran Kim-Vy H , Kewley Lisa J , Marinacci Federico , Nelson Dylan , Pillepich Annalisa , Hernquist Lars , Genel Shy , Springel Volker 
Published: March 2018

Abstract
We use the IllustrisTNG simulations to investigate the evolution of the mass–metallicity relation (MZR) for star-forming cluster galaxies as a function of the formation history of their cluster host. The simulations predict an enhancement in the gas-phase metallicities of star-forming cluster galaxies (109 &lt; M* &lt; 1010 M⊙ h−1) at z ≤ 1.0 in comparisons to field galaxies. This is qualitatively consistent with observations. We find that the metallicity enhancement of cluster galaxies appears prior to their infall into the central cluster potential, indicating for the first time a systematic ‘chemical pre-processing’ signature for infalling cluster galaxies. Namely, galaxies that will fall into a cluster by z = 0 show a ∼0.05 dex enhancement in the MZR compared to field galaxies at z ≤ 0.5. Based on the inflow rate of gas into cluster galaxies and its metallicity, we identify that the accretion of pre-enriched gas is the key driver of the chemical evolution of such galaxies, particularly in the stellar mass range (109 &lt; M* &lt; 1010 M⊙ h−1). We see signatures of an environmental dependence of the ambient/inflowing gas metallicity that extends well outside the nominal virial radius of clusters. Our results motivate future observations looking for pre-enrichment signatures in dense environments.
Sandifer syndrome
Authors: Moore Debora M. , Rizzolo Denise 
Published: March 2018

ABSTRACT
Sandifer syndrome is a rare complication of gastroesophageal reflux disease that may be more common than reported. This syndrome was first mentioned more than 50 years ago with minimal documentation in the medical literature. Because of the presentation, the patient may be referred for lengthy, expensive, and unnecessary neurologic testing. This may lead to a missed or delayed diagnosis, mismanagement, and the use of inappropriate medication. Providers should be aware of Sandifer syndrome when evaluating a child with torticollis or unusual posturing that is not associated with neuromuscular disease or injury.
Current and Optimal Training in High-Value Care in the Internal Medicine Clerkship: A National Curricular Needs Assessment
Authors: Cayea Danelle , Tartaglia Kim , Pahwa Amit , Harrell Heather , Shaheen Amy , Lang Valerie J. 
Published: March 2018

Purpose
The clinical skills needed to practice high-value care (HVC) are core to all medical disciplines. Medical students form practice habits early, and HVC instruction is essential to this formation. The purpose of this study was to describe the state of HVC instruction and assessment in internal medicine clerkships and identify needs for additional curricula.

Method
In 2014, the Clerkship Directors in Internal Medicine conducted its annual survey of 121 U.S. and Canadian medical schools. The authors evaluated a subset of questions from that survey asking clerkship directors about the perceived importance of HVC instruction, type and amount of formal instruction and assessment, achievement of student competence, prioritization of topics, and barriers to curriculum implementation. Descriptive statistics were used to summarize responses, and chi-square tests were used to examine associations between response categories.

Results
The overall response rate was 77.7% (94/121). The majority (85; 91.4%) agreed that medical schools have a responsibility to teach about HVC across all phases of the curriculum. Of respondents, 31 (32.9%) reported their curricula as having some formal instruction on HVC, and 66 (70.2%) felt the amount was inadequate. Highest-priority topics for inclusion included overuse of diagnostic tests and treatments, defining value and its application to clinical reasoning, and balancing benefit and harm. Only 11 (17.8%) assessed students’ competence in HVC.

Conclusions
Internal medicine clerkship directors reported that HVC is insufficiently taught and assessed in medical school, despite relevance to practice. Developing generalizable curricular materials, faculty development, and dedicated curricular time may enhance HVC education.
About Politeness, Face, and Feedback: Exploring Resident and Faculty Perceptions of How Institutional Feedback Culture Influences Feedback Practices
Authors: Ramani Subha , Könings Karen D. , Mann Karen V. , Pisarski Emily E. , van der Vleuten Cees P.M. 
Published: March 2018

Purpose
To explore resident and faculty perspectives on what constitutes feedback culture, their perceptions of how institutional feedback culture (including politeness concepts) might influence the quality and impact of feedback, feedback seeking, receptivity, and readiness to engage in bidirectional feedback.

Method
Using a constructivist grounded theory approach, five focus group discussions with internal medicine residents, three focus group discussions with general medicine faculty, and eight individual interviews with subspecialist faculty were conducted at Brigham and Women’s Hospital between April and December 2016. Discussions and interviews were audiotaped and transcribed verbatim; concurrent data collection and analysis were performed using the constant comparative approach. Analysis was considered through the lens of politeness theory and organizational culture.

Results
Twenty-nine residents and twenty-two general medicine faculty participated in focus group discussions, and eight subspecialty faculty participated in interviews. The institutional feedback culture was described by participants as (1) a culture of politeness, in which language potentially damaging to residents’ self-esteem was discouraged; and (2) a culture of excellence, in which the institution’s outstanding reputation and pedigree of trainees inhibited constructive feedback. Three key themes situated within this broader cultural context were discovered: normalizing constructive feedback to promote a culture of growth, overcoming the mental block to feedback seeking, and hierarchical culture impeding bidirectional feedback.

Conclusions
An institutional feedback culture of excellence and politeness may impede honest, meaningful feedback and may impact feedback seeking, receptivity, and bidirectional feedback exchanges. It is essential to understand the institutional feedback culture before it can be successfully changed.
A Call for Mixed Methods in Competency-Based Medical Education: How We Can Prevent the Overfitting of Curriculum and Assessment
Authors: Hoang Nam S. , Lau James N. 
Published: March 2018

Competency-based medical education (CBME) has been the subject of heated debate since its inception in medical education. Despite the many challenges and pitfalls of CBME that have been recognized by the medical education community, CBME is now seeing widespread implementation. However, the biggest problems with CBME still have not been solved. Two of these problems, reductionism and loss of authenticity, present major challenges when developing curricula and assessment tools.
The authors address these problems by making a call for flexibility in competency definitions and for the use of mixed methods in CBME. First, they present the issue of reductionism and a similar concept from the field of data science, overfitting. Then they outline several solutions, both conceptual and concrete, to prevent undue reductionist tendencies in both competency definitions and in tools of assessment. Finally, they propose the reintroduction of qualitative methods to balance the historically quantitative emphasis of assessment in medical education.
The authors maintain that mixed-methods assessment with multiple assessors in differing contexts can yield a more accurate representation of a medical trainee’s skills and abilities, deter the loss of authenticity, and increase the willingness of medical educators to adopt a feasible form of CBME. Finally, they propose the deployment of dedicated faculty assessors and physician coaches (which will reduce training requirements for other faculty), as well as the use of formal qualitative tools of assessment alongside established quantitative tools, to encourage a truly mixed-methods approach to assessment.
Sodium Channel Nav1.3 Is Expressed by Polymorphonuclear Neutrophils during Mouse Heart and Kidney Ischemia In Vivo and Regulates Adhesion, Transmigration, and Chemotaxis of Human and Mouse Neutrophils In Vitro
Authors: Poffers Marit , Bühne Nathalie , Herzog Christine , Thorenz Anja , Chen Rongjun , Güler Faikah , Hage Axel , Leffler Andreas , Echtermeyer Frank 
Published: March 2018

Abstract

Background
Voltage-gated sodium channels generate action potentials in excitable cells, but they have also been attributed noncanonical roles in nonexcitable cells. We hypothesize that voltage-gated sodium channels play a functional role during extravasation of neutrophils.

Methods
Expression of voltage-gated sodium channels was analyzed by polymerase chain reaction. Distribution of Nav1.3 was determined by immunofluorescence and flow cytometry in mouse models of ischemic heart and kidney injury. Adhesion, transmigration, and chemotaxis of neutrophils to endothelial cells and collagen were investigated with voltage-gated sodium channel inhibitors and lidocaine in vitro. Sodium currents were examined with a whole cell patch clamp.

Results
Mouse and human neutrophils express multiple voltage-gated sodium channels. Only Nav1.3 was detected in neutrophils recruited to ischemic mouse heart (25 ± 7%, n = 14) and kidney (19 ± 2%, n = 6) in vivo. Endothelial adhesion of mouse neutrophils was reduced by tetrodotoxin (56 ± 9%, unselective Nav-inhibitor), ICA121431 (53 ± 10%), and Pterinotoxin-2 (55 ± 9%; preferential inhibitors of Nav1.3, n = 10). Tetrodotoxin (56 ± 19%), ICA121431 (62 ± 22%), and Pterinotoxin-2 (59 ± 22%) reduced transmigration of human neutrophils through endothelial cells, and also prevented chemotactic migration (n = 60, 3 × 20 cells). Lidocaine reduced neutrophil adhesion to 60 ± 9% (n = 10) and transmigration to 54 ± 8% (n = 9). The effect of lidocaine was not increased by ICA121431 or Pterinotoxin-2.

Conclusions
Nav1.3 is expressed in neutrophils in vivo; regulates attachment, transmigration, and chemotaxis in vitro; and may serve as a relevant target for antiinflammatory effects of lidocaine.
Does Equi–Minimum Alveolar Concentration Value Ensure Equivalent Analgesic or Hypnotic Potency?
Authors: Ryu Kyoung-Ho , Song Keulame , Lim Tae-Young , Choi Won-Jun , Kim Yun-Hong , Kim Hyun-Soo 
Published: March 2018

Abstract

Background
Minimum alveolar concentration (MAC) has traditionally been used to compare the potency of volatile anesthetics. However, as it reflects the spinal mechanism of immobility rather than the cerebral mechanism of analgesia and hypnosis, it is doubtful that equi-MAC connotes equivalent analgesic or hypnotic potency. The level of analgesia and hypnosis can be assessed using surgical pleth index and bispectral index (BIS) values, respectively. This study was designed to compare the surgical pleth index and BIS values produced by equi-MAC of desflurane and sevoflurane in patients undergoing single-agent volatile anesthesia.

Methods
Eighty-nine patients were randomly allocated to two groups receiving either desflurane (n = 44) or sevoflurane (n = 45). Anesthesia was only maintained with assigned volatile anesthetic of age-corrected 1.0 MAC. Surgical pleth index values as an analgesic estimate and BIS values as a hypnotic estimate were obtained under standard tetanic stimulation.

Results
Post-stimulation surgical pleth index values (mean ± SD), the primary outcome, were significantly lower for the desflurane group than those for the sevoflurane group (49 ± 10 vs. 64 ± 14, difference, 15 [95% CI, 10 to 20], P < 0.001). The desflurane group showed significantly lower poststimulation BIS values (median [interquartile range]) than the sevoflurane group (36 [31 to 41] vs. 41 [38 to 47], difference, 6 [95% CI, 2 to 9], P = 0.001).

Conclusions
During a steady-state of 1.0 MAC, desflurane and sevoflurane did not cause similar surgical pleth index and BIS values under the standardized nociceptive stimulus. These findings suggest that equi-MAC of desflurane and sevoflurane may not ensure equivalent analgesic or hypnotic potency.
Optimizing Clinical Interpretation of Distortion Product Otoacoustic Emissions in Infants
Authors: Blankenship Chelsea M. , Hunter Lisa L. , Keefe Douglas H. , Feeney M. Patrick , Brown David K. , McCune Annie , Fitzpatrick Denis F. , Lin Li 
Published: March 2018

Objectives:
The purpose of this study was to analyze distortion product otoacoustic emission (DPOAE) level and signal to noise ratio in a group of infants from birth to 4 months of age to optimize prediction of hearing status. DPOAEs from infants with normal hearing (NH) and hearing loss (HL) were used to predict the presence of conductive HL (CHL), sensorineural HL (SNHL), and mixed HL (MHL). Wideband ambient absorbance was also measured and compared among the HL types.

Design:
This is a prospective, longitudinal study of 279 infants with verified NH and HL, including conductive, sensorineural, and mixed types that were enrolled from a well-baby nursery and two neonatal intensive care units in Cincinnati, Ohio. At approximately 1 month of age, DPOAEs (1–8 kHz), wideband absorbance (0.25–8 kHz), and air and bone conduction diagnostic tone burst auditory brainstem response (0.5–4 kHz) thresholds were measured. Hearing status was verified at approximately 9 months of age with visual reinforcement audiometry (0.5–4 kHz). Auditory brainstem response air conduction thresholds were used to assign infants to an NH or HL group, and the efficacy of DPOAE data to classify ears as NH or HL was analyzed using receiver operating characteristic (ROC) curves. Two summary statistics of the ROC curve were calculated: the area under the ROC curve and the point of symmetry on the curve at which the sensitivity and specificity were equal. DPOAE level and signal to noise ratio cutoff values were defined at each frequency as the symmetry point on their respective ROC curve, and DPOAE results were combined across frequency in a multifrequency analysis to predict the presence of HL.

Results:
Single-frequency test performance of DPOAEs was best at mid to high frequencies (3–8 kHz) with intermediate performance at 1.5 and 2 kHz and chance performance at 1 kHz. Infants with a conductive component to their HL (CHL and MHL combined) displayed significantly lower ambient absorbance values than the NH group. No differences in ambient absorbance were found between the NH and SNHL groups. Multifrequency analysis resulted in the best prediction of HL for the SNHL/MHL group with poorer sensitivity values when infants with CHL were included.

Conclusions:
Clinical interpretation of DPOAEs in infants can be improved by using age-appropriate normative ranges and optimized cutoff values. DPOAE interpretation is most predictive at higher F2 test frequencies in young infants (2–8 kHz) due to poor test performance at 1 to 1.5 kHz. Multifrequency rules can be used to improve sensitivity while balancing specificity. Last, a sensitive middle ear measure such as wideband absorbance should be included in the test battery to assess possibility of a conductive component to the HL.
Subspecialty Training Among Graduates of Pediatric Orthopaedic Fellowships: An 11-Year Analysis of the Database of American Board of Orthopaedic Surgery
Authors: Hosseinzadeh Pooya , Louer Craig , Sawyer Jeffrey , Flynn John , Albanese Stephen 
Published: March 2018

Background:
The field of pediatric orthopaedic surgery is evolving with a reported increase in the number of pediatric orthopaedic fellows being trained as well as an increase in the number of fellows completing additional fellowship training in another subspecialty. The purpose of this study was to examine the historic trends of trainees seeking multiple fellowships within pediatric orthopaedics over an 11-year period using the database of the American Board of Orthopaedic Surgery (ABOS).

Methods:
We queried the ABOS database for fellowship choice of applicants for the ABOS part II oral examination with the self-declared subspecialty of pediatric orthopaedics during the years of 2005 to 2015. Descriptive analysis was performed to determine the percentage of applicants who completed >1 fellowship, and the type of subspecialty fellowship completed. χ2 analysis was used to compare the proportion of multiple fellowship trainees between years.

Results:
From 2005 to 2015, 310 applicants for ABOS part II pediatric subspecialty examination had completed a fellowship in pediatric orthopaedic surgery, with that number increasing from 14 to 43/y over that span. Forty-five trainees (15%) completed 48 additional fellowships over that decade, with 2 recent trainees completing multiple additional fellowships. The most common additional fellowships were sports (n=22, 46%), hand (n=8, 17%), and spine (n=7, 15%). The rate of additional fellowship training increased over 5-fold from 5% in the first 3 years of the study to 28% in the last 2 years of the study (P=0.001).

Conclusions:
The proportion of trainees completing additional subspecialty fellowships in addition to pediatric orthopaedics has risen over the past decade. The precise cause and effect of such change is uncertain and likely multifactorial. Reexamination of our classic training paradigms may be warranted in light of these trends.

Level of Evidence:
Level III.
Liberal Glucose Control in ICU Patients With Diabetes: A Before-and-After Study*
Authors: Luethi Nora , Cioccari Luca , Biesenbach Peter , Lucchetta Luca , Kagaya Hidetoshi , Morgan Rhys , Di Muzio Francesca , Presello Barbara , Gaafar Duaa , Hay Alison , Crisman Marco , Toohey Roisin , Russell Hollie , Glassford Neil J. , Eastwood Glenn M. , Ekinci Elif I. , Deane Adam M. , Bellomo Rinaldo , Mårtensson Johan 
Published: March 2018

Objectives:
To assess the feasibility, biochemical efficacy, and safety of liberal versus conventional glucose control in ICU patients with diabetes.

Design:
Prospective, open-label, sequential period study.

Setting:
A 22-bed mixed ICU of a tertiary hospital in Australia.

Patients:
We compared 350 consecutive patients with diabetes admitted over 15 months who received liberal glucose control with a preintervention control population of 350 consecutive patients with diabetes who received conventional glucose control.

Interventions:
Liberal control patients received insulin therapy if glucose was greater than 14 mmol/L (target: 10–14 mmol/L [180–252 mg/dL]). Conventional control patients received insulin therapy if glucose was greater than 10 mmol/L (target: 6–10 mmol/L [108–180 mg/dL]).

Measurements and Main Results:
We assessed separation in blood glucose, insulin requirements, occurrence of hypoglycemia (blood glucose ≤ 3.9 mmol/L [70 mg/dL]), creatinine and white cell count levels, and clinical outcomes. The median (interquartile range) time-weighted average blood glucose concentration was significantly higher in the liberal control group (11.0 mmol/L [8.7–12.0 mmol/L]; 198 mg/dL [157–216 mg/dL]) than in the conventional control group (9.6 mmol/L [8.5–11.0 mmol/L]; 173 mg/dL [153–198 mg/dL]; p < 0.001). Overall, 132 liberal control patients (37.7%) and 188 conventional control patients (53.7%) received insulin in ICU (p < 0.001). Hypoglycemia occurred in 6.6% and 8.6%, respectively (p = 0.32). Among 314 patients with glycated hemoglobin A1c greater than or equal to 7%, hypoglycemia occurred in 4.1% and 9.6%, respectively (p = 0.053). Trajectories of creatinine and white cell count were similar in the groups. In multivariable analyses, we found no independent association between glucose control and mortality, duration of mechanical ventilation, or ICU-free days to day 30.

Conclusions:
In ICU patients with diabetes, during a period of liberal glucose control, insulin administration, and among patients with hemoglobin A1c greater than or equal to 7%, the prevalence of hypoglycemia was reduced, without negatively affecting serum creatinine, the white cell count response, or other clinical outcomes. (Trial Registration: Australian New Zealand Clinical Trials Registry; ACTRN12615000216516).