bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence: novel insight into DLX3 mutations leading to enhanced bone formation in Tricho-Dento-Osseous syndrome
Authors: Zhao Na , Han Dong , Liu Haochen , Li Yue , Wong Sing-Wai , Cao Zhengyi , Xu Jian , Zhang Xiaowei , Cai Tao , Wang Yixiang , Feng Hailan 
Published: December 2016

AbstractThe homeodomain transcription factor distal-less homeobox 3 gene (DLX3) is required for hair, tooth and skeletal development. DLX3 mutations have been found to be responsible for Tricho-Dento-Osseous (TDO) syndrome, characterized by kinky hair, thin-pitted enamel and increased bone density. Here we show that the DLX3 mutation (c.533 A>G; Q178R) attenuates osteogenic potential and senescence of bone mesenchymal stem cells (BMSCs) isolated from a TDO patient, providing a molecular explanation for abnormal increased bone density. Both DLX3 mutations (c.533 A>G and c.571_574delGGGG) delayed cellular senescence when they were introduced into pre-osteoblastic cells MC3T3-E1. Furthermore, the attenuated skeletal aging and bone loss in DLX3 (Q178R) transgenic mice not only reconfirmed that DLX3 mutation (Q178R) delayed cellular senescence, but also prevented aging-mediated bone loss. Taken together, these results indicate that DLX3 mutations act as a loss of function in senescence. The delayed senescence of BMSCs leads to increased bone formation by compensating decreased osteogenic potentials with more generations and extended functional lifespan. Our findings in the rare human genetic disease unravel a novel mechanism of DLX3 involving the senescence regulation of bone formation.
Birth of a W sex chromosome by horizontal transfer ofWolbachiabacterial symbiont genome
Authors: Leclercq Sébastien , Thézé Julien , Chebbi Mohamed Amine , Giraud Isabelle , Moumen Bouziane , Ernenwein Lise , Grève Pierre , Gilbert Clément , Cordaux Richard 
Published: December 2016

SignificanceSex determination is an evolutionarily ancient, key developmental pathway governing sexual differentiation in animals. Sex determination systems are remarkably variable between species or groups of species, however, and the evolutionary forces underlying transitions between these systems are poorly understood. Here we provide evidence indicating that the genome ofWolbachiabacterial endosymbionts was horizontally transferred into a chromosome of the common pillbugArmadillidium vulgare, which resulted in this chromosome evolving as a new female (W) sex chromosome. This represents a remarkable mechanism underpinning the birth of sex chromosomes. We conclude that bacteria can be powerful agents of evolutionary transitions in sex determination systems in animals.
Pegylated IFN-α suppresses hepatitis C virus by promoting the DAPK-mTOR pathway
Authors: Liu Wei-Liang , Yang Hung-Chih , Hsu Ching-Sheng , Wang Chih-Chiang , Wang Tzu-San , Kao Jia-Horng , Chen Ding-Shinn 
Published: December 2016

Significance
Death-associated protein kinase (DAPK) regulates several important biological functions through a diverse range of signal transduction pathways, including cell growth, the immune response, apoptosis, and autophagy, but its antiviral activity has not been explored. Our data provide evidence that DAPK is one of the major regulators for the pegylated IFN-α–induced antiviral activity against hepatitis C virus, suggesting that DAPK may serve as a novel antiviral target and also a new biomarker to predict the therapeutic efficacy of pegylated IFN-α and other antiviral agents.
The influence of race length on arterial compliance following an ultra‐endurance marathon
Authors: Bonsignore Alis , Bredin Shannon S. D. , Wollmann Holly , Morrison Barb , Jeklin Andrew , Buschmann Lauren , Robertson Josh , Buckler Elizabeth Jean , McGuinty Duncan , Rice Mark S. , Warburton Darren E. R. 
Published: December 2016

AbstractThere is inconclusive evidence concerning the effects of routine participation in ultra‐endurance events on cardiovascular disease (CVD) risk. Arterial compliance is a reliable, non‐invasive, and effective tool for evaluating CVD risk. The purpose of this research was to examine if race length influences acute changes in arterial compliance following an ultra‐marathon event. A total of 46 ultra‐marathon runners were recruited including 21 participants (39.8 ± 8.3 years, 6 females) in the 80‐km event and 25 participants (43.7 ± 9.8 years, 3 female) in the 195‐km event. Arterial compliance was measured via radial applanation tonometry (CR‐2000, HDI) for diastolic pulse contour analysis before and following the race. Significant between‐group differences were found for changes in large arterial compliance with a decrease (increase in stiffness) following the 195‐km event and an increase following the 80‐kilometre event (p < .05). Longer race lengths are associated with greater reductions in large arterial compliance following recreational ultra‐marathon running. Assessment of arterial compliance might be a useful prognostic tool to assess the long‐term risk of CVD among ultra‐marathon runners.
The MD–MEd Joint-Degree Program at Vanderbilt University: Training Future Expert Medical Educators
Authors: Sullivan William M. , DeVolder Jacob , Bhutiani Monica , Neal Kristen W. , Miller Bonnie M. 
Published: December 2016

Problem
Some medical students are drawn to medical education as an area of academic specialization. However, few options exist for medical students who wish to build a scholarly foundation for future careers in medical education.

Approach
In 2011, Vanderbilt University School of Medicine (VUSM) and Peabody College of Education and Human Development at Vanderbilt University partnered to establish a novel dual-degree program that, through transfer of credit, allows students to graduate with both an MD and a master of education (MEd) degree in five years. The MD–MEd joint-degree program equips students with robust knowledge and skills related to general education while providing opportunities through independent studies and capstone projects to contextualize these ideas in medical education.

Outcomes
This innovation at Vanderbilt University demonstrates the feasibility of an MD–MEd joint-degree program. MD–MEd graduates’ demonstrated commitment to medical education and credentials will allow them to take on greater educational responsibilities earlier in their careers and quickly gain experience. The three author participants feel their experiences allowed them to achieve desired competencies as educators. They have each gained early experience by chairing the Student Curriculum Committee and contributing to major curricular reform at VUSM.

Next Steps
The authors plan to integrate specific medical education competencies into the program, which will require MD–MEd students to develop and demonstrate proficiency in the knowledge and skills expected of dedicated medical educators. Graduates’ career trajectories will be tracked to explore whether they become medical educators, conduct educational research, and assume leadership positions.
Evaluation of the Financial and Health Burden of Infants at Risk for Respiratory Syncytial Virus
Authors: Blake Stephanie McCallum , Tanaka David , Bendz Lisa M. , Staebler Suzanne , Brandon Debra 
Published: December 2016

Background:
Respiratory syncytial virus (RSV) is the leading viral cause of death in infants younger than 1 year. In July 2014, the American Academy of Pediatrics (AAP) Committee on Infectious Diseases concluded that the “limited clinical benefit” for infants born at more than 29 weeks' gestation, together with the associated high cost of the immunoprophylaxis, no longer supported the routine use of palivizumab (Synagis).

Purpose:
To evaluate the impact of the newly adopted AAP palivizumab prophylaxis administration on health and subsequent hospital costs of infants born between 29 and less than 32 weeks' gestation.

Methods:
A retrospective cohort analysis from a single institution across the duration of the study comparing the clinical and financial outcomes of infants (aged < 32 weeks) treated under the 2009 AAP guidelines (PRE) and infants (aged >29 weeks) managed after the 2014 AAP guidelines (POST) took effect.

Results:
RSV-positive admissions were greater in the POST cohort versus the PRE cohort (P = .04). There were no readmission deaths due to RSV infection in either cohort. The number needed to treat to avoid a single RSV-positive hospitalization was 20 infants at an estimated palivizumab cost of $90,000 to avoid an estimated hospital cost of $29,000.

Implications for Practice:
Assessment of individual risk factors and their ability to predict severe RSV risk/disease, thus, would allow providers greater flexibility in determining need for prophylaxis therapy.

Implications for Research:
Longitudinal evaluation of financial and clinical outcomes is needed to determine the impact of the 2014 AAP revised regulatory guidelines.
Preeclampsia and Long-term Risk of Maternal Retinal Disorders
Authors: Auger Nathalie , Fraser William D. , Paradis Gilles , Healy-Profitós Jessica , Hsieh Ada , Rhéaume Marc-André 
Published: December 2016

OBJECTIVE:
To evaluate whether preeclampsia is associated with risk of maternal retinal disease in the decades after pregnancy.

METHODS:
We carried out a longitudinal cohort study of 1,108,541 women who delivered neonates in any hospital in Quebec, Canada, between 1989 and 2013. We tracked women for later hospitalizations until March 31, 2014. Preeclampsia was measured at delivery categorized by severity (mild or severe) and onset (before or at 34 weeks or more of gestation). Main outcomes were hospitalizations and inpatient procedures for retinal detachment, retinopathy, or other retinal disorders. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing preeclampsia with no preeclampsia adjusting for diabetes and hypertension.

RESULTS:
Compared with no preeclampsia, women with preeclampsia had a higher incidence of hospitalization for retinal detachment (52.9 compared with 23.9/10,000), retinopathy (60.5 compared with 8.0/10,000), and other retinal disorders (13.3 compared with 7.3/10,000). Preeclampsia was most strongly associated with traction detachments (HR 2.39, 95% CI 1.52–3.74), retinal breaks (HR 2.48, 95% CI 1.40–4.41), and diabetic retinopathy (HR 4.13, 95% CI 3.39–5.04). Severe and early-onset preeclampsia was associated with even higher risk compared with mild or late-onset preeclampsia.

CONCLUSION:
Preeclampsia, particularly severe or early-onset preeclampsia, is associated with an increased risk of maternal retinal disease in the decades after pregnancy.
Intraoperative Archive of Right Colonic Vascular Variability Aids Central Vascular Ligation and Redefines Gastrocolic Trunk of Henle Variants
Authors: Alsabilah Jamal F. , Razvi Syed A. , Albandar Mahdi H. , Kim Nam K. 
Published: December 2016

BACKGROUND:
Vascular supply to the right colon has become an issue because of high variability and subsequent impact on minimally invasive surgery. Past cadaveric or radiologic anatomic assessments are noncomprehensive.

OBJECTIVE:
Intraoperative charting of right colonic arteriovenous anatomy was undertaken to determine the incidence and scope of vascular variations.

DESIGN:
Vascular anatomy variations were documented in snapshot images, captured during laparoscopic video recordings or through open surgical digital photography.

SETTINGS:
Data were drawn from consecutive right hemicolectomies, routinely entailing complete mesocolic excision with central vascular ligation.

PATIENTS:
Seventy patients (mean age, 62.7 years; 37 women (52.8%); 33 men (47.2%)), each with surgically treatable right-sided colon cancer, were prospectively studied.

RESULTS:
Both ileocolic and middle colic arteries were regularly identified (100%), with right colic artery present in 41.4% of patients. Ileocolic and middle colic veins consistently drained into the right colon. Although the ileocolic vein always emptied into the superior mesenteric vein, drainage of the middle colic vein was split (superior mesenteric vein, 94.3%; gastrocolic trunk of Henle, 5.3%), as was drainage of the right colic (superior mesenteric vein, 43.3%; gastrocolic trunk of Henle, 56.7%) and accessory middle colic veins (superior mesenteric vein, 54.5%; gastrocolic trunk of Henle, 45.5%), present in 42.9% and 15.7% of patients. Gastrocolic trunk of Henle was found in 88.6% of patients, usually draining into the superior mesenteric vein. No significant sex-related differences were present regarding the incidence and scope of variability displayed by the right colic artery, right colic vein, accessory middle colic vein, or gastrocolic trunk of Henle classification (p > 0.05).

LIMITATIONS:
The inconsistency between cadaver and live surgery anatomy and the low BMI of the Asian population might be drawbacks of our study.

CONCLUSIONS:
Variations in right colonic arteriovenous channels, assessed intraoperatively, corroborate those established by cadaveric and radiologic means, prompting a new gastrocolic trunk of Henle classification.
Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler
Authors: Wang Muyao , Li Wei , Zhang Yan , Tian Weidong , Wang Hang 
Published: December 2016

BACKGROUNDHyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied.OBJECTIVETo evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections.MATERIALS AND METHODSThe authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2.RESULTSNearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups.CONCLUSIONA complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.
Clinical coordination in accountable care organizations: A qualitative study
Authors: Lewis Valerie A. , Schoenherr Karen , Fraze Taressa , Cunningham Aleen 
Published: December 2016

Background:
Accountable care organizations (ACOs) are becoming a common payment and delivery model. Despite widespread interest, little empirical research has examined what efforts or strategies ACOs are using to change care and reduce costs. Knowledge of ACOs' clinical efforts can provide important context for understanding ACO performance, particularly to distinguish arenas where ACOs have and have not attempted care transformation.

Purpose:
The aim of the study was to understand ACOs' efforts to change clinical care during the first 18 months of ACO contracts.

Methods:
We conducted semistructured interviews between July and December 2013. Our sample includes ACOs that began performance contracts in 2012, including Medicare Shared Savings Program and Pioneer participants, stratified across key factors. In total, we conducted interviews with executives from 30 ACOs. Iterative qualitative analysis identified common patterns and themes.

Results:
ACOs in the first year of performance contracts are commonly focusing on four areas: first, transforming primary care through increased access and team-based care; second, reducing avoidable emergency department use; third, strengthening practice-based care management; and fourth, developing new boundary spanner roles and activities. ACOs were doing little around transforming specialty care, acute and postacute care, or standardizing care across practices during the first 18 months of ACO performance contracts.

Practice Implications:
Results suggest that cost reductions associated with ACOs in the first years of contracts may be related to primary care. Although in the long term many hope ACOs will achieve coordination across a wide array of care settings and providers, in the short term providers under ACO contracts are focused largely on primary care-related strategies. Our work provides a template of the common areas of clinical activity in the first years of ACO contracts, which may be informative to providers considering becoming an ACO. Further research will be needed to understand how these strategies are associated with performance.
Vitamin D in pediatric gastrointestinal disease
Authors: Ahlawat Rajni , Weinstein Toba , Pettei Michael J. 
Published: December 2016

Purpose of review
The purpose of this review is to examine the prevalence of vitamin D deficiency in pediatric gastrointestinal disease, specifically celiac disease and inflammatory bowel disease (IBD); to discuss the role of vitamin D and its deficiency in gastrointestinal disease pathophysiology; and to present current literature regarding diagnosis and treatment of vitamin D deficiency in these pediatric gastrointestinal diseases.

Recent findings
Vitamin D deficiency is common in children with gastrointestinal symptoms and disease processes. In celiac disease, vitamin D status should be routinely assessed at the time of diagnosis and during subsequent follow up if deficient. There is growing evidence to suggest an inverse association between vitamin D and IBD activity; however, the therapeutic role of vitamin D in IBD patients requires further investigation.

Summary
Suboptimal vitamin D status commonly occurs in children with gastrointestinal disease. It is advisable to check serum 25-hydroxy vitamin D levels in children with newly diagnosed celiac disease and IBD. In celiac disease, vitamin D status should be assessed during subsequent follow up if deficient. In IBD, 25-hydroxy vitamin D levels should be checked at least yearly. Therapy should be provided to maintain a level of greater than 30 ng/ml but less than 100 ng/ml; however, the ideal vitamin D dosing regimen to treat vitamin D deficiency and to maintain this optimum level remains unknown. The role of vitamin D as a therapeutic agent in IBD is still under investigation.
Patient Simulation for Assessment of Layperson Management of Opioid Overdose With Intranasal Naloxone in a Recently Released Prisoner Cohort
Authors: Kobayashi Leo , Green Traci C. , Bowman Sarah E. , Ray Madeline C. , McKenzie Michelle S. , Rich Josiah D. 
Published: December 2016

Introduction
Investigators applied simulation to an experimental program that educated, trained, and assessed at-risk, volunteering prisoners on opioid overdose (OD) prevention, recognition, and layperson management with intranasal (IN) naloxone.

Methods
Consenting inmates were assessed for OD-related experience and knowledge then exposed on-site to standardized didactics and educational DVD (without simulation). Subjects were provided with IN naloxone kits at time of release and scheduled for postrelease assessment. At follow-up, the subjects were evaluated for their performance of layperson opioid OD resuscitative skills during video-recorded simulations. Two investigators independently scored each subject's resuscitative actions with a 21-item checklist; post hoc video reviews were separately completed to adjudicate subjects' interactions for overall benefit or harm.

Results
One hundred three prisoners completed the baseline assessment and study intervention and then were prescribed IN naloxone kits. One-month follow-up and simulation data were available for 85 subjects (82.5% of trained recruits) who had been released and resided in the community. Subjects' simulation checklist median score was 12.0 (interquartile range, 11.0–15.0) of 21 total indicated actions. Forty-four participants (51.8%) correctly administered naloxone; 16 additional subjects (18.8%) suboptimally administered naloxone. Nonindicated actions, primarily chest compressions, were observed in 49.4% of simulations. Simulated resuscitative actions by 80 subjects (94.1%) were determined post hoc to be beneficial overall for patients overdosing on opioids.

Conclusions
As part of an opioid OD prevention research program for at-risk inmates, investigators applied simulation to 1-month follow-up assessments of knowledge retention and skills acquisition in postrelease participants. Simulation supplemented traditional research tools for investigation of layperson OD management.
A Taxonomy of Delivery and Documentation Deviations During Delivery of High-Fidelity Simulations
Authors: McIvor William R. , Banerjee Arna , Boulet John R. , Bekhuis Tanja , Tseytlin Eugene , Torsher Laurence , DeMaria Samuel , Rask John P. , Shotwell Matthew S. , Burden Amanda , Cooper Jeffrey B. , Gaba David M. , Levine Adam , Park Christine , Sinz Elizabeth , Steadman Randolph H. , Weinger Matthew B. 
Published: December 2016

Introduction
We developed a taxonomy of simulation delivery and documentation deviations noted during a multicenter, high-fidelity simulation trial that was conducted to assess practicing physicians' performance. Eight simulation centers sought to implement standardized scenarios over 2 years. Rules, guidelines, and detailed scenario scripts were established to facilitate reproducible scenario delivery; however, pilot trials revealed deviations from those rubrics. A taxonomy with hierarchically arranged terms that define a lack of standardization of simulation scenario delivery was then created to aid educators and researchers in assessing and describing their ability to reproducibly conduct simulations.

Methods
Thirty-six types of delivery or documentation deviations were identified from the scenario scripts and study rules. Using a Delphi technique and open card sorting, simulation experts formulated a taxonomy of high-fidelity simulation execution and documentation deviations. The taxonomy was iteratively refined and then tested by 2 investigators not involved with its development.

Results
The taxonomy has 2 main classes, simulation center deviation and participant deviation, which are further subdivided into as many as 6 subclasses. Inter-rater classification agreement using the taxonomy was 74% or greater for each of the 7 levels of its hierarchy. Cohen kappa calculations confirmed substantial agreement beyond that expected by chance. All deviations were classified within the taxonomy.

Conclusions
This is a useful taxonomy that standardizes terms for simulation delivery and documentation deviations, facilitates quality assurance in scenario delivery, and enables quantification of the impact of deviations upon simulation-based performance assessment.