bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strengthening the Chain of Survival: Cardiopulmonary Resuscitation Workshop for Caregivers of Children at Risk
Authors: Tomatis Souverbielle Cristina , González-Martínez Felipe , González-Sánchez Maria I. , Carrón Marta , Guerra Miguez Luis , Butragueño Laura , Gonzalo Henar , Villalba Tomas , Perez Moreno Jimena , Toledo Blanca , Rodríguez-Fernández Rosa 
Published: June 2019

Background:
Parents and caregivers should receive training regarding pediatric cardiopulmonary resuscitation (CPR) because this knowledge improves survival. We conducted a study as part of a Patient Safety Project to improve caregivers’ CPR knowledge and skills. We also aimed to improve the quality of patient care.

Methods:
We performed a prospective, longitudinal study in 2013–2014 in a pediatric hospital. We enrolled the caregivers of all patients admitted with a diagnosis of an acute life-threatening event, apnea, or choking. We provided a 45-minute CPR workshop for parents at discharge and evaluated the results using a test before, immediately after, and at 1 and 3 months after the workshop. Participants also completed an evaluation survey about the CPR workshop.

Results:
We admitted 62 patients [median age, 1 mo (0.5–2 mo)]. We provided 62 pediatric CPR workshops to 106 enrolled relatives. The median score was 5 (CI, 3–6) out of 10 at baseline, which increased to 8 (CI, 7–10) immediately after the workshop (P < 0.01). After 1 and 3 months, the median score was 8 (CI, 6–9; P < 0.01). The severity of the acute life-threatening event episode correlated with a better score (P = 0.02). The utility of the workshop scored 9.9 out of 10.

Conclusions:
This CPR workshop significantly increased CPR knowledge and confidence, and this was maintained up to 3 months post-training. Caregiver satisfaction was high.
Co-designed PICU Family Stress Screening and Response System to Improve Experience, Quality, and Safety
Authors: Liaw K. Ron-Li , Cho Jeanne , Devins Lea , Daly Jennifer , Sklenar Dennis , Al-Qaqaa Yasir 
Published: June 2019

Objective:
Evidence for successful and sustainable models that systematically identify and address family stress in the pediatric intensive care unit (PICU) remains scarce. Using an integrated improvement science and family engagement framework, we implemented a standardized family stress screening tool and response protocol to improve family experience and reduce family crises through the timely coordination of parent support interventions.

Methods:
We conducted this improvement initiative in the 12-bed PICU of a children’s hospital within a large, urban academic medical center. Our team, which included 2 family advisors, adapted a validated Distress Thermometer for use in pediatric intensive care. A co-designed family stress screening tool and response protocol were iteratively tested, refined, and implemented in 2015–2017. Process and outcome measures included screening and response reliability, parent satisfaction, and security calls for distressed families.

Results:
Over the 18 months, the percentage of families screened for stress increased from 0% to 100%. Among families who rated stress levels ≥5, 100% received the recommended response protocol, including family support referrals made and completed within 24 hours of an elevated stress rating. From 2015 to 2017, PICU parent satisfaction scores regarding emotional support increased from a mean score of 81.7–87.0 (P < 0.01; 95% CI). The number of security calls for distressed families decreased by 50%.

Conclusions:
The successful implementation of a co-designed family stress screening tool and response protocol led to the timely coordination of parent support interventions, the improved family perception of emotional support, and reduced family crises in the PICU.
Standardized Implementation of Evidence-based Guidelines to Decrease Blood Transfusions in Pediatric Intensive Care Units
Authors: Hanson Sheila J. , Owen Erin B. , McDonald Mark J. , Woods Katherine J. , Montgomery Vicki L. 
Published: June 2019

Introduction:
Despite evidence that red blood cell (RBC) transfusions may be associated with more harm than benefit, current transfusion practices vary significantly. This multicenter, quality improvement study aimed to sustainably decrease the rate of RBC transfusions in pediatric intensive care units (PICUs).

Methods:
This 16-month prospective study included 5 PICUs. We implemented a standardized project plan including education, bedside tools, real-time reminders, and email feedback. We collected data from consecutive transfusions during pre-implementation (Phase I), postimplementation (Phase II), and post-stabilization phases (Phase III).

Results:
Of the 2,064 RBC transfusions, we excluded 35% (N = 729) from analysis in patients undergoing extracorporeal membrane oxygenation. Transfusion/1,000 admissions improved throughout the study periods from a baseline 209.6 -199.8 in Phase II and 195.8 in Phase III (P value < 0.05). There were fewer transfusions outside of the hemoglobin threshold guideline, decreasing from 81% of transfusions outside of guidelines in Phase I to 74% in Phases II and III, P < 0.05. Study phase, site, co-management status, service of requesting provider, admit reason, previous transfusion status, and age were associated with transfusion above guideline threshold.

Conclusions:
Multicenter collaboration can successfully deploy a standardized plan that adheres to implementation science principles to sustainably decrease the rate of RBC transfusion outside of guideline thresholds. However, we did not decrease the total number of transfusions in our study. The complexity of multiple specialties co-managing patients is common in the contemporary PICU. Educational initiatives aimed at one specialty may have limited effectiveness in a multifaceted system of care.
Multifaceted Quality Improvement Initiative Improves Retention in Treatment for Youth with Opioid Use Disorder
Authors: Cottrill Casey B. , Lemle Stephanie , Matson Steven C. , Bonny Andrea E. , McKnight Erin R. 
Published: June 2019

Introduction:
There is a critical need to develop interventions that help adolescents and young adults with opioid use disorders (OUDs) connect with, engage in, and remain consistent with the treatment given that patients who develop long-term OUDs experience long-term medical and mental health sequelae.

Methods:
We implemented quality improvement (QI) processes to increase early engagement and 6-month retention within a medication-assisted treatment clinic for youth with OUDs. QI interventions included motivational interviewing (MI) staff training, implementation of reduced initial treatment requirements, reduction of access barriers to treatment, and enhancement of patient treatment motivation. We monitored the impact of the interventions via a p-chart.

Results:
A statistically significant shift was seen in the 6-month retention rate following both MI staff training and the use of reduced initial treatment requirements. Second visit return rate also experienced a statistically significant shift following transportation support and an incentive program.

Discussion:
Our data demonstrate that following MI staff training, reduced initial clinic requirements, transportation support, and utilization of an incentive program, the second visit return rate, and 6-month retention rate improved within an outpatient medication-assisted treatment clinic for youth with OUDs.
Fostering Quality Improvement Capacity in a Network of Primary Care Practices Affiliated With a Pediatric Accountable Care Organization
Authors: Gowda Charitha , Toth Christina , Hoholik Suzanne , Brilli Richard J. , Gleeson Sean , Cardamone Stephen 
Published: June 2019

Objectives:
Quality improvement (QI) methodologies are not widely implemented in primary care practices. As an accountable care organization serving pediatric Medicaid recipients in Ohio, Partners For Kids (PFK) sought to build QI capacity in affiliated primary care practices to improve organizational performance on key quality measures.

Methods:
A team of QI specialists developed a comprehensive training program focused on pediatric QI initiatives. From 2014 to 2017, community-based, primary care practices affiliated with PFK were recruited to participate in QI. The primary outcome, assessed yearly, was the proportion of eligible PFK patients accessing care at a practice with ≥1 active QI project. The proportion of QI projects that demonstrated moderate improvement, defined as the implementation of ≥1 intervention and observed improvement in process measures, within 12 months of initiation was also calculated for 2017.

Results:
Over the study period, the PFK QI team supported 72 projects in 33 primary care practices throughout central and southeast Ohio. In 2017, 26 practices were engaged in ≥1 active QI project, reaching 26% of all eligible PFK patients. Of the 21 projects active as of January 2017, 11 (52%) showed moderate improvement within 12 months.

Conclusions:
The PFK QI team successfully supported QI capacity building in primary care practices throughout Ohio using a systematic approach to recruitment, training, and QI resource support. New, multilevel interventions are needed to promote the uptake of preventive services among patients.
A Multifaceted Quality Improvement Intervention to Improve Watchful Waiting in Acute Otitis Media Management
Authors: Sun Di , Rivas-Lopez Vanessa , Liberman Danica B. 
Published: June 2019

Introduction:
Despite the American Academy of Pediatrics (AAP) guidelines for acute otitis media (AOM) describing a watchful waiting (WW) approach in qualifying patients, immediate antibiotics are consistently overutilized. The study team developed a multifaceted quality improvement intervention that educated providers and families about WW and included a behavioral component to modify physician prescribing patterns.

Methods:
We used data from a prior study of 250 patients 18 years old and younger with AOM in a tertiary care children’s hospital emergency department (ED) to characterize baseline AOM management before interventions. In this study, interventions took place from September to December 2016. Following the interventions, 65 patients were randomly selected, which would allow for the detection of a 20% increase in adherence to AAP guidelines for management of AOM.

Results:
In the preintervention cohort of 250 patients, 247 had documented AOM. Two hundred thirty-one (93.5%) received immediate antibiotics, 7 (2.8%) underwent WW, and 9 (3.6%) were sent home without antibiotics. Overall management agreed with AAP guidelines at a rate of 44.1%. In the postintervention cohort of 65 patients, 63 met age and diagnostic criteria for AOM; 56 (88.9%) patients received immediate antibiotics; and 7 (11.1%) underwent WW. Postintervention, which the ED management of AOM agreed with AAP guidelines 60.3% of the time, was significantly increased from preintervention adherence (P = 0.02).

Conclusions:
A multipronged quality improvement intervention for AOM management in a single pediatric ED significantly improved adherence to AAP guidelines by increasing WW and reducing immediate antibiotic prescriptions.
Effects of germline and somatic events in candidate BRCAness genes on breast-tumor signatures
Authors: Bodily Weston R. , Shirts Brian H. , Walsh Tom , Gulsuner Suleyman , King Mary-Claire , Parker Alyssa , Roosan Moom , Piccolo Stephen R. 
Published: June 2019

AbstractBackgroundMutations inBRCA1andBRCA2cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCAness” describes tumors that harbor an HR defect but have no detectable germline mutation inBRCA1orBRCA2. A better understanding of the genes and molecular events associated with BRCAness could provide mechanistic insights and guide development of targeted treatments.MethodsUsing data from The Cancer Genome Atlas (TCGA) for 1101 breast-cancer patients, we identified individuals with a germline mutation, somatic mutation, homozygous deletion, and/or hypermethylation event inBRCA1,BRCA2, and 59 other cancer-predisposition genes. Based on the assumption that BRCAness events would have similar downstream effects on tumor biology asBRCA1/BRCA2germline mutations, we quantified these effects based on somatic-mutation signatures and gene-expression profiles. We reduced the dimensionality of the somatic-mutation signatures and expression data and used a statistical resampling approach to quantify similarities between patients who had aBRCA1/BRCA2germline mutation, another type of aberration inBRCA1orBRCA2, or any type of aberration in one of the other genes.ResultsSomatic-mutation signatures of tumors having a somatic mutation, homozygous deletion, or hypermethylation event inBRCA1/BRCA2(n = 80) were generally similar to each other and to tumors fromBRCA1/BRCA2germline carriers (n = 44). Additionally, somatic-mutation signatures of tumors with germline or somatic events inATR(n = 16) andBARD1(n = 8) showed high similarity to tumors fromBRCA1/BRCA2carriers. Other genes also showed high similarity but only for a small number of events or for a single event type. Tumors with germline mutations or hypermethylation ofBRCA1had relatively similar gene-expression profiles and overlapped considerably with the Basal-like subtype; but the transcriptional effects of the other events lacked consistency.ConclusionsOur findings confirm previously known relationships between molecular signatures and germline or somatic events inBRCA1/BRCA2and suggest additional genes that may be considered for inclusion in the definition of BRCAness.
Transcription factor LSF facilitiates lysine methylation of α-tubulin by microtubule-associated SET8
Authors: Chin Hang Gyeong , Estève Pierre Olivier , Ruse Cristian , Lee Jiyoung , Schaus Scott E. , Pradhan Sriharsa , Hansen Ulla 
Published: June 2019

AbstractMicrotubules are critical for mitosis, cell motility, and protein and organelle transport, and are a validated target for anticancer drugs. However, tubulin regulation and recruitment in these cellular processes is less understood. Post-translational modifications of tubulin are proposed to regulate microtubule functions and dynamics. Although many such modifications have been investigated, tubulin methylations and enzymes responsible for methylation have only recently begun to be described. Here we report that N-lysine methyl transferase KMT5A (SET8/PR-Set7), which methylates histone H4K20, also methylates α-tubulin. Furthermore, the transcription factor LSF binds both tubulin and SET8, and enhances α-tubulin methylationin vitro, countered by FQI1, a specific small molecule inhibitor of LSF. Thus, the three proteins SET8, LSF, and tubulin, all essential for mitotic progression, interact with each other. Overall, these results point to dual functions for both SET8 and LSF not only in chromatin regulation, but also for cytoskeletal modification.
Fraction and Spatial Organization of Tumor-Infiltrating Lymphocytes Correlating with Bladder Cancer Patient Survival
Authors: Xu Hongming , Park Sunho , Hwang Tae Hyun 
Published: June 2019

AbstractRecent studies based on deep learning on pathology images have shown the potential prognostic role of Tumor-infiltrating lymphocytes (TILs) in many cancer types. In general, most of these studies focused on detecting, quantifying and identifying TILs and spatial organization in entire whole slide images (WSIs) including both non-cancer and cancer regions. In this work, we hypothesize that TILs present in cancer regions not entire WSIs could have prognostic values. Here we present an automatic technique based on convolutional neural networks (CNN) that detects both cancer and TILs regions, and explores fraction and spatial organization of TILs in the detected cancer region from WSIs. A novel set of quantitative histological image features reflecting TILs fraction and spatial organization is extracted and used to stratify patients with distinct survival outcomes. In experiments using 277 different patient pathology slides selected from The Cancer Genome Atlas (TCGA) bladder cancer cohort, we show that bladder cancer patient survival is significantly correlated with our designed TIL-related image features, with a log-rank test p value below 0.05. Our method is extensible to histopathology images of other organs for predicting patient survival via TIL analysis.
Interkinetic nuclear movements promote apical expansion in pseudostratified epithelia at the expense of apicobasal elongation
Authors: Ferreira Marina A. , Despin-Guitard Evangeline , Duarte Fernando , Degond Pierre , Theveneau Eric 
Published: June 2019

AbstractPseudostratified epithelia (PSE) are a common type of columnar epithelia found in a wealth of embryonic and adult tissues such as ectodermal placodes, the trachea, the ureter, the gut and the neuroepithelium. PSE are characterized by the choreographed displacement of cells’ nuclei along the apicobasal axis according to phases of their cell cycle. Such movements, called interkinetic movements (INM) have been proposed to influence tissue expansion and shape and suggested as culprit in several congenital diseases such as CAKUT and esophageal atresia. INM rely on cytoskeleton dynamics just as adhesion, contractility and mitosis do. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. Here we bypassed this hurdle by generating a 2D agent-based model of a proliferating PSE and compared its output to the growth of the chick neuroepithelium to assess the interplay between INM and these other important cell processes during growth of a PSE. We found that INM directly generates apical expansion and apical nuclear crowding. In addition, our data strongly suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but rather requires a specific elongation program. We then discuss how such program might functionally link INM, tissue growth and differentiation.Authors SummaryPseudostratified epithelia (PSE) are a common type of epithelia characterized by the choreographed displacement of cells’ nuclei along the apicobasal axis during proliferation. These so-called interkinetic movements (INM) were proposed to influence tissue expansion and suggested as culprit in several congenital diseases. INM rely on cytoskeleton dynamics. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. We bypassed this hurdle by generating a mathematical model of PSE and compared it to the growth of an epithelium of reference. Our data show that INM drive expansion of the apical domain of the epithelium and suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but might rather requires a specific elongation program.
Detecting weak signals by combining small P-values in genetic association studies
Authors: Vsevolozhskaya Olga A. , Hu Fengjiao , Zaykin Dmitri V. 
Published: June 2019

AbstractWe approach the problem of combining top-ranking association statistics or P-values from a new perspective which leads to a remarkably simple and powerful method. Statistical methods, such as the Rank Truncated Product (RTP), have been developed for combining top-ranking associations and this general strategy proved to be useful in applications for detecting combined effects of multiple disease components. To increase power, these methods aggregate signals across top ranking SNPs, while adjusting for their total number assessed in a study. Analytic expressions for combined top statistics or P-values tend to be unwieldy, which complicates interpretation, practical implementation, and hinders further developments. Here, we propose the Augmented Rank Truncation (ART) method that retains main characteristics of the RTP but is substantially simpler to implement. ART leads to an efficient form of the adaptive algorithm, an approach where the number of top ranking SNPs is varied to optimize power. We illustrate our methods by strengthening previously reported associations ofµ-opioid receptor variants with sensitivity to pain.
Identification of TMEM206 proteins as pore of ASOR acid-sensitive chloride channels
Authors: Ullrich Florian , Blin Sandy , Lazarow Katina , Daubitz Tony , Kries Jens-Peter von , Jentsch Thomas J. 
Published: June 2019

ABSTRACTAcid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated anion channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying ASOR chloride channel. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.
Selective role of Nck1 in atherogenic inflammation and plaque formation
Authors: Alfaidi Mabruka , Acosta Christina H. , Wang Dongdong , Traylor James G. , Orr A. Wayne 
Published: June 2019

AbstractWhile CANTOS established the role of treating inflammation in atherosclerosis, our understanding of endothelial activation at atherosclerosis-prone sites remains limited. Disturbed flow at atheroprone regions primes plaque inflammation by enhancing endothelial NF-κB signaling. Herein, we demonstrate a novel role for the Nck adaptor proteins in disturbed flow-induced endothelial activation. Although highly similar, only Nck1 deletion, but not Nck2 deletion, limits flow-induced NF-κB activation and proinflammatory gene expression. Nck1 knockout mice show reduced endothelial activation and inflammation in both models of disturbed flow and high fat diet-induced atherosclerosis. Bone marrow chimeras confirm that vascular Nck1, but not hematopoietic Nck1, mediates this effect. In contrast, endothelial Nck2 depletion does not affect endothelial activation or atherosclerosis. Domain swap experiments and point mutations identify the Nck1 SH2 domain and the first SH3 domain as critical for flow-induced endothelial activation. We further characterize Nck1’s proinflammatory role by identifying interleukin-1 type I receptor kinase-1 (IRAK-1) as a Nck1-selective binding partner, demonstrating IRAK-1 activation by disturbed flow requires Nck1 in vitro and in vivo, showing endothelial Nck1 and IRAK-1 staining in early human atherosclerosis, and demonstrating that disturbed flow-induced endothelial activation requires IRAK-1. Taken together, our data reveal a hitherto unknown link between Nck1 and IRAK-1 in atherogenic inflammation.