bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin activity in an in vitro model of posterior capsule opacification
Authors: Lasiste Jade Marie , Zoroquiain Pablo , Miyamoto Denise , Burnier Miguel 
Published: January 2019

Purpose: To determine the activity of metformin in an in vitro model of posterior capsule opacification (PCO).Design: Experimental laboratory research. Methods: The HLE-B3 lens epithelial cell line was treated with PCO induction media (PCOM) supplemented with transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF). Different metformin concentrations (0-100 mM) were used. The following cellular parameters were assessed: (1) survival, using a viability assay; (2) morphology, via microscopy and image analysis; (3) migration, using the wound assay; (4) and expression of epithelial (Pax6, E-cadherin) and mesenchymal (α-smooth muscle actin or α-SMA, fibronectin) markers via Western blot. Expression of the uptake receptor SLC22A1 was evaluated in HLE-B3 and in human donor eyes with Western blot and immunohistochemistry, respectively. Statistical analysis of variance (ANOVA) with Tukey post-hoc test was done for analysis of cytotoxicity, morphology and migration data. Results: Metformin was lethal to half (LC50) of the cells at 30 mM, and a decrease in viability (P<0.05) was noted at 5 mM. LECs in PCOM treated with 1 mM metformin showed increased Pax6 and E-cadherin and decreased α-SMA and fibronectin expression. LECs in PCOM treated with metformin also maintained epithelial morphology. Migration was inhibited with 0.5 mM metformin (P<0.05). Both HLE-B3 and the lens epithelium in donor eyes were found to express SLC22A1.Conclusion: Metformin decreased survival and migration in LECs, maintaining epithelial phenotype and reducing mesenchymal marker expression. Metformin therefore has potential as an adjunct in PCO prevention.Financial Disclosures: This work was partially funded by Mitacs Canada.
Estimating the Fitness Effect of Deleterious Mutations During the Two Phases of the Life Cycle: A New Method Applied to the Root-Rot Fungus Heterobasidion parviporum
Authors: Clergeot Pierre-Henri , Rode Nicolas O , Glémin Sylvain , Brandström Durling Mikael , Ihrmark Katarina , Olson Åke 
Published: January 2019

Abstract
Many eukaryote species, including taxa such as fungi or algae, have a lifecycle with substantial haploid and diploid phases. A recent theoretical model predicts that such haploid-diploid lifecycles are stable over long evolutionary time scales when segregating deleterious mutations have stronger effects in homozygous diploids than in haploids and when they are partially recessive in heterozygous diploids. The model predicts that effective dominance—a measure that accounts for these two effects—should be close to 0.5 in these species. It also predicts that diploids should have higher fitness than haploids on average. However, an appropriate statistical framework to conjointly investigate these predictions is currently lacking. In this study, we derive a new quantitative genetic model to test these predictions using fitness data of two haploid parents and their diploid offspring, and genome-wide genetic distance between haploid parents. We apply this model to the root-rot basidiomycete fungus Heterobasidion parviporum—a species where the heterokaryotic (equivalent to the diploid) phase is longer than the homokaryotic (haploid) phase. We measured two fitness-related traits (mycelium growth rate and the ability to degrade wood) in both homokaryons and heterokaryons, and we used whole-genome sequencing to estimate nuclear genetic distance between parents. Possibly due to a lack of power, we did not find that deleterious mutations were recessive or more deleterious when expressed during the heterokaryotic phase. Using this model to compare effective dominance among haploid-diploid species where the relative importance of the two phases varies should help better understand the evolution of haploid-diploid life cycles.
Variation in Antibiotic Selection and Clinical Outcomes in Infants &lt;60 Days Hospitalized With Skin and Soft Tissue Infections
Authors: Markham Jessica L. , Hall Matthew , Queen Mary Ann , Aronson Paul L. , Wallace Sowdhamini S. , Foradori Dana M. , Hester Gabrielle , Nead Jennifer , Lopez Michelle A. , Cruz Andrea T. , McCulloh Russell J. 
Published: January 2019

OBJECTIVES:
To describe variation in empirical antibiotic selection in infants &lt;60 days old who are hospitalized with skin and soft-tissue infections (SSTIs) and to determine associations with outcomes, including length of stay (LOS), 30-day returns (emergency department revisit or readmission), and standardized cost.

METHODS:
Using the Pediatric Health Information System, we conducted a retrospective study of infants hospitalized with SSTI from 2009 to 2014. We analyzed empirical antibiotic selection in the first 2 days of hospitalization and categorized antibiotics as those typically administered for (1) staphylococcal infection, (2) neonatal sepsis, or (3) combination therapy (staphylococcal infection and neonatal sepsis). We examined the association of antibiotic selection and outcomes using generalized linear mixed-effects models.

RESULTS:
A total of 1319 infants across 36 hospitals were included; the median age was 30 days (interquartile range [IQR]: 17–42 days). We observed substantial variation in empirical antibiotic choice, with 134 unique combinations observed before categorization. The most frequently used antibiotics included staphylococcal therapy (50.0% [IQR: 39.2–58.1]) and combination therapy (45.4% [IQR: 36.0–56.0]). Returns occurred in 9.2% of infants. Compared with administration of staphylococcal antibiotics, use of combination therapy was associated with increased LOS (adjusted rate ratio: 1.35; 95% confidence interval: 1.17–1.53) and cost (adjusted rate ratio: 1.39; 95% confidence interval: 1.21–1.58), but not with 30-day returns.

CONCLUSIONS:
Infants who are hospitalized with SSTI experience wide variation in empirical antibiotic selection. Combination therapy was associated with increased LOS and cost, with no difference in returns. Our findings reveal the need to identify treatment strategies that can be used to optimize resource use for infants with SSTI.
Smoke Exposure, Cytokine Levels, and Asthma Visits in Children Hospitalized for Bronchiolitis
Authors: Willis Amy L. , Moss Angela , Torok Michelle , Lowary Michelle , Klein Jonathan D. , Wilson Karen M. 
Published: January 2019

BACKGROUND AND OBJECTIVE:
To determine if cigarette smoke exposure, marijuana smoke exposure, or cytokine levels at admission to the hospital for bronchiolitis are associated with follow-up visits for asthma.

METHODS:
We enrolled a cohort of children aged 31 days to 2 years who were hospitalized with bronchiolitis from January 2013 to April 2014. Data included the results of a baseline survey about children’s health and demographics, nasal wash samples, the results of a 6-month postdischarge follow-up survey, and a chart review. Nasal wash samples were tested for interleukin (IL)-6, IL-13, and tumor necrosis factor α (TNF-α); values were categorized for analysis. χ2, Fisher’s exact, and Wilcoxon rank tests were done to test bivariable differences; all analyses were done using SAS.

RESULTS:
We approached 180 families for enrollment; 99 consented to participate, and 74% of these completed follow-up surveys. Half of those with high levels of IL-13 had follow-up visits for asthma, whereas only 4.2% of those with low levels had follow-up visits for asthma (P = .02). Marijuana exposure was reported for 12.5% (n = 7) of study participants. There was a significant association between marijuana exposure and TNF-α levels (P = .03).

CONCLUSIONS:
Our study revealed an association between IL-13 and follow-up visits for asthma in children who were hospitalized with bronchiolitis. We found an association between family-reported marijuana smoke exposure and detectable but lower levels of TNF-α. Further research is needed to study these relationships.
Low Value of Thyroid Testing in the Pediatric Inpatient Setting
Authors: Torky Ahmed , LaRue Meredith , Kaplowitz Paul 
Published: January 2019

OBJECTIVES:
Our objective was to assess the frequency of pediatric inpatient thyroid testing, frequency of detection of abnormal results, and apparent impact on patient management.

METHODS:
This is a retrospective study of admissions from July 2015 to June 2016 at a large urban children’s hospital. Chart review was conducted on all hospitalized pediatric patients who underwent thyroid testing. We used a normal range of 0.5 to 5.0 μIU/mL for thyroid-stimulating hormone (TSH) and 1.0 to 2.0 ng/dL for free thyroxine (FT4), except for neonates for whom we used the higher reference ranges specified by the hospital laboratory.

RESULTS:
Thyroid testing occurred in 1202 (5.7%) of 20 907 hospitalizations; 79.3% had combined thyroid function tests (TFTs) with TSH + FT4 being most common, and 20.6% had TSH only. Combined TFTs were ordered routinely by psychiatry and frequently by endocrine, gastrointestinal, cardiology, and neurology services, but many cases had no identified reason for testing. Of the 205 abnormal tests (17.1%), the most common abnormalities in the combined TFTs group were normal FT4 and increased TSH (35.4%) (76% of which were between 5 and 10 μIU/mL), normal FT4 and TSH 0.1 to 0.5 μIU/mL (33.1%), and high FT4 but normal TSH (14.3%). Patients with new-onset type 1 diabetes had borderline low or high TSH in about 20% of cases, but all abnormalities resolved at outpatient follow-up. Overall, 8 patients (0.66%) were started on levothyroxine.

CONCLUSIONS:
Pediatric inpatient thyroid testing is relatively common at our institution, and although results are often abnormal, they do not point to thyroid disease that has contributed to the reason for hospitalization and do not identify patients in urgent need of starting therapy.
Encounters From Device Complications Among Children With Medical Complexity
Authors: Nackers Allison , Ehlenbach Mary , Kelly Michelle M. , Werner Nicole , Warner Gemma , Coller Ryan J. 
Published: January 2019

OBJECTIVES:
Children with medical complexity (CMC) are commonly assisted by medical devices to support essential body functions, although complications may lead to preventable emergency department (ED) and hospital use. Our objective was to identify predictors of device-complicated ED visits and hospitalizations.

METHODS:
This single-center retrospective cohort study included patients referred to a Pediatric Complex Care Program between April 1, 2014, and April 30, 2016, assisted by at least 1 medical device. Hospitalizations and ED visits in the year before enrollment were rated for likelihood for being due to device complications. Interrater reliability among 3 independent reviewers was assessed. Bivariate followed by multivariate logistic regression clustered by patient helped us identify associations between demographic, clinical, and device characteristics associated with device-complicated ED or hospital encounters.

RESULTS:
Interrater reliability was high (κ = 0.92). Among 98 CMC, device-complicated encounters represented 17% of 258 hospitalizations and 31% of 228 ED visits. Complications of 3 devices (central venous catheters, enteral tubes, and tracheostomy tubes) accounted for 13% of overall hospitalizations and 28% of overall ED visits. Central venous catheter presence (adjusted odds ratio [aOR] 3.2 [95% confidence interval (CI) 1.1–9.5]) was associated with device-complicated ED visits. Gastrojejunostomy/jejunostomy tube presence (aOR 3.3 [95% CI 1.5–7.5]) or tracheostomies with (aOR 8.1 [95% CI 2.3–28.5]) or without (aOR 4.5 [95% CI 1.7–7.5]) ventilator use was associated with device-complicated hospitalizations. Clinical variables were poor predictors of device-complicated encounters.

CONCLUSIONS:
Device-complicated ED visits and hospitalizations comprised a substantial proportion of total hospital and ED use. Developing interventions to prevent device complications may be a promising strategy to reduce overall CMC use.
Racial, Ethnic, and Socioeconomic Disparities in Patient Safety Events for Hospitalized Children
Authors: Stockwell David C. , Landrigan Christopher P. , Toomey Sara L. , Westfall Matthew Y. , Liu Shanshan , Parry Gareth , Coopersmith Ari S. , Schuster Mark A. ,   for the GAPPS Study Group
Published: January 2019

OBJECTIVES:
Previous studies have revealed racial/ethnic and socioeconomic disparities in quality of care and patient safety. However, these disparities have not been examined in a pediatric inpatient environment by using a measure of clinically confirmed adverse events (AEs). In this study, we do so using the Global Assessment of Pediatric Patient Safety (GAPPS) Trigger Tool.

METHODS:
GAPPS was applied to medical records of randomly selected pediatric patients discharged from 16 hospitals in the Pediatric Research in Inpatient Settings Network across 4 US regions from January 2007 to December 2012. Disparities in AEs for hospitalized children were identified on the basis of patient race/ethnicity (black, Latino, white, or other; N = 17 336 patient days) and insurance status (public, private, or self-pay/no insurance; N = 19 030 patient days).

RESULTS:
Compared with hospitalized non-Latino white children, hospitalized Latino children experienced higher rates of all AEs (Latino: 30.1 AEs per 1000 patient days versus white: 16.9 AEs per 1000 patient days; P ≤ .001), preventable AEs (Latino: 15.9 AEs per 1000 patient days versus white: 8.9 AEs per 1000 patient days; P = .002), and high-severity AEs (Latino: 12.6 AEs per 1000 patient days versus white: 7.7 AEs per 1000 patient days; P = .02). Compared with privately insured children, publicly insured children experienced higher rates of preventable AEs (public: 12.1 AEs per 1000 patient days versus private: 8.5 AEs per 1000 patient days; P = .02). No significant differences were observed among other groups.

CONCLUSIONS:
The GAPPS analysis revealed racial and/or ethnic and socioeconomic disparities in rates of AEs experienced by hospitalized children across a broad range of geographic and hospital settings. Further investigation may reveal underlying mechanisms of these disparities and could help hospitals reduce harm.
Safety of Peripherally Inserted Central Catheter Use in Children From Rural Versus Urban Settings Receiving Long-term Parenteral Antimicrobial Therapy
Authors: Beachum Natasha , Dehority Walter 
Published: January 2019

OBJECTIVES:
To determine the safety of peripherally inserted central catheter (PICC) use for delivery of outpatient parenteral antimicrobial therapy (PAT) in children discharged to rural or urban locales. We hypothesized that children from rural settings would experience higher complication rates.

PATIENTS AND METHODS:
We conducted a retrospective cohort study of children admitted to an academic medical center in the Southwestern United States over 9 years who were discharged with a PICC to complete a course of PAT with follow-up at our institution. To classify rural versus urban residence, we used rural-urban continuum codes from the US Department of Agriculture, the driving time in hours to the nearest trauma center, and the discharging center using Google Maps.

RESULTS:
In total, 221 children met inclusion criteria (mean age 9.8 years). Osteoarticular infections and cystic fibrosis exacerbations were the most common indications for PICC use (68.8%). The mean driving time to the discharging hospital was significantly longer for those children residing in the most rural regions of the state (3.6 vs 0.8 hours; P &lt; .001) as well as to the nearest level 1, 2, or 3 trauma center (2.2 vs 0.4 hours; P &lt; .001). PICC complications occurred in 47 children (21.3%). No association was found between rural-urban continuum codes, driving times to the discharging hospital, or nearest trauma center with any complication nor with complications overall.

CONCLUSIONS:
In our study, we demonstrate an equivalent safety profile for children in rural and urban settings with PICCs for receipt of outpatient PAT.
Perceived Benefits, Risks, and Utility of Newborn Genomic Sequencing in the BabySeq Project
Authors: Pereira Stacey , Robinson Jill Oliver , Gutierrez Amanda M. , Petersen Devan K. , Hsu Rebecca L. , Lee Caroline H. , Schwartz Talia S. , Holm Ingrid A. , Beggs Alan H. , Green Robert C. , McGuire Amy L. ,   on behalf of The BabySeq Project Group
Published: January 2019

BACKGROUND AND OBJECTIVES:There is interest in applying genomic sequencing (GS) to newborns’ clinical care. Here we explore parents’ and clinicians’ attitudes toward and perceptions of the risks, benefits, and utility of newborn GS compared with newborn screening (NBS) prior to receiving study results.METHODS:The BabySeq Project is a randomized controlled trial used to explore the impact of integrating GS into the clinical care of newborns. Parents (n = 493) of enrolled infants (n = 309) and clinicians (n = 144) completed a baseline survey at enrollment. We examined between-group differences in perceived utility and attitudes toward NBS and GS. Open-ended responses about risks and benefits of each technology were categorized by theme.RESULTS:The majority of parents (71%) and clinicians (51%) agreed that there are health benefits of GS, although parents and clinicians agreed more that there are risks associated with GS (35%, 70%) than with NBS (19%, 39%; all P &lt; .05). Parents perceived more benefit and less risk of GS than did clinicians. Clinicians endorsed concerns about privacy and discrimination related to genomic information more strongly than did parents, and parents anticipated benefits of GS that clinicians did not.CONCLUSIONS:Parents and clinicians are less confident in GS than NBS, but parents perceive a more favorable risk/benefit ratio of GS than do clinicians. Clinicians should be aware that parents’ optimism may stem from their perceived benefits beyond clinical utility.
Physician Communication of Genomic Results in a Diagnostic Odyssey Case Series
Authors: Rubanovich Caryn Kseniya , Cheung Cynthia , Torkamani Ali , Bloss Cinnamon S. 
Published: January 2019

BACKGROUND AND OBJECTIVES:The availability of whole genome sequencing (WGS) is increasing in clinical care, and WGS is a promising tool in diagnostic odyssey cases. Physicians’ ability to effectively communicate genomic information with patients, however, is unclear. In this multiperspective study, we assessed physicians’ communication of patient genome sequencing information in a diagnostic odyssey case series.METHODS:We evaluated physician communication of genome sequencing results in the context of an ongoing study of the utility of WGS for the diagnosis of rare and idiopathic diseases. A modified version of the Medical Communication Competence Scale was used to compare patients’ ratings of their physicians’ communication of general medical information to communication of genome sequencing information. Physician self-ratings were also compared with patient ratings.RESULTS:A total of 47 patients, parents, and physicians across 11 diagnostic odyssey cases participated. In 6 of 11 cases (54%), the patient respondent rated the physician’s communication of genome sequencing information as worse than that of general medical information. In 9 of 11 cases (82%), physician self-ratings of communication of genome sequencing information were worse than the patient respondent’s rating. Identification of a diagnosis via WGS was positively associated with physician self-ratings (P = .021) but was not associated with patient respondent ratings (P = .959).CONCLUSIONS:These findings reveal that even in diagnostic odyssey cases, in which genome sequencing may be clinically beneficial, physicians may not be well-equipped to communicate genomic information to patients. Future studies may benefit from multiperspective approaches to assessing and understanding physician-patient communication of genome-sequencing information.
The early onset of Chronic Kidney Disease stage five in 11 years old boy with Autosomal Dominant Polycystic Kidney Disease due to PKD-1 mutation
Authors: Agustini Ni Made Ayu , Suarta I Ketut , Nilawati Gusti Ayu Putu , Arijana I Gusti Kamasan Nyoman 
Published: January 2019

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Only a few renal cysts are detected in most affected individuals before 30 years of ages and only 2% of patients with ADPKD present with early clinical manifestations before 15 years old. The average age at onset of chronic kidney disease (CKD) was 50 years. ADPKD is caused by mutations in one of two genes, PKD 1 and PKD 2. PKD1 was associated with more severe disease than PKD2, with earlier age at diagnosis, higher number of kidney cysts, the earlier onset of hypertension and faster progression to CKD stage five. Â Objective: To describe of the factors that caused early onset of CKD stage five in ADPKD.Case: An 11 years old boy diagnosed with CKD stage 5 caused by ADPKD with urinary tract infection. The patient complaint with fatigue, pale, fever, flank pain and cloudy urine. The grandfather got the renal failure history and aunty got hypertension since she was young. The parents of patient have consanguinous mating. In the physical examination has been found hypertension grade 1. The laboratory test has been shown decrease of glomerular filtration rate, anemia, imbalance electrolite and metabolic acidosis. Urine investigationÂ with leucosituria and positive E. Colli. UltrasonographyÂ and CT stonography showed bilateral multiple cysts in the kidneys with left kidney enlargement. His parents also got multiple cysts in both of kidneys with the normal size of kidneys. Gene analysis showed homozygous for missense mutations 11734insC, in exon 43 of the PKD 1 gene. The patient got regular hemodialysis and other supportive therapy.Conclusion: The early onset of CKD stage five in ADPKD is related to PKD 1 homozygous gene mutation, male gender and enlargement of kidney.
Oncogenic role of miRNA-221/222 in breast cancer
Authors: Ardyan Sudharta Putra I Wayan , Supadmanaba I Gede Putu , Sudarsa I Wayan 
Published: January 2019

Breast cancer stills remains as one of the major health problems in the world which ranks as the top cause of death of women with a percentage of 21.4%. There is connection of microRNAs (miRNA) with carcinogenesis process. miRNAs are small non coding RNAs (18 to 24 nucleotides) and formed as single-stranded RNAs (ssRNAs). The action of miRNAs is depended from their expression levels and function which can either promote oncogenesis (oncomiRs) or act as tumor suppressor pathways. One of the oncomiRs is miR-221 and miR-222, both are expressed by single transcription that are found on the X chromosome. The regulation transcription of miR-221/222 gene is control by positive and negative feedback. miR-221/222 directly targets PTEN, pro-apoptotic protein and tumor suppression gene, SOCS1 and CDKN1B in order to promote the proliferation of the cells. Â miR-221/222 enhances the aggressiveness of tumor through regulates the epithelial to mesenchymal transition (EMT) by targeting Tricho-rhino phalangeal syndrome type 1 (TRPS1) gene. miR-221/222 induces resistance of endocrine therapy in breast cancer especially tamoxifen and fulvestrant. The role of miR-221/222 in carcinogenesis is very complex that can upregulate or downregulate a protein. In addition, overexpression of miR-221/222 also enhances aggressiveness characteristics of breast cancer.Â