bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic appropriateness and guideline adherence in hospitalized children: results of a nationwide study
Authors: McMullan Brendan J , Hall Lisa , James Rodney , Mostaghim Mona , Jones Cheryl A , Konecny Pamela , Blyth Christopher C , Thursky Karin A 
Published: October 2019

AbstractBackgroundInformation on the nature and appropriateness of antibiotic prescribing for children in hospitals is important, but scarce.ObjectivesTo analyse antimicrobial prescribing and appropriateness, and guideline adherence, in hospitalized children across Australia.Patients and methodsWe analysed data from the National Antimicrobial Prescribing Survey (NAPS) from 2014 to 2017. Surveys were performed in hospital facilities of all types (public and private; major city, regional and remote). Participants were admitted children <18 years old. Risk factors associated with inappropriate prescribing were explored using logistic regression models.ResultsAmong 6219 prescriptions for 3715 children in 253 facilities, 19.6% of prescriptions were deemed inappropriate. Risk factors for inappropriate prescribing included non-tertiary paediatric hospital admission [OR 1.37 (95% CI 1.20–1.55)] and non-major city hospital location [OR 1.52 (95% CI 1.30–1.77)]. Prescriptions for neonates, immunocompromised children and those admitted to an ICU were less frequently inappropriate. If a restricted antimicrobial was prescribed and not approved, the prescription was more likely to be inappropriate [OR 12.9 (95% CI 8.4–19.8)]. Surgical prophylaxis was inappropriate in 59% of prescriptions.ConclusionsInappropriate antimicrobial prescribing in children was linked to specific risk factors identified here, presenting opportunities for targeted interventions to improve prescribing. This information, using a NAPS dataset, allows for analysis of antimicrobial prescribing among different groups of hospitalized children. Further exploration of barriers to appropriate prescribing and facilitators of best practice in this population is recommended.
Evaluation of target attainment of oral posaconazole suspension in immunocompromised children
Authors: Lai Tony , Alffenaar Jan-Willem , Kesson Alison , Bandodkar Sushil , Roberts Jason A 
Published: October 2019

Abstract

Background
Posaconazole is a broad-spectrum antifungal that is not licensed for use in children &lt;13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease.

Objectives
To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children &lt;13 years of age.

Patients and methods
We performed a retrospective study of immunocompromised children &lt;13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded.

Results
A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P&lt;0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70).

Conclusions
The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.
Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307
Authors: Gralow Julie R , Barlow William E , Paterson Alexander H G , M'iao Jieling L , Lew Danika L , Stopeck Alison T , Hayes Daniel F , Hershman Dawn L , Schubert Mark M , Clemons Mark , Van Poznak Catherine H , Dees Elizabeth C , Ingle James N , Falkson Carla I , Elias Anthony D , Messino Michael J , Margolis Jeffrey H , Dakhil Shaker R , Chew Helen K , Dammann Kim Z , Abrams Jeffrey S , Livingston Robert B , Hortobagyi Gabriel N 
Published: October 2019

Abstract

Background
Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer.

Methods
Patients with stage I–III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided.

Results
A total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%).

Conclusions
We found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.
Targeted axillary dissection in breast cancer by marking lymph node metastasis with a magnetic seed before starting neoadjuvant treatment
Authors: García-Moreno Joaquín Luis , Benjumeda-Gonzalez Ana María , Amerigo-Góngora Marta , Landra-Dulanto Piero José , Gonzalez-Corena Yisela , Gomez-Menchero Julio 
Published: October 2019

Abstract
We report the first documented clinical case of the use of magnetic seeds to mark axillary lymph node metastasis in breast cancer before neoadjuvant chemotherapy. After chemotherapy, the patient showed a complete radiological response. One single sentinel lymph node was detected using a radiotracer, while the marked node was intraoperative magnetometer-guided identified. The analysis of the nodes showed negative sentinel lymph node and positive marked node, and the subsequent targeted axillary dissection was performed. Marking axillary positive lymph nodes with a magnetic seed is a simple and effective procedure for the intraoperative localisation of the node after neoadjuvant treatment.
Quantum ion thermodynamics in liquid interiors of white dwarfs
Authors: Baiko D A , Yakovlev D G 
Published: October 2019

ABSTRACT
We present an accurate analytic approximation for the energy of a quantum one-component Coulomb liquid of ions in a uniform electron background that has been recently calculated from first principles. The approximation enables us to develop in an analytic form a complete thermodynamic description of quantum ions in a practically important range of mass densities at temperatures above crystallization. We show that ionic quantum effects in liquid cores of white dwarfs (WDs) affect heat capacity, cooling, thermal compressibility, pulsation frequencies, and radii of sufficiently cold WDs, especially with relatively massive helium and carbon cores.
Chromospheric emission of solar-type stars with asteroseismic ages
Authors: Booth R S , Poppenhaeger K , Watson C A , Silva Aguirre V , Stello D , Bruntt H 
Published: October 2019

ABSTRACT
Stellar magnetic activity decays over the main-sequence life of cool stars due to the stellar spin-down driven by magnetic braking. The evolution of chromospheric emission is well studied for younger stars, but difficulties in determining the ages of older cool stars on the main sequence have complicated such studies for older stars in the past. Here, we report on chromospheric Ca ii H and K line measurements for 26 main-sequence cool stars with asteroseismic ages older than a gigayear and spectral types F and G. We find that for the G stars and the cooler F-type stars that still have convective envelopes the magnetic activity continues to decrease at stellar ages above 1 Gyr. Our magnetic activity measurements do not show evidence for a stalling of the magnetic braking mechanism, which has been reported for stellar rotation versus age for G- and F-type stars. We also find that the measured $R^{\prime }_{\mathrm{ HK}}$ indicator value for the cool F stars in our sample is lower than predicted by common age–activity relations that are mainly calibrated on data from young stellar clusters. We conclude that, within individual spectral type bins, chromospheric magnetic activity correlates well with stellar age even for old stars.
Diverse properties of Ly α emission in low-redshift compact star-forming galaxies with extremely high [O iii]/[O ii] ratios
Authors: Izotov Y I , Schaerer D , Worseck G , Verhamme A , Guseva N G , Thuan T X , Orlitová I , Fricke K J 
Published: October 2019

ABSTRACT
We present observations with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope of eight compact star-forming galaxies at redshifts z = 0.02811–0.06540, with low oxygen abundances 12 + log(O/H) = 7.43–7.82 and extremely high emission-line flux ratios O32 = [O iii] λ5007/[O ii] λ3727 ∼ 22–39, aiming to study the properties of Ly α emission in such conditions. We find a diversity in Ly α properties. In five galaxies Ly α emission line is strong, with equivalent width (EW) in the range 45–190 Å. In the remaining galaxies, weak Ly α emission with EW(Ly α) ∼ 2–7 Å is superposed on a broad Ly α absorption line, indicating a high neutral hydrogen column density N(H i) ∼ (1 – 3)× 1021 cm−2. We examine the relation between the Ly α escape fraction fesc(Ly α) and the Lyman continuum escape fraction fesc(LyC), using direct measures of the latter in eleven low-redshift LyC leakers, to verify whether fesc(Ly α) can be an indirect measure of escaping LyC radiation. The usefulness of O32, of the Ly α equivalent width EW(Ly α), and of the Ly α peak separation Vsep as indirect indicators of Ly α leakage is also discussed. It is shown that there is no correlation between O32 and fesc(Ly α). We find an increase of fesc(Ly α) with increasing EW(Ly α) for EW(Ly α) <100 Å, but for higher EW(Ly$\alpha)\gtrsim$150 Å the fesc(Ly α) is nearly constant attaining the value of ∼0.25. We find an anticorrelation between fesc(Ly α) and Vsep, though not as tight as the one found earlier between fesc(LyC) and Vsep. This finding makes Vsep a promising indirect indicator of both the Ly α and ionizing radiation leakage.
Dissecting the Transcriptomic Basis of Phenotypic Evolution in an Aquatic Keystone Grazer
Authors: Frisch Dagmar , Becker Dörthe , Wojewodzic Marcin W 
Published: October 2019

AbstractKnowledge of the molecular basis of phenotypic responses to environmental cues is key to understanding the process of adaptation. Insights to adaptation at an evolutionary time scale can be gained by observing organismal responses before and after a shift in environmental conditions, but such observations can rarely be made. Using the ecological and genomic model Daphnia, we linked transcriptomic responses and phosphorus (P)-related phenotypic traits under high and low P availability. We mapped weighted gene coexpression networks to traits previously assessed in resurrected ancient (600 years old) and modern Daphnia pulicaria from a lake with a historic shift in P-enrichment. Subsequently, we assessed evolutionary conservation or divergence in transcriptional networks of the same isolates. We discovered highly preserved gene networks shared between ancient genotypes and their modern descendants, but also detected clear evidence of transcriptional divergence between these evolutionarily separated genotypes. Our study highlights that phenotypic evolution is a result of molecular fine-tuning on different layers ranging from basic cellular responses to higher order phenotypes. In a broader context, these findings advance our understanding how populations are able to persist throughout major environmental shifts.
Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth
Authors: Heissenberger Clemens , Liendl Lisa , Nagelreiter Fabian , Gonskikh Yulia , Yang Guohuan , Stelzer Elena M , Krammer Teresa L , Micutkova Lucia , Vogt Stefan , Kreil David P , Sekot Gerhard , Siena Emilio , Poser Ina , Harreither Eva , Linder Angela , Ehret Viktoria , Helbich Thomas H , Grillari-Voglauer Regina , Jansen-Dürr Pidder , Koš Martin , Polacek Norbert , Grillari Johannes , Schosserer Markus 
Published: October 2019

AbstractModifications of ribosomal RNA expand the nucleotide repertoire and thereby contribute to ribosome heterogeneity and translational regulation of gene expression. One particular m5C modification of 25S ribosomal RNA, which is introduced by Rcm1p, was previously shown to modulate stress responses and lifespan in yeast and other small organisms. Here, we report that NSUN5 is the functional orthologue of Rcm1p, introducing m5C3782 into human and m5C3438 into mouse 28S ribosomal RNA. Haploinsufficiency of the NSUN5 gene in fibroblasts from William Beuren syndrome patients causes partial loss of this modification. The N-terminal domain of NSUN5 is required for targeting to nucleoli, while two evolutionary highly conserved cysteines mediate catalysis. Phenotypic consequences of NSUN5 deficiency in mammalian cells include decreased proliferation and size, which can be attributed to a reduction in total protein synthesis by altered ribosomes. Strikingly, Nsun5 knockout in mice causes decreased body weight and lean mass without alterations in food intake, as well as a trend towards reduced protein synthesis in several tissues. Together, our findings emphasize the importance of single RNA modifications for ribosome function and normal cellular and organismal physiology.
Betacellulin drives therapy resistance in glioblastoma
Authors: Fan Qiwen , An Zhenyi , Wong Robyn A , Luo Xujun , Lu Edbert D , Baldwin Albert , Mayekar Manasi K , Haderk Franziska , Shokat Kevan M , Bivona Trever G , Weiss William A 
Published: October 2019

Abstract

Background
The transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade.

Methods
Human glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor–treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown.

Results
We demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo.

Conclusion
These data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention.
Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study
Authors: Yates Mark , MacGregor Alexander J , Ledingham Jo , Norton Sam , Bechman Katie , Dennison Elaine M , Galloway James B 
Published: October 2019

Abstract

Objectives
Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists’ adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes.

Methods
A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates.

Results
A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P-value = 0.001]. The association was maintained following propensity modelling and imputation.

Conclusion
Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients.
Assessment for varicella zoster virus in patients newly suspected of having giant cell arteritis
Authors: Sammel Anthony M , Smith Susan , Nguyen Katherine , Laurent Rodger , Brewer Janice , Hall Nathan , Little Christopher B 
Published: October 2019

Abstract

Objectives
There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort.

Methods
Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies.

Results
A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen.

Conclusion
The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies.
Networks and new mutualism: how embeddedness influences commitment and trust in small mutuals
Authors: Vriens Eva , Buskens Vincent , de Moor Tine 
Published: October 2019

AbstractMutualism is reviving again in several countries, replying to state and market failure with an alternative, social insurance setup. We study participation in such new mutuals with a focus on embeddedness. We distinguish group-level embeddedness (network structure) and individual embeddedness (the type and quantity of ties to other group members) and study how these relate to members’ commitment to mutuals and their trust in the commitment of others. We show that group-level embeddedness primarily affects trust, while individual embeddedness more strongly associates with commitment. We reveal these dynamics for mutuals of different ages using a unique multilevel dataset on the motivations, beliefs and social relations of more than 5000 members of 230 small Dutch mutuals. Our results highlight the importance of thinking critically about the levels at which social embeddedness plays a role, as the dynamics are more subtle and not all means of embeddedness are equally fruitful.
A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of a Nicotine Mint Lozenge (2 and 4 mg) in Smoking Cessation
Authors: Xiao Dan , Kotler Mitchell , Kang Jian , Wang Chen 
Published: October 2019

Objective:
To evaluate the efficacy in smoking cessation and safety of 2 and 4 mg nicotine mint lozenges in Chinese adult smokers.

Methods:
This was a multicenter, randomized, stratified, double-blind, placebo-controlled, parallel-group study. The low-dependence stratum included 483 smokers (241 randomized to active 2 mg nicotine lozenge and 242 to placebo lozenge). The high-dependence stratum included 240 smokers (120 randomized to active 4 mg nicotine lozenge and 120 to placebo lozenge). The primary endpoint was successful smoking cessation at 6 weeks postquit, defined as continuous abstinence from smoking for the 28-day period up to and including the 6-week visit (verified by CO measurement). Cochran–Mantel–Haenszel tests were performed to compare quit rates between active nicotine and placebo separately for the high-dependence and low-dependence strata.

Results:
The primary analysis showed that in the low-dependence (2 mg) stratum, 59 subjects (24.5%) of 241 in the active nicotine group and 52 subjects (21.5%) of 242 in the placebo group were successful quitters (P = .3851). In the high-dependence (4 mg) stratum, 37 subjects (30.8%) of 120 in the active nicotine group and 24 subjects (20.2%) of 119 in the placebo group were successful quitters (P = .0565).

Conclusions:
The 4 mg nicotine lozenge provided a directionally significant improvement in smoking cessation rates compared with placebo in Chinese adult smokers with high nicotine dependence for the primary endpoint. The 2 mg nicotine lozenge provided higher, but nonsignificant, smoking cessation rates than placebo. Both nicotine lozenges were generally well tolerated in Chinese adult smokers.