bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Drivers of the Clear Sky Greenhouse Effect, 2000–2016
Authors: Raghuraman Shiv Priyam , Paynter David , Ramaswamy V.
Published: November 2019

The clear sky greenhouse effect (G) is defined as the trapping of infrared radiation by the atmosphere in the absence of clouds. The magnitude and variability of G is an important element in the understanding of Earth's energy balance; yet the quantification of the governing factors of G is poor. The global mean G averaged over 2000 to 2016 is 130–133 W m−2 across data sets. We use satellite observations from Clouds and the Earth's Radiant Energy System Energy Balance and Filled (CERES EBAF) to calculate the monthly anomalies in the clear sky greenhouse effect (ΔG). We quantify the contributions to ΔG due to changes in surface temperature, atmospheric temperature, and water vapor by performing partial radiation perturbation experiments using ERA‐Interim and Geophysical Fluid Dynamics Laboratory's Atmospheric Model 4.0 climatological data. Water vapor in the middle troposphere and upper troposphere is found to contribute equally to the global mean and tropical mean ΔG. Holding relative humidity (RH) fixed in the radiative transfer calculations captures the temporal variability of global mean ΔG while variations in RH control the regional ΔG signal. The variations in RH are found to help generate the clear sky super greenhouse effect (SGE). Thirty‐six percent of Earth's area exhibits SGE, and this disproportionately contributes to 70% of the globally averaged magnitude of ΔG. In the global mean, G's sensitivity to surface temperature is 3.1–4.0 W m−2 K−1, and the clear sky longwave feedback parameter is 1.5–2.0 W m−2 K−1. Observations from CERES EBAF lie at the more sensitive ends of these ranges and the spread arises from its cloud removal treatment, suggesting that it is difficult to constrain clear sky feedbacks.
New anthrahydrazone derivatives and their cisplatin-like complexes: synthesis, antitumor activity and structure–activity relationship
Authors: Liu Rui-Xue , Wu Ying-Shu , Liu Yan-Cheng , Luo Ru-Yi , Yang Li-Dong , Tang Meng-Ting , Chen Zhen-Feng , Liang Hong
Published: November 2019

Two new cisplatin-like platinum(ii) complexes of new anthrahydrazones showed significant in vitro antitumor efficacies, which were totally different from that of cisplatin.
Heteroleptic copper(i) halides with triphenylphosphine and acetylthiourea: synthesis, characterization and biological studies (experimental and molecular docking)
Authors: Khan Syed Ishtiaq , Ahmad Sajjad , Altaf Ataf Ali , Rauf Muhammad Khawar , Badshah Amin , Azam Syed Sikander , Tahir Muhammad Nawaz
Published: November 2019

This manuscript presents the synthesis of acetylthiourea and triphenylphosphene based hetroleptic copper(i) halides and their biological activities. H-bonding and hydrophobic pi-interactions were found important for their biological activities.
Cystic Fibrosis Diagnosis in Newborns, Children, and Adults
Authors: Castellani Carlo , Linnane Barry , Pranke Iwona , Cresta Federico , Sermet-Gaudelus Isabelle , Peckham Daniel
Published: November 2019

The diagnosis of cystic fibrosis (CF) has traditionally relied on the presence of clinical features of the disease. Today, diagnosis through newborn screening (NBS) is becoming the standard of modern CF care. CF NBS programs can identify CF prior to clinical presentation, but for the advantages of an early diagnosis to accrue a scrupulous system must be in place to ensure all steps in the program are performing. As we move rapidly into the era of CF transmembrane conductance regulator (CFTR) protein modulators, the opportunity to start a presymptomatic infant, identified through CF NBS, on these agents offers the prospect of true disease-modifying interventions which could result in a paradigm shift in CF care.

Conversely, the introduction of NBS has resulted in many children being asymptomatic at the time of diagnosis. Some screened newborns are classified as “CF Screening Positive, Inconclusive Diagnosis”, or “CFTR-related metabolic syndrome” when the diagnosis can neither be confirmed nor excluded. Appropriate assessment and follow-up should be arranged at specialist centers as a proportion of these infants and adults will eventually be diagnosed with CF.

Symptoms and signs are particularly pertinent when considering a diagnosis of CF outside the context of NBS. In older patients with a late diagnosis, the spectrum of clinical presentation can be very variable with vigilant clinicians from multiple specialties suspecting the diagnosis in conditions such as recurrent pulmonary infections, male infertility, pancreatitis, nasal polyposis, and malabsorption.

In addition to clinical symptoms or positive NBS results, sweat test and genetic analysis are cornerstones in the diagnosis of CF, but in some cases the diagnosis cannot be confirmed on genetic or sweat testing. Difficult diagnosis may be supported by in vivo or ex vivo electrophysiology measurements on respiratory or intestinal epithelia. This can be done by either measuring transepithelial nasal potential difference or intestinal current measurements.
Sexually transmissible infection testing among pregnant women in the US, 2011–15
Authors: Leichliter Jami S. , Haderxhanaj Laura T. , Gift Thomas L. , Dittus Patricia J.
Published: November 2019

Introduction
Sexually transmissible infections (STIs) are increasing in the US. Pregnant women and infants are susceptible to serious STI-related sequelae; however, some STIs can be cured during pregnancy with appropriate, timely screening. Methods: We used data from the 2011–15 National Survey of Family Growth to examine STI testing (in the past 12 months) among women who were pregnant in the past 12 months (n = 1155). In bivariate and multivariable analyses, we examined associations between demographics, health care access and two outcome variables, namely receipt of a chlamydia test and receipt of other STI tests. Results: Among women who were pregnant in the past 12 months, 48% reported receiving a chlamydia test and 54% reported that they received an STI test other than chlamydia in the past 12 months. In adjusted analyses, non-Hispanic Black women were more likely to receive a chlamydia test (adjusted odds ratio (aOR) 2.82; 95% confidence interval (CI) 1.86–4.26) and other STI tests (aOR 2.43; 95% CI 1.58–3.74) than non-Hispanic White women. Women living in a metropolitan statistical area but not the principal city were less likely to report chlamydia (aOR 0.62; 95% CI 0.44–0.86) and other STI (aOR 0.57; 95% CI 0.40–0.81) testing than women living in a principal city. Women born outside the US were significantly less likely to have received a chlamydia test (aOR 0.35; 95% CI 0.19–0.64) or other STI test (aOR 0.34; 95% CI 0.20–0.58), whereas those who had received prenatal care were more likely to receive a chlamydia test (aOR 2.10; 95% CI 1.35–3.28) or another STI test (aOR 2.32; 95% CI 1.54–3.49). Conclusions: The findings suggest that interventions are needed to increase adherence to recommended STI screenings during pregnancy.
The Effects of Stress Beliefs on Daily Affective Stress Responses
Authors: Laferton Johannes A C , Fischer Susanne , Ebert David D , Stenzel Nikola M , Zimmermann Johannes
Published: November 2019

Background

Negative beliefs about the effects of stress have been associated with poorer health and increased mortality. However, evidence on the psychological mechanisms linking stress beliefs to health is scarce, especially regarding real-life stress.

Purpose

The aim of the current study was to investigate the effects of stress beliefs on affect in the daily stress process in a population prone to health-impairing effects of stress: university students.

Methods

Using daily diaries, 98 university students reported on daily perceived social and work-related stressors as well as positive and negative affect for 10 consecutive days. Stress beliefs, depressive and anxiety symptoms, neuroticism, and demographic variables were assessed prior to the daily diary phase.

Results

Hierarchical linear models revealed a significant cross-level interaction between negative stress beliefs and the association of daily social stressors with negative affect (B = 0.24; 99% confidence interval [CI] = 0.08–0.41, p < .001). When experiencing social stress, participants who held high negative stress beliefs had higher daily negative affect (simple slope = 4.09; p < .001); however, for participants who held low negative stress beliefs the association between daily social stress and daily negative affect was considerably smaller (simple slope = 2.12; p < .001). Moreover, individuals believing stress to be controllable showed higher positive affect throughout the 10-day daily diary phase.

Conclusions

Negative stress beliefs were found to moderate the affective response to daily real-life stressors. Given the established relationship between affect and health, this study provides initial evidence of psychological mechanisms linking stress beliefs to health.
Development and Validation of Two Robust Stability-Indicating Chromatographic Methods for Determination of Metolazone in Drug Substance and Pharmaceutical Dosage Form in the Presence of Its Degradation Products and Characterization of Main Degradation Products Based on LC-MS
Authors: Zaazaa Hala E , Abdel-Ghany Rasha , Abdelkawy M , Sayed Mahmoud
Published: November 2019

Two robust and selective stability-indicating chromatographic methods were developed and validated for the determination of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The HPLC method employed a Kromasil C18 (250 × 4.6,5 μm) column and a mobile phase of acetonitrile: 0.2% orthophosphoric acid (32:68 v/v) at a flow rate 2 mL/min and detection at 238 nm. The separation was performed in HPLC isocratic mode. The robustness of the suggested method was assessed using the Plackett–Burman design, parameters affecting system suitability were established and non-significant intervals for the significant parameters were considered. The HPTLC method employed Nano-SIL-20 UV254 HPTLC plates as adsorbent, ethyl acetate: toluene: acetic acid solution (4:4:0.5, v/v/v), as a developing solvent system and densitometric detection at 238 nm. Metolazone was exposed to different stress conditions, including acid and alkaline hydrolysis and oxidative and photolytic degradation. The main degradation products obtained have been characterized and interpreted based on LC-MS. The linearity of the suggested methods was proved in the concentration range of 20–75 μg/mL for the HPLC method and 100–900 ng/spot for the HPTLC method. The suggested methods were validated according to international conference on harmonization guidelines. These methods were successfully dedicated for the estimation of metolazone in drug substance and pharmaceutical dosage form in the presence of its degradation products. The results of the suggested methods were evaluated and compared statistically with results obtained by an official method without finding any significant difference.
Quantitative and Chemical Fingerprint Analysis of Desmodium styracifolium by High-Performance Liquid Chromatography Combined with Chemometrics
Authors: Chen Liangyuan , Tang Xiaomin , Yang Quan , Cheng Xuanxuan
Published: November 2019

In this study, a valid and comprehensive evaluation method for assessing the quality of Desmodium styracifolium (Osb.) Merr has been established, based on analysis of high-performance liquid chromatography fingerprint combined with the similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), discriminant analysis (DA) and the quantitative analysis multi-components by single marker (QAMS) method. Eleven peaks of the common model were obtained and analyzed using SA, HCA, PCA and DA analysis. These methods indicated a similar conclusion that 31 batches of D. styracifolium samples were categorized into two clusters basically coincident with their geographical regions of origin. Four peaks were identified as schaftoside, isoorientin, isoschaftoside and isovitexin. Schaftoside was selected as the internal standard, and the relative correction factors between schaftoside and the other three flavonoids were calculated using the QAMS method. The accuracy of the QAMS method was verified by comparing with the results calculated by the external standard method. No significant difference between the two methods was found. In conclusion, the established methods were scientifically applied in the quality evaluation of D. styracifolium.
Plant Regulomics Portal (PRP): a comprehensive integrated regulatory information and analysis portal for plant genomes
Authors: Panzade Ganesh , Gangwar Indu , Awasthi Supriya , Sharma Nitesh , Shankar Ravi
Published: November 2019

Gene regulation is a highly complex and networked phenomenon where multiple tiers of control determine the cell state in a spatio-temporal manner. Among these, the transcription factors, DNA and histone modifications, and post-transcriptional control by small RNAs like miRNAs serve as major regulators. An understanding of the integrative and spatio-temporal impact of these regulatory factors can provide better insights into the state of a ‘cell system’. Yet, there are limited resources available to this effect. Therefore, we hereby report an integrative information portal (Plant Regulomics Portal; PRP) for plants for the first time. The portal has been developed by integrating a huge amount of curated data from published sources, RNA-, methylome- and sRNA/miRNA sequencing, histone modifications and repeats, gene ontology, digital gene expression and characterized pathways. The key features of the portal include a regulatory search engine for fetching numerous analytical outputs and tracks of the abovementioned regulators and also a genome browser for integrated visualization of the search results. It also has numerous analytical features for analyses of transcription factors (TFs) and sRNA/miRNA, spot-specific methylation, gene expression and interactions and details of pathways for any given genomic element. It can also provide information on potential RdDM regulation, while facilitating enrichment analysis, generation of visually rich plots and downloading of data in a selective manner. Visualization of intricate biological networks is an important feature which utilizes the Neo4j Graph database making analysis of relationships and long-range system viewing possible. Till date, PRP hosts 571-GB processed data for four plant species namely Arabidopsis thaliana, Oryza sativa subsp. japonica, Zea mays and Glycine max.

Database URL: https://scbb.ihbt.res.in/PRP
APOE ε4 Carriers Have a Greater Propensity to Glycation and sRAGE Which Is Further Influenced by RAGE G82S Polymorphism
Authors: Deo Permal , Dhillon Varinderpal S , Chua Ann , Thomas Philip , Fenech Michael
Published: November 2019

APOE ε4 allele is an established risk factor for Alzheimer’s disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal individuals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p < .001), glyoxal (p < .001), fluorescent AGEs (p < .001), Nε-carboxymethyllysine (p < .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.
Identification of Target Golimumab Levels in Maintenance Therapy of Crohn’s Disease and Ulcerative Colitis Associated With Mucosal Healing
Authors: Boland Karen , Greener Tomer , Kabakchiev Boyko , Stempak Joanne , Tessolini Jenna , Li Rachelle , Soriano Joelle , Croitoru Kenneth , Nguyen Geoffrey , Steinhart A Hillary , Weizman Adam V , Silverberg Mark S
Published: November 2019

Introduction

Golimumab is approved as a therapy for ulcerative colitis (UC) patients. Recent data also demonstrate efficacy in Crohn’s disease (CD); however, little is known about target drug levels to achieve endoscopic remission.

Methods

We performed a retrospective analysis of IBD patients on maintenance golimumab. Median trough levels were compared using Kruskal-Wallis test, and logistic regression was used to construct a probabilistic model to determine sensitivity and specificity of levels predicting mucosal healing.

Results

Fifty-eight patients on maintenance golimumab were included (n = 39 CD, n = 19 UC/IBD-unclassified [IBDU]). Forty percent (n = 23) were cotreated with an immunomodulator, 95% (n = 55) of patients were anti-TNF experienced, and 15.5% (n = 9) had 3 or more prior biologic therapies. Forty-four percent of patients achieved mucosal healing with endoscopic response in a further 26% of patients. Clinical remission was recorded in 41% of patients, and 82% had clinical response. Patients were treated with doses generally higher than the approved maintenance dose. In CD patients, median golimumab trough levels were higher in patients with mucosal healing (8.8 μg/mL vs 5.08 μg/mL, P = 0.03). After calculation of a receiver operating characteristic (ROC) curve for mucosal healing vs nonresponse, a trough level >8 μg/mL was associated with mucosal healing, with 67% sensitivity, 88% specificity, and a likelihood ratio of 3:4.

Conclusion

Treatment with golimumab was associated with mucosal healing in 44% of all IBD patients. Higher golimumab levels were associated with mucosal healing in CD. These findings support the need for prospective studies to determine target golimumab levels in IBD, which may impact current clinical practices in relation to selection of maintenance dosing.
No Increased Risk of Colorectal Neoplasia in Patients With Inflammatory Bowel Disease and Postinflammatory Polyps
Authors: de Jong Michiel E , Gillis Veerle E L M , Derikx Lauranne A A P , Hoentjen Frank
Published: November 2019

Background

Patients with inflammatory bowel disease (IBD) who have postinflammatory polyps (PIPs) may have an increased risk of developing colorectal neoplasia. Current guidelines recommend an intensified surveillance strategy in these patients, although the evidence for this recommendation is conflicting. The aim of our study was to assess whether IBD patients with PIPs are at increased risk of colorectal neoplasia.

Methods

We established a retrospective cohort in a tertiary IBD center with IBD patients undergoing colorectal cancer (CRC) surveillance in the current era. We compared cumulative incidences of colorectal neoplasia since IBD diagnosis between patients with and without PIPs and corrected for confounders. Second, we compared the risk of receiving a colectomy.

Results

In our cohort with >22 years of median follow-up, 154 of 519 patients had PIPs. PIPs were associated with extensive disease (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.61–4.42; P < 0.001) and with more severe inflammation at colonoscopy (OR, 3.54; 95% CI, 2.28–5.50; P < 0.001). After correction for confounders, the presence of PIPs was not associated with development of colorectal neoplasia (hazard ratio [HR], 1.28; 95% CI, 0.85–1.93; P = 0.24) or with development of advanced neoplasia (HR, 1.38; 95% CI, 0.52–3.68; P = 0.52). There was a higher risk of colectomy in patients with PIPs (HR, 3.41; 95% CI, 1.55–7.54; P = 0.002).

Conclusion

In this cohort, PIPs were associated with disease extent, inflammation, and higher rates of colectomy. However, the presence of PIPs was not associated with the development of neoplasia. These findings suggest that patients with PIPs may not need an intensified surveillance strategy.
Effects of inoculation of corn silage with Lactobacillus spp. or Saccharomyces cerevisiae alone or in combination on silage fermentation characteristics, nutrient digestibility, and growth performance of growing beef cattle
Authors: Nair Jayakrishnan , Xu Shanwei , Smiley Brenda , Yang Hee-Eun , McAllister Tim A , Wang Yuxi
Published: November 2019

This study evaluated the effects of a novel silage inoculant containing Saccharomyces cerevisiae strain 3 as a direct fed microbial (DFM) on the ensiling, aerobic stability, and nutrient digestibility of whole-crop corn silage and growth performance of beef cattle. Treatments included uninoculated corn silage (CON) or corn silage inoculated with a mixture of 1.1 × 105 cfu g−1 fresh forage Lactobacillus plantarum and Lactobacillus buchneri (INOC1) or 1.0 × 104 cfu g−1 fresh forage S. cerevisiae strain 3 (INOC2) or a mixture of INOC1 and INOC2 (INOC3). Silage in INOC1 had lower (P = 0.03) proportion of lactate, with acetate (Ac) proportion ranking as INOC1 > INOC3 > INOC2 (P < 0.01). In terminal silage, numbers of lactic acid bacteria were greater (P = 0.05) for INOC1 than CON and INOC2, while yeast counts tended (P = 0.08) to be greater for INOC2 than INOC3 on day 3 of aerobic exposure. Aerobic stability of corn silage was not impacted by inoculation with S. cerevisiae strain 3. Heifers fed INOC2 and INOC3 had lower (P < 0.01) ruminal Ac concentration than those fed CON. Apparent total tract digestibilities of DM, OM, ADF, and NDF were greater (P ≤ 0.03) for heifers fed INOC2 than those fed CON. Growth performance was similar across treatments, excepting DMI as percent of BW tended to be lower (P = 0.08) for INOC2 steers compared to CON steers. These results suggest that S. cerevisiae strain 3 has potential as a component in a fourth generation DFM silage inoculant.
Weaning age and post-weaning nursery feeding regime are important in improving the performance of lightweight pigs
Authors: Huting Anne M S , Wellock Ian , Tuer Steve , Kyriazakis Ilias
Published: November 2019

The aim was to investigate the effect of weaning age, weaning weight, and nursery feeding regime on post-weaning performance. The focus was on pigs weaned light, as they may be better off when weaned at a later age and/or offered a specialist nursery feeding regime. Piglets (n = 1,448) from one farrowing batch of 110 sows that farrowed over 2 wk were individually weighed and their morphometric measurements were taken at birth. Pigs were weaned on the same day, but variation in birth date resulted in variable weaning ages (mean age day 34.1, SD = 2.5). The youngest 50% at weaning were classified Y and the oldest 50% as O; within an age class, the lightest 50% were classified L, the heaviest 50% as H, and housed accordingly. Pigs were individually weighed at weaning, 7 and 15 wk post-weaning. At weaning, Y were 6 d younger and 1.4 kg lighter than O pigs, whereas L were 3.2 kg lighter than H pigs. Pigs were randomly allocated to a 3-stage superior (SUP) or control (CON) nursery feeding regime, with SUP pigs having a 65% greater allowance (on a kg/pig basis) of the first and second stage feeds than the CON. Pigs weaned Y had a higher mortality rate from weaning to 7 wk post-weaning than pigs weaned O (9.14% vs. 4.98%; P = 0.046). As expected, age and weight significantly (P < 0.001) affected performance to both 7 and 15 wk post-weaning: at 15-wk pigs weaned Y were 5.5 kg lighter than pigs weaned O; pigs weaned L were 9.0 kg lighter than H pigs. It was estimated that pigs weaned YL needed ~4 d more (P = 0.018) to reach 60 kg BW than pigs weaned OL. Feed intake was not affected by feeding regime, age and weight, or their interactions. Performance was not affected by feeding regime (P > 0.05), but was affected by the weight × feeding regime interaction (P = 0.044) to 7 wk post-weaning: L pigs on SUP were 1.2 kg heavier than L pigs on the CON regime; this was not the case for the H pigs. Performance up to 7 wk post-weaning was positively associated with birth weight to cranial circumference ratio and weaning weight (P < 0.05) for both YL and OL pigs; for the latter, additional performance predictors were weaning age (P = 0.044) and feeding (P = 0.027). Improved growth for L pigs up to 7 wk post-weaning could be obtained by a greater allowance of the nursery diets. However, weaning at a later age benefitted the performance of L pigs to a common BW, suggesting that this might be a strategy with longer term benefits.
Congruence-based proofs of the recognizability theorems for free many-sorted algebras
Authors: Climent Vidal J , Cosme LlÓpez E
Published: November 2019

We generalize several recognizability theorems for free single-sorted algebras to free many-sorted algebras and provide, in a uniform way and without using either regular tree grammars or tree automata, purely algebraic proofs of them based on congruences.
Divergent Selection and Primary Gene Flow Shape Incipient Speciation of a Riparian Tree on Hawaii Island
Authors: Choi Jae Young , Purugganan Michael , Stacy Elizabeth A
Published: November 2019

A long-standing goal of evolutionary biology is to understand the mechanisms underlying the formation of species. Of particular interest is whether or not speciation can occur in the presence of gene flow and without a period of physical isolation. Here, we investigated this process within Hawaiian Metrosideros, a hypervariable and highly dispersible woody species complex that dominates the Hawaiian Islands in continuous stands. Specifically, we investigated the origin of Metrosideros polymorpha var. newellii (newellii), a riparian ecotype endemic to Hawaii Island that is purportedly derived from the archipelago-wide M. polymorpha var. glaberrima (glaberrima). Disruptive selection across a sharp forest-riparian ecotone contributes to the isolation of these varieties and is a likely driver of newellii’s origin. We examined genome-wide variation of 42 trees from Hawaii Island and older islands. Results revealed a split between glaberrima and newellii within the past 0.3–1.2 My. Admixture was extensive between lineages within Hawaii Island and between islands, but introgression from populations on older islands (i.e., secondary gene flow) did not appear to contribute to the emergence of newellii. In contrast, recurrent gene flow (i.e., primary gene flow) between glaberrima and newellii contributed to the formation of genomic islands of elevated absolute and relative divergence. These regions were enriched for genes with regulatory functions as well as for signals of positive selection, especially in newellii, consistent with divergent selection underlying their formation. In sum, our results support riparian newellii as a rare case of incipient ecological speciation with primary gene flow in trees.
Impact on mortality of a bundle for the management of enterococcal bloodstream infection
Authors: Bartoletti Michele , Tedeschi Sara , Scudeller Luigia , Pascale Renato , Del Turco Elena Rosselli , Trapani Filippo , Tumietto Fabio , Virgili Giulio , Marconi Lorenzo , Ianniruberto Stefano , Rinaldi Matteo , Contadini Ilaria , Cristini Francesco , Bussini Linda , Campoli Caterina , Ambretti Simone , Berlingeri Andrea , Viale Pierluigi , Giannella Maddalena
Published: November 2019

BACKGROUND

In this study we evaluated the effectiveness of a management bundle for Enterococcus spp BSI (E-BSI).

METHODS

This was a single-center quasi-experimental (pre/post) study. In the “pre” phase (January 2014 to December 2015) patients with monomicrobial E-BSI were retrospectively enrolled. During the “post” or “intervention” phase (January 2016 to December 2017), all patients with incident E-BSI were prospectively enrolled in a non-mandatory intervention arm consisting in infectious disease consultation, echocardiography, follow-up blood cultures and early targeted antibiotic treatment. Patients were followed-up to 1 year after E-BSI. The primary outcome was 30-day mortality.

RESULTS

Overall, 368 patients were enrolled, 173 in the “pre” phase and 195 in the “post” phase. The entire bundle was applied in 15% and 61% patients during the “pre” and “post” phase, respectively (P<0.001). Patients enrolled in the post-phase had a significant lower 30-day mortality rate (20% vs 32%, P=0.0042). At multivariate analysis, factors independently associated to mortality were age [HR 1.03 (95%CI 1.00-1.05)], ICU admission [HR 2.51 (95%CI 1.18-3.89)] healthcare associated [HR 2.32 (95%CI 1.05-5.16)] and hospital-acquired infection [HR 2.85 (95%CI 1.34-4.76)] whereas being enrolled in the “post” period [HR 0.49 (95%CI 0.32-0.75)] was associated with improved survival. Results were consistent also in the subgroups with severe sepsis [HR 0.37 (95%CI 0.16-0.90)] or healthcare-associated infections [HR 0.53 (95%CI 0.31-0.93)]. A significative lower 1-year mortality was observed in patients enrolled in the “post” period (50% vs 68%,p<0.001).

CONCLUSION

The introduction of a bundle for the management of E-BSI was associated with improved 30-day and 1-year survival.
Predicting Clinical Dementia Rating Using Blood RNA Levels
Authors: Miller Justin B. , Kauwe John S.K. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2019

Structured Abstract

INTRODUCTION

The Clinical Dementia Rating (CDR) is commonly used to assess cognitive decline in Alzheimer’s disease patients.

METHODS

We divided 741 participants with blood microarray data in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) into three groups based on their most recent CDR assessment: cognitive normal (CDR=0), mild dementia (CDR=0.5), and probable AD (CDR≥1.0). We then used machine learning to predict cognitive status using only blood RNA levels.

RESULTS

One chloride intracellular channel 1 (CLIC1) probe was significant. By combining nonsignificant probes with p-values less than 0.1, we averaged 87.87 (s = 1.02)% predictive accuracy in classifying the three groups, compared to a 55.46% baseline for this study.

DISCUSSION

We identified one significant probe in CLIC1. However, CLIC1 levels alone were not sufficient to determine dementia status. We propose that combining individually suggestive, but nonsignificant, blood RNA levels can significantly improve diagnostic accuracy.
PARP1/2 imaging with 18F-PARPi in patients with head and neck cancer
Authors: Schöder Heiko , De Souza França Paula Demétrio , Nakajima Reiko , Burnazi Eva , Roberts Sheryl , Brand Christian , Grkovski Milan , Mauguen Audrey , Dunphy Mark P. , Ghossein Ronald A. , Lyashchenko Serge , Lewis Jason S. , O’Donoghue Joseph A. , Ganly Ian , Patel Snehal G. , Lee Nancy Y. , Reiner Thomas
Published: November 2019

Purpose

We performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with 18F-PARPi in patients with head and neck cancer.

Patients and Methods

Eleven patients (age 49 to 86 years) with newly diagnosed or recurrent oral and oropharyngeal cancer were injected intravenously with 18F-PARPi (331 ± 42 MBq) and dynamic PET/CT imaging was performed between 0 min and 25 min post-injection. Static PET/CT scans were obtained at 30 min, 60 min and 120 min p.i. Blood samples for tracer concentration and metabolite analysis were collected. Blood pressure, ECG, oxygen levels, clinical chemistry and CBC were obtained before and after administration of 18F-PARPi.

Results

18F-PARPi was well-tolerated by all patients without any safety concerns. Of the 11 patients included in the analysis, 18F-PARPi had focal uptake in all primary lesions (n = 10, SUVmax = 2.8 ± 1.2) and all 18F-FDG positive lymph nodes (n = 34). 18F-PARPi uptake was seen in 18F-FDG negative lymph nodes of three patients (n = 6). Focal uptake of tracer in primary and metastatic lesions was corroborated by CT alone or in combination with 18F-FDG. Contrast for 18F-PARPi and 18F-FDG was comparable (SUVmax(lesion)/SUVmax(genioglossus) = 3.3 and 3.0, respectively; p = 0.23), and SUVmax values for 18F-PARPi were less variable compared to 18F-FDG (1.3 versus 6.0, p = 0.001).

Conclusions

Imaging of head and neck cancer with 18F-PARPi is feasible and safe. 18F-PARPi detects primary and metastatic lesions, and retention in tumors is longer than in healthy tissues.
Aggregating Multiple Real-World Data Sources using a Patient-Centered Health Data Sharing Platform: an 8-week Cohort Study among Patients Undergoing Bariatric Surgery or Catheter Ablation of Atrial Fibrillation
Authors: Dhruva Sanket S. , Ross Joseph S. , Akar Joseph G. , Caldwell Brittany , Childers Karla , Chow Wing , Ciaccio Laura , Coplan Paul , Dong Jun , Dykhoff Hayley J. , Johnston Stephen , Kellogg Todd , Long Cynthia , Noseworthy Peter A. , Roberts Kurt , Saha Anindita , Yoo Andrew , Shah Nilay D.
Published: November 2019

Real-world data sources, including electronic health records (EHR) and personal digital device data, are increasingly available, but are often siloed and cannot be easily integrated for clinical, research, or regulatory purposes. We conducted a prospective cohort study of 60 patients undergoing bariatric surgery or catheter-based atrial fibrillation ablation at two U.S. tertiary care hospitals, testing the feasibility of using a patient-centered health data sharing platform to obtain and aggregate health data from multiple sources. We successfully obtained EHR data for all patients at both hospitals, as well as from 10 additional health systems, which were successfully aggregated with pharmacy data obtained for patients using CVS or Walgreens pharmacies, personal digital device data from activity monitors, digital weight scales, and single-lead ECGs, and patient-reported outcome measure data obtained through surveys to assess post-procedure recovery and disease-specific symptoms. A patient-centered health data sharing platform successfully aggregated data from multiple sources.
Predicting Current Juul use among Emerging Adults through Twitter Feeds
Authors: Tran Tung , Ickes Melinda , Hester Jakob W. , Kavuluru Ramakanth
Published: November 2019

Introduction

Can we predict whether someone uses Juul based on their social media activities? This is the central premise of the effort reported in this paper. Several recent social media-related studies on Juul use tend to focus on the characterization of Juul-related messages on social media. In this study, we assess the potential in using machine learning methods to automatically identify whether an individual uses Juul (past 30-day usage) based on their Twitter data.

Methods

We obtained a collection of 588 instances, for training and testing, of Juul use patterns (along with associated Twitter handles) via survey responses of college students. With this data, we built and tested supervised machine learning models based on linear and deep learning algorithms with textual, social network (friends and followers), and other hand-crafted features.

Results

The linear model with textual and follower network features performed best with a precision-recall trade-off such that precision (PPV) is 57% at 24% recall (sensitivity). Hence, at least every other college-attending Twitter user flagged by our model is expected to be a Juul user. Additionally, our results indicate that social network features tend to have a large impact (positive) on predictive performance.

Conclusion

There are enough predictive signals from social feeds for supervised modeling of Juul use, even with limited training data, implying that such models are highly beneficial to very focused intervention campaigns. Moreover, this initial success indicates potential for more involved automated surveillance of Juul use based on social media data, including Juul usage patterns, nicotine dependency, and risk awareness.
DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936
Authors: Seeboth Anne , McCartney Daniel L. , Wang Yunzhang , Hillary Robert F. , Stevenson Anna J. , Walker Rosie M. , Evans Kathryn L. , McIntosh Andrew M. , Hägg Sara , Deary Ian J. , Marioni Riccardo E.
Published: November 2019

DNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples. Here, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N=7,010, β=0.0091, p<2×10−16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N=430, β=0.033, p=7.9×10−4) and 1936 (N=898, β=7.9×10−3, p=0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, BMI, smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases and it was not heritable (SNP-based heritability of 4.4%, p=0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually but it was in a meta-analysis (HRmeta=1.12; 95%CImeta=[1.02; 1.21]; pmeta=0.021). These findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.
Effect of indoor air pollution on infant and child-mortality in Myanmar: Evidence from the first Demographic and Health Survey
Authors: Rana Juwel , Khan Md Nuruzzaman , Aliani Razia , Islam Rakibul M
Published: November 2019

Background

Indoor air pollution (IAP) from solid fuels for cooking has been considered as a public health threat, particularly for women and children in low- and lower-middle-income countries (LMICs). We investigated the effects of solid fuel use (SFU) on neonatal, infant and under-five child mortality in Myanmar.

Materials and Methods

We used data from Myanmar’s first Demographic and Health Survey conducted in 2016. The sample consists of ever-married mothers with under-five children in the household (n=3249). We calculated the adjusted odds ratio (aOR) to investigate the effects of SFU on neonatal, infant, and under-five mortality using multivariable logistic regression model accounting for survey weight and clustering. Additional analysis was conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking (high exposure, moderate, and unexposed).

Results

The prevalence of SFU was 79.0%, and the neonatal, infant and the under-five mortality rates were 26, 45 and 49 per 1,000 live births, respectively. The odds of infant (aOR 2.17, 95% CI: 1.21, 3.88) and under-five child mortality (aOR 2.22, 95% CI: 1.24, 3.95) were higher in households with SFU compared with households with clean fuel use. When applying an augmented measure of exposure to IAP by incorporating both SFU and the kitchen’s location, the likelihood of infant and under-five mortality was higher among moderately and highly exposed children compared to unexposed children with similar trends. Neonatal mortality was not associated with both SFU and levels of exposure to IAP.

Conclusion

Infants and under-five children are at higher risk of mortality from exposure to IAP. The findings suggest that the risk of infants and under-five child mortality may be reduced by increasing access to clean cookstoves and clean fuels in LMICs, especially in Myanmar.
Impact of Radiation on Cardiovascular Outcomes in Patients with Resectable Esophageal Cancer
Authors: Sarkar Reith R , Hatamipour Ahmadreza , Panjwani Neil , Courtney Patrick T , Cherry Daniel R , Salans Mia A , Yip Anthony T , Rose Brent S , Simpson Daniel R , Banegas Matthew P , Murphy James D
Published: November 2019

Purpose

Preoperative radiation therapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiation therapy and different radiation techniques on cardiovascular morbidity among a large cohort of esophageal cancer patients.

Methods

We identified 1,125 Medicare beneficiaries diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation. We used Medicare claims to identify severe adverse cardiovascular events in the perioperative and postoperative periods. Multivariable logistic regression and Fine-Gray models were used to determine the effect of pre-surgery treatment on the risk of perioperative and postoperative cardiovascular disease.

Results

Preoperative chemotherapy or preoperative chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared to surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a postoperative cardiovascular event compared to patients treated with surgery alone (subdistribution hazard ratio [SDHR] 1.36; p=0.035). There was no significant increase in cardiovascular events among patients treated with preoperative chemotherapy (SDHR 1.18; p=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy (IMRT) had a 68% decreased risk of having a cardiovascular event compared to patients receiving conventional radiation (SDHR 0.32; p=0.007).

Conclusions

This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as IMRT.
Validity of using cancer registry data for comparative effectiveness research
Authors: Kumar Abhishek , Guss Zachary D , Courtney Patrick T , Nalawade Vinit , Sheridan Paige , Sarkar Reith R , Banegas Matthew P , Rose Brent S , Xu Ronghui , Murphy James D
Published: November 2019

Purpose

Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective non-random design of these analyses raise questions about study validity. The purpose of this study was to determine the extent to which comparative effectiveness analyses using cancer registry data produces results concordant with randomized clinical trials.

Methods

We identified 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types. For each trial we identified subjects from the National Cancer Database (NCDB) matching the eligibility criteria of the randomized trial. With each trial we used three Cox regression models to determine hazard ratios (HRs) for overall survival including univariable, multivariable, and propensity score adjusted models. Multivariable and propensity score analyses controlled for potential confounders including demographic, comorbidity, clinical, treatment, and tumor-related variables. Each NCDB survival analysis was defined as discordant if the HR for the NCDB analysis fell outside the 95% confidence interval of the corresponding randomized trial.

Results

NCDB analyses produced HRs for survival discordant with randomized trials in 62 (44%) univariable analyses, 43 (30%) multivariable analyses, and 51 (36%) propensity score models. NCDB analyses produced p-values discordant with randomized trials in 83 (59%) univariable analyses, 76 (54%) multivariable analyses, and 78 (55%) propensity score models. We did not identify any clinical trial characteristic associated with discordance between NCDB analyses and randomized trials including disease site, type of clinical intervention, or severity of cancer.

Conclusion

Comparative effectiveness research with cancer registry data often produces survival outcomes discordant to randomized clinical data. These findings help provide context for providers interpreting observational comparative effectiveness research in oncology.
Physicians’ learning in the workplace: use of informal feedback cues in daily practice
Authors: Sehlbach Carolin , Teunissen Pim W , Driessen Erik W , Mitchell Sharon , Rohde Gernot GU , Smeenk Frank WJM , Govaerts Marjan JB
Published: November 2019

Purpose

We expect physicians to be lifelong learners. Learning from clinical practice is an important potential source for that learning. To support physicians in this process, a better understanding of how they learn in clinical practice is necessary. This study investigates how physicians use informal feedback as learning cues to adjust their communication from interactions with patients in the outpatient setting.

Methods

To understand physicians’ use of informal feedback, we combined non-participant ethnographic observations with semi-structured interviews. We enrolled 10 respiratory physicians and observed 100 physician-patient interactions at one academic and one non-academic hospital in the Netherlands. Data collection and analysis were performed iteratively according to the principles of constructivist grounded theory. Our conceptual model describes how physicians use cues to reflect on and adjust their communication as well as to further develop their adaptive expertise.

Results

In addition to vast variations within and across patient encounters, we observed recurring patterns in physicians’ communications in reaction to specific learning cues. Physicians had learnt to recognise and use different cues to adjust their communication in patient encounters. They established a ‘communication repertoire’ based on multiple patient interactions, which many saw as learning opportunities, contributing to the development of adaptive expertise. Our findings show differences in physicians’ sensitivity to recognising learning opportunities in daily practice which was further influenced by contextual, personal and interpersonal factors. Whereas some reported to have little inclination to change, others used critical incidents to fine-tune their communication repertoire, while others constantly reshaped it, seeking learning opportunities in their daily work.

Conclusions

There is a large variation in how physicians use learning cues from daily practice. Learning from daily practice is a collaborative effort and requires a culture that promotes lifelong learning. Raising physicians’ awareness of experiences as potential learning opportunities might enhance their development of adaptive expertise.