bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease and Human Capital Accumulation: Evidence from the Roll Back Malaria Partnership in Africa
Authors: Kuecken Maria , Thuilliez Josselin , Valfort Marie-Anne
Published: December 2020

We estimate the effects of a large-scale antimalaria campaign on a rich set of human capital outcomes in 27 sub-Saharan African countries. Using pre-campaign malaria risk as treatment probability, we exploit quasi-experimental variation in period and cohort exposure to antimalaria campaigns. A conservative interpretation of our results shows a globally positive impact of antimalaria campaigns: they reduced the probability of infant mortality (1 p.p.) and birth (0.4 p.p.) and increased educational attainment (0.4 years) and the likelihood of adult paid employment (6 p.p.). These findings demonstrate how the effects of sweeping disease reduction efforts extend beyond health outcomes.
British Universities and Transatlantic Slavery: the University of Glasgow Case
Authors: Mullen Stephen
Published: December 2020

On 16 September 2018, the University of Glasgow released the report ‘Slavery, Abolition and the University of Glasgow’. This acknowledged that slave-owners, merchants and planters with connections to New World slavery – and their descendants – donated capital between 1697 and 1937 that influenced the development of the institution. In producing this report, the institution became the first British university to declare historical income derived from transatlantic slavery. In response, a nine-point programme reported as reparative justice was launched, the first British university to launch a project on such a scale. This article traces both the methodological approach undertaken in the study and the historical evidence related to the University of Glasgow. This provides insights into the process of collecting and analysing the evidence on which the report and strategy was based. Current understandings about British universities and transatlantic slavery are shaped by the institutional relationship with owners of enslaved people. This article underlines the importance of merchant capital – in this case, mainly via West India commerce – to the development of one institution.
Finite-time control of uncertain time-varying systems in p-normal form
Authors: Rattanamongkhonkun Kanya , Pongvuthithum Radom , Likasiri Chulin
Published: December 2020

This paper addresses a finite-time regulation problem for time-varying nonlinear systems in p-normal form. This class of time-varying systems includes a well-known lower-triangular system and a chain of power integrator systems as special cases. No growth condition on time-varying uncertainties is imposed. The control law can guarantee that all closed-loop trajectories are bounded and well defined. Furthermore, all states converge to zero in finite time.
Building longitudinal medication dose data using medication information extracted from clinical notes in electronic health records
Authors: McNeer Elizabeth , Beck Cole , Weeks Hannah L , Williams Michael L , James Nathan T , Bejan Cosmin A , Choi Leena
Published: December 2020

Objective

To develop an algorithm for building longitudinal medication dose datasets using information extracted from clinical notes in electronic health records (EHRs).

Materials and Methods

We developed an algorithm that converts medication information extracted using natural language processing (NLP) into a usable format and builds longitudinal medication dose datasets. We evaluated the algorithm on 2 medications extracted from clinical notes of Vanderbilt’s EHR and externally validated the algorithm using clinical notes from the MIMIC-III clinical care database.

Results

For the evaluation using Vanderbilt’s EHR data, the performance of our algorithm was excellent; F1-measures were ≥0.98 for both dose intake and daily dose. For the external validation using MIMIC-III, the algorithm achieved F1-measures ≥0.85 for dose intake and ≥0.82 for daily dose.

Discussion

Our algorithm addresses the challenge of building longitudinal medication dose data using information extracted from clinical notes. Overall performance was excellent, but the algorithm can perform poorly when incorrect information is extracted by NLP systems. Although it performed reasonably well when applied to the external data source, its performance was worse due to differences in the way the drug information was written. The algorithm is implemented in the R package, “EHR,” and the extracted data from Vanderbilt’s EHRs along with the gold standards are provided so that users can reproduce the results and help improve the algorithm.

Conclusion

Our algorithm for building longitudinal dose data provides a straightforward way to use EHR data for medication-based studies. The external validation results suggest its potential for applicability to other systems.
Effectiveness of Entomopathogenic Nematodes Against Ceratitis capitata (Diptera: Tephritidae) Pupae and Nematode Compatibility with Chemical Insecticides
Authors: Jean-Baptiste Maguintontz Cedney , de Brida Andressa Lima , Bernardi Daniel , da Costa Dias Sérgio , de Bastos Pazini Juliano , Leite Luis Garrigós , Wilcken Silvia Renata Siciliano , Garcia Flávio Roberto Mello
Published: December 2020

The Mediterranean fruit fly Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae) is among the main pests of fruit crops worldwide. Biological control using entomopathogenic nematodes (EPNs) may be an alternative to suppress populations of this pest. Thus, the aim of this study was to evaluate the pathogenicity and virulence of six EPN isolates (Heterorhabditis bacteriophora HB, H. amazonensis IBCB-n24, Steinernema carpocapsae IBCB-n02, S. rarum PAM-25, S. glaseri IBCB-n47, and S. brazilense IBCB-n06) against C. capitata pupae. The compatibility of EPNs with different chemical insecticides that are registered for management of C. capitata was also assessed. Isolates of H. bacteriophora HB and S. brazilense IBCB-n06 at a concentration of 1,000 infective juveniles (IJ)/ml proved to be most pathogenic to C. capitata (70 and 80% mortality, respectively). In contrast, the isolates H. amazonensis IBCB-n24, Steinernema carpocapsae IBCB-n02, S. rarum PAM-25, S. glaseri IBCB-n47 provided pupal mortality of less than 60%. Bioassays to determine lethal concentrations indicated that concentrations of 600 IJ/ml (H. bacteriophora HB) and 1,000 IJ/ml (S. brazilense IBCB-n06) showed the highest virulence against C. capitata pupae. In contrast, the highest numbers of IJs emerged at concentrations of 1,200 and 200 IJ/ml. In compatibility bioassays, malathion, spinetoram, phosmet, acetamiprid, and novaluron were considered compatible with and harmless (Class 1) to H. bacteriophora HB and S. brazilense IBCB-n06, according to IOBC/WPRS. This information is important for implementing integrated management programs for C. capitata, using biological control with EPNs, whether alone or in combination with chemical insecticides.
Assessing Cotton Genotypes for Resistance to Aphis gossypii (Hemiptera: Aphididae)
Authors: Morando Rafaela , da Silva Ivana Fernandes , da Silva Santana Alisson , Sampaio Guilherme Sicca Lopes , Lourenção André Luiz , Baldin Edson Luiz Lopes
Published: December 2020

Aphis gossypii Glover (Hemiptera: Aphididae) is a polyphagous species frequently associated with the presence of sooty mold and viruses lethal to plants. The purpose of this work was to characterize possible resistance categories of cotton genotypes against A. gossypii. Initially, a preliminary test was carried out with 78 genotypes, 15 of which were selected for infestation ability assays and the determination of the cumulative aphid-day rates. Posteriorly, these genotypes were also evaluated through antixenosis and antibiosis assays. The genotypes FM 910, FM 966 LL, Mocó, Gossypium hirsutum var. punctatum L. (Malvaceae), Variedade Reba = BTK-12, Deltapine, Hi-Bred, Acala 4–42, IAC PV010-1664, IAC 21, Reba B-50 PR and FMT 709 inhibited the aphid colonization. In the infestation ability assay, G. hirsutum punctatum, IAC PV010-1664 and Acala 4–42 were the least infested. In a multiple-choice assay, Deltapine Smooth Leaf and Variedade Reba = BTK-12 were significantly less infested, suggesting antixenosis. In the antibiosis assay, Gossypium arboreum L. (Malvaceae) 1 showed the lowest number of nymphs, number of nymphs per adult per day and, number of nymphs at 10 d after the birth of the first nymph in addition to reducing the reproductive period, nymphal survival, adult longevity and, developmental time. In the FM 910, the number of nymphs produced per day and, at 10 d after the birth of the first nymph decreased, which also indicated resistance. The results obtained here are unprecedented and can be explored in breeding programs to develop insect-resistant cotton cultivars.
Bernini’s painting collection: a reconstructed inventory raisonné
Authors: Mormando Franco
Published: December 2020

Here presented is the first comprehensive inventory of the paintings on display in Gian Lorenzo Bernini’s home by artists other than himself at the time of his death in November 1680. Although inventories of Bernini’s household dating from 1681 to 1771 have previously been published, none by itself is sufficient to provide a complete catalogue of the artist’s collection. By collating the family inventories with what is known of Bernini’s career, personal and professional relationships, the oeuvre of the artists identified in the inventories, and data from art market records and provenance databases, the author has compiled the most detailed description of Bernini’s collection so far available, including, wherever possible, proposed new attributions, more accurate subject descriptions, and indications of the present whereabouts of the works.
21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma In Situ
Authors: Rakovitch Eileen , Sutradhar Rinku , Nofech-Mozes Sharon , Gu Sumei , Fong Cindy , Hanna Wedad , Paszat Lawrence
Published: December 2020

Background

The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown.

Methods

We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided.

Results

With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC.

Conclusion

The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.
Grids of stellar models with rotation – V. Models from 1.7 to 120 M⊙ at zero metallicity
Authors: Murphy Laura J , Groh Jose H , Ekström Sylvia , Meynet Georges , Pezzotti Camila , Georgy Cyril , Choplin Arthur , Eggenberger Patrick , Farrell Eoin , Haemmerlé Lionel , Hirschi Raphael , Maeder André , Martinet Sebastién
Published: December 2020

Understanding the nature of the first stars is key to understanding the early Universe. With new facilities such as James Webb Space Telescope (JWST) we may soon have the first observations of the earliest stellar populations, but to understand these observations we require detailed theoretical models. Here we compute a grid of stellar evolution models using the Geneva code with the aim to improve our understanding of the evolution of zero-metallicity stars, with particular interest in how rotation affects surface properties, interior structure, and metal enrichment. We produce a range of models of initial masses (Mini) from $1.7$ to $120\, \mathrm{M}_{\odot }$, focusing on massive models of $9 \le M_{\rm ini}\le 120\, \mathrm{M}_{\odot }$. Our grid includes models with and without rotation, with rotating models having an initial velocity of 40 per cent of the critical velocity. We find that rotation strongly impacts the evolution of the first stars, mainly through increased core size and stronger H-burning shells during core He-burning. Without radiative mass loss, angular momentum builds at the surface in rotating models, thus models of initial masses $M_{\rm ini}\ge 60 \, \mathrm{M}_{\odot }$ reach critical rotation on the main sequence and experience mass loss. We find that rotational mixing strongly affects metal enrichment, but does not always increase metal production as we see at higher metallicities. This is because rotation leads to an earlier CNO boost to the H shell during He-burning, which may hinder metal enrichment depending on initial mass and rotational velocity. Electronic tables of this new grid of Population III models are publicly available.
A complete search for redshift z ≳ 6.5 quasars in the VIKING survey
Authors: Barnett R , Warren S J , Cross N J G , Mortlock D J , Fan X , Wang F , Hewett P C
Published: December 2020

We present the results of a new, deeper, and complete search for high-redshift 6.5 < z < 9.3 quasars over 977 deg2 of the VISTA Kilo-Degree Infrared Galaxy (VIKING) survey. This exploits a new list-driven data set providing photometry in all bands Z, Y, J, H, Ks, for all sources detected by VIKING in J. We use the Bayesian model comparison (BMC) selection method of Mortlock et al., producing a ranked list of just 21 candidates. The sources ranked 1, 2, 3, and 5 are the four known z > 6.5 quasars in this field. Additional observations of the other 17 candidates, primarily DESI Legacy Survey photometry and ESO FORS2 spectroscopy, confirm that none is a quasar. This is the first complete sample from the VIKING survey, and we provide the computed selection function. We include a detailed comparison of the BMC method against two other selection methods: colour cuts and minimum-χ2 SED fitting. We find that: (i) BMC produces eight times fewer false positives than colour cuts, while also reaching 0.3 mag deeper, (ii) the minimum-χ2 SED-fitting method is extremely efficient but reaches 0.7 mag less deep than the BMC method, and selects only one of the four known quasars. We show that BMC candidates, rejected because their photometric SEDs have high χ2 values, include bright examples of galaxies with very strong [O iii] λλ4959,5007 emission in the Y band, identified in fainter surveys by Matsuoka et al. This is a potential contaminant population in Euclid searches for faint z > 7 quasars, not previously accounted for, and that requires better characterization.
Pulsating ULXs: large pulsed fraction excludes strong beaming
Authors: Mushtukov Alexander A , Portegies Zwart Simon , Tsygankov Sergey S , Nagirner Dmitrij I , Poutanen Juri
Published: December 2020

The recent discovery of pulsating ultraluminous X-ray sources (ULXs) shows that the apparent luminosity of accreting neutron stars can exceed the Eddington luminosity by a factor of 100s. The relation between the actual and apparent luminosity is a key ingredient in theoretical models of ULXs, but it is still under debate. A typical feature of the discovered pulsating ULXs is a large pulsed fraction (PF). Using Monte Carlo simulations, we consider a simple geometry of accretion flow and test the possibility of simultaneous presence of a large luminosity amplification due the geometrical beaming and a high PF. We argue that these factors largely exclude each other and only a negligible fraction of strongly beamed ULX pulsars can show PF above 10 per cent. Discrepancy between this conclusion and current observations indicates that pulsating ULXs are not strongly beamed and their apparent luminosity is close to the actual one.
Minimizing the impact of scale-dependent galaxy bias on the joint cosmological analysis of large-scale structures
Authors: Asgari Marika , Friswell Indiarose , Yoon Mijin , Heymans Catherine , Dvornik Andrej , Joachimi Benjamin , Simon Patrick , Zuntz Joe
Published: December 2020

We present a mitigation strategy to reduce the impact of non-linear galaxy bias on the joint ‘3 × 2pt’ cosmological analysis of weak lensing and galaxy surveys. The Ψ-statistics that we adopt are based on Complete Orthogonal Sets of E/B Integrals. As such they are designed to minimize the contributions to the observable from the smallest physical scales where models are highly uncertain. We demonstrate that Ψ-statistics carry the same constraining power as the standard two-point galaxy clustering and galaxy–galaxy lensing statistics, but are significantly less sensitive to scale-dependent galaxy bias. Using two galaxy bias models, motivated by halo model fits to data and simulations, we quantify the error in a standard 3 × 2pt analysis where constant galaxy bias is assumed. Even when adopting conservative angular scale cuts, that degrade the overall cosmological parameter constraints, we find of order 1σ biases for Stage III surveys on the cosmological parameter S8 = σ8(Ωm/0.3)α. This arises from a leakage of the smallest physical scales to all angular scales in the standard two-point correlation functions. In contrast, when analysing Ψ-statistics under the same approximation of constant galaxy bias, we show that the bias on the recovered value for S8 can be decreased by a factor of ∼2, with less conservative scale cuts. Given the challenges in determining accurate galaxy bias models in the highly non-linear regime, we argue that 3 × 2pt analyses should move towards new statistics that are less sensitive to the smallest physical scales.
Predicting regulatory variants using a dense epigenomic mapped CNN model elucidated the molecular basis of trait-tissue associations
Authors: Pei Guangsheng , Hu Ruifeng , Dai Yulin , Manuel Astrid Marilyn , Zhao Zhongming , Jia Peilin
Published: December 2020

Assessing the causal tissues of human complex diseases is important for the prioritization of trait-associated genetic variants. Yet, the biological underpinnings of trait-associated variants are extremely difficult to infer due to statistical noise in genome-wide association studies (GWAS), and because >90% of genetic variants from GWAS are located in non-coding regions. Here, we collected the largest human epigenomic map from ENCODE and Roadmap consortia and implemented a deep-learning-based convolutional neural network (CNN) model to predict the regulatory roles of genetic variants across a comprehensive list of epigenomic modifications. Our model, called DeepFun, was built on DNA accessibility maps, histone modification marks, and transcription factors. DeepFun can systematically assess the impact of non-coding variants in the most functional elements with tissue or cell-type specificity, even for rare variants or de novo mutations. By applying this model, we prioritized trait-associated loci for 51 publicly-available GWAS studies. We demonstrated that CNN-based analyses on dense and high-resolution epigenomic annotations can refine important GWAS associations in order to identify regulatory loci from background signals, which yield novel insights for better understanding the molecular basis of human complex disease. We anticipate our approaches will become routine in GWAS downstream analysis and non-coding variant evaluation.
Pseudouridine-mediated translation control of mRNA by methionine aminoacyl tRNA synthetase
Authors: Levi Ofri , Arava Yoav S
Published: December 2020

Modification of nucleotides within an mRNA emerges as a key path for gene expression regulation. Pseudouridine is one of the most common RNA modifications; however, only a few mRNA modifiers have been identified to date, and no one mRNA pseudouridine reader is known. Here, we applied a novel genome-wide approach to identify mRNA regions that are bound by yeast methionine aminoacyl tRNAMet synthetase (MetRS). We found a clear enrichment to regions that were previously described to contain pseudouridine (Ψ). Follow-up in vitro and in vivo analyses on a prime target (position 1074 within YEF3 mRNA) demonstrated the importance of pseudouridine for MetRS binding. Furthermore, polysomal and protein analyses revealed that Ψ1074 mediates translation. Modification of this site occurs presumably by Pus6, a pseudouridine synthetase known to modify MetRS cognate tRNA. Consistently, the deletion of Pus6 leads to a decrease in MetRS association with both tRNAMet and YEF3 mRNA. Furthermore, while global protein synthesis decreases in pus6Δ, translation of YEF3 increases. Together, our data imply that Pus6 ‘writes’ modifications on tRNA and mRNA, and both types of RNAs are ‘read’ by MetRS for translation regulation purposes. This represents a novel integrated path for writing and reading modifications on both tRNA and mRNA, which may lead to coordination between global and gene-specific translational responses.
Mapping DNA conformations and interactions within the binding cleft of bacteriophage T4 single-stranded DNA binding protein (gp32) at single nucleotide resolution
Authors: Camel Benjamin R , Jose Davis , Meze Katarina , Dang Anson , von Hippel Peter H
Published: December 2020

In this study, we use single-stranded DNA (oligo-dT) lattices that have been position-specifically labeled with monomer or dimer 2-aminopurine (2-AP) probes to map the local interactions of the DNA bases with the nucleic acid binding cleft of gp32, the single-stranded binding (ssb) protein of bacteriophage T4. Three complementary spectroscopic approaches are used to characterize these local interactions of the probes with nearby nucleotide bases and amino acid residues at varying levels of effective protein binding cooperativity, as manipulated by changing lattice length. These include: (i) examining local quenching and enhancing effects on the fluorescence spectra of monomer 2-AP probes at each position within the cleft; (ii) using acrylamide as a dynamic-quenching additive to measure solvent access to monomer 2-AP probes at each ssDNA position; and (iii) employing circular dichroism spectra to characterize changes in exciton coupling within 2-AP dimer probes at specific ssDNA positions within the protein cleft. The results are interpreted in part by what we know about the topology of the binding cleft from crystallographic studies of the DNA binding domain of gp32 and provide additional insights into how gp32 can manipulate the ssDNA chain at various steps of DNA replication and other processes of genome expression.
Retrobulbar Hemangioblastomas in von Hippel-Lindau Disease: Clinical Course and Management
Authors: Alvarez Reinier , Mastorakos Panagiotis , Hogan Elizabeth , Scott Gretchen , Lonser Russell R , Wiley Henry E , Chew Emily Y , Chittiboina Prashant
Published: December 2020

BACKGROUND

Retrobulbar hemangioblastomas involving the optic apparatus in patients with von Hippel-Lindau disease (VHL) are rare, with only 25 reported cases in the literature.

OBJECTIVE

To analyze the natural history of retrobulbar hemangioblastomas in a large cohort of VHL patients in order to define presentation, progression, and management.

METHODS

Clinical history and imaging of 250 patients with VHL in an ongoing natural history trial and 1774 patients in a neurosurgical protocol were reviewed. The clinical course, magnetic resonance images, treatment, and outcomes were reviewed for all included patients.

RESULTS

A total of 18 patients with retrobulbar hemangioblastoma on surveillance magnetic resonance imaging met the inclusion criteria for this study. Of the 17 for whom clinical information was available, 10 patients presented with symptoms related to the hemangioblastoma, and 7 were asymptomatic. The mean tumor volume was larger for symptomatic (810.6 ± 545.5 mm3) compared to asymptomatic patients (307.6 ± 245.5 mm3; P < .05). A total of 5 of the symptomatic patients were treated surgically and all experienced improvement in their symptoms. All 3 symptomatic patients that did not undergo intervention had continued symptom progression. Long-term serial imaging on asymptomatic patients showed that these tumors can remain radiographically stable and asymptomatic for extended periods of time (101.43 ± 71 mo).

CONCLUSION

This study suggests that retrobulbar hemangioblastomas may remain stable and clinically asymptomatic for long durations. Recent growth and larger tumor volume were associated with symptom occurrence. Surgical treatment of symptomatic retrobulbar hemangioblastomas can be safe and may reverse the associated symptoms.
An updated histology recode for the analysis of primary malignant and nonmalignant brain and other central nervous system tumors in the Surveillance, Epidemiology, and End Results Program
Authors: Forjaz Gonçalo , Barnholtz-Sloan Jill S , Kruchko Carol , Siegel Rebecca , Negoita Serban , Ostrom Quinn T , Dickie Lois , Ruhl Jennifer , Van Dyke Alison , Patil Nirav , Cioffi Gino , Miller Kimberly D , Waite Kristin , Mariotto Angela B
Published: December 2020

Background

There are over 100 histologically distinct types of primary malignant and nonmalignant brain and other central nervous system (CNS) tumors. Our study presents recent trends in the incidence of these tumors using an updated histology recode that incorporates major diagnostic categories listed in the 2016 World Health Organization Classification of Tumours of the CNS.

Methods

We used data from the SEER-21 registries for patients of all ages diagnosed in 2000–2017. We calculated age-adjusted incidence rates and fitted a joinpoint regression to the observed data to estimate the Annual Percent Change and 95% confidence intervals over the period 2000–2017.

Results

There were 315,184 new malignant (34.2%; 107,890) and nonmalignant (65.8%; 207,294) brain tumor cases during 2004–2017. Nonmalignant meningioma represented 46.5% (146,498) of all brain tumors (malignant and nonmalignant), while glioblastoma represented 50.8% (54,832) of all malignant tumors. Temporal trends were stable or declining except for nonmalignant meningioma (0.7% per year during 2004–2017). Several subtypes presented decreases in trends in the most recent period (2013–2017): diffuse/anaplastic astrocytoma (−1.3% per year, oligodendroglioma (−2.6%), pilocytic astrocytoma (−3.8%), and malignant meningioma (−5.9%).

Conclusions

Declining trends observed in our study may be attributable to recent changes in diagnostic classification and the coding practices stemming from those changes. The recode used in this study enables histology reporting to reflect the changes. It also provides a first step toward the reporting of malignant and nonmalignant brain and other CNS tumors in the Surveillance, Epidemiology, and End Results (SEER) Program by clinically relevant histology groupings.
Rurality of Residence and Inappropriate Antibiotic Use for Acute Respiratory Infections Among Young Tennessee Children
Authors: Dantuluri Keerti L , Bruce Jean , Edwards Kathryn M , Banerjee Ritu , Griffith Hannah , Howard Leigh M , Grijalva Carlos G
Published: December 2020

Background

Antibiotic use is common for acute respiratory infections (ARIs) in children, but much of this use is inappropriate. Few studies have examined whether rurality of residence is associated with inappropriate antibiotic use. We examined whether rates of ARI-related inappropriate antibiotic use among children vary by rurality of residence.

Methods

We conducted a retrospective cohort study of children aged 2 months–5 years enrolled in Tennessee Medicaid between 2007 and 2017 and diagnosed with ARI in the outpatient setting. Study outcomes included ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. Multivariable Poisson regression was used to measure associations between rurality of residence, defined by the US Census Bureau, and the rate of study outcomes, while accounting for other factors including demographics and underling comorbidities.

Results

A total of 805 332 children met selection criteria and contributed 1 840 048 person-years (p-y) of observation. Children residing in completely rural, mostly rural, and mostly urban counties contributed 70 369 (4%) p-y, 479 121 (26%) p-y, and 1 290 558 p-y (70%), respectively. Compared with children in mostly urban counties (238 per 1000 p-y), children in mostly rural (450 per 1000 p-y) and completely rural counties (468 per 1000 p-y) had higher rates of inappropriate antibiotic use (adjusted incidence rate ratio [aIRR] = 1.34, 95% confidence interval [CI] = 1.33–1.35 and aIRR = 1.33, 95% CI = 1.32–1.35, respectively).

Conclusions

Inappropriate antibiotic use is common among young children with ARI, with higher rates in rural compared with urban counties. These differences should inform targeted outpatient antibiotic stewardship efforts.
Viral Ribonucleic Acid Shedding and Transmission Potential of Asymptomatic and Paucisymptomatic Coronavirus Disease 2019 Patients
Authors: Samaddar Arghadip , Gadepalli Ravisekhar , Nag Vijaya Lakshmi , Misra Sanjeev , Bhardwaj Pankaj , Singh Pankaj , Meena Mahadev , Sharma Prem Prakash , Grover Malika , Kumar Garg Mahendra , Chauhan Nishant Kumar , Dutt Naveen , Niwas Ram , Kumar Deepak , Sharma Praveen , Goel Akhil Dhanesh , Kumar Gupta Manoj , Saurabh Suman , Rai Shubham , Lawdiya Chunnilal , Saini Jinesh , Singh Deepak
Published: December 2020

We studied the pattern and duration of viral ribonucleic acid (RNA) shedding in 32 asymptomatic and 11 paucisymptomatic coronavirus disease 2019 cases. Viral RNA shedding in exhaled breath progressively diminished and became negative after 6 days of a positive reverse-transcription polymerase chain reaction test. Therefore, the duration of isolation can be minimized to 6 days.
Bertolotti Syndrome With Articulated L5 Transverse Process Causing Intractable Back Pain: Surgical Video Showcasing a Minimally Invasive Approach for Disconnection: 2-Dimensional Operative Video
Authors: Johnson Zachary D , Aoun Salah G , Ban Vin Shen , El Ahmadieh Tarek Y , Kafka Benjamin , Wolfe Cody , Adogwa Owoicho , Bagley Carlos A , Tamimi Mazin Al
Published: December 2020

Bertolotti syndrome is a commonly missed cause of intractable back pain that affects 4% to 8% of the general population. It involves the congenital malformation of a transitional lumbosacral vertebra, with total or partial and unilateral or bilateral transverse process (TP) fusion or articulation to the sacrum. The pain can be debilitating, and the tethering of the spine to the sacrum can encourage deformity formation in the coronal plane and lead to early degenerative changes, especially if present only unilaterally. We present the case of a 24-yr-old woman with no notable prior medical history who presented with years of lower axial back pain radiating to her thighs, which limited her activities of daily living and was resistant to conservative management. Her imaging showed an abnormally large left L5 TP, which was articulated to the sacrum, and signs of early coronal deformity. She had responded almost completely to repeated steroid injections into the TP-sacral joint, but that effect was very transient. Informed patient consent was obtained prior to her surgery. She underwent a minimally invasive tube disconnection of the abnormal joint with partial distal resection of the TP, and her symptoms completely resolved. This case highlights the importance of correlating clinical symptoms with aberrant anatomy, and the role of selective surgery in providing symptomatic relief. This case report was written in compliance with our institutional ethical review board approval, and patient consent was waived in light of the retrospective and deidentified nature of the data presented in accordance with the University of Texas Southwestern institutional review board.
Evaluating Real-World Adherence and Effectiveness of the “Reboot Online” Program for the Management of Chronic Pain in Routine Care
Authors: Lim Derek Z , Newby Jill M , Gardner Tania , Haskelberg Hila , Schultz Regina , Faux Steven G , Shiner Christine T
Published: December 2020

Objective

Chronic pain is a prevalent and disabling condition. Reboot Online was developed as a multidisciplinary and widely accessible online treatment program for chronic pain. It has been shown to be effective in clinical trials, but the effectiveness of this program in routine care settings remains unknown. This study aimed to examine program adherence and effectiveness in a real-world sample of participants completing Reboot Online in the community.

Design and subjects

A retrospective cohort study was conducted using real-world data from participants referred the Reboot Online program by clinicians as part of their routine care, from April 2017 to April 2019.

Methods

Routinely collected data on program adherence, participant demography and clinical outcomes were included in the analyses. Measures included the Pain Self Efficacy Questionnaire, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain-Disability Index, and Patient Health Questionnaire 9-item (depression). Logistic regression was used to investigate whether certain factors predict program adherence (completion versus noncompletion), and linear mixed models were used to examine effectiveness.

Results

In total, 867 participants were included in the analyses, and 583 engaged with at least one Reboot Online lesson. Of these, 42% (n = 247) completed the course in its entirety, with rurality and lower Tampa scores being significant predictors of adherence. Completers demonstrated significant improvements across all outcome measures (effect sizes ranging from 0.22 to 0.51).

Conclusions

Reboot Online is an effective treatment for chronic pain in the routine care setting. Adherence was variable (overall 42%), and could be predicted by rurality and less fear of movement at baseline.
Comparative effectiveness and persistence of TNFi and non-TNFi in juvenile idiopathic arthritis: a large paediatric rheumatology centre in the USA
Authors: Yue Xiaomeng , Huang Bin , Hincapie Ana L , Wigle Patricia R , Li Yuxiang , Qiu Tingting , Lovell Daniel J , Morgan Esi M , Guo Jeff J
Published: December 2020

Objective

To evaluate the persistence and effectiveness of TNF inhibitors (TNFi) vs non-TNFi among newly diagnosed JIA patients after initiation of biologic DMARD (bDMARD).

Methods

Using longitudinal patient-level data extracted from electronic medical records in a large Midwestern paediatric hospital from 2009 to 2018, we identified JIA patients initiating TNFi and non-TNFi treatment. Treatment effectiveness was assessed based on disease activity. Inverse probability of treatment weighting of propensity score was used to estimate the treatment effectiveness and Kaplan–Meier analyses were conducted to assess persistence.

Results

Of 667 JIA patients, most (92.0%) were prescribed one of the class of TNFi as their initial biologic treatment. Etanercept was the most frequently prescribed (67.1%) treatment, followed by adalimumab (27.5%). Only around 5% of patients were prescribed off-label bDMARDs as their first-course treatment; however, >20% were prescribed off-label biologics as their second-course therapy. Some 7.2% of patients received four or more bDMARDs. The median persistence of the first-course bDMARD is 320 days, with TNFi being significantly longer than the non-TNFi (395 vs 320 days, P = 0.010). The clinical Juvenile Disease Activity Score (cJADAS) reduction of TNFi users (6.6, 95% CI 5.7, 7.5) was significant greater compared with non-TNFi users (3.0, 95% CI 1.5, 4.6, P < 0.0001) at 6-month follow-up visit.

Conclusion

Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients receiving TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patients in the non-TNF cohort.
“Let’s Chat”: process evaluation of an intergenerational group chat intervention to increase cancer prevention screening among Vietnamese American families
Authors: Duong Huong T , Hopfer Suellen
Published: December 2020

Vietnamese Americans have a higher rate of cervical and colorectal cancer (CRC) compared to other ethnicities. Increasing CRC screening, Pap testing, and HPV vaccination is critical to preventing disproportionate cancer burden among Vietnamese families. To describe the successes and challenges of implementing a novel intergenerational family group chat intervention that encourages CRC screening, Pap testing, and HPV vaccination. Young adult Family Health Advocates (FHAs) were trained to facilitate online family group chat conversations to encourage cancer screenings. Ten families participated in a 4-week intervention. Data collection included screenshot data of family group chat conversations, family member surveys, and post-intervention FHA interviews. Intervention implementation successes included (a) cultural and language brokering, (b) active co-facilitation by family members to follow up on cancer screenings, (c) high levels of family group chat engagement, (d) high acceptability of intervention among families, and (e) accessibility of intervention curriculum. FHA challenges to implement the intervention included (a) sustaining cancer prevention conversations, (b) comfort with navigating family conversations around cancer screening, (c) relevance for all family members, and (d) missed opportunities for correcting misinformation. Researcher challenges included family recruitment and retention. The intervention made cancer-screening messages more accessible and was well accepted by Vietnamese families. Scaling up the intervention will require (a) training FHAs to monitor family conversations and build confidence in sharing medical accurate messages, (b) segmenting group chats by age and gender, and (c) employing multiple family engagement strategies.
In-Season Monitoring of Postharvest Rot Pathogens on European Pears (Pyrus communis) in Southern Oregon and Subsequent Management Strategies
Authors: KC Achala N. , Rasmussen Ann L.
Published: December 2020

Postharvest decay in pears is a disease complex caused by several fungal pathogens. To understand the presence of these pathogens on flower and fruit tissues at early stages of fruit development, we collected samples from two commercial pear orchards in southern Oregon at five stages of fruit development: cluster bud, full bloom, petal fall, fruitlets, and field bins during commercial harvest. We recovered four common postharvest decay pathogens, Alternaria spp., Botrytis cinerea, Cladosporium herbarum, and Penicillium expansum, which varied in frequency across these stages, suggesting that pathogens may initially infect flowers and fruitlets well before conventional preharvest fungicide sprays. In a separate experiment, we applied four fungicides early in the growing season and/or shortly before harvest to determine when treatment was most effective in reducing the recovery rate of these pathogens and reducing storage rot. The recovery of Alternaria spp., B. cinerea, and P. expansum from flowers and fruitlets was reduced by 33, 47, and 33%, respectively, with bloom-time fungicide applications compared with nontreated control treatments. In addition, the fungicide program that included bloom-time application, preharvest application, and postharvest application resulted in significantly lower storage rot incidence compared with preharvest and postharvest application only. Syllit (dodine) reduced the storage rot incidence by 71%, Inspire Super (difenoconazole + cyprodinil) by 52%, Nevado (iprodione) by 36%, and Merivon (fluxapyroxad + pyraclostrobin) by 33% compared with nontreated control treatments.
Queen pheromone modulates the expression of epigenetic modifier genes in the brain of honeybee workers
Authors: Cardoso-Junior Carlos Antônio Mendes , Ronai Isobel , Hartfelder Klaus , Oldroyd Benjamin P.
Published: December 2020

Pheromones are used by many insects to mediate social interactions. In the highly eusocial honeybee (
Apis mellifera
), queen mandibular pheromone (QMP) is involved in the regulation of the reproductive and other behaviour of workers. The molecular mechanisms by which QMP acts are largely unknown. Here, we investigate how genes responsible for epigenetic modifications to DNA, RNA and histones respond to the presence of QMP in the environment. We show that several of these genes are upregulated in the honeybee brain when workers are exposed to artificial QMP. We propose that pheromonal communication systems, such as those used by social insects, evolved to respond to environmental signals by making use of existing epigenomic machineries.
Unsupervised learning of control signals and their encodings in
Caenorhabditis elegans
whole-brain recordings
Authors: Fieseler Charles , Zimmer Manuel , Kutz J. Nathan
Published: December 2020

A major goal of computational neuroscience is to understand the relationship between synapse-level structure and network-level functionality.
Caenorhabditis elegans
is a model organism to probe this relationship due to the historic availability of the synaptic structure (connectome) and recent advances in whole brain calcium imaging techniques. Recent work has applied the concept of network controllability to neuronal networks, discovering some neurons that are able to drive the network to a certain state. However, previous work uses a linear model of the network dynamics, and it is unclear if the real neuronal network conforms to this assumption. Here, we propose a method to build a global, low-dimensional model of the dynamics, whereby an underlying global linear dynamical system is actuated by temporally sparse control signals. A key novelty of this method is discovering candidate control signals that the network uses to control itself. We analyse these control signals in two ways, showing they are interpretable and biologically plausible. First, these control signals are associated with transitions between behaviours, which were previously annotated via expert-generated features. Second, these signals can be predicted both from neurons previously implicated in behavioural transitions but also additional neurons previously unassociated with these behaviours. The proposed mathematical framework is generic and can be generalized to other neurosensory systems, potentially revealing transitions and their encodings in a completely unsupervised way.
Accumulation of dead cells from contact killing facilitates coexistence in bacterial biofilms
Authors: Steinbach Gabi , Crisan Cristian , Ng Siu Lung , Hammer Brian K. , Yunker Peter J.
Published: December 2020

Bacterial communities are governed by a wide variety of social interactions, some of which are antagonistic with potential significance for bacterial warfare. Several antagonistic mechanisms, such as killing via the type VI secretion system (T6SS), require killer cells to directly contact target cells. The T6SS is hypothesized to be a highly potent weapon, capable of facilitating the invasion and defence of bacterial populations. However, we find that the efficacy of contact killing is severely limited by the material consequences of cell death. Through experiments withVibrio choleraestrains that kill via the T6SS, we show that dead cell debris quickly accumulates at the interface that forms between competing strains, preventing physical contact and thus preventing killing. While previous experiments have shown that T6SS killing can reduce a population of target cells by as much as 106-fold, we find that, as a result of the formation of dead cell debris barriers, the impact of contact killing depends sensitively on the initial concentration of killer cells. Killer cells are incapable of invading or eliminating competitors on a community level. Instead, bacterial warfare itself can facilitate coexistence between nominally antagonistic strains. While a variety of defensive strategies against microbial warfare exist, the material consequences of cell death provide target cells with their first line of defence.
Estimating the distribution of time to extinction of infectious diseases in mean-field approaches
Authors: Aliee Maryam , Rock Kat S. , Keeling Matt J.
Published: December 2020

A key challenge for many infectious diseases is to predict the time to extinction under specific interventions. In general, this question requires the use of stochastic models which recognize the inherent individual-based, chance-driven nature of the dynamics; yet stochastic models are inherently computationally expensive, especially when parameter uncertainty also needs to be incorporated. Deterministic models are often used for prediction as they are more tractable; however, their inability to precisely reach zero infections makes forecasting extinction times problematic. Here, we study the extinction problem in deterministic models with the help of an effective ‘birth–death’ description of infection and recovery processes. We present a practical method to estimate the distribution, and therefore robust means and prediction intervals, of extinction times by calculating their different moments within the birth–death framework. We show that these predictions agree very well with the results of stochastic models by analysing the simplified susceptible–infected–susceptible (SIS) dynamics as well as studying an example of more complex and realistic dynamics accounting for the infection and control of African sleeping sickness (Trypanosoma brucei gambiense).
How can contemporary climate research help understand epidemic dynamics? Ensemble approach and snapshot attractors
Authors: Kovács T.
Published: December 2020

Standard epidemic models based on compartmental differential equations are investigated under continuous parameter change as external forcing. We show that seasonal modulation of the contact parameter superimposed upon a monotonic decay needs a different description from that of the standard chaotic dynamics. The concept of snapshot attractors and their natural distribution has been adopted from the field of the latest climate change research. This shows the importance of the finite-time chaotic effect and ensemble interpretation while investigating the spread of a disease. By defining statistical measures over the ensemble, we can interpret the internal variability of the epidemic as the onset of complex dynamics—even for those values of contact parameters where originally regular behaviour is expected. We argue that anomalous outbreaks of the infectious class cannot die out until transient chaos is presented in the system. Nevertheless, this fact becomes apparent by using an ensemble approach rather than a single trajectory representation. These findings are applicable generally in explicitly time-dependent epidemic systems regardless of parameter values and time scales.