bluuebunny/crossref_metadata_2025_split huggingface dataset:
Executive summary from American Radium Society’s appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases
Authors: Milano Michael T , Chiang Veronica L S , Soltys Scott G , Wang Tony J C , Lo Simon S , Brackett Alexandria , Nagpal Seema , Chao Samuel , Garg Amit K , Jabbari Siavash , Halasz Lia M , Gephart Melanie Hayden , Knisely Jonathan P S , Sahgal Arjun , Chang Eric L 
Published: August 2020

Abstract

Background
The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.

Methods
The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.

Results
The panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for &gt;20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.

Conclusions
For patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.
Calling for a united action to defeat COVID-19
Authors: Overby Madison , Pu Qinqin , Wei Xiawei , Wu Min 
Published: August 2020

AbstractThe widespread and lingering pandemic of COVID-19 is partly due to disjointed international countermeasures and policies enforced by different countries. We have been witnessing disparity in policies and measures in different countries and regions: some are in much better control than others. To effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crises, and life and economic losses.
Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol
Authors: Dunstan Mark S , Robinson Christopher J , Jervis Adrian J , Yan Cunyu , Carbonell Pablo , Hollywood Katherine A , Currin Andrew , Swainston Neil , Feuvre Rosalind Le , Micklefield Jason , Faulon Jean-Loup , Breitling Rainer , Turner Nicholas , Takano Eriko , Scrutton Nigel S 
Published: August 2020

Abstract
Natural plant-based flavonoids have drawn significant attention as dietary supplements due to their potential health benefits, including anti-cancer, anti-oxidant and anti-asthmatic activities. Naringenin, pinocembrin, eriodictyol and homoeriodictyol are classified as (2S)-flavanones, an important sub-group of naturally occurring flavonoids, with wide-reaching applications in human health and nutrition. These four compounds occupy a central position as branch point intermediates towards a broad spectrum of naturally occurring flavonoids. Here, we report the development of Escherichia coli production chassis for each of these key gatekeeper flavonoids. Selection of key enzymes, genetic construct design and the optimization of process conditions resulted in the highest reported titers for naringenin (484 mg/l), improved production of pinocembrin (198 mg/l) and eriodictyol (55 mg/l from caffeic acid), and provided the first example of in vivo production of homoeriodictyol directly from glycerol (17 mg/l). This work provides a springboard for future production of diverse downstream natural and non-natural flavonoid targets.
Lipoarabinomannan Antigen Assay (TB-LAM) for Diagnosing Pulmonary Tuberculosis in Children with Severe Acute Malnutrition in Mozambique
Authors: Osório Dulce-Vasco , Munyangaju Isabelle , Muhiwa Argentina , Nacarapa Edy , Nhangave Amancio-Vicente , Ramos Jose-Manuel 
Published: August 2020

Abstract

Background
Tuberculosis (TB) and malnutrition are important causes of morbidity and mortality in children in the developing world.

Aims
To assess the prevalence of pulmonary TB in severely malnourished children and evaluate TB detection using the urine lipoarabinomannan antigen assay (TB-LAM).

Methods
A retrospective analysis was conducted in all pediatric inpatients with severe acute malnutrition at a rural health center in Mozambique, from February to August 2018. All children underwent a physical examination and chest X-ray, and their nasopharyngeal aspirates and stool specimens were studied for mycobacterial culture and subjected to the Xpert MTB/RIF assay. TB-LAM tests were performed on urine.

Results
Of 45 included cases, 17 (37.8%) were clinically diagnosed as pulmonary TB. None of these were detected by the Xpert MTB test; 4 (8.9%) nasopharyngeal aspirates were TB-culture positive. Seventeen patients (37.8%)—all clinically diagnosed with TB—tested positive on the TB-LAM, while 23 (51.1%) were negative. In 5 (11.1%), the urine LAM was not done.

Conclusion
Although our sample size was small, TB was diagnosed and treated in more than a third of included children. The urine TB-LAM test showed a perfect correlation with clinical diagnosis of childhood TB.

LAY SUMMARY
Severe acute malnutrition makes children more vulnerable to tuberculosis (TB) infections, but it is difficult to detect TB in children because they cannot always cough up phlegm, which is used in diagnostic processes. This study aimed to find out how many severely malnourished children had TB in Gaza, Mozambique, and to test the accuracy of a less-used diagnostic test: the lipoarabinomannan assay (TB-LAM). Of the 45 severely malnourished children who were admitted to our hospital, 17 were diagnosed with TB by their doctor. The TB-LAM corroborated the clinical diagnosis in all cases, while the other tests (Xpert MTB/RIF assay) and cultures failed to detect most of them. Overall, more than a third of severely malnourished children had TB, and the TB-LAM test—a simple, point-of-care method—was a highly accurate way to diagnose them. While larger studies are needed to confirm these results, our findings suggest that the TB-LAM could vastly improve TB diagnosis in malnourished children.
Neonatal and Maternal Composite Adverse Outcomes Among Low-Risk Nulliparous Women Compared With Multiparous Women at 39–41 Weeks of Gestation
Authors: Chauhan Suneet P. , Rice Madeline Murguia , Grobman William A. , Bailit Jennifer , Reddy Uma M. , Wapner Ronald J. , Varner Michael W. , Thorp John M. , Caritis Steve N. , Prasad Mona , Tita Alan T. N. , Saade George R. , Sorokin Yoram , Rouse Dwight J. , Tolosa Jorge E. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: August 2020

OBJECTIVE:
To estimate whether the frequency of adverse maternal and neonatal outcomes differs between low-risk nulliparous and multiparous women at 39–41 weeks of gestation.

METHODS:
This is a secondary analysis of an observational obstetrics cohort of maternal–neonatal dyads at 25 hospitals. Low-risk women with nonanomalous singletons who delivered between 39 0/7 and 41 6/7 weeks of gestation were included. The composite neonatal adverse outcome included 5-minute Apgar score less than five, ventilator support or cardiopulmonary resuscitation, seizure, hypoxic ischemic encephalopathy, sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, necrotizing enterocolitis, birth injury or perinatal death. The composite maternal adverse outcome included infection, third- or fourth-degree perineal laceration, thromboembolism, transfusion of blood products, or maternal death. Small for gestational age (SGA), large for gestational age (LGA), and shoulder dystocia requiring maneuvers were also evaluated. Multivariable regression was used to estimate adjusted relative risks (aRRs) and adjusted odds ratios (aORs) with 95% CIs.

RESULTS:
Of the 115,502 women in the overall cohort, 39,870 (34.5%) met eligibility criteria for this analysis; 18,245 (45.8%) were nulliparous. The risk of the composite neonatal adverse outcome (1.5% vs 1.0%, aRR 1.80, 95% CI 1.48–2.19), composite maternal adverse outcome (15.1% vs 3.3%, aRR 5.04, 95% CI 4.62–5.49), and SGA (8.9% vs 5.8%, aOR 1.45, 95% CI 1.33–1.57) was significantly higher in nulliparous than multiparous patients. The risk of LGA (aOR 0.65, 95% CI 0.60–0.71) and shoulder dystocia with maneuvers (aRR 0.68, 95% CI 0.60–0.77) was significantly lower in nulliparous rather than multiparous patients.

CONCLUSION:
The risk of composite adverse outcomes and SGA among low-risk nulliparous women at 39–41 weeks of gestation is significantly higher than among multiparous counterparts. However, nulliparous women had a lower risk of shoulder dystocia with maneuvers and LGA.
Per- and polyfluoroalkyl substances in drinking water and birthweight in the US
Authors: Zhu Yachen , Bartell Scott M. 
Published: August 2020

Background:
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population, and were detected in public water systems serving approximately 16.5 million US residents during 2013–2015. Low birthweight was associated with PFAS exposures in previous studies.

Methods:
Birthweights for singleton births during 2013–2015 were obtained from CDC WONDER, multiply stratified by county, maternal age, race, education, smoking status, and parity. PFAS water concentrations were obtained from EPA UCMR3 database and aggregated by county. Multiple regression weighted by inverse variance was used to produce effect estimates equivalent to those that would be obtained from individual-level data on birthweight and confounders.

Results:
Adjusting for stratification demographic confounders (maternal age, race, education, smoking status, and parity), we found an average change in birthweight of 0.9 g (95% confidence interval [CI] = −0.5, 2.2), −1.3 g (−1.6, −0.9), −3.8 g (−4.9, −2.7), and −3.8 g (−4.3, −3.3) per ng/L increase in the population-weighted average perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid in public water supplies by county, respectively. We found an average change in birthweight of −1.0 g (95% CI = −1.2, −0.8) per ng/L increase in the sum of perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid concentrations in public water supplies.

Conclusions:
The direction and magnitude of association between PFAS and birthweight varied by PFAS chemical in this study. Conclusions are tempered by inherent limitations of the 2 public-use datasets, and by the sensitivity of our results to alternative methods such as mutual adjustment for co-exposures.
Diurnal Temperature Variation and Using Fever to Screen for Infectious Diseases
Authors: Miller Aaron C. , Koeneman Scott , Polgreen Philip M. 
Published: August 2020

AbstractFevers have been used as marker of disease state for hundreds of years and are frequently used to screen for infectious diseases during infectious disease outbreaks. However, body temperature and fevers have been shown to vary over the course of a day and across individuals by age, sex and other characteristics. The objective of this paper is to describe the individual variation in diurnal temperature patterns during episodes of febrile activity using a database of millions of recorded temperatures across the United States. We then model the probability of recording a fever during a single reading at given time for individuals who are experiencing a febrile episode. We find a wide variation in body temperatures over the course of a day and across individual characteristics. Similarly, the likelihood of recording a fever may vary widely by the time of day when the reading is taken and by an individual’s age or sex. These results suggest diurnal temperature variation and demographics should be considered when using body temperature to screen for disease, especially for diseases that are contagious.
Testing for SARS-CoV-2 in care home staff and residents in English care homes: A service evaluation
Authors: Smith Emma , Aldus Clare F , Brainard Julii , Dunham Sharon , Hunter Paul R , Steel Nicholas , Everden Paul 
Published: August 2020

BackgroundCOVID-19 has especially affected care home residents.AimTo evaluate a nurse-led Enhanced Care Home Team (ECHT) enhanced SARS-CoV-2 testing strategy.Design and settingService evaluation in care homes in Norfolk UK.MethodResidents and staff received nose and throat swab tests (7 April to 29 June 2020). Resident test results were linked with symptoms on days 0-14 after test and mortality to 13 July 2020.ResultsResidents (n=518) in 44 homes and staff (n=340) in 10 care homes were tested. SARS-CoV-2 positivity was identified in 103 residents in 14 homes and 49 staff in seven homes. Of 103 SARS-CoV-2+ residents, just 38 had typical symptom(s) at time of test (new cough and/or fever). Amongst 54 residents who were completely asymptomatic when tested, 12 (22%) developed symptoms within 14 days. Compared to SARS-CoV-2 negative residents, SARS-CoV-2+ residents were more likely to exhibit typical symptoms (new cough (n=26, p=0.001); fever (n=24, p=<0.001)) or as ‘generally unwell’ (n=18, p=0.001). Of 38 resident deaths, 21 (55%) were initially attributed to SARS-CoV-2, all of whom tested SARS-CoV-2+. One death not initially attributed to SARS-CoV-2 also tested positive.ConclusionTesting identified asymptomatic and pre-symptomatic SARS-CoV-2+ residents and staff. Being ‘generally unwell’ was common amongst symptomatic residents and may indicate SARS-CoV-2 infection in older people in the absence of more ‘typical’ symptoms. Where a resident appears generally unwell SARS-CoV-2-infection should be suspected. Protocols for testing involved integrated health and social care teams.
Novel Diffuse White Matter Abnormality Biomarker at Term-Equivalent Age Enhances Prediction of Long-term Motor Development in Children Born Very Preterm
Authors: Parikh Nehal A. , Harpster Karen , He Lili , Illapani Venkata Sita Priyanka , Khalid Fatima Chughtai , Klebanoff Mark A. , O’Shea T. Michael , Altaye Mekibib 
Published: August 2020

ABSTRACTOur objective was to evaluate the independent prognostic value of a novel MRI biomarker – objectively diagnosed diffuse white matter abnormality volume (DWMA; diffuse excessive high signal intensity) – for prediction of motor outcomes in very preterm infants. We prospectively enrolled a geographically-based cohort of very preterm infants without severe brain injury and born before 32 weeks gestational age. Structural brain MRI was obtained at term-equivalent age and DWMA volume was objectively quantified using a published validated algorithm. These results were compared with visually classified DWMA. We used multivariable linear regression to assess the value of DWMA volume, independent of known predictors, to predict motor development as assessed using the Bayley Scales of Infant & Toddler Development, Third Edition at 3 years of age. The mean (SD) gestational age of the cohort was 28.3 (2.4) weeks. In multivariable analyses, controlling for gestational age, sex, and abnormality on structural MRI,DWMA volume was an independent prognostic biomarker of Bayley Motor scores (β= –12.59 [95% CI: –18.70, –6.48] R2=0.41). Conversely, visually classified DWMA was not predictive of motor development. In conclusion, objectively quantified DWMA is an independent prognostic biomarker of long-term motor development in very preterm infants and warrants further study.
ANMerge: A comprehensive and accessible Alzheimer’s disease patient-level dataset
Authors: Birkenbihl Colin , Westwood Sarah , Shi Liu , Nevado-Holgado Alejo , Westman Eric , Lovestone Simon , Hofmann-Apitius Martin 
Published: August 2020

AbstractBackgroundAccessible datasets are of fundamental importance to the advancement of Alzheimer’s disease (AD) research. The AddNeuroMed consortium conducted a longitudinal observational cohort study with the aim to discover AD biomarkers. During this study, a broad selection of data modalities was measured including clinical assessments, magnetic resonance imaging, genotyping, transcriptomic profiling and blood plasma proteomics. Some of the collected data were shared with third-party researchers. However, this data was incomplete, erroneous and lacking in interoperability.MethodsWe systematically addressed several limitations of the originally shared data and provide additional unreleased data to enhance the patient-level dataset.ResultsIn this work, we publish and describe ANMerge, a new version of the AddNeuroMed dataset. ANMerge includes multimodal data from 1702 study participants and is accessible to the research community via a centralized portal.ConclusionsANMerge is an information rich patient-level data resource that can serve as a discovery and validation cohort for data-driven AD research, such as for example machine learning and artificial intelligence approaches.ANMerge can be downloaded here: https://doi.org/10.7303/syn22252881
Inhomogeneous mixing and asynchronic transmission between local outbreaks account for the spread of COVID-19 epidemics
Authors: Mendoza Carlos I. 
Published: August 2020

AbstractThe ongoing epidemic of COVID-19 originated in China has reinforced the need to develop epidemiological models capable of describing the progression of the disease to be of use in the formulation of mitigation policies. Here, this problem is addressed using a metapopulation approach to show that the delay in the transmission of the spread between different subsets of the total population, can be incorporated into a SIR framework through a time-dependent transmission rate. Thus, the reproduction number decreases with time despite the population dynamics remains uniform and the depletion of susceptible individuals is small. The obtained results are consistent with the early subexponential growth observed in the cumulated number of confirmed cases even in the absence of containment measures. We validate our model by describing the evolution of the COVID-19 using real data from different countries with an emphasis in the case of Mexico and show that it describes correctly also the long-time dynamics of the spread. The proposed model yet simple is successful at describing the onset and progression of the outbreak and considerably improves accuracy of predictions over traditional compartmental models. The insights given here may probe be useful to forecast the extent of the public health risks of epidemics and thus improving public policy-making aimed at reducing such risks.
SWITCHES: Searchable Web Interface for Topologies of CHEmical Switches
Authors: HarshaRani G.V. , Moza S. , Ramakrishnan N. , Bhalla U.S. 
Published: August 2020

ABSTRACTBistable biochemical switches are key motifs in cellular state decisions and long-term storage of cellular ‘memory’. There are a few known biological switches that have been well characterized, however these examples are insufficient for systematic surveys of properties of these important systems. Here we present a resource of all possible bistable biochemical reaction networks with up to 6 reactions between 3 molecules, and 3 reactions between 4 molecules. Over 35,000 reaction topologies were constructed by identifying unique combinations of reactions between a fixed number of molecules. Then, these topologies were populated with rates within a biologically realistic range. The Searchable Web Interface for Topologies of CHEmical Switches (SWITCHES,https://switches.ncbs.res.in) provides a bistability and parameter analysis of over 7 million models from this systematic survey of chemical reaction space. This database will be useful for theoreticians interested in analyzing stability in chemical systems and also experimentalists for creating robust synthetic biological switches.Availability and ImplementationFreely available on the web athttps://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz, and Apache, with all major browsers supported.Supplementary InformationNot applicable.
Concerted evolution reveals co-adapted amino acid substitutions in Na+K+-ATPase of frogs that prey on toxic toads
Authors: Mohammadi Shabnam , Yang Lu , Harpak Arbel , Herrera-Álvarez Santiago , Rodríguez-Ordoñez María del Pilar , Peng Julie , Zhang Karen , Storz Jay F. , Dobler Susanne , Crawford Andrew J. , Andolfatto Peter 
Published: August 2020

ABSTRACTGene duplication is an important source of evolutionary innovation, but the adaptive division-of-labor between duplicates can be opposed by ongoing gene conversion between them. Here we document a tandem duplication of Na+,K+-ATPase subunit α1 (ATP1A1) shared by frogs in the genusLeptodactylus, a group of species that feeds on toxic toads. One ATP1A1 paralog evolved resistance to toad toxins while the other paralog retained ancestral susceptibility. We show that the twoLeptodactylusparalogs are distinguished by 12 amino acid substitutions that were maintained by strong selection that counteracted the homogenizing effect of gene conversion. Protein-engineering experiments show that two major-effect substitutions confer toxin resistance, whereas the 10 additional substitutions mitigate deleterious pleiotropic effects on enzyme function. Our results highlight how trans-specific, neofunctionalized gene duplicates can provide unique insights into interactions between adaptive substitutions and the genetic backgrounds on which they arise.One Sentence SummarySelection counteracts gene conversion to maintain an adaptive division-of-labor between tandemly duplicated genes.