bluuebunny/crossref_metadata_2025 huggingface dataset:
A marginally fast-cooling proton–synchrotron model for prompt GRBs
Authors: Florou Ioulia , Petropoulou Maria , Mastichiadis Apostolos
Published: May 2021

A small fraction of gamma-ray bursts (GRBs) with available data down to soft X-rays (∼0.5 keV) has been shown to feature a spectral break in the low-energy part (∼1–10 keV) of their prompt emission spectrum. The overall spectral shape is consistent with optically thin synchrotron emission from a population of particles that have cooled on a time-scale comparable to the dynamic time to energies that are still much higher than their rest-mass energy (marginally fast cooling regime). We consider a hadronic scenario and investigate if the prompt emission of these GRBs can originate from relativistic protons that radiate synchrotron in the marginally fast cooling regime. Using semi-analytical methods, we derive the source parameters, such as magnetic field strength and proton luminosity, and calculate the high-energy neutrino emission expected in this scenario. We also investigate how the emission of secondary pairs produced by photopion interactions and γγ pair production affect the broad-band photon spectrum. We support our findings with detailed numerical calculations. Strong modification of the photon spectrum below the break energy due to the synchrotron emission of secondary pairs is found, unless the bulk Lorentz factor is very large (Γ ≳ 103). Moreover, this scenario predicts unreasonably high Poynting luminosities because of the strong magnetic fields (106–107 G) that are necessary for the incomplete proton cooling. Our results strongly disfavour marginally fast cooling protons as an explanation of the low-energy spectral break in the prompt GRB spectra.
Late-time radio observations of the short GRB 200522A: constraints on the magnetar model
Authors: Bruni G , O’Connor B , Matsumoto T , Troja E , Piran T , Piro L , Ricci R
Published: May 2021

GRB 200522A is a short duration gamma-ray burst (GRB) at redshift z= 0.554 characterized by a bright infrared counterpart. A possible, although not unambiguous, interpretation of the observed emission is the onset of a luminous kilonova powered by a rapidly rotating and highly magnetized neutron star, known as magnetar. A bright radio flare, arising from the interaction of the kilonova ejecta with the surrounding medium, is a prediction of this model. Whereas the available data set remains open to multiple interpretations (e.g. afterglow, r-process kilonova, magnetar-powered kilonova), long-term radio monitoring of this burst may be key to discriminate between models. We present our late-time upper limit on the radio emission of GRB 200522A, carried out with the Karl G. Jansky Very Large Array at 288 d after the burst. For kilonova ejecta with energy Eej $\approx 10^{53}\, \rm erg$, as expected for a long-lived magnetar remnant, we can already rule out ejecta masses $M_{\rm ej}\lesssim 0.03\, \mathrm{M}_\odot$ for the most likely range of circumburst densities n ≳ 10−3 cm−3. Observations on timescales of ≈ 3–10 yr after the merger will probe larger ejecta masses up to Mej ∼ 0.1 M⊙, providing a robust test to the magnetar scenario.
LipidSig: a web-based tool for lipidomic data analysis
Authors: Lin Wen-Jen , Shen Pei-Chun , Liu Hsiu-Cheng , Cho Yi-Chun , Hsu Min-Kung , Lin I-Chen , Chen Fang-Hsin , Yang Juan-Cheng , Ma Wen-Lung , Cheng Wei-Chung
Published: May 2021

With the continuing rise of lipidomic studies, there is an urgent need for a useful and comprehensive tool to facilitate lipidomic data analysis. The most important features making lipids different from general metabolites are their various characteristics, including their lipid classes, double bonds, chain lengths, etc. Based on these characteristics, lipid species can be classified into different categories and, more interestingly, exert specific biological functions in a group. In an effort to simplify lipidomic analysis workflows and enhance the exploration of lipid characteristics, we have developed a highly flexible and user-friendly web server called LipidSig. It consists of five sections, namely, Profiling, Differential Expression, Correlation, Network and Machine Learning, and evaluates lipid effects on cellular or disease phenotypes. One of the specialties of LipidSig is the conversion between lipid species and characteristics according to a user-defined characteristics table. This function allows for efficient data mining for both individual lipids and subgroups of characteristics. To expand the server's practical utility, we also provide analyses focusing on fatty acid properties and multiple characteristics. In summary, LipidSig is expected to help users identify significant lipid-related features and to advance the field of lipid biology. The LipidSig webserver is freely available at http://chenglab.cmu.edu.tw/lipidsig
Nutrient cycling is an important mechanism for homeostasis in plant cells
Authors: Dreyer Ingo
Published: May 2021

Homeostasis in living cells refers to the steady state of internal, physical, and chemical conditions. It is sustained by self-regulation of the dynamic cellular system. To gain insight into the homeostatic mechanisms that maintain cytosolic nutrient concentrations in plant cells within a homeostatic range, we performed computational cell biology experiments. We mathematically modeled membrane transporter systems and simulated their dynamics. Detailed analyses of ‘what-if’ scenarios demonstrated that a single transporter type for a nutrient, irrespective of whether it is a channel or a cotransporter, is not sufficient to calibrate a desired cytosolic concentration. A cell cannot flexibly react to different external conditions. Rather, at least two different transporter types for the same nutrient, which are energized differently, are required. The gain of flexibility in adjusting a cytosolic concentration was accompanied by the establishment of energy-consuming cycles at the membrane, suggesting that these putatively “futile” cycles are not as futile as they appear. Accounting for the complex interplay of transporter networks at the cellular level may help design strategies for increasing nutrient use efficiency of crop plants.
Phylloquinone is the principal Mehler reaction site within photosystem I in high light
Authors: Kozuleva Marina , Petrova Anastasia , Milrad Yuval , Semenov Alexey , Ivanov Boris , Redding Kevin E , Yacoby Iftach
Published: May 2021

Photosynthesis is a vital process, responsible for fixing carbon dioxide, and producing most of the organic matter on the planet. However, photosynthesis has some inherent limitations in utilizing solar energy, and a part of the energy absorbed is lost in the reduction of O2 to produce the superoxide radical (O2•−) via the Mehler reaction, which occurs principally within photosystem I (PSI). For decades, O2 reduction within PSI was assumed to take place solely in the distal iron–sulfur clusters rather than within the two asymmetrical cofactor branches. Here, we demonstrate that under high irradiance, O2 photoreduction by PSI primarily takes place at the phylloquinone of one of the branches (the A-branch). This conclusion derives from the light dependency of the O2 photoreduction rate constant in fully mature wild-type PSI from Chlamydomonas reinhardtii, complexes lacking iron–sulfur clusters, and a mutant PSI, in which phyllosemiquinone at the A-branch has a significantly longer lifetime. We suggest that the Mehler reaction at the phylloquinone site serves as a release valve under conditions where both the iron–sulfur clusters of PSI and the mobile ferredoxin pool are highly reduced.
Using Data from Reddit, Public Deliberation, and Surveys to Measure Public Opinion about Autonomous Vehicles
Authors: Chen Kaiping , Tomblin David
Published: May 2021

When and how can researchers synthesize survey data with analyses of social media content to study public opinion, and when and how can social media data complement surveys to better inform researchers and policymakers? This paper explores how public opinions might differ between survey and social media platforms in terms of content and audience, focusing on the test case of opinions about autonomous vehicles. The paper first extends previous overviews comparing surveys and social media as measurement tools to include a broader range of survey types, including surveys that result from public deliberation, considering the dialogic characteristics of different social media, and the range of issue publics and marginalized voices that different surveys and social media forums can attract. It then compares findings and implications from analyses of public opinion about autonomous vehicles from traditional surveys, results of public deliberation, and analyses of Reddit posts, applying a newly developed computational text analysis tool. Findings demonstrate that social media analyses can both help researchers learn more about issues that are uncovered by surveys and also uncover opinions from subpopulations with specialized knowledge and unique orientations toward a subject. In light of these findings, we point to future directions on how researchers and policymakers can synthesize survey and social media data, and the corresponding data integration techniques, to study public opinion.
Fundamental Arbitrage under the Microscope: Evidence from Detailed Hedge Fund Transaction Data
Authors: von Beschwitz Bastian , Lunghi Sandro , Schmidt Daniel
Published: May 2021

We exploit detailed transaction and position data for a sample of long-short equity hedge funds to study the trading activity of fundamental investors. We find that hedge funds exhibit skill in opening positions, but that they close their positions too early, thereby forgoing about one-third of the trades’ potential profitability. We explain this behavior with the limits of arbitrage: hedge funds close positions early in order to reallocate their capital to more profitable investments and/or to accommodate tightened financial constraints. Consistent with this view, we document that hedge funds leave more money on the table after opening new positions, negative returns, or increases in funding constraints and volatility. (JEL G11, G12, G14, G15)
How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants
Authors: Charpentier Caroline J , Faulkner Paul , Pool Eva R , Ly Verena , Tollenaar Marieke S , Kluen Lisa M , Fransen Aniek , Yamamori Yumeya , Lally Níall , Mkrtchian Anahit , Valton Vincent , Huys Quentin J M , Sarigiannidis Ioannis , Morrow Kelly A , Krenz Valentina , Kalbe Felix , Cremer Anna , Zerbes Gundula , Kausche Franziska M , Wanke Nadine , Giarrizzo Alessio , Pulcu Erdem , Murphy Susannah , Kaltenboeck Alexander , Browning Michael , Paul Lynn K , Cools Roshan , Roelofs Karin , Pessoa Luiz , Harmer Catherine J , Chase Henry W , Grillon Christian , Schwabe Lars , Roiser Jonathan P , Robinson Oliver J , O’Doherty John P
Published: May 2021

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.
Low competitive status elicits aggression in healthy young men: behavioural and neural evidence
Authors: Buades-Rotger Macià , Göttlich Martin , Weiblen Ronja , Petereit Pauline , Scheidt Thomas , Keevil Brian G , Krämer Ulrike M
Published: May 2021

Winners are commonly assumed to compete more aggressively than losers. Here, we find overwhelming evidence for the opposite. We first demonstrate that low-ranking teams commit more fouls than they receive in top-tier soccer, ice hockey and basketball men’s leagues. We replicate this effect in the laboratory, showing that male participants deliver louder sound blasts to a rival when placed in a low-status position. Using neuroimaging, we characterize brain activity patterns that encode competitive status as well as those that facilitate status-dependent aggression in healthy young men. These analyses reveal three key findings. First, anterior hippocampus and striatum contain multivariate representations of competitive status. Second, interindividual differences in status-dependent aggression are linked with a sharper status differentiation in the striatum and with greater reactivity to status-enhancing victories in the dorsal anterior cingulate cortex. Third, activity in ventromedial, ventrolateral and dorsolateral prefrontal cortex is associated with trial-wise increases in status-dependent aggressive behaviour. Taken together, our results run counter to narratives glorifying aggression in competitive situations. Rather, we show that those in the lower ranks of skill-based hierarchies are more likely to behave aggressively and identify the potential neural basis of this phenomenon.
Analysis of Paralogs in Target Enrichment Data Pinpoints Multiple Ancient Polyploidy Events in Alchemilla s.l. (Rosaceae)
Authors: Morales-Briones Diego F , Gehrke Berit , Huang Chien-Hsun , Liston Aaron , Ma Hong , Marx Hannah E , Tank David C , Yang Ya
Published: May 2021

Target enrichment is becoming increasingly popular for phylogenomic studies. Although baits for enrichment are typically designed to target single-copy genes, paralogs are often recovered with increased sequencing depth, sometimes from a significant proportion of loci, especially in groups experiencing whole-genome duplication (WGD) events. Common approaches for processing paralogs in target enrichment data sets include random selection, manual pruning, and mainly, the removal of entire genes that show any evidence of paralogy. These approaches are prone to errors in orthology inference or removing large numbers of genes. By removing entire genes, valuable information that could be used to detect and place WGD events is discarded. Here, we used an automated approach for orthology inference in a target enrichment data set of 68 species of Alchemilla s.l. (Rosaceae), a widely distributed clade of plants primarily from temperate climate regions. Previous molecular phylogenetic studies and chromosome numbers both suggested ancient WGDs in the group. However, both the phylogenetic location and putative parental lineages of these WGD events remain unknown. By taking paralogs into consideration and inferring orthologs from target enrichment data, we identified four nodes in the backbone of Alchemilla s.l. with an elevated proportion of gene duplication. Furthermore, using a gene-tree reconciliation approach, we established the autopolyploid origin of the entire Alchemilla s.l. and the nested allopolyploid origin of four major clades within the group. Here, we showed the utility of automated tree-based orthology inference methods, previously designed for genomic or transcriptomic data sets, to study complex scenarios of polyploidy and reticulate evolution from target enrichment data sets.[Alchemilla; allopolyploidy; autopolyploidy; gene tree discordance; orthology inference; paralogs; Rosaceae; target enrichment; whole genome duplication.]
Psychosocial correlates of objectively measured in-school and out-of-school physical activity among Brazilian adolescents
Authors: Lopes Marcus V V , da Costa Bruno G G , Knebel Margarethe T G , Matias Thiago S , Silva Kelly S
Published: May 2021

Physical activity is influenced by an interplay of time and setting, thus, the role of psychosocial factors on behavior is expected to vary across the day. This cross-sectional study identified the psychosocial correlates of time spent in physical activity during in-school (i.e., 08:00–11:59) and out-of-school (i.e., 12:00–22:00) time segments. The sample consisted of adolescents (7th to 9th grade) of two public schools in Florianópolis, Brazil. Accelerometer measured light-intensity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) were estimated. Psychosocial correlates of physical activity (i.e., outcome expectations, attitude, self-efficacy, support from parents, and support from peers) were self-reported. Linear mixed models were applied and interaction effects of gender and age were also analyzed. From a total of 194 participants, 138 and 112 provided in-school and out-of-school valid data, respectively. Outcome expectations were associated with out-of-school MVPA (β = 0.18; p = .006). Age interaction effects were observed for the associations between outcome expectations and out-of-school LPA (β = 0.21; p = .009) and between self-efficacy and out-of-school MVPA (β = 0.19; p = .009). In conclusion, psychosocial correlates were positively associated with out-of-school physical activity and the effects varied according to age. No psychosocial correlates were identified for LPA and MVPA performed during schooltime.
RETINAL FLUID AND THICKNESS AS MEASURES OF DISEASE ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kaiser Peter K. , Wykoff Charles C. , Singh Rishi P. , Khanani Arshad M. , Do Diana V. , Patel Hersh , Patel Nikhil
Published: May 2021

Purpose:

Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration, as evidenced by clinical trials that have used these features for inclusion criteria, retreatment criteria, and outcome measures of the efficacy of intravitreal injections of anti–vascular endothelial growth factor agents.

Methods:

A literature review of anatomical measures of disease activity was conducted.

Results:

Treatment goals for neovascular age-related macular degeneration include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. The change in retinal thickness has been found to correlate with the change in the visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity, whereas the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice.

Conclusion:

Retinal thickness and retinal fluid are common anatomical measures of disease activity in neovascular age-related macular degeneration. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in neovascular age-related macular degeneration.
Pharmacological Management of Heart Failure: A Century of Expert Opinions in Cecil Textbook of Medicine
Authors: Manu Peter , Rogozea Liliana M. , Dan Gheorghe-Andrei
Published: May 2021

Background:

Drug therapy for heart failure influences quality of life and work potential of affected persons and has contributed to decrease in hospitalizations and cardiovascular mortality. The current approach is the result of incremental progress in understanding the pathophysiology of the syndrome, introduction of new molecules, and repurposing existing drugs.

Study Question:

What are the milestones of the changes in the expert clinicians' approach to the pharmacological management in the past century?

Study Design:

To determine the changes in the experts' approach to the management of heart failure, as presented in a widely used textbook in the United States.

Data Sources:

The chapters on the management of heart failure in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.

Results:

In 1927, heart failure was treated with powdered leaf or tincture of digitalis, mercury chloride, and theophylline. Patients with acute pulmonary edema received injections of atropine, adrenaline, and ouabain. The therapeutic milestones in heart failure were the introduction of loop diuretics and aldosterone antagonists (1971), vasodilator treatment with hydralazine and nitroglycerine (1979–1985), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and selective beta-adrenergic blockers (1992–2000), and sacubitril–valsartan (2016). For acute pulmonary edema, the durable milestone was the treatment with morphine and furosemide (1971).

Conclusions:

The pharmacological management of heart failure in the past century has progressed in fits and starts, with latent periods between significant advances lasting 8–40 years. In chronological order, the major advances were efficient diuresis, afterload reduction, and blunting the neurohormonal response to hemodynamic stress and cardiac remodeling.
Design of a Randomized Controlled Trial of Percutaneous Posterior Tibial Nerve Stimulation for the Treatment of Refractory Fecal Incontinence in Women: The NeurOmodulaTion for Accidental Bowel Leakage Study
Authors: Zyczynski Halina M. , Arya Lily A. , Lukacz Emily S. , Richter Holly E. , Rahn David D. , Sung Vivian W. , Visco Anthony G. , Shaffer Amanda , Jelovsek J. Eric , Rogers Rebecca , Mazloomdoost Donna , Gantz Marie G. ,   for the Eunice Kennedy Shriver NICHD Pelvic Floor Disorders Network (PFDN)
Published: May 2021

Objectives

High-level evidence for second-line noninvasive treatments for fecal incontinence in women is limited. We present the rationale for and design of the NeuromOdulaTion for Accidental Bowel Leakage trial, a randomized controlled trial of percutaneous tibial nerve stimulation (PTNS) and validated sham stimulation in women with refractory accidental bowel leakage.

Methods

The rationale and goals for a 2-part study with a run-in phase, use of a generic pulse generator for PTNS and sham stimulation, masking, participant inclusion, primary and secondary outcome measures, and adverse event collection are described. A superiority design will be used to compare change from baseline in St. Mark’s score after 12 weekly stimulation sessions between PTNS and sham. Responders to initial treatment (PTNS or sham) will be assigned to scheduled or “as needed” intervention for up to 1 year. Secondary outcome measures include incontinence episodes and other bowel events recorded in a 14-day electronic bowel diary, general and condition-specific quality of life instruments, adaptive behavior, global impression of improvement, symptom control, and sexual function.

Results

Sample size calculations determined that 165 participants (110 PTNS and 55 sham) would provide 90% power to detect greater than or equal to 4-point difference between PTNS and sham in change from baseline in St. Mark’s score at 12 weeks.

Conclusions

The methods for the NeuromOdulaTion for Accidental Bowel Leakage trial will provide high-level evidence of the effectiveness and optimal maintenance therapy schedule of a low-cost PTNS protocol in community-dwelling women seeking second-line intervention for refractory accidental bowel leakage.
Framing in multiple public goods games and donation to charities
Authors: Maciel Cardoso F. , Meloni S. , Gracia-Lázaro C. , Antonioni A. , Cuesta J. A. , Sánchez A. , Moreno Y.
Published: May 2021

The vast amount of research devoted to public goods games has shown that contributions may be dramatically affected by varying framing conditions. This is particularly relevant in the context of donations to charities and non-governmental organizations. Here, we design a multiple public goods experiment by introducing five types of funds, each differing in the fraction of the contribution that is donated to a charity. We found that people contribute more to public goods when the associated social donations are presented as indirect rather than as direct donations. At the same time, the fraction of the donations devoted to charity is not affected by the framing. We have also found that, on average, women contribute to public goods and donate to charity significantly more than men. These findings are of potential interest to the design of social investment tools, in particular for charities to ask for better institutional designs from policy makers.
Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
Authors: Goubet Anne-Gaëlle , Dubuisson Agathe , Geraud Arthur , Danlos François-Xavier , Terrisse Safae , Alves Costa Silva Carolina , Drubay Damien , Touri Lea , Picard Marion , Mazzenga Marine , Silvin Aymeric , Dunsmore Garett , Haddad Yacine , Pizzato Eugenie , Ly Pierre , Flament Caroline , Melenotte Cléa , Solary Eric , Fontenay Michaela , Garcia Gabriel , Balleyguier Corinne , Lassau Nathalie , Maeurer Markus , Grajeda-Iglesias Claudia , Nirmalathasan Nitharsshini , Aprahamian Fanny , Durand Sylvère , Kepp Oliver , Ferrere Gladys , Thelemaque Cassandra , Lahmar Imran , Fahrner Jean-Eudes , Meziani Lydia , Ahmed-Belkacem Abdelhakim , Saïdani Nadia , La Scola Bernard , Raoult Didier , Gentile Stéphanie , Cortaredona Sébastien , Ippolito Giuseppe , Lelouvier Benjamin , Roulet Alain , Andre Fabrice , Barlesi Fabrice , Soria Jean-Charles , Pradon Caroline , Gallois Emmanuelle , Pommeret Fanny , Colomba Emeline , Ginhoux Florent , Kazandjian Suzanne , Elkrief Arielle , Routy Bertrand , Miyara Makoto , Gorochov Guy , Deutsch Eric , Albiges Laurence , Stoclin Annabelle , Gachot Bertrand , Florin Anne , Merad Mansouria , Scotte Florian , Assaad Souad , Kroemer Guido , Blay Jean-Yves , Marabelle Aurélien , Griscelli Frank , Zitvogel Laurence , Derosa Lisa
Published: May 2021

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and non-cancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer, 89% COVID-19+), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Chronic viral RNA carriers exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of non-conventional monocytes and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T helper cells, and non-naive Granzyme B+ FasL+, EomehighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Manual curation of TCGA treatment data and identification of potential markers of therapy response
Authors: Moiso Enrico
Published: May 2021

The Cancer Genome Atlas (TCGA) represents a valuable source of genomic and clinical data across different tumor types. In this work, TCGA treatment response information have been manually curated in order to be computationally exploited. Drug names were manually corrected to remove typos and to unify commercial and molecule names. Moreover the drug therapy related information has been reorganized in a table to facilitate readability and analysis. The data were benchmarked with uni and multivariable statistical analyses to identify putative markers of response.
Smart Testing with Vaccination: A Bandit Algorithm for Active Sampling for Managing COVID-19
Authors: Wang Yingfei , Yahav Inbal , Padmanabhan Balaji
Published: May 2021

This paper presents methods to choose individuals to test for infection during a pandemic such as COVID-19, characterized by high contagion and presence of asymptomatic carriers. The smart-testing ideas presented here are motivated by active learning and multi-armed bandit techniques in machine learning. Our active sampling method works in conjunction with vaccination and quarantine policies and is adaptive to changes in real-time data. Using a data-driven agent-based model simulating New York City we show that the algorithm samples individuals to test in a manner that rapidly traces infected individuals. The results show that smart-testing is effective in significantly reducing infection and death rates as compared to current policies, with or without vaccination.
Does the Data Tell the True Story? A Modelling Study of Early COVID-19 Pandemic Suppression and Mitigation Strategies in Ghana
Authors: Frempong Nana Kena , Acheampong Theophilus , Apenteng Ofosuhene O. , Nakua Emmanuel , Amuasi John H.
Published: May 2021

This paper uses publicly available data and various statistical models to estimate the basic reproduction number (R0) and other disease parameters for the early COVID-19 pandemic outbreak in Ghana. We also test the effectiveness of government imposition of public health measures to reduce the risk of transmission and impact of the pandemic, especially in the early phase. R0 is estimated from the statistical model as 3.21 using a 0.147 estimated growth rate [95% C.I.: 0.137-0.157] and a 15-day time to recovery after COVID-19 infection. This estimate of the initial R0 is consistent with others reported in the literature from other parts of Africa, China and Europe. Our results also indicate that COVID-19 transmission reduced consistently in Ghana after the imposition of public health interventions - such as border restrictions, intra-city movement, quarantine and isolation - during the first phase of the pandemic from March to May 2020. However, the time-dependent reproduction number (Rt) beyond mid-May 2020 does not represent the true situation given there was not a consistent testing regime in place. This is also confirmed by our Jack-knife bootstrap estimates which show that the positivity rate over-estimates the true incidence rate from mid-May 2020. Given concerns about virus mutations, delays in vaccination and a possible new wave of the pandemic, there is a need for systematic testing of a representative sample of the population to monitor the reproduction number. There is also an urgent need to increase the availability of testing for the general population to enable early detection, isolation and treatment of infected individuals to reduce progression to severe disease and mortality.
ATLAS: An automated association test using probabilistically linked health records with application to genetic studies
Authors: Zhang Harrison G. , Hejblum Boris P. , Weber Griffin M. , Palmer Nathan P. , Churchill Susanne E. , Szolovits Peter , Murphy Shawn N. , Liao Katherine P. , Kohane Isaac S. , Cai Tianxi
Published: May 2021

Objective

Large amounts of health data are becoming available for biomedical research. Synthesizing information across databases with no gold standard mappings between records may provide a more complete picture of patient health and enable novel research studies. To do so, researchers may probabilistically link databases and conduct inference using the linked data. However, previous inference methods for linked data are constrained to specific linkage settings and exhibit low power. Here, we present ATLAS, an automated, flexible, and robust association testing algorithm for probabilistically linked data.

Materials and Methods

Missing variables are imputed at various thresholds using a weighted average method that propagates uncertainty from the linkage process. Next, an estimated effect size is obtained using a generalized linear model. ATLAS then conducts the threshold combination test by optimally combining p-values obtained from data imputed at varying thresholds using Fisher’s method and perturbation resampling.

Results

In simulations, ATLAS controls for type I error and exhibits high power compared to previous methods. In a real-world application study, incorporation of linked data-enabled analyses using ATLAS yielded two additional signifigant associations between rheumatoid arthritis genetic risk score and biomarkers.

Discussion

The ATLAS weighted average imputation weathers false matches and increases contribution of true matches to mitigate linkage error induced bias. ATLAS’ threshold combination test avoids arbitrarily choosing a threshold to rule a match, thus automating linked data-enabled analyses and preserving power.

Conclusion

ATLAS promises to enable novel and powerful research studies using linked data to capitalize on all available data sources.
Seizure likelihood varies with day-to-day variations in sleep duration in patients with refractory focal epilepsy: A longitudinal EEG investigation
Authors: Dell Katrina L. , Payne Daniel E. , Kremen Vaclav , Maturana Matias I. , Gerla Vaclav , Nejedly Petr , Worrell Gregory A. , Lenka Lhotska , Mivalt Filip , Boston Raymond C. , Brinkmann Benjamin H. , D’Souza Wendyl , Burkitt Anthony N. , Grayden David B. , Kuhlmann Levin , Freestone Dean R. , Cook Mark J.
Published: May 2021

Background

While the effects of prolonged sleep deprivation (≥24 hours) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management.

Methods

To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial EEG recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities. A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories.

Findings

Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 hours, lowered the odds of seizure by 27% in the following 48 hours. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced REM sleep.

Interpretation

Our results demonstrate that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 hours, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.

Funding

Australian National Health and Medical Research Council, US National Institutes of Health and Czech Technical University in Prague and Epilepsy Foundation of America Innovation Institute
Outbreaks of Covid-19 Variants in Prisons: A Mathematical Modeling Analysis of Vaccination and Re-Opening Policies
Authors: Ryckman Theresa , Chin Elizabeth T. , Prince Lea , Leidner David , Long Elizabeth , Studdert David M. , Salomon Joshua A. , Alarid-Escudero Fernando , Andrews Jason R. , Goldhaber-Fiebert Jeremy D.
Published: May 2021

Background

Residents of correctional facilities have experienced disproportionately higher rates of SARS-CoV-2 infection and Covid-19-related mortality. To protect against outbreaks, many prisons and jails imposed heavy restrictions on in-person activities, which are now beginning to lift. Uncertainty surrounds the safety of these moves.

Methods and Findings

We obtained system-wide resident-day level data for the California state prison system, the nation’s third largest. We used the data to develop a transmission-dynamic stochastic microsimulation model that projects the impact of various policy scenarios on risks of SARS-CoV-2 infections and related hospitalization among residents after an initial infection is introduced to a prison. The policy scenarios vary according to levels of vaccine coverage, baseline immunity, resumption of activities, and use of non-pharmaceutical interventions (e.g., masking, physical distancing). The analyses were conducted across 5 types of prisons that differed in their residential layouts, security levels, and resident demographics.

If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage, and has no baseline immunity, 23-74% of residents are expected to be infected over 200 days. High vaccination coverage coupled with use of non-pharmaceutical measures reduces cumulative infections to 2-54% of residents. In prisons consisting mostly of dormitory housing, even with high vaccine coverage and non-pharmaceutical interventions, resumption of in-person activities is associated with substantial risk, unless there is high baseline immunity (e.g., ≥50%) from prior outbreaks. In prisons consisting mostly of cell housing, <10% of residents are expected to become infected, even with no baseline immunity. However, hospitalization risks are substantial in prisons that house medically vulnerable populations, even for prisons consisting mostly of cells. Risks of large outbreaks are substantially higher if there is continued introduction of infections into a prison. Some findings may not be transportable to other carceral settings, and our assumptions regarding viral variants will not be accurate for all variants.

Conclusions

Balancing the benefits of resuming normal in-person activities against the risks of Covid-19 outbreaks is a difficult challenge for correctional systems. The policy choices are not strictly binary. To protect against viral variants, prisons should focus on achieving both high vaccine coverage and maintaining widespread use of non-pharmaceutical interventions. With both in place, some prisons, especially those with lower room occupancy that have already had large outbreaks, could safely resume in-person activities, while continuing testing and measures to protect the medically-vulnerable.
Declining Opioid Distribution to US Hospitals
Authors: Eidbo Sarah A. , Kropp Lopez Amalie K. , Hagedorn Joseph D. , Mathew Varkey , Kaufman Daniel E. , McCall Kenneth L. , Piper Brian J.
Published: May 2021

The United States is enduring a preventable opioid crisis, particularly involving a population specifically being treated in a hospital setting. This project analyzed trends in distribution of opioids by hospitals in the United States from 2000 to 2019. Opioids monitored included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, powdered opium, remifentanil, and tapentadol. The Automation of Reports and Consolidated Orders System (ARCOS) reports controlled substances via the Drug Enforcement Administration (DEA). Data from ARCOS reports 5 and 7 from 2000 to 2019 were utilized for an observational study on hospital opioid distribution in the US. Morphine milligram equivalents (MME) were calculated using oral conversion factors for each opioid. The MME per person per state was calculated to compare data from the peak year, 2012, to data from 2019. Opioid use in the United States peaked in 2012 with a 46.6% decline from 2012 to 2019. Within the US, 25 of 50 states have seen a decrease of 50% or greater. Of the opioid compounds observed, buprenorphine has seen increased (123%) hospital use from 2000 to 2019. All other opioids have been experiencing a slow decline (>40%) in hospital use since that time. This study demonstrated the progress made thus far by hospitals in curbing the US opioid epidemic.
Population behavioural dynamics can mediate the persistence of emerging infectious diseases
Authors: Fair Kathyrn R , Karatayev Vadim A , Anand Madhur , Bauch Chris T
Published: May 2021

The critical community size (CCS) is the minimum closed population size in which a pathogen can persist indefinitely. Below this threshold, stochastic extinction eventually causes pathogen extinction. Here we use a simulation model to explore behaviour-mediated persistence: a novel mechanism by which the population response to the pathogen determines the CCS. We model severe coronavirus 2 (SARS-CoV-2) transmission and non-pharmaceutical interventions (NPIs) in a population where both individuals and government authorities restrict transmission more strongly when SARS-CoV-2 case numbers are higher. This results in a coupled human-environment feedback between disease dynamics and population behaviour. In a parameter regime corresponding to a moderate population response, this feedback allows SARS-CoV-2 to avoid extinction in the trough of pandemic waves. The result is a very low CCS that allows long term pathogen persistence. Hence, an incomplete pandemic response represents a “sour spot” that not only ensures relatively high case incidence and unnecessarily long lockdown, but also promotes long-term persistence of the pathogen by reducing the CCS. Given the worldwide prevalence of small, isolated populations in which a pathogen with low CCS can persist, these results emphasize the need for a global approach to coronavirus disease 2019 (COVID-19) vaccination.
CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection
Authors: Vanderheiden Abigail , Thomas Jeronay , Soung Allison L. , Davis-Gardner Meredith E. , Floyd Katharine , Jin Fengzhi , Cowan David A. , Pellegrini Kathryn , Creanga Adrian , Pegu Amarendra , Derrien-Colemyn Alexandrine , Shi Pei-Yong , Grakoui Arash , Klein Robyn S. , Bosinger Steven E. , Kohlmeier Jacob E. , Menachery Vineet D. , Suthar Mehul S.
Published: May 2021

SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. We find that a recently developed mouse-adapted MA-SARS-CoV-2 strain, as well as the emerging B. 1.351 variant, trigger an inflammatory response in the lung characterized by expression of pro-inflammatory cytokines and interferon-stimulated genes. scRNA-seq analysis of lung homogenates identified a hyper-inflammatory monocyte profile. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes infiltration of classical monocytes into the lung and expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
Does the elevated (thrombosis risk of males relative to females help account for the excess male mortality observed in Covid-19? An observational study
Authors: Cohen Kenneth , Anderson David , Ren Sheng , Cook David J.
Published: May 2021

Objectives

We sought to determine whether underlying thrombophilia helps account for excess Covid-19 mortality rates in males relative to females. Specifically, we asked: What is the contribution of thrombophilia to the excess Covid-19 mortality risk among malesã

Design

Cross-sectional observational study.

Setting

Data were sourced from electronic medical records (EMRs) drawn from over 200 US hospital systems.

Participants

16,576 patients hospitalized with Covid-19, aged 40 and above.

Main outcome measures

The primary study outcome was Covid-19 mortality. We measured: 1) the mortality rate of male patients relative to female patients, 2) the rate of thrombotic diagnoses occurring during hospitalization for Covid-19 in male and female patients, and 3) the mortality rate when evidence of thrombosis was present. We used hospital EMR data to determine the rates of a thrombotic diagnosis by sex, and D-dimer levels to help identify undiagnosed thrombosis.

Results

The Covid-19 mortality rate of males was higher than that of females by 16.1%. Males with Covid-19 also had a 25.4% higher rate of receiving a thrombotic diagnosis compared to females with Covid-19. The mortality rate of all patients with a thrombotic diagnosis was 42.4%—a rate over twice that of Covid-19 patients without a thrombotic diagnosis (adjusted OR 2.4 (2.17 to 2.65), p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or markedly elevated D-dimer levels, over half of the excess mortality in male patients could be explained by thrombophilia.

Conclusions

Our findings suggest the higher Covid-19 mortality rate in males may be significantly accounted for by the increased propensity for thrombophilia among males. This thrombotic tendency is additive to the thrombotic risk associated with Covid-19. Understanding the mechanisms that underlie male thrombophilia may allow for the advancement of effective anticoagulation strategies that reduce Covid-19 mortality.

Strengths and limitations of this study

To our knowledge, this population study is the first to provide evidence of a sex-based clinical association that may help explain the excess Covid-19 mortality in males compared to females.

This was an observational study using diagnosis codes and natural language processing (NLP) extractions of detailed electronic health record (EHR) data for 16,576 hospitalized patients with Covid-19.

We evaluated underlying thrombosis based on both an inpatient thrombotic diagnosis as well as a markedly elevated D-dimer level relative to CRP level.

A limitation of this study was that a portion of the estimated excess male mortality was based on the analysis of a subset of 3,442 patients that had serial D-dimer and CRP levels measured in the hospital, and that a potential undercount of these patients was possible due to the use of NLP.