bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Outcomes After Controlled Oxygenated Rewarming of Human Livers Before Transplantation
Authors: Hoyer Dieter P. , Benkö Tamas , Manka Paul , von Horn Charlotte , Treckmann Juergen W. , Paul Andreas , Minor Thomas
Published: March 2020

Background.

Controlled oxygenated rewarming (COR) has been shown to be a feasible and safe method in clinical practice and to reduce peak serum transaminases after liver transplantation. This study aimed to demonstrate further clinical experience of this method of now 18 clinical liver transplantations utilizing COR and demonstrate the long-term results.

Methods.

In this extended series of 18 patients, cold-stored livers were subjected to machine-assisted slow COR for ≈120 minutes before transplantation. A cohort of 178 patients transplanted during the same period with similar clinical characteristics were used for comparison of key outcomes.

Results.

All livers were perfused in accordance to the COR protocol without incidences and transplanted successfully. Early allograft dysfunction was observed in 2 (11.1%) cases after COR. Liver elasticity measurements indicated normal healthy liver parenchyma at the last follow-up. Graft survival demonstrated excellent outcomes after COR. The 1-, 3-, and 5-year patient survival rates were 100%, 100%, and 93.8% compared with 84.5%, 82.0%, and 75.8% in the control group (P = 0.12).

Conclusions.

The present study demonstrates excellent clinical outcomes after COR before liver transplantation. Comparison with a control cohort shows superiority of graft survival. Further evidence is needed to assess this promising method to improve organ preservation, finally.
Identification of Subtle Verbal Memory Deficits in Premanifest Huntington Disease Using the California Verbal Learning Test
Authors: Holden Heather M. , Tierney Savanna M. , Graves Lisa V. , Beltran-Najera Ilex , Woods Steven Paul , Snell Chase M. , Delis Dean C. , Corey-Bloom Jody , Gilbert Paul E.
Published: March 2020

Background:

Verbal memory impairment in individuals with Huntington disease (HD) is well-documented; however, the nature and extent of verbal memory impairment in individuals with premanifest HD (pre-HD) are less understood.

Objective:

To evaluate verbal memory function in individuals with pre-HD by comparing their performance on the California Verbal Learning Test to that of individuals with a clinical diagnosis of HD and that of a demographically similar group of adults with no family history of, or genetic risk for, HD, thereby reducing possible complications of psychiatric difficulties commonly experienced by individuals who are at risk for HD but are gene negative.

Methods:

Participant groups included 77 adults with a diagnosis of HD, 23 premanifest gene carriers for HD (pre-HD), and 54 demographically similar, healthy adults. The California Verbal Learning Test—Second Edition (CVLT–II) was used to evaluate the participants’ immediate and delayed recall, recognition, learning characteristics, errors, and memory retention.

Results:

The pre-HD group performed significantly worse than the healthy group, yet significantly better than the HD group, on Short and Long Delay Recall (Free and Cued) and Recognition Discriminability. On Total Immediate Recall, Learning Slope, Semantic Clustering, and Intrusions, the pre-HD group performed similarly to the healthy group and significantly better than the HD group. None of the groups differed in their performance on Repetitions and a measure of retention.

Conclusions:

Subtle memory deficits can be observed during the premanifest stage of HD with use of a subset of indices from the CVLT–II.
Effect of Compound Muscle Action Potential After Peripheral Nerve Stimulation Normalization on Anesthetic Fade of Intraoperative Transcranial Motor-Evoked Potential
Authors: Tanaka Satoshi , Watanabe Tomoko , Takanashi Junko , Oka Hidehiro , Hashimoto Ryo , Akimoto Jiro
Published: March 2020

Purpose:

Anesthetic fade refers to the time-dependent decrease in the amplitude of the intraoperative motor-evoked potential. It is thought to be caused by the accumulation of propofol. The authors examined whether normalization by the compound muscle action potential (CMAP) after peripheral nerve stimulation could compensate for anesthetic fade.

Methods:

In 1,842 muscles in 578 surgeries, which did not exhibit a motor-neurologic change after the operation, the motor-evoked potential amplitude was normalized by the CMAP amplitude after peripheral nerve stimulation, and the CMAP amplitude and operation times were analyzed.

Results:

The amplitudes of both motor-evoked potential and CMAP increased over time after peripheral nerve stimulation because of the disappearance of muscle-relaxant action. Especially, after peripheral nerve stimulation, CMAP significantly increased from the beginning to the end of the operation. Anesthetic fade in transcranial motor-evoked potential monitoring seemed to occur at more than 235 minutes of surgery based on the results of a receiver operating characteristic analysis of the operation time and relative amplitudes. Although the mean amplitude without CMAP normalization at more than 235 minutes was significantly lower than that at less than 235 minutes, the mean amplitude with normalization by CMAP after peripheral nerve stimulation at more than 235 minutes was not significantly different from that at less than 235 minutes.

Conclusions:

Compound muscle action potential after peripheral nerve stimulation normalization was able to avoid the effect of anesthetic fade. Anesthetic fade was seemed to be caused by a decrease in synaptic transmission at the neuromuscular junction because of propofol accumulation by this result.
Drug checking to detect fentanyl and new psychoactive substances
Authors: Palamar Joseph J. , Salomone Alberto , Barratt Monica J.
Published: March 2020

Purpose of review

Drug checking services invite drug consumers to anonymously submit drug samples for chemical analysis and provide feedback of results. Drugs are tested for strength/dose and/or presence of adulterants. Drug checking appears to be more common in recent years in response to increases in fentanyl-related deaths and the proliferation of new psychoactive substances (NPS). We aim to provide information regarding the current state of drug checking in relation to analysis methods, adulteration rates, and behavioral responses to results.

Recent findings

Various technologies are being used to detect the presence of fentanyl, its analogs, and other NPS in drug samples. Proxy drug checking, which we define as biospecimen testing for drug exposure postconsumption, is also becoming common. However, there appears to a dichotomy between research focusing on populations at high risk for fentanyl exposure and to exposure to NPS such as synthetic cathinones.

Drug checking research and services largely focus on opioid consumers and nightclub and dance festival attendees, but more focus may be needed on the general population. Drug checking results can inform surveillance efforts, and more research is needed to overcome barriers to drug checking and to focus on whether test results indeed affect behavior change.
Does kin discrimination promote cooperation?
Authors: Faria Gonçalo S. , Gardner Andy
Published: March 2020

Genetic relatedness is a key driver of the evolution of cooperation. One mechanism that may ensure social partners are genetically related is kin discrimination, in which individuals are able to distinguish kin from non-kin and adjust their behaviour accordingly. However, the impact of kin discrimination upon the overall level of cooperation remains obscure. Specifically, while kin discrimination allows an individual to help more-related social partners over less-related social partners, it is unclear whether and how the population average level of cooperation that is evolutionarily favoured should differ under kin discrimination versus indiscriminate social behaviour. Here, we perform a general mathematical analysis in order to assess whether, when and in which direction kin discrimination changes the average level of cooperation in an evolving population. We find that kin discrimination may increase, decrease or leave unchanged the average level of cooperation, depending upon whether the optimal level of cooperation is a convex, concave or linear function of genetic relatedness. We develop an extension of the classic ‘tragedy of the commons' model of cooperation in order to provide an illustration of these results. Our analysis provides a method to guide future research on the evolutionary consequences of kin discrimination.
Uncovering dark multichromophoric states in Peridinin–Chlorophyll–Protein
Authors: Taffet Elliot J. , Fassioli Francesca , Toa Zi S. D. , Beljonne David , Scholes Gregory D.
Published: March 2020

It has long been recognized that visible light harvesting in Peridinin–Chlorophyll–Protein is driven by the interplay between the bright (S
2
) and dark (S
1
) states of peridinin (carotenoid), along with the lowest-lying bright (Q
y
) and dark (Q
x
) states of chlorophyll-
a
. Here, we analyse a chromophore cluster in the crystal structure of Peridinin–Chlorophyll–Protein, in particular, a peridinin–peridinin and a peridinin–chlorophyll-
a
dimer, and present quantum chemical evidence for excited states that exist beyond the confines of single peridinin and chlorophyll chromophores. These dark multichromophoric states, emanating from the intermolecular packing native to Peridinin–Chlorophyll–Protein, include a correlated triplet pair comprising neighbouring peridinin excitations and a charge-transfer interaction between peridinin and the adjacent chlorophyll-
a
. We surmise that such dark multichromophoric states may explain two spectral mysteries in light-harvesting pigments: the sub-200-fs singlet fission observed in carotenoid aggregates, and the sub-200-fs chlorophyll-
a
hole generation in Peridinin–Chlorophyll–Protein.
Galenizing the New World: Joseph-François Lafitau's ‘Galenization’ of Canadian Ginseng,
CA
1716–1724
Authors: Giovannetti-Singh Gianamar
Published: March 2020

This essay situates the French Jesuit missionary Joseph-François
Lafitau's (1681–1746) ‘discovery’ of Canadian
ginseng within its social, commercial and religious contexts, and illustrates
how the missionary's upbringing and education in France shaped the way he
perceived nature in the New World. It elucidates the manner in which Lafitau
‘Galenized’ Canadian flora, fauna and peoples. It explores the
role of Lafitau's dual enculturation in both a mercantile household and
later the Society of Jesus in his application of Galenic categories to Canadian
nature. The essay then examines the tensions between localism and universalism
in Galenic medicine in the eighteenth century. It links these dichotomies to
Lafitau's Galenization of Canadian ginseng. Finally, it suggests that
since the Jesuits were prohibited from trading goods they had
purchased
, they sold medicinal plants they had
cultivated
themselves, which played a central role in
financing the Society's missions in a manner they believed to be morally
acceptable.
The crosstalk between microtubules, actin and membranes shapes cell division
Authors: Rizzelli Francesca , Malabarba Maria Grazia , Sigismund Sara , Mapelli Marina
Published: March 2020

Mitotic progression is orchestrated by morphological and mechanical changes
promoted by the coordinated activities of the microtubule (MT) cytoskeleton, the
actin cytoskeleton and the plasma membrane (PM). MTs assemble the mitotic
spindle, which assists sister chromatid separation, and contact the rigid and
tensile actomyosin cortex rounded-up underneath the PM. Here, we highlight the
dynamic crosstalk between MTs, actin and cell membranes during mitosis, and
discuss the molecular connections between them. We also summarize recent views
on how MT traction forces, the actomyosin cortex and membrane trafficking
contribute to spindle positioning in isolated cells in culture and in epithelial
sheets. Finally, we describe the emerging role of membrane trafficking in
synchronizing actomyosin tension and cell shape changes with
cell–substrate adhesion, cell–cell contacts and extracellular
signalling events regulating proliferation.
Drones and global navigation satellite systems: current evidence from polar scientists
Authors: Sheridan Iain
Published: March 2020

Aerial unmanned vehicles, so-called drones, present a paradigm shift away from the long-term use by scientists of manned aeroplanes and helicopters. This is evident from the number of research articles that focus on data obtained with drones. This article examines the use of aerial drones for scientific research in cryospheric regions, especially Antarctica and the Arctic. Specifically, it aims to provide insights into the choices and performance of global navigation satellite systems (GNSS) use for drones, including augmentation systems. Data on drone GNSS navigation and positioning in the context of scientific polar research have been scarce. Drone survey data obtained from polar scientists in April 2019 is the first representative sample from this close-knit global community across the specialisms of climatology, ecology, geology, geomorphology, geophysics and oceanography. The survey results derived from 16 countries revealed that 14.71% of scientists used GALILEO, 27.94% used GLONASS and 45.59% used GPS. Many used a combination of two or more GNSS. Multiple regression analysis showed that there is no strong relationship between a specific pattern of GNSS augmentation and greater positioning accuracy. Further polar drone studies should assess the effects of phase scintillation on all GNSS, therefore BEIDOU, GALILEO, GLONASS and GPS.
Evidence for localization and urbanization economies in urban scaling
Authors: Sarkar Somwrita , Arcaute Elsa , Hatna Erez , Alizadeh Tooran , Searle Glen , Batty Michael
Published: March 2020

We study the scaling of (i) numbers of workers and aggregate incomes by occupational categories against city size, and (ii) total incomes against numbers of workers in different occupations, across the functional metropolitan areas of Australia and the USA. The number of workers and aggregate incomes in specific high-income knowledge economy-related occupations and industries show increasing returns to scale by city size, showing that localization economies within particular industries account for superlinear effects. However, when total urban area incomes and/or gross domestic products are regressed using a generalized Cobb–Douglas function against the number of workers in different occupations as labour inputs, constant returns to scale in productivity against city size are observed. This implies that the urbanization economies at the whole city level show linear scaling or constant returns to scale. Furthermore, industrial and occupational organizations, not population size, largely explain the observed productivity variable. The results show that some very specific industries and occupations contribute to the observed overall superlinearity. The findings suggest that it is not just size but also that it is the diversity of specific intra-city organization of economic and social activity and physical infrastructure that should be used to understand urban scaling behaviours.
Did awarding badges increase data sharing inBMJ Open? A randomized controlled trial
Authors: Rowhani-Farid Anisa , Aldcroft Adrian , Barnett Adrian G.
Published: March 2020

Sharing data and code are important components of reproducible research. Data sharing in research is widely discussed in the literature; however, there are no well-established evidence-based incentives that reward data sharing, nor randomized studies that demonstrate the effectiveness of data sharing policies at increasing data sharing. A simple incentive, such as an Open Data Badge, might provide the change needed to increase data sharing in health and medical research. This study was a parallel group randomized controlled trial (protocol registration:doi:10.17605/OSF.IO/PXWZQ) with two groups, control and intervention, with 80 research articles published inBMJ Openper group, with a total of 160 research articles. The intervention group received an email offer for an Open Data Badge if they shared their data along with their final publication and the control group received an email with no offer of a badge if they shared their data with their final publication. The primary outcome was the data sharing rate. Badges did not noticeably motivate researchers who published inBMJ Opento share their data; the odds of awarding badges were nearly equal in the intervention and control groups (odds ratio = 0.9, 95% CI [0.1, 9.0]). Data sharing rates were low in both groups, with just two datasets shared in each of the intervention and control groups. The global movement towards open science has made significant gains with the development of numerous data sharing policies and tools. What remains to be established is an effective incentive that motivates researchers to take up such tools to share their data.
Antimicrobial resistance prevalence in commensal Escherichia coli from broilers, fattening turkeys, fattening pigs and veal calves in European countries and association with antimicrobial usage at country level
Authors: Ceccarelli Daniela , Hesp Ayla , van der Goot Jeanet , Joosten Philip , Sarrazin Steven , Wagenaar Jaap A. , Dewulf Jeroen , Mevius Dik J. , EFFORT consortium on behalf of the
Published: March 2020

The aim of this article is to report on antimicrobial resistance (AMR) in commensal

Escherichia coli

from livestock from several European countries. The relationships with antimicrobial usage (AMU) at country level and harmonized indicators to cover the most relevant AMR aspects for human health in animal production were also investigated.

E. coli

were isolated in faeces from broilers and fattening pigs (from nine countries), and fattening turkeys and veal calves (from three countries) and screened against a fixed antimicrobial panel. AMU data were collected at farm and average treatment incidences stratified by antimicrobial class, country and livestock species were calculated. Associations between AMR and AMU at country level were analysed. Independent of animal species, the highest resistance was observed for ampicillin, sulphamethoxazole, tetracycline and trimethoprim.

E. coli

from broilers showed the highest resistance level for (fluoro)quinolones, and multidrug resistance peaked in broilers and fattening turkeys. Colistin resistance was observed at very low levels with the exception of fattening turkeys. High resistance to third- and fourth-generation cephalosporins was detected in broilers and fattening turkeys. The lowest levels of resistance were for meropenem, azithromycin and tigecycline (<1 %). Significant correlations between resistance and usage at country level were detected in broilers for polymyxins and aminoglycosides, and in fattening pigs for cephalosporins, amphenicols, fluoroquinolones and polymyxins. None of the correlations observed between AMR and AMU were statistically significant for fattening turkey and veal calves. The strength of the analysis performed here is the correlation of aggregated data from the same farms at country level for both AMU and AMR within antimicrobial classes.
Association between device measured and self-reported sitting in relation to depression: the 1970 British Cohort Study
Authors: Webster Andrew , Batty G David , Pearson Natalie , Stamatakis Emmanuel , Hamer Mark
Published: March 2020

Aims

While physical activity appears to confer protection against depression, the relationship between sedentary behaviour and mental health is uncertain. Self-reported methods provide information about context although there may be error in the quantification of sedentary behaviour. Accordingly, we examined associations of both device-measured and self-reported sedentary behaviour with depression.

Method

Participants (n=4,704; 52.4% Female; aged 46-48) were drawn from the 1970 British Cohort Study. Sitting time and moderate-vigorous physical activity was measured using a thigh-worn accelerometer device (ActivPAL) over a seven day period. A range of self-reported sedentary behaviours was measured to provide context. Depression diagnosis was captured using a combination of self-reported consultation with a physician and use of anti-depressant medication. Malaise inventory was used to assess depressive symptoms.

Results

Relative to those who spent <8 hr/d sitting, those in the highest tertile of device measured sitting (>10 hr/d) had increased odds of depression diagnosis (odds ratio= 1.48 [95% confidence interval 1.05-2.08]). There was no association between self-reported TV viewing and depression diagnosis (1.07; 0.71-1.63). We observed protective associations between moderate-vigorous physical activity and depression diagnosis (highest tertile vs. the lowest tertile; 0.70;0.49-1.00). Associations of sitting time and physical activity with depression were mutually independent. Relative to <1 hours of internet usage, 2-3 and >3 hours of internet weekday usage were associated with increased odds of depressive symptoms (1.60;1.30-1.97 and 1.63;1.32-2.03, respectively).

Conclusion

Device-measured sitting is associated depression diagnosis, although less consistent associations are observed with self-reported sedentary behaviours. Regular physical activity and reducing sedentary time may be beneficial for prevention of depression.
Newborn Differential DNA Methylation and Subcortical Brain Volumes as Early Signs of Severe Neurodevelopmental Delay in a South African Birth Cohort Study
Authors: Hüls Anke , Wedderburn Catherine J , Groenewold Nynke A , Gladish Nicole , Jones Meaghan , Koen Nastassja , MacIsaac Julia L , Lin David TS , Ramadori Katia E , Epstein Michael P , Donald Kirsten A. , Kobor Michael S , Zar Heather J , Stein Dan J
Published: March 2020

Objective

The first two years of life are a critical period of rapid brain development. Since early neurodevelopment is influenced by prenatal risk factors and genetics, neonatal biomarkers can potentially provide the opportunity to detect early signs of neurodevelopmental delay. We analyzed associations between DNA methylation (DNAm) levels from cord blood, neonatal magnetic resonance imaging (MRI) neuroimaging data, and neurodevelopment at two years of age.

Methods

Neurodevelopment was assessed in 161 children from the South African Drakenstein Child Health Study at two years of age using the Bayley Scales of Infant and Toddler Development III. We performed an epigenome-wide association study of neurodevelopmental delay using DNAm levels from cord blood. A mediation analysis was conducted in 51 children to analyze if associations between differential DNAm and neurodevelopmental delay were mediated by altered neonatal brain volumes.

Results

We found epigenome-wide significant associations between differential DNAm at the SPTBN4 locus (cg26971411, p-value=3.10×10−08), an intergenic region on chromosome 11 (cg00490349, p-value=2.41×10−08) and a differentially methylated region on chromosome 1 (FDR p-value for the region=9.06×10−05) and severe neurodevelopmental delay. While these associations were not mediated by neonatal brain volume, neonatal caudate volumes were independently associated with neurodevelopmental delay, particularly in language (p=0.0443) and motor (p=0.0082) domains.

Conclusion

Differential DNAm levels from cord blood and increased neonatal caudate volumes were independently associated with severe neurodevelopmental delay at two years of age. These findings suggest that neurobiological signals for severe developmental delay may be detectable in very early life with implications for identification and intervention design.
Combined Utility of 25 Disease and Risk Factor Polygenic Risk Scores for Stratifying Risk of All-Cause Mortality
Authors: Meisner Allison , Kundu Prosenjit , Zhang Yan Dora , Lan Lauren V. , Kim Sungwon , Ghandwani Disha , Choudhury Parichoy Pal , Berndt Sonja I. , Freedman Neal D. , Garcia-Closas Montserrat , Chatterjee Nilanjan
Published: March 2020

While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry (i.e., middle age for most participants). The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.
Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic
Authors: Jagodnik Kathleen M. , Ray Forest , Giorgi Federico M. , Lachmann Alexander
Published: March 2020

The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.

The full analysis workflow and data is available at: https://github.com/lachmann12/covid19
Temporal relationship between outbound traffic from Wuhan and the 2019 coronavirus disease (COVID-19) incidence in China
Authors: Shi Zaixing , Fang Ya
Published: March 2020

Background

The city of Wuhan is the epicenter of the 2019 coronavirus disease (COVID-19) outbreak and a central Chinese hub for transportation and industry. Mass migration prior to the Chinese New Year may have accelerated the spread of COVID-19 across China. This analysis investigated the temporal relationship between daily outbound traffic from Wuhan and the incidence of COVID-19 in 31 Chinese provinces during January-February 2020.

Methods

We collected incidence of confirmed COVID-19 cases from National and Provincial Health Committee reports from January 10 to February 29, 2020. Volume of outbound traffic from Wuhan to other provinces was measured by Baidu Migration Index, a widely used metric that tracks migration based on cellphone location. We used cross-correlation function and autoregressive integrated moving average (ARIMA) model to examine time-lagged association between traffic volume and COVID-19 incidence by province. Contributors to the provincial variation in the temporal associations were investigated. Additionally, we estimated the reduction in cumulative incidence of COVID-19 cases following the travel ban for Wuhan.

Results

Cross-correlation function analyses suggested that the volume of outbound traffic from Wuhan was positively associated with COVID-19 incidence in all provinces, with correlation coefficients between 0.22-0.78 (all P<0.05). Approximately 42% of provinces showed <1 week of lag between traffic volume and COVID-19 incidence, 39% with 1 week, and 19% with 2-3 weeks. Migration had more prolonged impacts in provinces closer to Wuhan and with more passenger influx from Wuhan, but affected economically advantaged provinces to a lesser extent. We further estimated that the travel ban may have prevented approximately 19,768 COVID-19 cases (95% CI: 13,589, 25,946) outside of Wuhan by February 29, 2020.

Conclusions

Outflowing migration from Wuhan facilitated the COVID-19 transmission to other parts of China with varying time-lagged effects dependent on provincial characteristics. The travel ban led to a significant reduction in COVID-19 outside of Wuhan.
Estimating unobserved SARS-CoV-2 infections in the United States
Authors: Perkins T. Alex , Cavany Sean M. , Moore Sean M. , Oidtman Rachel J. , Lerch Anita , Poterek Marya
Published: March 2020

By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved SARS-CoV-2 infections during its initial invasion of the US remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the US through March 12, we estimated that 22,876 (95% posterior predictive interval: 7,451 - 53,044) infections occurred in the US by this date. By comparing the model’s predictions of symptomatic infections to local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between February 21 and March 12, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.97, 95% PPI: 0.85 - 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the US.

Significance Statement

Countries across the world observed dramatic rises in COVID-19 cases and deaths in March 2020. In the United States, delays in the availability of diagnostic testing prompted questions about the extent of unobserved community transmission. Using a simulation model informed by reported cases and deaths, we estimated that tens of thousands of people were infected by the time a national emergency was declared on March 13. Our results indicate that fewer than 20% of locally acquired, symptomatic infections in the US were detected over a period of a month. The existence of a large, unobserved reservoir of infection argues for the necessity of large-scale social distancing that went into effect to mitigate the impacts of SARS-CoV-2 on the US.
Learning Phenotypic Associations for Parkinson’s Disease with Longitudinal Clinical Records
Authors: Pan Weishen , Su Chang , Chen Kun , Henchcliffe Claire , Wang Fei
Published: March 2020

Background

Parkinson’s disease (PD) is associated with multiple clinical manifestations including motor and non-motor symptoms, and understanding of its etiologies has been informed by a growing number of genetic mutations, and various fluid-based and brain imaging biomarkers. However, the precise mechanisms by which these phenotypic features interact remain elusive. Therefore, we aimed to generate the phenotypic association graph of multiple heterogeneous features within PD to reveal pathological pathways of the complex disease.

Methods

A data-driven approach was introduced to generate the phenotypic association graphs using data from the Parkinson’s Progression Markers Initiative (PPMI) and Fox Investigation for New Discovery of Biomarkers (BioFIND) studies. We grouped features based on the structure of the learned graphs in both cohorts, and investigated their dynamic patterns in the longitudinal PPMI cohort.

Findings

424 patients with PD from the PPMI study and 126 patients with PD from the BioFIND study were available for analysis. For PPMI, the phenotypic association graphs were generated at different time points of the disease, including baseline (without any PD treatments), and 1-, 2-, 3-, 4-, and 5-year follow-up time points. Based on topological structure of the learned graph, clinical features were classified into homogeneous groups, that were densely intra-connected while sparsely inter-connected. Importantly, we observed both stable and longitudinally changing relations in the graphs generated, likely reflecting the dynamic pathologies of PD. By cross-cohort comparison, we observed very similar structure for graphs constructed from BioFIND (in which patients have a much longer duration of PD at enrollment than PPMI) and later-period (4- and 5-year follow-up) data from PPMI. This consistency demonstrates the effectiveness of our method.

Interpretation

We analyzed the heterogeneous features of PD by generating the phenotypic association graphs. By analyzing the structural relationships among the features over time, our findings could improve the understanding of the pathologies of PD.

Funding

Michael J Fox Foundation for Parkinson’s Research.
Stability of SARS-CoV-2 in different environmental conditions
Authors: Chin Alex W.H. , Chu Julie T.S. , Perera Mahen R.A. , Hui Kenrie P.Y. , Yen Hui-Ling , Chan Michael C.W. , Peiris Malik , Poon Leo L.M.
Published: March 2020

Stability of SARS-CoV-2 in different environmental conditions.
Temporal dynamics in viral shedding and transmissibility of COVID-19
Authors: He Xi , Lau Eric HY , Wu Peng , Deng Xilong , Wang Jian , Hao Xinxin , Lau Yiu Chung , Wong Jessica Y , Guan Yujuan , Tan Xinghua , Mo Xiaoneng , Chen Yanqing , Liao Baolin , Chen Weilie , Hu Fengyu , Zhang Qing , Zhong Mingqiu , Wu Yanrong , Zhao Lingzhai , Zhang Fuchun , Cowling Benjamin J , Li Fang , Leung Gabriel M
Published: March 2020

We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.
Motivational Strategies for Stroke Rehabilitation: A Delphi Study
Authors: Oyake Kazuaki , Suzuki Makoto , Otaka Yokei , Momose Kimito , Tanaka Satoshi
Published: March 2020

Background and Purpose

Although various strategies are used to motivate patients during rehabilitation, consensus regarding the optimal motivational strategies for stroke rehabilitation has not been established. Expert consensus may aid rehabilitation professionals in effectively utilizing motivational strategies to produce the most beneficial outcome for their patients. The primary purpose of this study was to provide a comprehensive list of effective motivational strategies based on consensus among rehabilitation experts, generated using the Delphi technique. In addition, we sought to identify the types of information that are important when selecting motivational strategies.

Methods

A total of 198 rehabilitation experts participated in a three-round Delphi survey. The rehabilitation experts included physicians, physical therapists, occupational therapists, and speech-language-hearing therapists who had worked in stroke rehabilitation for at least five years. Panelists were asked to rate the effectiveness of motivational strategies and to rate the importance of different types of information using a 5-point Likert scale. Consensus was defined as having been reached for items with an interquartile range of 1 or less.

Results

A total of 116 experts (58.6%) completed the third round of the Delphi survey. Consensus was reached on all of the 26 presented strategies. Seven strategies, such as control of task difficulty and goal setting, were considered to be very effective in increasing patient motivation. In addition, all 11 of the presented types of information were deemed very important or important in determining which motivational strategies to use.

Conclusions

We generated a list of effective motivational strategies for stroke rehabilitation based on expert consensus. Our results suggest that experts consider a comprehensive range of patient information when choosing motivational strategies. These findings represent a group of consensus-based recommendations for increasing patient adherence to stroke rehabilitation programs, which may be beneficial to many medical professionals working in stroke rehabilitation.
Recovery Units under the Endangered Species Act could be used more widely
Authors: Evans Michael , Li Ya-Wei , Malcom Jacob
Published: March 2020

Recovering species is one of the main goals of the Endangered Species Act (ESA). In the face of limited budgets, diverse tools are needed to find efficient solutions. Recovery units may be one such tool - designated portions of a species’ range that must be recovered individually before an entire species can be considered recovered. Recovery units allow for spatial flexibility in recovery goals and may be used in regulatory decisions such as section 7 consultation. Despite their availability, there is very little information on how recovery units have been developed and used. We mined available public data to determine the number and types of species for which recovery units have been designated; evaluated species and geographic characteristics associated with recovery unit designation; and examined how recovery units have been used in the implementation of the ESA, such as during consultation. We found 49 listed species have designated recovery units through 2017, and that these species had similar characteristics. Namely, they had relatively large ranges and were well-studied. We found taxonomic biases in recovery unit designation as well, with fish species being disproportionately likely to have recovery units and plants disproportionately less. Improvements in recovery priority numbers among species with recovery units indicate that the theoretical benefits of this tool may have translated to improved status. These data indicate that recovery units could be applied to more wide-ranging species to improve recovery under the ESA.
The positive evidence bias in perceptual confidence is not post-decisional
Authors: Samaha Jason , Denison Rachel
Published: March 2020

Confidence in a perceptual decision is a subjective estimate of the accuracy of one’s choice. As such, confidence is thought to be an important computation for a variety of cognitive and perceptual processes, and it features heavily in theorizing about conscious access to perceptual states. Recent experiments have revealed a “positive evidence bias” (PEB) in the computations underlying confidence reports. A PEB occurs when confidence, unlike objective choice, over-weights the evidence for the chosen option, relative to evidence against the chosen option. Accordingly, in a perceptual task, appropriate stimulus conditions can be arranged that produce selective changes in confidence reports but no changes in accuracy. Although the PEB is generally assumed to reflect the observer’s perceptual and/or decision processes, post-decisional accounts have not been ruled out. We therefore asked whether the PEB persisted under novel conditions that eliminated two possible post-decisional accounts: 1) post-decision evidence accumulation that contributes to a confidence report solicited after the perceptual choice, and 2) a memory bias that emerges in the delay between the stimulus offset and the confidence report. We found that even when the stimulus remained on the screen until observers responded, and when observers reported their choice and confidence simultaneously, the PEB still emerged. Signal detection-based modeling also showed that the PEB was not associated with changes to metacognitive efficiency, but rather to confidence criteria. We conclude that once-plausible post-decisional accounts of the PEB do not explain the bias, bolstering the idea that it is perceptual or decisional in nature.
Functional Organization of the Maternal and Paternal Human 4D Nucleome
Authors: Lindsly Stephen , Jia Wenlong , Chen Haiming , Liu Sijia , Ronquist Scott , Chen Can , Wen Xingzhao , Stansbury Cooper , Dotson Gabrielle A. , Ryan Charles , Rehemtulla Alnawaz , Omenn Gilbert S. , Wicha Max , Li Shuai Cheng , Muir Lindsey , Rajapakse Indika
Published: March 2020

Every human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data, we investigate this relationship both globally and locally. We introduce the maternal and paternal 4D Nucleome, enabling detailed analysis of the mechanisms and dynamics of genome structure and gene function for diploid organisms. Our analyses find significant coordination between allelic expression biases and local genome conformation, and notably absent expression bias in universally essential cell cycle and glycolysis genes. We propose a model in which coordinated biallelic expression reflects prioritized preservation of essential gene sets.
Adversarial manipulation of human decision-making
Authors: Dezfouli Amir , Nock Richard , Dayan Peter
Published: March 2020

Adversarial examples are carefully crafted input patterns that are surprisingly poorly classified by artificial and/or natural neural networks. Here we examine adversarial vulnerabilities in the processes responsible for learning and choice in humans. Building upon recent recurrent neural network models of choice processes, we propose a general framework for generating adversarial opponents that can shape the choices of individuals in particular decision-making tasks towards the behavioural patterns desired by the adversary. We show the efficacy of the framework through two experiments involving action selection and response inhibition. We further investigate the strategy used by the adversary in order to gain insights into the vulnerabilities of human choice. The framework may find applications across behavioural sciences in helping detect and avoid flawed choice.
Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers
Authors: Hu Chih-Fen , Luxton G. W. Gant , Lee Feng-Chin , Hsu Chih-Sin , Huang Shih-Ming , Hong Jau-Shyong , Wu San-Pin
Published: March 2020

Background

DYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by theTOR1Agene. The low penetrance of the ΔE mutation (∼30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia.

Methods

To identify these modifiers, we performed whole exome sequencing of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative.

Results

A total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders.

Conclusion

The DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.
Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatomSeminavis robusta
Authors: Bilcke Gust , Van den Berge Koen , De Decker Sam , Bonneure Eli , Poulsen Nicole , Bulankova Petra , Osuna-Cruz Cristina Maria , Dickenson Jack , Sabbe Koen , Pohnert Georg , Vandepoele Klaas , Mangelinckx Sven , Clement Lieven , De Veylder Lieven , Vyverman Wim
Published: March 2020

Sexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in nature and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets, in order to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatomSeminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S-phase progression, chloroplast division, mitosis and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin (dsCyc). Our data further suggest an important role for reactive oxygen species, energy metabolism and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological responses such as the production of the attraction pheromone diproline and mate-searching behaviour in MT+. Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations.
miRNome profiling of clonal stem cells in Ph+CML
Authors: Ruiz María Sol , Sánchez María Belén , Bonecker Simone , Furtado Carolina , Koile Daniel , Yankilevich Patricio , Cranco Santiago , del Rosario Custidiano María , Freitas Josefina , Moiraghi Beatriz , Peréz Mariel Ana , Pavlovsky Carolina , Varela Ana Inés , Ventriglia Verónica , Sánchez Ávalos Julio César , Larripa Irene , Zalcberg Ilana , Mordoh José , Valent Peter , Bianchini Michele
Published: March 2020

Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence ofBCR-ABL1expression, showed an altered miRNome.In silicoanalysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes betweenBCR-ABL1+LSC and theirBCR-ABL1-counterparts, providing valuable data for future studies.