bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic value of neutrophil-to-lymphocyte ratio across all stages of coronary artery disease
Authors: Agarwal Raksheeth , Aurora Ruth G. , Siswanto Bambang B. , Muliawan Hary S.
Published: April 2021

The natural history of coronary heart disease (CAD) commonly begins with atherosclerosis, progressing to chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and eventually, heart failure. Despite advancements in preventive and therapeutic strategies, there is room for further cardiovascular risk reduction. Recently, inflammation has emerged as a potential therapeutic target. The neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker which predicts poor prognosis in several conditions such as metabolic syndrome, sepsis, malignancy and CAD. In atherosclerosis, a high NLR predicts plaque vulnerability and severe stenosis. This is consistent with observations in CCS, where an elevated NLR predicts long-term major adverse cardiac events (MACEs). In ACS patients, high NLR levels are associated with larger infarct sizes and poor long-term outcomes. Possible reasons for this include failure of fibrinolysis, ischemia-reperfusion injury and in-stent restenosis, all of which are associated with raised NLR levels. Following myocardial infarction, an elevated NLR correlates with pathological cardiac remodeling which propagates chronic heart failure. Finally, in heart failure patients, an elevated NLR predicts long-term MACEs, mortality, and poor left ventricular assist device and transplant outcomes. Further studies must evaluate whether the addition of NLR to current risk-stratification models can better identify high-risk CAD patients.
Physical and Psychological Health Interdependence Among Dyads in Hematological Cancer
Authors: Streck Brennan Parmelee , Wardell Diane Wind , Derrick Jaye , Wood Geri LoBiondo
Published: April 2021

Background

Hematological cancer impacts both patients and their caregivers. Although only patients experience direct physical effects from cancer, both patients and caregivers experience psychological effects from cancer-related stressors. Theories suggest that patient-caregiver dyads, although experiencing individual effects from cancer, may also indirectly affect one another's health. This is called interdependence.

Objective

This study investigated physical and psychological health interdependence among patient-caregiver dyads facing hematological cancer, and whether their relationship quality was a moderator of interdependence.

Methods

Thirty patient-caregiver dyads were assessed for their self-reported physical function, anxiety, and depression using the Patient-Reported Outcomes Measurement Information System and relationship quality using the Mutuality Scale. Data were analyzed using the Actor Partner Interdependence Model, a dyadic data methodology for estimating interdependence.

Results

Individual physical and psychological health were related within both patients and caregivers. Patients and caregivers did not significantly differ in their reported depression, anxiety, or mutuality. Partner effects were detected among caregivers' anxiety and patients' physical function and depression. Mutuality did not moderate partner effects.

Conclusions

Findings suggest that health interdependence is present among patients with hematological cancer and their caregivers. In addition, there is a strong link between physical and psychological health within individuals, regardless of role.

Implications for Practice

Healthcare teams should consider dyadic assessment in their cancer care plans to identify risks for health decline in patients with hematological cancer and their caregivers. Assessment of caregivers, especially their anxiety levels and physical health, may yield integral information about the patients' physical and psychological health status.
Is the Postsurgical Quality of Life of Patients With Esophageal or Gastric Cancer Influenced by Emotional Competence and Neoadjuvant Treatments?
Authors: Baudry Anne-Sophie , Gehenne Lucie , Grynberg Delphine , Lelorain Sophie , Piessen Guillaume , Christophe Veronique ,   the FREGAT Working Group
Published: April 2021

Background

Emotional competence (EC) via anxiety and depressive symptoms impacts the postoperative health-related quality of life (HRQoL) of esophageal and gastric cancer patients after surgery.

Objective

The aim of this study was to confirm the involvement of emotional processes in postsurgery HRQoL according to the presence or absence of neoadjuvant treatments.

Methods

After diagnosis (T1) and after surgery (T2), 271 patients completed 3 questionnaires, assessing their intrapersonal and interpersonal EC, HRQoL, and anxiety and depressive symptoms. Patients were categorized into 2 groups: patients with only surgery (group 1) and patients who received neoadjuvant treatment in addition to surgery (group 2). Analyses were based on hierarchical regression analyses and the SPSS PROCESS Macro to test the indirect effect of EC on HRQoL through anxiety and depression.

Results

Results showed an increase in depressive symptoms and a decrease in both anxiety symptoms and HRQoL between diagnosis and surgery, regardless of neoadjuvant treatment. At T1 and T2, EC predicted fewer anxiety and depressive symptoms and a less impaired HRQoL in the surgery-only group (group 1). Emotional competence, particularly intrapersonal EC, showed a significant indirect effect on HRQoL after surgery via fewer depressive symptoms.

Conclusion

Emotional competence promotes fewer anxiety and depressive symptoms and less impaired HRQoL after diagnosis and after surgery, especially for patients without neoadjuvant treatments.

Implications for Practice

It is important for oncology nurses and other clinicians to consider the role of emotional processes in postsurgical HRQoL in relation to the type of received treatments and to reinforce the use of EC by cancer patients to improve their adjustment.
The impact of noise and topology on opinion dynamics in social networks
Authors: Stern Samuel , Livan Giacomo
Published: April 2021

We investigate the impact of noise and topology on opinion diversity in social networks. We do so by extending well-established models of opinion dynamics to a stochastic setting where agents are subject both to assimilative forces by their local social interactions, as well as to idiosyncratic factors preventing their population from reaching consensus. We model the latter to account for both scenarios where noise is entirely exogenous to peer influence and cases where it is instead endogenous, arising from the agents’ desire to maintain some uniqueness in their opinions. We derive a general analytical expression for opinion diversity, which holds for any network and depends on the network’s topology through its spectral properties alone. Using this expression, we find that opinion diversity decreases as communities and clusters are broken down. We test our predictions against data describing empirical influence networks between major news outlets and find that incorporating our measure in linear models for the sentiment expressed by such sources on a variety of topics yields a notable improvement in terms of explanatory power.
Better strategies for containing COVID-19 pandemic: a study of 25 countries via a vSIADR model
Authors: Yan Han , Zhu Yuru , Gu Jia , Huang Yaxuan , Sun Haoxuan , Zhang Xinyu , Wang Yuqing , Qiu Yumou , Xi Chen Song
Published: April 2021

We study epidemiological characteristics of 25 early COVID-19 outbreak countries, which emphasizes on the reproduction of infection and effects of government control measures. The study is based on a vSIADR model which allows asymptomatic and pre-diagnosis infections to reflect COVID-19 clinical realities, and a linear mixed-effect model to analyse the association between each country’s control measures and the effective reproduction numberRt. It finds significant effects of higher stringency measures in lowering the reproduction, and a significant shortening effect on the time to the epidemic turning point by applying stronger early counter measures. Epidemic projections under scenarios of the counter measures (China and Korea, the USA and the UK) show substantial reduction in the epidemic size and death by taking earlier and forceful actions. The governments’ response before and after the start of the second wave epidemics were alarmingly weak, which made the average duration of the second wave more than doubled that of the first wave. We identify countries which urgently need to restore to at least the maximum stringency measures implemented so far in the pandemic in order to avoid even higher infection size and death.
The onset time of Fermi’s golden rule
Authors: Debierre V. , Lassalle E.
Published: April 2021

Fermi’s golden rule describes the decay dynamics of unstable quantum systems coupled to a reservoir, and predicts a linear decay in time. Although it arises at relatively short times, the Fermi regime does not take hold in the earliest stages of the quantum dynamics. The standard criterion in the literature for the onset time of the Fermi regime is
t

F

 ∼ 1/Δ
ω
, with Δ
ω
the frequency interval around the resonant transition frequency
ω
0
of the system, over which the coupling to the reservoir does not vary appreciably. In this work, this criterion is shown to be inappropriate in general for broadband reservoirs, where the reservoir coupling spectrum takes the form
R
(
ω
) ∝ 
ω

η

, and for which it is found that for
η
 > 1, the onset time of the Fermi regime is given by
t

F

 ∝ (
ω
X
/
ω
0
)

η
−1

 × 1/
ω
0
where
ω
X
is the high-frequency cutoff of the reservoir. Therefore, the onset of the Fermi regime can take place at times orders of magnitude larger than those predicted by the standard criterion. This phenomenon is shown to be related to the excitation of the off-resonant frequencies of the reservoir at short times. For broadband reservoirs with
η
 ≤ 1, and for narrowband reservoirs, it is shown that the standard criterion is correct.
Machine learning-based security-aware spatial modulation for heterogeneous radio-optical networks
Authors: Khadr Monette H. , Elgala Hany , Rahaim Michael , Khreishah Abdallah , Ayyash Moussa , Little Thomas
Published: April 2021

In this article, we propose a physical layer security (PLS) technique, namely security-aware spatial modulation (SA-SM), in a multiple-input multiple-output-based heterogeneous network, wherein both optical wireless communications and radio-frequency (RF) technologies coexist. In SA-SM, the time-domain signal is altered prior to transmission using a key at the physical layer for combating eavesdropping. Unlike conventional PLS techniques, SA-SM does not rely on channel characteristics for securing the information, as its perception is self-imposed, which allows its adoption in radio-optical networks. Additionally, a novel periodical key selection algorithm is proposed. Instead of having multiple keys stored in the nodes, by using off-the-shelf and low-complexity machine learning (ML) methods, including a support vector machine, logistic regression and a single-layer neural network, SA-SM nodes can estimate the used key. Results show that a positive secrecy capacity can be achieved for both the RF and optical links by using 1000 different keys, with a minimal signal-to-noise ratio penalty of less than 5 dB for the legitimate user using SA-SM versus conventional transmission at a bit-error-rate of 10−4. The analysis also includes computational time and classification accuracy evaluation of the various proposed ML techniques using different hardware architectures.
On a mixed energetic–dissipative constitutive law for non-proportional loading, with focus on small-scale plasticity
Authors: Bardella Lorenzo
Published: April 2021

We analyse the mixed energetic–dissipative potential (MP) recently proposed by our group to predict, within higher-order strain gradient plasticity (SGP), reliable size-dependent responses under general loading histories. Such an MP follows former proposals by Chaboche, Ohno and co-workers for nonlinear kinematic hardening in the context of size-independent metal plasticity. The MP is given by
M
quadratic addends that each transitions, at a different threshold value, into a linear dissipative contribution. Hence, the MP involves 2
M
positive material parameters, given by the
M
threshold values and the
M
moduli weighing each quadratic recoverable term. We analytically demonstrate that, under proportional loading, the MP limit for
M
 → ∞ converges to a
less-than-quadratic
potential with well-defined properties. This result is of crucial importance for identifying the material parameters of any model adopting the MP. Moreover, our analysis provides a formula for the characterization of the energetic and dissipative parts of any possible MP limit, showing that, regarding the capability to describe the effect of diminishing size within SGP, the MP can be selected such that its contribution to the strengthening (i.e. an increase in yield point) is mostly dissipative, whereas its contribution to the increase in strain hardening is mostly recoverable.
Specialized terminology reduces the number of citations of scientific papers
Authors: Martínez Alejandro , Mammola Stefano
Published: April 2021

Words are the building blocks of communicating science. As our understanding of the world progresses, scientific disciplines naturally enrich their specialized vocabulary (jargon). However, in the era of interdisciplinarity, the use of jargon may hinder effective communication among scientists that do not share a common scientific background. The question of how jargon limits the transmission of scientific knowledge has long been debated but rarely addressed quantitatively. We explored the relationship between the use of jargon and citations, using 21 486 articles focusing on cave research, a multidisciplinary field particularly prone to terminological specialization, and where linguistic disagreement among peers is frequent. We demonstrate a significant negative relationship between the proportion of jargon words in the title and abstract and the number of citations a paper receives. Given that these elements are the hook to readers, we urge scientists to restrict jargon to sections of the paper where its use is unavoidable.
Habitat loss, predation pressure and episodic heat-shocks interact to impact arthropods and photosynthetic functioning of microecosystems
Authors: Vanbergen Adam J. , Boissieres Claire , Gray Alan , Chapman Daniel S.
Published: April 2021

Ecosystems face multiple, potentially interacting, anthropogenic pressures that can modify biodiversity and ecosystem functioning. Using a bryophyte–microarthropod microecosystem we tested the combined effects of habitat loss, episodic heat-shocks and an introduced non-native apex predator on ecosystem function (chlorophyll fluorescence as an indicator of photosystem II function) and microarthropod communities (abundance and body size). The photosynthetic function was degraded by the sequence of heat-shock episodes, but unaffected by microecosystem patch size or top-down pressure from the introduced predator. In small microecosystem patches without the non-native predator, Acari abundance decreased with heat-shock frequency, while Collembola abundance increased. These trends disappeared in larger microecosystem patches or when predators were introduced, although Acari abundance was lower in large patches that underwent heat-shocks and were exposed to the predator. Mean assemblage body length (Collembola) was reduced independently in small microecosystem patches and with greater heat-shock frequency. Our experimental simulation of episodic heatwaves, habitat loss and non-native predation pressure in microecosystems produced evidence of individual and potentially synergistic and antagonistic effects on ecosystem function and microarthropod communities. Such complex outcomes of interactions between multiple stressors need to be considered when assessing anthropogenic risks for biota and ecosystem functioning.
Population genomic, climatic and anthropogenic evidence suggest the role of human forces in endangerment of green peafowl (
Pavo muticus
)
Authors: Dong Feng , Kuo Hao-Chih , Chen Guo-Ling , Wu Fei , Shan Peng-Fei , Wang Jie , Chen De , Lei Fu-Min , Hung Chih-Ming , Liu Yang , Yang Xiao-Jun
Published: April 2021

Both anthropogenic impacts and historical climate change could contribute to population decline and species extinction, but their relative importance is still unclear. Emerging approaches based on genomic, climatic and anthropogenic data provide a promising analytical framework to address this question. This study applied such an integrative approach to examine potential drivers for the endangerment of the green peafowl (
Pavo muticus
). Several demographic reconstructions based on population genomes congruently retrieved a drastic population declination since the mid-Holocene. Furthermore, a comparison between historical and modern genomes suggested genetic diversity decrease during the last 50 years. However, climate-based ecological niche models predicted stationary general range during these periods and imply the little impact of climate change. Further analyses suggested that human disturbance intensities were negatively correlated with the green peafowl's effective population sizes and significantly associated with its survival status (extirpation or persistence). Archaeological and historical records corroborate the critical role of humans, leaving the footprint of low genomic diversity and high inbreeding in the survival populations. This study sheds light on the potential deep-time effects of human disturbance on species endangerment and offers a multi-evidential approach in examining underlying forces for population declines.
Age at first reproduction in wolves: different patterns of density dependence for females and males
Authors: Wikenros Camilla , Gicquel Morgane , Zimmermann Barbara , Flagstad Øystein , Åkesson Mikael
Published: April 2021

Age at first reproduction constitutes a key life-history trait in animals and is evolutionarily shaped by fitness benefits and costs of delayed versus early reproduction. The understanding of how intrinsic and extrinsic changes affects age at first reproduction is crucial for conservation and management of threatened species because of its demographic effects on population growth and generation time. For a period of 40 years in the Scandinavian wolf (
Canis lupus
) population, including the recolonization phase, we estimated age at first successful reproduction (pup survival to at least three weeks of age) and examined how the variation among individuals was explained by sex, population size (from 1 to 74 packs), primiparous or multiparous origin, reproductive experience of the partner and inbreeding. Median age at first reproduction was 3 years for females (
n
= 60) and 2 years for males (
n
= 74), and ranged between 1 and 8–10 years of age (
n
= 297). Female age at first reproduction decreased with increasing population size, and increased with higher levels of inbreeding. The probability for males to reproduce later first decreased, reaching its minimum when the number of territories approached 40–60, and then increased with increasing population size. Inbreeding for males and reproductive experience of parents and partners for both sexes had overall weak effects on age at first reproduction. These results allow for more accurate parameter estimates when modelling population dynamics for management and conservation of small and vulnerable wolf populations, and show how humans through legal harvest and illegal hunting influence an important life-history trait like age at first reproduction.
Strange eyes, stranger brains: exceptional diversity of optic lobe organization in midwater crustaceans
Authors: Lin Chan , Hoving Henk-Jan T. , Cronin Thomas W. , Osborn Karen J.
Published: April 2021

Nervous systems across Animalia not only share a common blueprint at the biophysical and molecular level, but even between diverse groups of animals the structure and neuronal organization of several brain regions are strikingly conserved. Despite variation in the morphology and complexity of eyes across malacostracan crustaceans, many studies have shown that the organization of malacostracan optic lobes is highly conserved. Here, we report results of divergent evolution to this ‘neural ground pattern’ discovered in hyperiid amphipods, a relatively small group of holopelagic malacostracan crustaceans that possess an unusually wide diversity of compound eyes. We show that the structure and organization of hyperiid optic lobes has not only diverged from the malacostracan ground pattern, but is also highly variable between closely related genera. Our findings demonstrate a variety of trade-offs between sensory systems of hyperiids and even within the visual system alone, thus providing evidence that selection has modified individual components of the central nervous system to generate distinct combinations of visual centres in the hyperiid optic lobes. Our results provide new insights into the patterns of brain evolution among animals that live under extreme conditions.
From infection niche to therapeutic target: the intracellular lifestyle of Mycobacterium tuberculosis
Authors: Rankine-Wilson Leah Isobella , Shapira Tirosh , Sao Emani Carine , Av-Gay Yossef
Published: April 2021

Mycobacterium tuberculosis

(Mtb) is an obligate human pathogen killing millions of people annually. Treatment for tuberculosis is lengthy and complicated, involving multiple drugs and often resulting in serious side effects and non-compliance. Mtb has developed numerous complex mechanisms enabling it to not only survive but replicate inside professional phagocytes. These mechanisms include, among others, overcoming the phagosome maturation process, inhibiting the acidification of the phagosome and inhibiting apoptosis. Within the past decade, technologies have been developed that enable a more accurate understanding of Mtb physiology within its intracellular niche, paving the way for more clinically relevant drug-development programmes. Here we review the molecular biology of Mtb pathogenesis offering a unique perspective on the use and development of therapies that target Mtb during its intracellular life stage.
Brain Networks Associated With COVID-19 Risk: Data From 3,662 Participants
Authors: Abdallah Chadi G.
Published: April 2021

Background

Our behavioral traits, and subsequent actions, could affect the risk of exposure to the coronavirus disease of 2019 (COVID-19). The current study aimed to determine whether unique brain networks are associated with the COVID-19 infection risk.

Methods

This research was conducted using the UK Biobank Resource. Functional magnetic resonance imaging scans in a cohort of general population (n=3,662) were used to compute the whole-brain functional connectomes. A network-informed machine learning approach was used to identify connectome and nodal fingerprints that are associated with positive COVID-19 status during the pandemic up to February 4th, 2021.

Results

The predictive models successfully identified 6 fingerprints that were associated with COVID-19 positive, compared to negative status (all p values < 0.005). Overall, lower integration across the brain modules and increased segregation, as reflected by internal within module connectivity, were associated with higher infection rates. More specifically, COVID-19 positive status was associated with 1) reduced connectivity between the central executive and ventral salience, as well as between the dorsal salience and default mode networks; 2) increased internal connectivity within the default mode, ventral salience, subcortical and sensorimotor networks; and 3) increased connectivity between the ventral salience, subcortical and sensorimotor networks.

Conclusion

Individuals are at increased risk of COVID-19 infections if their brain connectome is consistent with reduced connectivity in the top-down attention and executive networks, along with increased internal connectivity in the introspective and instinctive networks. These identified risk networks could be investigated as target for treatment of illnesses with impulse control deficits.
Industry and workplace characteristics associated with the use of a COVID-19 contact tracing app in Japan: a nation-wide employee survey
Authors: Ishimaru Tomohiro , Ibayashi Koki , Nagata Masako , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Ogami Akira , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: April 2021

Objectives

To combat coronavirus disease 2019 (COVID-19), many countries have used contact tracing apps, including Japan’s voluntary-use contact-confirming application (COCOA). The current study aimed to identify industry and workplace characteristics associated with the use of this COVID-19 contact tracing app.

Methods

This cross-sectional study of full-time workers used an online survey. Multiple logistic regression analysis was used to evaluate the associations of industry and workplace characteristics with contact tracing app use.

Results

Of the 27,036 participants, 25.1% had downloaded the COCOA. Workers in the public service (adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI]: 1.14–1.45) and information technology (aOR = 1.38, 95% CI: 1.20–1.58) industries were more likely to use the app than were those in the manufacturing industry. In contrast, app usage was less common among workers in the retail and wholesale (aOR = 0.87, 95% CI: 0.76–0.99) and food/beverage (aOR = 0.81, 95% CI: 0.70–0.94) industries, but further adjustment for business size attenuated these associations. Workers at larger companies were more likely to use the app. Compared with permanent employees, the odds of using the app were higher for managers and civil servants but lower for those who were self-employed.

Conclusions

One possible reason for the under-implementation of the contact tracing app in the retail and wholesale and food/beverage industries is small business size, as suggested by the fully adjusted model results. An awareness campaign should be conducted to promote the widespread use of the contact tracing app in these industries.
Pre-pandemic mental health and disruptions to healthcare, economic, and housing outcomes during COVID –19: evidence from 12 UK longitudinal studies
Authors: Gessa Giorgio Di , Maddock Jane , Green Michael J. , Thompson Ellen J. , McElroy Eoin , Davies Helena L. , Mundy Jessica , Stevenson Anna J. , Kwong Alex S.F. , Griffith Gareth J. , Katikireddi Srinivasa Vittal , Niedzwiedz Claire L. , Ploubidis George B. , Fitzsimons Emla , Henderson Morag , Silverwood Richard J. , Chaturvedi Nish , Breen Gerome , Steves Claire J. , Steptoe Andrew , Porteous David J , Patalay Praveetha
Published: April 2021

Background

The COVID-19 pandemic and associated virus suppression measures have disrupted lives and livelihoods and people already experiencing mental ill-health may have been especially vulnerable.

Aim

To quantify mental health inequalities in disruptions to healthcare, economic activity and housing.

Method

59,482 participants in 12 UK longitudinal adult population studies with data collected prior to and during the COVID-19 pandemic. Within each study we estimated the association between psychological distress assessed pre-pandemic and disruptions since the start of the pandemic to three domains: healthcare (medication access, procedures, or appointments); economic activity (employment, income, or working hours); and housing (change of address or household composition). Meta-analyses were used to pool estimates across studies.

Results

Across the analysed datasets, one to two-thirds of participants experienced at least one disruption, with 2.3-33.2% experiencing disruptions in two or more domains. One standard deviation higher pre-pandemic psychological distress was associated with: (i) increased odds of any healthcare disruptions (OR=1.30; [95% CI:1.20–1.40]) with fully adjusted ORs ranging from 1.24 [1.09–1.41] for disruption to procedures and 1.33 [1.20– 1.49] for disruptions to prescriptions or medication access; (ii) loss of employment (OR=1.13 [1.06–1.21]) and income (OR=1.12 [1.06 –1.19]) and reductions in working hours/furlough (OR=1.05 [1.00–1.09]); (iii) no associations with housing disruptions (OR=1.00 [0.97–1.03]); and (iv) increased likelihood of experiencing a disruption in at least two domains (OR=1.25 [1.18–1.32]) or in one domain (OR=1.11 [1.07–1.16]) relative to no disruption.

Conclusion

People experiencing psychological distress pre-pandemic have been more likely to experience healthcare and economic disruptions, and clusters of disruptions across multiple domains during the pandemic. Failing to address these disruptions risks further widening the existing inequalities in mental health.
Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies
Authors: Thomas Paul J. , Leow Alex , Klumpp Heide , Phan K. Luan , Ajilore Olusola
Published: April 2021

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that best maps to resting state functional connectivity and applied it towards a heterogenous dataset of internalizing psychopathologies (IPs), a set of psychiatric conditions in which similar brain network deficits are found across the swath of the disorders, but a unifying neuropathological substrate for transdiagnostic symptom expression is currently unknown. This research provides preliminary evidence of a transdiagnostic brain subnetwork deficit characterized by information diffusion impairment of the right area 8BM, a key brain region involved in organizing a broad spectrum of cognitive tasks, that may underlie previously reported dysfunction of multiple brain circuits in the IPs. We also demonstrate that models of neuromodulation involving targeting this brain region normalize IP diffusion dynamics towards those of healthy controls. These analyses provide a framework for multimodal methods that identify both brain subnetworks with disrupted information diffusion and potential targets of these subnetworks for therapeutic neuromodulatory intervention based on previously well-characterized methodology.
Mean time to infection by small diffusing droplets containing SARS-CoV-2 during close social contacts
Authors: Dobramysl U. , Sieben C. , Holcman D.
Published: April 2021

Airborne viruses such as SARS-CoV-2 are partly spreading through aerosols containing viral particles. Inhalation of infectious airborne particles can lead to infection, a route that can even be more predominant compared with droplet or contact transmission. To study the transmission between a susceptible and an infected person, we estimate the distribution of arrival times of small diffusing aerosol particles to the inhaled region located below the nose until the number of particles reaches a critical threshold. Our results suggest that although contamination by continuous respiration can take around 90 minutes at a distance of one meter, it is reduced to a few minutes when coughing or sneezing. Interestingly, there is not much differences between outdoors and indoors when the air is still. When a window is open inside an office, the infection time is reduced. Finally, wearing a mask leads to a delay in the time to infection. To conclude, diffusion analysis provides several key time scale of viral airborne transmission.
Predicting the severity of disease progression in COVID-19 at the individual and population level: A mathematical model
Authors: Chirmule Narendra , Nair Pradip , Desai Bela , Khare Ravindra , Nerurkar Vivek , Gaur Amitabh
Published: April 2021

The impact of COVID-19 disease on health and economy has been global, and the magnitude of devastation is unparalleled in modern history. Any potential course of action to manage this complex disease requires the systematic and efficient analysis of data that can delineate the underlying pathogenesis. We have developed a mathematical model of disease progression to predict the clinical outcome, utilizing a set of causal factors known to contribute to COVID-19 pathology such as age, comorbidities, and certain viral and immunological parameters. Viral load and selected indicators of a dysfunctional immune response, such as cytokines IL-6 and IFNα, which contribute to the cytokine storm and fever, parameters of inflammation d-dimer and ferritin, aberrations in lymphocyte number, lymphopenia, and neutralizing antibodies were included for the analysis. The model provides a framework to unravel the multi-factorial complexities of the immune response manifested in SARS-CoV-2 infected individuals. Further, this model can be valuable to predict clinical outcome at an individual level, and to develop strategies for allocating appropriate resources to mitigate severe cases at a population level.
Clusterin in Alzheimer’s disease: an amyloidogenic inhibitor of amyloid formation
Authors: Spatharas Panagiotis M. , Nasi Georgia I. , Tsiolaki Paraskevi L. , Theodoropoulou Marilena K. , Papandreou Nikos C. , Hoenger Andreas , Trougakos Ioannis P. , Iconomidou Vassiliki A.
Published: April 2021

Clusterin is a heterodimeric glycoprotein (α- and β-chain), which has been described as an extracellular molecular chaperone. In humans, clusterin is an amyloid associated protein, co-localizing with fibrillar deposits in several amyloidoses, including Alzheimer’s disease. To clarify its potential implication in amyloid formation, we located aggregation-prone regions within the sequence of clusterin α-chain, via computational methods. We had peptide-analogues of each region chemically synthesized and experimentally demonstrated that all of them can form amyloid-like fibrils. We also provide evidence that the same peptide-analogues can inhibit amyloid-β fibril formation. These findings elucidate parts of the molecular mechanism in which clusterin inhibits amyloid formation. At the same time, they hint that molecular chaperones with amyloidogenic properties might have a role in the regulation of amyloid formation, essentially acting as functional amyloids.
The spatial configuration of biotic interactions shapes coexistence-area relationships in an annual plant community
Authors: García-Callejas David , Bartomeus Ignasi , Godoy Oscar
Published: April 2021

The increase of species richness with area is a universal phenomenon on Earth. How-ever, this observation contrasts with our poor understanding of how these species-area relationships (SARs) emerge from the collective effects of area, spatial heterogeneity, and local interactions. By combining a structuralist approach with five years of empirical observations in a highly-diverse Mediterranean grassland, we show that spatial hetero-geneity plays a little role in the accumulation of species richness with area in our system. Instead, as we increase the sampled area more species combinations are realized, and they coexist mainly due to direct pairwise interactions rather than by changes in single-species dominance or by indirect interactions. We also identify a small set of transient species with small population sizes that are consistently found across spatial scales. These findings empirically support the importance of the architecture of species interactions together with stochastic events for driving coexistence- and species-area relationships.
Curvature-driven feedback on aggregation-diffusion of proteins in lipid bilayers
Authors: Mahapatra Arijit , Saintillan David , Rangamani Padmini
Published: April 2021

Abstract

Membrane bending is an extensively studied problem from both modeling and experimental perspectives because of the wide implications of curvature generation in cell biology. Many of the curvature generating aspects in membranes can be attributed to interactions between proteins and membranes. These interactions include protein diffusion and formation of aggregates due to protein-protein interactions in the plane of the membrane. Recently, we developed a model that couples the in-plane flow of lipids and diffusion of proteins with the out-of-plane bending of the membrane. Building on this work, here, we focus on the role of explicit aggregation of proteins on the surface of the membrane in the presence of membrane bending and diffusion. We develop a comprehensive framework that includes lipid flow, membrane bending energy, the entropy of protein distribution, and an explicit aggregation potential and derive the governing equations. We compare this framework to the Cahn-Hillard formalism to predict the regimes in which the proteins form patterns on the membrane. We demonstrate the utility of this model using numerical simulations to predict how aggregation and diffusion, coupled with curvature generation, can alter the landscape of membrane-protein interactions.
Phylomedicine of mutational processes in somatic cancer cell populations
Authors: Miura Sayaka , Vu Tracy , Choi Jiyeong , Kumar Sudhir
Published: April 2021

Mutational processes in somatic cancer cell populations are constantly changing, leaving their signatures in the accumulated genomic variation in tumors. The inference of mutational signatures from the observed genetic variation enables spatiotemporal tracking of tumor mutational processes that evolve due to cellular environmental changes, mutations, and treatment regimes. Ultimately, mutational patterns illuminate the mechanistic understanding of their evolution in cancer progression. We show that the integration of cancer cell phylogeny with mutational signature deconvolution enables higher-resolution detection of gain and loss of mutational processes within the phylogeny. This approach to analyzing somatic genomic variations in 61 lung cancer patients revealed a high turn-over of mutational processes over time and closely related clonal lineages. Some mutational signatures (e.g., smoking-related) showed a higher propensity to be lost, whereas others (e.g., AID/APOBEC) were gained during lung tumors evolution. These observations shed light on the evolution of mutational processes in somatic cell evolution.
Study of the effectiveness of partial quarantines applied to control the spread of the Covid-19 virus
Authors: León A.
Published: April 2021

In Chile and in many countries of the world, partial quarantines have been used as part of the strategy to contain and control the Covid-19 virus. However, there is no certainty of its effectiveness and efficiency due to the lack of comparison with similar scenarios. In this work, we formulated a theoretical model of individual mobility, which also incorporates the infection dynamics of Covid-19. The model is based on a cellular automaton, which includes individuals moving through the represented spatial region and interacting according to the dynamics of Covid-19. In addition, we include mobile and partial health barriers, and different mobility regimes. Our results show that, partial quarantines would not be effective in general, to reduce the peak of active individuals infected with the virus, except for some proportions of territorial area involved in the division of the global region. Another interesting result of our research is that the passage restrictions in a sanitary barrier would not be relevant to the impact of the pandemic indicators in a sanitary quarantine regime. A possible explanation for the ineffectiveness of partial quarantines lies in the fact that the sanitary barriers are permeable to infected individuals and therefore when one of these individuals passes, an outbreak occurs in the virus-free zone that is independent of the original one.
Dipeptides are minimalistic but sufficient for liquid-liquid phase separation
Authors: Tang Yiming , Bera Santu , Yao Yifei , Zeng Jiyuan , Lao Zenghui , Dong Xuewei , Gazit Ehud , Wei Guanghong
Published: April 2021

Liquid-liquid phase separation (LLPS) of proteins mediates the assembly of biomolecular condensates involved in physiological and pathological processes. Identifying the minimalistic building blocks and the sequence determinant of protein phase separation is of urgent importance but remains challenging due to the enormous sequence space and difficulties of existing methodologies in characterizing the phase behavior of ultrashort peptides. Here we demonstrate computational tools to efficiently quantify the microscopic fluidity and density of liquid-condensates/solid-aggregates and the temperature-dependent phase diagram of peptides. Utilizing our approaches, we comprehensively predict the LLPS abilities of all 400 dipeptide combinations of coded amino acids based on 492 micro-second molecular dynamics simulations, and observe the occurrences of spontaneous LLPS. We identify 54 dipeptides that form solid-like aggregates and three categories of dipeptides with high LLPS propensity. Our predictions are validated by turbidity assays and differential interference contrast (DIC) microscopy on four representative dipeptides (WW, QW, GF, and VI). Phase coexistence diagrams are constructed to explore the temperature dependence of LLPS. Our results reveal that aromatic moieties are crucial for a dipeptide to undergo LLPS, and hydrophobic and polar components are indispensable. We demonstrate for the first time that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, suggesting that LLPS is a general property of peptides/proteins, independent of their sequence length. This study provides a computational and experimental approach to the prediction and characterization of the phase behavior of minimalistic peptides, and will be helpful for understanding the sequence-dependence and molecular mechanism of protein phase separation.

Significance

Protein liquid-liquid phase separation (LLPS) is associated with human health and diseases. Identifying the minimalistic building blocks and sequence determinants of LLPS is of urgent importance but remains computationally challenging partially due to the lack of methodologies characterizing the liquid condensates. Herein we provide approaches to evaluate LLPS ability of dipeptides, and screen all 400 dipeptides by MD simulations combined with multi-bead-per-residue models which capture key interactions driving LLPS that are missing in one-bead-per-residue models. Three categories of LLPS dipeptides are identified and the experimentally-verified QW dipeptide is by far the smallest LLPS system. Our results suggest that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, and LLPS is a general property of peptides/proteins, independent of their length.
THEM6-mediated lipid remodelling sustains stress resistance in cancer
Authors: Blomme Arnaud , Peter Coralie , Mui Ernest , Blanco Giovanny Rodriguez , Mason Louise M. , Jamieson Lauren E. , McGregor Grace H. , Lilla Sergio , Ntala Chara , Patel Rachana , Thiry Marc , Kung Sonia H. Y. , Ford Catriona A. , Rushworth Linda K. , McGarry David J. , Mason Susan , Repiscak Peter , Nixon Colin , Salji Mark J. , Markert Elke , MacKay Gillian M. , Kamphorst Jurre J. , Graham Duncan , Faulds Karen , Fazli Ladan , Gleave Martin E. , Avezov Edward , Edwards Joanne , Yin Huabing , Sumpton David , Blyth Karen , Close Pierre , Murphy Daniel J. , Zanivan Sara , Leung Hing Y.
Published: April 2021

Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reducesin vivotumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducingde novosterol biosynthesis and preventing lipid-mediated induction of ATF4. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether, our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
Detection of two CAL.20C SARS-CoV-2 variants in Monterrey metropolitan area in Northeast Mexico
Authors: Galán-Huerta Kame A. , Rivas-Estilla Ana M. , Lozano-Sepúlveda Sonia A. , Martínez-Acuña Natalia , Arellanos-Soto Daniel , Montes-de-Oca-Luna Roberto , Treviño-Garza Consuelo , de-la-O-Cavazos Manuel E. , Ramos-Jiménez Javier
Published: April 2021

SARS-CoV-2 variants of concern (VOC) are a worldwide problem. CAL.20C is considered a VOC and its distribution should be monitored. We detected two CAL.20C variants in Monterrey, Mexico in patients who had no recent travel history. This indicates that this variant is now transmitted locally in Northeast Mexico.
Strategies for antigen testing: An alternative approach to widespread PCR testing
Authors: Reddy Sanjay G. , Das Saumya
Published: April 2021

Multiple applications of low cost and rapid antigen tests for individuals, in parallel (at the same time) or at times sufficiently close to each other, when appropriately interpreted can considerably increase sensitivity of these tests, improving on their performance greatly. Under reasonable assumptions, this occurs when considering a positive to arise in a composite test if at least one of two underlying repeated tests are positive. Parallel Rapid Testing can potentially provide a form of testing that is accessible (combining wide availability and lack of expense) and quick. Moreover, it can provide a level of sensitivity that is comparable to seemingly more sophisticated but more expensive alternatives. In combination with sequential testing, this strategy offers an alternative method of testing that can be applied immediately and on a widespread basis.