bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice
Authors: Meloto Carolina B. , Ingelmo Pablo , Perez Eduardo Vega , Pitt Rebecca , González Cárdenas Víctor Hugo , Mohamed Nada , Sotocinal Susana G. , Bourassa Valerie , Lima Lucas Vasconcelos , Ribeiro-da-Silva Alfredo , Mogil Jeffrey S. , Diatchenko Luda
Published: June 2021

Introduction:

Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain.

Objective:

We aimed to test the effect of treatment with KF in pain assays in mice and in a case series of patients with chronic widespread pain.

Methods:

The analgesic effect of KF was tested in CD-1 mice injected with formalin, complete Freund's adjuvant, or subjected to spared nerve injury. In addition, wild-type (C57BL/6) and MC-deficient (C57BL/6-Kit
W-sh/W-sh) mice were injected with formalin or complete Freund's adjuvant and treated with KF. Patients with chronic widespread pain (n = 5; age: 13–16 years) who failed to respond to standard of care participated in a 16-week treatment trial with KF (6 mg/d). Ketotifen fumarate's therapeutic effect was evaluated using the patient global impression of change.

Results:

In the mouse experiments, KF produced dose- and MC-dependent analgesic effects against mechanical allodynia in the acute and chronic inflammatory pain but not neuropathic pain assays. In the patient case series, 4 patients reported that activity limitations, symptoms, emotions, and overall quality of life related to their pain condition were “better” or “a great deal better” since beginning treatment with KF. This was accompanied by improvements in pain comorbid symptoms.

Conclusion:

Treatment with KF is capable of reducing established inflammatory-induced mechanical nociception in an MC-dependent manner in mice, and it may be beneficial for the treatment of chronic pain conditions.
HIV Viral Suppression and Pre-exposure Prophylaxis in HIV and Syphilis Contact Tracing Networks: An Analysis of Disease Surveillance and Prescription Claims Data
Authors: Billock Rachael M. , Samoff Erika , Lund Jennifer L. , Pence Brian W. , Powers Kimberly A.
Published: June 2021

Background:

HIV and syphilis contact tracing networks offer efficient platforms for HIV treatment and prevention interventions, but intervention coverage within these networks has not been characterized.

Setting:

HIV and syphilis sexual contact tracing networks among men who have sex with men (MSM) in North Carolina (NC).

Methods:

Using surveillance data, we identified 2 types of “network events” that occurred between January 2013 and June 2017 among MSM in NC: being diagnosed with early syphilis or being named as a recent sexual contact of a person diagnosed with HIV or early syphilis. We estimated prevalent and incident HIV viral suppression among persons diagnosed with HIV before the network event, and we assessed the effect of contact tracing services on a 6-month cumulative incidence of viral suppression among previously HIV-diagnosed, virally unsuppressed persons. Using linked prescription claims data, we also evaluated prevalent and incident pre-exposure prophylaxis (PrEP) use in an insured subset of HIV-negative network members.

Results:

Viral suppression prevalence among previously HIV-diagnosed persons was 52.6%. The 6-month cumulative incidence of viral suppression was 35.4% overall and 13.1 (95% confidence interval: 8.8 to 17.4) percentage points higher among persons reached than among those not reached by contact tracing services. Few HIV-negative persons had prevalent (5.4%) or incident (4.1%) PrEP use in the 6 months before or after network events, respectively.

Conclusions:

Suboptimal viral suppression and PrEP use among MSM in NC in HIV/syphilis contact tracing networks indicate a need for intensified intervention efforts. In particular, expanded services for previously HIV-diagnosed persons could improve viral suppression and reduce HIV transmission within these networks.
Molecular insights on potato yellow vein crinivirus infections in the highlands of Colombia
Authors: Niño Ángela , del Toro Francisco J. , Tenllado Francisco , Canto Tomás , Franco-Lara Liliana
Published: June 2021

Potato yellow vein virus (PYVV) was detected in potatoes grown in the Central highlands, north of Bogotá (~3000 m altitude), Colombia. At this altitude viral whitefly vectors are largely absent, but infection persists because of the use of uncertified tubers. Plants with typical PYVV-induced yellowing symptoms, as well as with atypical yellowing or non-symptomatic symptoms were sampled at three separate geographical locations. PYVV presence was assessed by RT-PCR, and several plants were subjected to high-throughput sequencing (HTS) of their small RNA (sRNA) populations. Complete or almost complete sequences of four PYVV isolates were thus reconstructed, all from symptomatic plants. Three viral isolates infected plants singly, while the fourth co-infected the plant together with a potyvirus. Relative proportions of sRNAs to each of the three crinivirus genomic RNAs were found to remain comparable among the four infections. Genomic regions were identified as hotspots of sRNA formation, or as regions that poorly induced sRNAs. Furthermore, PYVV titres in the mixed versus single infections remained comparable, indicating an absence of synergistic/antagonistic effects of the potyvirus on the accumulation of PYVV. Daughter plants raised in the greenhouse from tubers of the infected, field-sampled plants displayed mild PYVV infection symptoms that disappeared with time, demonstrating the occurrence of recovery and asymptomatic infection phenotypes in this pathosystem.
Prospective comparison of Bayesian and frequentist adaptive clinical trials : The SHADOW - SHINE project
Authors: Broglio Kristine , Meurer William J. , Durkalski Valerie , Pauls Qi , Connor Jason , Berry Donald , Lewis Roger J. , Johnston Karen C. , Barsan William G.
Published: June 2021

Importance

Bayesian adaptive trial design has the potential to create more efficient clinical trials. However, one of the barriers to the uptake of Bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared to a frequentist design.

Objective

Compare the performance of a Bayesian and a frequentist adaptive clinical trial design.

Design

Prospective observational study comparing two trial designs using individual patient level data from a completed stroke trial, including the timing and order of enrollments and outcome ascertainment. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses when 90-days post-randomization was met for 500, 700, 900, and 1,100 patients. The Bayesian alternative utilized predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients, and subsequent interims after every 100 randomizations.

Setting

Multi-center, acute stroke study conducted within a National Institutes of Health neurological emergencies clinical trials network.

Participants

Patient level data from 1,151 patients randomized in a clinical trial comparing intensive insulin therapy to standard in acute stroke patients with hyperglycemia.

Main Outcome(s) and Measure(s)

Sample size at end of study. This was defined as the sample size at which each of the studies stopped accrual of patients.

Results

As conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the Bayesian alternative crossed the futility boundary about 3 months earlier after 800 participants were randomized.

Conclusions and Relevance

Both trial designs stopped for futility prior to reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trial’s primary question earlier. The common feature across the two designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how this was implemented between the two trials resulted in the differences in early stopping.

Trial Registration

The SHINE trial was registered and results are reported on clinicaltrials.gov under identifier: NCT01369069
Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals
Authors: Melbourne Carl A. , Erzurumluoglu A. Mesut , Shrine Nick , Chen Jing , Tobin Martin D. , Hansell Anna , Wain Louise V.
Published: June 2021

Impaired lung function is predictive of mortality and is a key component in the diagnosis of chronic obstructive pulmonary disease. Lung function has a strong genetic component but is also affected by environmental factors such as increased exposure to air pollution. How genetic factors and air pollution interact to affect lung function is however less understood.

We conducted a genome-wide gene-air pollution interaction analysis of spirometry measures with three measures of air pollution at home address: particulate matter (PM2.5& PM10) and nitrogen dioxide (NO2), in approximately 300,000 unrelated European individuals from UK Biobank. We explored air pollution interactions with previously identified lung function signals and determined their combined interaction effect using a polygenic risk score (PRS).

We identified seven genome-wide interaction signals (P< 5 × 10−8), and a further ten suggestive interaction signals (P< 5 × 10−7). We found statistical evidence of interaction with PM2.5for previous lung function signal, rs10841302, nearAEBP2, suggesting increased susceptibility of FEV1/FVC to PM2.5, as copies of the G allele increased (interaction beta: −0.073 percentage points, 95%CI: −0.105, −0.041). There was no observed interaction between air pollutants and the weighted genetic risk score.

We carried out the largest genome-wide gene-air pollution interaction study of lung function and identified effects of clinically relevant size and significance. We observed up to 440ml lower lung function for certain genotypes associated with mean levels of outdoor air pollution at baseline, which is approximately equivalent to nine years of normal loss of lung function.
Comparison of antigen- and RT-PCR-based testing strategies for detection of Sars-Cov-2 in two high-exposure settings
Authors: Love Jay , Wimmer Megan T. , Toth Damon J.A. , Chandran Arthi , Makhija Dilip , Cooper Charles K. , Samore Matthew H. , Keegan Lindsay T.
Published: June 2021

Surveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when administered to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.
SARS-CoV-2 Seroprevalence Among Firefighters in Los Angeles, California
Authors: Mulligan Karen , Berg Anders H. , Eckstein Marc , Hori Acacia , Rodriguez Anna , Toubat Omar , Sood Neeraj
Published: June 2021

Objective

We estimate the seroprevalence of SARS-CoV-2 antibodies among firefighters in the Los Angeles, California fire department in October 2020 and compare demographic and contextual factors for seropositivity.

Methods

We conducted a serologic survey of firefighters in Los Angeles, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for immunoglobulin G, immunoglobulin M, or both. We compared demographic and contextual factors for seropositivity.

Results

Of 713 participants, 8.9% tested positive for SARS-CoV-2 antibodies. Seropositivity was not associated with gender, age, or race/ethnicity. Furthermore, firefighters who worked in zip codes with lower income or higher share of minority population did not have higher rates of SARS-CoV-2 infection. Seropositivity was highest among firefighters who reported working in the vicinity of Los Angeles International Airport, which had a known outbreak in July 2020.

Conclusions

Seroprevalence among firefighters was no higher than seroprevalence in the general population, suggesting that workplace safety protocols, such as access to PPE and testing, can mitigate increased risk of infection at work. Workplace safety protocols for firefighters also eliminated differences in disease burden by geography and race/ethnicity observed in the general population.
Lead exposure and serum metabolite profiles in pregnant women in Mexico City
Authors: Niedzwiecki Megan M. , Eggers Shoshannah , Joshi Anu , Dolios Georgia , Cantoral Alejandra , Lamadrid-Figueroa Héctor , Amarasiriwardena Chitra , Téllez-Rojo Martha M. , Wright Robert O. , Petrick Lauren
Published: June 2021

Background

Lead (Pb) exposure is a global health hazard causing a wide range of adverse health outcomes. Yet, the mechanisms of Pb toxicology remain incompletely understood, especially during pregnancy. To uncover biological pathways impacted by Pb exposure, this study investigated serum metabolomic profiles during the third trimester of pregnancy that are associated with blood Pb and bone Pb.

Methods

We used data and specimens collected from 99 women enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort based in Mexico City. Maternal Pb exposure was measured in whole blood samples from the third trimester of pregnancy and in the tibia and patella bones at 1 month postpartum. Third-trimester serum samples underwent metabolomic analysis; metabolites were identified based on matching to an in-house analytical standard library. A metabolome-wide association study was performed with all three Pb measurements using multiple linear regression models, adjusted for confounders and batch effects. Class enrichment analyses were also conducted.

Results

The median (interquartile range) blood Pb concentration was 2.9 (2.6) μg/dL. Median bone Pb, measured in the patella and tibia, were 2.5 (7.3) μg/g and 3.6 (9.5) μg/g, respectively. Of 248 total metabolites identified in serum, 31 were associated with blood Pb (p<0.05). Class enrichment analysis identified significant overrepresentation of metabolites classified as fatty acids and conjugates, amino acids and peptides, and purines. Tibia and patella Pb were associated with 14 and 11 metabolites, respectively (p<0.05). Comparing results from bone and blood Pb, glycochenodeoxycholic acid and glycocholic acid were negatively associated with blood Pb and tibia Pb, while 5-aminopentanoic acid and 7-methylguanine were negatively associated with blood Pb and patella Pb. One metabolite, 5-aminopentanoic acid, was associated with all three Pb measures.

Conclusion

This study identified serum metabolites in pregnant women associated with Pb measured in blood (31 metabolites) and bone (tibia: 14 metabolites, patella: 11 metabolites). These findings provide insights on the metabolic profile around Pb exposure in pregnancy and may provide important links to guide detailed studies of toxicological effects for both mothers and children.
The role of HIV infection in the clinical spectrum of COVID-19: a population-based cohort analysis based on US National COVID Cohort Collaborative (N3C) Enclave data
Authors: Yang Xueying , Zhang Jiajia , Guo Siyuan , Olatosi Bankole , Weissman Sharon , Li Xiaoming
Published: June 2021

The authors have withdrawn this manuscript because of the accidental low cell size in the supplementary materials. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Comparison of bacterial communities from the surface and adjacent bottom layers water of Billings reservoir
Authors: Marcondes Marta Angela , Nascimento Andrezza , Pessôa Rodrigo , Victor Jefferson Russo , da Silva Duarte Alberto José , Sanabani Sabri Saeed
Published: June 2021

Here, we describe the microbial diversity and physicochemical properties in freshwater samples from the surface and bottom layer of Billings reservoir in São Paulo state, Brazil. Twenty-two matched samples were characterized using the 16S rRNA gene Illumina MiSeq platform. Taxonomical composition revealed an abundance ofCyanobacteriaphyla, followed byProteobacteria, with 1903 and 2689 known bacterial genera in the surface and deep-water layers, respectively. Shannon diversity index ranging from 2.3 - 5.39 and 4.04 - 6.86 in the surface and bottom layer, respectively. Among the 120 pathogenic genera identified,Flavobacteriumwas the most predominant genus. Temperature and phosphorus concentration were the most influential factors in shaping the microbial communities of both layers. Predictive functional analysis suggests that the reservoir is enriched in motility genes involved in the flagellar assembly. The overall results present new information on the significantly altered diversity composition of the bacterial community detected in Billings freshwater reservoir.

IMPORTANCE

In this study, we investigated the bacterial distribution, community composition, potential metabolic activity, potentially pathogenic bacteria, and toxin genes ofCyanobacteriain the bottom layers and surface along Billings reservoir in the southeast of Brazi. Our results provide essential information about the pattern of bacterioplankton communities’ variation inhabiting the Billings reservoir and the combination of environmental that shaped their structure. These results may help pave the way for future studies devoted to control and improve the water quality in the Billings reservoir, which is facing rapid urban development and urbanization.
Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD
Authors: Mandel-Brehm Caleigh , Benson Leslie A. , Tran Baouyen , Kung Andrew F. , Mann Sabrina A. , Vazquez Sara E. , Retallack Hanna , Sample Hannah A. , Zorn Kelsey C. , Khan Lillian M. , Kerr Lauren M. , McAlpine Patrick L. , Zhang Lichao , McCarthy Frank , Elias Joshua E. , Katwa Umakanth , Astley Christina M. , Tomko Stuart , Dalmau Josep , Seeley William W. , Pleasure Samuel J. , Wilson Michael R. , Gorman Mark P. , DeRisi Joseph L.
Published: June 2021

ROHHAD (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.
Introduction and transmission of SARS-CoV-2 B.1.1.7 in Denmark
Authors: Michaelsen Thomas Y. , Bennedbæk Marc , Christiansen Lasse E. , Jørgensen Mia S. F. , Møller Camilla H. , Sørensen Emil A. , Knutsson Simon , Brandt Jakob , Jensen Thomas B. N. , Chiche-Lapierre Clarisse , Collados Emilio F. , Sørensen Trine , Petersen Celine , Le-Quy Vang , Sereika Mantas , Hansen Frederik T. , Rasmussen Morten , Fonager Jannik , Karst Søren M. , Marvig Rasmus L. , Stegger Marc , Sieber Raphael N. , Skov Robert , Legarth Rebecca , Krause Tyra G. , Fomsgaard Anders ,   The Danish Covid-19 Genome Consortium (DCGC), Albertsen Mads
Published: June 2021

In early 2021, the SARS-CoV-2 lineage B.1.1.7 became dominant across large parts of the world. In Denmark, comprehensive and real-time test, contact-tracing, and sequencing efforts were applied to sustain epidemic control. Here, we use these data to investigate the transmissibility, introduction, and onward transmission of B.1.1.7 in Denmark. In a period with stable restrictions, we estimated an increased B.1.1.7 transmissibility of 58% (95% CI: [56%,60%]) relative to other lineages. Epidemiological and phylogenetic analyses revealed that 37% of B.1.1.7 cases were related to the initial introduction in November 2020. Continuous introductions contributed substantially to case numbers, highlighting the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants.
The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials
Authors: Wafa Ifan Ali , Pratama Nando Reza , Budi David Setyo , Sutanto Henry , Rosyid Alfian Nur , Wungu Citrawati Dyah Kencono
Published: June 2021

Objectives

The use of monoclonal antibody for COVID-19 showed conflicting results in prior studies and its efficacy remains unclear. We aimed to comprehensively determine the efficacy and safety profile of monoclonal antibodies in COVID-19 patients.

Methods

Sixteen RCTs were analyzed using RevMan 5.4 to measure the pooled estimates of risk ratios (RRs) and standardized mean differences (SMDs) with 95% CIs.

Results

The pooled effect of monoclonal antibodies demonstrated mortality risk reduction (RR=0.89 (95%CI 0.82-0.96), I2=13%, fixed-effect). Individually, tocilizumab reduced mortality risk in severe to critical disease (RR=0.90 (95%CI 0.83-0.97), I2=12%, fixed-effect)) and lowered mechanical ventilation requirements (RR=0.76 (95%CI 0.62-0.94), I2=42%, random-effects). Moreover, it facilitated hospital discharge (RR=1.07 (95%CI 1.00-1.14), I2=60%, random-effects). Meanwhile, bamlanivimab-etesevimab and REGN-COV2 decrease viral load ((SMD=-0.33 (95%CI -0.59 to -0.08); (SMD=-3.39 (95%CI -3.82 to -2.97)). Interestingly, monoclonal antibodies did not improve hospital discharge at day 28-30 (RR=1.05 (95%CI 0.99–1.12), I2=71%, random-effects) and they displayed similar safety profile with placebo/standard therapy (RR=1.04 (95%CI 0.76-1.43), I2=54%, random-effects).

Conclusion

Tocilizumab improved hospital discharge and reduced mortality as well as the need for mechanical ventilation, while bamlanivimab-etesevimab and REGN-COV2 reduced viral load in mild to moderate outpatients. In general, monoclonal antibodies are safe and should be considered in severe to critical COVID-19 patients.

Registration

PROSPERO (CRD42021235112)
Estimating Time-Dependent Disease Transmission Intensity using Reported Data: An Application to Ebola and Selected Public Health Problems
Authors: Mubayi Anuj , Pandey Abhishek , Brasic Christine , Mubayi Anamika , Ghosh Parijat , Ghosh Aditi
Published: June 2021

Obtaining reasonable estimates for transmission rates from observed data is a challenge when using mathematical models to study the dynamics of “infectious” diseases, like Ebola. Most models assume the transmission rate of a contagion does not vary over time. However, these rates do vary during an epidemic due to environmental conditions, social behaviors, and public-health interventions deployed to control the disease. Therefore, obtaining time-dependent rates can aid in understanding the progression of disease through a population. We derive an analytical expression using a standard SIR-type mathematical model to compute time-dependent transmission rate estimates for an epidemic in terms of either incidence or prevalence type available data. We illustrate applicability of our method by applying data on various public health problems, including infectious diseases (Ebola, SARS, and Leishmaniasis) and social issues (obesity and alcohol drinking) to compute transmission rates over time. We show that transmission rate estimates can have a large variation over time, depending on the type of available data and other epidemiological parameters. Time-dependent estimation of transmission rates captures the dynamics of the problem and can be utilized to understand disease progression through population accurately. Alternatively, constant estimations may provide unacceptable results that could have major public health consequences.
Low frequency interictal EEG biomarker for localizing seizures
Authors: Lundstrom Brian Nils , Brinkmann Benjamin , Worrell Gregory
Published: June 2021

Objective

We want to identify seizure onset zone (SOZ) from interictal EEG biomarkers. We hypothesize that a combination of interictal EEG biomarkers, including a novel low frequency marker, can predict mesial temporal involvement and can assist in prognosis related to surgical resections.

Methods

Interictal direct current wide bandwidth invasive EEG recordings from 83 patients implanted with 5,111 electrodes were retrospectively studied. Logistic regression was used to classify electrodes and patient outcomes. A feed-forward neural network was implemented to understand putative mechanisms.

Results

Interictal infraslow frequency EEG activity was decreased for SOZ electrodes while faster frequencies such as delta (2-4 Hz) and beta-gamma (20-50 Hz) activity were increased. These spectral changes comprised a novel interictal EEG biomarker that was significantly increased for mesial temporal SOZ electrodes compared to non-SOZ electrodes. Interictal EEG biomarkers correctly classified mesial temporal SOZ electrodes with a specificity of 87% and positive predictive value of 80%. These interictal EEG biomarkers also correctly classified patient outcomes after surgical resection with a specificity of 91% and positive predictive value of 87%.

Interpretation

Interictal infraslow EEG activity is decreased near the SOZ while higher frequency power is increased, suggesting distinct underlying physiologic mechanisms. Decreased interictal infraslow activity may reflect the loss of neural inhibition. Narrowband interictal EEG power bands provide information about the SOZ and can help predict mesial temporal involvement in seizure onset. Together with interictal epileptiform discharges and high frequency oscillations, these interictal biomarkers may provide prognostic information prior to surgical resection.
What is the main driver of unsustainable natural resource use in the Comoro Islands?
Authors: Ibouroi Mohamed Thani , Dhurham Said Ali Ousseni , Besnard Aurélien , Lescureux Nicolas
Published: June 2021

The Comoros archipelago is a biodiversity hotspot by virtue of its high level of endemism. However, it suffers one of the highest rates of forest loss worldwide, mainly due to strong anthropogenic pressures. As Comorian populations depend on forest resources for subsistence, establishing relevant conservation strategies for their sustainable management requires the consideration of multiple stakeholders’ perspectives toward biodiversity and habitat conservation. To better understand the relationships between humans and nature; how comorian people use natural resource and the relevance of a protected area for long-term biodiversity conservation, we used Q-methodology to assess local people‘s perceptions regarding biodiversity and conservation actions. Three discourses are identified during analysis: “Pro-environment discourse”, “Keeping things as usual” and “Social and environmental concerns”. According to the results, employed respondents, were favorable to long-term forest and biodiversity conservation. In contrast, unemployed respondents were in favor of more immediate benefits while unemployed but educated respondents were in favor to both long-term forest conservation and immediate benefits from forests. This suggests that the lack of livelihoods for rural people is the main factor leading them to overharvest natural resources. These results suggest that biodiversity conservation of the Comoros archipelagos may benefit for plan aiming at (1) developing tourism and maintaining sustainable production of crops and livestock that could allow enhancing the livelihoods and well-being of all social groups, (2) developing projects such as local markets that could allow villagers to sell their agricultural production, (3) setting up awareness campaign for tree-planting and reforestation. Reforestation could allow re-establishing natural plants and make large trees available for long-term purposes.
Consumers’ active choice behavior promotes coevolutionary units
Authors: de Alvarenga Allan Maurício Sanches Baptista , Borges Marcelo Eduardo , Jorge Leonardo Ré , Varassin Isabela Galarda , Araújo Sabrina Borges Lino
Published: June 2021

Individual behavior and local context are processes that can influence the structure and evolution of ecological interactions. In trophic interactions, consumers can increase their fitness by actively choosing resources that enhance their chances of exploring them successfully. Upon searching for potential resources, they are able to decide which one to choose according to their fitness benefit and maneuverability. Mathematical modeling is often employed in theoretical studies to understand the coevolutionary dynamics between these species. However, they often disregard the individual consumer behavior since the complexity of these systems usually requires simplifying assumptions about interaction details. Using an individual-based model, we model a community of several species that interact antagonistically. The trait of each individual is modeled explicitly and is subjected to the interaction pressure. In addition, consumers can actively choose the resources that guarantee greater fitness. We show that active consumer choice can generate coevolutionary units over time. It means that the traits of both consumers and resources converge into multiple groups with similar traits, exerting reciprocal selective pressure between them. We also observed that network structure has a greater dependence on the parameter that delimits active consumer choice than on the intensity of selective pressure. Consequently, this parameter can closely match empirical networks. Thus, we consider that the inclusion of consumers’ active choice behavior in the models plays an important role in the ecological and evolutionary processes that structure these communities.
Microbiota and stress: a loop that impacts memory
Authors: Kraimi Narjis , Lormant Flore , Calandreau Ludovic , Kempf Florent , Zemb Olivier , Lemarchand Julie , Constantin Paul , Parias Céline , Germain Karine , Dupont Christèle , Rabot Sylvie , Philippe Catherine , Foury Aline , Moisan Marie-Pierre , Carvalho Anaïs Vitorino , Coustham Vincent , Dardente Hugues , Velge Philippe , Cousin Patrice , Chaumeil Thierry , Leterrier Christine
Published: June 2021

Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower α and β diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress.
COBREXA.jl: constraint-based reconstruction and exascale analysis
Authors: Kratochvíl Miroslav , Heirendt Laurent , Wilken St. Elmo , Pusa Taneli , Arreckx Sylvain , Noronha Alberto , van Aalst Marvin , Satagopam Venkata P , Ebenhöh Oliver , Schneider Reinhard , Trefois Christophe , Gu Wei
Published: June 2021

COBREXA.jl is a Julia package for scalable, high-performance constraint-based reconstruction and analysis of very large-scale biological models. Its primary purpose is to facilitate the integration of modern high performance computing environments with the processing and analysis of large-scale metabolic models of challenging complexity. We report the architecture of the package, and demonstrate how the design promotes analysis scalability on several use-cases with multi-organism community models.

Availability and implementation

https://doi.org/10.17881/ZKCR-BT30.

Contact

christophe.trefois@uni.lu,wei.gu@uni.lu
Risk of Bias Assessment in Preclinical Literature using Natural Language Processing
Authors: Wang Qianying , Liao Jing , Lapata Mirella , Macleod Malcolm
Published: June 2021

Objective

We sought to apply natural language processing to the task of automatic risk of bias assessment in preclinical literature, which could speed the process of systematic review, provide information to guide research improvement activity, and support translation from preclinical to clinical research.

Materials and Methods

We use 7,840 full-text publications describing animal experiments with yes/no annotations for five risk of bias items. We implement a series of models including baselines (support vector machine, logistic regression, random forest), neural models (convolutional neural network, recurrent neural network with attention, hierarchical neural network) and models using BERT with two strategies (document chunk pooling and sentence extraction). We tune hyperparameters to obtain the highest F1 scores for each risk of bias item on the validation set and compare evaluation results on the test set to our previous regular expression approach.

Results

The F1 scores of best models on test set are 82.0% for random allocation, 81.6% for blinded assessment of outcome, 82.6% for conflict of interests, 91.4% for compliance with animal welfare regulations and 46.6% for reporting animals excluded from analysis. Our models significantly outperform regular expressions for four risk of bias items.

Conclusion

For random allocation, blinded assessment of outcome, conflict of interests and animal exclusions, neural models achieve good performance, and for animal welfare regulations, BERT model with sentence extraction strategy works better.
WeightedLD: The Application of Sequence Weights to Linkage Disequilibrium
Authors: Charles Oscar J. , Roberts Joseph , Breuer Judith , Goldstein Richard A.
Published: June 2021

Sequence-weighting methods are commonly employed to account for biases in sequence datasets. We use a weighting scheme which considers the observed distinctiveness of sequences and apply it to calculations of linkage disequilibrium. Each sequence now contributes a weighted score to linkage disequilibrium measurements of pairwise loci. We demonstrate that this reduces the effect of uneven sampling, as underrepresented groups of sequences will each contribute more individually than redundant, similar sequences.

Availability

Source code for a python and rust implementation are freely available at under an MIT license at github.com/ojcharles/WeightedLD.

Contact

r.goldstein@ucl.ac.uk or oscar.charles.18@ucl.ac.uk
Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers
Authors: Louros Nikolaos , Ramakers Meine , Michiels Emiel , Konstantoulea Katerina , Morelli Chiara , Garcia Teresa , D’Haeyer Sam , Goossens Vera , Audenaert Dominique , Rousseau Frederic , Schymkowitz Joost
Published: June 2021

Heterotypic amyloid interactions between related protein sequences have been observed in functional and disease amyloids. While sequence homology seems to favour heterotypic amyloid interactions, we have no systematic understanding of the structural rules determining such interactions nor whether they inhibit or facilitate amyloid assembly. Using structure-based thermodynamic calculations and extensive experimental validation, we performed a comprehensive exploration of the defining role of sequence promiscuity in amyloid interactions. Using this knowledge, we demonstrate, using tau as a model system, that predicted cross-interactions driven by sequence homology indeed can modify nucleation, fibril morphology, kinetic assembly and cellular spreading of aggregates. We also find that these heterotypic amyloid interactions can result in the mis-localisation of brain-expressed protein sequences with prevalent activities in neurodegenerative disorders. Our findings suggest a structural mechanism by which the proteomic background can modulate the aggregation propensity of amyloidogenic proteins and discuss how such sequence-specific proteostatic perturbations could contribute to the selective cellular susceptibility of amyloid disease progression.
Experimental depletion of gut microbiota diversity reduces host thermal tolerance and fitness under heat stress in a vertebrate ectotherm
Authors: Fontaine Samantha S. , Mineo Patrick M. , Kohl Kevin D.
Published: June 2021

Predicting the responses of ectotherms to climate change is a global conservation priority which requires identifying factors that influence how animals respond physiologically to changing temperature. Host-associated microbial communities impact animal physiology and have been shown to influence host thermal tolerance in invertebrate systems. However, the role of commensal microbiota in thermal tolerance of ectothermic vertebrates is unknown. Here we show that experimentally depleting the diversity of the tadpole gut microbiome through environmental water sterilization reduces the host’s acute thermal tolerance to both heat and cold, alters the thermal sensitivity of locomotor performance, and reduces animal survival under acute heat stress. We show that these tadpoles have reduced activities of mitochondrial enzymes and altered metabolic rates compared to tadpoles colonized with a diverse microbiota, which could underlie differences in thermal phenotypes. Our results demonstrate, for the first time, a link between the gut microbiome of an ectothermic vertebrate and the host’s thermal tolerance, performance, and fitness, thus highlighting the importance of considering host-associated microbial communities when predicting species’ responses to climate change.
Meta-ecosystem dynamics drive the spatial distribution of functional groups in river networks
Authors: Jacquet Claire , Carraro Luca , Altermatt Florian
Published: June 2021

The meta-ecosystem concept provides a theoretical framework to study the effect of local and regional flows of resources on ecosystem dynamics. Meta-ecosystem theory has hitherto been applied to highly abstract landscapes, and meta-ecosystem dynamics in real-world landscapes remain largely unexplored. River networks constitute a prime example of meta-ecosystems, being characterized by directional resource flows from upstream to downstream communities and from the terrestrial to the aquatic realm. These flows have been thoroughly described by the River Continuum Concept (RCC), a seminal concept in freshwater ecology, stating that observed spatial variations in the relative abundances of invertebrate functional groups reflect systematic shifts in types and locations of food resources, which are in turn determined by the physical attributes of river reaches. Hence, the RCC represents a solid conceptual basis for determining how changes in landscape structure and resource flows will translate into local and regional changes in community composition. Here, we develop and analyse a riverine meta-ecosystem model inspired by the RCC, which builds upon a physically-based landscape model of dendritic river networks. We show that the spatial distributions and regional biomass of invertebrate functional groups observed in stream communities are determined by the spatial structure and scaling attributes of dendritic river networks, as well as by specific rates of resource flows. Neglecting any of these aspects in modelling river meta-ecosystems would result in unrealistic community patterns. Moreover, we observed that high rates of resource flow, for example due to river anthropization, have a negative effect on the regional biomass of all functional groups studied, and can lead to cascading extinctions at the meta-ecosystem scale. Our work paves the way for the development of physically-based meta-ecosystem models to understand the structure and functioning of real-world ecosystems.
STENCIL: A web templating engine for visualizing and sharing life science datasets
Authors: Sun Qi , Nematbakhsh Ali , Kuntala Prashant K , Kellogg Gretta , Pugh B. Franklin , Lai William KM
Published: June 2021

The ability to aggregate experimental data analysis and results into a concise and interpretable format is a key step in evaluating the success of an experiment. This critical step determines baselines for reproducibility and is a key requirement for data dissemination. However, in practice it can be difficult to consolidate data analyses that encapsulates the broad range of datatypes available in the life sciences. We present STENCIL, a web templating engine designed to organize, visualize, and enable the sharing of interactive data visualizations. STENCIL leverages a flexible web framework for creating templates to render highly customizable visual front ends. This flexibility enables researchers to render small or large sets of experimental outcomes, producing high-quality downloadable and editable figures that retain their original relationship to the source data. REST API based back ends provide programmatic data access and supports easy data sharing. STENCIL is a lightweight tool that can stream data from Galaxy, a popular bioinformatic analysis web platform. STENCIL has been used to support the analysis and dissemination of two large scale genomic projects containing the complete data analysis for over 2,400 distinct datasets. Code and implementation details are available on GitHub: https://github.com/CEGRcode/stencil
A Novel Organoid Model of In Vitro Spermatogenesis Using Human Induced Pluripotent Stem Cells
Authors: Robinson Meghan , Witherspoon Luke , Willerth Stephanie , Flannigan Ryan
Published: June 2021

Infertility is thought to be caused by genetic mutations and dysfunction in the cellular niche where spermatogenesis takes place. An understanding of the specialized cellular processes which drive spermatogenesis is needed to develop treatments; however, the development ofin vitrosystems to study these cells has been hindered by our reliance on rarely available human testicular tissues for research. Human induced pluripotent stem cells (hiPSCs) can be used to derive human testicular-like cells, and thus provide an avenue for the development ofin vitrotesticular model systems. Therefore, this study set out to engineer a human testicular tissue model using hiPSCs for the first time. We demonstrate the ability of hiPSC-derived testicular cells to self-organize and mature into testicular-like tissues using organoid culture. Moreover, we show that hiPSC-derived testicular organoids promote testicular somatic cell maturation and spermatogenesis up to the post-meiotic spermatid stage. These hiPSC-derived testicular organoids have the potential to replace rarely available primary testicular tissues to further infertility research in anin vitrosetting.
Microfluidic bioprinting for the in vitro generation of novel biomimetic human testicular tissues
Authors: Robinson Meghan , Bedford Erin , Witherspoon Luke , Willerth Stephanie M. , Flannigan Ryan
Published: June 2021

Advances in cancer treatments have greatly improved pediatric cancer survival rates, leading to quality of life considerations and in particular fertility restoration. Accordingly, pre-pubertal patients have the option to cryopreserve testicular tissue for experimental restorative therapies, including in vitro spermatogenesis, wherein testicular tissue is engineered in vitro and spermatozoa are collected for in vitro fertilization (IVF). Current in vitro systems have been unable to reliably support the generation of spermatozoa from human testicular tissues, likely due to the inability for the dissociated testicular cells to recreate the native architecture of testicular tissue found in vivo. Recent advances in 3-D bioprinting can place cells into geometries at fine resolutions comparable to microarchitectures found in native tissues, and therefore hold promise as a tool for the development of a biomimetic in vitro system for human spermatogenesis. This study assessed the utility of bioprinting technology to recreate the precise architecture of testicular tissue and corresponding spermatogenesis for the first time. We printed testicular cell-laden hollow microtubules at similar resolutions to seminiferous tubules, and compared the results to testicular organoids. We show that the human testicular cells retain their viability and functionality post-printing, and illustrate an intrinsic ability to reorganize into their native cytoarchitecture. This study provides a proof of concept for the use of 3-D bioprinting technology as a tool to create biomimetic human testicular tissues.