bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Neuromonitoring Modalities in Children Beyond Neonatal Period After Cardiac Arrest*
Authors: Hunfeld Maayke , Ketharanathan Naomi , Catsman Coriene , Straver Dirk C. G. , Dremmen Marjolein H. G. , Bramer Wichor , Wildschut Enno , Tibboel Dick , Buysse Corinne
Published: June 2020

Objectives:

Postresuscitation care in children focuses on preventing secondary neurologic injury and attempts to provide (precise) prognostication for both caregivers and the medical team. This systematic review provides an overview of neuromonitoring modalities and their potential role in neuroprognostication in postcardiac arrest children.

Data Resources:

Databases EMBASE, Web of Science, Cochrane, MEDLINE Ovid, Google Scholar, and PsycINFO Ovid were searched in February 2019.

Study Selection:

Enrollment of children after in- and out-of-hospital cardiac arrest between 1 month and 18 years and presence of a neuromonitoring method obtained within the first 2 weeks post cardiac arrest. Two reviewers independently selected appropriate studies based on the citations.

Data Extraction:

Data collected included study characteristics and methodologic quality, populations enrolled, neuromonitoring modalities, outcome, and limitations. Evidence tables per neuromonitoring method were constructed using a standardized data extraction form. Each included study was graded according to the Oxford Evidence-Based Medicine scoring system.

Data Synthesis:

Of 1,195 citations, 27 studies met the inclusion criteria. There were 16 retrospective studies, nine observational prospective studies, one observational exploratory study, and one pilot randomized controlled trial. Neuromonitoring methods included neurologic examination, routine electroencephalography and continuous electroencephalography, transcranial Doppler, MRI, head CT, plasma biomarkers, somatosensory evoked potentials, and brainstem auditory evoked potential. All evidence was graded 2B-2C.

Conclusions:

The appropriate application and precise interpretation of available modalities still need to be determined in relation to the individual patient. International collaboration in standardized data collection during the (acute) clinical course together with detailed long-term outcome measurements (including functional outcome, neuropsychologic assessment, and health-related quality of life) are the first steps toward more precise, patient-specific neuroprognostication after pediatric cardiac arrest.
Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-COV-2 infection: a retrospective cohort study
Authors: Giacomelli Andrea , Pagani Gabriele , Ridolfo Anna Lisa , Oreni Letizia , Conti Federico , Pezzati Laura , Bradanini Lucia , Casalini Giacomo , Bassoli Cinzia , Morena Valentina , Passerini Simone , Rizzardini Giuliano , Cogliati Chiara , Ceriani Elisa , Colombo Riccardo , Rusconi Stefano , Gervasoni Cristina , Cattaneo Dario , Antinori Spinello , Galli Massimo
Published: June 2020

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy.

The aim of this retrospective intent-to-treat analysis of the hospitalized patients who started off-label treatment with LPV/ritonavir (LPV/r)+HCQ between 21 February and 20 March 2020 was to compare the rate of clinical improvement between those who started the treatment within five days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). The association between the timing of treatment and the probability of 30-day mortality was also assessed using uni- and multivariable logistic models.

The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray’s test P = 0.213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment because of severe gastrointestinal disorders attributable to LPV/r.

The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.
Interregional SARS-CoV-2 spread from a single introduction outbreak in a meat-packing plant in northeast Iowa
Authors: Richmond Craig S. , Sabin Arick P. , Jobe Dean A. , Lovrich Steven D. , Kenny Paraic A.
Published: June 2020

SARS-CoV-2 spread has proven to be especially difficult to mitigate in high risk settings, including nursing homes, cruises, prisons and various industrial settings. Among industrial settings, meat processing facilities in the United States have experienced particularly challenging outbreaks. We have sequenced SARS-CoV-2 whole viral genomes from individuals testing positive in an integrated regional healthcare system serving 21 counties in southwestern Wisconsin, northeastern Iowa and southeastern Minnesota, providing an overview of SARS-CoV-2 introduction and spread in a region spanning multiple jurisdictions with differing mitigation policies. While most viral introductions we detected were contained with only minor transmission chains, a striking exception was an outbreak associated with a meatpacking plant in Postville, IA. In this case, a single viral introduction led to unrestrained spread within the facility, affecting many staff and members of their households. Importantly, by surveilling viral sequences from the surrounding counties, we have documented the spread of this SARS-CoV-2 substrain from this epicenter to individuals in 13 cities in 7 counties in Iowa, Wisconsin and Minnesota, a region spanning 185 square miles. This study highlights the regional public health consequences of failures to rapidly act to mitigate viral spread in a single industrial setting.
Effects of physical activity and exercise on well-being in the context of the Covid-19 pandemic
Authors: de Abreu Juliana Marques , de Souza Roberta Andrade , Viana-Meireles Livia Gomes , Landeira-Fernandez J. , Filgueiras Alberto
Published: June 2020

Background

A disease discovered in China, COVID-19, was characterized by the World Health Organization (WHO) as a pandemic in March 2020. Many countries in the world implemented social isolation as a strategy to contain the virus transmission. The same physical distancing which protects society from COVID-19 from spreading may have an impact on the mental health and well-being of the population This study aims to shed some light on this phenomenon by assessing the relationship between physical activity and SWB among individuals in the social isolation period of COVID-19.

Methods

Data were collected in Brazil between March 31st and April 2nd, 2020. All volunteers agreed to participate by digitally checking the option of agreement right after reading the Consent Terms. The inclusion criteria were participants over 18 years old who had been in social isolation for at least one week and agreed to the Consent Terms. Three instruments were used: a questionnaire was built for this study which aimed to assess the participants’ exercise routine. The second instrument called Psychosocial Aspects, Well-being and Exercise in Confinement (PAWEC) was also created by these researchers and aimed to assess the relationship between well-being and physical activity during the social isolation period. And the third measure was the Brazilian Portuguese-adapted version of the Positive and Negative Affect Schedule (PANAS).

Findings

A total of 592 participants reported being in social isolation for an average of 14.4 (SD=3.3) days. The amount of participants who reported strength training as exercise increased from 31 (5.2%) before isolation to 82 (13.9%) during quarantine. The study shows that well-being related to the practice of physical activity during quarantine is linked to an established routine of physical activity prior to the social isolation period.

Interpretation

People who already practiced physical activity feel more motivated to continue practicing during this period and this causes the appearance of positive affects, unlike people who are only now starting to exercise; according to the study, negative aspects can occur for those who are only just starting. In a period of social isolation, it is important that the practice of physical activity is closer to previous habits, also finding that an obligation to exercise during this period when this was not a reality for the person can contribute to an increase in malaise.
Remarks on pooling Coronavirus tests
Authors: Pikovski Alexander , Bentele Kajetan
Published: June 2020

Diagnostic testing for the novel Coronavirus is an important tool to fight the Covid-19 pandemic. However, testing capacities are limited. A modified testing protocol, whereby a number of probes are “pooled” (that is, grouped), is known to increase the capacity for testing. Here, we model pooled testing with a double-average model, which we think to be close to reality for Covid-19 testing. The optimal pool size and the effect of test errors are considered. Results show that the best pool size is three to five, under reasonable assumptions. Pool testing even reduces the number of false positives in the absence of dilution effects.
Fear not: avoidance behavior missing in species sympatric with the critically endangered West African lion
Authors: Harris Nyeema C. , Mills Kirby L.
Published: June 2020

Predators are major regulators in communities through trophic and non-trophic pathways. However, as human pressures continue to threaten apex predators, including Africa’s iconic lion, predators’ functional role in their ecosystems may be compromised. Where lions are critically endangered, we found no evidence of avoidance behavior in either competitor or prey species from a camera survey in the largest protected area complex in West Africa. Our findings raise concerns that lions have already become functionally extinct in portions of their West African range, highlighting the urgency of restorative efforts and environmental investments to reverse current declining population trends and the loss of regulatory roles.
Causal evidence of network communication in whole-brain dynamics through a multiplexed neural code
Authors: Salvan Piergiorgio , Lazari Alberto , Vidaurre Diego , Mandino Francesca , Johansen-Berg Heidi , Grandjean Joanes
Published: June 2020

An important question in neuroscience is how local activity can be flexibly and selectively routed across the brain network. A proposed mechanism to flexibly route information is frequency division multiplexing: selective readout can be achieved by segregating the signal into non-overlapping frequency bands. Here, in wild-type mice and in a transgenic model (3xTgAD) of Alzheimer’s Disease (AD), we use optogenetic activation of the entorhinal cortex, concurrent whole-brain fMRI, and hidden Markov modeling. We demonstrate how inducing neuronal spiking with different theta frequencies causes spatially distinct states of brain network dynamics to emerge and to preferentially respond to one frequency, showing how selective information streams can arise from a single neuronal source of activity. This theta modulation mechanism, however, is impaired in the AD model. This work demonstrates that neuronal multiplexing is a sufficient mechanism to enable flexible brain network communication, and provides insight into the aberrant mechanisms underlying cognitive decline.
Automated objective dystonia identification using smartphone-quality gait videos acquired in clinic
Authors: Miao Hanyang , Ueda Keisuke , Pearson Toni S. , Aravamuthan Bhooma R.
Published: June 2020

Background

Dystonia diagnosis is subjective and often difficult, particularly when co-morbid with spasticity as occurs in cerebral palsy.

Objective

To develop an objective clinical screening method for dystonia

Methods

We analyzed 30 gait videos (640×360 pixel resolution, 30 frames/second) of subjects with spastic cerebral palsy acquired during routine clinic visits. Dystonia was identified by consensus of three movement disorders specialists (15 videos with and 15 without dystonia). Limb position was calculated using deep neural network-guided pose estimation (DeepLabCut) to determine inter-knee distance variance, foot angle variance, and median foot angle difference between limbs.

Results

All gait variables were significant predictors of dystonia. An inter-knee distance variance greater than 14 pixels together with a median foot angle difference greater than 10 degrees yielded 93% sensitivity and specificity for dystonia.

Conclusions

Open-source automated video gait analysis can identify features of expert-identified dystonia. Methods like this could help clinically screen for dystonia.
Differences in antibody kinetics and functionality between severe and mild SARS-CoV-2 infections
Authors: Rijkers Ger , Murk Jean-Luc , Wintermans Bas , Looy Bieke van , van den Berge Marcel , Veenemans Jacobien , Stohr Joep , Reusken Chantal , van der Pol Pieter , Reimerink Johan
Published: June 2020

We determined and compared the humoral immune response in severe, hospitalized and mild, non-hospitalized COVID-19 patients. Severe patients (n=38) develop a robust antibody response to SARS-CoV-2, including IgG and IgA antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infected hospital personnel (n=24), who developed mild symptoms necessitating leave of absence, self-isolation, but not hospitalization, 75 % develop antibodies, but with low/absent virus neutralization (60% < 1:20).

While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long term monitoring will show whether these responses predict protection against future infections.
Serial Interval Distribution of SARS-CoV-2 Infection in Brazil
Authors: Prete Carlos A. , Buss Lewis , Dighe Amy , Porto Victor Bertollo , Candido Darlan da Silva , Ghilardi Fábio , Pybus Oliver G. , de Oliveira Wanderson K. , Croda Júlio H. R. , Sabino Ester C. , Faria Nuno Rodrigues , Donnelly Christl A. , Nascimento Vítor H.
Published: June 2020

Using 65 transmission pairs of SARS-CoV-2 reported to the Brazilian Ministry of Health we estimate the mean and standard deviation for the serial interval to be 2.97 and 3.29 days respectively. We also present a model for the serial interval probability distribution using only two parameters.
A systematic review on the levels of antibodies in COVID-19 virus exposed but negative newborns: a possible vertical transmission of IgG/ IgM
Authors: Bwire George M. , Njiro Belinda J.
Published: June 2020

Background

Currently, there is no doubt on human-to-human transmission of Coronavirus Disease 2019 (COVID-19). Now, the debates remain on whether, vertical transmission of Severe Respiratory Syndrome Virus 2 (SARS-CoV-2) and antibodies against the virus do exist. We therefore, conducted a systematic review to determine the immunoglobulin G and M (IgG/IgM) levels among infants born to mothers with COVID-19.

Methods

The systematic search was done using PubMed/MEDLINE and Google Scholar database. The research included studies on IgG/ IgM against SARS-CoV-2 among infants born to mother with COVID-19 published in English from December 1, 2019 onwards. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) guidelines. We synthesized a narrative from eligible studies and performed two tailed non-parametric Mann-Whitney test to determine and compare the median IgG/IgM levels.

Results

In total, 486 abstracts were screened and 63 full-text articles were assessed. Of 63 articles, 6 met the inclusion criteria for qualitative analysis. Two articles were included in quantitative analysis of anti-SARS-CoV-2 IgG/ IgM levels. The median antibody levels was 75.49AU/mL (range: 7.25AU/mL-140.32AU/mL) and for 3.79AU/mL (range: 0.16AU/mL-45.83AU/mL) (P = 0.0041) for anti-SARS-CoV-2 IgG and IgM, respectively.

Conclusion

There were high levels of IgG but low IgM against SARS-CoV-2 (using <10 AU/mL as a reference range) among COVID-19 virus exposed but negative newborns. This review suggest a possible natural passive immunity (IgG/ IgM) against COVID-19 virus.

Impact

A systematic review of infants born to mothers with COVID-19 was conducted to characterize the magnitude of antibodies generated against SARS-CoV-2 among infants who were vertically exposed to the virus. These findings were necessary to inform the ongoing vaccine development and research on the background natural passive immunity among COVID-19 exposed newborns. Furthermore, evidence are revealing the possibility of vertical transmission of anti-SARS-CoV-2 IgG/ IgM among the exposed newborns who tested negative for the virus.
Macrophage-mediated antibody dependent effector function in aggressive B-cell lymphoma treatment is enhanced by Ibrutinib via inhibition of JAK2
Authors: Barbarino Verena , Henschke Sinika , Blakemore Stuart James , Izquierdo Elena , Michalik Michael , Nickel Nadine , Möllenkotte Indra , Vorholt Daniela , Brinker Reinhild , Fedorchenko Oleg , Mikhael Nelly , Seeger-Nukpezah Tamina , Hallek Michael , Pallasch Christian P.
Published: June 2020

Targeted inhibition of Bruton’s Tyrosine Kinase (BTK) with ibrutinib and other agents has become important treatment options in chronic lymphocytic leukemia, Waldenström’s Macroglobulinemia, Mantle cell lymphoma and non-GCB DLBCL. Clinical trials combining small molecule inhibitors with monoclonal antibodies have been initiated at rapid pace, with the biological understanding between their synergistic interactions lagging behind. Here, we have evaluated the synergy between BTK inhibitors and monoclonal antibody therapy via macrophage mediated antibody dependent cellular phagocytosis (ADCP). Initially, we observed increased ADCP with ibrutinib, whilst second generation BTK inhibitors failed to synergistically interact with monoclonal antibody treatment. Kinase activity profiling under BTK inhibition identified significant loss of Janus Kinase 2 (JAK2) only under ibrutinib treatment. We validated this potential off-target effect via JAK inhibitionin vitroas well as with CRISPR/Cas9 JAK2−/−experimentsin vivo, showing increased ADCP and prolonged survival, respectively. This data supports inhibition of the JAK-STAT signaling pathway in B-cell malignancies in combination with monoclonal antibody therapy to increase macrophage mediated immune responses.
Inhibition underlies fast undulatory locomotion inC. elegans
Authors: Deng Lan , Denham Jack , Arya Charu , Yuval Omer , Cohen Netta , Haspel Gal
Published: June 2020

Inhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contraction of antagonist muscles, whether along the body axis or within and among limbs. In the nematodeC. elegans, a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GABA transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, either genetically or optogenetically, induces lower undulation frequency and lower translocation speed during crawling and swimming in both directions. The activity patterns of GABAergic motoneurons are different during low and high undulation frequencies. During low undulation frequency, GABAergic VD and DD motoneurons show similar activity patterns, while during high undulation frequency, their activity alternates. The experimental results suggest at least three non-mutually exclusive roles for inhibition that could underlie fast undulatory locomotion inC. elegans, which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or inhibitory reset.

Significance Statement

Inhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive program and supports the alternating activation of antagonistic muscles. When the locomotor frequency increases, more inhibition is required. To better understand the role of inhibition in locomotion, we usedC. elegansas an animal model, and challenged a prevalent hypothesis that cross-inhibition supports the dorsoventral alternation. We find that inhibition is related to the speed rather than the direction of locomotion and demonstrate that inhibition is unnecessary for muscle alternation during slow undulation in either direction but crucial to sustain rapid dorsoventral alternation. We combined calcium imaging of motoneurons and muscle with computational models to test hypotheses for the role of inhibition in locomotion.
High resilience of the mycorrhizal community to prescribed seasonal burnings in a Mediterranean woodland
Authors: Livne-Luzon Stav , Shemesh Hagai , Osem Yagil , Carmel Yohay , Migael Hen , Avidan Yael , Tsafrir Anat , Glassman Sydney I. , Bruns Thomas D. , Ovadia Ofer
Published: June 2020

Fire effects on ecosystems range from destruction of aboveground vegetation to direct and indirect effects on belowground microorganisms. Although variation in such effects is expected to be related to fire severity, another potentially important and poorly understood factor is the effects of fire seasonality on soil microorganisms. We carried out a large-scale field experiment examining the effects of spring versus autumn burns on the community composition of soil fungi in a typical Mediterranean woodland. Although the intensity and severity of our prescribed burns were largely consistent between the two burning seasons, we detected differential fire season effects on the composition of the soil fungal community, driven by changes in the saprotrophic fungal guild. The community composition of ectomycorrhizal fungi, assayed both in pine seedling bioassays and from soil sequencing, appeared to be resilient to the variation inflicted by seasonal fires. Since changes in the soil saprotrophic fungal community can directly influence carbon emission and decomposition rates, we suggest that regardless of their intensity and severity, seasonal fires may cause changes in ecosystem functioning.

Declarations

Funding

This research was co-supported by the United States-Israel Binational Science Foundation (BSF Grant 2012081) and Tel-Hai College.

Conflicts of interest/Competing interests

We declare no conflicts of interest and that this material has not been submitted for publication elsewhere.

Ethics approval

Not applicable

Consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and material

Sequences were submitted to the National Center for Biotechnology Information Sequence Read Archive under accession numbers SRRXXX◻SRRXXX.

Code availability

Not applicable

Authors’ contributions

OO HS TB YO YC conceived and designed the experiment. SSL YA HM AT performed the experiment. SIG provided the pipeline scripts, and guidance in bioinformatics work and analyses. SLL OO HS wrote the paper and analyzed the data, and all authors contributed substantially to revisions.
Deep sequencing revealsCampylobacterin commercial meat chickens less than 8 days old
Authors: Colles F.M. , Hedges S.J. , Dixon R. , Preston S.G. , Thornhill P. , Barfod K.K. , Gebhardt-Henrich S.G. , Creach P. , Maiden M.C.J. , Dawkins M.S. , Smith A.L.
Published: June 2020

Campylobacterfrom contaminated poultry meat is a major source of human gastroenteritis worldwide. To date, attempts to control this zoonotic infection with on-farm biosecurity measures have been inconsistent. A cornerstone of these efforts has been the detection of chicken infection with microbiological culture, which typically does not occur until birds are at least 21 days old. Using molecular methods for detectingCampylobacterpresence, 16S microbiome analysis and deep sequencing of theCampylobacter porA gene,Campylobactercan be identified at very low levels in most or all flocks fewer than 8 days old. These young chicks exhibit a much greater diversity ofporAtypes than older birds testing positive forCampylobacterby culture or qPCR. This suggests that, as the bacteria multiply sufficiently to be detected by culture methods, one or two strains, as indicated byporAtype, dominate the infection. The findings that (i) most young chicks carry someCampylobacterand (ii) not all flocks becomeCampylobacterpositive by culture, suggests that efforts to control infection should concentrate on how to maintainCampylobacterat low levels by the prevention of the overgrowth of single strains, which ultimately leads to the contamination of food.
Mechanistic insights into volatile anesthetic modulation of K2P channels
Authors: Wague Aboubacar , Joseph Thomas T. , Woll Kellie A. , Bu Weiming , Vaidya Kiran A. , Bhanu Natarajan V. , Garcia Benjamin A. , Nimigean Crina M. , Eckenhoff Roderic G. , Riegelhaupt Paul M.
Published: June 2020

K2P potassium channels are known to be modulated by volatile anesthetic (VA) drugs and play important roles in clinically relevant effects that accompany general anesthesia. Here, we utilize a photoaffinity analog of the VA isoflurane to identify a VA binding site in the TREK1 K2P channel. The functional importance of the identified site was validated by mutagenesis and biochemical modification. Molecular dynamic simulations of TREK1 in the presence of VA found multiple neighboring residues on TREK1 TM2, TM3 and TM4 that contribute to anesthetic binding. The identified VA binding region contains residues that play roles in the mechanisms by which heat, mechanical stretch, and pharmacological modulators alter TREK1 channel activity and overlaps with positions found to modulate TASK K2P channel VA sensitivity. Our findings define molecular contacts that mediate VA binding to TREK1 channels and suggest a mechanistic basis to explain how K2P channels are modulated by VAs.
Tirant stealthily invaded naturalDrosophila melanogasterpopulations during the last century
Authors: Schwarz Florian , Wierzbicki Filip , Senti Kirsten-André , Kofler Robert
Published: June 2020

It was long thought that solely three different transposable elements - the I-element, the P-element and hobo - invaded naturalD. melanogasterpopulations within the last century. By sequencing the ‘living fossils’ ofDrosophilaresearch, i.e.D. melanogasterstrains sampled from natural populations at different time points, we show that a fourth TE, Tirant, invadedD. melanogasterpopulations during the past century. Tirant likely spread inD. melanogasterpopulations around 1938, followed by the I-element, hobo, and, lastly, the P-element. In addition to the recent insertions of the canonical Tirant,D. melanogasterstrains harbour degraded Tirant sequences in the heterochromatin which are likely due to an ancient invasion, possibly predating the split ofD. melanogasterandD. simulans. In contrast to the I-element, P-element and hobo, we did not find that Tirant induces any hybrid dysgenesis symptoms. This absence of apparent phenotypic effects may explain the late discovery of the Tirant invasion. Recent Tirant insertions were found in all investigated natural populations. Populations from Tasmania carry distinct Tirant sequences, likely due to a founder effect. By investigating the TE composition of natural populations and strains sampled at different time points, insertion site polymorphisms, piRNAs and phenotypic effects, we provide a comprehensive study of a natural TE invasion.
Sex-dependent effects of chronic exercise on cognitive flexibility in aging mice
Authors: Short Annabel K. , Bui Viet , Zbukvic Isabel C. , Hannan Anthony J. , Pang Terence Y. , Kim Jee Hyun
Published: June 2020

Cognitive impairments associated with advanced age are a growing concern in our aging society. Such impairments are associated with alterations in brain structure and function, especially in the hippocampus, which changes to experience throughout life. It is well-known that regular exercise can maintain hippocampus volume. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. Therefore, we asked whether voluntary chronic exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared to standard housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder treatment in the form of a single footshock. Both male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared to young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression ofBdnfmRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not rescuing their impaired reinstatement, exercise also increasedBdnfgene expression in the female hippocampus, which could potentially benefit other forms of hippocampal-dependent cognition.
Assessment ofLIN28Avariants in Parkinson’s disease
Authors: Diez-Fairen Monica , Makarious Mary B. , Bandres-Ciga Sara , Blauwendraat Cornelis
Published: June 2020

Parkinson’s disease (PD) is a complex neurodegenerative disease with a strong genetic component in which both rare and common genetic variants contribute to disease risk, onset and progression. Despite that several genes have been associated with familial forms of disease, validation of novel genes associated with PD remains extremely challenging. Recently, a heterozygous loss-of-function variant in LIN28A was associated with PD pathogenesis in the Asian population. Here, we comprehensively assess the role of LIN28A variants in PD susceptibility using individual-level genotyping data from 14,671 PD cases and 17,667 controls, as well as whole-genome sequencing data from 1,647 PD patients and 1,050 controls. Additionally, we further assessed the summary statistics from the most recent GWAS meta-analyses to date for PD risk and age at onset. After evaluating these data, we did not find evidence to support a role for LIN28A as a major causal gene for PD. However, additional large-scale familial and case-control studies in non-European ancestry populations are necessary to further evaluate the role of LIN28A in PD etiology.
Evaluation of Sample Pooling for Screening of SARS CoV-2
Authors: Mulu Andargachew , Alemayehu Dawit Hailu , Alemu Fekadu , Tefera Dessalegn Abeje , Wolde Sinknesh , Aseffa Gebeyehu , Seyoum Tamrayehu , Habtamu Meseret , Abdissa Alemseged , Bayih Abebe Genetu , Beyene Getachew Tesfaye
Published: June 2020

Background

The coronavirus disease (COVID-19) pandemic has revealed the global public health importance of robust diagnostic testing. To overcome the challenge of nucleic acid (NA) extraction and testing kit availability efficient method is urgently needed.

Objectives

To establish an efficient, time and resource-saving and cost-effective methods, and to propose an ad hoc pooling approach for mass screening of SARS-CoV-2

Methods

Direct clinical sample and NA pooling approach was used for the standard reverse transcriptase polymerase chain reaction (RT-PCR) test of the SARS CoV-2 targeting the envelop (E) and open reading frame (ORF1ab) genomic region of the virus. In this approach, experimental pools were created using SARS CoV-2 positive clinical samples spiked with up to 9 negative samples prior to NA extraction step to have a final extraction volume of 200 μL (maximum dilution factor of 10). Viral NA was also subsequently extracted from each pool and tested using the SARS CoV-2 RT-PCR assay.

Results

We found that a single positive sample can be amplified and detected in pools of up to 7 samples depending on the ct value of the original sample, corresponding to high, medium, and low SARS CoV-2 viral copies/reaction. However, to minimize false negativity of the assay with pooling strategies and with unknown false negativity rate of the assay under validation, we recommend poling of 4 in 1 using the standard protocols of the assay, reagents and equipment. The predictive algorithm indicated a pooling ratio of 4 in 1 was expected to retain accuracy of the test irrespective of the ct value (relative RNA copy number) of the sample spiked and result in a 237% increase in testing efficiency.

Conclusions

The approaches showed its concept in easily customized and resource-saving manner and would allow expanding of current screening capacities and enable the expansion of detection in the community.
The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity
Authors: Nichols Brooke E , Jamieson Lise , Zhang Sabrina RC , Silal Sheetal , Pulliam Juliet R.C. , Sanne Ian , Meyer-Rath Gesine
Published: June 2020

Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of COVID-19 patients requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.
INTRAREGIONAL PROPAGATION OF COVID-19 CASES IN PARÁ, BRAZIL. ASSESSMENT OF ISOLATION REGIME TO LOCKDOWN
Authors: da Silva Félix Lélis , Pita Javier Dias , Gomes Maryjane Diniz A. , da Silva Andréa P. Lélis , da Silva Gabriel Lélis P.
Published: June 2020

Due to the high incidence of COVID-19 case numbers internationally, the World Health Organization (WHO) declared a Public Health Emergency of global relevance, advising countries to follow protocols to combat pandemic advance through actions that can reduce spread and consequently avoid a collapse in the local health system. On March 18, 2020, Pará notified the first case of COVID-19. After seven weeks, the number of confirmed cases reached 4,756 with 375 deaths. Knowing that infected people may be asymptomatic, the disease symptomatology absence and the population’s neglect of isolation influence the spread, and factors such as chronic pneumonia, high age, obesity, chronic kidney diseases and other comorbidities favor the mortality rate. On the other hand, social isolation, quarantine and lockdown seek to contain the intraregional contagion advance. This study analyzes the dynamics of COVID-19 new cases advance among municipalities in the state of Pará, Brazil. The results show it took 49 days for 81% of the state’s municipalities to register COVID-19 cases. The association between social isolation, quarantine and lockdown as an action to contain the infection was effective in reducing the region’s new cases registration of COVID-19 in the short-term.
AdipoR2 is Essential for Membrane Lipid Homeostasis in Response to Dietary Saturated Fats
Authors: Devkota Ranjan , Ruiz Mario , Palmgren Henrik , Ståhlman Marcus , Jaiswal Himjyot , Maresca Marcello , Bohlooly-Y Mohammad , Peng Xiao-Rong , Borén Jan , Pilon Marc
Published: June 2020

Membrane lipid composition influences vital processes in all types of cells. The mechanisms by which cells maintain membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remain largely unknown. In an attempt to discover such mechanisms, we performed an unbiased forward genetic screen inCaenorhabditis elegansand conclude that the adiponectin receptor 2 (AdipoR2) pathway is essential to prevent saturated fat-mediated cellular toxicity. Transcriptomics, lipidomics and membrane property analyses in human HEK293 cells and primary human endothelial cells further support our conclusion that the essential function of AdipoR2 is to respond to membrane rigidification by promoting fatty acid desaturation. Our results demonstrate that AdipoR2-dependent regulation of membrane homeostasis is a fundamental mechanism conserved from nematodes to mammals that prevents saturated fat-mediated lipotoxicity.

ONE SENTENCE SUMMARY

The AdipoR2 protein insures membrane homeostasis in response to dietary saturated fatty acids that promote membrane rigidification.
Pacing strategy in horse racing
Authors: Mercier Quentin , Aftalion Amandine
Published: June 2020

Thanks to velocity data on races in Chantilly (France), we set a mathematical model which provides the optimal pacing strategy for horses on a fixed distance. It relies on mechanics, energetics (both aerobic and anaerobic) and motor control. We identify the parameters useful for the model from the data. Then it allows to understand the velocity, the oxygen uptake evolution in a race, as well as the energy or the propulsive force and predict the changes in pacing according to the properties (altitude and bending) of the track.
Examining the effects of transcranial direct current stimulation on human episodic memory with machine learning
Authors: Petrovskaya Aleksandra , Kirillov Bogdan , Asmolova Anastasiya , Galli Giulia , Feurra Matteo , Medvedeva Angela
Published: June 2020

We aimed to replicate a published effect of transcranial direct-current stimulation (tDCS)-induced recognition enhancement over the human ventrolateral prefrontal cortex [1] and analyse the data with machine learning. We investigated effects over an adjacent region, the dorsolateral PFC. We found weak or absent effects over the VLPFC and DLPFC. We conducted machine learning studies to examine the effects of semantic and phonetic features on memorization, which revealed no effect of VLPFC tDCS on the original dataset or the current data. The highest contributing factor to memory performance was individual differences in memory not explained by word features, tDCS group, or sample size, while semantic, phonetic, and orthographic word characteristics did not contribute significantly. To our knowledge, this is the first tDCS study to investigate cognitive effects with machine learning, and future studies may benefit from studying physiological as well as cognitive effects with data-driven approaches and computational models.

Author summary

Non-Invasive Brain Stimulation techniques (in our case, transcranial direct current stimulation) are widely used among neuroscientists to map cognitive processes, for example, memory, decision making, emotional processing. In many cases, the sample size is limited, or methods applied for the data analysis are questionable. Here we propose a replication study aiming at confirmation of memory enhancement as a result of the application of anodal transcranial direct stimulation over the ventrolateral prefrontal cortex. Additionally, the involvement of the dorsolateral prefrontal cortex into episodic memory was analyzed. We used a larger sample size and applied different data analysis methods, including machine learning techniques. Surprisingly, we did not replicate the results of the original study, and we found weak effects of memory impairment after stimulating the DLPFC. However, what is most remarkable is that we have observed no significant effect of tDCS involvement on memory performance. Machine learning methods revealed no effect of linguistic factors on tDCS effect for both the original study and the replication at the level of individual trials and participants. Our findings highlight the importance of considering individual differences and data on the level of a single trial; in our data, participants’ memory responses resembled guessing behavior when recognition performance was measured by AUROC and highlight the need for modifications in the memory test and the use of other performance measures.
SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness
Authors: Corbett Kizzmekia S. , Edwards Darin , Leist Sarah R. , Abiona Olubukola M. , Boyoglu-Barnum Seyhan , Gillespie Rebecca A. , Himansu Sunny , Schäfer Alexandra , Ziwawo Cynthia T. , DiPiazza Anthony T. , Dinnon Kenneth H. , Elbashir Sayda M. , Shaw Christine A. , Woods Angela , Fritch Ethan J. , Martinez David R. , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Hutchinson Geoffrey B. , Bahl Kapil , Garcia-Dominguez Dario , Ma LingZhi , Renzi Isabella , Kong Wing-Pui , Schmidt Stephen D. , Wang Lingshu , Zhang Yi , Stevens Laura J. , Phung Emily , Chang Lauren A. , Loomis Rebecca J. , Altaras Nedim Emil , Narayanan Elisabeth , Metkar Mihir , Presnyak Vlad , Liu Catherine , Louder Mark K. , Shi Wei , Leung Kwanyee , Yang Eun Sung , West Ande , Gully Kendra L. , Wang Nianshuang , Wrapp Daniel , Doria-Rose Nicole A. , Stewart-Jones Guillaume , Bennett Hamilton , Nason Martha C. , Ruckwardt Tracy J. , McLellan Jason S. , Denison Mark R. , Chappell James D. , Moore Ian N. , Morabito Kaitlyn M. , Mascola John R. , Baric Ralph S. , Carfi Andrea , Graham Barney S.
Published: June 2020

A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.
Influence of nanobody binding on fluorescence emission, mobility and organization of GFP-tagged proteins
Authors: Schneider Falk , Eggeling Christian , Sezgin Erdinc
Published: June 2020

Advanced fluorescence microscopy studies require specific and monovalent molecular labelling with bright and photostable fluorophores. This necessity led to the widespread use of fluorescently labelled nanobodies against commonly employed fluorescent proteins. However, very little is known how these nanobodies influence their target molecules. Here, we observed clear changes of the fluorescence properties, mobility and organisation of green fluorescent protein (GFP) tagged proteins after labelling with an anti-GFP nanobody. Intriguingly, we did not observe any co-diffusion of fluorescently-labelled nanobodies with the GFP-labelled proteins. Our results suggest significant binding of the nanobodies to a non-emissive, oligomerized form of the fluorescent proteins, promoting disassembly into more monomeric forms after binding. Our findings show that great care must be taken when using nanobodies for studying dynamic and quantitative protein organisation.
Insights into glycan import by a prominent gut symbiont
Authors: Gray Declan A. , White Joshua B. R. , Oluwole Abraham O. , Rath Parthasarathi , Glenwright Amy J. , Mazur Adam , Zahn Michael , Baslé Arnaud , Morland Carl , Evans Sasha L. , Cartmell Alan , Robinson Carol V. , Hiller Sebastian , Ranson Neil A. , Bolam David N. , van den Berg Bert
Published: June 2020

In Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD fromBacteroides thetaiotaomicron(Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ∼2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studiesin vivoprovide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.
Divergent effects ofWolbachiaon host temperature preference
Authors: Hague Michael T.J. , Caldwell Chelsey N. , Cooper Brandon S.
Published: June 2020

Heritable symbionts can modify a range of ecologically important host traits, including behavior. About half of all insect species are infected with maternally transmittedWolbachia, a bacterial endosymbiont known to alter host reproduction, nutrient acquisition, and virus susceptibility. Here, we broadly test the hypothesis thatWolbachiamodify host behavior by assessing the effects of eight differentWolbachiastrains on the temperature preference of sixDrosophila melanogaster-subgroup species. Four of the seven host genotypes infected with A-groupWolbachiastrains (wRi inD. simulans, wHa inD. simulans, wSh inD. sechellia, andwTei inD. teissieri) prefer significantly cooler temperatures relative to uninfected genotypes. Contrastingly, when infected with divergent B-groupwMau,D. mauritianaprefer a warmer temperature. For most strains, changes to host temperature preference do not alterWolbachiatiter. However, males infected withwSh andwTei experience an increase in titer when shifted to a cooler temperature for 24 hours, suggesting thatWolbachia-induced changes to host behavior may promote bacterial replication and influenceWolbachiatransmission rates. Modifications to host temperature preference likely influence host thermoregulation, and understanding the fitness consequences of these effects is crucial for predicting evolutionary outcomes of host-symbiont interactions, including howWolbachiaspread to become common.