bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased red blood cell distribution width might predict left ventricular hypertrophy in patients with atrial fibrillation
Authors: Yao Hui-Ming , Wang Xiao-Lei , Peng Xiong , Chen Shu-Yun , Wan Xuan , Zuo Wei , Gan Xin
Published: September 2020

The presence of left ventricular hypertrophy has been confirmed to be an independent risk factor for stroke and death in patients with atrial fibrillation. This retrospective study aimed to evaluate the potential risk factors for left ventricular hypertrophy in patients with atrial fibrillation.

A series of consecutive patients diagnosed with atrial fibrillation between June 2018 and December 2019 were included. The patients’ clinical data were analyzed. The cut-off values, sensitivity and specificity of the independent risk factors were calculated using a receiver operating characteristic curve.

Among 87 patients with atrial fibrillation, 39 patients with left ventricular hypertrophy and 48 patients without left ventricular hypertrophy were included. Multivariate logistic regression analysis showed that red blood cell distribution width (odds ratio [OR] 4.89, 95% confidence interval [CI]: 1.69–14.13, P < .05) was an independent risk factor, while the concentration of low-density lipoprotein (OR 0.37, 95% CI: 0.17–0.83, P < .05) and left ventricular ejection fraction (OR 0.88, 95% CI: 0.82–0.95, P < .05) were inversely associated with left ventricular hypertrophy in atrial fibrillation patients. The receiver operating characteristic curve demonstrated that the area under the curve was 0.80 (95% CI: 0.71–0.90, P < .05) with a cut-off value of 13.05, and the red blood cell distribution width predicted left ventricular hypertrophy status among atrial fibrillation patients with a sensitivity of 72.1% and a specificity of 76.9%.

Red blood cell distribution width was associated with left ventricular hypertrophy in patients with atrial fibrillation.
Vasectomy and male sexual dysfunction risk
Authors: Yang Fang , Dong Liang , Zhang Xiaojin , Li Junjun , Tan Kun , Li Yulin , Yu Xujun
Published: September 2020

Background:

Unintended pregnancy is popular all over the world, accounting for 40% to 50% of all pregnancies. The condition not only exerts pressure on the relationship of couples and severely impacts the quality of life, but also imposes a heavy burden on the health of women and child. Recently, more than 220 million couples have chosen to be sterilized to obtain contraception, 47.3% of married couples select sterilization, of which vasectomy accounts for 17.1%. Vasectomy is currently the most convenient and effective method of male contraception. We will perform the systematic review and meta-analysis to assess the correlation between vasectomy and male sex dysfunction and provide evidence-based evidence for the couple

Methods:

The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Clinicaltrials.org., China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry, and Cochrane Library will be retrieved before November 20, 2021. We will search English literature and Chinese literature with proper Medical Subject Heading or text key words. RevMan 5.3 and Stata 14.0 will be used for Systematic review and Meta-analysis. This protocol reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.

Conclusion and dissemination:

The aim of this study was to evaluate the effect of vasectomy on the sexual function of patients after operation. The results will be published in a public issue journal to provide evidence-based medical evidence for urologists and andrologists to make clinical decisions.

Registration information:

INPLASY202080014.
Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade
Authors: Shen Yanyun , Chen Yunfeng , Wang Duoqin , Zhu Zhidong
Published: September 2020

Background:

Immune checkpoint blockade (ICB) brings hope to many late-stage cancer patients yet its marker for response remains elusive.

Methods:

We developed a hypothesis that treatment-related adverse events (TrAEs) could predict objective response rate (ORR) to ICB. We plotted ORR against corresponding any and grade 3 to 5 (G3–5) TrAEs across a variety of cancer types by performing a meta-analysis using linear regression.

Results:

We identified 113 eligible studies encompassing 25 types of malignancies that were treated with ICB or ICB-based regimes. A significant linear correlation was observed for any and severe TrAEs, respectively. The correlation coefficient was 0.57 (r
2 = 0.324) for any TrAE and 0.61 (r
2 = 0.37) for G3–5 TrAE. For melanoma, the correlation coefficient was 0.81 (r
2 = 0.57) for any TrAE and 0.65 (r
2 = 0.42) for G3–5 TrAEs. For RCC, the correlation coefficient was 0.86 (r
2 = 0.74) for any TrAE and 0.91 (r
2 = 0.83) for G3–5 TrAE. For NSCLC, the correlation coefficient was 0.55 (r
2 = 0.3) for any TrAE and 0.74 (r
2 = 0.86) for G3–5 TrAE. For UC, the correlation coefficient was 0.47 (r
2 = 0.68) for any TrAE and 0.27 (r
2 = 0.52) for G3–5 TrAE, yet the correlation was insignificant for severe AEs.

Conclusion:

Our findings suggest that over half of ICB responses could be reflected by any adverse events and ∼60% of responses could be reflected by severe AEs. Further validation is needed in individual trials.
Correlations among peripapillary vasculature, macular superficial capillaries, and eye structure in healthy and myopic eyes of Chinese young adults (STROBE)
Authors: Guo Yuxia , Pang Yunlei , Kang YanJie , Zhang Xiaoguang , Zhang Han , Zhang Guisen , Liu Lei
Published: September 2020

The correlations between retinal vessel distribution, anterior chamber depth (ACD) and other myopic eye structural parameters remains elusive. This study aims to investigate retinal vasculature and eye structure correlations in healthy and myopic eyes of Chinese young adults.

In this cross-sectional study, 181 eyes (97 adults) were recruited. Macular and peripapillary vasculature was quantified by optical coherence tomography angiography. Correlations between retinal vasculature and eye structure were analyzed using multivariable linear regression.

There were significant differences in ACD, spherical equivalent, axial length (AL), superficial macular vascular density (MVD), peripapillary vascular density (PVD) and circumference of foveal avascular zone (FAZ) among emmetropia, low-myopia, moderate-myopia, and high-myopia groups (both P < 0.05). Furthermore, ACD had significant positive correlation with AL and FAZ, but negative correlation with PVD. MVD also had a negative correlation with AL (beta = –0.247, P < .001). In addition, there was a significant negative correlation between circumference of the FAZ and spherical equivalent as well as central subfield thickness (beta = –0.20, P = .005; beta = –0.334, P < .001, respectively).

The degree of myopia affected ACD, MVD, PVD, and circumference of the FAZ in eyes of young healthy adults. Meanwhile, ACD has a positive, while retinal vascular system measurements have a negative correlation with increasing severity of myopia.
Plum-blossom needle for coronavirus disease 2019-related headache
Authors: Gao Wei , Li Jingfei , Huang Guoxiang
Published: September 2020

Background:

Assessing the effectiveness and safety of plum-blossom needle for (COVID-19) related headache is the main purpose of this systematic review protocol.

Methods:

We will search the following sources for the identification of trials: The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science and Technique Journals Database (VIP), and the Wanfang Database. The searches were limited to articles published in 2020, but no language restrictions were imposed. Only include randomised controlled trials (RCTs), with or without blinding, and participant or observer reported outcomes, will be included.

The primary outcome is the time and rate of appearance of headache induced by COVID-19. The secondary outcome is the length of hospital stay. Two independent reviewers will conduct the study selection, data extraction and assessment. Review Manager Software V.5.3 will be used for the assessment of risk of bias and data synthesis.

Results:

The results will provide a high-quality synthesis of current evidence for researchers in this subject area.

Conclusion:

The conclusion of our study will provide an evidence to judge whether plum-blossom needle is effective and safe for COVID-19-related headache.

Ethics and dissemination:

This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports.

PROSPERO registration number:

CRD42020199508.
Investigating potential molecular mechanisms of serum exosomal miRNAs in colorectal cancer based on bioinformatics analysis
Authors: Wang Haifeng , Chen Xiliang , Bao Lingling , Zhang Xuede
Published: September 2020

Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor worldwide. Serum exosomal microRNAs (miRNAs) play a critical role in tumor progression and metastasis. However, the underlying molecular mechanisms are poorly understood.

The miRNAs expression profile (GSE39833) was downloaded from Gene Expression Omnibus (GEO) database. GEO2R was applied to screen the differentially expressed miRNAs (DEmiRNAs) between healthy and CRC serum exosome samples. The target genes of DEmiRNAs were predicted by starBase v3.0 online tool. The gene ontology (GO) and Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. The protein-protein interaction (PPI) network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) visualized using Cytoscape software. Molecular Complex Detection (MCODE) and cytohubba plug-in were used to screen hub genes and gene modules.

In total, 102 DEmiRNAs were identified including 67 upregulated and 35 downregulated DEmiRNAs, and 1437 target genes were predicted. GO analysis showed target genes of upregulated DEmiRNAs were significantly enriched in transcription regulation, protein binding, and ubiquitin protein ligase activity. While the target genes of downregulated DEmiRNAs were mainly involved in transcription from RNA polymerase II promoter, SMAD binding, and DNA binding. The KEGG pathway enrichment analyses showed target genes of upregulated DEmiRNAs were significantly enriched in proteoglycans in cancer, microRNAs in cancer, and phosphatidylinositol-3 kinases/Akt (PI3K-Akt) signaling pathway, while target genes of downregulated DEmiRNAs were mainly enriched in transforming growth factor-beta (TGF-beta) signaling pathway and proteoglycans in cancer. The genes of the top 3 modules were mainly enriched in ubiquitin mediated proteolysis, spliceosome, and mRNA surveillance pathway. According to the cytohubba plugin, 37 hub genes were selected, and 4 hub genes including phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), SRC, cell division cycle 42 (CDC42), E1A binding protein p300 (EP300) were identified by combining 8 ranked methods of cytohubba.

The study provides a comprehensive analysis of exosomal DEmiRNAs and target genes regulatory network in CRC, which can better understand the roles of exosomal miRNAs in the development of CRC. However, these findings require further experimental validation in future studies.
Prevalence of dry eye disease in the elderly
Authors: Zhang Xinyue , Wang Lizhen , Zheng Yanlin , Deng Lu , Huang Xiaoying
Published: September 2020

Introduction:

Dry eye disease (DED) is one of the most prevalent ocular diseases which remains widely underestimated. New lifestyles driven by information technology and the rapid ageing process have brought DED a severe public health concern. And DED is highly related to the reduction in vision-related quality of life and interfere with daily activities. Since advanced age has been suggested as an important risk factor for DED, the aim of our study was to obtain the pooled prevalence of DED in the elderly over 60 years of age.

Methods and analysis:

The following databases will be searched from their inception to August 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure (CNKI). Primary outcomes: the number of participants and DED cases. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0.

Results:

The results of this study will systematically evaluate the prevalence of DED in the elderly population over 60 years of age.

Conclusion:

The systematic review of this study will summarize the current published evidence of epidemiological investigations of DED with advanced age classification.

Ethics and dissemination:

This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.

Open Science Fra network (OSF) registration number:

August 12, 2020. osf.io/3jyb4. (https://osf.io/3jyb4).
Impact of Inappropriate Antibiotic Therapy in Vancomycin-Resistant Enterococcus Bacteremia
Authors: Aslam Waqas , Mathew Naomi E. , Shaver Courtney , Brito Veronica , Jones Shirley , Arroliga Alejandro C. , Ghamande Shekhar
Published: September 2020

Background:

Vancomycin-resistant Enterococcus (VRE) bacteremia has significant morbidity and mortality. Empiric antibiotic regimens for treating patients with risk factors for multidrug-resistant organisms may not have medications directed at treating VRE.

Study Question:

To evaluate the impact of antibiotic therapy (and other risk factors) on mortality in VRE bacteremia.

Study Design:

We identified 146 patients with VRE bacteremia, admitted at our institution over an 11 years period (2004–2014). All inpatients with an initial positive VRE blood culture were included only once in the analysis. Eighteen patients were excluded from the study because of inability to retrieve medical information regarding one or more important study variables. The retrospectively collected data from electronic medical records of 128 patients were analyzed.

Results:

The inpatient, 30-day, and 1-year mortality rates from VRE bacteremia were 23%, 31%, and 59%, respectively. Only 19% patients were discharged home. Inappropriate antibiotics were prescribed in 19% patients. Appropriate antibiotics were prescribed in 81% patients (62% daptomycin and 37% linezolid); however, only 58% patients received appropriate antibiotics within 24 hours of the reported positive blood cultures. The 30-day and 1-year mortality rates for patients treated with inappropriate antibiotics were 54% and 67% compared with 26% and 50%, respectively, for those treated with appropriate antibiotics. The median survival rate for patients treated with inappropriate antibiotics was 1 month (95% confidence interval: 0.0–1.0) compared with 11 months (95% confidence interval: 4.0–13.0) for those treated with appropriate antibiotics. The advanced patient age (median age 75 years vs. 63 years) was a significant risk factor for inappropriate antibiotic therapy (P value = 0.02). The multivariate Cox regression model revealed inappropriate antibiotic therapy (P value = 0.003), septic shock (P value = 0.0004), albumin (P value = 0.04), and dementia (P value = 0.003) to be associated with 30-day mortality.

Conclusions:

Our study highlights the detrimental effect of inappropriate antibiotic therapy and other risk factors on morbidity and mortality associated with VRE bacteremia.
Pediatric Firearm Injuries and Fatalities: Do Racial Disparities Exist?
Authors: Sakran Joseph V. , Nance Michael , Riall Taylor , Asmar Samer , Chehab Mohamad , Joseph Bellal
Published: September 2020

Objective:

To evaluate racial disparities among White and Black pediatric firearm injury patients on a national level.

Background:

Pediatric firearm-related morbidity and mortality are rising in the United States. There is a paucity of data examining racial disparities in those patients.

Methods:

The Pediatric Trauma Quality Improvement Program (2017) was queried for pediatric (age ≤17 years) patients admitted with firearm injuries. Patients were stratified by race: White and Black. Injury characteristics were assessed. Outcomes were mortality, hospital length of stay, and discharge disposition. Hierarchical regression models were performed to determine predictors of mortality and longer hospital stays.

Results:

A total of 3717 pediatric firearm injury patients were identified: Blacks (67.0%) and Whites (33.0%). The majority of patients were male (84.2%). The most common injury intent in both groups was assault (77.3% in Blacks vs in 45.4% Whites; P<0.001), followed by unintentional (21.1% vs 35.4%; P<0.001), and suicide (1.0% vs 14.0%; P<0.001). The highest fatality rate was in suicide injuries (62.6%). On univariate analysis, White children had higher mortality (17.5% vs 9.8%; P<0.001), longer hospital stay [3 (1–7) vs 2 (1–5) days; P = 0.021], and more psychiatric hospital admissions (1.3% vs 0.1%; P<0.001). On multivariate analysis, suicide intent was found to be an independent predictor of mortality (aOR 2.67; 95% CI 1.35–5.29) and longer hospital stay (β + 4.13; P<0.001), while White race was not.

Conclusion:

Assault is the leading intent of injury in both Black and White children, but White children suffer more from suicide injuries that are associated with worse outcomes.

Level of Evidence: Level III Prognostic.
MexXY RND pump of Pseudomonas aeruginosa PA7 effluxes bi-anionic β-lactams carbenicillin and sulbenicillin when it partners with the outer membrane factor OprA but not with OprM
Authors: Singh Manu , Sykes Ellen M. E. , Li Yanqi , Kumar Ayush
Published: September 2020

Antibiotic resistance in

Pseudomonas aeruginosa

is a serious concern in healthcare systems. Among the determinants of antibiotic resistance in

P. aeruginosa

, efflux pumps belonging to the resistance–nodulation–division (RND) family confer resistance to a broad range of antibacterial compounds. The MexXY efflux system is widely overexpressed in

P. aeruginosa

isolates from cystic fibrosis (CF) patients. MexXY can form functional complexes with two different outer membrane factors (OMFs), OprA and OprM. In this study, using state-of-the-art genetic tools, the substrate specificities of MexXY–OprA and MexXY–OprM complexes were determined. Our results show, for the first time, that the substrate profile of the MexXY system from

P. aeruginosa

PA7 can vary depending on which OM factor (OprM or OprA) it complexes with. While both MexXY–OprA and MexXY–OprM complexes are capable of effluxing aminoglycosides, the bi-anionic β-lactam molecules carbenicillin and sulbenicillin were found to only be the substrate of MexXY–OprA. Our study therefore shows that by partnering with different OMF proteins MexY can expand its substrate profile.
Safety and Efficacy of Antiviral Drugs for the Treatment of Patients with SARS-CoV-2 Infection: A Systematic Review and Meta-analyses
Authors: Torres Zuleika Aponte , Leon Sandra Lopez , Muthuvel Thirumugam , Manivannan Subha , Srivastava Krutika , Pavesi Marco
Published: September 2020

Objective

To systematically review the safety and efficacy outcomes of using antivirals for the treatment of COVID-19.

Methods

Five databases were screened from inception to 27-Aug-2020. The effects of specific drug interventions on safety and efficacy were assessed in COVID-19 patients. Risk Ratios (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models.

Results

A total of 10 studies were identified which fulfill the inclusion criteria. Patients taking antivirals had 26% less risk of having a severe adverse event (SAE) compared to controls (RR, 0.74, CI:0.62 to 0.89, P=0.002). Clinical improvement at day 14 was observed among the cases treated with antivirals compared to the control group (RR 1.24, CI: 1.00 to 1.53 p=0.05).

Conclusion

There is evidence that Remdesivir and LPV/r reduces the hospital length of stay and that patients to which antivirals were administered had less SAE and improvement when compared to patients not prescribed with antivirals. Due to a lack of power and the quality of the studies, it was not possible to determine which antivirals have a greater risk-benefit balance, and therefore the optimal approach to antiviral treatment is still uncertain.
Fish avoid visually noisy environments that reduce their perceptual abilities
Authors: Attwell Joanna R. , Ioannou Christos C. , Reid Chris R. , Herbert-Read James E.
Published: September 2020

The environment contains different forms of ecological noise that can reduce the ability of animals to detect information. Here we ask whether animals can adapt their behaviour to either exploit or avoid areas of their environment with increased dynamic visual noise. By immersing three-spined sticklebacks (Gasterosteus aculeatus) into environments with a simulated form of naturally occurring visual noise – light bands created by the refraction of light from surface waves termed caustic networks – we tested how such visual noise affected the movements, habitat use, and perceptual abilities of these fish. Fish avoided areas of higher visual noise, and achieved this by increasing their activity as a function of the locally perceived noise level, resulting in individuals moving away from noisier areas. By projecting virtual prey into the environment with different levels of visual noise, we found that the fish’s ability to visually detect prey decreased as visual noise increased. We found no evidence that fish increased their exploration (and decreased their refuge use) in environments with increased visual noise, which would have been predicted if they were exploiting increased visual noise to reduce their own likelihood of being detected. Our results indicate that animals can use simple behavioural strategies to mitigate the impacts of dynamic visual noise on their perceptual abilities, thereby improving their likelihood of gathering information in dynamically changing and noisy environments.
Nutrient Export and Periphyton Biomass in a Stream-Lake Basin from the Patagonian Andean Region
Authors: Sosnovsky Alejandro , Lallement Mailén Elizabeth , Rechencq Magalí , Fernández María Valeria , Zattara Eduardo Enrique , Feijoó Claudia Silvina
Published: September 2020

We characterized how land use influenced dissolved nutrients and periphytic algal biomass in an Andean basin from Northwest Patagonia. Nutrient export, especially dissolved inorganic nitrogen increased with human population density. However, no correlation between nutrient concentration and algal biomass was found, which could instead be limited by light availability. Our results suggest that local N-limited ecosystems are liable to eutrophication by increased demographic pressure and that alternative wastewater treatment strategies are necessary for sustainable growth.
Fine–mapping identifiesNAD–ME1as a candidate underlying a major locus controlling temporal variation in primary and specialized metabolism in Arabidopsis
Authors: Francisco Marta , Kliebenstein Daniel J. , Rodríguez Víctor M. , Soengas Pilar , Abilleira Rosaura , Cartea María E.
Published: September 2020

Plant metabolism is modulated by a complex interplay between internal signals and external cues. A major goal of all quantitative metabolomic studies is to clone the underlying genes to understand the mechanistic basis of this variation. Using fine-scale genetic mapping, in this work we report the identification and initial characterization ofNAD-DEPENDENT MALIC ENZYME 1(NAD-ME1) as the candidate gene underlying the pleiotropic network Met.II.15 QTL controlling variation in plant metabolism and circadian clock outputs in the Bay × Sha Arabidopsis population. Transcript abundance and promoter analysis inNAD-ME1Bay-0andNAD-ME1Shaalleles confirmed allele-specific expression that appears to be due a polymorphism disrupting a putative circadian cis-element binding site. Analysis of T-DNA insertion lines and heterogeneous inbred families (HIFs) showed that transcript variation of theNAD-ME1gene led to temporal shifts of tricarboxylic acid cycle (TCA) intermediates, glucosinolate (GSL) accumulation and altered regulation of several GSL biosynthesis pathway genes. Untargeted metabolomics analyses reveal complex regulatory networks ofNAD-ME1dependent upon the day-time. The mutant lead to shifts in plant primary metabolites, cell-wall components, isoprenoids, fatty acids and plant immunity phytochemicals, among others. Our findings suggest thatNAD-ME1may act as a key component to coordinate plant primary and secondary metabolism in a time-dependent manner.
The power to detect cultural transmission in the Nuclear Twin Family design with and without polygenic risk scores and in the Transmitted-Non-transmitted (alleles) design
Authors: Bruins S. , Dolan C. V. , Boomsma D. I.
Published: September 2020

The aim of our study is to compare the power of two different approaches to detect passive genotype-environment covariance originating from simultaneous cultural and genetic transmission. In the traditional Nuclear Twin Family Design cultural transmission is estimated on the basis of the phenotypic covariance matrices of the mono- and dizygotic twins and their parents, where phenotyping is required in all family members. A more recent method is the Transmitted-Nontransmitted allele design, which exploits measured genetic variants in parents and offspring to test for effects of nontransmitted alleles from parents. This design requires genome-wide data and a powerful GWA (genome-wide association) study for the phenotype in addition to phenotyping in offspring. We compared the power of both designs. Using exact data simulation, we demonstrate that compared to the Transmitted-Nontransmitted design, the Nuclear Twin Family Design is relatively well-powered to detect cultural transmission and genotype-environment covariance. The power of the Transmitted-Nontransmitted design depends on the predictive power of polygenic risk scores. Adding polygenic risk scores of realistic effect size to the Nuclear Twin Family Design did not result in an appreciable increase the power to detect cultural transmission.
Information-based signal selection improves decoding of attention spotlight from multi-units & local field potentials and enhances correlation with behavior
Authors: De Sousa Ferreira C. , Gaillard C. , Di Bello F. , Ben Hadj Hassen S. , Ben Hamed S.
Published: September 2020

The ability to access brain information in real-time is crucial both for a better understanding of cognitive functions and for the development of therapeutic applications based on brain-machine interfaces. Great success has been achieved in the field of neural motor prosthesis. Progress is still needed in the real-time decoding of higher-order cognitive processes such as covert attention. Recently, we showed that we can track the location of the attentional spotlight using classification methods applied to prefrontal multi-unit activity (MUA) in the non-human primate (Astrand et al., 2016). Importantly, we demonstrated that the decoded (x,y) attentional spotlight parametrically correlates with the behavior of the monkeys thus validating our decoding of attention. We also demonstrate that this spotlight is extremely dynamic (Gaillard et al., 2020). Here, in order to get closer to non-invasive decoding applications, we extend our previous work to local field potential signals (LFP). Specifically, we achieve, for the first time, high decoding accuracy of the (x,y) location of the attentional spotlight from prefrontal LFP signals, to a degree comparable to that achieved from MUA signals, and we show that this LFP content is predictive of behavior. This LFP attention-related information is maximal in the gamma band. In addition, we introduce a novel two-step decoding procedure based on the labelling of maximally attention-informative trials during the decoding procedure. This procedure strongly improves the correlation between our real-time MUA and LFP based decoding and behavioral performance, thus further refining the functional relevance of this real-time decoding of the (x,y) locus of attention. This improvement is more marked for LFP signals than for MUA signals, suggesting that LFP signals may contain other sources of task-related variability than spatial attention information. Overall, this study demonstrates that the attentional spotlight can be accessed from LFP frequency content, in real-time, and can be used to drive high-information content cognitive brain machine interfaces for the development of new therapeutic strategies.

Highlights

We use machine learning to decode attention spotlight from prefrontal MUA & LFP.

We achieve high decoding accuracy of (x,y) spatial attention spotlight.

(x,y) attention spotlight position accuracy is maximal from LFP gamma frequency range.

MUA and LFP decoded attention position predicts behavioral performances.

Selecting high information signals improves decoding and behavioral correlates.
Parallel evolution of direct development in frogs – Skin and thyroid gland development in African Squeaker Frogs (Anura: Arthroleptidae:Arthroleptis)
Authors: Naumann Benjamin , Schweiger Susan , Hammel Jörg U. , Müller Hendrik
Published: September 2020

Cases of parallel evolution offer the possibility to identify adaptive traits and to uncover developmental constraints on the evolutionary trajectories of these traits. The independent evolution of direct development, from the ancestral biphasic life history in frogs is such a case of parallel evolution. In frogs, aquatic larvae (tadpoles) differ profoundly from their adult forms and exhibit a stunning diversity regarding their habitats, morphology and feeding behaviors. The transition from the tadpole to the adult is a climactic, thyroid hormone (TH)-dependent process of profound and fast morphological rearrangement called metamorphosis. One of the organ systems that experiences the most comprehensive metamorphic rearrangements is the skin. Direct-developing frogs lack a free-swimming tadpole and hatch from terrestrial eggs as fully formed froglets. In the few species examined, development is characterized by the condensed and transient formation of some tadpole-specific features and the early formation of adult-specific features during a “cryptic” metamorphosis. In this study we show that skin in direct-developing African squeaker frogs (Arthroleptis) is also repatterned from a tadpole-like to an adult-like histology during a cryptic metamorphosis. This repatterning correlates with an increase of thyroid gland activity. A comparison with data from the Puerto Rican coqui (Eleutherodactylus coqui) reveals that direct development might have evolved in parallel in these frogs by a comparable heterochronic shift of thyroid gland activity. This suggests that the development of many adult-features is still constrained by the ancestral dependency on thyroid hormone signaling.
Model-informed COVID-19 vaccine prioritization strategies by age and serostatus
Authors: Bubar Kate M. , Kissler Stephen M. , Lipsitch Marc , Cobey Sarah , Grad Yonatan H. , Larremore Daniel B.
Published: September 2020

When a vaccine for COVID-19 becomes available, limited initial supply will raise the question of how to prioritize the available doses and thus underscores the need for transparent, evidence-based strategies that relate knowledge of, and uncertainty in, disease transmission, risk, vaccine efficacy, and existing population immunity. Here, we employ a model-informed approach to vaccine prioritization that evaluates the impact of prioritization strategies on cumulative incidence and mortality and accounts for population factors such as age, contact structure, and seroprevalence, and vaccine factors including imperfect and age-varying efficacy. This framework can be used to evaluate and compare existing strategies, and it can also be used to derive an optimal prioritization strategy to minimize mortality or incidence. We find that a transmission-blocking vaccine should be prioritized to adults ages 20-49y to minimize cumulative incidence and to adults over 60y to minimize mortality. Direct vaccination of adults over 60y minimizes mortality for vaccines that do not block transmission. We also estimate the potential benefit of using individual-level serological tests to redirect doses to only seronegative individuals, improving the marginal impact of each dose. We argue that this serology-informed vaccination approach may improve the efficiency of vaccination efforts while partially addressing existing inequities in COVID-19 burden and impact.
Transcranial direct current stimulation over the left inferior frontal gyrus improves sentence comprehension
Authors: Peristeri Eleni , Wang Zeyi , Herrmann Olivia , Caffo Brian , Frangakis Constantine , Tsapkini Kyrana
Published: September 2020

Background

The left inferior frontal gyrus (IFG) has been shown to be involved in sentence comprehension in many studies through its involvement in both semantic and syntactic computations. However, causal evidence for its involvement in sentence comprehension is scarce. We used transcranial direct current stimulation (tDCS) to test the causal involvement of the left IFG in sentence comprehension in a group of individuals with primary progressive aphasia (PPA). These individuals participated in a tDCS study targeting lexical retrieval only, not sentence comprehension, therefore in the present study we report on far-transfer effects of tDCS in sentence comprehension.

Objective

We sought to determine whether tDCS over the left inferior frontal gyrus (IFG) coupled with lexical retrieval treatment may improve sentence comprehension in PPA.

Method

Within a sham-controlled, double-blind design, we tested whether 15 daily sessions of anodal tDCS over the left IFG may improve sentence comprehension in 27 people with PPA, and whether the tDCS effects were sustained up to two months post-treatment.

Results

We found that immediately post-treatment, and up to 2-months post-treatment, there was significantly larger improvement of sentence comprehension in the tDCS condition compared to sham. There were, however, differential effects of tDCS in each PPA variant and sentence-type. Importantly, participants with the epicenter of atrophy over the stimulated area (non-fluent PPA) benefited most from tDCS.

Conclusion

TDCS over the left IFG induces far-transfer effects and may improve sentence comprehension in PPA. We provide causal evidence that left IFG is a critical area for sentence comprehension.
Periodic variations in the Covid-19 infection and fatality rates
Authors: Peirani S. , Icard Ph. , de Freitas Pacheco J.A.
Published: September 2020

Power spectra of infection and mortality rate curves for nineteen countries of different continents were computed. Nine of them show the presence of oscillations with a period of about seven says either in the infection or in the mortality data sets. The computed power spectra for seven countries do no indicate any significant signal of periodicity while the three remaining countries indicate periodic oscillations only in the infection or only in the mortality curve. Data indicate that minima occur generally on weekends. The seven-day periodicity present in infection data of nine countries is robust and seems to be the consequence of different factors as, for instance, higher testing frequency during weekdays or/and an enhanced contamination during social activities during weekends. For the moment, there is no convincing explanation for the seven-day oscillations observed in the mortality curves of some countries.
Examining the relationship between adolescent health behaviors, brain health, and academic achievement using fNIRS
Authors: Papasideris Mia , Safati Adrian , Ayaz Hasan , Morita Plinio , Hall Peter
Published: September 2020

Background

Several adolescent health behaviors have been hypothesized to improve academic performance via their beneficial impact on cognitive control and functional aspects of the prefrontal cortex (PFC). Specifically, exercise, restorative sleep, and proper diet are thought to improve PFC function, while substance abuse is thought to reduce it. Few studies have examined the relationships among all of these in the same sample, while quantifying downstream impacts on academic performance.

Objective

The primary objective of this study is to examine the association between lifestyle behaviors and academic performance in a sample of adolescents, and to examine the extent to which activity within the PFC and behavioural indices of inhibition may mediate this relationship.

Methods

Sixty-seven adolescents underwent two study sessions five days apart. Sleep and physical activity were measured using wrist-mounted accelerometry; eating habits, substance use and academic achievement were measured by self-report. Prefrontal function was quantified by performance on the Multi-Source Interference Task (MSIT), and task-related brain activity via functional near-infrared spectroscopy (fNIRS).

Results

Higher levels of accelerometer-assessed physical activity predicted higher MSIT accuracy scores (ϐ= .321,ρ= 0.019) as well as greater task-related increases in activation within the right dlPFC (ϐ=.008,SE= .004,ρ=.0322). Frequency of fast-food consumption and substance use were both negatively associated with MSIT accuracy scores (ϐ= −.307,ρ= .023) and Math grades (β= −3.702,SE= 1.563,ρ= .022) respectively. However, these effects were not mediated by indicators of PFC function.

Conclusion

Physical activity and eating behaviors predicted better interference task performance in adolescents, with the former mediated by greater task-related increases in right dlPFC activation. Substance use predicted worse Math grades, however, no other reliable effects of health behaviors on academic outcomes were evident.
Label-free imaging and classification of liveP. falciparum
Authors: Lebel Paul M. , Dial Rebekah L. , Vemuri Venkata N. P. , Garcia Valentina , DeRisi Joseph , Gómez-Sjöberg Rafael
Published: September 2020

Manual microscopic inspection of fixed and stained blood smears has remained the gold standard forPlasmodiumparasitemia analysis for over a century. Unfortunately, smear preparation consumes time and reagents, while manual microscopy is skill-dependent and labor-intensive. Here, we demonstrate that label-free microscopy combined with deep learning enables both life stage classification and accurate parasitemia quantification. Using a custom-built microscope, we find that deep-ultraviolet light enhances image contrast and resolution, achieving four-category classification ofPlasmodium falciparumblood stages at an overall accuracy greater than 99%. To increase accessibility, we extended our method to a commercial brightfield microscope using near-ultraviolet and visible light. Both systems were tested extrinsically by parasitemia titration, revealing superior performance over manually-scored Giemsa-stained smears, and a limit of detection below 0.1%. Our results suggest that label-free microscopy combined with deep learning could eliminate the need for conventional blood smear analysis.
KuLGaP: A Selective Measure for Assessing Therapy Response in Patient-Derived Xenografts
Authors: Ortmann Janosch , Rampášek Ladislav , Tai Elijah , Mer Arvind Singh , Shi Ruoshi , Stewart Erin L , Mascaux Celine , Fares Aline , Pham Nhu-An , Beri Gangesh , Eeles Christopher , Tkachuk Denis , Ho Chantal , Sakashita Shingo , Weiss Jessica , Jiang Xiaoqian , Liu Geoffrey , Cescon David W. , O’Brien Catherine , Guo Sheng , Tsao Ming-Sound , Haibe-Kains Benjamin , Goldenberg Anna
Published: September 2020

Quantifying response to drug treatment in mouse models of human cancer is important for treatment development and assignment, and yet remains a challenging task. A preferred measure to quantify this response should take into account as much of the experimental data as possible, i.e. both tumor size over time and the variation among replicates. We propose a theoretically grounded measure, KuLGaP, to compute the difference between the treatment and control arms. KuLGaP is more selective than currently existing measures, reduces the risk of false positive calls and improves translation of the lab results to clinical practice.
Genotypic differences in wheat yield determinants within a NAM population based on elite parents
Authors: Basavaraddi Priyanka A. , Savin Roxana , Sukumaran Sivakumar , Reynolds Matthew P. , Griffiths Simon , Slafer Gustavo A.
Published: September 2020

Future grain yield (GY) improvements require the identification of beneficial traits within the context of high yield potential and not just based on the pleiotropic effect of traits such as crop height and heading date. We evaluated 1937 lines from Nested Association Mapping (NAM) population derived from 13 bi-parental varietal crosses under field conditions. We selected 493 lines with similar time to anthesis to that of the two checks used in the study (across and within each family) which reduced the range of plant height in the selected lines. Yield components were measured in these 493 lines from which 231 lines were selected by excluding lines with lowest number of grains so excluded low yielding lines. Later the subset of 231 lines were evaluated in two field experiments (2016-17, CS1 and 2017-18, CS2). Numerical and physiological components of grain yield were measured. The two-step selection maximised GY within an acceptable range of variation for height and anthesis. GY in 231 lines showed very high G×E interaction. Taking both seasons together, we selected lines from upper and lower quartile GY groups to identify stable beneficial trait combinations for improved GY. Differences in GY were explained by grain number driven by increased spike dry weight at anthesis (SDWa) and fruiting efficiency (FE). Increased GY was accompanied by sink limitation. The data points towards increases in grain number as the route towards future GY increases in wheat breeding.
Learning a genome-wide score of human-mouse conservation at the functional genomics level
Authors: Kwon Soo Bin , Ernst Jason
Published: September 2020

Identifying genomic regions with functional genomic properties that are conserved between human and mouse is an important challenge in the context of mouse model studies. To address this, we take a novel approach and learn a score of evidence of conservation at the functional genomics level by integrating large-scale information in a compendium of epigenomic, transcription factor binding, and transcriptomic data from human and mouse. The computational method we developed to do this, Learning Evidence of Conservation from Integrated Functional genomic annotations (LECIF), trains a neural network, which is then used to generate a genome-wide score in human and mouse. The resulting LECIF score highlights human and mouse regions with shared functional genomic properties and captures correspondence of biologically similar human and mouse annotations even though it was not explicitly given such information. LECIF will be a resource for mouse model studies.
Heritable variation in resistance to the endonuclear parasiteHolospora undulataacross clades ofParamecium caudatum
Authors: Weiler Jared , Zilio Giacomo , Zeballos Nathalie , Noergaard Louise , Alberto Winiffer D. Conce , Krenek Sascha , Kaltz Oliver , Bright Lydia
Published: September 2020

Resistance is a key determinant in interactions between hosts and their parasites. Understanding the amount and distribution of genetic variation in this trait can provide insights into (co)evolutionary processes and their potential to shape patterns of diversity in natural populations. Using controlled inoculation in experimental mass cultures, we investigated the quantitative genetic variation in resistance to the bacterial parasiteHolospora undulataacross a worldwide collection of strains of its ciliate hostParamecium caudatum. We combined the observed variation with available information on the phylogeny and biogeography of the strains. We found substantial variation in resistance among strains (with broad-sense heritability > 0.5), repeatable between laboratories and ranging from total resistance to near-complete susceptibility. Early (one week post inoculation) measurements provided higher estimates of resistance heritability than did later measurements (2-3 weeks), possibly due to diverging epidemiological dynamics in replicate cultures of the same strains. Genetic distance (based on a neutral marker) was positively correlated with the difference in resistance phenotype between strains (r = 0.45), essentially reflecting differences between highly divergent clades (haplogroups) within the host species. Haplogroup A strains, mostly European, were less resistant to the parasite (49% infection prevalence) than non-European haplogroup B strains (28%). At a smaller geographical scale (within Europe), strains that are geographically closer to the parasite origin (Southern Germany) were more susceptible to infection than those from further away. These patterns are consistent with a picture of local parasite adaptation. Our study demonstrates ample natural genetic variation in resistance on which selection can act and hints at symbiont adaptation producing signatures in geographic and lineage-specific patterns of resistance in this model system.
Genome-wide Chromatin Accessibility is Restricted by ANP32E
Authors: Murphy Kristin E. , Meng Fanju W. , Makowski Claire E. , Murphy Patrick J.
Published: September 2020

Genome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning contribute to the accessibility of DNA, but widespread regulators of chromatin state are largely unknown. Our study investigates how control of genomic H2A.Z localization by ANP32E contributes to chromatin state in mouse fibroblasts. We define H2A.Z as a universal chromatin accessibility factor, and demonstrate that through antagonism of H2A.Z, ANP32E restricts genome-wide DNA access. In the absence of ANP32E, H2A.Z accumulates at promoters in a hierarchical manner. H2A.Z initially localizes downstream of the transcription start site, and if H2A.Z is already present downstream, additional H2A.Z accumulates upstream. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor binding, and increased expression of neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.