bluuebunny/crossref_metadata_2025 huggingface dataset:
A unified Method for assessing the Observability of Dynamic Complex Systems
Authors: Diaz Ochoa Juan G.
Published: January 2022

Abstract

Problem

Systems theory applied to biology and medicine assumes that the complexity of a system can be described by quasi-generic models to predict the behavior of many other similar systems. To this end, the aim of various research works in systems theory is to developinductive modeling(based on data-intensive analysis) ordeductive modeling(based on the deduction of mechanistic principles) to discover patterns and identify plausible correlations between past and present events, or to connect different causal relationships of interacting elements at different scales and compute mathematical predictions. Mathematical principles assume that there are constant and observable universal causal principles that apply to all biological systems. Nowadays, there are no suitable tools to assess the soundness of these universal causal principles, especially considering that organisms not only respond to environmental stimuli (and inherent processes) across multiple scales but also integrate information about and within these scales. This implies an uncontrollable degree of uncertainty.

Methodology

A method has been developed to detect the stability of causal processes by evaluating the information contained in the trajectories identified in a phase space. Time series patterns are analyzed using concepts from geometric information theory and persistent homology. In essence, recognizing these patterns in different time periods and evaluating their geometrically integrated information leads to the assessment of causal relationships. With this method, and together with the evaluation of persistent entropy in trajectories in relation to different individual systems, we have developed a method calledΦ-S diagramas a complexity measure to recognize when organisms follow causal pathways leading to mechanistic responses.

Results

We calculated the Φ-S diagram of a deterministic dataset available in the ICU repository to test the method’s interpretability. We also calculated the Φ-S diagram of time series from health data available in the same repository. This includes patients’ physiological response to sport measured with wearables outside laboratory conditions. We confirmed the mechanistic nature of both datasets in both calculations. In addition, there is evidence that some individuals show a high degree of autonomous response and variability. Therefore, persistent individual variability may limit the ability to observe the cardiac response. In this study, we present the first demonstration of the concept of developing a more robust framework for representing complex biological systems.
PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER INDUCTION OF LTD AT CORTICAL INPUTS TO INDIRECT PATHWAY STRIATAL NEURONS
Authors: Abburi Chandrika , Thome Jason , Rodriguez Braeden , Zhaung Xiaoxi , McGehee Daniel S
Published: January 2022

In Parkinson’s disease (PD) patients, dopamine replacement therapy requires days to reach maximal effects, and the return of symptoms without treatment is similarly delayed. We previously postulated that these phenomena are mediated by plasticity of coritcostriatal synapses. As dopamine depletion is expected to promote aberrant potentiation of the cortical inputs onto indirect pathway neurons, we reasoned that induction of LTD here could reduce motor deficits in a PD model. Optogenetic cortical stimulation combined with a D2 receptor agonist, quinpirole, induces robust optical LTD (oLTD) in brain slices from 6-OHDA lesioned mice. When lesioned mice were subjected to corticostriatal oLTD treatment over 5 days, motor performance was improved for >3 weeks. Consistent with LTD induction, oLTD-treated mice had reduced VGLUT1 expression in striatum and greater excitability of D2 neurons. These findings suggest that reversing aberrant corticostriatal synaptic plasticity in the indirect pathway may lead to persistent relief of PD motor symptoms.
Becoming metrics literate: An analysis of brief videos that teach about the h-index
Authors: Maggio Lauren A. , Jeffrey Alyssa , Haustein Stefanie , Samuel Anita
Published: January 2022

Introduction

Academia uses scholarly metrics, such as the h-index, to make hiring, promotion, and funding decisions. These high-stakes decisions require that those using scholarly metrics be able to recognize, interpret, critically assess and effectively and ethically use them. This study aimed to characterize educational videos about the h-index to understand available resources and provide recommendations for future educational initiatives.

Methods

The authors analyzed videos on the h-index posted to YouTube. Videos were identified by searching YouTube and were screened by two authors. To code the videos the authors created a coding sheet, which assessed content and presentation style with a focus on the videos’ educational quality based on Cognitive Load Theory. Two authors coded each video independently with discrepancies resolved by group consensus.

Results

Thirty-one videos met inclusion criteria. Twenty-one videos (68%) were screencasts and seven used a “talking head” approach. Twenty-six videos defined the h-index (83%) and provided examples of how to calculate and find it. The importance of the h-index in high-stakes decisions was raised in 14 (45%) videos. Sixteen videos (52%) described caveats about using the h-index, with potential disadvantages to early researchers the most prevalent (n=7; 23%). All videos incorporated various educational approaches with potential impact on viewer cognitive load. Most videos (n=21; 68%) displayed amateurish production quality.

Discussion

The videos featured content with potential to enhance viewers’ metrics literacies such that many defined the h-index and described its calculation, providing viewers with skills to recognize and interpret the metric. However, less than half described the h-index as an author quality indicator, which has been contested, and caveats about h-index use were inconsistently presented, suggesting room for improvement. While most videos integrated practices to facilitate balancing viewers’ cognitive load, few (32%) were of professional production quality. Some videos missed opportunities to adopt particular practices that could benefit learning.
Remdesivir for the Treatment of COVID-19: An Updated Systematic Review and Meta-Analysis
Authors: Lee Todd C. , Murthy Srinivas , Del Corpo Olivier , Senécal Julien , Butler-Laporte Guillaume , Sohani Zahra N , Brophy James M. , McDonald Emily G.
Published: January 2022

Background

The benefits of remdesivir in the treatment of hospitalized patients with Covid-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.

Methods

We performed a systematic review of randomized controlled trials (RCTs) of remdesivir for the treatment of hospitalized patients with COVID-19. The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio (RR) scale and, to better contextualize the probabilistic benefits, we also performed a bayesian random effects meta-analysis on the risk difference scale.

Results

We identified 8 randomized trials, totaling 9157 participants. The RR for mortality comparing remdesivir versus control was 0.71 (95% confidence interval [CI] 0.42-1.22; I2=0.0%) in the patients who did not require supplemental oxygen; 0.83 (95%CI 0.73-0.95; I2=0.0%) for nonventilated patients requiring oxygen; and 1.19 (95%CI 0.98-1.44 I2=0.0%) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 74.7%, 96.9% and 8.9%, respectively. The probability that remdesivir reduced mortality by more than 1% was 88.1% for nonventilated patients requiring oxygen.

Conclusion

Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy.
Genetic Associations with Polycystic Ovary Syndrome: The Role of The Mitochondrial Genome; A Systematic Review and Meta-analysis
Authors: Moosa Almira , Ghani Meeladah , O’Neill Helen
Published: January 2022

1.

Background

Polycystic Ovary Syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, whilst the contribution of mitochondrial genetics in PCOS remains largely unknown.

Aim

This study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS.

Methods

A literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) was extracted. Quantitative data was presented in forest plots, and where this was not possible, data was analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool.

Results

Of the 13,812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9-bp deletion, and aberrant SNPs in the ND5, A6, and 7 tRNA-encoding genes. They also showed lower frequencies of two SNPs in the D-Loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number.

Conclusion

Women with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations.
Population-Based Model of the Fraction of Incidental COVID-19 Hospitalizations During the Omicron BA.1 Wave in the United States
Authors: Harris Jeffrey E.
Published: January 2022

Background

Some reports have suggested that as many as one-half of all hospital inpatients identified as COVID-19-positive during the Omicron BA.1 variant-driven wave were incidental cases admitted primarily for reasons other than their viral infections. To date, however, there are no prospective longitudinal studies of a representative panel of hospitals based on pre-established criteria for determining whether a patient was in fact admitted as a result of the disease.

Materials and Methods

To fill this gap, we developed a formula to estimate the fraction of incidental COVID-19 hospitalizations that relies upon measurable, population-based parameters. We applied our approach to a longitudinal panel of 164 counties throughout the United States, covering a 4-week interval ending in the first week of January 2022.

Results

Within this panel, we estimated that COVID-19 incidence was rising exponentially at a rate of 9.34% per day (95% CI, 8.93-9.87). Assuming that only one-quarter of all Omicron BA.1 infections had been reported by public authorities, we further estimated the aggregate prevalence of active SARS-CoV-2 infection during the first week of January to be 3.45%. During the same week, among 250 high-COVID-volume hospitals within our 164-county panel, an estimated 1 in 4 inpatients was COVID-positive. Based upon these estimates, we computed that 10.6% of such COVID-19-positive hospitalized patients were incidental infections. Across individual counties, the median fraction of incidental COVID-19 hospitalizations was 9.5%, with an interquartile range of 6.7 to 12.7%.

Conclusion

Incidental COVID-19 infections appear to have been a nontrivial fraction of all COVID-19-positive hospitalized patients during the Omicron BA.1 wave. In the aggregate, however, the burden of patients admitted for complications of their viral infections was far greater.
Bacteriophage-derived dsRNA exerts anti-SARS-CoV-2 activity in vitro and in Golden Syrian hamsters in vivo
Authors: Kristine Vaivode , Irina Verhovcova , Dace Skrastina , Ramona Petrovska , Madara Kreismane , Daira Lapse , Diana Rubene , Zane Kalnina , Dace Pjanova
Published: January 2022

Purpose

Bacteriophage-derived dsRNA, also known as Larifan, is nationally well-known broad-spectrum antiviral medication. The goal of this study was to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2.

Methods

The antiviral activity of Larifan against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC) using cytopathic effect assay, viral RNA copy number detection by digital droplet PCR (ddPCR) and infectious virus titration in cells supernatants in Vero E6 cells by end-point titration method. The antiviral effect of Larifan in vivo was detected in SARS-CoV-2 infection model in Golden Syrian hamsters. Larifan (5 mg/kg) was administered either subcutaneously or intranasally twice before and after virus infection with a 24-hour interval between doses. The viral RNA copies and infectious virus titre were detected in animal lungs at day three and five post-infection using ddPCR and end-point titration in Vero E6 cells, respectively. Histopathology of lungs was analysed as well.

Results

Larifan inhibited SARS-CoV-2 replication in Calu3 cells both after the drug addition pre- and post-infection with a substantial drop in the supernatant viral RNA copy numbers from eight (p = 0.0013) to twenty (p = 0.0042) times, respectively. Similarly, infectious virus titre in Vero E6 cells dropped by 3.6log10 TCID50 and 2.8log10 TCID50 after the drug addition pre- and post-infection, respectively. In HSAEC, Larifan inhibited SARS-CoV-2 replication at the similar level. Larifan also markedly reduced virus numbers in the lungs of infected hamsters (p = 0.0032) both at day three and five post-infection with a more pronounced effect after intranasal administration reaching a drop by 2.7log10 at day three and 2.0log10 at day five. The administration of Larifan also reduced the amount of infections virus titer in lungs (p = 0.0039) by 4.3log10 TCID50 and 2.8log10 TCID50 at day three and five post-infection, respectively. Improvements in the infection-induced pathological lesion severity in the lungs of animals treated with Larifan were also demonstrated by histological analyses.

Conclusions

The inhibition of SARS-CoV-2 replication in vitro and the reduction of the viral load in the lungs of infected hamsters treated with Larifan alongside the improved lung histopathology, suggests a potential use of Larifan in controlling the COVID-19 disease in humans.
Amacrine cells differentially balance zebrafish colour circuits in the central and peripheral retina
Authors: Wang Xinwei , Roberts Paul A , Yoshimatsu Takeshi , Lagnado Leon , Baden Tom
Published: January 2022

In vertebrate vision, the feature-extracting circuits of the inner retina are driven by photoreceptors whose outputs are already pre-processed. In zebrafish, for example, outer retinal circuits split “colour” from “greyscale” information across all four cone-photoreceptor types. How does the inner retina process this incoming spectral information while also combining cone-signals to shape new greyscale functions?

We address this question by imaging the light driven responses of amacrine cells (ACs) and bipolar cells (BCs) in larval zebrafish, in the presence and pharmacological absence of inner retinal inhibition. We find that amacrine cells exert distinct effects on greyscale processing depending on retinal region, as well as contributing to the generation of colour opponency in the central retina. However, in the peripheral retina amacrine cells enhanced opponency in some bipolar cells while at the same time suppressing pre-existing opponency in others, such that the net change in the number of colour-opponent units was essentially zero. To achieve this ‘dynamic balance’ ACs counteracted intrinsic colour opponency of BCs via the On-channel. Consistent with these observations, Off-stratifying ACs were exclusively achromatic, while all colour opponent ACs stratified in the On-sublamina.

This study reveals that the central and peripheral retina of larval zebrafish employ fundamentally distinct inhibitory circuits to control the interaction between greyscale- and colour-processing. Differential actions on the On- and Off-channels control the transmission of colour-opponent signals in the periphery.
An in vitro neuronal model replicating the in vivo maturation and heterogeneity of perineuronal nets
Authors: Dickens S , Goodenough A , Kwok JCF
Published: January 2022

The perineuronal net (PNN) is a condensed form of extracellular matrix (ECM) that enwraps specific populations of neurons and regulates plasticity. To create a PNN, only three classes of components are needed: membrane bound hyaluronan by its synthetic enzyme hyaluronan synthases (HASs), a link protein and a CSPG. However, there is redundancy within the classes as multiple HAS isoforms, link proteins and CSPGs have been found in the PNN in vivo. The effect of this heterogeneity has on PNN function is unresolved. Currently, the most common way to address this question is through the creation and study of PNN component in knockout animals. Here, we reported the development of a primary neuronal culture model which reproduces the in vivo maturation and heterogeneity of PNNs. This model accurately replicated mature cortical PNNs, both in terms of the heterogeneity in PNN composition and its maturation. PNNs transitioned from an immature punctate morphology to the reticular morphology as observed in the mature CNS. We also observed a small population of PNNs that were mature at an earlier time point and a distinct composition, highlighting further heterogeneity. This model will provide a valuable tool for the study of PNN biology, their roles in diseases and the development of PNN focused plasticity treatment.
LITERATUR REVIEW : DEVELOPMENT OF DISASTER EDUCATION IN MULTI AGENT BASED EARLY EMERGENCY HANDLING IN THE PRE-HOSPITALS AREA
Authors: Winoto Priyo Mukti Pribadi , Wijayanti Lono , Pandin Moses Glorino Rumambo
Published: January 2022

Background

Disaster risk reduction involves several sectors, legal, social, structural, economic, technological, educational, environmental health, with improved preparedness will be able to reduce the impact of disasters. Capacity that continues to be added with knowledge about rapid disaster response to disasters can make resilience dealing with disasters and preventing the emergence of disaster risks.

Purpose

Conduct a literature review on articles that examine the importance of disaster education in the initial handling of emergencies in the hospital area

Design

Literature review

Method

Using databases with electronic search on ProQuest, SAGE, and Science Direct published in 2017-2021

Results

100 articles were used in the review. These articles discuss the importance of disaster education in the initial handling of emergencies in the hospital area. The 15 articles reviewed are original research.

Conclusion

Local communities are well placed to play a central role in hazard identification, development of preparedness plans, detection and response to emergencies, and implementation of recovery efforts. Community leaders and local health workers (e.g. family doctors, nurses, midwives, pharmacists, community health workers) can build public trust, disseminate information, and identify people at risk
Values and preferences of the general population in Indonesia in relation to COVID-19 self-testing: A cross-sectional survey
Authors: Thomas Caroline , Shilton Sonjelle , Thomas Catherine , Batheja Deepshikha , Goel Srishti , Iye Claudius Mone , Ivanova Elena , Martínez-Pérez Guillermo Z.
Published: January 2022

Objectives

Innovative diagnostics are essential to assist members of the general population become active agents of case detection. In Indonesia, a country with an over-burdened healthcare system, individuals could use self-tests for SARS-CoV-2 to determine their COVID-19 status. To assess the acceptability of SARS-CoV-2 self-testing among the general population in Indonesia, a cross-sectional, population-based survey was conducted in mid-2021 in Jakarta and the provinces of Banten and North Sulawesi.

Methods

This was a survey that approached respondents in >600 randomly selected street-points in the three study geographies. A 35-item questionnaire was used to collect data on key variables, such as willingness to use and to pay for a SARS-CoV-2 self-test and likely actions following a positive result. Bivariate and multivariate regression analyses were performed.

Results

Of 630 respondents, (318 were female), 14% knew about COVID-19 self-testing, while 62.7% agreed with the concept of people being able to self-test at home, unassisted, for COVID-19. If self-tests were available in Indonesia, >60% of respondents would use them if they felt it necessary and would undertake regular self-testing e.g., weekly if recommended. Upon receiving a positive self-test result, most respondents would communicate it (86.03%), request post-test counseling (80.79%), self-isolate (97.46%), and/or warn their close contacts (n=570, 90.48%).

Conclusions

SARS-CoV-2 self-testing would be acceptable to a majority of the Indonesian public, to learn whether they have COVID-19. Self-testing could contribute to an over-burdened healthcare system by helping COVID-19-infected people become agents of change in epidemiological surveillance of SARS-CoV-2 in their communities.
Vaccinia virus attenuation by codon deoptimization of the A24R gene for vaccine development
Authors: Lorenzo María M , Nogales Aitor , Chiem Kevin , Blasco Rafael , Martínez-Sobrido Luis
Published: January 2022

Poxviruses have large DNA genomes and they are able to infect multiple vertebrate and invertebrate animals, including humans. Despite the eradication of smallpox, poxvirus infections still remain a significant public health concern. Vaccinia virus (VV) is the prototypic member in the poxviridae family and it has been used extensively for different therapeutic applications, including the generation of vaccines against multiple infectious diseases and/or for oncolytic treatment. Many attempts have been pursued to develop novel attenuated forms of VV with improved safety profiles for their implementation as vaccines and/or vaccines vectors. We and others have previously demonstrated how RNA viruses encoding codon-deoptimized viral genes are attenuated, immunogenic and able to protect, upon a single administration, against challenge with parental viruses. In this study, we employed the same experimental approach based on the use of misrepresented codons for the generation of a recombinant (r)VV encoding a codon-deoptimized A24R gene, which is a key component of the viral RNA polymerase. Similar to our previous studies with RNA viruses, the A24R codon-deoptimized rVV (v-A24cd) was highly attenuated in vivo but able to protect, after a single intranasal dose administration, against an otherwise lethal challenge with parental VV. These results indicate that poxviruses can be effectively attenuated by synonymous codon deoptimization and open the possibility of using this methodology alone or in combination with other experimental approaches for the development of attenuated vaccines for the treatment of poxvirus infection, or to generate improved VV-based vectors. Moreover, this approach could be applied to other DNA viruses.

IMPORTANCE

The family poxviridae includes multiple viruses of medical and veterinary relevance, being vaccinia virus (VV) the prototypic member in the family. VV was used during the smallpox vaccination campaign to eradicate variola virus (VARV), which is considered a credible bioterrorism threat. Because of novel innovations in genetic engineering and vaccine technology, VV has gained popularity as a viral vector for the development of vaccines against several infectious diseases. Several approaches have been used to generate attenuated VV for its implementation as vaccine and/or vaccine vector. Here, we generated a rVV containing a codon-deoptimized A24R gene (v-A24cd), which encodes a key component of the viral RNA polymerase. v-A24cd was stable in culture cells and highly attenuated in vivo but able to protect against a subsequent lethal challenge with parental VV. Our findings support the use of this approach for the development of safe, stable, and protective live-attenuated VV and/or vaccine vectors.
The interplay of active and passive mechanisms in slow axonal transport
Authors: Maiya Reshma , Dey Swagata , Ray Krishanu , Menon Gautam I.
Published: January 2022

A combination of intermittent active movement of transient aggregates and a paused state that intervenes between periods of active transport has been proposed to underly the slow, directed transport of soluble proteins in axons. A component of passive diffusion in the axoplasm may also contribute to slow axonal transport, although quantitative estimates of the relative contributions of diffusive and active movement in the slow transport of a soluble protein, and in particular how they might vary across developmental stages, are lacking. Here, we propose and study a model for slow axonal transport, addressing data from bleach-recovery measurements on a small, soluble, protein, Choline Acetyltransferase (ChAT), in thin axons of the lateral chordotonal (lch5) sensory neurons of Drosophila. ChAT is mainly present in soluble form in the axon and catalyses the acetylation of choline at the synapse. It does not form particulate structures in axons and moves at rates characteristic of slow component b (≈ 1-10 mm/day or 0.01-0.1 μm/s). Using our model, which incorporates active transport, paused and diffusive states, we predict bleach recovery and cargo trajectories obtained through kymographs, comparing these to experimental observations at different developmental stages. We show that changes in the diffusive fraction of cargo during these developmental stages dominate bleach recovery and that a combination of active motion with a paused state alone cannot reproduce the data. We compared predictions of the model with results from photoactivation experiments. The importance of the diffusive state in reproducing the bleach recovery signal in the slow axonal transport of small soluble proteins is our central result.

STATEMENT OF SIGNIFICANCE

While the fast axonal transport of cargo in axons is by now well-understood, the nature of slow transport remains controversial. A number of different models having been proposed for slow axonal transport, including models which allow for transitions between an intermittently moving molecular-motor driven state and a stalled state. How mechanisms for slow axonal transport are modulated during development is unexplored. We study a number of different models for slow axonal transport, comparing their predictions to data on transport of the enzyme Choline Acetyltransferase (ChAT) in thin lateral chordotonal (lch5) sensory neurons of Drosophila larva, across developmental stages where flux increases significantly. We show that accounting for changes in the diffusive fraction of cargo during these developmental stages is essential and diffusion cannot be neglected in the modelling of the slow axonal transport of small soluble proteins.
PyRodentTracks: flexible computer vision and RFID based system for multiple rodent tracking and behavioral assessment
Authors: Fong Tony , Jury Braeden , Hu Hao , Murphy Timothy H.
Published: January 2022

PyRodentTracks (PRT) is a scalable and customizable computer vision and RFID- based system for multiple rodent tracking and behavior assessment that can be set up within minutes in any user-defined arena at minimal cost. PRT is composed of the online Raspberry Pi-based video and RFID acquisition and the subsequent offline analysis tools. The system is capable of tracking up to 6 mice in experiments ranging from minutes to days. PRT maintained a minimum of 88% detections tracked with an overall accuracy >85% when compared to manual validation of videos containing 1-4 mice in a modified home-cage. As expected, chronic recording in home-cage revealed diurnal activity patterns. Moreover, it was observed that novel non-cagemate mice pairs exhibit more similarity in travel trajectory patterns over a 10-minute period in the openfield than cagemates. Therefore, shared features within travel trajectories between animals may be a measure of sociability that has not been previously reported. Moreover, PRT can interface with open-source packages such as Deeplabcut and Traja for pose estimation and travel trajectory analysis, respectively. In combination with Traja, PRT resolved motor deficits exhibited in stroke animals. Overall, we present an affordable, open-sourced, and customizable/scalable rodent-specific behavior recording and analysis system.

Statement of Significance

An affordable, customizable, and easy-to-use open-source rodent tracking system is described. To tackle the increasingly complex questions in neuroscience, researchers need a flexible system to track rodents of different coat colors in various complex experimental paradigms. The majority of current tools, commercial or otherwise, can only be fully automated to track multiple animals of the same type in a single defined environment and are not easily setup within custom arenas or cages. Moreover, many tools are not only expensive but are also difficult to set up and use, often requiring users to have extensive hardware and software knowledge. In contrast, PRT is easy to install and can be adapted to track rodents of any coat color in any user-defined environment with few restrictions. We believe that PRT will be an invaluable tool for researchers that are quantifying behavior in identified animals.
Correction of the scientific production: publisher performance evaluation using a dataset of 4844 PubMed retractions
Authors: Toma Catalin , Padureanu Liliana , Toma Bogdan
Published: January 2022

Background

Withdrawal of problematic scientific articles after publication is one of the mechanisms for correcting the literature available to publishers, especially in the conditions of the ever-increasing trend of publishing activity in the medical field. The market volume and the business model justify publishers’ involvement in the post-publication quality control(QC) of scientific production. The limited information about this subject determined us to analyze retractions and the main retraction reasons for publishers with many withdrawn articles. We also propose a score to measure the evolution of their performance. The data set used for this article consists of 4844 PubMed retracted papers published between 1.01.2009 and 31.12.2020.

Methods

We have analyzed the retraction notes and retraction reasons, grouping them by publisher. To evaluate performance, we formulated an SDTP score whose calculation formula includes several parameters: speed (article exposure time(ET)), detection rate (percentage of articles whose retraction is initiated by the editor/publisher/institution without the authors’ participation), transparency (percentage of retracted articles available online and clarity of retraction notes), precision (mention of authors’ responsibility and percentage of retractions for reasons other than editorial errors).

Results

The 4844 withdrawn articles were published in 1767 journals by 366 publishers, the average number of withdrawn articles/journal being 2.74. Forty-five publishers have more than ten withdrawn articles, holding 88% of all papers and 79% of journals. Combining our data with data from another study shows that less than 7% of PubMed journals withdrew at least one article. Only 10.5% of the withdrawal notes included the individual responsibility of the authors. Nine of the top 11 publishers had the largest number of articles withdrawn in 2020, in the first 11 places finding, as expected, some big publishers. Retraction reasons analysis shows considerable differences between publishers concerning the articles ET: median values between 9 and 43 months (mistakes), 9 and 73 months (images), 10 and 42 months (plagiarism & overlap).

The SDTP score shows, between 2018 and 2020, an improvement in QC of four publishers in the top 11 and a decrease in the gap between 1st and 11th place. The group of the other 355 publishers also has a positive evolution of the SDTP score.

Conclusions

Publishers have to get involved actively and measurably in the post-publication evaluation of scientific products. The introduction of reporting standards for retraction notes and replicable indicators for quantifying publishing QC can help increase the overall quality of scientific literature.
Rapid Selectivity to Natural Images Across Layers of Primate V1
Authors: Chen Xiaomo , Zhu Shude , Bai Kunlun , Xia Ruobing , Kong Nathan C.L. , Norcia Anthony M , Moore Tirin
Published: January 2022

Visual systems are thought to have adapted to the statistical properties of natural scenes. However, the extent to which visual neurons respond selectively to natural images, and the stage at which that selectivity emerges remains unclear. To address these questions, we recorded the visual activity of neurons in macaque V1 using high-density electrode arrays (Neuropixels), and compared neuronal responses to images presented at three levels of naturalness. We found that within 60 ms of stimulus onset, neurons in all cortical layers, including input layers 4C alpha and beta, responded more vigorously to natural images than to statistically matched naturalistic texture and noise images. The result remained when residual variations in the local image statistics were factored out. V1 neurons also showed high population and lifetime sparseness for natural images. Across the population of V1 neurons, sensitivity to natural images exceeded the sensitivity to other image categories. The results reveal a rapid and pervasive preference for natural images is present at the earliest stages of cortical processing.
Variant to function mapping at single-cell resolution through network propagation
Authors: Yu Fulong , Cato Liam D. , Weng Chen , Liggett L. Alexander , Jeon Soyoung , Xu Keren , Chiang Charleston W.K. , Wiemels Joseph L. , Weissman Jonathan S. , de Smith Adam J. , Sankaran Vijay G.
Published: January 2022

With burgeoning human disease genetic associations and single-cell genomic atlases covering a range of tissues, there are unprecedented opportunities to systematically gain insights into the mechanisms of disease-causal variation. However, sparsity and noise, particularly in the context of single-cell epigenomic data, hamper the identification of disease- or trait-relevant cell types, states, and trajectories. To overcome these challenges, we have developed the SCAVENGE method, which maps causal variants to their relevant cellular context at single-cell resolution by employing the strategy of network propagation. We demonstrate how SCAVENGE can help identify key biological mechanisms underlying human genetic variation including enrichment of blood traits at distinct stages of human hematopoiesis, defining monocyte subsets that increase the risk for severe coronavirus disease 2019 (COVID-19), and identifying intermediate lymphocyte developmental states that are critical for predisposition to acute leukemia. Our approach not only provides a framework for enabling variant-to-function insights at single-cell resolution, but also suggests a more general strategy for maximizing the inferences that can be made using single-cell genomic data.
LMM-MQM time series mapping - An application in a murine advanced intercross line identifies novel growth QTLs
Authors: Arends Danny , Hesse Deike , Kärst Stefan , Heise Sebastian , Lyu Shijie , Korkuc Paula , Delpero Manuel , Mulligan Megan K. , Prins Pjotr , Brockmann Gudrun A.
Published: January 2022

The Berlin Fat Mouse Inbred line 860 (BFMI860) is a mouse model for juvenile obesity. Previously, a recessive major effect locus (jObes1) was identified on chromosome 3 explaining around 26% of the body weight variance in an BFMI860xC57BL/6NCrl advanced intercross line. The aim of this study was to discover additional QTL.

Time series body weight data were modeled using linear mixed models (LMM), while a multiple QTL mapping (MQM) approach compensated for the jObes1 locus effect. LMM-MQM identified five additional loci significantly associated with body weight. Variance explained by the jObes1 locus increased to 38.1% when using LMM-MQM mapping, while the additional loci explained between 2.0% and 3.9% of the body weight variance. Several positional candidate genes within the novel QTL regions were found in KEGG pathways for insulin signaling and insulin resistance. Strong distortion with preference for the BFMI allele was observed within a newly identified QTL containing the well-known Foxo1 regulator of adipocyte differentiation.

Here, we present a novel method for QTL detection in time series data: LMM-MQM time series mapping. We show that our method is more powerful in detecting QTLs compared to single timepoint mapping approaches. Thus, the time series structure should be considered for optimal detection of small effect QTLs. LMM-MQM time series mapping can be used to find genetic determinants of all kind of “phenotypes over time” be it lactation curves in cattle, plant biomass, drug clearance in human clinical trials, or cognitive decline during disease.
Interactions between nuclear and mitochondrial SNPs and Parkinson’s disease risk
Authors: Pickett Sarah J. , Deen Dasha , Pyle Angela , Santibanez-Koref Mauro , Hudson Gavin
Published: January 2022

Interactions between the products of the nuclear and mitochondrial genomes are critical for the function of most eukaryotic cells. Recently the introduction of mitochondrial replacement therapy has raised the question of incompatibilities between mitochondrial and nuclear variants, and their potential influence on the genetic makeup of human populations. Such interactions could also contribute to the variability of the penetrance of pathogenic DNA variants. This led us to investigate the frequencies of combinations of nuclear and mitochondrial SNP alleles (mitonuclear combinations) in healthy individuals (n=5375) and in a cohort of patients with Parkinson’s disease (PD, n=2210). In the unaffected population, we were not able to find associations between nuclear and mitochondrial variants with a false discovery rate below 0.05 after accounting for multiple testing (i.e., the number of combinations examined). However, in the PD cohort, five combinations surpassed this threshold. Next, combining both cohorts, we investigated whether these associations were modulated by disease status. All five combinations were significant (p<10−3 for all tests).These combinations also showed significant evidence for an effect of the interaction between the mitochondrial and nuclear variants on disease risk. Their nuclear components mapped to TBCA, NIBAN3 and GLT25D1 and an uncharacterised intergenic region. In summary, starting from a single cohort design we identified combinations of nuclear and mitochondrial variants affecting PD disease risk.
Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics
Authors: Cancino-Muñoz Irving , López Mariana G. , Torres-Puente Manuela , Villamayor Luis M. , Borrás Rafael , Borrás-Máñez María , Bosque Montserrat , Camarena Juan J. , Colijn Caroline , Colomer-Roig Ester , Colomina Javier , Escribano Isabel , Esparcia-Rodríguez Oscar , García-García Francisco , Gil-Brusola Ana , Gimeno Concepción , Gimeno-Gascón Adelina , Gomila-Sard Bárbara , González-Granda Daminana , Gonzalo-Jiménez Nieves , Guna-Serrano María Remedio , López-Hontangas José Luis , Martín-González Coral , Moreno-Muñoz Rosario , Navarro David , Navarro María , Orta Nieves , Pérez Elvira , Prat Josep , Rodríguez Juan Carlos , Ruiz-García Ma. Montserrat , Vanaclocha Hermelinda ,   Valencia Region Tuberculosis Working Group, Comas Iñaki
Published: January 2022

Background

Transmission has been proposed as a driver of tuberculosis (TB) epidemics in high-burden regions, with negligible impact in low-burden areas. Genomic epidemiology can greatly help to quantify transmission in different settings but the lack of whole genome sequencing population-based studies has hampered its use to compare transmission dynamics and contribution across settings.

Methods

We generated an additional population-based sequencing dataset from Valencia Region, a low burden setting, and compared it with available datasets from different TB settings to reveal heterogeneity of transmission dynamics and its public health implications. We sequenced the whole genome of 785 M. tuberculosis strains and linked genomes to patient epidemiological data. We applied a pairwise distance clustering approach and phylodynamics methods to characterize transmission events over the last 150 years, in Valencia, Spain (low burden), Oxfordshire, United Kingdom (low burden) and a high-burden (Karonga, Malawi).

Results

Our results revealed high local transmission in the Valencia Region (47.4% clustering), in contrast to Oxfordshire (27% clustering), and similar to a high-burden setting like Malawi (49.8% clustering). By modelling times of the transmission events, we observed that settings with high transmission are associated with uninterrupted transmission of strains over decades, irrespective of burden.

Conclusions

Our results underscore significant differences in transmission between TB settings even with similar burdens, reveal the role of past epidemic in on-going TB epidemic and highlight the need for in-depth characterization of transmission dynamics and specifically-tailored TB control strategies.

Funding

European Research Council under the European Union’s Horizon 2020 research and innovation program (Grants 638553-TB-ACCELERATE, 101001038-TB-RECONNECT), and Ministerio de Ciencia e Innovación (Spanish Government, SAF2016-77346-R and PID2019-104477RB-I00)
Reduced resilience of brain state transitions in anti-N-Methyl-D-Aspartate receptor encephalitis
Authors: von Schwanenflug Nina , Ramirez-Mahaluf Juan P , Krohn Stephan , Romanello Amy , Heine Josephine , Prüss Harald , Crossley Nicolas A , Finke Carsten
Published: January 2022

Objective

Patients with anti-NMDA receptor encephalitis suffer from a severe neuropsychiatric syndrome, yet most patients show no abnormalities in routine magnetic resonance imaging. In contrast, advanced neuroimaging studies have consistently identified disrupted functional connectivity in these patients, with recent work suggesting increased volatility of functional state dynamics. Here, we investigate these network dynamics through the spatiotemporal trajectory of meta-state transitions, yielding a time-resolved account of brain state exploration in anti-NMDA receptor encephalitis.

Methods

Resting-state functional magnetic resonance imaging data were acquired in 73 patients with NMDAR encephalitis and 73 age- and sex-matched healthy controls. Time-resolved functional connectivity was clustered into brain meta-states, giving rise to a time-resolved transition network graph with states as nodes and transitions between brain meta-states as weighted, directed edges. Network topology, robustness, and transition cost of these transition networks were compared between groups.

Results

Transition networks of patients showed significantly lower local efficiency (t = -2.54, pFDR = 0.026), lower robustness (t = -2.01, pFDR = 0.048) and higher leap size (t = 2.33, pFDR = 0.026) compared to controls. Furthermore, the ratio of within-to-between module transitions and state similarity was significantly lower in patients. Importantly, alterations of brain state transitions correlated with disease severity.

Interpretation

These findings reveal systematic alterations of transition networks in patients, suggesting that anti-NMDA receptor encephalitis is characterized by reduced stability of brain state transitions and that this reduced resilience of transition networks plays a clinically relevant role in the manifestation of the disease.
A metric and its derived protein network for evaluation of ortholog database inconsistency
Authors: Yang Weijie , Ji Jingsi , Ling Shuyang , Fang Gang
Published: January 2022

Orthology prediction is challenging yet rewarding. Orthologs are the cornerstone of almost all comparative genomics studies. Dozens of ortholog resources have been available and broadly used over the past decades. However, the inconsistency between these resources has drawn growing concerns, especially when more proteomes are available and ortholog databases expand. It is no longer easy to decide which ortholog database to use, and it becomes necessary to compare conclusions based on different resources. We are presenting here a metric to assess ortholog functional consistency. Using this metric, we built a network connecting proteins based on their functional similarity. We then detected network communities as ortholog groups, and each protein in our ortholog group inherited the network degree centrality. By benchmarking Quest for Orthologs (QfO) and some representative ortholog resources, we concluded the degree centrality could serve as the index for the reliability of functional consistency. The numerical nature of degree centrality could also open a door for quantitative study in pan-genome and other comparative genomics studies.
Tuned geometries of hippocampal representations meet the demands of social memory
Authors: Boyle Lara M. , Posani Lorenzo , Irfan Sarah , Siegelbaum Steven A. , Fusi Stefano
Published: January 2022

Social recognition consists of multiple memory processes, including the detection of familiarity – the ability to rapidly distinguish familiar from novel individuals – and recollection – the effortful recall of where a social episode occurred and who was present. At present, the neural mechanisms for these different social memory processes remain unknown. Here, we investigate the population code for novel and familiar individuals in mice using calcium imaging of neural activity in a region crucial for social memory, the dorsal CA2 area of the hippocampus. We report that familiarity changes CA2 representations of social encounters to meet the different demands of social memory. While novel individuals are represented in a low-dimensional geometry that allows for rapid generalization, familiar individuals are represented in a higher-dimensional geometry that supports high-capacity memory storage. The magnitude of the change in dimensionality of CA2 representations for a given individual predicts the performance of that individual in a social recognition memory test, suggesting a direct relationship between the representational geometry and memory-guided behavior. Finally, we show that familiarity is encoded as an abstract variable with neural responses generalizing across different identities and spatial locations. Thus, through the tuning of the geometry of structured neural activity, CA2 is able to meet the complex demands of multiple social memory processes.