bluuebunny/crossref_metadata_2025 huggingface dataset:
Running System of Flipped Teaching Based on Video Conference
Authors: Zhang Xiao-Yu
Published: October 2022

Objective

I aimed to provide a basis for the standardized operation of Flipped Teaching based on Video Conference for reference by other institutions or organizations.

Methods

The teaching and research materials of Flipped Teaching with Video Conference as carrier carried out in April and June 2022 were collected. Based on the “Structure-Process-Outcome” theory, the induction method and SWOT analysis method were used for systematic analysis.

Results

A total of 43 residents participated in the teaching project, and 40 of them passed the examination, accounting for 93.0%. And the teaching project had been analyzed and reported in 3 literature. For the successful operation of this project, the following five dimensions were summarized. First, the preparatory dimension of teaching: clear teaching form, objectives, content, reference materials and assignments; Second, the carrier of teaching implementation: the selection, function and debugging of teaching equipment; Third, the teaching management dimension: the management mode, management team, lecturers team, trainees management and emergency response; Fourth, the teaching evaluation dimension: trainees’ systematic evaluation of the teaching; Fifth, the teaching assessment dimension: attendance rate, assignments completion rate and exam pass rate.

Conclusion

The core of the running system is to carry out Flipped Teaching with Video Conference as carrier to realize the standardized training for residents, and ensure the smooth progress and the quality of teaching through teaching management, evaluation and assessment.
A causal model of human growth and its estimation using temporally-sparse data
Authors: Bunce John A. , Fernández Catalina I. , Revilla-Minaya Caissa
Published: October 2022

Existing models of human growth provide little insight into underlying mechanisms responsible for inter-individual and inter-population variation in children’s growth trajectories. Building on general theories linking growth to metabolic rates, we develop a causal parametric model of height and weight growth incorporating a representation of human body allometry and a process-partitioned representation of ontogeny. This model permits separation of metabolic causes of growth variation, potentially influenced by nutrition and disease, from allometric factors, potentially under stronger genetic control. We estimate model parameters using a Bayesian multilevel statistical design applied to temporally-dense height and weight measurements of U.S. children, and temporally-sparse measurements of Indigenous Amazonian children. This facilitates a comparison of the contributions of metabolism and allometry to observed cross-cultural variation in the growth trajectories of the two populations, and permits simulation of the effects of healthcare interventions on growth. This theoretical model provides a new framework for exploring the causes of growth variation in our species, while potentially guiding the development of appropriate, and desired, healthcare interventions in societies confronting growth-related health challenges, such as malnutrition and stunting.
Newly formed place cells are stabilized by coordinated population activity during REM sleep
Authors: Boyce Richard , Yong Hyun Choong , Carmichael James E , Brandon Mark P , Williams Sylvain
Published: October 2022

The involvement of rapid-eye-movement sleep (REMs) in spatial memory formation was recently demonstrated, although how neural activity during REMs influences newly-formed place field stability remains unclear. Here, we combined large-scale single-unit recordings of mouse hippocampal CA1 with an established optogenetic approach enabling REMs-selective inhibition of medial septum GABAergic neurons (MSGABA), resulting in spatial memory deficits when applied post-learning. Although individual neural activity was unaffected by REMs-selective MSGABA inhibition during a post-learning rest session, both the synchrony of population-level activity bursts observed during REMs occurring in the rest session and place field stability measured during subsequent memory recall testing were reduced vs controls. However, the latter effect was limited to place cells participating in population activity during REMs, as stability of non-participant place cells was relatively weak and indifferent between groups. This suggests that synchronous CA1 population activity during REMs stabilizes spatial representations in a plastic subpopulation of participating CA1 neurons.
Magnetically powered chitosan milliwheels for rapid translation, barrier function rescue, and delivery of therapeutic proteins to the inflamed gut epithelium
Authors: Osmond M.J. , Korthals E. , Zimmermann C.J. , Roth E.J. , Marr D.W.M. , Neeves K.B.
Published: October 2022

Inflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability. To overcome these shortcomings, we demonstrate magnetically powered hydrogel particles that roll along mucosal surfaces, provide protection from degradation, and sustain local release of anti-TNF. Iron oxide nanoparticles are embedded into a crosslinked chitosan hydrogel and sieved to produce 100-200 μm particles called milliwheels (m-wheels). Once loaded with anti-TNF, these m-wheels release 10% to 80% of their payload over one week at a rate that depends on crosslinking density and pH. A rotating magnetic field induces a torque on the m-wheels that results in rolling velocities greater than 500 μm/s on glass and mucus-secreting cells. The permeability of TNF challenged gut epithelial cell monolayers was rescued in the presence of anti-TNF carrying m-wheels which both neutralized the TNF and created an impermeable patch over leaky cell junctions. With the ability to translate over mucosal surfaces at high speed, provide sustained release directly to the inflamed epithelium, and provide barrier rescue, m-wheels demonstrate a potential strategy to deliver therapeutic proteins for the treatment of IBD.
Correlating basal gene expression across chemical sensitivity data to screen for novel synergistic interactors of HDAC inhibitors in pancreatic carcinoma
Authors: Djokovic Nemanja , Djuric Ana , Ruzic Dusan , Srdic-Rajic Tatjana , Nikolic Katarina
Published: October 2022

Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive and lethal malignancies. Development of chemoresistance in PDAC is one of the key contributors for the poor survival outcomes of PDAC patients and the major reason for urgent development of novel pharmacological approaches for effective treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC, but number of possible combinations considering all approved drugs and drug candidates is too large to be explored empirically. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as a game changer but available data indicates their efficacy only in combined therapy settings. In this work, we explored possibility of using drug-sensitivity data together with basal gene expression data on pancreatic cell lines to predict the combinatorial options available for HDACi and developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC. Our results identified sphingolipid signaling pathway with associated downstream effectors as a promising novel target for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod.
On the Origin of Obligate Parthenogenesis inDaphnia pulex
Authors: Snyman Marelize , Xu Sen
Published: October 2022

Despite the presence of obligately parthenogenetic (OP) lineages derived from sexual ancestors in diverse phylogenetic groups, the genetic mechanisms giving rise to the OP lineages remain poorly understood. The freshwater microcrustaceanDaphnia pulextypically reproduces via cyclical parthenogenesis. However, some populations of OPD. pulexhave emerged due to ancestral hybridization and introgression events between two cyclically parthenogenetic (CP) speciesD. pulexandD. pulicaria. These OP hybrids produce both subitaneous and resting eggs parthenogenetically, deviating from CP isolates where resting eggs are produced via conventional meiosis and mating. This study examines the genome-wide expression and alternative splicing patterns of early subitaneous versus early resting egg production in OPD. pulexisolates to gain insight into the genes and mechanisms underlying this transition to obligate parthenogenesis. Our differential expression and functional enrichment analyses revealed a downregulation of meiosis and cell cycle genes during early resting egg production, as well as divergent expression patterns of metabolism, biosynthesis, and signaling pathways between the two reproductive modes. These results provide important gene candidates for future experimental verification, including the CDC20 gene that activates the anaphase-promoting complex in meiosis.
Developmental Validation of the Illumina Infinium Assay using the Global Screening Array (GSA) on the iScan System for use in Forensic Laboratories
Authors: Russell David A. , Gorden Erin M. , Peck Michelle A. , Neal Christina M. , Heaton Mary C. , Bouchet Jessica , Koeppel Alexander F. , Ciuzio Elayna , Turner Stephen D. , Reedy Carmen R.
Published: October 2022

Microarray processing, which interrogates hundreds of thousands of single nucleotide polymorphisms (SNPs) across the human genome, has recently gained traction in forensics due to its use in forensic genetic genealogy, which is based on analysis using SNPs to compare distant relatives in publicly curated databases for the purposes of developing investigative leads or identifying human remains. To date, there has been no published developmental validation of microarray processing using the Scientific Working Group on DNA Analysis Methods (SWGDAM) Validation Guidelines for DNA Analysis Methods and Federal Bureau of Investigation Quality Assurance Standards. Validation of these methods are warranted to identify samples suitable for microarray analysis and to assess the quality of the data obtained prior to upload to genealogical databases. In this study, we validated the Global Screening Array (GSA) for use in forensic investigations according to SWGDAM guidelines, including the following studies: precision and accuracy, sensitivity, contamination, degradation, species specificity, mock case-type samples, mixtures, repeatability and reproducibility, and stability. Results indicated accurate genotype calls with SNP call rates >95% at DNA input as low as 0.20 ng. In addition to SNP call rate, we developed interpretation thresholds for signal intensity and heterozygosity to allow for sample quality assessment and identification of highly degraded and/or non-human DNA. This study demonstrates that high quality data can be generated from multiple sample types, including mock forensic evidence that simulated the challenges that are often encountered in forensic cold cases.
An enhanced transcription factor repressilator that buffers stochasticity and entrains to an erratic external circadian signal
Authors: Frank Steven A.
Published: October 2022

How do cellular regulatory networks solve the challenges of life? This article presents computer software to study that question, focusing on how transcription factor networks transform internal and external inputs into cellular response outputs. The example challenge concerns maintaining a circadian rhythm of molecular concentrations. The system must buffer intrinsic stochastic fluctuations in molecular concentrations and entrain to an external circadian signal that appears and disappears randomly. The software optimizes a stochastic differential equation of transcription factor protein dynamics and the associated mRNAs that produce those transcription factors. The cellular network takes as inputs the concentrations of the transcription factors and produces as outputs the transcription rates of the mRNAs that make the transcription factors. An artificial neural network encodes the cellular input-output function, allowing efficient search for solutions to the complex stochastic challenge. Several good solutions are discovered, measured by the probability distribution for the tracking deviation between the stochastic cellular circadian trajectory and the deterministic external circadian pattern. The solutions differ significantly from each other, showing that overparameterized cellular networks may solve a given challenge in a variety of ways. The computation method provides a major advance in its ability to find transcription factor network dynamics than can solve environmental challenges. The article concludes by drawing an analogy between overparameterized cellular networks and the dense and deeply connected overparameterized artificial neural networks that have succeeded so well in deep learning. Understanding how overparameterized networks solve challenges may provide insight into the evolutionary design of cellular regulation.
Statistical challenges for inferring multiple SARS-CoV-2 spillovers with early outbreak phylodynamics
Authors: Washburne Alex , Jones Adrian , Zhang Daoyu , Deigin Yuri , Quay Steven , Massey Steven E
Published: October 2022

Understanding how SARS-CoV-2 entered the human population, thereby causing the COVID-19 pandemic, is one of the most urgent questions in science today. Two hypotheses are widely acknowledged as being most likely to explain the pandemic’s origin in late 2019: (i) the “natural origin” hypothesis that one or more cross-species transmissions from animals into humans occurred, most likely at the Huanan Seafood Market in Wuhan, China; (ii) the “laboratory origin” hypothesis, that scientific research activities led to the unintentional leak of SARS-CoV-2 from a laboratory into the general population.

A recent analysis of SARS-CoV-2 genomes by Pekar et al. [Science377:960-966 (2022)] claims to establish at least two separate spillover events from animals into humans, thus claiming to provide strong evidence for the natural origin hypothesis. However, here we use outbreak simulations to show that the findings of Pekar et al. are heavily impacted by two methodological artifacts: the dubious exclusion of informative SARS-CoV-2 genomes, and their reliance on unrealistic phylodynamic models of SARS-CoV-2. Absent models that incorporate these effects, one cannot conclude multiple SARS-CoV-2 spillovers into humans. Our results cast doubt on a primary point of evidence in favor of the natural origin hypothesis.

Lay Summary

It is not known if SARS-CoV-2 spilled over from animals into humans at the Huanan Seafood Market, or arose as a result of research activities studying bat coronaviruses. Two recent papers had claimed to answer this question, but here we show those papers are both inconclusive as they fail to account for biases in how medical managers became alerted to SARS-CoV-2 and how public health authorities sampled early cases. Additionally, key data points conflicting with the authors’ conclusions were improperly excluded from the analysis. The papers’ methods do not justify their conclusions, and the origin of SARS-CoV-2 remains an urgent, open question for science.
Characterizing amblyopic perception under naturalistic viewing conditions
Authors: Meier Kimberly , Tarczy-Hornoch Kristina , Boynton Geoffrey M. , Fine Ione
Published: October 2022

Current assessments of interocular interactions in amblyopia use rivalrous stimuli, with conflicting stimuli in each eye, which does not reflect vision under typical circumstances. Here we measure interocular interactions in observers with amblyopia, strabismus with equal vision, and controls using a non-rivalrous stimulus. Observers used a joystick to continuously report perceived contrast of dichoptic grating stimuli, identical except that the stimulus was contrast-modulated independently in each eye over time. Consistent with previous studies, a model predicting the time-course of perceived contrast found increased amblyopic eye attenuation, and reduced contrast normalization of the fellow eye by the amblyopic eye, in amblyopic participants compared to controls. However, these suppressive interocular effects were weaker than those found in previous studies, suggesting that rivalrous stimuli may overestimate the effects of amblyopia on interocular interactions during naturalistic viewing conditions.
Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma
Authors: Patel Kunal S. , Tessema Kaleab K. , Kawaguchi Riki , Alvarado Alvaro G. , Muthukrishnan Sree Deepthi , Hagiwara Akifumi , Swarup Vivek , Liau Linda M. , Wang Anthony , Yong William , Geschwind Daniel H. , Nakano Ichiro , Goldman Steven A. , Everson Richard , Ellingson Benjamin M. , Kornblum Harley I.
Published: October 2022

Background

Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma.

Methods

We leveraged single-nucleus RNA-sequencing on 15 specimens from 5 high grade gliomas to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining for Ki67 to identify proliferative cell burden.

Results

Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched for mesenchymal-like states. These NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki67 staining. Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Cell-, gene-, and pathway-level analyses of the tumor microenvironment in the NE region reveal relative downregulation of tumor-mediated neovascularization and presence of cell-mediated immune response, but increased glioma-to-non-pathological cellular interactions.

Conclusions

This comprehensive analysis illustrates differing tumor and non-tumor landscapes of CE and NE regions in high-grade gliomas, highlighting the NE region as an area harboring likely initiators of recurrence in a pro-tumor microenvironment and identifying possible targets for future design of NE-specific adjuvant therapy.

Key Points

Significant proliferating tumor burden exist in non-enhancing regions of glioma; non-enhancing regions have unique tumor and non-tumor expression properties

Importance of Study

Standard of care treatment for glioblastoma relies on visualization of tumor via contrast-enhanced magnetic resonance imaging. However, non-enhancing regions harbor tumor cells that should be targets for adjuvant therapy given these regions are not resected in surgery. To begin addressing these infiltrating non-enhancing tumor cells, we thoroughly characterize the tumor and non-tumor microenvironment of non-enhancing regions in high grade gliomas. Understanding the total tumor burden, proliferating tumor ratio, and presence of putative glioma stem cells may help design adjuvant therapies for these unique population of tumor cells. Understanding the non-tumor immune and vascular microenvironment may help target these areas in regards to drug delivery and immunotherapy. Overall, in a disease marked by significant intratumoral heterogeneity, we focus identifying therapeutic strategies for areas not addressed at surgery.
Pre-saccadic enhancement of target stimulus motion influences post-saccadic smooth eye movements
Authors: Coop Shanna H. , Crutcher Garrett W. , Abrham Yonatan T. , Bucklaew Amy , Mitchell Jude F.
Published: October 2022

Primates move their eyes 2-3 times per second to bring objects of interest to central, high-resolution vision. For moving objects, they use a combination of rapid saccadic eye movements along with smooth following movements to track targets continuously. Each saccadic eye movement produces perceptual enhancements for the target. And for saccades that are made to moving targets, or stationary apertures that contain motion, there is a smooth post-saccadic following response (PFR) of the target motion (Kwon et al, 2019). This PFR occurs involuntarily even when the motion is task irrelevant and could provide an automatic behavioral read-out of the target’s motion. However, PFR movements are small, so it is unclear how reliable they would be as a trial-by-trial read-out. Here we examined PFR in marmoset monkeys performing a foraging task that requires almost no training and which has been shown to involve pre-saccadic neural enhancements of motion selective responses in visual area MT (Coop et al., 2024). We found that PFR in marmosets is highly consistent with humans and could be used to read-out the target motion. More so, we found that the motion in non-target apertures also influenced PFR but to a lesser extent than the target. The gain of PFR was distributed equally between target and non-target apertures before the saccade, and then was rapidly enhanced only for the target motion in driving the post-saccadic following. Thus, PFR provides a behavioral measure of target enhancement relative to distracters in addition to providing a read-out of the target’s motion.

Significance Statement

Using a saccade foraging paradigm in marmoset monkeys we measured visual motion integration and pre-saccadic enhancement based on the smooth following eye movements made after a saccade to a motion aperture. We find that marmosets exhibit post-saccadic following behaviors akin to humans, underscoring the evolutionary continuity in visual processing across primates. This following response provided an estimate of target motion that was half as accurate as explicitly trained reports but required minimal training to achieve. It also provided an estimate of the pre-saccadic enhancement for the target relative to distracters in the visual field.
Isotopic niches do not follow the expectations of niche conservatism in the bird genusCinclodes
Authors: Rader Jonathan A. , Matute Daniel R.
Published: October 2022

Phenotypic traits are expected to be more similar among closely related species than among species that diverged long ago (all else being equal). This pattern, known as phylogenetic niche conservatism, also applies to traits that are important to determine the niche of species. To test this hypothesis on ecological niches, we analyzed isotopic data from 254 museum study skins from 12 of the 16 species of the bird genusCinclodesand measured stable isotope ratios for four different elements: Carbon, Nitrogen, Hydrogen and Oxygen. We find that all traits, measured individually, or as a composite measurement, lack any phylogenetic signal, which in turn suggests a high level of lability in ecological niches. We compared these metrics to the measurements of morphological traits in the same genus and found that isotopic niches are uniquely evolutionarily labile compared to other traits. Our results suggest that, inCinclodes, the realized niche evolves much faster than expected by the constraints of phylogenetic history and poses the question of whether this is a general pattern across the tree of life.
Partitioning variance in a signaling trade-off under sexual selection reveals among-individual covariance in trait allocation
Authors: Reichert Michael S. , de la Hera Iván , Moiron Maria
Published: October 2022

Understanding the evolution of traits subject to trade-offs is challenging because phenotypes can (co)vary at both the among- and within-individual levels. Among-individual covariation indicates consistent, possibly genetic, differences in how individuals resolve the trade-off, while within-individual covariation indicates trait plasticity. There is also the potential for consistent among-individual differences in behavioral plasticity, although this has rarely been investigated. We studied the sources of (co)variance in two characteristics of an acoustic advertisement signal that trade off with one another and are under sexual selection in the gray treefrog,Hyla chrysoscelis: call duration and call rate. We recorded males on multiple nights calling spontaneously and in response to playbacks simulating different competition levels. Call duration, call rate, and their product, call effort, were all repeatable both within and across social contexts. Call duration and call rate covaried negatively, and the largest covariance was at the among-individual level. There was extensive plasticity in calling with changes in social competition, and we found some evidence for among-individual variance in call rate plasticity. The significant negative among-individual covariance in trait values is perpendicular to the primary direction of sexual selection in this species, indicating potential limits on the response to selection.
Seg2Link: an efficient and versatile solution for semi-automatic cell segmentation in 3D image stacks
Authors: Wen Chentao , Matsumoto Mami , Sawada Masato , Sawamoto Kazunobu , Kimura Koutarou D
Published: October 2022

Recent advances in microscopy techniques, especially in electron microscopy, are transforming biomedical studies by acquiring large quantities of high-precision 3D cell image stacks. However, to study cell morphology and connectivity in organs such as brains, scientists must first perform cell segmentation, which involves extracting individual cell regions of various shapes and sizes from a 3D image. This remains a great challenge because automatic cell segmentation can contain numerous errors, even with advanced deep learning methods. For biomedical research that requires cell segmentation in large 3D image stacks, an efficient semi-automated software solution is still needed. We created Seg2Link, which generates automatic segmentations based on deep learning predictions and allows users to quickly correct errors in the segmentation results. It can perform automatic instance segmentation of 2D cells in each slice, 3D cell linking across slices, and various manual corrections, in order to efficiently transform inaccurate deep learning predictions into accurate segmentation results. Seg2Link’s data structure and algorithms were also optimized to process 3D images with billions of voxels on a personal computer quickly. Thus, Seg2Link offers a simple and effective way for scientists to study cell morphology and connectivity in 3D image stacks.
Architecture and topologies of gene regulatory networks associated with breast cancer, adjacent normal, and normal tissues
Authors: Kumar Swapnil , Vindal Vaibhav
Published: October 2022

Most cancer studies employ adjacent normal tissues to tumors (ANTs) as controls, which are not completely normal and represent a pre-cancerous state. However, the regulatory landscape of ANTs and how it differs from tumor and non-tumor-bearing normal tissues is largely unexplored. Among cancers, breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide, with a lack of sufficient treatment regimens due to various reasons. Hence, we aimed to gain deeper insights into normal, pre-cancerous, and cancerous regulatory systems of the breast tissues towards the identification of ANT and subtype-specific candidate genes. For this, we constructed and analyzed eight gene regulatory networks (GRNs), including five different subtypes (viz.Basal, Her2, LuminalA, LuminalB, and Normal-Like), one ANT, and two normal tissue networks. Whereas several topological properties of these GRNs enabled us to identify tumor-related features of ANT; escape velocity centrality (EVC+) identified 24 functionally significant common genes, including well-known genes such asE2F1, FOXA1, JUN, BRCA1, GATA3, ERBB2,andERBB3across different subtypes and ANT. Similarly, the EVC+ also helped us to identify tissue-specific key genes (Basal: 18, Her2: 6, LuminalA: 5, LuminalB: 5, Normal-Like: 2, and ANT: 7). Additionally, differential correlation along with functional, pathway, and disease annotations highlighted the cancer-associated role of these genes. In a nutshell, the present study revealed ANT and subtype-specific regulatory features and key candidate genes which can be explored further usingin vitroandin vivoexperiments for better and effective disease management at an early stage.
Feasibility of linking markers of dementia-related health in primary care medical records to cognitive function assessed in a specialist dementia service
Authors: Marshall Michelle , Campbell Paul , Bailey James , Chew-Graham Carolyn A , Croft Peter , Frisher Martin , Hayward Richard , Negi Rashi , Rathod-Mistry Trishna , Singh Swaran , Robinson Louise , Sumathipala Athula , Thein Nwe , Walters Kate , Weich Scott , Jordan Kelvin P
Published: October 2022

Objectives

To assess the feasibility of linking and comparing markers of dementia-related health recorded in primary care electronic health records (EHR) to assessments of cognitive function undertaken in a specialist dementia service.

Methods

One thousand patients in a UK secondary care specialist dementia service were invited to take part. Primary care EHR were requested from 72 general practices of consenting patients. Sixty-three previously established individual markers within 13 broader domains of dementia-related health were then extracted from primary care EHR and compared to cognitive assessments scores recorded in the dementia service EHR.

Results

258 (26%) patients consented to take part. At least one cognitive assessment score was recorded for 242 (94%) patients, but primary and secondary care EHR records could only be linked in 93 patients. 56 of these 93 patients had two cognitive assessments scores at least 12 months apart. In the patients with data available for analysis individuals with a higher number of markers and domains recorded in their primary care records had lower mean cognitive assessment scores (range 1.6-2.1 points), and after adjustment for earlier cognitive scores (range 2.0-2.5 points), indicating poorer cognitive function, although differences were not statistically significant.

Conclusion

This feasibility study highlights the challenges in obtaining consent and linking primary and secondary care EHR in dementia, and in extracting cognitive function scores from dementia service EHR.
Vegetarianism and mental health: longitudinal evidence in the 1970 British Cohort Study
Authors: Gagné Thierry , Kurdi Vanessa
Published: October 2022

Background

Reducing animal product consumption has benefits for population health and the environment. The relationship between vegetarianism and mental health, however, remains poorly understood. This study explores this relationship in a nationally representative birth cohort in Great Britain.

Methods

We use data from the 1970 British Cohort Study, which collected information on diet at age 30 (n= 11,204) and psychological distress (PD) using the nine-item Malaise Inventory at ages 26, 30, 34, 42, and 46-48. We first developed a statistical adjustment strategy by regressing PD at age 30 on vegetarianism and 14 potential confounders measured at ages 10 and 26 (including PD at age 26). We then ran multilevel growth curve models, testing whether within-person changes in PD between ages 30 and 46-48 differed by vegetarianism, before and after statistical adjustment. Models were reproduced using red meat consumption at age 30 as a sensitivity analysis.

Results

At age 30, 4.5% of participants reported being vegetarian. In the cross-sectional models at age 30, vegetarians reported more distress compared with non-vegetarians in bivariate analysis (b = 0.30, 95%CI 0.09, 0.52), but this difference disappeared in the fully-adjusted model (b = 0.02, 95%CI -0.17, 0.21). In the longitudinal models between ages 30 and 46/48, there were no differences in within-person changes in psychological distress between vegetarians and non-vegetarians (p= .723). Sensitivity analyses yielded similar findings.

Conclusion

In this British cohort, vegetarianism at age 30 was not associated with changes in psychological distress during mid-adulthood. Since psychological distress in early adulthood predicted vegetarianism at age 30, more studies are needed to disentangle the progression of this relationship over the life-course.
Understanding maternity care providers’ use of data: A qualitative study in Southern Tanzania
Authors: Unkels Regine , Al-beity Fadhlun Alwy , Julius Zamoyoni , Mkumbo Elibariki , Pembe Andrea B , Hanson Claudia , Mölsted-Alvesson Helle
Published: October 2022

Introduction

Health information management system data is collected for national planning and evaluation but rarely used for health care improvements at the sub-national or facility-level in low-and-middle-income countries. Research suggests that perceived data quality and lack of feedback are contributing factors. We aimed to understand maternity care providers’ perceptions of data and how they use them, with a view to co-design interventions to improve data quality and use.

Methods

We based our research on constructivist grounded theory. We conducted 14 in-depth interviews, two focus group discussions with maternity care providers and 48 hours of observations in maternity wards of two rural hospitals in Southern Tanzania. Constant comparative data analysis was applied to develop initial and focused codes, sub-categories and categories continuously validated through peer and member checks.

Results

Maternity care providers appropriated numeric data on service provision to reconcile their professional values and demands from managers and the community with effects of a challenging working environment. They felt controlled by their managers’ data requirements and alienated from service provision data. Providers added informal documentation ways for their own narrative data needs to reflect on and improve service quality. These also assisted them to recreate social relationships with managers, clients and the community. The resulting documentation system led to duplication and increased systemic complexity.

Conclusions

Data from health information systems does not represent an independent and neutral entity but is embedded into the social realities of different users. Appropriation and use of data reflect these realities and users’ working environment. Interventions to improve data quality and use may need to incorporate the multitude of clinical and administrative documentation and data needs to avoid duplication and inefficiencies.
Geospatial assessment of racial/ethnic composition, social vulnerability, and lead service lines in New York City
Authors: Nigra Anne E. , Lieberman-Cribbin Wil , Bostick Benjamín C. , Chillrud Steven N. , Carrión Daniel
Published: October 2022

Background

The state of New York expects to receive $115 million in 2022 alone from the US Infrastructure Investment and Jobs Act to support the replacement of lead water service lines.

Objectives

To determine the number and proportion ofPotential Leadwater service lines across New York City (NYC), and the association between racial/ethnic composition, housing vulnerability, and child lead exposure vulnerability with service line type (Potential Lead, Unknown) at the census tract level for N= 2,083 NYC tracts.

Methods

We used conditional autoregressive Bayesian Poisson models to assess the relative risk (median posterior estimates, and 95% credible interval, CrI) of service line type per 20% higher proportion of residents in a given racial/ethnic group, and per higher housing vulnerability and child lead exposure vulnerability index scores corresponding to the interquartile range. We also evaluated the associations in flexible natural cubic spline models.

Results

Out of 854,672 residential service line records, 136,891 (16.0%) werePotential Leadand 227,443 (26.6%) wereUnknown. In fully adjusted models, higher proportions of Hispanic/Latino residents and higher child lead exposure vulnerability were associated withPotential Leadservice lines in flexible spline models and linear models (RR 1.15, 95% CrI 1.11, 1.21, and RR 1.11, 95% CrI 1.02, 1.20, respectively). Associations were modified by borough;Potential Leadservice lines were associated with higher proportions of non-Hispanic White and non-Hispanic Asian residents in the Bronx and Manhattan, and with higher proportions of non-Hispanic Black residents in Queens.

Discussion

NYC has a high number ofPotential LeadandUnknownservice lines. Communities with a high proportion of Hispanic/Latino residents and those with children who are already highly vulnerable to lead exposures from numerous sources are disproportionately impacted byPotential Leadservice lines. These findings can inform equitable service line replacement across NY state and NYC.
Hepatitis C care cascade among patients with and without tuberculosis: findings from nationwide programs in the country of Georgia, 2015-2020
Authors: Baliashvili Davit , Blumberg Henry M. , Gandhi Neel R. , Averhoff Francisco , Benkeser David , Shadaker Shaun , Gvinjilia Lia , Turdziladze Aleksandre , Tukvadze Nestani , Chincharauli Mamuka , Butsashvili Maia , Sharvadze Lali , Tsertsvadze Tengiz , Zarkua Jaba , Kempker Russell R.
Published: October 2022

Background

The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to evaluate loss to follow-up (LTFU) from the hepatitis C care cascade among persons diagnosed with active tuberculosis (TB) disease.

Methods

Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015, to September 30, 2020. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes.

Results

Among 11,985 patients with active TB, 9,065 (76%) were tested for HCV antibodies, and 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 20% of patients with a positive antibody test not undergoing viremia testing, and 43% of patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last three years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019.

Conclusions

LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes. Existing large-scale programs for both TB and hepatitis C in Georgia create a unique opportunity for such integration to contribute to hepatitis C elimination efforts.
A meta-analysis of the effect of protein synthesis inhibitors on rodent fear conditioning
Authors: Carneiro Clarissa F. D. , Amorim Felippe E. , Amaral Olavo B.
Published: October 2022

Systematic reviews and meta-analyses have been increasingly recognized for their potential value in pre-clinical research, but their applications have not been extensively explored in behavioral neuroscience. In this work, we studied protein synthesis inhibition, a classic intervention used to disrupt fear learning, reconsolidation, and extinction in rodents, to explore how meta-analyses can identify potential moderators of its effect. We initially performed separate meta-analyses for different injection sites and target sessions to evaluate the effect of the intervention in various scenarios. Heterogeneity was further investigated by multilevel meta-regression models aggregating various sites, with article or research group as additional levels. We detected robust effects of protein synthesis inhibitors on training and reconsolidation, but not on extinction, possibly due to the lower number of studies on the latter. Our analyses identified some well-established moderators, such as intervention timing and reexposure duration. However, other factors proposed as boundary conditions for reconsolidation, such as memory age and training strength, were not associated with effect size. While our results point to the value of meta-analyses in consolidating findings from the literature, we believe that associations suggested by data synthesis should ideally be verified by well-powered, rigorous confirmatory experiments.
What is hidden in the darkness? Characterization of AlphaFold structural space
Authors: Durairaj Janani , Pereira Joana , Akdel Mehmet , Schwede Torsten
Published: October 2022

The recent public release of the latest version of the AlphaFold database has given us access to over 200 million predicted protein structures. We use a “shape-mer” approach, a structural fragmentation method analogous to sequencek-mers, to describe these structures and look for novelties - both in terms of proteins with rare or novel structural composition and possible functional annotation of under-studied proteins. Data and code will be made available athttps://github.com/TurtleTools/afdb-shapemer-darkness
Recurrent impairments in visual perception and place avoidance across autism models are causally linked in the haploinsufficiency model of intellectual disabilitySetd5
Authors: Burnett Laura E. , Koppensteiner Peter , Symonova Olga , Masson Tomás , Vega-Zuniga Tomas , Contreras Ximena , Rülicke Thomas , Shigemoto Ryuichi , Novarino Gaia , Jösch Maximilian
Published: October 2022

Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in three independent models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments - a non-perceptual trait. Focusing on a common cause of ASDs, theSetd5gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1) mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment, and define a non-developmental source of such deficits in ASD.
Functional annotation of the animal genomes: an integrated annotation resource for the horse
Authors: Peng Sichong , Dahlgren Anna R. , Donnelly Callum G. , Hales Erin N. , Petersen Jessica L. , Bellone Rebecca R. , Kalbfleisch Ted , Finno Carrie J.
Published: October 2022

The genomic sequence of the horse has been available since 2009, providing critical resources for discovering important genomic variants regarding both animal health and population structures. However, to fully understand the functional implications of these variants, detailed annotation of the horse genome is required. Currently, the horse genome is annotated using limited available RNA-seq data, as well as through comparative genomics by translating human and mouse genome annotation. While this approach has served the equine researchers well and led to various discoveries that would improve care and management of horses, many important questions remain unanswered. The limitation of the current annotation is two pronged. First, the heavy reliance on short-read sequencing-based RNA-seq data meant that alternate isoforms could not be accurately resolved. Second, epigenomic regulatory elements are crucial to detailed understanding of gene expression network but are yet to be systemically identified in the horse. Many of these regulatory elements, including enhancers, promoters, and insulators, are either not transcribed or transcribed at a very low level, necessitating alternate approaches to identify them. To solve above problems, the Functional Annotation of the Animal Genomes (FAANG) project proposed a systemic approach to tissue collection, phenotyping, and data generation, adopting the blueprint laid out by the Encyclopedia of DNA Elements (ENCODE) project. Here we detail the first comprehensive overview of gene expression and regulation in the horse, providing the equine research community an expanded set of genomics resources for studies of complex traits in the horse.

Author Summary

Functional annotation of a reference genome provides critical information that pertains the tissue-specific gene expression and regulation. Non-model organisms often rely on existing annotations of human and mouse genomes and the conservation between species for their genome annotation. This approach has limited power in annotating transcripts and regulatory elements that are less evolutionarily conserved. Such are the cases of alternatively spliced isoforms and enhancer elements. In a large-scale collaborated effort, Functional Annotation of Animal Genome (FAANG) aims to generate species-specific and tissue-aware functional annotation for farm animals. In this study, we present the overall annotation efforts and findings from the equine FAANG group. This integrated annotation for the horse genome provides, for the first time, a comprehensive overview of gene expression and regulation landscape in nine major equine tissues, as well as an analytical framework for further inclusion of other important tissues.