bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile Health Application-Based Interventions to Improve Self-management of Chemotherapy-Related Symptoms Among People with Breast Cancer Who Are Undergoing Chemotherapy: A Systematic Review
Authors: Shi Nuo , Wong Arkers K C , Wong Frances K Y , Sha Liyan
Published: February 2023

Background

Since the COVID-19 pandemic, there have been an increasing number of studies on using mobile health (mHealth) to support the symptom self-management of patients with breast cancer (BC). However, the components of such programs remain unexplored. This systematic review aimed to identify the components of existing mHealth app-based interventions for patients with BC who are undergoing chemotherapy and to uncover self-efficacy enhancement elements from among them.

Methods

A systematic review was conducted for randomized controlled trials published from 2010 to 2021. Two strategies were used to assess the mHealth apps: The Omaha System, a structured classification system for patient care, and Bandura’s self-efficacy theory, which assesses sources of influence that determine an individual’s confidence in being able to manage a problem. Intervention components identified in the studies were grouped under the 4 domains of the intervention scheme of the Omaha System. Four hierarchical sources of self-efficacy enhancement elements were extracted from the studies using Bandura’s self-efficacy theory.

Results

The search uncovered 1,668 records. Full-text screening was conducted on 44 articles, and 5 randomized controlled trials (n = 537 participants) were included. Self-monitoring under the domain of “Treatments and procedure” was the most frequently used mHealth intervention for improving symptom self-management in patients with BC undergoing chemotherapy. Most mHealth apps used various “mastery experience” strategies including reminders, self-care advice, videos, and learning forums.

Conclusion

Self-monitoring was commonly utilized in mHealth-based interventions for patients with BC undergoing chemotherapy. Our survey uncovered evident variation in strategies to support self-management of symptoms and standardized reporting is required. More evidence is required to make conclusive recommendations related to mHealth tools for BC chemotherapy self-management.
PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials
Authors: Ramnaraign Brian , Sartor Oliver
Published: February 2023

Radiopharmaceuticals have been utilized for men with advanced prostate cancer for decades. Older agents, seldom used today, provided palliation for bone metastatic pain. In 2013, the alpha emitter radium-223 provided a catalyst for the field by prolonging survival in men with metastatic castrate-resistant prostate cancer (mCRPC). Recently radioisotopic therapies have gained further interest with the development and FDA approval of 177 lutetium (177Lu)-PSMA-617 (also known as lutetium Lu-177 vipivotide tetraxetan). This agent targets the prostate-specific membrane antigen (PSMA) expressed on the cell surface of prostate cancer cells with a beta-emitting isotope (177Lu). This clinical review summarizes key data reported from 177Lu-PSMA-617 clinical trials, including data from the phase III VISION trial which were pivotal for regulatory approval in heavily pretreated PSMA-PET-positive patients with mCRPC. The current field of radiopharmaceuticals is in a rapid state of flux. Additional phase III trials are now ongoing in patients with mCRPC and in patients with metastatic castrate-sensitive prostate cancer. The results from these potential practice-changing trials are highly anticipated. Earlier phase trials (I/II) are in progress examining combination therapies, radiolabeled monoclonal antibodies, and novel compounds. Studies of PSMA-targeted therapies using both beta emitters such as 177Lu and novel alpha emitters such 225 actinium are in progress. During the next decade, radiopharmaceuticals will likely play a central role in the management of patients with advanced prostate cancer.
Root-Expressed Rice PAP3b Enhances Secreted APase Activity and Helps Utilize Organic Phosphate
Authors: Bhadouria Jyoti , Mehra Poonam , Verma Lokesh , Pazhamala Lekha T , Rumi Rumi , Panchal Poonam , Sinha Alok K , Giri Jitender
Published: February 2023

Phosphate (Pi) deficiency leads to the induction of purple acid phosphatases (PAPs) in plants, which dephosphorylate organic phosphorus (P) complexes in the rhizosphere and intracellular compartments to release Pi. In this study, we demonstrate that OsPAP3b belongs to group III low-molecular weight PAP and is low Pi-responsive, preferentially in roots. The expression of OsPAP3b is negatively regulated with Pi resupply. Interestingly, OsPAP3b was found to be dual localized to the nucleus and secretome. Furthermore, OsPAP3b is transcriptionally regulated by OsPHR2 as substantiated by DNA–protein binding assay. Through in vitro biochemical assays, we further demonstrate that OsPAP3b is a functional acid phosphatase (APase) with broad substrate specificity. The overexpression (OE) of OsPAP3b in rice led to increased secreted APase activity and improved mineralization of organic P sources, which resulted in better growth of transgenics compared to the wild type when grown on organic P as an exogenous P substrate. Under Pi deprivation, OsPAP3b knock-down and knock-out lines showed no significant changes in total P content and dry biomass. However, the expression of other phosphate starvation–induced genes and the levels of metabolites were found to be altered in the OE and knock-down lines. In addition, in vitro pull-down assay revealed multiple putative interacting proteins of OsPAP3b. Our data collectively suggest that OsPAP3b can aid in organic P utilization in rice. The APase isoform behavior and nuclear localization indicate its additional role, possibly in stress signaling. Considering its important roles, OsPAP3b could be a potential target for improving low Pi adaptation in rice.
The transcriptional landscape of plant infection by the rice blast fungus Magnaporthe oryzae reveals distinct families of temporally co-regulated and structurally conserved effectors
Authors: Yan Xia , Tang Bozeng , Ryder Lauren S , MacLean Dan , Were Vincent M , Eseola Alice Bisola , Cruz-Mireles Neftaly , Ma Weibin , Foster Andrew J , Osés-Ruiz Miriam , Talbot Nicholas J
Published: February 2023

The rice blast fungus Magnaporthe oryzae causes a devastating disease that threatens global rice (Oryza sativa) production. Despite intense study, the biology of plant tissue invasion during blast disease remains poorly understood. Here we report a high-resolution transcriptional profiling study of the entire plant-associated development of the blast fungus. Our analysis revealed major temporal changes in fungal gene expression during plant infection. Pathogen gene expression could be classified into 10 modules of temporally co-expressed genes, providing evidence for the induction of pronounced shifts in primary and secondary metabolism, cell signaling, and transcriptional regulation. A set of 863 genes encoding secreted proteins are differentially expressed at specific stages of infection, and 546 genes named MEP (Magnaportheeffector protein) genes were predicted to encode effectors. Computational prediction of structurally related MEPs, including the MAX effector family, revealed their temporal co-regulation in the same co-expression modules. We characterized 32 MEP genes and demonstrate that Mep effectors are predominantly targeted to the cytoplasm of rice cells via the biotrophic interfacial complex and use a common unconventional secretory pathway. Taken together, our study reveals major changes in gene expression associated with blast disease and identifies a diverse repertoire of effectors critical for successful infection.
The Pain and PRAYER Scale (PPRAYERS): development and validation of a scale to measure pain-related prayer
Authors: Meints Samantha M , Illueca Marta , Miller Megan M , Osaji Dikachi , Doolittle Benjamin
Published: February 2023

Objectives

Prayer is a devotional practice used across religious traditions to commune with the sacred and has been used as a coping strategy for pain. Previous research on prayer as a pain coping strategy has had mixed results, with prayer associated with both greater and lesser pain depending on prayer type. To date, there has been only 1 measure of pain-related prayer, the prayer subscale of the Coping Strategies Questionnaire–Revised, which measures solely passive prayer, neglecting other types of prayer (eg, active and neutral). To better understand the relationship between pain and prayer, a comprehensive measure of prayer for pain is needed. The aim of this study was to develop and validate the Pain-related PRAYER Scale (PPRAYERS), a questionnaire exploring active, passive, and neutral petitionary prayers to God or a higher power in response to pain.

Methods

Adults with chronic pain (n = 411) completed demographic, health, and pain-related questionnaires, including PPRAYERS.

Results

Results of an exploratory factor analysis yielded a 3-factor structure consistent with active, passive, and neutral subscales. A confirmatory factor analysis resulted in adequate fit after the removal of 5 items. PPRAYERS showed good internal consistency and convergent and discriminant validity.

Discussion

These results provide preliminary validation for PPRAYERS, a novel measure for pain-related prayer.
Diagnostic Business Cycles
Authors: Bianchi Francesco , Ilut Cosmin , Saijo Hikaru
Published: February 2023

A large psychology literature argues that, due to selective memory recall, decision-makers’ forecasts of the future are overly influenced by the perceived news. We adopt the diagnostic expectations (DE) paradigm [Bordalo et al. (2018), Journal of Finance, 73, 199–227] to capture this feature of belief formation, develop a method to incorporate DE in business cycle models, and study the implications for aggregate dynamics. First, we address (1) the theoretical challenges associated with modelling the feedback between optimal actions and agents’ DE beliefs and (2) the time-inconsistencies that arise under distant memory (i.e. when news is perceived with respect to a more distant past than just the immediate one). Second, we show that under distant memory the interaction between actions and DE beliefs naturally generates repeated boom–bust cycles in response to a single initial shock. We also propose a portable solution method to study DE in dynamic stochastic general equilibrium models and use it to estimate a quantitative DE New Keynesian model. Both endogenous states and distant memory play a critical role in successfully replicating the boom–bust cycle observed in response to a monetary policy shock.
Leasing as a Mitigation of Financial Accelerator Effects
Authors: Li Kai , Yu Jun
Published: February 2023

We document that leased capital accounts for about 20% of total physical productive assets used by US public firms, and its proportion is more than 40% among small and financially constrained firms. The leased capital ratio exhibits a strong countercyclical pattern over business cycles and a positive correlation with cross-sectional idiosyncratic uncertainty. We argue that existing macro models with financial frictions assume that firms cannot rent capital and overlook the effects of leasing activities on business cycle dynamics. We explicitly introduce a buy-versus-lease decision into the Bernanke–Gertler–Gilchrist financial accelerator model setting to demonstrate a novel and quantitatively important economic mechanism: that the increased use of leased capital when financial constraints become tighter in bad states significantly mitigates the financial accelerator mechanism and thus also mitigates the response of macroeconomic variables to negative total factor productivity shocks and risk shocks. We provide strong empirical evidence to support our mechanism.
Are women more empathetic than men? Questionnaire and EEG estimations of sex/gender differences in empathic ability
Authors: Pang Chenyu , Li Wenxin , Zhou Yuqing , Gao Tianyu , Han Shihui
Published: February 2023

The debate regarding whether women are more empathetic than men has broad scientific, social and clinical implications. However, previous independent questionnaires and brain imaging studies that tested different samples reported inconsistent results regarding sex/gender differences in empathic ability. We conducted three studies to investigate sex/gender differences in empathic ability using large-sample questionnaires and electroencephalography (EEG) measures. We showed that the estimation of empathic ability using the Interpersonal Reactivity Index questionnaire showed higher rating scores in women than in men in all studies. However, our EEG measures of empathy, indexed by both phase-locked and non–phased-locked neural responses to others’ painful (vs neutral) facial expressions, support a null hypothesis of the sex/gender difference in empathic ability. In addition, we showed evidence that priming social expectations of women and men’s ability to share and care about others’ feelings eliminated the sex/gender difference in questionnaire measures of empathic ability. Our large-sample EEG results challenge the notion of women’s superiority in empathy that is built based on subjective questionnaire measures that are sensitive to social desirability. Our findings indicate that whether the notion of women’s superiority in empathic ability reflects a biological/social difference between women and men or a gender-role stereotype remains an open question.
Functional phenotypic plasticity mediated by water stress and [CO2] explains differences in drought tolerance of two phylogenetically close conifers
Authors: Férriz M , Martin-Benito D , Fernández-de-Simón M B , Conde M , García-Cervigón A I , Aranda I , Gea-Izquierdo G
Published: February 2023

Forests are threatened globally by increased recurrence and intensity of hot droughts. Functionally close coexisting species may exhibit differences in drought vulnerability large enough to cause niche differentiation and affect forest dynamics. The effect of rising atmospheric [CO2], which could partly alleviate the negative effects of drought, may also differ between species. We analysed functional plasticity in seedlings of two taxonomically close pine species (Pinus pinaster Ait., Pinus pinea L.) under different [CO2] and water stress levels. The multidimensional functional trait variability was more influenced by water stress (preferentially xylem traits) and [CO2] (mostly leaf traits) than by differences between species. However, we observed differences between species in the strategies followed to coordinate their hydraulic and structural traits under stress. Leaf 13C discrimination decreased with water stress and increased under elevated [CO2]. Under water stress both species increased their sapwood area to leaf area ratios, tracheid density and xylem cavitation, whereas they reduced tracheid lumen area and xylem conductivity. Pinus pinea was more anisohydric than P. pinaster. Pinus pinaster produced larger conduits under well-watered conditions than P. pinea. Pinus pinea was more tolerant to water stress and more resistant to xylem cavitation under low water potentials. The higher xylem plasticity in P. pinea, particularly in tracheid lumen area, expressed a higher capacity of acclimation to water stress than P. pinaster. In contrast, P. pinaster coped with water stress comparatively more by increasing plasticity of leaf hydraulic traits. Despite the small differences observed in the functional response to water stress and drought tolerance between species, these interspecific differences agreed with ongoing substitution of P. pinaster by P. pinea in forests where both species co-occur. Increased [CO2] had little effect on the species-specific relative performance. Thus, a competitive advantage under moderate water stress of P. pinea compared with P. pinaster is expected to continue in the future.
Single-cell transcriptomics analysis reveals extracellular matrix remodelling in carious human dental pulp
Authors: Balic Anamaria , Perver Dilara , Pagella Pierfrancesco , Rehrauer Hubert , Stadlinger Bernd , Moor Andreas E. , Vogel Viola , Mitsiadis Thimios A.
Published: February 2023

The carious lesion is a bacteria caused destruction of tooth mineralized matrices marked by concurrent tissue reparative and immune responses in the dental pulp. While major molecular players in tooth pulp decay have been uncovered, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. Here we used single-cell RNA sequencing analysis, to generate a comprehensive single-cell atlas of the carious human dental pulp tissue. Our data demonstrated modifications in various cell clusters of the carious pulp, such as immune cells, mesenchymal stem cells (MSC) and fibroblasts, when compared to the healthy dental pulp. These changes include upregulation of genes encoding extracellular matrix (ECM) components and the enrichment of the fibroblast cluster with myofibroblasts. Assessment of the Fibronectin fibres’ mechanical strain showed a significant tension reduction in the carious human pulp, compared to the healthy one. Collectively, the present data demonstrate molecular, cellular and biomechanical alterations in the carious pulp tissue, indicative of extensive ECM remodelling and reminiscent of fibrosis observed in other organs.
Long-term outdoor air pollution and COVID-19 mortality in London: an individual-level analysis
Authors: Charlton Loes , Gale Chris , Morgan Jasper , Glickman Myer , Beevers Sean , Hansell Anna L , Nafilyan Vahé
Published: February 2023

Background

The risk of COVID-19 severity and mortality differs markedly by age, socio-demographic characteristics and pre-existing health status. Various studies have suggested that higher air pollution exposures also increase the likelihood of dying from COVID-19.

Objectives: To assess the association between long-term outdoor air pollution (NO2, NOx, PM10and PM2.5) concentrations and the risk of death involving COVID-19, using a large individual-level dataset.

Methods

We used comprehensive individual-level data from the Office for National Statistics’ Public Health Data Asset for September 2020 to January 2022 and London Air Quality Network modelled air pollution concentrations available for 2016. Using Cox proportional hazard regression models, we adjusted for potential confounders including age, sex, vaccination status, dominant virus variants, geographical factors (such as population density), ethnicity, area and household-level deprivation, and health comorbidities.

Results

There were 737,356 confirmed COVID-19 cases including 9,315 COVID-related deaths. When only adjusting for age, sex, and vaccination status, there was an increased risk of dying from COVID-19 with increased exposure to all air pollutants studied (NO2: HR 1.07 [95% confidence interval: 1.04-1.12] per 10 μg/m3; NOx: 1.05[1.02-1.09] per 20 μg/m3; PM10: 1.32[1.15-1.51] per 10 μg/m3; PM2.5: 1.29[1.12-1.49] per 5 μg/m3). However, after adjustment including ethnicity and socio-economic factors the HRs were close to unity (NO2: 0.98[0.90-1.06]; NOx: 0.99[0.94-1.04]; PM10: 0.95[0.74-1.22]; PM2.5: 0.90[0.67-1.20]). Additional adjustment for dominant variant or pre-existing health comorbidities did not alter the results.

Conclusions

Observed associations between long-term outdoor air pollution exposure and COVID-19 mortality in London are strongly confounded by geography, ethnicity and deprivation.

Using a large individual-level dataset, we found that a positive association between long-term outdoor air pollution and COVID-19 mortality in London did not persist after adjusting for confounders including population density, ethnicity and deprivation.
Non-invasive SARS-CoV-2 genome surveillance and its utility in resource-poor settings during the Delta wave of the COVID-19 pandemic
Authors: Khairnar Krishna , Tomar Siddharth Singh
Published: February 2023

Voluntary participation of the public in disease surveillance can be encouraged by deploying user-friendly sample collection processes that can minimise the discomfort to the participants. This study evaluated the suitability of saline gargle-based sample collection for genomic surveillance of SARS-CoV-2, which included 589 SARS-CoV-2 positive samples collected from Nagpur city in central India from March to December 2021. The SARS-CoV-2 positive samples were subjected to whole genome sequencing (WGS) using the oxford nanopore technologies next-generation sequencing platform. Out of 589 samples, 500 samples qualified for the WGS, and the results revealed eight different clades of SARS-CoV-2 encompassing 37 different Pango-lineage types. The mutation mapping analysis of the variants identified in this study showed six mutations of interest and one mutation of concern E484K in the spike glycoprotein region. Our findings indicate that non-invasive gargle-based genomic surveillance is scalable and does not need significant changes to the existing workflow post-sample collection.
NeuroRehabilitation OnLine (NROL): Description of a multidisciplinary group telerehabilitation innovation for stroke and neurological conditions using the TIDieR checklist
Authors: Ackerley Suzanne , Wilson Neil , Boland Paul , Peel Rosemary , Connell Louise
Published: February 2023

Background

Providing recommended amounts of rehabilitation for stroke and neurological patients is challenging. Telerehabilitation is viable for delivering rehabilitation and an acceptable adjunct to in-person therapy. NeuroRehabilitation OnLine (NROL) was developed as a pilot and subsequently operationalised as a regional innovation embedded across four National Health Service (NHS) Trusts.

Objective

To describe the NROL innovation to assist future implementation and replication efforts.

Methods

The Template for Intervention Description and Replication (TIDieR) checklist, with guidance from the TIDieR-Telehealth extension, was used to describe NROL. The description was developed collaboratively by clinical-academics, therapists, managers, and researchers. Updated Consolidated Framework for Implementation Research domains were used to describe the context in which the innovation was delivered.

Results

NROL delivers online group-based real-time neurorehabilitation with technology assistance. It incorporates multidisciplinary targeted therapy and peer support to complement existing therapy. Procedures, materials and structure are detailed to demonstrate how NROL is embedded within a healthcare system. NROL uses existing NHS therapy workforce alongside dedicated NROL roles, including an essential technology support role. Selection of NROL groups is dependent on patient need. The NROL innovation is tailored over time in response to feedback. NROL described here is situated within a regional stroke and neurorehabilitation network, aligns with local and national strategies, and capitalises on an existing clinical-academic partnership.

Conclusion

This comprehensive description of a regional NROL innovation, and clarification of core components, should facilitate other healthcare settings to adapt and implement NROL for their context. Continuous evaluation alongside implementation will ensure maximal impact for neurorehabilitation.
Impact of Measurement Imprecision on Genetic Association Studies of Cardiac Function
Authors: Vukadinovic Milos , Renjith Gauri , Yuan Victoria , Kwan Alan , Cheng Susan C. , Li Debiao , Clarke Shoa L. , Ouyang David
Published: February 2023

Background

Recent studies have leveraged quantitative traits from imaging to amplify the power of genome-wide association studies (GWAS) to gain further insights into the biology of diseases and traits. However, measurement imprecision is intrinsic to phenotyping and can impact downstream genetic analyses.

Methods

Left ventricular ejection fraction (LVEF), an important but imprecise quantitative imaging measurement, was examined to assess the impact of precision of phenotype measurement on genetic studies. Multiple approaches to obtain LVEF, as well as simulated measurement noise, were evaluated with their impact on downstream genetic analyses.

Results

Even within the same population, small changes in the measurement of LVEF drastically impacted downstream genetic analyses. Introducing measurement noise as little as 7.9% can eliminate all significant genetic associations in an GWAS with almost forty thousand individuals. An increase of 1% in mean absolute error (MAE) in LVEF had an equivalent impact on GWAS power as a decrease of 10% in the cohort sample size, suggesting optimizing phenotyping precision is a cost-effective way to improve power of genetic studies.

Conclusions

Improving the precision of phenotyping is important for maximizing the yield of genome-wide association studies.

Clinical perspective

What Is New?

Measurement imprecision in cardiac imaging phenotypes can substantially impact downstream genetic association studies, explaining much of the difference in identified genetic variants between echocardiography and cardiac magnetic resonance imaging.

Using the example of left ventricular ejection fraction as an important but imprecise clinical measurement, the analysis suggests that the measurement variation within the range of clinician interpretation reduced genome-wide association studies’ power to detect genetic risk factors as much as decreasing the study population size by 20%.

What Are the Clinical Implications?

More precise measurements can result in a better understanding of the genetics of cardiac phenotypes and accelerate the development of precision medicine.

Rather than simply increasing population size, improving measurement precision allows for cost-effective discovery of genetic associations.
How Well Do We Do Social Distancing?
Authors: Yamamoto Naohide , Nightingale Mia
Published: February 2023

During the pandemic of coronavirus disease 2019 (COVID-19), many jurisdictions around the world introduced a ‘social distance’ rule under which people are instructed to keep a certain distance from others. Generally, this rule is implemented simply by telling people how many metres or feet of separation should be kept, without giving them precise instructions as to how the specified distance can be measured. Consequently, the rule is effective only to the extent that people are able to gauge this distance through their space perception. To examine the effectiveness of the rule from this point of view, the present study empirically investigated how much distance people would leave from another person when they relied on their perception of this distance. Participants (N= 153) were asked to stand exactly 1.5-m away from a researcher, and resultant interpersonal distances showed that while their mean was close to the correct 1.5-m distance, they exhibited large individual differences. These results suggest that a number of people would not stay sufficiently away from others even when they intend to do proper social distancing. Given this outcome, it is suggested that official health advice include measures that compensate for this tendency.
Atherosclerotic plaque epigenetic age acceleration is characterized by mesenchymal reprogramming and poor prognosis
Authors: Hartman Robin J. G. , Benavente Ernest Diez , Slenders Lotte , Boltjes Arjan , Mol Barend M. , de Borst Gert J. , de Kleijn Dominique P. V. , Prange Koen H. M. , de Winther Menno P. J. , Kuiper Johan , Civelek Mete , van der Laan Sander W. , Horvath Steve , Onland-Moret Charlotte , Mokry Michal , Pasterkamp Gerard , den Ruijter Hester M.
Published: February 2023

Epigenetic age estimators (clocks) are known to be predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques can be used for predicting secondary events. Here we estimated an age adjusted measure of epigenetic age, epigenetic age acceleration (EAA), using DNA methylation of human atherosclerotic plaques and of blood. EAA of plaque, but not blood, independently predicted secondary events in a 3-year follow-up (HR=1.3, p= 0.018). Plaque EAA concurred with a high metabolic epigenetic and transcriptional state in plaques. Patients with diabetes and a high body mass index had a higher plaque EAA. EAA was lower in female plaques compared to male plaques by approximately 2 years. Single-cell RNA-seq revealed mesenchymal smooth muscle cells and endothelial cells as main drivers of EAA. Plaque-specific ageing may help identify processes that explain poor health outcomes.
Mismatch between human early visual cortex and perception in spatial extent representation: Radial bias shapes cortical representation while co-axial bias shapes perception
Authors: Ryu Juhyoung , Lee Sang-Hun
Published: February 2023

An object occupies an enclosed region in the visual field, which defines its spatial extent. Humans display exquisite finesse in spatial extent perception. Recent series of human neuroimaging and monkey single-cell studies suggest the spatial representation encoded in the early visual cortex (EVC) as the neural substrate of spatial extent estimation. Guided by this “EVC hypothesis” on spatial extent estimation, we predicted that human estimation of spatial extents would reflect the topographic biases known to exist in EVC’s spatial representation, the co-axial and radial biases. To test this prediction, we concurrently assessed those two spatial biases in both EVC’s and perceptual spatial representations by probing the anisotropy of EVC’s population receptive fields, on the one hand, and that of humans’ spatial extent estimation, on the other hand. To our surprise, we found a marked topographic mismatch between EVC’s and perceptual representations of oriented visual patterns, the radial bias in the former and the co-axial bias in the latter. Amid this topographic mismatch, the extent to which the anisotropy of spatial extents is modulated by stimulus orientation is correlated across individuals between EVC and perception. Our findings seem to require a revision of the current understanding of EVC’s functional architecture and contribution to visual perception: EVC’s spatial representation (i) is governed by the radial bias but only weakly modulated by the co-axial bias, and (ii) do contribute to spatial extent perception, but in a limited way where additional neural mechanisms are called in to counteract the radial bias in EVC.

Significant statement

Previous anatomical and functional studies suggest both radial and co-axial biases as topographic factors governing the spatial representation of the early visual cortex (EVC). On the other hand, EVC’s fine-grained spatial representation has been considered the most plausible neural substrate for exquisite human perception of spatial extents. Based on these suggestions, we reasoned that these two topographic biases are likely to be shared between EVC’s and perceptual representations of spatial extents. However, our neuroimaging and psychophysics experiments implicate a need for revising those two suggestions. Firstly, the co-axial bias seems to exert only a modulatory influence on EVC’s functional architecture. Secondly, human spatial extent perception requires further contribution from neural mechanisms that correct EVC’s spatial representation for its radial bias.
Pangolin genomes offer key insights and resources for the world’s most trafficked wild mammals
Authors: Heighton Sean P. , Allio Rémi , Murienne Jérôme , Salmona Jordi , Meng Hao , Scornavacca Céline , Bastos Armanda D.S. , Njiokou Flobert , Pietersen Darren W. , Tilak Marie-Ka , Luo Shu-Jin , Delsuc Frédéric , Gaubert Philippe
Published: February 2023

Pangolins form a group of scaly mammals that are trafficked at record numbers for their meat and medicinal properties. Despite their great conservation concern, knowledge of their evolution is limited by a paucity of genomic data. We aim to produce exhaustive genomic resources that include 3 238 orthologous genes and whole-genome polymorphisms to assess the evolution of all eight pangolin species. Robust orthologous gene-based phylogenies recovered the monophyly of the three genera of pangolins, and highlighted the existence of an undescribed species closely related to South-East Asian pangolins. Signatures of middle Miocene admixture between an extinct, possibly European, lineage and the ancestor of South-East Asian pangolins, provides new insights into the early evolutionary history of the group. Demographic trajectories and genome-wide heterozygosity estimates revealed contrasts between continentalvs. island populations and species lineages, suggesting that conservation planning should consider intra-specific patterns. With the expected loss of genomic diversity from recent, extensive trafficking not yet been realized in pangolins, we recommend that populations are genetically surveyed to anticipate any deleterious impact of the illegal trade. Finally, we produce a complete set of genomic resources that will be integral for future conservation management and forensic endeavors required for conserving pangolins, including tracing their illegal trade. These include the completion of whole-genomes for pangolins through the first reference genome with long reads for the giant pangolin (Smutsia gigantea) and new draft genomes (~43x–77x) for four additional species, as well as a database of orthologous genes with over 3.4 million polymorphic sites.
The Antarctic Seafloor Annotated Imagery Database
Authors: Jansen Jan , Shelamoff Victor , Gros Charley , Windsor Thomas , Hill Nicole A. , Barnes David K. , Bowden David A. , Gutt Julian , Bax Narissa , Downey Rachel , Eléaume Marc , Post Alexandra L. , Griffiths Huw , Linse Katrin , Piepenburg Dieter , Purser Autun , Smith Craig R. , Ziegler Amanda F. , Johnson Craig R.
Published: February 2023

Marine imagery is a comparatively cost-effective way to collect data on seafloor organisms, biodiversity and habitat morphology. However, annotating these images to extract detailed biological information is time-consuming and expensive, and reference libraries of consistently annotated seafloor images are rarely publicly available. Here, we present the Antarctic Seafloor Annotated Imagery Database (AS-AID), a result of a multinational collaboration to collate and annotate regional seafloor imagery datasets from 19 Antarctic research cruises between 1985 and 2019. AS-AID comprises of 3,599 georeferenced downward facing seafloor images that have been labelled with a total of 615,051 expert annotations. Annotations are based on the CATAMI (Collaborative and Automated Tools for Analysis of Marine Imagery) classification scheme and have been reviewed by experts. In addition, because the pixel location of each annotation within each image is available, annotations can be viewed easily and customised to suit individual research priorities.

This dataset can be used to investigate species distributions, community patterns, it provides a reference to assess change through time, and can be used to train algorithms to automatically detect and annotate marine fauna.
Genome wide variation in the Angolan Namib desert reveals unique Pre-Bantu ancestry
Authors: Oliveira Sandra , Fehn Anne-Maria , Amorim Beatriz , Stoneking Mark , Rocha Jorge
Published: February 2023

The populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as “peripatetic”. Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.
Transcriptional heterogeneity in human diabetic foot wounds
Authors: Sandoval-Schaefer Teresa , Phan Quan , Dash Biraja C. , Prassinos Alexandre J. , Duan Kaiti , Gazes Michael I. , Vyce Steven D. , Driskell Ryan , Hsia Henry C. , Horsley Valerie
Published: February 2023

Wound repair requires the coordination of multiple cell types including immune cells and tissue resident cells to coordinate healing and return of tissue function. Diabetic foot ulceration is a type of chronic wound that impacts over 4 million patients in the US and over 7 million worldwide (Edmonds et al., 2021). Yet, the cellular and molecular mechanisms that go awry in these wounds are not fully understood. Here, by profiling chronic foot ulcers from non-diabetic (NDFUs) and diabetic (DFUs) patients using single-cell RNA sequencing, we find that DFUs display transcription changes that implicate reduced keratinocyte differentiation, altered fibroblast function and lineages, and defects in macrophage metabolism, inflammation, and ECM production compared to NDFUs. Furthermore, analysis of cellular interactions reveals major alterations in several signaling pathways that are altered in DFUs. These data provide a view of the mechanisms by which diabetes alters healing of foot ulcers and may provide therapeutic avenues for DFU treatments.
Genetic Screen Uncovers a Dual Role for Phospholipids in Mitochondrial-Derived Compartment Biogenesis
Authors: Xiao Tianyao , English Alyssa M. , Maschek J. Alan , Cox James E. , Hughes Adam L.
Published: February 2023

Cells utilize multiple mechanisms to maintain mitochondrial homeostasis in response to stress. We recently identified a cellular structure, called the mitochondria-derived compartment (MDC), that is generated from mitochondria in response to amino acid overabundance. MDCs selectively sequester proteins from mitochondria for subsequent degradation, and loss of MDCs sensitizes cells to amino acid stress. Here, we conducted a microscopy-based screen in budding yeast to identify factors that regulate MDC formation. We found that levels of two mitochondrial phospholipids, cardiolipin (CL) and phosphatidylethanolamine (PE), regulate MDC biogenesis in opposing directions. CL depletion impairs MDC biogenesis, whereas PE reduction leads to constitutive MDC formation. Additionally, in response to MDC-inducing agents, cellular and mitochondrial PE declines in an amino acid-dependent manner. Overexpressing mitochondrial PE synthesis pathway components suppresses MDC biogenesis during amino acid stress. Altogether, our data indicate a requirement for CL in MDC biogenesis, and suggest that PE depletion may serve as a regulatory signal for MDC formation downstream of MDC-inducing metabolic stress.

Xiao et al. identify distinct roles for the phospholipids cardiolipin and phosphatidylethanolamine in mitochondria-derived compartment (MDC) biogenesis. They show that cardiolipin is required for MDC formation, whereas a decline in phosphatidylethanolamine in response to amino acid stress triggers MDC biogenesis.
Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase
Authors: Arcos Sarah , Han Alvin X. , te Velthuis Aartjan J. W. , Russell Colin A. , Lauring Adam S.
Published: February 2023

The influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI metric (wMI) and demonstrate that wMI outperforms raw MI through simulations using a well-sampled SARS-CoV-2 dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included HA in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitchhiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.
SOURSOP: A Python package for the analysis of simulations of intrinsically disordered proteins
Authors: Lalmansingh Jared M. , Keeley Alex T. , Ruff Kiersten M. , Pappu Rohit V. , Holehouse Alex S.
Published: February 2023

Conformational heterogeneity is a defining hallmark of intrinsically disordered proteins and protein regions (IDRs). The functions of IDRs and the emergent cellular phenotypes they control are associated with sequence-specific conformational ensembles. Simulations of conformational ensembles that are based on atomistic and coarse-grained models are routinely used to uncover the sequence-specific interactions that may contribute to IDR functions. These simulations are performed either independently or in conjunction with data from experiments. Functionally relevant features of IDRs can span a range of length scales. Extracting these features requires analysis routines that quantify a range of properties. Here, we describe a new analysis suite SOURSOP, an object-oriented and open-source toolkit designed for the analysis of simulated conformational ensembles of IDRs. SOURSOP implements several analysis routines motivated by principles in polymer physics, offering a unique collection of simple-to-use functions to characterize IDR ensembles. As an extendable framework, SOURSOP supports the development and implementation of new analysis routines that can be easily packaged and shared.
FriendlyClearMap: An optimized toolkit for mouse brain mapping and analysis
Authors: Negwer Moritz , Bosch Bram , Bormann Maren , Hesen Rick , Lütje Lukas , Aarts Lynn , Rossing Carleen , Kasri Nael Nadif , Schubert Dirk
Published: February 2023

Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory’s use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2’s CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline.

For more precise alignment, we add a landmark-based atlas registration to ClearMap’s functions as well as include young mouse reference atlases for developmental studies. We provide alternative cell segmentation method besides ClearMap’s threshold-based approach: Ilastik’s Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3D visualization of the annotated cells.

As a proof-of-principle, we use FriendlyClearMap to quantify the distribution of the three main GABAergic interneuron subclasses (Parvalbumin+, Somatostatin+, and VIP+) in the mouse fore- and midbrain. For PV+neurons, we provide an additional dataset with adolescent vs. adult PV+neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.
The Essential Role of O-GlcNAcylation in Hepatic Differentiation
Authors: Robarts Dakota R. , Kotulkar Manasi , Paine-Cabrera Diego , Venneman Kaitlyn K. , Hanover John A. , Zachara Natasha E. , Slawson Chad , Apte Udayan
Published: February 2023

Background & Aims

O-GlcNAcylation is a post-translational modification catalyzed by the enzyme O-GlcNAc transferase (OGT), which transfers a single N-acetylglucosamine sugar from UDP-GlcNAc to the protein on serine and threonine residues on proteins. Another enzyme, O-GlcNAcase (OGA), removes this modification. O-GlcNAcylation plays an important role in pathophysiology. Here, we report that O-GlcNAcylation is essential for hepatocyte differentiation, and chronic loss results in fibrosis and hepatocellular carcinoma.

Methods

Single-cell RNA-sequencing was used to investigate hepatocyte differentiation in hepatocyte-specific OGT-KO mice with increased hepatic O-GlcNAcylation and in OGA-KO mice with decreased O-GlcNAcylation in hepatocytes. HCC patient samples and the DEN-induced hepatocellular carcinoma (HCC) model were used to investigate the effect of modulation of O-GlcNAcylation on the development of liver cancer.

Results

Loss of hepatic O-GlcNAcylation resulted in disruption of liver zonation. Periportal hepatocytes were the most affected by loss of differentiation characterized by dysregulation of glycogen storage and glucose production. OGT-KO mice exacerbated DEN-induced HCC development with increased inflammation, fibrosis, and YAP signaling. Consistently, OGA-KO mice with increased hepatic O-GlcNAcylation inhibited DEN-induced HCC. A progressive loss of O-GlcNAcylation was observed in HCC patients.

Conclusions

Our study shows that O-GlcNAcylation is a critical regulator of hepatic differentiation, and loss of O-GlcNAcylation promotes hepatocarcinogenesis. These data highlight increasing O-GlcNAcylation as a potential therapy in chronic liver diseases, including HCC.

Lay Summary

Proteins in cells are modified by the addition of a single glucosamine sugar molecule called O-GlcNAcylation. Loss of O-GlcNAcylation in hepatocytes, the most common type of cells in the liver, causes the liver to lose its function and can result in increased liver diseases such as fibrosis and cancer.

Graphical Abstract

Highlights

Single-Cell RNA-sequencing reveals loss of metabolic liver zonation in O-GlcNAcylation deficient livers.

Loss of O-GlcNAcylation promoted DEN-Induced HCC.

Increase of hepatic O-GlcNAcylation prevented HCC progression.