bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical thermomechanical modelling of lava dome growth during the 2007–2009 dome-building eruption at Volcán de Colima
Authors: Zeinalova Natalya , Ismail-Zadeh Alik , Tsepelev Igor , Melnik Oleg , Schilling Frank
Published: October 2023

Lava domes form during effusive eruptions due to an extrusion of highly viscous magmas from volcanic vents. In this paper we present a numerical study of the lava dome growth at Volcán de Colima, Mexico during 2007–2009. The mathematical model treats the lava dome extrusion dynamics as a thermomechanical problem. The equations of motion, continuity and heat transfer are solved with the relevant boundary and initial conditions in the assumption that magma viscosity depends on the volume fraction of crystals and temperature. We perform several sets of numerical experiments to analyse the internal structure of the lava dome (i.e. the distributions of the temperature, crystal content, viscosity and velocity) depending on various heat sources and thermal boundary conditions. Although the lava dome growth at Volcán de Colima during short (a few months) dome-building episodes can be explained by an isothermal model of lava extrusion with the viscosity depending on the volume fraction of crystals, we show here that cooling plays a significant role during long (up to several years) episodes of dome building. A carapace develops as a response to a convective cooling at the lava dome–air interface. The carapace becomes thicker if the radiative heat loss at the interface is also considered. The thick carapace influences the lava dome dynamics preventing its lateral advancement. The release of the latent heat of crystallization leads to an increase of the temperatures in the lava dome interior and to a relative flattening of the dome. Meanwhile, the heat source due to viscous dissipation inside the lava dome is negligible, and it does not influence the lava dome growth. The developed thermomechanical model of the lava dome dynamics at Volcán de Colima can be used elsewhere to analyse effusive eruptions, dome morphology and carapace evolution including its failure potentially leading to pyroclastic flow hazards.
Pivot: partisan policy responses to COVID-19 health disparities
Authors: Creary Melissa S , Greer Scott L , Kitzmiller Sydney , Singer Phillip M , Unwala Naquia A , Vaziri Soha , Willison Charley E
Published: October 2023

How did partisanship influence rhetoric about, public opinion of, and policies that prioritize racial and ethnic health disparities of COVID-19 during the first wave of the pandemic between March and July 2020? In this retrospective, mixed-methods analysis using national administrative and survey data, we found that the rhetoric and policy of shared sacrifice diminished and partisan differences in pandemic policy increased once it became clear to political elites that there were major racial disparities in COVID-19 cases and deaths. We trace how first disparities emerged in data and then were reported in elite, national media, discussed in Congress, and reflected in public opinion. Once racial disparities were apparent, partisan divides opened in media, public opinion, and legislative activity, with Democrats foregrounding inequality and Republicans increasingly downplaying the pandemic. This temporal dimension, focusing on how the diffusion of awareness of inequalities among elites shaped policy in the crucial months of early 2020, is the principal novel finding of our analysis. Overall, there is a clear, partisan policy response to addressing COVID-19 racial disparities across media, public opinion, subnational legislative activity, and congressional deliberations.
Lobbying by omission: what is known and unknown about harmful industry lobbyists in Australia
Authors: Lacy-Nichols Jennifer , Christie Shirae , Cullerton Katherine
Published: October 2023

What is unknown about commercial lobbying is far greater than what is known. These omissions distort our understanding of the extent and nature of business influence on politics. Especially when businesses engage in practices that harm health, it is crucial for public health advocates to understand corporate lobbying to counter its influence. Our study proceeded in three phases. First, based on an international audit, we developed a list of the categories of information about lobbying that could be disclosed under four groups (lobby firms, lobbyists, organizations and activities) and benchmarked Australian lobbyist registers against this list. Second, we manually extracted data from lobbyist registers in eight jurisdictions, cleaned the data and created a relational model for analysis. Finally, we classified a sample of organizations as public health organizations or harmful industries to compare their activities. We identified 61 possible categories of information about lobbying in international lobbyist registers. When applied to Australian lobbyist registers, Queensland covered the widest range of categories (13, 21%), though many lacked detail and completeness. Australian lobbyist registers provided data on 462 third-party lobby firms across Australia, currently employing 1036 lobbyists and representing 4101 organizations. Several of these represented harmful industries, with gambling interests hiring the most third-party lobby firms. Ultimately, Australian lobbyist registers do not provide enough information to understand the full extent of lobbying activities taking place. Political transparency is important for public health actors to be able to monitor corporate political activity and to protect policy-making from vested interests.
The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression
Authors: Galaj Ewa , Barrera Eddy D , Persaud Kirk , Nisanov Rudolf , Vashisht Apoorva , Goldberg Hindy , Patel Nima , Lenhard Hayley , You Zhi-Bing , Gardner Eliot L , Ranaldi Robert
Published: October 2023

Background

There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction.

Methods

Here we investigated the role of midbrain CRF1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions.

Results

Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and dopamine reuptake transporter mRNA in VTA neurons were not affected by heroin. The western-blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus, and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA.

Conclusions

Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.
Augmented surveillance of antimicrobial resistance with high-throughput robotics detects transnational flow of fluoroquinolone-resistant Escherichia coli strain into poultry
Authors: Truswell Alec , Lee Zheng Zhou , Stegger Marc , Blinco John , Abraham Rebecca , Jordan David , Milotic Marin , Hewson Kylie , Pang Stanley , Abraham Sam
Published: October 2023

Background

Food animal AMR surveillance programs assess only small numbers of Escherichia coli (from 100 to 600 per animal class) nationally each year, severely limiting the evaluation of public health risk(s). Here we demonstrate an affordable approach for early detection of emerging resistance on a broad scale that can also accurately characterize spatial and temporal changes in resistance.

Methods

Caecal samples (n = 295) obtained from 10 meat poultry were screened using high-throughput robotics. Initial screening via agar dilution (5310 plates) quantified AMR carriage (cfu/g) for each sample. Ciprofloxacin-resistant isolates (n = 91) proceeded to downstream broth microdilution susceptibility testing. A subset of 28 ciprofloxacin-resistant isolates underwent WGS and phylogenetic analysis.

Results

Intra- and inter-flock carriage of resistance varied with drug class. Ampicillin and tetracycline resistance was ubiquitous to most birds in all flocks with an average carriage rate of 5.8 log10 cfu/g. Gentamicin and ciprofloxacin-resistant E. coli colonized fewer birds, and had an average carriage rate of 1.2 log10 cfu/g and 1.0 log10 cfu/g of faeces, respectively. Resistance to extended-spectrum cephalosporins was absent. ST354 was the dominant ST among the WGS isolates, but they demonstrated markedly lower resistance gene carriage than their international counterparts.

Conclusions

These data amply demonstrate the ineffectiveness of commonly relied-on approaches to AMR surveillance for achieving early detection of emergence, or for measuring spatial and temporal resistance trends. Genetic analysis suggested there has been transnational flow of a ciprofloxacin-resistant strain into Australian poultry flocks, explaining their detection in a nation that prohibits fluoroquinolone use in poultry.
The value affordances of social media engagement features
Authors: Scharlach Rebecca , Hallinan Blake
Published: October 2023

Social media engagement is ubiquitous but contested, simultaneously framed as an everyday form of support and an urgent societal risk. To make sense of these competing claims, we introduce the concept of value affordances, defined as the set of ethical, aesthetic, and relational principles that emerge from the interaction between different stakeholders and technological infrastructures. We develop a novel method involving focus groups and value cards to study the value affordances of engagement features and explore how international students attribute values to the Like, Comment, and Share buttons of TikTok, Instagram, and YouTube. Across platforms, participants agree that engagement features promote expression, care, and community and hinder privacy, mindfulness, peace, and safety. We discuss how our participants navigate value tradeoffs, emphasizing individual agency over structural factors when evaluating the design of platforms, using social media creatively, and assigning responsibility for harm to other users.
From gender segregation to epistemic segregation: a case study of the school system in Iran
Authors: Heidarifar Shadi
Published: October 2023

In this paper, I show that there is a bidirectional relationship between gender-based social norms and gender-segregated education policies that excludes girls from knowledge production within the Iranian school system. I argue that gender segregation in education reproduces hermeneutic inequality through the reinforcement of epistemic segregation as a form of epistemic injustice. In particular, I focus on gender-based instructional epistemic injustice, which refers to a set of epistemic practices that actively exclude a student or an education professional in their capacity as a knower from the process of knowledge production within an education system based on gender dynamics, roles, norms, or expectations. This, in addition, has an impact on schoolboys through the reproduction of active ignorance. I conclude that in societies such as Iran, where highly gendered norms play out in the school system and are further reinforced by that system, the result is not limited to gender segregation itself, but extends beyond it to a form of epistemic injustice that wrongs students by reproducing and reinforcing those highly gendered norms.
Establishment of real-time fluorescence and visual LAMP for rapid detection of Escherichia coli O157:H7 and kits construction
Authors: Wang Zuwei , Cui Xinping , Hu Antuo , Lu Zhaoxin , Meng Fanqiang , Zhou Libang , Bie Xiaomei
Published: October 2023

Escherichia coli O157:H7 is a common pathogenic bacterium in food and water that can pose a threat to human health. The aim of this study was to develop loop-mediated isothermal amplification (LAMP) method for the detection of E. coli O157:H7 in food based on the specific gene Ecs_2840 and to construct rapid detection kits based on the established methods. Specifically, we established two methods of real-time fluorescent LAMP (RT-LAMP) and visual LAMP with calcein as an indicator. In pure bacterial culture, the cell sensitivity and genomic sensitivity of the RT-LAMP kit were 8.8 × 100 CFU ml−1 and 4.61 fg µl−1, respectively. The sensitivity of the visual LAMP kit was 2.35 × 100 CFU ml−1 and 4.61 fg µl−1. Both kits had excellent specificity and anti-interference performance. In addition, milk inoculated with 2.26 × 100 CFU ml−1E. coli O157:H7 could be detected within the reaction time after enrichment for 3 h. The results showed that the LAMP kits were rapid, sensitive, and specific for the detection of E. coli O157:H7 in food and had good application prospects in food safety surveillance.
Anterior Cruciate Ligament Reconstruction in French Army: Return to Prior Level of Running on Selected Military Tests
Authors: de Geofroy Bernard , Trescos Florent , Ghabi Ammar , Choufani Camille , Peras Mathieu , Barbier Olivier , de Landevoisin Emmanuel , Jouvion Arnaud-Xavier
Published: October 2023

Introduction

Anterior cruciate ligament (ACL) rupture is frequently encountered in athletes as well as in military personnel. In civilian population, many studies have looked at the return to sport, but return to duty in Army is a topic that requires further research.

The purpose of this study was to determine through annual military fitness tests in real conditions, the return to sport in soldiers after ACL reconstruction and factors influencing failure.

Materials and Methods

This was a retrospective comparative study. Patients were all soldiers and had followed up in a Military Hospital. The SUCCESS group was military personnel who obtained a result of the specific aptitude test greater than or equal to this same test carried out before reconstruction of the ACL, the FAILURE group comprised the others. Results of the annual specific aerobic fitness tests were collected before and after ACL reconstruction. Preoperative epidemiological data, intraoperative information, and isokinetic test results were collected.

Results

One hundred forty four soldiers were included between January 2011 and December 2017 (94.9% of men with a median age of 27.6 years); 40.3% obtained a result greater than or equal to the preoperative fitness test after ACL reconstruction. Among the soldiers who did not regain their performance, 24.3% were declared unfit or discharged. In the FAILURE group, we found patients with a higher body mass index (25.5 vs. 24.4; P = .04), less patients with isokinetic deficit < 30% on the knee flexors and extensors (26.6% vs. 62.9%; P < .01), more long sick leave (39.5% vs. 13.7%; P < .01), and late resumption of military activities (10.5 vs. 8.9 months; P < .01).

Conclusion

Rupture of ACL has a significant impact on the operational capacity of the French army. The proportion of return to the same level in annual specific fitness tests after ACL reconstruction is 40% among soldiers. Several variables are important to consider in the follow-up of these patients to optimize their recovery of sports performance and therefore their operational capacity.
Support for Complicated Grief in Military Primary Care: Associations, Challenges, and Opportunities
Authors: Gibson Lauren P
Published: October 2023

Objective

This study examined whether service members and their families engage in communication with their primary care managers (PCMs) regarding their losses and to what extent PCMs provide counseling or referrals for grief-related concerns. Additionally, the study explored the potential associations between ethnicity, age, military status (dependent, service member, or veteran), gender, patients’ disclosure of loss to their PCM, receipt of referrals for grief-related services, and treatment seeking.

Methods

A survey was administered to 161 patients enrolled in primary care at William Beaumont Army Medical Center, with 138 reporting a significant loss. Bereaved respondents completed the Inventory of Complicated Grief and the Prolonged Grief Disorder-13 Revised scale (PG-13). Respondents were also asked questions related to their loss and their interactions with their PCM related to the loss.

Results

One hundred twenty-five bereaved respondents completed the measures, 13 had missing information related to PCM interactions. Twenty-nine percent (n = 36) of the 112 respondents reported a significant loss to their PCM. These respondents exhibited significantly higher symptom severity, as indicated by their total mean scores on the Inventory of Complicated Grief and the PG13. Seventeen percent (n = 6) of these respondents reported receiving counseling on topics related to grief or a referral for grief care from their PCM. A moderate relationship was identified between military status and communication with PCM, such that current service members were least likely to report, followed by veterans, then dependents. A moderate relationship was also found between ethnicity and treatment seeking.

Conclusion

The study’s findings have implications for primary care and highlight opportunities for improved outcomes, including the development of appropriate assessment protocols, interventions, and educational initiatives to address grief-related concerns within the military healthcare system. Future research should further investigate the specific needs and preferences of military personnel and their families to enhance the delivery of targeted and effective healthcare services.
The Need for Artificial Intelligence Curriculum in Military Medical Education
Authors: Spirnak Jonathan R , Antani Sameer
Published: October 2023

The success of deep-learning algorithms in analyzing complex structured and unstructured multidimensional data has caused an exponential increase in the amount of research devoted to the applications of artificial intelligence (AI) in medicine in the past decade. Public release of large language models like ChatGPT the past year has generated an unprecedented storm of excitement and rumors of machine intelligence finally reaching or even surpassing human capability in detecting meaningful signals in complex multivariate data. Such enthusiasm, however, is met with an equal degree of both skepticism and fear over the social, legal, and moral implications of such powerful technology with relatively little safeguards or regulations on its development. The question remains in medicine of how to harness the power of AI to improve patient outcomes by increasing the diagnostic accuracy and treatment precision provided by medical professionals. Military medicine, given its unique mission and resource constraints,can benefit immensely from such technology. However, reaping such benefits hinges on the ability of the rising generations of military medical professionals to understand AI algorithms and their applications. Additionally, they should strongly consider working with them as an adjunct decision-maker and view them as a colleague to access and harness relevant information as opposed to something to be feared. Ideas expressed in this commentary were formulated by a military medical student during a two-month research elective working on a multidisciplinary team of computer scientists and clinicians at the National Library of Medicine advancing the state of the art of AI in medicine. A motivation to incorporate AI in the Military Health System is provided, including examples of applications in military medicine. Rationale is then given for inclusion of AI in education starting in medical school as well as a prudent implementation of these algorithms in a clinical workflow during graduate medical education. Finally, barriers to implementation are addressed along with potential solutions. The end state is not that rising military physicians are technical experts in AI; but rather that they understand how they can leverage its rapidly evolving capabilities to prepare for a future where AI will have a significant role in clinical care. The overall goal is to develop trained clinicians that can leverage these technologies to improve the Military Health System.
The MASSIVE survey – XVIII. Deep wide-field K-band photometry and local scaling relations for massive early-type galaxies
Authors: Quenneville Matthew E , Blakeslee John P , Ma Chung-Pei , Greene Jenny E , Gwyn Stephen D J , Ciccone Stephanie , Nyiri Blanka
Published: October 2023

We present wide-field, deep K-band photometry of 98 luminous early-type galaxies (ETGs) from the MASSIVE survey based on observations taken with the WIRCam instrument on the Canada–France–Hawaii Telescope. Using these images, we extract accurate total K-band luminosities (LK) and half-light radii (Re) for this sample of galaxies. We use these new values to explore the size–luminosity and Faber–Jackson relations for massive ETGs. Within this volume-limited sample, we find clear evidence for curvature in both relations, indicating that the most luminous galaxies tend to have larger sizes and smaller velocity dispersions than expected from a simple power-law fit to less luminous galaxies. Our measured relations are qualitatively consistent with the most massive elliptical galaxies forming largely through dissipationless mergers. When the sample is separated into fast and slow rotators, we find the slow rotators to exhibit similar changes in slope with increasing LK, suggesting that low-mass and high-mass slow rotators have different formation histories. The curvatures in the Re–LK and σ–LK relations cancel, leading to a relation between dynamical mass and luminosity that is well described by a single power law: Reσ2 ∝ LKb with b ≈ 1.2. This is consistent with the tilt of the fundamental plane observed in lower mass elliptical galaxies.
Conserved cobalamin acquisition protein 1 is essential for vitamin B12 uptake in both Chlamydomonas and Phaeodactylum
Authors: Sayer Andrew P , Llavero-Pasquina Marcel , Geisler Katrin , Holzer Andre , Bunbury Freddy , Mendoza-Ochoa Gonzalo I , Lawrence Andrew D , Warren Martin J , Mehrshahi Payam , Smith Alison G
Published: October 2023

Microalgae play an essential role in global net primary productivity and global biogeochemical cycling. Despite their phototrophic lifestyle, over half of algal species depend for growth on acquiring an external supply of the corrinoid vitamin B12 (cobalamin), a micronutrient produced only by a subset of prokaryotic organisms. Previous studies have identified protein components involved in vitamin B12 uptake in bacterial species and humans. However, little is known about its uptake in algae. Here, we demonstrate the essential role of a protein, cobalamin acquisition protein 1 (CBA1), in B12 uptake in Phaeodactylum tricornutum using CRISPR-Cas9 to generate targeted knockouts and in Chlamydomonas reinhardtii by insertional mutagenesis. In both cases, CBA1 knockout lines could not take up exogenous vitamin B12. Complementation of the C. reinhardtii mutants with the wild-type CBA1 gene restored B12 uptake, and regulation of CBA1 expression via a riboswitch element enabled control of the phenotype. When visualized by confocal microscopy, a YFP-fusion with C. reinhardtii CBA1 showed association with membranes. Bioinformatics analysis found that CBA1-like sequences are present in all major eukaryotic phyla. In algal taxa, the majority that encoded CBA1 also had genes for B12-dependent enzymes, suggesting CBA1 plays a conserved role. Our results thus provide insight into the molecular basis of algal B12 acquisition, a process that likely underpins many interactions in aquatic microbial communities.
An investigation into the effect of exposing XMM–Newton’s Optical Monitor to the light of Jupiter
Authors: Sullivan S , Page M J , Breeveld A A , Rosen S , Talavera A
Published: October 2023

After nearly 18 yr of successful and safe operations, on 2017 July 17 and 18, XMM–Newton’s Optical Monitor (OM) observed Jupiter – an object 10 magnitudes brighter than safe brightness limits – in its visual (V) filter. The object was exposed  40 arcsec from the nominal European Photon Imaging Cameras pn boresight in the negative Y direction, creating a patch of depleted sensitivity. Two exposures of 4000 s each in the V filter left the sensitivity depleted in an area 70 by 40 arcsec; with the decrease in throughput varying from 34 per cent in the V filter to 15 per cent in the ultraviolet bands, but reaching a depth of 45 per cent in flat-field exposures. The wavelength dependency suggests the majority of the detector damage is due to loss of sensitivity in the photocathode from damage inflicted by ion feedback, while up to 15 per cent could be due to gain depletion of the MCP. The physical mechanisms causing the damage to the detector are discussed as well as possible solutions and opportunities that exist for the future operation of the OM.
Trends in clinical features and severity of Plasmodium vivax malaria among children at tertiary care center in North India
Authors: Arya Aditi , Meena Shyam Sundar , Matlani Monika , Chaudhry Shewta , Singh Vineeta
Published: October 2023

Background

Malaria is a significant cause of morbidity and mortality in adults and children. Plasmodium falciparum is the primary cause of severe malaria, but recently Plasmodium vivax is also recognized to cause severe malaria-associated morbidity and mortality. The study focuses on determining the mortality related to severity parameters in individuals under 12 years and their critical presentation in P.vivax malaria-infected children.

Methods

A prospective cross-sectional hospital-based study was conducted at Safdarjung Hospital, New Delhi, and ICMR-NIMR, New Delhi. All clinically suspected cases were admitted for screening. Exclusion criteria (rapid malaria antigen test, microscopy and medication history) were applied to all the admitted patients (n = 221) to obtain P.vivax patients only. Patients aged ≤ 12 years were included in the study. DNA was extracted from dried blood spots and amplified by nested PCR, followed by visualization on gel electrophoresis.

Result

A total of 221 clinically suspected cases of malaria were screened for P.vivax. After implementing various exclusion criteria, 45/221 cases were enrolled for the study, among which 44.4% (20/45) of children had the symptoms of severe malaria in terms of cerebral malaria, thrombocytopenia, anemia, pancytopenia, acute respiratory distress syndrome and hemophagocytic lymphohistiocytosis.

Conclusion

Plasmodium vivax mono-infection can cause severe manifestation and must be treated as P.falciparum without any delay because it may lead to increased morbidity and mortality. A changing trend in clinical symptoms has shown in P.vivax which was an earlier phenomenon of P.falciparum.
Mapping Pathways to Neuronal Atrophy in Healthy, Mid-aged Adults: From Chronic Stress to Systemic Inflammation to Neurodegeneration?
Authors: Schaefer Julia K , Engert Veronika , Valk Sofie L , Singer Tania , Puhlmann Lara MC
Published: October 2023

Growing evidence implicates systemic inflammation in the loss of structural brain integrity in natural ageing and disorder development. Chronic stress and glucocorticoid exposure can potentiate inflammatory processes and have also been linked to neuronal atrophy, particularly in the hippocampus and the human neocortex. To improve understanding of emerging maladaptive interactions between stress and inflammation, this study examined evidence for glucocorticoid- and inflammation-mediated neurodegeneration in healthy mid-aged adults.

N=169 healthy adults (mean age = 39.4, 64.5% female) were sampled from the general population in the context of the ReSource Project. Stress, inflammation and neuronal atrophy were quantified using physiological indices of chronic stress (hair cortisol and cortisone concentration), systemic inflammation (interleukin-6, high-sensitive C-reactive protein), the systemic inflammation index (SII), hippocampal volume (HCV) and cortical thickness (CT) in regions of interest. Structural equation models were used to examined evidence for pathways from stress and inflammation to neuronal atrophy.

Model fit indices indicated good representation of stress, inflammation, and neurological data through the constructed models (CT model: robust RMSEA = 0.041, robustχ2= 910.90; HCV model: robust RMSEA < 0.001, robustχ2= 40.95). We replicated typical negative age-cortical thickness associations (Anterior cingulate cortex (β =-0.51, p < .001), Parahippocampal Cortex (β = −0.50, p = .012), Frontal Lobe (β = −0.56, p < .001) and Temporal Lobe (β = −0.61, p < .001). Among inflammatory indices, only the SII was positively associated with hair cortisol as one indicator of chronic stress (β = 0.18, p<.05). Direct and indirect pathways from chronic stress and systemic inflammation to cortical thickness or hippocampal volume were non-significant.

We identify the SII as a potential marker of systemic inflammation in human psychobiological studies. More generally, these data suggest that neurophysiological associations found in at-risk populations are not detectable in healthy, mid-aged populations. We conclude that inflammation and glucocorticoid-mediated neurodegeneration may only emerge during advanced ageing and disorder processes and may thus have limited use as early risk markers. Future work should examine these pathways in prospective longitudinal designs, for which the present investigation serves as a baseline.
Short-stranded zein fibers for muscle tissue engineering in alginate-based hydrogels
Authors: Melzener Lea , Spaans Sergio , Hauck Nicolas , Pötgens André J. G. , Flack Joshua E. , Post Mark J. , Doğan Arın
Published: October 2023

Cultivated meat is a nascent technology that aims to produce an environmentally and animal-friendly alternative to conventional meat. Producing skeletal muscle tissue in an animal-free system allowing for high levels of myofusion and maturation is important for the nutritional and sensorial value of cultivated meat. Alginate is an attractive biomaterial to support muscle formation as it is food-safe, sustainable, cheap, and can be cross-linked using non-toxic methods. Although alginate can be functionalized to promote cell attachment, limitations in its mechanical properties, including form, viscosity and stress relaxation, hinder cellular capacity for myogenic differentiation and maturation in alginate-based hydrogels. Here, we show that the addition of electrospun short-stranded zein fibers increased hydrogel degradation, resulting in faster compaction, improved cell-gel interaction and enhanced alignment of bovine muscle precursor cells. We conclude that fiber-hydrogel composites are a promising approach to support optimal formation of 3D constructs, by improving tissue stability and thus prolonging culture duration. Together, this improves muscle-related protein content by facilitating myogenic differentiation and priming muscle organoids for maturation.
Single-Molecule Morphology of Topologically Digested Olympic Networks
Authors: Ramakrishnan Saminathan , Chen Zihao , Fosado Yair Augusto Gutierrez , Tubiana Luca , Vanderlinden Willem , Savill Nicholas Jon , Schnaufer Achim , Michieletto Davide
Published: October 2023

The kinetoplast DNA (kDNA) is the archetype of a two-dimensional Olympic network, composed of thousands of DNA minicircles and found in the mitochondrion of certain parasites. The evolution, replication and self-assembly of this structure are fascinating open questions in biology that can also inform us how to realise synthetic Olympic networksin vitro. To obtain a deeper understanding of the structure and assembly of kDNA networks, we sequenced theCrithidia fasciculatakDNA genome and performed high-resolution Atomic Force Microscopy (AFM) and analysis of kDNA networks that had been partially digested by selected restriction enzymes. We discovered that these topological perturbations lead to networks with significantly different geometrical features and morphologies with respect to the unperturbed kDNA, and that these changes are strongly dependent on the class of DNA circles targeted by the restriction enzymes. Specifically, cleaving maxicircles leads to a dramatic reduction in network size once adsorbed onto the surface, whilst cleaving both maxicircles and a minor class of minicircles yields non-circular and deformed structures. We argue that our results are a consequence of a precise positioning of the maxicircles at the boundary of the network, and we discuss our findings in the context of kDNA biogenesis, design of artificial Olympic networks and detection ofin vivoperturbations.
Refining the resolution of the yeast genotype-phenotype map using single-cell RNA-sequencing
Authors: N’Guessan Arnaud , Tong Wen Yuan , Heydari Hamed , Nguyen Ba Alex N
Published: October 2023

Genotype-phenotype mapping (GPM), or the association of trait variation to genetic variation, has been a long-lasting problem in biology. The existing approaches to this problem allowed researchers to partially understand within– and between-species variation as well as the emergence or evolution of phenotypes. However, traditional GPM methods typically ignore the transcriptome or have low statistical power due to challenges related to dataset scale. Thus, it is not clear to what extent selection modulates transcriptomes and whether cis-or trans-regulatory elements are more important. To overcome these challenges, we leveraged the cost efficiency and scalability of single-cell RNA sequencing (scRNA-seq) by collecting data from 18,233 yeast cells from 4,489 F2 segregants derived from an F1 cross between the laboratory strain BY4741 and the vineyard strain RM11-1a. More precisely, we performed eQTL mapping with the scRNA-seq data to identify single-cell eQTL (sc-eQTL) and transcriptome variation patterns associated with fitness variation inferred from the segregant bulk fitness assay. Due to the larger scale of our dataset and its multidimensionality, we could recapitulate results from decades of work in GPM from yeast bulk assays while revealing new associations between phenotypic and transcriptomic variations at a broad scale. We evaluated the strength of the association between phenotype variation and expression variation, revealed new hotspots of gene expression regulation associated to trait variation, revealed new gene function with high expression heritability and highlighted the larger aggregate effect of trans-regulation compared to cis-regulation Altogether these results suggest that integrating large-scale scRNA-seq data into GPM improves our understanding of trait variation in the context of transcriptomic regulation.
CENsible: Interpretable Insights into Small-Molecule Binding with Context Explanation Networks
Authors: Bhatt Roshni , Koes David Ryan , Durrant Jacob D.
Published: October 2023

We present a novel and interpretable approach for predicting small-molecule binding affinities using context explanation networks (CENs). Given the specific structure of a protein/ligand complex, our CENsible scoring function uses a deep convolutional neural network to predict the contributions of pre-calculated terms to the overall binding affinity. We show that CENsible can effectively distinguish active vs. inactive compounds for many systems. Its primary benefit over related machine-learning scoring functions, however, is that it retains interpretability, allowing researchers to identify the contribution of each pre-calculated term to the final affinity prediction, with implications for subsequent lead optimization.
Evolutionary Rate Covariation is a reliable predictor of co-functional interactions but not necessarily physical interactions
Authors: Little Jordan , Chikina Maria , Clark Nathan
Published: October 2023

Co-functional proteins tend to have rates of evolution that covary over time. This correlation between evolutionary rates can be measured over the branches of a phylogenetic tree through methods such as evolutionary rate covariation (ERC), and then used to construct gene networks by the identification of proteins with functional interactions. The cause of this correlation has been hypothesized to result from both compensatory coevolution at physical interfaces and non-physical forces such as shared changes in selective pressure. This study explores whether coevolution due to compensatory mutations has a measurable effect on the ERC signal. We examined the difference in ERC signal between physically interacting protein domains within complexes as compared to domains of the same proteins that do not physically interact. We found no generalizable relationship between physical interaction and high ERC, although a few complexes ranked physical interactions higher than non-physical interactions. Therefore, we conclude that coevolution due to physical interaction is weak, but present in the signal captured by ERC, and we hypothesize that the stronger signal instead comes from selective pressures on the protein as a whole and maintenance of the general function.
NeurostimML: A machine learning model for predicting neurostimulation-induced tissue damage
Authors: Li Yi , Frederick Rebecca A. , George Daniel , Cogan Stuart F. , Pancrazio Joseph J. , Bleris Leonidas , Hernandez-Reynoso Ana G.
Published: October 2023

Objective

The safe delivery of electrical current to neural tissue depends on many factors, yet previous methods for predicting tissue damage rely on only a few stimulation parameters. Here, we report the development of a machine learning approach that could lead to a more reliable method for predicting electrical stimulation-induced tissue damage by incorporating additional stimulation parameters.

Approach

A literature search was conducted to build an initial database of tissue response information after electrical stimulation, categorized as either damaging or non-damaging. Subsequently, we used ordinal encoding and random forest for feature selection, and investigated four machine learning models for classification: Logistic Regression, K-nearest Neighbor, Random Forest, and Multilayer Perceptron. Finally, we compared the results of these models against the accuracy of the Shannon equation.

Main Results

We compiled a database with 387 unique stimulation parameter combinations collected from 58 independent studies conducted over a period of 47 years, with 195 (51%) categorized as non-damaging and 190 (49%) categorized as damaging. The features selected for building our model with a Random Forest algorithm were: waveform shape, geometric surface area, pulse width, frequency, pulse amplitude, charge per phase, charge density, current density, duty cycle, daily stimulation duration, daily number of pulses delivered, and daily accumulated charge. The Shannon equation yielded an accuracy of 63.9% using a k value of 1.79. In contrast, the Random Forest algorithm was able to robustly predict whether a set of stimulation parameters was classified as damaging or non-damaging with an accuracy of 88.3%.

Significance

This novel Random Forest model can facilitate more informed decision making in the selection of neuromodulation parameters for both research studies and clinical practice. This study represents the first approach to use machine learning in the prediction of stimulation-induced neural tissue damage, and lays the groundwork for neurostimulation driven by machine learning models.
The combination of topological data analysis and mathematical modeling improves sleep stage prediction from consumer-grade wearables
Authors: Lee Minki P. , Kim Dae Wook , Walch Olivia , Forger Daniel B.
Published: October 2023

Wearable devices have become commonplace tools for tracking behavioral and physiological parameters in real-world settings. Nonetheless, the practical utility of these data for clinical and research applications, such as sleep analysis, is hindered by their noisy, large-scale, and multidimensional characteristics. Here, we develop a neural network algorithm that predicts sleep stages by tracking topological features (TFs) of wearable data and model-driven clock proxies reflecting the circadian propensity for sleep. To evaluate its accuracy, we apply it to motion and heart rate data from the Apple Watch worn by subjects undergoing polysomnography (PSG) and compare the predicted sleep stages with the corresponding ground truth PSG records. We find that TFs and clock proxies can improve the overall performance of wake/REM/NREM sleep classification, particularly in identifying REM and NREM sleep (AUROC/AUPRC improvements > 9% and REM/NREM accuracy improvement “ 12%). We find that this improvement is mainly attributed to the heart rate TFs. To confirm this, we compare the heart rate TFs between two groups, expected to have different cardiovascular conditions: younger, healthy subjects from the Apple Watch cohort and elderly subjects from the Multi-ethnic Study of Atherosclerosis cohort. Indeed, TFs largely vary across REM and NREM sleep in younger individuals while the variations disappear in elderly individuals, explaining the enhanced improvements in REM or NREM sleep classification problems only in the younger individuals. This study demonstrates the benefits of combining topological data analysis and mathematical modeling to extract hidden inputs of neural networks from puzzling wearable data.
Deletion of NuRD componentMta2in nephron progenitor cells causes developmentally programmed FSGS
Authors: Basta Jeannine , Robbins Lynn , Stout Lisa , Brennan Michelle , Shapiro John , Chen Mary , Denner Darcy , Baldan Angel , Messias Nidia , Madhavan Sethu , Parikh Samir V. , Rauchman Michael
Published: October 2023

Low nephron endowment at birth is a risk factor for chronic kidney disease. The prevalence of this condition is increasing due to higher survival rates of preterm infants and children with multi- organ birth defect syndromes that affect the kidney and urinary tract. We created a mouse model of congenital low nephron number due to deletion ofMta2in nephron progenitor cells.Mta2is a core component of the Nucleosome Remodeling and Deacetylase (NuRD) chromatin remodeling complex. These mice developed albuminuria at 4 weeks of age followed by focal segmental glomerulosclerosis (FSGS) at 8 weeks, with progressive kidney injury and fibrosis. Our studies reveal that altered mitochondrial metabolism in the post-natal period leads to accumulation of neutral lipids in glomeruli at 4 weeks of age followed by reduced mitochondrial oxygen consumption. We found that NuRD cooperated with Zbtb7a/7b to regulate a large number of metabolic genes required for fatty acid oxidation and oxidative phosphorylation. Analysis of human kidney tissue also supported a role for reduced mitochondrial lipid metabolism and ZBTB7A/7B in FSGS and CKD. We propose that an inability to meet the physiological and metabolic demands of post-natal somatic growth of the kidney promotes the transition to CKD in the setting of glomerular hypertrophy due to low nephron endowment.
The genetic consequences of range expansion and its influence on diploidization in polyploids
Authors: Booker William W. , Schrider Daniel R.
Published: October 2023

Despite newly formed polyploids being subjected to myriad fitness consequences, the relative prevalence of polyploidy both contemporarily and in ancestral branches of the tree of life suggests alternative advantages that outweigh these consequences. One proposed advantage is that polyploids may more easily colonize novel habitats such as deglaciated areas. However, previous research conducted in diploids suggests that range expansion comes with a fitness cost as deleterious mutations may fix rapidly on the expansion front. Here, we interrogate the potential consequences of expansion in polyploids by conducting spatially explicit forward-in-time simulations to investigate how ploidy and inheritance patterns impact the relative ability of polyploids to expand their range. We show that under realistic dominance models, autopolyploids suffer greater fitness reductions than diploids as a result of range expansion due to the fixation of increased mutational load that is masked in the range core. Alternatively, the disomic inheritance of allopolyploids provides a shield to this fixation resulting in minimal fitness consequences. In light of this advantage provided by disomy, we investigate how range expansion may influence cytogenetic diploidization through the reversion to disomy in autotetraploids. We show that under a wide range of parameters investigated for two models of diploidization, disomy frequently evolves more rapidly on the expansion front than in the range core, and that this dynamic inheritance model has additional effects on fitness. Together our results point to a complex interaction between dominance, ploidy, inheritance, and recombination on fitness as a population spreads across a geographic range.
(1→3)-β-D-glucan derivatives with unique structural properties differentially affect murine lung inflammation and histology
Authors: Metwali N. , Stapleton E.M. , Hadina S. , Thorne P.S.
Published: October 2023

Background

β-D-glucan (BDG) compounds are proinflammatory fungal cell wall polysaccharides known to cause respiratory pathology. However, the specific immunological effect of unique BDG structures on pulmonary inflammation is understudied. We sought to characterize the effect of four unique fungal BDGs with unique branching patterns, solubility, molecular weights and higher order structure in murine airways.

Methods

Scleroglucan (1→3) (1→6)-highly branched BDG, laminarin (1→3) (1→6)-branched BDG, curdlan (1→3)-linear BDG, and pustulan (1→6)-linear BDG were assessed by nuclear magnetic resonance spectroscopy (NMR). Glucan compounds were confirmed negative for endotoxin by kinetic chromogenic Limulus amebocyte lysate assay. Each BDG was tested using an inhalation model with C3HeB/FeJ mice and compared to control mice exposed to saline and unexposed sentinels (all, n=3-19). Inhalation studies were performed using all BDGs ±heat-inactivation (1-hr. autoclave) given BDG solubility increases after heat-inactivation. Outcomes included bronchoalveolar lavage (BAL), differential cell counts (macrophages, neutrophils, lymphocytes, and eosinophils), BALF cytokine and serum IgE and IgG2a expression (by multiplex immunoassay and ELISA). Lastly,ex vivocultured left lung cells were BDG stimulated, and cytokines (multiplex) compared to unstimulated cells. Right lung histology was performed.

Results

While each BDG affected lung inflammatory outcomes, pustulan exposure led to the most pro-inflammatory profile of all BDGs tested, including increased inflammatory infiltrate into BAL, increased serum IgE and IgG2a and increased cytokine production. Secondary stimulation of sensitized lung cells by lipopolysaccharide (LPS) significantly increased cytokine expression. Lung histology revealed significant fibrosis in lungs exposed to soluble BDGs pustulan and scleroglucan.

Conclusion

Inhalation of BDGs with distinct branching patterns exhibited varying inflammatory potency and immunogenicity, which lichen-derived pustulan having the greatest effect. Glucan source and solubility should be considered in exposure and toxicological studies.