bluuebunny/crossref_metadata_2025 huggingface dataset:
High traffic roads and adverse birth outcomes: comparing births upwind and downwind of the same road
Authors: Larkin Andrew , Willis Mary D , Harris Lena , Ritz Beate , Hill Elaine L , Hystad Perry
Published: June 2024

Traffic-related air pollution is a major concern for perinatal health. Determining causal associations, however, is difficult because high-traffic areas tend to correspond with lower socioeconomic neighborhoods and other environmental exposures. To overcome confounding, we compared pregnant individuals living downwind and upwind of the same high-traffic road. We leveraged vital statistics data for Texas from 2007 to 2016 (n = 3 570 272 births) and computed hourly wind estimates for residential addresses within 500 m of high-traffic roads (ie, annual average daily traffic >25 000 vehicles) (10.9% of births). We matched pregnant individuals predominantly upwind with pregnant neighbors downwind of the same road segment (n = 37 631 pairs). Living downwind was associated with a decrease of 11.6 g (95% CI, -18.01 to -5.21) in term birth weight. No associations were observed with low term birth weight, preterm birth, or very preterm birth. In distance-stratified models, living downwind within 50 m was associated with a decrease of 36.3 g (95% CI, -67.74 to -4.93) in term birth weight and living 51-100 m downwind was associated with an odds ratio of 3.68 (95% CI, 1.71-7.90) for very preterm birth. These results suggest traffic air pollution is associated with adverse birth outcomes, with steep distance decay gradients around major roads.

This article is part of a Special Collection on Environmental Epidemiology.
Learning optimal dynamic treatment regimes from longitudinal data
Authors: Williams Nicholas T , Hoffman Katherine L , Díaz Iván , Rudolph Kara E
Published: June 2024

Investigators often report estimates of the average treatment effect (ATE). While the ATE summarizes the effect of a treatment on average, it does not provide any information about the effect of treatment within any individual. A treatment strategy that uses an individual’s information to tailor treatment to maximize benefit is known as an optimal dynamic treatment rule (ODTR). Treatment, however, is typically not limited to a single point in time; consequently, learning an optimal rule for a time-varying treatment may involve not just learning the extent to which the comparative treatments’ benefits vary across the characteristics of individuals, but also learning the extent to which the comparative treatments’ benefits vary as relevant circumstances evolve within an individual. The goal of this paper is to provide a tutorial for estimating ODTR from longitudinal observational and clinical trial data for applied researchers. We describe an approach that uses a doubly robust unbiased transformation of the conditional ATE. We then learn a time-varying ODTR for when to increase buprenorphine-naloxone dose to minimize a return to regular opioid use among patients with opioid use disorder. Our analysis highlights the utility of ODTRs in the context of sequential decision-making: The learned ODTR outperforms a clinically defined strategy.

This article is part of a Special Collection on Pharmacoepidemiology.
Multiple effects of weather on common waxbill group foraging and social behavior
Authors: Beltrão Patrícia , Gomes Ana Cristina R , Saldanha Beatriz C , Lima Fernando P , Cardoso Gonçalo C
Published: June 2024

The weather poses challenges for wildlife. Environmental challenges can be responded to at the group level by social animals, but the influence of weather on group behavior is poorly understood. We investigated how weather affects behavior in a gregarious species by monitoring common waxbills (Estrilda astrild) in a large mesocosm during 5 yr. We found seasonal patterns in collective foraging, aggressiveness, and the structure of the social network, usually showing 2 cycles per year: one peaking in Spring and a smaller one peaking in late Summer. Controlling for seasonality, we found behavioral changes related to increased energy demands in colder and/or cloudier days, such as more frequent and larger foraging groups that resulted in less-structured social networks. Rain and wind disturb movement, and we found that, on rainy days, foraging group journeys became briefer and more synchronous, resulting in stronger associations between individuals and less-structured networks, and that on windy days foraging groups were less frequent, larger, and with more within-group aggression. The results show that the weather has more varied effects than anticipated on ecologically relevant group behavior. We discuss how such weather-related effects can improve predictions of how social animals will react to environmental changes.
The Relationship between Work and Family Interference and Service Quality among Chinese Social Workers: The Roles of Emotional Exhaustion and Work Support
Authors: Xin Zhaoyang , Zhang Jingyue , Liu Zhifa
Published: June 2024

Service quality is important to social workers and service recipients. However, limited research has explored the relationship between interference between work and family and service quality among social workers. According to conservation of resources theory, this study investigated how interference between work and family affects social workers’ service quality through emotional exhaustion and the moderating role of work support. The hypotheses were examined using data from 1,417 Chinese social workers collected during the China Social Work Longitudinal Study in 2019. The methodological design of this study includes hierarchical regression analysis and moderated mediation analysis. The results reveal that interference between work and family domains negatively affected service quality through emotional exhaustion as a mediating factor, whereas work support mitigated the direct (indirect) effects of work–family interference on emotional exhaustion (service quality through emotional exhaustion). This study presents a holistic understanding of how and when interference between family and work influences service quality. The findings encourage social work organisations to develop appropriate interventions targeting work–family conflict and emotional exhaustion to improve service quality.
Serial platelet count as a dynamic prediction marker of hospital mortality among septic patients
Authors: Ye Qian , Wang Xuan , Xu Xiaoshuang , Chen Jiajin , Christiani David C , Chen Feng , Zhang Ruyang , Wei Yongyue
Published: June 2024

Background

Platelets play a critical role in hemostasis and inflammatory diseases. Low platelet count and activity have been reported to be associated with unfavorable prognosis. This study aims to explore the relationship between dynamics in platelet count and in-hospital morality among septic patients and to provide real-time updates on mortality risk to achieve dynamic prediction.

Methods

We conducted a multi-cohort, retrospective, observational study that encompasses data on septic patients in the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The joint latent class model (JLCM) was utilized to identify heterogenous platelet count trajectories over time among septic patients. We assessed the association between different trajectory patterns and 28-day in-hospital mortality using a piecewise Cox hazard model within each trajectory. We evaluated the performance of our dynamic prediction model through area under the receiver operating characteristic curve, concordance index (C-index), accuracy, sensitivity, and specificity calculated at predefined time points.

Results

Four subgroups of platelet count trajectories were identified that correspond to distinct in-hospital mortality risk. Including platelet count did not significantly enhance prediction accuracy at early stages (day 1 C-indexDynamic  vs C-indexWeibull: 0.713 vs 0.714). However, our model showed superior performance to the static survival model over time (day 14 C-indexDynamic  vs C-indexWeibull: 0.644 vs 0.617).

Conclusions

For septic patients in an intensive care unit, the rapid decline in platelet counts is a critical prognostic factor, and serial platelet measures are associated with prognosis.
The brain can develop conflicting multisensory principles to guide behavior
Authors: Smyre Scott A , Bean Naomi L , Stein Barry E , Rowland Benjamin A
Published: June 2024

Midbrain multisensory neurons undergo a significant postnatal transition in how they process cross-modal (e.g. visual–auditory) signals. In early stages, signals derived from common events are processed competitively; however, at later stages they are processed cooperatively such that their salience is enhanced. This transition reflects adaptation to cross-modal configurations that are consistently experienced and become informative about which correspond to common events. Tested here was the assumption that overt behaviors follow a similar maturation. Cats were reared in omnidirectional sound thereby compromising the experience needed for this developmental process. Animals were then repeatedly exposed to different configurations of visual and auditory stimuli (e.g. spatiotemporally congruent or spatially disparate) that varied on each side of space and their behavior was assessed using a detection/localization task. Animals showed enhanced performance to stimuli consistent with the experience provided: congruent stimuli elicited enhanced behaviors where spatially congruent cross-modal experience was provided, and spatially disparate stimuli elicited enhanced behaviors where spatially disparate cross-modal experience was provided. Cross-modal configurations not consistent with experience did not enhance responses. The presumptive benefit of such flexibility in the multisensory developmental process is to sensitize neural circuits (and the behaviors they control) to the features of the environment in which they will function. These experiments reveal that these processes have a high degree of flexibility, such that two (conflicting) multisensory principles can be implemented by cross-modal experience on opposite sides of space even within the same animal.
Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report
Authors: Lavrador José Pedro , Rajwani Kapil , Patel Sabina , Kalaitzoglou Dimitrios , Soumpasis Christos , Gullan Richard , Ashkan Keyoumars , Bhangoo Ranjeev , Dell’Acqua Flavio , Vergani Francesco
Published: June 2024

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.
The use of venoarterial extracorporeal membrane oxygenation in cardiogenic shock: a narrative review
Authors: Gédéon Tara , Zolotarova Tetiana , Eisenberg Mark J
Published: June 2024

Aims

Cardiogenic shock (CS) develops in up to 10% of patients with acute myocardial infarction (AMI) and carries a 50% risk of mortality. Despite the paucity of evidence regarding its benefits, venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in clinical practice in patients with AMI in CS (AMI-CS). This review aims to provide an in-depth description of the four available randomized controlled trials to date designed to evaluate the benefit of VA-ECMO in patients with AMI-CS.

Methods and results

The literature search was conducted on PubMed, Google Scholar, and clinicaltrials.gov to identify the four relevant randomized control trials from years of inception to October 2023. Despite differences in patient selection, nuances in trial conduction, and variability in trial endpoints, all four trials (ECLS-SHOCK I, ECMO-CS, EUROSHOCK, and ECLS-SHOCK) failed to demonstrate a mortality benefit with the use of VA-ECMO in AMI-CS, with high rates of device-related complications. However, the outcome of these trials is nuanced by the limitations of each study that include small sample sizes, challenging patient selection, and high cross-over rates to the intervention group, and lack of use of left ventricular unloading strategies.

Conclusion

The presented literature of VA-ECMO in CS does not support its routine use in clinical practice. We have yet to identify which subset of patients would benefit most from this intervention. This review emphasizes the need for designing adequately powered trials to properly assess the role of VA-ECMO in AMI-CS, in order to build evidence for best practices.
Emotional Transformations and Activist Communities: Harnessing Emotion in German Anti-Racist and Anti-Fascist Political Essays
Authors: Calvert Katherine E
Published: June 2024

This article examines how authors of political essays harness emotion to promote activist causes. Drawing examples from the German anthologies Eure Heimat ist unser Albtraum (2019), Sisters and Souls (2015) and Sisters and Souls 2 (2021), I argue that political essays depict processes of emotional transformation that allow individuals to overcome inertia arising from fear or despair. I show that an important aim of anti-racist, anti-fascist and feminist activism is to model emotional freedom, understood as the possibility safely to experience and express any range of emotions including those perceived as ‘negative’. My discussion builds on sociological research on activist burnout and cultural theories about the relationships between emotions and politics. I contend that activist communities that are imagined as sites of emotional freedom also demand a degree of emotional alignment. If not carefully managed, such alignment can reproduce the harmful regulation of feelings that anti-racist and anti-fascist movements seek to overcome.
Modeling Length Changes in De Novo Open Reading Frames during Neutral Evolution
Authors: Lebherz Marie Kristin , Iyengar Bharat Ravi , Bornberg-Bauer Erich
Published: June 2024

For protein coding genes to emerge de novo from a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newborn de novo gene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that older de novo genes have longer ORF, but it is not clear if they elongated with time or remained of the same length since their inception. To address this question we developed a mathematical model of ORF elongation as a Markov-jump process, and show that ORFs tend to keep their length in short evolutionary timescales. We also show that if change occurs it is likely to be a truncation. Our genomics and transcriptomics data analyses of seven Drosophila melanogaster populations are also in agreement with the model’s prediction. We conclude that selection could facilitate ORF length extension that may explain why longer ORFs were observed in old de novo genes in studies analysing longer evolutionary time scales. Alternatively, shorter ORFs may be purged because they may be less likely to yield functional proteins.
Inversion of marine magnetotelluric and controlled source electromagnetic data with site gap and low signal-to-noise ratio
Authors: Jiang Feng , Yang Dikun , Sun Zhen , Li Fucheng
Published: June 2024

Marine magnetotelluric (MT) and controlled source electromagnetic (CSEM) methods have been routinely applied to survey the crustal and upper mantle electrical resistivity structures beneath the sea floor. In practice, there are inevitably site gaps and contamination by noises in the collected data because of lost ocean bottom electromagnetic receivers, unusable data, and difficulties in deploying instruments near deep trenches. So far, it remains unclear to what degree those factors will lower the resolution and the credibility of marine MT and CSEM inversion models. In this paper, we investigate the individual and combined effects of site gaps and data noises on the inversion models through synthetic analyses based on a simple block resistivity model and a realistic resistivity structure derived from the Mariana Trench. The results suggest that data with a sufficiently high signal-to-noise ratio can reasonably recover the subseafloor structures in the area of data gap. The transverse electric mode and tipper data from the MT method are much more sensitive to the structure near the site gap. The joint inversion of MT and CSEM data would improve the model's resolution at the site gap area. The inversion of data with a relatively low signal-to-noise ratio, for example, 10 per cent, can recover the structures with few artefacts if there is no site gap. But if the site gap and noisy data are combined, even a joint inversion cannot correctly recover the burial depths and geometries of the anomalous bodies beneath the site gap where vertical strips are likely present. To improve the model's resolution and suppress inversion artefacts, we propose constraining part of the model with as much a prior information as possible. Specifically, for a survey in the subduction zone, we could reduce the penalties on the model's smoothness at the upper and low interfaces of the resistive subduction slab, or even fix the resistivity of the resistive slab with the help of other information, if any. The inversion models shown in this paper provide valuable references for the site design before marine MT and CSEM surveys as well as for interpreting real data inversion models that may be subject to the same biases introduced by the site gap and noise.
Fertility clinics have a duty of care towards patients who do not have children with treatment
Authors: Gameiro S , Leone D , Mertes H
Published: June 2024

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients’ hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize ‘success’ and ‘failure’ in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop ‘plan(s) B’, to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.
Two Cycle Class Maps on Torsion Cycles
Authors: Alexandrou Theodosis
Published: June 2024

We compare two cycle class maps on torsion cycles and show that they agree up to a minus sign. The first one goes back to Bloch [6], with recent generalizations to non-closed fields. The second is the étale motivic cycle class map $\alpha ^{i}_{X}\colon \operatorname{CH}^{i}(X)_{{\mathbb{Z}}_{\ell }}\to H^{2i}_{L}(X,{\mathbb{Z}}_{\ell }(i))$ restricted to torsion cycles.
Supersulphides suppress type-I and type-II interferon responses by blocking JAK/STAT signalling in macrophages
Authors: Li Xiaoyan , Toyomoto Touya , Zhang Tianli , Guo Chunyu , Lindahl Stephen , Tsutsuki Hiroyasu , Xian Ming , Sawa Tomohiro
Published: June 2024

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumour cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumour effects. The main subclasses of IFNs include type-I (e.g. IFN-α and IFN-β) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulphide donors, which have polysulphide structures in which three or more sulphur atoms are linked within the molecules, IFN-β-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulphides and the mechanism of this suppression are unknown. This study demonstrated that supersulphide donor N-acetyl-L-cysteine tetrasulphide (NAC-S2) can inhibit IFN signalling in macrophages stimulated not only with IFN-α/β but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributing to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, the hydrogen sulphide (H2S) donor NaHS failed to inhibit IFN signalling. Similar to NAC-S2, the carbohydrate-based supersulphide donor thioglucose tetrasulphide (TGS4) was capable of strongly inhibiting tumour necrosis factor-α production, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of the molecular mechanisms by which supersulphide donors exhibit their inhibitory actions towards JAK/STAT signalling is a necessary basis for the development of supersulphide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signalling.
A publishing infrastructure for Artificial Intelligence (AI)-assisted academic authoring
Authors: Pividori Milton , Greene Casey S
Published: June 2024

Objective

Investigate the use of advanced natural language processing models to streamline the time-consuming process of writing and revising scholarly manuscripts.

Materials and Methods

For this purpose, we integrate large language models into the Manubot publishing ecosystem to suggest revisions for scholarly texts. Our AI-based revision workflow employs a prompt generator that incorporates manuscript metadata into templates, generating section-specific instructions for the language model. The model then generates revised versions of each paragraph for human authors to review. We evaluated this methodology through 5 case studies of existing manuscripts, including the revision of this manuscript.

Results

Our results indicate that these models, despite some limitations, can grasp complex academic concepts and enhance text quality. All changes to the manuscript are tracked using a version control system, ensuring transparency in distinguishing between human- and machine-generated text.

Conclusions

Given the significant time researchers invest in crafting prose, incorporating large language models into the scholarly writing process can significantly improve the type of knowledge work performed by academics. Our approach also enables scholars to concentrate on critical aspects of their work, such as the novelty of their ideas, while automating tedious tasks like adhering to specific writing styles. Although the use of AI-assisted tools in scientific authoring is controversial, our approach, which focuses on revising human-written text and provides change-tracking transparency, can mitigate concerns regarding AI’s role in scientific writing.
Structuring medication signeturs as a language regression task: comparison of zero- and few-shot GPT with fine-tuned models
Authors: Garcia-Agundez Augusto , Kay Julia L , Li Jing , Gianfrancesco Milena , Rai Baljeet , Hu Angela , Schmajuk Gabriela , Yazdany Jinoos
Published: June 2024

Importance

Electronic health record textual sources such as medication signeturs (sigs) contain valuable information that is not always available in structured form. Commonly processed through manual annotation, this repetitive and time-consuming task could be fully automated using large language models (LLMs). While most sigs include simple instructions, some include complex patterns.

Objectives

We aimed to compare the performance of GPT-3.5 and GPT-4 with smaller fine-tuned models (ClinicalBERT, BlueBERT) in extracting the average daily dose of 2 immunomodulating medications with frequent complex sigs: hydroxychloroquine, and prednisone.

Methods

Using manually annotated sigs as the gold standard, we compared the performance of these models in 702 hydroxychloroquine and 22 104 prednisone prescriptions.

Results

GPT-4 vastly outperformed all other models for this task at any level of in-context learning. With 100 in-context examples, the model correctly annotates 94% of hydroxychloroquine and 95% of prednisone sigs to within 1 significant digit. Error analysis conducted by 2 additional manual annotators on annotator-model disagreements suggests that the vast majority of disagreements are model errors. Many model errors relate to ambiguous sigs on which there was also frequent annotator disagreement.

Discussion

Paired with minimal manual annotation, GPT-4 achieved excellent performance for language regression of complex medication sigs and vastly outperforms GPT-3.5, ClinicalBERT, and BlueBERT. However, the number of in-context examples needed to reach maximum performance was similar to GPT-3.5.

Conclusion

LLMs show great potential to rapidly extract structured data from sigs in no-code fashion for clinical and research applications.
IDeRare: a lightweight and extensible open-source phenotype and exome analysis pipeline for germline rare disease diagnosis
Authors: Harsono Ivan William , Ariani Yulia , Benyamin Beben , Fadilah Fadilah , Pujianto Dwi Ari , Hafifah Cut Nurul
Published: June 2024

Objectives

Diagnosing rare diseases is an arduous and challenging process in clinical settings, resulting in the late discovery of novel variants and referral loops. To help clinicians, we built IDeRare pipelines to accelerate phenotype-genotype analysis for patients with suspected rare diseases.

Materials and Methods

IDeRare pipeline is separated into phenotype and genotype parts. The phenotype utilizes our handmade Python library, while the genotype part utilizes command line (bash) and Python script to combine bioinformatics executable and Docker image.

Results

We described various implementations of IDeRare phenotype and genotype parts with real-world clinical and exome data using IDeRare, accelerating the terminology conversion process and giving insight on the diagnostic pathway based on disease linkage analysis until exome analysis and HTML-based reporting for clinicians.

Conclusion

IDeRare is freely available under the BSD-3 license, obtainable via GitHub. The portability of IDeRare pipeline could be easily implemented for semi-technical users and extensible for advanced users.
Governance of intersecting value chains in an era of polycentric trade: the case of Kenyan fresh fruit and vegetables
Authors: Alford Matthew , Pasquali Giovanni P , Barrientos Stephanie , Opondo Maggie
Published: June 2024

Domestic value chains (DVCs) led by retailers within the global South often overlap with global value chains (GVCs) as well as domestic arm’s length markets. DVCs incorporate some private governance, but we know little about the role of public governance. Based on analysis of Kenyan fresh fruit and vegetables, we ask: How is the power (or ability) of lead firms to govern producers being reshaped by the increased complexity of polycentric trade in the Kenyan horticultural sector? We reveal constraints to lead firms’ ability to directly exercise bargaining power; and shifts towards institutional power in a context of polycentric trade.
Volatility Shocks, Leverage Effects, and Time-Varying Conditional Skewness
Authors: Kirby Chris
Published: June 2024

I use GARCH-X specifications for stock index returns to investigate the connections between conditional skewness and variance shocks computed from realized variances. The evidence indicates that the conditional skewness of index returns is strongly influenced by variance shocks and displays a remarkable degree of persistence. Indeed, variance shocks not only drive changes in conditional skewness, but also act as a common factor that generates substantial negative correlation between contemporaneous changes in the conditional volatility and conditional skewness of index returns. The resultant linkages between these conditional moments could have important implications in asset pricing, portfolio selection, and risk management applications.
Cytoplasmic aggregation of TDP43 and topographic correlation with tau and α-synuclein accumulation in the rTg4510 mouse model of tauopathy
Authors: Nakayama Yutaro , Chambers James K , Takaichi Yuta , Uchida Kazuyuki
Published: June 2024

In patients with TDP43 proteinopathy, phosphorylated TDP43 (p-TDP43) accumulates in the cytoplasm of neurons. The accumulation of p-TDP43 has also been reported in patients with tauopathy and α-synucleinopathy. We investigated spatiotemporal changes in p-TDP43 accumulation in the brains of rTg4510 mice that overexpressed human mutant tau (P301L) and exhibited hyperphosphorylated tau (hp-tau) and phosphorylated αSyn (p-αSyn) accumulation. Immunohistochemically, p-TDP43 aggregates were observed in the cytoplasm of neurons, which increased with age. A significant positive correlation was observed between the number of cells with p-TDP43 aggregates and hp-tau and p-αSyn aggregates. Suppression of the human mutant tau (P301L) expression by doxycycline treatment reduces the accumulation of p-TDP43, hp-tau, and p-αSyn. Proteinase K-resistant p-TDP43 aggregates were found in regions with high hp-tau, and p-αSyn accumulation. Western blotting of the sarkosyl-insoluble fraction revealed bands of monomeric TDP43 and p-TDP43. These results indicate that the accumulation of mouse p-TDP43 is associated with the accumulation of human mutant tau (P301L) in rTg4510 mouse brains. The accumulation of hp-tau and p-αSyn may promote sarkosyl-insoluble p-TDP43 aggregates that are resistant to proteinase K. The synergistic effects of tau, TDP43, and αSyn may be involved in the pathology of proteinopathies, leading to the accumulation of multiple abnormal proteins.
Diffuse interstellar bands in the near-infrared: expanding the reddening range
Authors: Castellanos R , Najarro F , Garcia M , Patrick L R , Geballe T R
Published: June 2024

We have investigated the behaviour of three strong near-infrared diffuse interstellar bands (DIBs) at λ13177 Å, λ14680 Å, and λ15272 Å, on a larger sample of sightlines and over a wider range of extinctions than previously studied, utilizing spectra from three observatories. We applied two telluric correction techniques to reduce atmospheric contamination and have used Gaussian fits to characterize the DIB profiles and measure equivalent widths. We confirmed strong and approximately linear correlations with reddening of the λ13177 Å, λ14680 Å, and λ15272 Å DIBs, extending them to higher reddening values and strengthening their link to interstellar matter. Modelling of the λ14680 Å DIB profiles revealed intrinsic variations, including line broadening, linked to their formation processes. This effect is particularly pronounced in the Galactic Centre (GC) environment, where multiple diffuse molecular clouds along the line of sight contribute to line broadening. We have detected one new DIB candidate at λ14795 Å on sightlines with high reddening.
LMC stars and where to find them: inferring birth radii for external galaxies
Authors: Lu Yuxi(Lucy) , Buck Tobias , Nidever David , Ratcliffe Bridget , Minchev Ivan , Macciò Andrea V , Obreja Aura
Published: June 2024

It is well known that stars are subject to radial migration, i.e. over time, they move away from their birth location. This dynamical process tends to mix different stellar populations and hence hinders the determination of the true chemical evolution of a galaxy (e.g. metallicity gradients). One way to account for radial migration is to infer stellar birth radii for individual stars. Many attempts to do so have been performed over the last few years, but are limited to the Milky Way, as computing the birth position of stars requires precise measurements of stellar metallicity and age for individual stars that cover large Galactic radii. Fortunately, recent and future surveys will provide numerous opportunities for inferring birth radii for external galaxies such as the LMC. In this paper, we investigate the possibility of doing so using the NIHAO cosmological zoom-in simulations. We find that it is theoretically possible to infer birth radii with a ∼25 per cent median uncertainty for individual stars in galaxies with i) orderliness of the orbits, $\langle v_\phi \rangle /\sigma _{v} > 2 $, ii) a dark matter halo mass greater or equal to approximately the LMC mass (∼2 × 1011 ${\rm M}_\odot$), and iii) after the average azimuthal velocity of the stellar disc reaches ∼70 per cent of its maximum. From our analysis, we conclude that it is possible and useful to infer birth radii for the LMC and other external galaxies that satisfy the above criteria.
Influence of cosmic voids on the propagation of TeV gamma-rays and the puzzle of GRB 221009A
Authors: Abdalla Hassan , Razzaque Soebur , Böttcher Markus , Finke Justin , Domínguez Alberto
Published: June 2024

The recent detection of gamma-ray burst GRB 221009A has attracted attention due to its record brightness and first-ever detection of $\gtrsim 10$ TeV gamma-rays from a GRB. Despite being the second-nearest GRB ever detected, at a redshift of $z=0.151$, the distance is large enough for severe attenuation of gamma-ray flux at these energies due to $\gamma \gamma \rightarrow e^\pm$ pair production with the extragalactic background light (EBL). Here, we investigate whether the presence of cosmic voids along the line of sight can significantly impact the detectability of very high energy (VHE, $\gt $100 GeV) gamma-rays from distant sources. Notably, we find that the gamma–gamma opacity for VHE gamma-rays can be reduced by approximately 10 per cent and up to 30 per cent at around 13 TeV, the highest-energy photon detected from GRB 221009A, for intervening cosmic voids along the line of sight with a combined radius of 110 Mpc, typically found from void catalogues, and 250 Mpc, respectively. This reduction is substantially higher for TeV photons compared to GeV photons, attributable to the broader target photon spectrum that TeV photons interact with. This finding implies that VHE photons are more susceptible to variations in the EBL spectrum, especially in regions dominated by cosmic voids. Our study sheds light on the detection of $\gtrsim 10$ TeV gamma-rays from GRB 221009A in particular, and on the detection of extragalactic VHE sources in general.
Self-consistent dynamical models with a finite extent – IV. Wendland models based on compactly supported radial basis functions
Authors: Baes Maarten
Published: June 2024

We present a new step in our systematic effort to develop self-consistent dynamical models with a finite radial extent. The focus is on models with simple analytical density profiles allowing for analytical calculations of many dynamical properties. In this paper, we introduce a family of models, termed Wendland models, based on compactly supported radial basis functions. The family of models is characterized by a parameter k that controls the smoothness of the transition at the truncation radius. In the limit $k\rightarrow \infty$, the Wendland model reduces to a non-truncated model with a Gaussian density profile. For each Wendland model, the density, mass and gravitational potential are simple truncated polynomial functions of radius. Via the sphecow tool we demonstrate that all Wendland models can be supported by isotropic distribution functions. Surprisingly, the isotropic distribution function exhibits varied behaviour across different Wendland models. Additionally, each model can be supported by a continuum of Osipkov–Merritt orbital structures, ranging from radially anisotropic to completely tangential at the truncation radius. To the best of our knowledge, the Wendland models presented here are the first family of models accommodating both radial and tangential Osipkov–Merritt distribution functions. Using linear superposition, these models can easily be combined to generate Wendland models with even more diverse orbital structures. While the Wendland models are not fully representative of real dynamical systems due to their Gaussian-like density profile, this study lays important groundwork for constructing more realistic models with truncated density profiles that can be supported by a range of orbital structures.
JWST observations of galaxy-damping wings during reionization interpreted with cosmological simulations
Authors: Keating Laura C , Bolton James S , Cullen Fergus , Haehnelt Martin G , Puchwein Ewald , Kulkarni Girish
Published: June 2024

Spectra of the highest redshift galaxies taken with JWST are now allowing us to see into the heart of the reionization epoch. Many of these observed galaxies exhibit strong damping wing absorption redward of their Lyman-$\alpha$ emission. These observations have been used to measure the redshift evolution of the neutral fraction of the intergalactic medium and sizes of ionized bubbles. However, these estimates have been made using a simple analytic model for the intergalactic damping wing. We explore the recent observations with models of inhomogeneous reionization from the Sherwood–Relics simulation suite. We carry out a comparison between the damping wings calculated from the simulations and from the analytic model. We find that although the agreement is good on the red side of the Lyman-$\alpha$ emission, there is a discrepancy on the blue side due to residual neutral hydrogen present in the simulations, which saturates the intergalactic absorption. For this reason, we find that it is difficult to reproduce the claimed observations of large bubble sizes at $z \sim 7$, which are driven by a detection of transmitted flux blueward of the Lyman-$\alpha$ emission. We suggest instead that the observations can be explained by a model with smaller ionized bubbles and larger intrinsic Lyman-$\alpha$ emission from the host galaxy.
Evolutionary Dynamics of Accelerated Antiviral Resistance Development in Hypermutator Herpesvirus
Authors: Höfler Thomas , Nascimento Mariana Mara , Zeitlow Michaela , Kim Ji Yoon , Trimpert Jakob
Published: June 2024

Antiviral therapy is constantly challenged by the emergence of resistant pathogens. At the same time, experimental approaches to understand and predict resistance are limited by long periods required for evolutionary processes. Here, we present a herpes simplex virus 1 mutant with impaired proofreading capacity and consequently elevated mutation rates. Comparing this hypermutator to parental wild type virus, we study the evolution of antiviral drug resistance in vitro. We model resistance development and elucidate underlying genetic changes against three antiviral substances. Our analyzes reveal no principle difference in the evolutionary behavior of both viruses, adaptive processes are overall similar, however significantly accelerated for the hypermutator. We conclude that hypermutator viruses are useful for modeling adaptation to antiviral therapy. They offer the benefit of expedited adaptation without introducing apparent bias and can therefore serve as an accelerator to predict natural evolution.
Synteruptor: mining genomic islands for non-classical specialized metabolite gene clusters
Authors: Haas Drago , Barba Matthieu , Vicente Cláudia M , Nezbedová Šarká , Garénaux Amélie , Bury-Moné Stéphanie , Lorenzi Jean-Noël , Hôtel Laurence , Laureti Luisa , Thibessard Annabelle , Le Goff Géraldine , Ouazzani Jamal , Leblond Pierre , Aigle Bertrand , Pernodet Jean-Luc , Lespinet Olivier , Lautru Sylvie
Published: June 2024

Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of genomic data available, very efficient bioinformatic tools for automatic SMBGC detection have been developed. Nevertheless, most of these tools identify SMBGCs based on sequence similarity with enzymes typically involved in specialised metabolism and thus may miss SMBGCs coding for undercharacterised enzymes. Here we present Synteruptor (https://bioi2.i2bc.paris-saclay.fr/synteruptor), a program that identifies genomic islands, known to be enriched in SMBGCs, in the genomes of closely related species. With this tool, we identified a SMBGC in the genome of Streptomyces ambofaciens ATCC23877, undetected by antiSMASH versions prior to antiSMASH 5, and experimentally demonstrated that it directs the biosynthesis of two metabolites, one of which was identified as sphydrofuran. Synteruptor is also a valuable resource for the delineation of individual SMBGCs within antiSMASH regions that may encompass multiple clusters, and for refining the boundaries of these SMBGCs.
The Effect of Adult Smoking Behavior on Children’s Exposure to Secondhand Smoke. An Analysis Based on Salivary Cotinine Levels Among Children in Dhaka and Karachi
Authors: Siddiqi Kamran , Welch Charlie , Huque Rumana , Iqbal Romania , Kanaan Mona , Mishu Masuma Pervin , Khokhar Mariam Ahmad , Semple Sean ,   CLASS III Trial Team, Sheikh Aziz , Hewitt Catherine , Jackson Catherine , Kellar Ian , Parrott Steve
Published: June 2024

Introduction

Exposure to secondhand smoke (SHS) risks children’s health. However, biomarkers are rarely used to study SHS exposure among children in low- and middle-income countries.

Aims and Methods

We analyzed cross-sectional data collected between March and November 2022 for a cluster-randomized controlled trial investigating a Smoke-Free Intervention in 2769 children aged 9–15 in 74 schools (34 in Dhaka, Bangladesh, and 40 in Karachi, Pakistan). Children’s saliva was tested for the concentration of cotinine—a highly sensitive and specific biomarker for SHS exposure. Based on their reports, children’s homes were categorized as Nonsmoking Homes (NSH) when residents were nonsmokers; Smoke-free Homes (SFH) when residents and visitors smoked outdoors only; and Smoke-permitted Homes (SPH) when either residents or visitors smoked indoors. We compared cotinine concentrations across these home types and the two cities using a proportional odds model.

Results

Overall, 95.7% of children (92% in Dhaka; and 99.4% in Karachi) had cotinine levels between 0.1 and 12 ng/mL, indicating SHS exposure. Median cotinine levels were higher in Karachi (0.58 ng/mL, IQR 0.37 to 0.93) than in Dhaka (0.27 ng/mL, IQR 0.16 to 0.49). Median cotinine concentration was also higher among children living in SPH than those in either NSH or SFH; with absolute differences of approximately 0.1–0.3 and 0.05 ng/mL, respectively.

Conclusions

The level of SHS exposure in Dhaka and Karachi indicates widespread and unrestricted smoking. Smoking restrictions in households and enforcement of smoking bans are urgently needed.

Implications

The high levels of SHS exposure in children living in SFH suggest parental behavior to hide their smoking and/or exposure in private vehicles or public spaces. It is important to advocate for SFH and cars to protect children from SHS exposure. However, these initiatives alone may not be enough. There is a need to enforce smoking bans in enclosed public places and transportation, as well as extend these bans to playgrounds, parks, fairgrounds, and other public spaces that children frequently visit. It is essential to complement smoking restrictions with tobacco cessation advice and support in these settings.
Renal Hyperfiltration as a New Mechanism of Smoking-Related Mortality
Authors: Aissani Mohamed Smail , Niskanen Leo , Tuomainen Tomi-Pekka , Ould Setti Mounir
Published: June 2024

Introduction

Renal hyperfiltration (RHF), an established risk factor for mortality, is prevalent among tobacco smokers. The aim of this study was to assess the mediating role of RHF in the association between smoking and mortality.

Aims and Methods

Data of this study were retrieved from the cohort of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), including 2064 males from Finland. Study participants were followed over a 35-year period. Using classic and counterfactual mediation analysis approaches, we estimated the mediative effect of RHF in the association between smoking and each of the following outcomes: All-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality.

Results

The risk of all-cause mortality in smokers was twice that in nonsmokers (hazard ratio [HR], 2.06; 95% confidence interval [CI]: 1.84 to 2.31). Under the counterfactual framework the direct effect of smoking on all-cause mortality, controlled for RHF, corresponded to an HR of 2.00 (95% CI: 1.78 to 2.30). Of the effect of smoking on mortality, 5% (p-value = .016) was mediated by RHF. This finding concerned particularly non-CVD mortality.

Conclusions

RHF mediated the effect of smoking on non-CVD and all-cause mortality, but not on CVD mortality. The generalizability of our study results is however limited by its focus on a Finnish male cohort, underscoring the need for further investigation into RHF’s broader implications across diverse populations.

Implications

This study elucidates the complex interplay between smoking, renal hyperfiltration (RHF), and mortality, offering novel insights into the mediating role of RHF. Our findings demonstrate that RHF significantly mediates the relationship between smoking and non-cardiovascular disease (non-CVD), but not CVD mortality. This distinction underscores the multifaceted role of RHF beyond its established association with cardiovascular events. By highlighting the specific pathways through which RHF mediates some of the smoking-attributed mortality, this research contributes to our understanding of the mechanisms linking smoking to mortality.