bluuebunny/crossref_metadata_2025 huggingface dataset:
BIA-ALCL in patients with genetic predisposition for breast cancer: our experience and a review of the literature
Authors: Carbonaro Riccardo , Accardo Giuseppe , Mazzocconi Luca , Pileri Stefano , Derenzini Enrico , Veronesi Paolo , Caldarella Pietro , De Lorenzi Francesca
Published: July 2023

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging non-Hodgkin’s lymphoma that occurs exclusively in patients with breast implants. The estimated risk of developing BIA-ALCL from exposure to breast implants is largely based on approximations about patients at risk. There is a growing body of evidence regarding the presence of specific germline mutations in patients developing BIA-ALCL, rising interest regarding possible markers of genetic predisposition to this type of lymphoma. The present paper focuses attention on BIA-ALCL in women with a genetic predisposition for breast cancer. We report our experience at the European Institute of Oncology, Milan, Italy, describing a case of BIA-ALCL in a BRCA1 mutation carrier who developed BIA-ALCL 5 years after implant-based post mastectomy reconstruction. She was treated successfully with an en-bloc capsulectomy. Additionally, we review the available literature on inherited genetic factors predisposing to the development of BIA-ALCL. In patients with genetic predisposition to breast cancer (mainly TP53 and BRCA1/2 germline mutations), BIA-ALCL prevalence seems to be higher and time to onset appears to be shorter in comparison to the general population. These high-risk patients are already included in close follow-up programs allowing the diagnosis of early-stage BIA-ALCL. For this reason, we do not believe that a different approach should be followed for postoperative surveillance.
Determinants and changes in adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer-prevention recommendations over the past 25 years in Switzerland
Authors: Suter Flurina , Karavasiloglou Nena , Hämmig Oliver , Rohrmann Sabine , Pestoni Giulia
Published: July 2023

Objectives

The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) established 10 lifestyle recommendations for cancer prevention. The current study examines the proportion and changes over 25 years of adherence to these recommendations and their determinants in Switzerland.

Methods

On the basis of six Swiss Health Surveys (1992–2017, N = 110 478), an index reflecting adherence to the 2018 WCRF/AICR cancer-prevention recommendations was created. Multinomial logistic regression models were fitted to investigate changes over time and determinants of a cancer-protective lifestyle.

Results

Adherence to cancer-prevention recommendations was moderate and higher in the years 1997–2017 compared to 1992. Higher adherence was observed among women (odds ratio [OR]high vs. low adherence ranging from 3.31 to 3.74) and participants with a tertiary education level (ORhigh vs. low adherence ranging from 1.71 to 2.18), and lower adherence among participants of the oldest age group (ORhigh vs. low adherence ranging from 0.28 to 0.44) and participants of the Switzerland (lat.: Confoederatio helvetica)-French language regions (ORhigh vs. low adherence ranging from 0.53 to 0.73).

Conclusion

Our results showed that cancer-prevention recommendations are not well followed by the general Swiss population, as the adherence to a cancer-protective lifestyle was generally moderate; however, adherence to cancer-prevention recommendations improved over the past 25 years. Sex, age group, education level, and language regions were significant determinants of adherence to a cancer-protective lifestyle. Further actions at the governmental and individual levels promoting the adoption of a cancer-protective lifestyle are needed.
Self-consistent and detailed opacities from a non-equilibrium average-atom model
Authors: Hansen S. B.
Published: July 2023

Modern density functional theory (DFT) is a powerful tool for accurately predicting self-consistent material properties such as equations of state, transport coefficients and opacities in high energy density plasmas, but it is generally restricted to conditions of local thermodynamic equilibrium (LTE) and produces only averaged electronic states instead of detailed configurations. We propose a simple modification to the bound-state occupation factor of a DFT-based average-atom model that captures essential non-LTE effects in plasmas—including autoionization and dielectronic recombination—thus extending DFT-based models to new regimes. We then expand the self-consistent electronic orbitals of the non-LTE DFT-AA model to generate multi-configuration electronic structure and detailed opacity spectra.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Theoretical study on time response of semiconductor photorefractive effects under subpicosecond ultra-fast X-rays
Authors: Zhou Hao , Huang Qi , He Kai , Gao GuiLong , Yan Xin , Yao Dong , Wang Tao , Tian Jinshou , Hu RongHao , Lv Meng
Published: July 2023

A theoretical model that can efficiently calculate the refractive index response of semiconductors under ultrafast X-ray radiation is established based on the photorefractive effect of semiconductors. The proposed model is used to interpret X-ray diagnostics experiments, and the results are in good agreement with experiments. In the proposed model, a rate equation model of free carrier density calculation is adopted with the X-ray absorption cross-sections calculated by atomic codes. The two-temperature model is used to describe the electron-lattice equilibration and the extended Drude model is applied to calculate the transient refractive index change. It is found that faster time response can be achieved for semiconductors with shorter carrier lifetime and sub-picosecond resolution can be obtained for InP and

Al

0.5

Ga

0.5

As

. The material response time is not sensitive to X-ray energy and the diagnostics can be used in the 1–10 keV energy range.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Application of Boltzmann kinetic equations to model X-ray-created warm dense matter and plasma
Authors: Ziaja Beata , Bekx John Jasper , Masek Martin , Medvedev Nikita , Lipp Vladimir , Saxena Vikrant , Stransky Michal
Published: July 2023

In this review, we describe the application of Boltzmann kinetic equations for modelling warm dense matter and plasma formed after irradiation of solid materials with intense femtosecond X-ray pulses. Classical Boltzmann kinetic equations are derived from the reduced N-particle Liouville equations. They include only single-particle densities of ions and free electrons present in the sample. The first version of the Boltzmann kinetic equation solver was completed in 2006. It could model non-equilibrium evolution of X-ray-irradiated finite-size atomic systems. In 2016, the code was adapted to study plasma created from X-ray-irradiated materials. Additional extension of the code was then also performed, enabling simulations in the hard X-ray irradiation regime. In order to avoid treatment of a very high number of active atomic configurations involved in the excitation and relaxation of X-ray-irradiated materials, an approach called ‘predominant excitation and relaxation path’ (PERP) was introduced. It limited the number of active atomic configurations by following the sample evolution only along most PERPs. The performance of the Boltzmann code is illustrated in the examples of X-ray-heated solid carbon and gold. Actual model limitations and further model developments are discussed.

This article is part of the theme issue 'Dynamic and transient processes in warm dense matter'.
Analysing the dynamic structure of warm dense matter in the imaginary-time domain: theoretical models and simulations
Authors: Dornheim Tobias , Vorberger Jan , Moldabekov Zhandos A. , Böhme Maximilian
Published: July 2023

Rigorous diagnostics of experiments with warm dense matter are notoriously difficult. A key method is X-ray Thomson scattering (XRTS), but the interpretation of XRTS measurements is usually based on theoretical models that entail various approximations. Recently, Dornheimet al.[Nat. Commun.13, 7911 (2022)] introduced a new framework for temperature diagnostics of XRTS experiments that is based on imaginary-time correlation functions. On the one hand, switching from the frequency to the imaginary-time domain gives one direct access to a number of physical properties, which facilitates the extraction of the temperature of arbitrarily complex materials without relying on any models or approximations. On the other hand, the bulk of theoretical work in dynamic quantum many-body theory is devoted to the frequency domain, and, to the best of our knowledge, the manifestation of physics properties within the imaginary-time density–density correlation function (ITCF) remains poorly understood. In the present work, we aim to fill this gap by introducing a simple, semi-analytical model for the imaginary-time dependence of two-body correlations within the framework of imaginary-time path integrals. As a practical example, we compare our new model to extensiveab initiopath integral Monte Carlo results for the ITCF of a uniform electron gas, and find excellent agreement over a broad range of wavenumbers, densities and temperatures.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Dynamic and transient processes in warm dense matter
Authors: White Thomas G. , Dai Jiayu , Riley David
Published: July 2023

In this paper, we discuss some of the key challenges in the study of time-dependent processes and non-equilibrium behaviour in warm dense matter. We outline some of the basic physics concepts that have underpinned the definition of warm dense matter as a subject area in its own right and then cover, in a selective, non-comprehensive manner, some of the current challenges, pointing along the way to topics covered by the papers presented in this volume.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Development of a new quantum trajectory molecular dynamics framework
Authors: Svensson Pontus , Campbell Thomas , Graziani Frank , Moldabekov Zhandos , Lyu Ningyi , Batista Victor S. , Richardson Scott , Vinko Sam M. , Gregori Gianluca
Published: July 2023

An extension to the wave packet description of quantum plasmas is presented, where the wave packet can be elongated in arbitrary directions. A generalized Ewald summation is constructed for the wave packet models accounting for long-range Coulomb interactions and fermionic effects are approximated by purpose-built Pauli potentials, self-consistent with the wave packets used. We demonstrate its numerical implementation with good parallel support and close to linear scaling in particle number, used for comparisons with the more common wave packet employing isotropic states. Ground state and thermal properties are compared between the models with differences occurring primarily in the electronic subsystem. Especially, the electrical conductivity of dense hydrogen is investigated where a 15% increase in DC conductivity can be seen in our wave packet model compared with other models.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Disentangling the effects of non-adiabatic interactions upon ion self-diffusion within warm dense hydrogen
Authors: Angermeier William A. , Scheiner Brett S. , Shaffer Nathaniel R. , White Thomas G.
Published: July 2023

Warm dense matter is a material state in the region of parameter space connecting condensed matter to classical plasma physics. In this intermediate regime, we investigate the significance of non-adiabatic electron-ion interactions upon ion dynamics. To disentangle non-adiabatic from adiabatic electron-ion interactions, we compare the ion self-diffusion coefficient from the non-adiabatic electron force field computational model with an adiabatic, classical molecular dynamics simulation. A classical pair potential developed through a force-matching algorithm ensures the only difference between the models is due to the electronic inertia. We implement this new method to characterize non-adiabatic effects on the self-diffusion of warm dense hydrogen over a wide range of temperatures and densities. Ultimately we show that the impact of non-adiabatic effects is negligible for equilibrium ion dynamics in warm dense hydrogen.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Children develop Immunity to cryptosporidiosis in a high transmission intensity area
Authors: Petri William A. O. , Hossain Biplop , Kabir Mamun , So Hannah H , Moreau G. Brett , Nayak Uma , Ma Jennie Z , Noor Zannthan , Faruque ASG , Alum Masud , Haque Rashidul , Petri William A , Gilchrist Carol A
Published: July 2023

Background

Cryptosporidiumis one of the top causes of diarrhea in Bangladesh infants.Cryptosporidiuminfections lead to the production of antibody immune responses, which were associated with a decrease in parasite burden and decreased disease severity in subsequent infections.

Methods

We conducted a longitudinal study of cryptosporidiosis from birth to five years of age in an urban slum of Dhaka Bangladesh. We then retrospectively tested the concentration of anti-Cryptosporidium Cp17 or Cp23 IgA in surveillance stool samples collected from 54 children during their first 3 years of life by enzyme-linked immunosorbent assay (ELISA). We also assessed the concentration of both IgA and IgG antibodies specific to Cryptosporidium Cp17 and Cp23 in the concentration of anti-Cryptosporidium Cp17 or Cp23 IgA and IgG antibodies in the children’s plasma (1-5 years).

Results

The seroprevalence of both anti-Cp23 and Cp17 antibodies was high at ≤ one year of age and reflected the exposure of these children in this community to cryptosporidiosis. In Bangladesh, the prevalence of cryptosporidiosis is high during the rainy season (June to October) but decreases during the dry season. In younger infants’ plasma anti-Cp17 and Cp23 IgG and anti-Cp17 IgA levels were markedly increased during the rainy season in line with the higher initial exposure to the parasite at this time. Both anti-Cp17, anti-Cp23 fecal IgA and the parasite burden declined during repeat infections.

Conclusions

We found that anti-Cryptosporidium plasma and fecal antibody levels in children could contribute to the decrease in new infections in this study population.
Plasma-treatment with the virucidal beta-propiolactone does not preclude analysis by large panel affinity proteomics, including the discovery of biomarker candidates
Authors: Beutgen Vanessa M. , Bhagwat Aditya M. , Reinartz Silke , Müller Rolf , Graumann Johannes
Published: July 2023

Virus inactivation is a prerequisite for safe handling of high-risk infectious samples. Beta-propiolactone (BPL) is an established and commonly used reagent with proven virucidal efficacy. BPL primarily reacts with DNA and RNA, but also amino acids. The latter may yield modified antigenic protein epitopes and thus interfere with the binding properties of affinity reagents such as antibodies and aptamers, including panels of such reagents used in affinity proteomic screens. We investigated the impact of BPL-treatment on the analysis of protein levels in plasma samples using the commercial aptamer-based affinity proteomic platform SomaScan. Heparin-plasma samples from patients with ovarian cancer (n = 12) and benign tumors (n = 12) were analyzed using the SomaScan v4.1 platform, which led to the identification of COL10A1 as a novel ovarian cancer biomarker, a protein strongly associated with poor clinical outcome. BPL-related changes in protein detection were evaluated comparing native and BPL-treated state, simulating virus inactivation, and impact on measurable group differences was assessed. While approximately one third of protein measurements were significantly changed by the BPL treatment, a majority of antigen/aptamer interactions remained unaffected. Interaction effects of BPL treatment and disease state, potentially altering detectability of group differences, were observable for less than one percent of targets (0.6%). Accordingly, noticeable global effects of BPL treatment did not interfere with detectability of differential protein expression between benign and ovarian cancer samples, as measurements are altered in both groups to the same extent. Global effect sizes (Cohen’s d) between benign and cancer in BPL-treated samples and the number of significantly altered protein abundance observed in limma-based linear modeling appeared minimally increased, slightly enhancing the probability of false positive hits. Taken together, the results indicate the SomaScan platform as well suited for the analysis of high biosafety risk samples inactivated using BPL and the identification of novel biomarkers.
The relative effects of staying in school and attending university on smoking, BMI and systolic blood pressure: evidence from multivariable Mendelian randomization
Authors: Sanderson Eleanor , Davies Neil M.
Published: July 2023

Objectives

To investigate which levels of educational attainment affect health.

Design

Multivariable Mendelian randomization study (MVMR).

Setting

UK Biobank.

Participants

European ancestry participants born in England.

Exposure Educational

attainment was defined as leaving school before age 18, leaving school after 18, or getting a university degree. Randomly allocated genetic variants were used as instruments for these traits.

Main outcome measures

Body mass index (BMI), smoking initiation, and systolic blood pressure.

Results

The MVMR estimates provided little evidence that remaining in school to age 18 affected BMI (mean difference=0.04, 95% CI: -0.42, 0.50), but evidence getting a degree reduced BMI by 0.47 standard deviation 95% CI: (0.01 to 0.97). The MVMR estimates provided evidence that remaining in school to age 18 reduced the odds of initiating smoking (odds ratio (OR): 0.48, 95% CI: 0.30 to 0.76), whereas it provided little evidence of effects of getting a degree (OR: 1.14, 95% CI: 0.69 to 1.88). MVMR suggested that both remaining in school to age 18 and getting a degree had similar effects on systolic blood pressure (mean difference=-2.60 95% CI: -3.73 to -1.46 and mean difference=-3.63 95% CI: -4.92 to -2.34, respectively).

Conclusions

Multivariable Mendelian randomization can be used to estimate the effects of complex longitudinal exposures such as educational attainment. This approach can help elucidate how and when factors such as educational attainment affect health outcomes.

Key messages

Previous studies have estimated the average effect an additional year of education has on health, irrespective of educational level.

However, this assumes that each educational level has the same effect, e.g., an additional year of education in primary school has the same effect as an additional year at university; this assumption is implausible.

Multivariable Mendelian randomization can be used to relax this assumption and estimate the independent effects of educational levels.

Previously reported effects of education on smoking initiation appear to be due to remaining in school until age 18. In contrast, effects on BMI are due to attending university, and effects on systolic blood pressure are similar across education levels.
Joint models reveal genetic architecture of transitions between pubertal stages and their association with BMI in a Latino population
Authors: Vicuña Lucas , Barrientos Esteban , Leiva-Yamaguchi Valeria , Alvares Danilo , Mericq Veronica , Pereira Ana , Eyheramendy Susana
Published: July 2023

Early or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale. We performed genome-wide association studies (GWAS) on the GOCS cohort composed of admixed children with European and Native American ancestry. Using joint models that integrate time-to-event survival parameters and longitudinal trajectories of body-mass index (BMI), we identified genetic variants associated with phenotypic transitions between pairs of Tanner stages. We identified 43 novel significant associations, most of them in boys. The GWAS on Tanner 3→4 transition in boys captured an association peak around the growth-related genesLARS2andLIMD1genes, the former of which causes ovarian dysfunction when mutated. The associated variants are expression– and splicing Quantitative Trait Loci regulating gene expression and alternative splicing in multiple tissues. Further, higher individual Native American genetic ancestry proportions predicted a significantly earlier arrival to Tanner 2 stage in boys but not in girls. Finally, the joint models identified longitudinal BMI parameters significantly associated in several Tanner stages’ transitions, confirming the association of BMI on pubertal timing.
Patterns in Repeat Reinfections: Pre and Post Omicron Emergence
Authors: Chemaitelly Hiam , Ayoub Houssein H. , Tang Patrick , Coyle Peter , Yassine Hadi M. , Al Thani Asmaa A. , Hasan Mohammad R. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar H. , Latif Ali N. , Shaik Riyazuddin M. , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed G. , Butt Adeel A. , Al-Romaihi Hamad E. , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J.
Published: July 2023

Our understanding of SARS-CoV-2 reinfection patterns remains limited. We conducted a longitudinal study using Qatar’s national SARS-CoV-2 data from February 28, 2020 to June 11, 2023 to investigate incidence of reinfections both prior to and after omicron emergence. The latter analysis excluded individuals with pre-omicron infections. Before omicron introduction, the proportion of incident infections classified as reinfections gradually increased but remained minimal, reaching 1.8% just before omicron emerged. During the first omicron wave, this proportion reached 9.0%, a 5-fold increase. After the conclusion of the first omicron wave, the proportion of incident infections identified as reinfections rapidly increased, reaching 43.3% towards the end of the study. In the pre-omicron era, a total of 3,131 reinfections were documented, of which 99.6% were first reinfections and 0.4% were second reinfections. Meanwhile, a total of 20,962 reinfections were documented after an omicron primary infection of which 99.0% were first reinfections, 1.0% were second reinfections, and 0.01% were third reinfections. Reinfections were rare before omicron’s emergence but became widespread during the omicron era, including among individuals previously infected with omicron. Our findings may indicate accelerated viral evolution in the omicron era aimed at evading population immunity, but with minimal impact on COVID-19 severity, or potentially suggest immune imprinting effects that require further investigation.
Environmental predictors of malaria infection in Sussundenga, Mozambique
Authors: Steiber Alexa , Ferrão João L. , Francisco Albino B. , Muhiro Valy , Novela Anísio , Earland Dominique E. , Searle Kelly M.
Published: July 2023

Malaria is highly sensitive to environmental conditions, including climate variability and land use practices. Ecologically, Sussundenga district has a significantly lower elevation compared to the Zimbabwe border and a more tropical climate compared to southern and northern Mozambique due to high seasonal rainfall. We aimed to evaluate the effects of climate and environmental factors at the household level on rapid diagnostic test results for Malaria in Sussundenga, Mozambique. To understand this association, we collected publicly available United States Geological Survey satellite data on elevation, vegetation, and land use cover. Additionally, we collected satellite data on day and night land surface temperatures and evapotranspiration which we assessed at 1- and 2-week lags. We spatially and temporally joined these data with malaria infection data at the household level. Using this database, we assessed whether these environmental factors were good predictors for having a positive rapid diagnostic test result using spatio-temporal models that accounted for the underlying correlation structure. Risk factor surveillance is an important tool for controlling the spread of infectious diseases. The results from modeling of the ecological predictors of malaria infection and spatial maps provided in this study could aid in developing frameworks to mitigate malaria transmission and predict future malaria transmission in this region. Understanding how environmental changes impacts malaria transmission and infection at the household level may have important implications for vector control and disease surveillance strategies utilized by the district.
Phylogenomics of the ecdysteroid kinase-like (EcKL) gene family in insects highlights roles in both steroid hormone metabolism and detoxification
Authors: Scanlan Jack L. , Robin Charles
Published: July 2023

The evolutionary dynamics of large gene families can offer important insights into the functions of their individual members. While the ecdysteroid kinase-like (EcKL) gene family has previously been linked to the metabolism of both steroid moulting hormones and xenobiotic toxins, the functions of nearly all EcKL genes are unknown and there is little information on their evolution across all insects. Here, we perform comprehensive phylogenetic analyses on a manually annotated set of EcKL genes from 140 insect genomes, revealing the gene family is comprised of at least 13 subfamilies that differ in retention and stability. Our results show the only two genes known to encode ecdysteroid kinases belong to different subfamilies and therefore ecdysteroid metabolism functions must be spread throughout the EcKL family. We also provide comparative phylogenomic evidence that EcKLs are involved in detoxification across insects, with positive associations between family size and dietary chemical complexity, and also find similar evidence for the cytochrome P450 and glutathione S-transferase gene families. Unexpectedly, we find that the size of the clade containing a known ecdysteroid kinase is positively associated with host plant taxonomic diversity in Lepidoptera, possibly suggesting multiple functional shifts between hormone and xenobiotic metabolism. This work provides a robust framework for future functional studies into the EcKL gene family and opens promising new avenues for exploring the genomic basis of dietary adaptation in insects, including the classically studied co-evolution of butterflies with their host plants.

Significance statement

The ecdysteroid kinase-like (EcKL) gene family has been linked to both steroid inactivation and detoxification in insects, but the functions of most of its members are unknown. Here, we study the evolutionary history of the EcKLs and showcase how phylogenetics can inform the functional characterisation of enzyme families. EcKL family size varies over an order of magnitude and is associated with chemically complex diets, implicating numerous genes in detoxification. We also find a surprising link between a steroid-metabolising clade and host plant diversity in butterflies and moths, suggesting new detoxification functions may evolve through an insect-plant ‘chemical arms-race’. This work advances numerous functional hypotheses for multiple EcKL clades and proposes a new classification system for this poorly characterised gene family.
Competitive Amplification Networks enable molecular pattern recognition with PCR
Authors: Goertz John P , Sedgwick Ruby , Smith Francesca , Kaforou Myrsini , Wright Victoria J , Herberg Jethro A. , Kote-Jarai Zsofia , Eeles Ros , Levin Mike , Misener Ruth , van der Wilk Mark , Stevens Molly M
Published: July 2023

Gene expression has great potential to be used as a clinical diagnostic tool. However, despite the progress in identifying these gene expression signatures, clinical translation has been hampered by a lack of purpose-built. readily deployable testing platforms. We have developed Competitive Amplification Networks. CANs to enable analysis of an entire gene expression signature in a single PCR reaction. CANs consist of natural and synthetic amplicons that compete for shared primers during amplification, forming a reaction network that leverages the molecular machinery of PCR. These reaction components are tuned such that the final fluorescent signal from the assay is exactly calibrated to the conclusion of a statistical model. In essence, the reaction acts as a biological computer, simultaneously detecting the RNA targets, interpreting their level in the context of the gene expression signature, and aggregating their contributions to the final diagnosis. We illustrate the clinical validity of this technique, demonstrating perfect diagnostic agreement with the gold-standard approach of measuring each gene independently. Crucially, CAN assays are compatible with existing qPCR instruments and workflows. CANs hold the potential to enable rapid deployment and massive scalability of gene expression analysis to clinical laboratories around the world, in highly developed and low-resource J settings alike.

Abstract Figure
Geometric Epitope and Paratope Prediction
Authors: Pegoraro Marco , Dominé Clémentine , Rodolà Emanuele , Veličković Petar , Deac Andreea
Published: July 2023

Antibody-antigen interactions play a crucial role in identifying and neutralizing harmful foreign molecules. In this paper, we investigate the optimal representation for predicting the binding sites in the two molecules and emphasize the importance of geometric information. Specifically, we compare different geometric deep learning methods applied to proteins’ inner (I-GEP) and outer (O-GEP) structures. We incorporate 3D coordinates and spectral geometric descriptors as input features to fully leverage the geometric information. Our research suggests that surface-based models are more efficient than other methods, and our O-GEP experiments have achieved state-of-the-art results with significant performance improvements.
Revisiting the role of mean annual precipitation in shaping functional trait distributions at a continental scale
Authors: Towers Isaac R. , Vesk Peter A. , Wenk Elizabeth H. , Gallagher Rachael V. , Windecker Saras M. , Wright Ian J. , Falster Daniel S.
Published: July 2023

1

Mean annual precipitation (MAP) plays an undisputed role in determining the spatial distribution of the vegetative ecosystems on Earth. Nevertheless, the relationship between MAP and plant functional traits remains unclear. Here, we test the relationship between eight key functional traits and MAP. Our analysis reveals a strong, coordinated response of several plant traits including leaf mass per area, leaf nitrogen, the leaf carbon isotope ratio and plant height from resource-conservative to resource-acquisitive values as MAP increased. These results establish an important role for MAP in driving trait selection across space and, therefore, a need for these effects to be included in future theoretical frameworks.
Integrative analysis of CAKUT multi-omics data
Authors: Bayjanov Jumamurat R. , Doornbos Cenna , Ozisik Ozan , Shin Woosub , Queralt-Rosinach Núria , Wijnbergen Daphne , Saulnier Blache Jean-Sébastien , Schanstra Joost P. , Fernández José M. , Kaliyaperumal Rajaram , Baudot Anaïs , ’t Hoen Peter A.C. , Ehrhart Friederike
Published: July 2023

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood end-stage renal disease and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. Multi-omics experiments, including amniotic fluid miRNome, peptidome, and proteome analyses, can shed light on foetal kidney development in non-severe CAKUT patients compared to severe CAKUT cases. We performed FAIRification of these omics data sets to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.
Definitive environmental DNA research on aquatic insects: Analysis optimization using the recently developed MtInsects-16S primers set
Authors: Takenaka Masaki , Hasebe Yuta , Yano Koki , Okamoto Seiya , Tojo Koji
Published: July 2023

Long-term biodiversity monitoring is necessary for the conservation and management of water resources. Notably, aquatic insects have been used as an indicator of water quality because they provide important basic information about freshwater ecosystems and water resources. Although environmental DNA (eDNA) surveys can enable easy and effective biomonitoring of aquatic insects, previous studies have not successfully detected all insect species, and there has been frequent amplification of nontarget taxa (e.g., algae and diatoms). Therefore, we developed a universal primers set, MtInsects-16S, for eDNA analyses of insects in the mtDNA 16SrRNA region. Furthermore, a well-established database of aquatic insects, especially the MtInsects-16S DNA region of Ephemeroptera, Plecoptera, and Trichoptera in Kanagawa Prefecture, which was the target area in this study, was constructed. Therefore, in this study, we conducted eDNA analyses using a universal primers set and using a well-established database. We conducted and compared capture surveys at the same sites to examine the detection capability of eDNA for Insecta. As a result, eDNA analyses using MtInsects- 16S not only detected almost all of the captured species but also detected many more species without amplifying nontarget taxa. This study demonstrated the application of eDNA analyses with unprecedented accuracy and reliability. It was also shown that community structure by eDNA reflected a relatively narrow range at the water sampling point. Although the data accumulation for constructing locally specific databases is an urgent issue, using the MtInsects-16S region is expected to be a breakthrough in the metabarcoding of insects.
Exploring Motor Network Connectivity in State-Dependent Transcranial Magnetic Stimulation: A Proof-of-Concept Study
Authors: Marzetti Laura , Basti Alessio , Guidotti Roberto , Baldassarre Antonello , Metsomaa Johanna , Zrenner Christoph , D’Andrea Antea , Makkinayeri Saeed , Pieramico Giulia , Ilmoniemi Risto J. , Ziemann Ulf , Romani Gian Luca , Pizzella Vittorio
Published: July 2023

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focused on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks.

This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the motor network (MN) and how MN state affects responses to transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to left M1 in 8 subjects at rest, with simultaneous EEG. Motor evoked potentials (MEPs) were measured from the right hand. Source-space functional connectivity of left M1 to the whole-brain was assessed using the imaginary part of the Phase Locking Value at the frequency of the sensorimotor µ-rhythm in a 1-second window before the pulse. Group-level connectivity revealed functional links between left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At single-subject level, this relation is more expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity based NIBS.

Highlights

EEG pre-stimulus connectivity of left M1 largely corresponds to the motor network

Stronger motor network (MN) connectivity corresponds to greater MEP amplitudes

Linear regression models based on MN connectivity predicts MEP amplitude
Competition between induced fit- and conformational selection binding: how different flux-based approaches help clarifying their interplay
Authors: Vauquelin Georges , Maes Dominique
Published: July 2023

Background

Binding kinetics has become a popular discipline in pharmacology. Yet, it was recommended a decade ago to look on ligand-target binding in terms of fluxes instead of rate constants. Like product formation in enzymology, these binding fluxes stand for the rate/velocity by which the target converts form one state into another. Several thereon-based approaches can be used for studying the functioning binding mechanisms.

Objectives

Although the relative contribution/importance of the induced fit and conformational selection binding pathways within a thermodynamic cycle is still hotly debated, only a single flux-based approach is customarily addressed for such calculations. There is a need to better understand the relevance of this peculiar approach.

Methods

The present findings relied on differential equation-based simulations, using the provided forward- and reverse rate constants for four reported cases as input.

Results

Both pathways may act in unison and even in tandem rather than being mutually exclusive. Also, calculating their relative contribution by distinct flux-based approaches may yield different outcomes for some of the cases under pre-equilibrium as well as equilibrium conditions. Additional flux-based approaches offer a rationale for the occurrence of those disparities.

Conclusions

The interplay between the induced fit- and conformational selection pathways is even more intricate than hitherto expected. It may me preferable to quantitate their relative contribution in terms of target occupancies instead of binding fluxes when genuine equilibrium can be reached.

Perspectives

Compared to the often-used elaborate algebraic equations, combining different binding flux-based approaches may offer better intuitive and visual insight into the functioning of complex binding mechanisms. More attention should also be paid to physiologically more relevant non-equilibrium situations.
TrkB-dependent regulation of molecular signaling across septal cell types
Authors: Rodriguez Lionel A. , Tran Matthew Nguyen , Garcia-Flores Renee , Pattie Elizabeth A. , Divecha Heena R. , Kim Sun Hong , Shin Joo Heon , Lee Yong Kyu , Montoya Carly , Jaffe Andrew E. , Collado-Torres Leonardo , Page Stephanie C. , Martinowich Keri
Published: July 2023

The lateral septum (LS), a GABAergic structure located in the basal forebrain, is implicated in social behavior, learning and memory. We previously demonstrated that expression of tropomyosin kinase receptor B (TrkB) in LS neurons is required for social novelty recognition. To better understand molecular mechanisms by which TrkB signaling controls behavior, we locally knocked down TrkB in LS and used bulk RNA-sequencing to identify changes in gene expression downstream of TrkB. TrkB knockdown induces upregulation of genes associated with inflammation and immune responses, and downregulation of genes associated with synaptic signaling and plasticity. Next, we generated one of the first atlases of molecular profiles for LS cell types using single nucleus RNA-sequencing (snRNA-seq). We identified markers for the septum broadly, and the LS specifically, as well as for all neuronal cell types. We then investigated whether the differentially expressed genes (DEGs) induced by TrkB knockdown map to specific LS cell types. Enrichment testing identified that downregulated DEGs are broadly expressed across neuronal clusters. Enrichment analyses of these DEGs demonstrated that downregulated genes are uniquely expressed in the LS, and associated with either synaptic plasticity or neurodevelopmental disorders. Upregulated genes are enriched in LS microglia, associated with immune response and inflammation, and linked to both neurodegenerative disease and neuropsychiatric disorders. In addition, many of these genes are implicated in regulating social behaviors. In summary, the findings implicate TrkB signaling in the LS as a critical regulator of gene networks associated with psychiatric disorders that display social deficits, including schizophrenia and autism, and with neurodegenerative diseases, including Alzheimer’s.
Stochastic model of Alzheimer’s Disease progression using two-state Markov chains
Authors: Parks Meaghan
Published: July 2023

In 2016, Hao and Friedman developed a deterministic model of Alzheimer’s disease progression using a system of partial differential equations. This model describes the general behavior of the disease, however, it does not incorporate the molecular and cellular stochasticity intrinsic to the underlying disease processes. Here we extend the Hao and Friedman model by modeling each event in disease progression as a stochastic Markov process. This model identifies stochasticity in disease progression, as well as changes to the mean dynamics of key agents. We find that the pace of neuron death increases whereas the production of the two key measures of progression, Tau and Amyloid beta proteins, decelerates when stochasticity is incorporated into the model. These results suggest that the non-constant reactions and time-steps have a significant effect on the overall progression of the disease.
Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice
Authors: Scott Karen A. , Tan Yalun , Johnson Dominique N. , Elsaafien Khalid , Baumer-Harrison Caitlin , Eikenberry Sophia A. , Sa Jessica M. , de Lartigue Guillaume , de Kloet Annette D. , Krause Eric G.
Published: July 2023

Interoception broadly refers to awareness of one’s internal milieu. Vagal sensory afferents monitor the internal milieu and maintain homeostasis by engaging brain circuits that alter physiology and behavior. While the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferents and corresponding brain circuits that shape perception of the viscera are largely unknown. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine vagal sensory afferents expressing the oxytocin receptor, hereafter referred to as NDGOxtr, send projections to the aortic arch or stomach and duodenum with molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NDGOxtrsignificantly decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature, and energy expenditure. Chemogenetic excitation of NDGOxtralso creates patterns of brain activity associated with augmented hypothalamic-pituitary-adrenal axis activity and behavioral indices of vigilance. Recurrent excitation of NDGOxtrsuppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole body metabolism and mental health.
Microvascular plasticity in stroke recovery: Longitudinal snapshots, network statistical analysis, and dynamics
Authors: Mihelic Samuel A , Engelmann Shaun A , Sadr Mahdi , Jafari Chakameh Z , Zhou Annie , Williamson Michael R , Dunn Andrew K
Published: July 2023

This research article quantitatively investigates neuro-microvascular network remodeling dynamics following stroke using a novel in vivo two-photon angiography (cubic millimeter volume, weekly snapshots) and high throughput (thousands of connected capillaries) vascular vectorization method. The results suggest distinct temporal patterns of cere-brovascular plasticity, with acute remodeling peaking at one week post-stroke. The network architecture then gradually stabilizes, returning to a new steady state after four weeks. These findings align with previous literature on neuronal plasticity, highlighting the correlation between neuronal and neurovascular remodeling. Quantitative analysis of neurovascular networks using length- and strand-based statistical measures reveals intri-cate changes in network anatomy and topology. The distance and strand-length statistics show significant alterations, with a peak of plasticity observed at one week post-stroke, followed by a gradual return to baseline. The orientation statistic plasticity peaks at two weeks, gradually approaching the (conserved across subjects) stroke signature. The underlying mechanism of the vascular response (angiogenesis vs. tissue deformation), however, is yet unelucidated, requiring network registration advancements. Overall, the combination of two-photon angiography, vectorization, reconstruction/visualization, and statistical analysis enables both qualitative and quantitative assessments of neu-rovascular remodeling dynamics, demonstrating an impactful method for investigating neuro-microvascular network disorders and the therapeutic modes of action thereof. Understanding the timing and nature of neurovascular remodeling allows for optimized interventions, including personalized medicine for stroke rehabilitation. Additionally, the evaluation of pharmaceutical interventions using these tools may facilitate targeted drug development. Furthermore, neurovascular coupling dynamics have implications for neurodegenerative diseases, brain aging, and the field of brain-computer interfaces.
Evolutionary dynamics and ecological influences on Felidae
Authors: Porto Lucas M. V. , de Olveira Gabriel P. , Fiedler Maico S.
Published: July 2023

In the field of evolutionary biology, researchers have long been interested in comprehending the patterns of diversification and elucidating the mechanisms responsible for the impressive variety of lifeforms observed within taxonomic groups. Based on the fossil records of Felidae, and using a Bayesian framework, we assess here how speciation and extinction rates vary across the last 25 Myr, and how it can potentially be associated with changes in two major ecomorphological traits of Felidae, body mass and carnassial teeth, over such time span. We found two coupled independent increases in both traits along Felidae evolution, one in Machairodontinae, which gradually increases over the last 15 Myr, and the second inPanthera, which rapidly increases within 5 million years. Furthermore, gradual reductions in body mass and carnassial teeth were also observed for some genera such asLeopardus, Lynx, andFelis. Diversification rates showed a gradual reduction throughout the Miocene and Pliocene, with significant rate shifts occurring around 9 and 2 Myr. We suggest that felids were influenced by major environmental changes over the last 17 Myr that probably shaped both traits studied here in order to hunt larger herbivores, but also to explore new niches that became available.