bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of detritivore sea cucumbers from reefs increases coral disease
Authors: Clements Cody S. , Pratte Zoe A. , Stewart Frank J. , Hay Mark E.
Published: February 2024

Coral reefs are in global decline with coral diseases playing a significant role. This is especially true for Acroporid corals that represent ~25% of all Pacific coral species and generate much of the topographic complexity supporting reef biodiversity. Coral diseases are commonly sediment-associated and could be exacerbated by overharvest of sea cucumber detritivores that clean reef sediments and may suppress microbial pathogens as they feed. Here we show, via field manipulations in both French Polynesia and Palmyra Atoll, that historically overharvested sea cucumbers strongly suppress disease among corals in contact with benthic sediments. Sea cucumber removal increased tissue mortality of Acropora pulchra by ~370% and colony mortality by ~1500%. Additionally, farmerfish that kill Acropora pulchra bases to culture their algal gardens further suppress disease by separating corals from contact with the disease-causing sediment—functioning as mutualists rather than parasites despite killing coral bases. Historic overharvesting of sea cucumbers increases coral disease and threatens the persistence of tropical reefs. Enhancing sea cucumbers may enhance reef resilience by suppressing disease.
Engineering surface dipoles on mixed conducting oxides with ultra-thin oxide decoration layers
Authors: Siebenhofer Matthäus , Nenning Andreas , Rameshan Christoph , Blaha Peter , Fleig Jürgen , Kubicek Markus
Published: February 2024

Improving materials for energy conversion and storage devices is deeply connected with an optimization of their surfaces and surface modification is a promising strategy on the way to enhance modern energy technologies. This study shows that surface modification with ultra-thin oxide layers allows for a systematic tailoring of the surface dipole and the work function of mixed ionic and electronic conducting oxides, and it introduces the ionic potential of surface cations as a readily accessible descriptor for these effects. The combination of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) illustrates that basic oxides with a lower ionic potential than the host material induce a positive surface charge and reduce the work function of the host material and vice versa. As a proof of concept that this strategy is widely applicable to tailor surface properties, we examined the effect of ultra-thin decoration layers on the oxygen exchange kinetics of pristine mixed conducting oxide thin films in very clean conditions by means of in-situ impedance spectroscopy during pulsed laser deposition (i-PLD). The study shows that basic decorations with a reduced surface work function lead to a substantial acceleration of the oxygen exchange on the surfaces of diverse materials.
Statistical method scDEED for detecting dubious 2D single-cell embeddings and optimizing t-SNE and UMAP hyperparameters
Authors: Xia Lucy , Lee Christy , Li Jingyi Jessica
Published: February 2024

Two-dimensional (2D) embedding methods are crucial for single-cell data visualization. Popular methods such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP) are commonly used for visualizing cell clusters; however, it is well known that t-SNE and UMAP’s 2D embeddings might not reliably inform the similarities among cell clusters. Motivated by this challenge, we present a statistical method, scDEED, for detecting dubious cell embeddings output by a 2D-embedding method. By calculating a reliability score for every cell embedding based on the similarity between the cell’s 2D-embedding neighbors and pre-embedding neighbors, scDEED identifies the cell embeddings with low reliability scores as dubious and those with high reliability scores as trustworthy. Moreover, by minimizing the number of dubious cell embeddings, scDEED provides intuitive guidance for optimizing the hyperparameters of an embedding method. We show the effectiveness of scDEED on multiple datasets for detecting dubious cell embeddings and optimizing the hyperparameters of t-SNE and UMAP.
Type 1 interferons and Foxo1 down-regulation play a key role in age-related T-cell exhaustion in mice
Authors: Durand Aurélie , Bonilla Nelly , Level Théo , Ginestet Zoé , Lombès Amélie , Guichard Vincent , Germain Mathieu , Jacques Sébastien , Letourneur Franck , Do Cruzeiro Marcio , Marchiol Carmen , Renault Gilles , Le Gall Morgane , Charvet Céline , Le Bon Agnès , Martin Bruno , Auffray Cédric , Lucas Bruno
Published: February 2024

Foxo family transcription factors are critically involved in multiple processes, such as metabolism, quiescence, cell survival and cell differentiation. Although continuous, high activity of Foxo transcription factors extends the life span of some species, the involvement of Foxo proteins in mammalian aging remains to be determined. Here, we show that Foxo1 is down-regulated with age in mouse T cells. This down-regulation of Foxo1 in T cells may contribute to the disruption of naive T-cell homeostasis with age, leading to an increase in the number of memory T cells. Foxo1 down-regulation is also associated with the up-regulation of co-inhibitory receptors by memory T cells and exhaustion in aged mice. Using adoptive transfer experiments, we show that the age-dependent down-regulation of Foxo1 in T cells is mediated by T-cell-extrinsic cues, including type 1 interferons. Taken together, our data suggest that type 1 interferon-induced Foxo1 down-regulation is likely to contribute significantly to T-cell dysfunction in aged mice.
A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study
Authors: Chen Hui , Wang Zeyang , Gong Lihai , Wang Qixuan , Chen Wenyan , Wang Jia , Ma Xuelian , Ding Ruofan , Li Xing , Zou Xudong , Plass Mireya , Lian Cheng , Ni Ting , Wei Gong-Hong , Li Wei , Deng Lin , Li Lei
Published: February 2024

Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.
Pooled effector library screening in protoplasts rapidly identifies novel Avr genes
Authors: Arndell Taj , Chen Jian , Sperschneider Jana , Upadhyaya Narayana M. , Blundell Cheryl , Niesner Nathalie , Outram Megan A. , Wang Aihua , Swain Steve , Luo Ming , Ayliffe Michael A. , Figueroa Melania , Vanhercke Thomas , Dodds Peter N.
Published: February 2024

Crop breeding for durable disease resistance is challenging due to the rapid evolution of pathogen virulence. While progress in resistance (R) gene cloning and stacking has accelerated in recent years1–3, the identification of corresponding avirulence (Avr) genes in many pathogens is hampered by the lack of high-throughput screening options. To address this technology gap, we developed a platform for pooled library screening in plant protoplasts to allow rapid identification of interacting R–Avr pairs. We validated this platform by isolating known and novel Avr genes from wheat stem rust (Puccinia graminis f. sp. tritici) after screening a designed library of putative effectors against individual R genes. Rapid Avr gene identification provides molecular tools to understand and track pathogen virulence evolution via genotype surveillance, which in turn will lead to optimized R gene stacking and deployment strategies. This platform should be broadly applicable to many crop pathogens and could potentially be adapted for screening genes involved in other protoplast-selectable traits.
Robust training of machine learning interatomic potentials with dimensionality reduction and stratified sampling
Authors: Qi Ji , Ko Tsz Wai , Wood Brandon C. , Pham Tuan Anh , Ong Shyue Ping
Published: February 2024

Machine learning interatomic potentials (MLIPs) enable accurate simulations of materials at scales beyond that accessible by ab initio methods and play an increasingly important role in the study and design of materials. However, MLIPs are only as accurate and robust as the data on which they are trained. Here, we present DImensionality-Reduced Encoded Clusters with sTratified (DIRECT) sampling as an approach to select a robust training set of structures from a large and complex configuration space. By applying DIRECT sampling on the Materials Project relaxation trajectories dataset with over one million structures and 89 elements, we develop an improved materials 3-body graph network (M3GNet) universal potential that extrapolates more reliably to unseen structures. We further show that molecular dynamics (MD) simulations with the M3GNet universal potential can be used instead of expensive ab initio MD to rapidly create a large configuration space for target systems. We combined this scheme with DIRECT sampling to develop a reliable moment tensor potential for titanium hydrides without the need for iterative augmentation of training structures. This work paves the way for robust high-throughput development of MLIPs across any compositional complexity.
Transitions in health insurance among continuously insured patients with schizophrenia
Authors: Ranchoff Brittany L. , Jeung Chanup , Zeber John E. , Simon Gregory E. , Ericson Keith M. , Qian Jing , Geissler Kimberley H.
Published: February 2024

Changes in health insurance coverage may disrupt access to and continuity of care, even for those who remain insured. Continuity of care is especially important in schizophrenia, which requires ongoing medical and pharmaceutical treatment. However, little is known about continuity of insurance coverage among those with schizophrenia. The objective was to examine the probability of insurance transitions for individuals with schizophrenia who were continuously insured and whether this varied across insurance types. The Massachusetts All-Payer Claims Database identified individuals with schizophrenia aged 18–64 who were continuously insured during a two-year period between 2014 and 2018. A logistic regression estimated the association of having an insurance transition – defined as having a change in insurance type – with insurance type at the start of the period, adjusting for age, sex, ZIP code in the lowest quartile of median income, and ZIP code with concentrated poverty. Overall, 15.1% had at least one insurance transition across a 24-month period. Insurance transitions were most frequent among those with plans from the Marketplace. In regression adjusted results, individuals covered by the traditional Medicaid program were 20.2 percentage points [pp] (95% confidence interval [CI]: 24.6 pp, 15.9 pp) less likely to have an insurance transition than those who were insured by a Marketplace plan. Insurance transitions among individuals with schizophrenia were common, with more than one in six people having at least one transition in insurance type during a two-year period. Given that even continuously insured individuals with schizophrenia commonly experience insurance transitions, attention to insurance transitions as a barrier to care access and continuity is warranted.
Impact of sex on humoral immunity with live influenza B virus vaccines in mice
Authors: Cardenas-Garcia Stivalis , Cáceres C. Joaquín , Jain Aarti , Geiger Ginger , Mo Jong-Suk , Gay L. Claire , Seibert Brittany , Jasinskas Algimantas , Nakajima Rie , Rajao Daniela S. , Davies D. Huw , Perez Daniel R.
Published: February 2024

Influenza B virus (FLUBV) poses a significant infectious threat, with frequent vaccine mismatch limiting its effectiveness. Our previous work investigated the safety and efficacy of modified live attenuated FLUBV vaccines with rearranged genomes (FluB-RAM and FluB-RANS) or a temperature-sensitive PB1 segment with a C-terminal HA tag (FluB-att). In this study, we compared the immune responses of female and male DBA/2J mice vaccinated with these vaccines, including versions containing a chimeric HA segment with an N-terminal IgA-inducing peptide (IGIP). Importantly, both recombinant viruses with and without IGIP remained genetically stable during egg passage. We found that introducing IGIP strengthened vaccine attenuation, particularly for FluB-RAM/IGIP. Prime-boost vaccination completely protected mice against lethal challenge with a homologous FLUBV strain. Notably, recombinant viruses induced robust neutralizing antibody responses (hemagglutination inhibition titers ≥40) alongside antibodies against NA and NP. Interestingly, female mice displayed a consistent trend of enhanced humoral and cross-reactive IgG and IgA responses against HA, NA, and NP compared to male counterparts, regardless of the vaccine used. However, the presence of IGIP generally led to lower anti-HA responses but higher anti-NA and anti-NP responses, particularly of the IgA isotype. These trends were further reflected in mucosal and serological responses two weeks after challenge, with clear distinctions based on sex, vaccine backbone, and IGIP inclusion. These findings hold significant promise for advancing the development of universal influenza vaccines.
Physical properties of asteroid Dimorphos as derived from the DART impact
Authors: Raducan S. D. , Jutzi M. , Cheng A. F. , Zhang Y. , Barnouin O. , Collins G. S. , Daly R. T. , Davison T. M. , Ernst C. M. , Farnham T. L. , Ferrari F. , Hirabayashi M. , Kumamoto K. M. , Michel P. , Murdoch N. , Nakano R. , Pajola M. , Rossi A. , Agrusa H. F. , Barbee B. W. , Syal M. Bruck , Chabot N. L. , Dotto E. , Fahnestock E. G. , Hasselmann P. H. , Herreros I. , Ivanovski S. , Li J. -Y. , Lucchetti A. , Luther R. , Ormö J. , Owen M. , Pravec P. , Rivkin A. S. , Robin C. Q. , Sánchez P. , Tusberti F. , Wünnemann K. , Zinzi A. , Epifani E. Mazzotta , Manzoni C. , May B. H.
Published: February 2024

On 26 September 2022, NASA’s Double Asteroid Redirection Test (DART) mission successfully impacted Dimorphos, the natural satellite of the binary near-Earth asteroid (65803) Didymos. Numerical simulations of the impact provide a means to find the surface material properties and structures of the target that are consistent with the observed momentum deflection efficiency, ejecta cone geometry and ejected mass. Our simulation that best matches the observations indicates that Dimorphos is weak, with a cohesive strength of less than a few pascals, like asteroids (162173) Ryugu and (101955) Bennu. We find that the bulk density of Dimorphos ρB is lower than ~2,400 kg m−3 and that it has a low volume fraction of boulders (≲40 vol%) on the surface and in the shallow subsurface, which are consistent with data measured by the DART experiment. These findings suggest that Dimorphos is a rubble pile that might have formed through rotational mass shedding and reaccumulation from Didymos. Our simulations indicate that the DART impact caused global deformation and resurfacing of Dimorphos. ESA’s upcoming Hera mission may find a reshaped asteroid rather than a well-defined crater.
Reassessment of the risks of climate change for terrestrial ecosystems
Authors: Conradi Timo , Eggli Urs , Kreft Holger , Schweiger Andreas H. , Weigelt Patrick , Higgins Steven I.
Published: February 2024

Forecasting the risks of climate change for species and ecosystems is necessary for developing targeted conservation strategies. Previous risk assessments mapped the exposure of the global land surface to changes in climate. However, this procedure is unlikely to robustly identify priority areas for conservation actions because nonlinear physiological responses and colimitation processes ensure that ecological changes will not map perfectly to the forecast climatic changes. Here, we combine ecophysiological growth models of 135,153 vascular plant species and plant growth-form information to transform ambient and future climatologies into phytoclimates, which describe the ability of climates to support the plant growth forms that characterize terrestrial ecosystems. We forecast that 33% to 68% of the global land surface will experience a significant change in phytoclimate by 2070 under representative concentration pathways RCP 2.6 and RCP 8.5, respectively. Phytoclimates without present-day analogue are forecast to emerge on 0.3–2.2% of the land surface and 0.1–1.3% of currently realized phytoclimates are forecast to disappear. Notably, the geographic pattern of change, disappearance and novelty of phytoclimates differs markedly from the pattern of analogous trends in climates detected by previous studies, thereby defining new priorities for conservation actions and highlighting the limits of using untransformed climate change exposure indices in ecological risk assessments. Our findings suggest that a profound transformation of the biosphere is underway and emphasize the need for a timely adaptation of biodiversity management practices.
Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition
Authors: Kobayashi Wataru , Sappler Anna H. , Bollschweiler Daniel , Kümmecke Maximilian , Basquin Jérôme , Arslantas Eda Nur , Ruangroengkulrith Siwat , Hornberger Renate , Duderstadt Karl , Tachibana Kikuë
Published: February 2024

Gene expression during natural and induced reprogramming is controlled by pioneer transcription factors that initiate transcription from closed chromatin. Nr5a2 is a key pioneer factor that regulates zygotic genome activation in totipotent embryos, pluripotency in embryonic stem cells and metabolism in adult tissues, but the mechanism of its pioneer activity remains poorly understood. Here, we present a cryo-electron microscopy structure of human NR5A2 bound to a nucleosome. The structure shows that the conserved carboxy-terminal extension (CTE) loop of the NR5A2 DNA-binding domain competes with a DNA minor groove anchor of the nucleosome and releases entry-exit site DNA. Mutational analysis showed that NR5A2 D159 of the CTE is dispensable for DNA binding but required for stable nucleosome association and persistent DNA ‘unwrapping’. These findings suggest that NR5A2 belongs to an emerging class of pioneer factors that can use DNA minor groove anchor competition to destabilize nucleosomes and facilitate gene expression during reprogramming.
Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice
Authors: Burke Marissa , Wong Kelly , Talyansky Yuli , Mhatre Siddhita D. , Mitchell Carol , Juran Cassandra M. , Olson Makaila , Iyer Janani , Puukila Stephanie , Tahimic Candice G. T. , Christenson Lane K. , Lowe Moniece , Rubinstein Linda , Shirazi-Fard Yasaman , Sowa Marianne B. , Alwood Joshua S. , Ronca April E. , Paul Amber M.
Published: February 2024

Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.
Atomic soliton transmission and induced collapse in scattering from a narrow barrier
Authors: Lorenzi Francesco , Salasnich Luca
Published: February 2024

We report systematic numerical simulations of the collision of a bright matter-wave soliton made of Bose-condensed alkali-metal atoms through a narrow potential barrier by using the three-dimensional Gross–Pitaevskii equation. In this way, we determine how the transmission coefficient depends on the soliton impact velocity and the barrier height. Quite remarkably, we also obtain the regions of parameters where there is the collapse of the bright soliton induced by the collision. We compare these three-dimensional results with the ones obtained by three different one-dimensional nonlinear Schrödinger equations. We find that a specifically modified nonpolynomial Schrödinger equation is able to accurately assess the transmission coefficient even in a region in which the usual nonpolynomial Schrödinger equation collapses. In particular, this simplified but very effective one-dimensional model takes into account the transverse width dynamics of the soliton with an ordinary differential equation coupled to the partial differential equation of the axial wave function of the Bose–Einstein condensate.
Synthetic angiotensin II peptide derivatives confer protection against cerebral and severe non-cerebral malaria in murine models
Authors: Silva Adriana F. , Torres Marcelo D. T. , Silva Leandro S. , Alves Flavio L. , Miranda Antonio , Oliveira Vani X. , de la Fuente-Nunez Cesar , Pinheiro Ana Acacia S.
Published: February 2024

Malaria can have severe long-term effects. Even after treatment with antimalarial drugs eliminates the parasite, survivors of cerebral malaria may suffer from irreversible brain damage, leading to cognitive deficits. Angiotensin II, a natural human peptide hormone that regulates blood pressure, has been shown to be active against Plasmodium spp., the etiologic agent of malaria. Here, we tested two Ang II derivatives that do not elicit vasoconstriction in mice: VIPF, a linear tetrapeptide, which constitutes part of the hydrophobic portion of Ang II; and Ang II-SS, a disulfide-bridged derivative. The antiplasmodial potential of both peptides was evaluated with two mouse models: an experimental cerebral malaria model and a mouse model of non-cerebral malaria. The latter consisted of BALB/c mice infected with Plasmodium berghei ANKA. The peptides had no effect on mean blood pressure and significantly reduced parasitemia in both mouse models. Both peptides reduced the SHIRPA score, an assay used to assess murine health and behavior. However, only the constrained derivative (Ang II-SS), which was also resistant to proteolytic degradation, significantly increased mouse survival. Here, we show that synthetic peptides derived from Ang II are capable of conferring protection against severe manifestations of malaria in mouse models while overcoming the vasoconstrictive side effects of the parent peptide.
A diallel study to detect genetic background variation for FHB resistance in winter wheat
Authors: Neupane Bipin , Bisek Bradley , Marais Francois
Published: February 2024

Breeding for resistance to Fusarium head blight (FHB) relies strongly on a limited number of larger-effect resistance QTL that have been mapped and associated with nearby markers. Smaller-effect (background) resistance QTL may also contribute moderate levels of resistance yet are mostly poorly characterized. Overall resistance of a genotype is determined by the combined action of both types of resistance QTL. This study aimed to identify well-adapted, advanced hard red winter (HRW) wheat breeding lines with useful background resistance QTL. A diallel trial consisting of 11 parents and 55 non-reciprocal F1 hybrids was tested for Type II FHB resistance in a replicated greenhouse experiment. Significant differences were detected among entries for disease severity (DS), general combining ability (GCA) and specific combining ability (SCA) with four parents being identified as the best general combiners with lowest DS. The ratio of GCA:SCA effects suggested that additive QTL effects were of primary importance. Overall, resistance QTL showed incomplete dominance, an excess of dominant alleles, and a greater contribution of positive effect genes. F2 of the six best F1 hybrids with the lowest DS were compared in a second greenhouse FHB trial to select possible transgressive segregates for continued evaluation and line development.
The potential of generative AI for personalized persuasion at scale
Authors: Matz S. C. , Teeny J. D. , Vaid S. S. , Peters H. , Harari G. M. , Cerf M.
Published: February 2024

Matching the language or content of a message to the psychological profile of its recipient (known as “personalized persuasion”) is widely considered to be one of the most effective messaging strategies. We demonstrate that the rapid advances in large language models (LLMs), like ChatGPT, could accelerate this influence by making personalized persuasion scalable. Across four studies (consisting of seven sub-studies; total N = 1788), we show that personalized messages crafted by ChatGPT exhibit significantly more influence than non-personalized messages. This was true across different domains of persuasion (e.g., marketing of consumer products, political appeals for climate action), psychological profiles (e.g., personality traits, political ideology, moral foundations), and when only providing the LLM with a single, short prompt naming or describing the targeted psychological dimension. Thus, our findings are among the first to demonstrate the potential for LLMs to automate, and thereby scale, the use of personalized persuasion in ways that enhance its effectiveness and efficiency. We discuss the implications for researchers, practitioners, and the general public.
Enhanced conductive body heat loss during sleep increases slow-wave sleep and calms the heart
Authors: Herberger Sebastian , Penzel Thomas , Fietze Ingo , Glos Martin , Cicolin Alessandro , Fattori Elisa , Grimaldi Daniela , Reid Kathryn , Zee Phyllis , Mason Matteo , Kräuchi Kurt
Published: February 2024

Substantial evidence suggests that the circadian decline of core body temperature (CBT) triggers the initiation of human sleep, with CBT continuing to decrease during sleep. Although the connection between habitual sleep and CBT patterns is established, the impact of external body cooling on sleep remains poorly understood. The main aim of the present study is to show whether a decline in body temperatures during sleep can be related to an increase in slow wave sleep (N3). This three-center study on 72 individuals of varying age, sex, and BMI used an identical type of a high-heat capacity mattress as a reproducible, non-disturbing way of body cooling, accompanied by measurements of CBT and proximal back skin temperatures, heart rate and sleep (polysomnography). The main findings were an increase in nocturnal sleep stage N3 (7.5 ± 21.6 min/7.5 h, mean ± SD; p = 0.0038) and a decrease in heart rate (− 2.36 ± 1.08 bpm, mean ± SD; p < 0.0001); sleep stage REM did not change (p = 0.3564). Subjects with a greater degree of body cooling exhibited a significant increase in nocturnal N3 and a decrease in REM sleep, mainly in the second part of the night. In addition, these subjects showed a phase advance in the NREM-REM sleep cycle distribution of N3 and REM. Both effects were significantly associated with increased conductive inner heat transfer, indicated by an increased CBT- proximal back skin temperature -gradient, rather than with changes in CBT itself. Our findings reveal a previously far disregarded mechanism in sleep research that has potential therapeutic implications: Conductive body cooling during sleep is a reliable method for promoting N3 and reducing heart rate.
Investigation of factors regarding the effects of COVID-19 pandemic on college students’ depression by quantum annealer
Authors: Choi Junggu , Kim Kion , Park Soo Hyun , Hur Juyoen , Yang Hyunjung , Kim Young-Hoon , Lee Hakbae , Han Sanghoon
Published: February 2024

Diverse cases regarding the impact, with its related factors, of the COVID-19 pandemic on mental health have been reported in previous studies. In this study, multivariable datasets were collected from 751 college students who could be easily affected by pandemics based on the complex relationships between various mental health factors. We utilized quantum annealing (QA)-based feature selection algorithms that were executed by commercial D-Wave quantum computers to determine the changes in the relative importance of the associated factors before and after the pandemic. Multivariable linear regression (MLR) and XGBoost models were also applied to validate the QA-based algorithms. Based on the experimental results, we confirm that QA-based algorithms have comparable capabilities in factor analysis research to the MLR models that have been widely used in previous studies. Furthermore, the performance of the QA-based algorithms was validated through the important factor results from the algorithms. Pandemic-related factors (e.g., confidence in the social system) and psychological factors (e.g. decision-making in uncertain situations) were more important in post-pandemic conditions. Although the results should be validated using other mental health variables or national datasets, this study will serve as a reference for researchers regarding the use of the quantum annealing approach in factor analysis with validation through real-world survey dataset analysis.
Temporal recalibration in response to delayed visual feedback of active versus passive actions: an fMRI study
Authors: Kufer Konstantin , Schmitter Christina V. , Kircher Tilo , Straube Benjamin
Published: February 2024

The brain can adapt its expectations about the relative timing of actions and their sensory outcomes in a process known as temporal recalibration. This might occur as the recalibration of timing between the sensory (e.g. visual) outcome and (1) the motor act (sensorimotor) or (2) tactile/proprioceptive information (inter-sensory). This fMRI recalibration study investigated sensorimotor contributions to temporal recalibration by comparing active and passive conditions. Subjects were repeatedly exposed to delayed (150 ms) or undelayed visual stimuli, triggered by active or passive button presses. Recalibration effects were tested in delay detection tasks, including visual and auditory outcomes. We showed that both modalities were affected by visual recalibration. However, an active advantage was observed only in visual conditions. Recalibration was generally associated with the left cerebellum (lobules IV, V and vermis) while action related activation (active > passive) occurred in the right middle/superior frontal gyri during adaptation and test phases. Recalibration transfer from vision to audition was related to action specific activations in the cingulate cortex, the angular gyrus and left inferior frontal gyrus. Our data provide new insights in sensorimotor contributions to temporal recalibration via the middle/superior frontal gyri and inter-sensory contributions mediated by the cerebellum.
Nutrient patterns in relation to metabolic health status and serum levels of brain-derived neurotrophic factor (BDNF) and adropin in adults
Authors: Balali Arghavan , Tirani Shahnaz Amani , Rouhani Parisa , Shahdadian Farnaz , Hajhashemy Zahra , Mohammadi Sobhan , Mokhtari Elahe , Saneei Parvane
Published: February 2024

The present study aimed to investigate the association of nutrient patterns (NPs) with metabolic health status and serum levels of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. This cross-sectional survey was performed on 527 adults aged 20–60 years in Isfahan, Iran. To evaluate dietary intake, a validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used. Participants were categorized as metabolically healthy (MH) and metabolically unhealthy (MU) according to their glycemic and lipid profile, insulin resistance (IR), and inflammation status. An overnight fasting blood sample was collected from each participant and serum levels of BDNF and adropin were assessed. A total of 42.50% of participants were recognized as MU. Three NPs were recognized by factor analysis that labeled as “high animal protein” (NP1), “high vegetable” (NP2), and “high carbohydrate” (NP3) patterns. Moderate adherence to NP2 was related to a lower risk of MU (ORT2 vs. T1 = 0.38, 95% CI: 0.18–0.76). Moreover, high adherence of NP2 (T3 vs. T1) was inversely associated with hypertriglyceridemia (OR = 0.27, 95% CI: 0.11–0.65; P-trend < 0.001) and high hs-CRP values (OR = 0.29, 95% CI: 0.09–1.00; P-trend = 0.03). No significant association was observed between adherence of NP1 and NP3 with MU in crude and adjusted models. However, negative associations were found between moderate adherence to NP3 and insulin resistance (IR) (OR = 0.23, 95% CI: 0.06–0.91) as well as high adherence to NP1 and hypertension (OR = 0.23, 95% CI: 0.09–0.61; P-trend < 0.001). NPs were not associated with serum BDNF and adropin values.
Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature
Authors: Yang Yang , Yang Chenxi , Yang Qiying , Lu Shun , Liu Bisheng , Li Dongyun , Li Dongliang , Zhang Peng , Xu Peng , Lang Jinyi , Zhou Jie
Published: February 2024

With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.
Quantitative microvascular analysis in different stages of retinitis pigmentosa using optical coherence tomography angiography
Authors: Oh Richul , Bae Kunho , Yoon Chang Ki , Park Un Chul , Park Kyu Hyung , Lee Eun Kyoung
Published: February 2024

As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 μm; moderate, < 2500 μm; advanced, absence. Using optical coherence tomography angiography, quantitative microvascular parameters were analyzed. In total, 91 eyes from 49 patients were included. For the superficial capillary plexus (SCP) and deep capillary plexus (DCP), perfusion densities (PDs) in the early stage (SCP: 37.32 ± 8.11%; DCP: 21.19 ± 9.15%) were greater than those in moderate (SCP: 34.16 ± 6.65%, P = 0.011; DCP: 15.67 ± 8.85%, P = 0.031) and advanced stages (SCP: 33.71 ± 9.02%, P = 0.030; DCP: 12.83 ± 6.29%, P < 0.001). The choroidal vascularity index in the early stage (0.58 ± 0.03) was greater than those in the moderate (0.57 ± 0.02, P = 0.017) and advanced stage (0.56 ± 0.02, P = 0.033). The area and perimeter of foveal avascular zone (FAZ) in advanced stage (0.44 ± 0.26 mm2, 2.96 ± 0.86 mm, respectively) were larger than those in early (0.26 ± 0.11 mm2, P = 0.020; 2.19 ± 0.53 mm, P = 0.006, respectively) and moderate stage (0.28 ± 0.13 mm2, P = 0.043; 2.24 ± 0.67 mm, P = 0.013, respectively). During RP disease progression, retinal and choroidal microvascular vessel density decreases in the early stage, followed by FAZ enlargement in the advanced stage.
Large extracellular vesicle (EV) and neutrophil extracellular trap (NET) interaction captured in vivo during systemic inflammation
Authors: Ortmann Weronika , Such Anna , Cichon Iwona , Baj-Krzyworzeka Monika , Weglarczyk Kazimierz , Kolaczkowska Elzbieta
Published: February 2024

Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we report the interactions between EVs and NETs during murine endotoxemia studied in situ directly in the vasculature (cremaster muscle, liver sinusoids) using intravital microscopy (IVM). We captured NETs and EV release in real time by both non- and polarized neutrophils in liver but not in cremaster vasculature. When comparing numbers of circulating EVs of various origin (nanoparticle tracking analysis—NTA, flow cytometry) with those interacting with endothelium and NETs (IVM) we observed that whereas platelet and monocyte/macrophage-derived EVs dominate in blood and peritoneal lavage, respectively, mostly neutrophil-derived EVs interact with the vascular lining, NETs and leukocytes. Despite the interaction, NETs do not affect EV formation as NET release inhibition did not alter EV release. However, EVs inhibit NETs formation and in particular, erythrocyte-derived EVs downregulate NET release and this effect is mediated via Siglec-E-dependent interactions with neutrophils. Overall, we report that EVs are present in NETs in vivo and they do modulate their release but the process in not bidirectional. Moreover, EVs isolated from body fluids might not reflect their importance in direct endothelial- and leukocyte-related interactions.
Indices of airway resistance and reactance from impulse oscillometry correlate with aerosol particle emission in different age groups
Authors: Schumm Benedikt , Bremer Stephanie , Knödlseder Katharina , Schönfelder Martin , Hain Rainer , Semmler Luisa , Lorenz Elke , Wackerhage Henning , Kähler Christian J. , Jörres Rudolf
Published: February 2024

Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the peripheral airways. In the present study we investigated eighty lung-healthy subjects of two age groups (20–39, 60–76 years) at rest and during exercise whether lung function parameters indicative of peripheral airway function were correlated with individual differences in aerosol particle emission. Lung function comprised spirometry and impulse oscillometry during quiet breathing and an expiratory vital capacity manoeuvre, using resistance (R5) and reactance at 5 Hz (X5) as indicators potentially related to peripheral airway function. The association between emission at different ventilation rates relative to maximum ventilation and lung function was assessed by regression analysis. In multiple regression analyses including age group, only vital capacity manoeuvre R5 at 15% to 50% of end-expiratory vital capacity as well as quiet breathing X5 were independently linked to particle emission at 20% to 50% of maximum ventilation, in addition to age group. The fact that age as predictive factor was still significant, although to a lower degree, points towards further effects of age, potentially involving surface properties not accounted for by impulse oscillometry parameters.
Disease resistance and infectivity of virus susceptible and resistant common carp strains
Authors: Dorfman Batya , Marcos-Hadad Evgeniya , Tadmor-Levi Roni , David Lior
Published: February 2024

Infectious diseases challenge health and welfare of humans and animals. Unlike for humans, breeding of genetically resistant animals is a sustainable solution, also providing unique research opportunities. Chances to survive a disease are improved by disease resistance, but depend also on chances to get infected and infect others. Considerable knowledge exists on chances of susceptible and resistant animals to survive a disease, yet, almost none on their infectivity and if and how resistance and infectivity correlate. Common carp (Cyprinus carpio) is widely produced in aquaculture, suffering significantly from a disease caused by cyprinid herpes virus type 3 (CyHV-3). Here, the infectivity of disease-resistant and susceptible fish types was tested by playing roles of shedders (infecting) and cohabitants (infected) in all four type-role combinations. Resistant shedders restricted spleen viral load and survived more than susceptible ones. However, mortality of susceptible cohabitants infected by resistant shedders was lower than that of resistant cohabitants infected by susceptible shedders. Virus levels in water were lower in tanks with resistant shedders leading to lower spleen viral loads in cohabitants. Thus, we empirically demonstrated that disease resistant fish survive better and infect less, with implications to epidemiology in general and to the benefit of aquaculture production.
Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients
Authors: Ciepiela Izabela , Szczepaniak Magdalena , Ciepiela Przemysław , Hińcza-Nowak Kinga , Kopczyński Janusz , Macek Paweł , Kubicka Kamila , Chrapek Magdalena , Tyka Magdalena , Góźdź Stanisław , Kowalik Artur
Published: February 2024

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.
Community detection with Greedy Modularity disassembly strategy
Authors: Rustamaji Heru Cahya , Kusuma Wisnu Ananta , Nurdiati Sri , Batubara Irmanida
Published: February 2024

Community detection recognizes groups of densely connected nodes across networks, one of the fundamental procedures in network analysis. This research boosts the standard but locally optimized Greedy Modularity algorithm for community detection. We introduce innovative exploration techniques that include a variety of node and community disassembly strategies. These strategies include methods like non-triad creating, feeble, random as well as inadequate embeddedness for nodes, as well as low internal edge density, low triad participation ratio, weak, low conductance as well as random tactics for communities. We present a methodology that showcases the improvement in modularity across the wide variety of real-world and synthetic networks over the standard approaches. A detailed comparison against other well-known community detection algorithms further illustrates the better performance of our improved method. This study not only optimizes the process of community detection but also broadens the scope for a more nuanced and effective network analysis that may pave the way for more insights as to the dynamism and structures of its functioning by effectively addressing and overcoming the limitations that are inherently attached with the existing community detection algorithms.
Optimal cutoff value of the dry eye-related quality-of-life score for diagnosing dry eye disease
Authors: Zou Xinrong , Nagino Ken , Okumura Yuichi , Midorikawa-Inomata Akie , Eguchi Atsuko , Yee Alan , Fujimoto Keiichi , Miura Maria , Sung Jaemyoung , Huang Tianxiang , Fujio Kenta , Akasaki Yasutsugu , Nakao Shintaro , Kobayashi Hiroyuki , Inomata Takenori
Published: February 2024

This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.