bluuebunny/crossref_metadata_2025 huggingface dataset:
Interplay of valley polarized dark trion and dark exciton-polaron in monolayer WSe2
Authors: Cong Xin , Mohammadi Parisa Ali , Zheng Mingyang , Watanabe Kenji , Taniguchi Takashi , Rhodes Daniel , Zhang Xiao-Xiao
Published: September 2023

The interactions between charges and excitons involve complex many-body interactions at high densities. The exciton-polaron model has been adopted to understand the Fermi sea screening of charged excitons in monolayer transition metal dichalcogenides. The results provide good agreement with absorption measurements, which are dominated by dilute bright exciton responses. Here we investigate the Fermi sea dressing of spin-forbidden dark excitons in monolayer WSe2. With a Zeeman field, the valley-polarized dark excitons show distinct p-doping dependence in photoluminescence when the carriers reach a critical density. This density can be interpreted as the onset of strongly modified Fermi sea interactions and shifts with increasing exciton density. Through valley-selective excitation and dynamics measurements, we also infer an intervalley coupling between the dark trions and exciton-polarons mediated by the many-body interactions. Our results reveal the evolution of Fermi sea screening with increasing exciton density and the impacts of polaron-polaron interactions, which lay the foundation for understanding electronic correlations and many-body interactions in 2D systems.
Clustering predicted structures at the scale of the known protein universe
Authors: Barrio-Hernandez Inigo , Yeo Jingi , Jänes Jürgen , Mirdita Milot , Gilchrist Cameron L. M. , Wein Tanita , Varadi Mihaly , Velankar Sameer , Beltrao Pedro , Steinegger Martin
Published: September 2023

Proteins are key to all cellular processes and their structure is important in understanding their function and evolution. Sequence-based predictions of protein structures have increased in accuracy1, and over 214 million predicted structures are available in the AlphaFold database2. However, studying protein structures at this scale requires highly efficient methods. Here, we developed a structural-alignment-based clustering algorithm—Foldseek cluster—that can cluster hundreds of millions of structures. Using this method, we have clustered all of the structures in the AlphaFold database, identifying 2.30 million non-singleton structural clusters, of which 31% lack annotations representing probable previously undescribed structures. Clusters without annotation tend to have few representatives covering only 4% of all proteins in the AlphaFold database. Evolutionary analysis suggests that most clusters are ancient in origin but 4% seem to be species specific, representing lower-quality predictions or examples of de novo gene birth. We also show how structural comparisons can be used to predict domain families and their relationships, identifying examples of remote structural similarity. On the basis of these analyses, we identify several examples of human immune-related proteins with putative remote homology in prokaryotic species, illustrating the value of this resource for studying protein function and evolution across the tree of life.
A foundation model for generalizable disease detection from retinal images
Authors: Zhou Yukun , Chia Mark A. , Wagner Siegfried K. , Ayhan Murat S. , Williamson Dominic J. , Struyven Robbert R. , Liu Timing , Xu Moucheng , Lozano Mateo G. , Woodward-Court Peter , Kihara Yuka ,   UK Biobank Eye & Vision Consortium, Allen Naomi , Gallacher John E. J. , Littlejohns Thomas , Aslam Tariq , Bishop Paul , Black Graeme , Sergouniotis Panagiotis , Atan Denize , Dick Andrew D. , Williams Cathy , Barman Sarah , Barrett Jenny H. , Mackie Sarah , Braithwaite Tasanee , Carare Roxana O. , Ennis Sarah , Gibson Jane , Lotery Andrew J. , Self Jay , Chakravarthy Usha , Hogg Ruth E. , Paterson Euan , Woodside Jayne , Peto Tunde , Mckay Gareth , Mcguinness Bernadette , Foster Paul J. , Balaskas Konstantinos , Khawaja Anthony P. , Pontikos Nikolas , Rahi Jugnoo S. , Lascaratos Gerassimos , Patel Praveen J. , Chan Michelle , Chua Sharon Y. L. , Day Alexander , Desai Parul , Egan Cathy , Fruttiger Marcus , Garway-Heath David F. , Hardcastle Alison , Khaw Sir Peng T. , Moore Tony , Sivaprasad Sobha , Strouthidis Nicholas , Thomas Dhanes , Tufail Adnan , Viswanathan Ananth C. , Dhillon Bal , Macgillivray Tom , Sudlow Cathie , Vitart Veronique , Doney Alexander , Trucco Emanuele , Guggeinheim Jeremy A. , Morgan James E. , Hammond Chris J. , Williams Katie , Hysi Pirro , Harding Simon P. , Zheng Yalin , Luben Robert , Luthert Phil , Sun Zihan , McKibbin Martin , O’Sullivan Eoin , Oram Richard , Weedon Mike , Owen Chris G. , Rudnicka Alicja R. , Sattar Naveed , Steel David , Stratton Irene , Tapp Robyn , Yates Max M. , Petzold Axel , Madhusudhan Savita , Altmann Andre , Lee Aaron Y. , Topol Eric J. , Denniston Alastair K. , Alexander Daniel C. , Keane Pearse A.
Published: September 2023

Medical artificial intelligence (AI) offers great potential for recognizing signs of health conditions in retinal images and expediting the diagnosis of eye diseases and systemic disorders1. However, the development of AI models requires substantial annotation and models are usually task-specific with limited generalizability to different clinical applications2. Here, we present RETFound, a foundation model for retinal images that learns generalizable representations from unlabelled retinal images and provides a basis for label-efficient model adaptation in several applications. Specifically, RETFound is trained on 1.6 million unlabelled retinal images by means of self-supervised learning and then adapted to disease detection tasks with explicit labels. We show that adapted RETFound consistently outperforms several comparison models in the diagnosis and prognosis of sight-threatening eye diseases, as well as incident prediction of complex systemic disorders such as heart failure and myocardial infarction with fewer labelled data. RETFound provides a generalizable solution to improve model performance and alleviate the annotation workload of experts to enable broad clinical AI applications from retinal imaging.
Bile salts enhance the susceptibility of the peach allergenic lipid transfer protein, Pru p 3, to in vitro gastrointestinal proteolysis
Authors: Wang Kai , Gali-Moya Judit , Ruano-Zaragoza Maria , Cain Kathleen , D’Auria Giovanni , Daly Matthew , Barran Perdita , Crevel René , Mills E. N. Clare
Published: September 2023

Sensitisation to the lipid transfer protein Pru p 3 is associated with severe allergic reactions to peach, the proteins stability being thought to play a role in its allergenicity. Lipid binding increases susceptibility of Pru p 3 to digestion and so the impact of bile salts on the in vitro gastrointestinal digestibility of Pru p 3 was investigated and digestion products mapped by SDS-PAGE and mass spectrometry. Bile salts enhanced the digestibility of Pru p 3 resulting in an ensemble of around 100 peptides spanning the protein’s sequence which were linked by disulphide bonds into structures of ~ 5–6 kDa. IgE binding studies with a serum panel from peach allergic subjects showed digestion reduced, but did not abolish, the IgE reactivity of Pru p 3. These data show the importance of including bile salts in vitro digestion systems and emphasise the need to profile of digestion in a manner that allows identification of immunologically relevant disulphide-linked peptide aggregates.
Differential abundance of lipids and metabolites related to SARS-CoV-2 infection and susceptibility
Authors: Albóniga Oihane E. , Moreno Elena , Martínez-Sanz Javier , Vizcarra Pilar , Ron Raquel , Díaz-Álvarez Jorge , Rosas Cancio-Suarez Marta , Sánchez-Conde Matilde , Galán Juan Carlos , Angulo Santiago , Moreno Santiago , Barbas Coral , Serrano-Villar Sergio
Published: September 2023

The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. To understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. We collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. We show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. This study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.
The fructose-bisphosphate, Aldolase A (ALDOA), facilitates DNA-PKcs and ATM kinase activity to regulate DNA double-strand break repair
Authors: Sobanski Thais , Suraweera Amila , Burgess Joshua T. , Richard Iain , Cheong Chee Man , Dave Keyur , Rose Maddison , Adams Mark N. , O’Byrne Kenneth J. , Richard Derek J. , Bolderson Emma
Published: September 2023

Glucose metabolism and DNA repair are fundamental cellular processes frequently dysregulated in cancer. In this study, we define a direct role for the glycolytic Aldolase A (ALDOA) protein in DNA double-strand break (DSB) repair. ALDOA is a fructose biphosphate Aldolase that catalyses fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), during glycolysis. Here, we show that upon DNA damage induced by ionising radiation (IR), ALDOA translocates from the cytoplasm into the nucleus, where it partially co-localises with the DNA DSB marker γ-H2AX. DNA damage was shown to be elevated in ALDOA-depleted cells prior to IR and following IR the damage was repaired more slowly. Consistent with this, cells depleted of ALDOA exhibited decreased DNA DSB repair via non-homologous end-joining and homologous recombination. In support of the defective repair observed in its absence, ALDOA was found to associate with the major DSB repair effector kinases, DNA-dependent Protein Kinase (DNA-PK) and Ataxia Telangiectasia Mutated (ATM) and their autophosphorylation was decreased when ALDOA was depleted. Together, these data establish a role for an essential metabolic protein, ALDOA in DNA DSB repair and suggests that targeting ALDOA may enable the concurrent targeting of cancer metabolism and DNA repair to induce tumour cell death.
IBA and melatonin increase trigonelline and caffeine during the induction and initiation of adventitious roots in Coffea arabica L. cuttings
Authors: de Andrade Francisco Hélio Alves , Ferreira Ana Maria Oliveira , Azevedo Lillian Magalhães , de Oliveira Santos Meline , Carvalho Gladyston Rodrigues , de Resende Mário Lucio Vilela , Bicalho Elisa Monteze , Silva Vânia Aparecida
Published: September 2023

Caffeine and trigonelline are found in Coffea arabica, and show antioxidant roles and growth and development functions. However, there are no reports on trigonelline and caffeine in relation to coffee rooting. The aim was to evaluate the impact of application of indole-3-butyric acid (IBA) and melatonin on caffeine and trigonelline at different stages of adventitious rooting in cuttings. In addition, to study the correlation between these metabolites and H2O2, phenols, and antioxidant enzymes. Four treatments (Control, melatonin 21 µM (M21), melatonin 43 µM (M43), and IBA 7380 µM (IBA)) were used, with four replications. The growth and biochemical parameters of the antioxidant system were performed in induction, initiation, and extension rooting stages. Higher concentrations of trigonelline and caffeine quantified in the induction and initiation stages were positively correlated with higher percentage of rooted cuttings. Trigonelline and caffeine were positively correlated with H2O2 in all stages of development of adventitious roots. The correlations of trigoneline and caffeine with phenols and antioxidant enzymes reveal different profiles, depending on the phases. The results indicate that IBA and melatonin increase trigonelline and caffeine during the induction and initiation of adventitious roots in Coffea arabica cuttings, which is correlated with a higher percentage of rooted cuttings.
Prefrontal hypoactivation induced via social stress is more strongly associated with state rumination than depressive symptomatology
Authors: Int-Veen Isabell , Fallgatter Andreas J. , Ehlis Ann-Christine , Rosenbaum David
Published: September 2023

Previous studies have consistently shown a pattern of prefrontal hypoactivation in depressed patients (DP); however, it remains unclear whether this neural correlate is a consequence or concomitant feature of depression and/or whether ruminative thinking might be underlying. Using a sample comprising 65 healthy controls (HC) and 77 DP, we investigated the behavioral and neural correlates in response to stress and their association with depressive symptomatology, trait and state rumination. Fitting repeated-measurement MANOVAs including 21 fNIRS-channels covering the bilateral Inferior Frontal Gyrus (IFG), Dorsolateral Prefrontal Cortex (DLPFC) and Somatosensory Association Cortex (SAC), we investigated the predictive value of diagnostic group (HC vs. DP) and state rumination. In DP, we observed significantly lower increases in cortical oxygenation under stress in channels of the right IFG and bilateral DLPFC. Participants reporting lower state rumination and no increases in state rumination under stress showed higher increases in cortical oxygenation compared to the other groups and in more channels compared to the analysis on diagnostic group. Re-running our fNIRS-analysis while correcting for performance resulted in time-dependent changes dependent on group (DP vs. HC) no longer yielding significance, however for the differentiation of state rumination groups.
Research on wheel-legged robot based on LQR and ADRC
Authors: Feng Xujiong , Liu Shuaishuai , Yuan Qiang , Xiao Junbo , Zhao Daxu
Published: September 2023

The traditional two-wheeled self-balancing robot can travel quickly in a flat road environment, and it is easy to destabilize and capsize when passing through a bumpy road. To improve the passing ability of a two-wheeled robot, a new wheel-legged two-wheeled robot is developed. A seven-link leg structure is proposed through the comprehensive design of mechanism configuration, which decouples the balanced motion and leg motion of the robot. Based on the Euler–Lagrange method, the dynamic model of the system is obtained by applying the nonholonomic dynamic Routh equation in the generalized coordinate system. The robot’s state space is divided according to the robot’s height, and the Riccati equation is solved in real-time by the linear quadratic regulator (LQR) method to complete the balance and motion control of the robot. The robot leg motion control is achieved based on the active disturbance rejection control (ADRC) way. A robot simulation model is built on Recurdyn to verify the algorithm’s feasibility, and then an experimental prototype is built to demonstrate the algorithm’s effectiveness. The experimental results show that the control method based on LQR and ADRC can make the robot pass through the bumpy road.
Health-related quality of life and its influencing factors in patients with breast cancer based on the scale QLICP-BR
Authors: Chen Shu , Liu Yuxi , Fong Daniel Yee Tak , Zhou Jiali , Chen Huanwei , Wan Chonghua
Published: September 2023

Breast cancer is the most common cancer and the leading cause of cancer death among females worldwide. During the past 15 years, quality of life (QOL) has become an important aspect of breast cancer treatment. The purpose of this study was to evaluate QOL of breast cancer patients in China, and investigate its associations with sociodemographic and clinical variables. A cross-sectional study was conducted in 246 breast cancer patients in China. Recruited patients were surveyed for QOL using the QOL instruments for cancer patients-breast cancer QLICP-BR (V2.0). We assessed the associations between potential influencing factors and QOL using multiple linear regression models. The general mean QOL score for our population was 70.24 with SD = 8.70. Results indicated that medical insurance, drinking history, alkaline phosphatase, serum chloride ion level, serum calcium ion level, serum phosphorus ion level, mean corpuscular volume, mean corpuscular hemoglobin, red cell volume distribution width and platelet had significant associations with QOL of breast cancer patients. Our results emphasized that many factors are affecting QOL of breast cancer patients, which may provide a reference for targeted management or intervention strategies of breast cancer patients to improve their QOL.
Development of multiplex gold nanoparticles biosensors for ultrasensitive detection and genotyping of equine herpes viruses
Authors: Ghoniem Shimaa M. , ElZorkany Heba E. , Hagag Naglaa M. , El-Deeb Ayman H. , Shahein Momtaz A. , Hussein Hussein A.
Published: September 2023

Gold nanoparticles (GNPs) biosensors can detect low viral loads and differentiate between viruses types, enabling early diagnosis and effective disease management. In the present study, we developed GNPs biosensors with two different capping agent, citrate-GNPs biosensors and polyvinylpyrrolidone (PVP)-GNPs biosensors for detection of EHV-1 and EHV-4 in multiplex real time PCR (rPCR). Citrate-GNPs and PVP-GNPs biosensors can detect dilution 1010 of EHV-1 with mean Cycle threshold (Ct) 11.7 and 9.6, respectively and one copy as limit of detection, while citrate-GNPs and PVP-GNPs biosensors can detect dilution 1010 of EHV-4 with mean Ct 10.5 and 9.2, respectively and one copy as limit of detection. These findings were confirmed by testing 87 different clinical samples, 4 more samples were positive with multiplex GNPs biosensors rPCR than multiplex rPCR. Multiplex citrate-GNPs and PVP-GNPs biosensors for EHV-1 and EHV-4 are a significant breakthrough in the diagnosis of these virus types. These biosensors offer high sensitivity and specificity, allowing for the accurate detection of the target viruses at very low concentrations and improve the early detection of EHV-1 and EHV-4, leading to faster control of infected animals to prevent the spread of these viruses.
Holopelagic Sargassum aggregations provide warmer microhabitats for associated fauna
Authors: Gulick Alexandra G. , Constant Nerine , Bolten Alan B. , Bjorndal Karen A.
Published: September 2023

Drifting aggregations of Sargassum algae provide critical habitat for endemic, endangered, and commercially important species. They may also provide favorable microclimates for associated fauna. To quantify thermal characteristics of holopelagic Sargassum aggregations, we evaluated thermal profiles of 50 aggregations in situ in the Sargasso Sea. Sea surface temperature (SST) in the center of aggregations was significantly higher than in nearby open water, and SST differential was independent of aggregation volume, area, and thickness. SST differential between aggregation edge and open water was smaller than those between aggregation center and aggregation edge and between aggregation center and open water. Water temperature was significantly higher inside and below aggregations compared to open water but did not vary inside aggregations with depth. Holopelagic Sargassum aggregations provide warmer microhabitats for associated fauna, which may benefit marine ectotherms, though temperature differentials were narrow (up to 0.7 °C) over the range of aggregation sizes we encountered (area 0.01–15 m2). We propose a hypothetical curve describing variation in SST differential with Sargassum aggregation size as a prediction for future studies to evaluate across temporal and geographic ranges. Our study provides a foundation for investigating the importance of thermal microhabitats in holopelagic Sargassum ecosystems.
Association between anticoagulation strategy and quality of life in chronic hemodialysis patients
Authors: Eloot Sunny , Vanommeslaeghe Floris , Josipovic Iván , Boone Matthieu , Van Biesen Wim
Published: September 2023

Prevention of clotting in hemodialysis (HD) is a concern, but tools to monitor anticoagulation strategies as well as data on bleeding and its impact on quality of life (QoL) are scant. In this prospective longitudinal observational study, bleeding tendency in 70 HD patients was scored with ISTH-BAT and HAS-BLED at week 0, 4, and 8. Patient’s limbs were visually scored for bruises and hematomas, and Quality of Life (QoL) was assessed using EQ5D-3L and Visual Analogue Scale (VAS) questionnaires. At week 0, the used hemodialyzer was scanned in a micro-CT scanner to quantify the number of patent fibers. Bleeding scores were 0 [0; 1] and 3 [2; 4] for ISTH-BAT and HAS-BLED, and visual scoring showed 2 [0; 4] bruises/hematomas. QoL was 0.85 [0.77; 1.00] for EQ5D and 70 [60; 80] for VAS. Fiber patency was 81 [70; 90]%, but was not associated with anticoagulation dose (p = 0.103). Patients in the highest tertile of anticoagulation dose had a worse VAS score (p = 0.027), and patients identified as having bleeding tendency by ISTH also had a worse VAS score (p = 0.010). This supports our postulate that in maintenance HD patients the current personal anticoagulation dose regimens may be too high, leading to more mainly minor bleeding that may negatively impact health related quality of life.
Copper-decorated core–shell structured ordered mesoporous containing cobalt ferrite nanoparticles as high-performance heterogeneous catalyst toward synthesis of tetrazole
Authors: Molaei Somayeh , Ghadermazi Mohammad
Published: September 2023

The present work describes the synthesis of copper immobilization on CoFe2O4/MCM-41 as a catalyst, which is created by attaching copper and ligand (N-phenyl anthranilic acid (PA)) on the surface of CoFe2O4/MCM-41 (CoFe2O4/MCM-41/PA/Cu). The synthesized CoFe2O4/MCM-41 support and immobilized copper were identified by FTIR, TEM, VSM, SEM XRD, and nitrogen adsorption–desorption analysis. The results showed that MCM-41 silica was coated with magnetite nanoparticles and copper was successfully immobilized on this structure. The catalytic performance of synthesized catalyst was tested in the synthesis of tetrazole. It was shown that the solid catalyst exhibited a strong magnetic response and showed good catalytic activity in the synthesis of tetrazole. The catalytic test showed that copper supported on CoFe2O4/MCM-41 hybrid showed much better catalytic activity than copper supported on CoFe2O4, indicating that MCM-41 plays an important role in CoFe2O4/MCM-41 hybrid for the synthesis of tetrazole. Separation of the solid catalyst from the reaction mixture was easily performed by external magnetism without apparent mass loss. And the catalyst could be reused six times for the synthesis of heterogeneous tetrazole.
Identification of essential genes associated with SARS-CoV-2 infection as potential drug target candidates with machine learning algorithms
Authors: Taheri Golnaz , Habibi Mahnaz
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide concern. Several genes associated with the SARS-CoV-2, which are essential for its functionality, pathogenesis, and survival, have been identified. These genes, which play crucial roles in SARS-CoV-2 infection, are considered potential therapeutic targets. Developing drugs against these essential genes to inhibit their regular functions could be a good approach for COVID-19 treatment. Artificial intelligence and machine learning methods provide powerful infrastructures for interpreting and understanding the available data and can assist in finding fast explanations and cures. We propose a method to highlight the essential genes that play crucial roles in SARS-CoV-2 pathogenesis. For this purpose, we define eleven informative topological and biological features for the biological and PPI networks constructed on gene sets that correspond to COVID-19. Then, we use three different unsupervised learning algorithms with different approaches to rank the important genes with respect to our defined informative features. Finally, we present a set of 18 important genes related to COVID-19. Materials and implementations are available at: https://github.com/MahnazHabibi/Gene_analysis.
Characteristics of wood apple (Limonia acidissima L.) and soybean powder jelly for emergency food alternatives
Authors: Afifah Diana Nur , Ayustaningwarno Fitriyono , Rahmawati Anisa , Cantikatmaka Dhara Nabila , Wigati Ningsih , Noer Etika Ratna , Widyastuti Nurmasari , Wijayanti Hartanti Sandi , Sugianto Denny Nugroho , Ningrum Yesi Pratama Aprilia , Hastuti Vivilia Niken
Published: September 2023

The substitution of wood apple juice and soybean powder in the seaweed jelly product can be used as an alternative to emergency supplementary feeding (ESF) for children under five years of age, which contains high protein, fiber, and calories. This study aimed to determine the effect of adding wood apple juice and soybean powder to the nutrition content, vitamin C, zinc, magnesium, total phenol, antioxidant activity, acceptability, and shelf-life of seaweed jelly products. This study was an experimental study with a completely randomized design with two treatment factors, which consisted of making seaweed jelly products with three different ratios of wood apple juice and soybean powder, 60:40 (F1), 50:50 (F2), and 40:60 (F3), dried at 40 °C (T1) and 50 °C (T2). Macronutrients were determined using proximate analysis. The total phenol and vitamin C were measured using Folin-ciocalteu reagent and UV–Vis spectrophotometry. Antioxidant activity was analyzed by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH). The contents of zinc and magnesium were evaluated through Atomic Absorption Spectrophotometry (AAS). Estimation of shelf life was determined with Accelerated Shelf-Life Test (ASLT) method and Arrhenius equation model. The best formula based on proximate analysis was F3, which contained 361.98 kcal of energy and 33.79 g of protein. The best formula (F1) dried at 40 °C; contains 56.28 mg/100 g vitamin C; zinc was 1.55 mg/100 g; magnesium was 79.25 mg/100 g; antioxidant activity (IC50) was 88.39 μg/mL; and total phenol was 8.59 mg GAE/g. The quality attributes of the best formula show the potential of the jelly as an emergency food despite its short shelf-life.
TnaA, a trithorax group protein, modulates wingless expression in different regions of the Drosophila wing imaginal disc
Authors: Rosales-Vega Marco , Reséndez-Pérez Diana , Zurita Mario , Vázquez Martha
Published: September 2023

wingless expression is exquisitely regulated by different factors and enhancers in the imaginal wing discs of Drosophila melanogaster in four domains: the dorsal band, the dorso-ventral boundary, and the inner and outer ring domains. tonalli is a trithorax group gene that encodes a putative SUMO E3 ligase that binds to chromatin to regulate the expression of its targets, including the Hox genes. However, its role in modulating gene expression is barely known. Here, we show that TnaA modulates the wingless expression at two domains of the wing disc, the dorso-ventral boundary and the inner ring. At first, tonalli interacts genetically with Notch to form the wing margin. In the inner ring domain, TnaA modulates wingless transcription. When the dosage of TnaA increases in or near the inner ring since early larval stages, this domain expands with a rapid increase in wingless expression. TnaA occupies the wingless Inner Ring Enhancer at the wing disc, meanwhile it does not affect wingless expression directed by the Ventral Disc Enhancer in leg discs, suggesting that TnaA acts as a wingless enhancer-specific factor. We describe for the first time the presence of TnaA at the Inner Ring Enhancer as a specific regulator of wingless in the development of wing boundaries.
High-status individuals are held to higher ethical standards
Authors: Trautmann Stefan T. , Wang Xianghong , Wang Yijie , Xu Yilong
Published: September 2023

Although there is evidence for the generosity of high-status individuals, there seems to be a strong perception that the elites are selfish and contribute little to others’ welfare, and even less so than poorer people. We argue that this perception may derive from a gap between normative and empirical expectations regarding the behavior of the elites. Using large-scale survey experiments, we show that high-status individuals are held to higher ethical standards in both the US and China, and that there is a strong income gradient in normatively expected generosity. We also present evidence for a gap between people’s normative expectations of how the rich should behave, and their empirical expectations of how they actually do: empirical expectations are generally lower than both normative expectations and actual giving.
Exploration of common genomic signatures of systemic juvenile rheumatoid arthritis and type 1 diabetes
Authors: Zheng Jie , Wang Yong , Fang Xin , Hu Jun
Published: September 2023

To explore the genetic characteristics of systemic juvenile rheumatoid arthritis (sJRA) and type 1 diabetes mellitus (T1D). The microarray data of sJRA and T1D from Gene Expression Omnibus (GEO) were analyzed. The shared differentially expressed genes (SDEGs) were identified by the Meta-analysis, and genes of extracellular proteins were identified. Then, transcription factors (TFs) and their target genes in SDEGs were obtained by comparing databases from HumanTFDB, and hTFtarget. After that, functional enrichment analyses of the previously identified gene sets were performed by metascape tool. Finally, immune infiltration was analysed by CIBERSORT. We found 175 up-regulated and 245 down-regulated SDEGs, and by constructing a TFs-targeted SDEGs network, 3 key TFs (ARID3A, NEF2, RUNX3) were screened. Functional enrichment analyses and immune infiltration results suggested not only the adaptive immune system but also the innate immune system, and signaling pathways like JAK-STAT are important in the pathogenesis of sJRA and T1D, involving biological processes such as CD4 T cell functions and neutrophil degranulation. This work suggests that innate immune abnormalities also play important roles in sJRA and T1D, CD4 T cell functions, neutrophil degranulation and the JAK-STAT pathway may be involved. The regulatory roles of ARID3A, NEF2, and RUNX3 in this network need to be further investigated.
A pilot prospective cohort study using experimental quantification of early peripheral nerve regeneration with high-frequency three-dimensional tomographic ultrasound (HFtUS)
Authors: Murphy Ralph N. A. , Rogers Steven K. , Bhatti Waqar , Wong Jason K. , Reid Adam J.
Published: September 2023

Quantification of peripheral nerve regeneration after injury relies upon subjective outcome measures or electrophysiology assessments requiring fully regenerated neurons. Nerve surgeons and researchers lack objective, quantifiable information on the site of surgical repair and regenerative front. To address this need, we developed a quantifiable, visual, clinically available measure of early peripheral nerve regeneration using high-frequency, three-dimensional, tomographic ultrasound (HFtUS). We conducted a prospective, longitudinal study of adult patients with ulnar and/or median nerve injury of the arm undergoing direct epineurial repair within 5 days of injury. Assessment of morphology, volumetric and 3D grey-scale quantification of cross-sectional views were made at baseline up to 15 months post-surgery. Sensory and motor clinical outcome measures and patient reported outcome measures (PROMs) were recorded. Five participants were recruited to the study. Our data demonstrated grey-scale values (an indication of axonal density) increased in distal stumps within 2–4 months after repair, returning to normal as regeneration completed (4–6 months) with concomitant reduction in intraneural volume as surgical oedema resolved. Two patients with abnormal regeneration were characterized by increased intraneural volume and minimal grey-scale change. HFtUS may quantify early peripheral nerve regeneration offering a window of opportunity for surgical intervention where early abnormal regeneration is detected.
Artificial intelligence-enhanced electrocardiography for early assessment of coronavirus disease 2019 severity
Authors: Baek Yong-Soo , Jo Yoonsu , Lee Sang-Chul , Choi Wonik , Kim Dae-Hyeok
Published: September 2023

Despite challenges in severity scoring systems, artificial intelligence-enhanced electrocardiography (AI-ECG) could assist in early coronavirus disease 2019 (COVID-19) severity prediction. Between March 2020 and June 2022, we enrolled 1453 COVID-19 patients (mean age: 59.7 ± 20.1 years; 54.2% male) who underwent ECGs at our emergency department before severity classification. The AI-ECG algorithm was evaluated for severity assessment during admission, compared to the Early Warning Scores (EWSs) using the area under the curve (AUC) of the receiver operating characteristic curve, precision, recall, and F1 score. During the internal and external validation, the AI algorithm demonstrated reasonable outcomes in predicting COVID-19 severity with AUCs of 0.735 (95% CI: 0.662–0.807) and 0.734 (95% CI: 0.688–0.781). Combined with EWSs, it showed reliable performance with an AUC of 0.833 (95% CI: 0.830–0.835), precision of 0.764 (95% CI: 0.757–0.771), recall of 0.747 (95% CI: 0.741–0.753), and F1 score of 0.747 (95% CI: 0.741–0.753). In Cox proportional hazards models, the AI-ECG revealed a significantly higher hazard ratio (HR, 2.019; 95% CI: 1.156–3.525, p = 0.014) for mortality, even after adjusting for relevant parameters. Therefore, application of AI-ECG has the potential to assist in early COVID-19 severity prediction, leading to improved patient management.
A generalisation of the method of regression calibration
Authors: Little Mark P. , Hamada Nobuyuki , Zablotska Lydia B.
Published: September 2023

There is direct evidence of risks at moderate and high levels of radiation dose for highly radiogenic cancers such as leukaemia and thyroid cancer. For many cancer sites, however, it is necessary to assess risks via extrapolation from groups exposed at moderate and high levels of dose, about which there are substantial uncertainties. Crucial to the resolution of this area of uncertainty is the modelling of the dose–response relationship and the importance of both systematic and random dosimetric errors for analyses in the various exposed groups. It is well recognised that measurement error can alter substantially the shape of this relationship and hence the derived population risk estimates. Particular attention has been devoted to the issue of shared errors, common in many datasets, and particularly important in occupational settings. We propose a modification of the regression calibration method which is particularly suited to studies in which there is a substantial amount of shared error, and in which there may also be curvature in the true dose response. This method can be used in settings where there is a mixture of Berkson and classical error. In fits to synthetic datasets in which there is substantial upward curvature in the true dose response, and varying (and sometimes substantial) amounts of classical and Berkson error, we show that the coverage probabilities of all methods for the linear coefficient$$\alpha$$αare near the desired level, irrespective of the magnitudes of assumed Berkson and classical error, whether shared or unshared. However, the coverage probabilities for the quadratic coefficient$$\beta$$βare generally too low for the unadjusted and regression calibration methods, particularly for larger magnitudes of the Berkson error, whether this is shared or unshared. In contrast Monte Carlo maximum likelihood yields coverage probabilities for$$\beta$$βthat are uniformly too high. The extended regression calibration method yields coverage probabilities that are too low when shared and unshared Berkson errors are both large, although otherwise it performs well, and coverage is generally better than these other three methods. A notable feature is that for all methods apart from extended regression calibration the estimates of the quadratic coefficient$$\beta$$βare substantially upwardly biased.
Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment
Authors: Burmeister Thomas , Gröger Daniela , Gökbuget Nicola , Spriewald Bernd , Starck Michael , Elmaagacli Ahmet , Hoelzer Dieter , Keller Ulrich , Schwartz Stefan
Published: September 2023

The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia and accounts for 3–5% of cases. The molecular background of this translocation has been incompletely studied, especially in adult cases. We characterized the chromosomal breakpoints of 49 patients with TCF3::PBX1 and the corresponding reciprocal PBX1::TCF3 breakpoints in 15 cases at the molecular level, thus providing an extensive molecular overview of this translocation in a well-defined study patient population. Breakpoints were found to be remarkably clustered not only in TCF3 but also in PBX1. No association with DNA repeats or putative cryptic recombination signal sequence sites was observed. A simplified detection method for breakpoint identification was developed and the feasibility of patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD) was explored. A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established that could serve as a useful alternative to the classical method utilizing rearranged immune gene loci. This study provides the first extensive molecular data set on the chromosomal breakpoints of the t(1;19)/TCF3::PBX1 aberration in adult ALL. Based on the obtained data a generic MRD method was developed that has several theoretical advantages, including an on average higher sensitivity and a greater stability of the molecular marker in the course of disease.
The diffusion metrics of African swine fever in wild boar
Authors: Lentz Hartmut H. K. , Bergmann Hannes , Conraths Franz J. , Schulz Jana , Sauter-Louis Carola
Published: September 2023

To control African swine fever (ASF) efficiently, easily interpretable metrics of the outbreak dynamics are needed to plan and adapt the required measures. We found that the spread pattern of African Swine Fever cases in wild boar follows the mechanics of a diffusion process, at least in the early phase, for the cases that occurred in Germany. Following incursion into a previously unaffected area, infection disseminates locally within a naive and abundant wild boar population. Using real case data for Germany, we derive statistics about the time differences and distances between consecutive case reports. With the use of these statistics, we generate an ensemble of random walkers (continuous time random walks, CTRW) that resemble the properties of the observed outbreak pattern as one possible realization of all possible disease dissemination patterns. The trained random walker ensemble yields the diffusion constant, the affected area, and the outbreak velocity of early ASF spread in wild boar. These methods are easy to interpret, robust, and may be adapted for different regions. Therefore, diffusion metrics can be useful descriptors of early disease dynamics and help facilitate efficient control of African Swine Fever.
Morphological and semiconductive properties of the anodic oxide layers made on Fe3Al alloy by anodizing in tartaric-sulfuric acid mixture
Authors: del Olmo Rubén , Łazińska Magdalena , Czerwiński Mateusz , Durejko Tomasz , Michalska-Domańska Marta
Published: September 2023

It has recently been found that the anodizing of FeAl alloys allows the formation of iron-aluminum oxide layers with interesting semiconducting properties. However, the lack of systematic research on different anodizing regimes is hampering their full exploitation in numerous photoelectrochemical-related applications. This study address, for the first time, the systematic effect of the electrolyte composition on the formation of self-ordered oxide films by anodizing on cast Fe3Al alloy. The Fe3Al alloy was anodized in 3 electrolytes with different water-ethylene glycol (EG) ratios (pure water, 25 vol.%-EG, and 50 vol.%-EG solutions) at a constant tartaric-sulfuric acids concentration, different voltages (10–20 V) and treatment times (2–60 min). After anodizing, all anodic oxide layers were annealed at 900 °C to form semiconductive iron-aluminum crystalline phases. Conventional techniques were used to systematically ascertain the morphological (SEM/EDS, XRD, eddy-current measurements) and semiconductive (UV–VIS reflectance spectroscopy) properties of these oxide layers. The results confirmed the formation of homogeneous and self-ordered anodic oxide layers at 10 and 15 V, regardless of the electrolyte composition. Namely, anodic films formed in electrolytes containing EG showed lower pore sizes, growth rates, and film thicknesses than those anodic films formed in the aqueous-based electrolyte. The annealing post-treatment results in different Fe-Al oxides (FexOy, FeAl2O4, etc.) with superior band gap values than those for non-annealed films.
Application of an analytical approach to characterize the target strength of ancillary pelagic fish species
Authors: Palermino Antonio , De Felice Andrea , Canduci Giovanni , Biagiotti Ilaria , Costantini Ilaria , Centurelli Michele , Leonori Iole
Published: September 2023

The lack of data on the species-specific Target Strength (TS) on ancillary species limits the application of acoustic surveys in assessing their abundance and distribution worldwide. The TS values of Scomber colias and Trachurus mediterraneus in use in the Mediterranean Sea rely on studies conducted on other species in the Atlantic and Pacific oceans. Nevertheless, the application of backscattering models offers the possibility to overcome the absence of empirical data handling the parameters that most affect the TS. X-ray scans were performed on 82 specimens to get digital representations of the swimbladder and the fish body which were used as input for the application of the Kirchhoff Ray Mode model to measure the TS as a function of frequency and tilt angle. The morphometric differences between the two species produced divergent relative frequency responses and broadband TS patterns. Moreover, comparing the results with one ex-situ experiment, we found a good agreement considering a mean tilt angle of − 10°, standard deviation = 12°. Our results provide the first theoretical insights into the use of backscattering models as a tool to distinguish between species in the Mediterranean Sea by acoustic method, increasing the knowledge of the acoustic reflectivity of ancillary species.
Ultrastructural features mirror metabolic derangement in human endothelial cells exposed to high glucose
Authors: Scrimieri Roberta , Locatelli Laura , Cazzaniga Alessandra , Cazzola Roberta , Malucelli Emil , Sorrentino Andrea , Iotti Stefano , Maier Jeanette A.
Published: September 2023

High glucose-induced endothelial dysfunction is the early event that initiates diabetes-induced vascular disease. Here we employed Cryo Soft X-ray Tomography to obtain three-dimensional maps of high d-glucose-treated endothelial cells and their controls at nanometric spatial resolution. We then correlated ultrastructural differences with metabolic rewiring. While the total mitochondrial mass does not change, high d-glucose promotes mitochondrial fragmentation, as confirmed by the modulation of fission–fusion markers, and dysfunction, as demonstrated by the drop of membrane potential, the decreased oxygen consumption and the increased production of reactive oxygen species. The 3D ultrastructural analysis also indicates the accumulation of lipid droplets in cells cultured in high d-glucose. Indeed, because of the decrease of fatty acid β-oxidation induced by high d-glucose concentration, triglycerides are esterified into fatty acids and then stored into lipid droplets. We propose that the increase of lipid droplets represents an adaptive mechanism to cope with the overload of glucose and associated oxidative stress and metabolic dysregulation.
Machine learning approaches for biomarker discovery to predict large-artery atherosclerosis
Authors: Sun Ting-Hsuan , Wang Chia-Chun , Wu Ya-Lun , Hsu Kai-Cheng , Lee Tsong-Hai
Published: September 2023

Large-artery atherosclerosis (LAA) is a leading cause of cerebrovascular disease. However, LAA diagnosis is costly and needs professional identification. Many metabolites have been identified as biomarkers of specific traits. However, there are inconsistent findings regarding suitable biomarkers for the prediction of LAA. In this study, we propose a new method integrates multiple machine learning algorithms and feature selection method to handle multidimensional data. Among the six machine learning models, logistic regression (LR) model exhibited the best prediction performance. The value of area under the receiver operating characteristic curve (AUC) was 0.92 when 62 features were incorporated in the external validation set for the LR model. In this model, LAA could be well predicted by clinical risk factors including body mass index, smoking, and medications for controlling diabetes, hypertension, and hyperlipidemia as well as metabolites involved in aminoacyl-tRNA biosynthesis and lipid metabolism. In addition, we found that 27 features were present among the five adopted models that could provide good results. If these 27 features were used in the LR model, an AUC value of 0.93 could be achieved. Our study has demonstrated the effectiveness of combining machine learning algorithms with recursive feature elimination and cross-validation methods for biomarker identification. Moreover, we have shown that using shared features can yield more reliable correlations than either model, which can be valuable for future identification of LAA.
The minimal SUF system is not required for Fe–S cluster biogenesis in the methanogenic archaeon Methanosarcina acetivorans
Authors: Saini Jasleen , Deere Thomas M. , Lessner Daniel J.
Published: September 2023

Iron–sulfur (Fe–S) proteins are essential for the ability of methanogens to carry out methanogenesis and biological nitrogen fixation (diazotrophy). Nonetheless, the factors involved in Fe–S cluster biogenesis in methanogens remain largely unknown. The minimal SUF Fe–S cluster biogenesis system (i.e., SufBC) is postulated to serve as the primary system in methanogens. Here, the role of SufBC in Methanosarcina acetivorans, which contains two sufCB gene clusters, was investigated. The CRISPRi-dCas9 and CRISPR-Cas9 systems were utilized to repress or delete sufC1B1 and sufC2B2, respectively. Neither the dual repression of sufC1B1 and sufC2B2 nor the deletion of both sufC1B1 and sufC2B2 affected the growth of M. acetivorans under any conditions tested, including diazotrophy. Interestingly, deletion of only sufC1B1 led to a delayed-growth phenotype under all growth conditions, suggesting that the deletion of sufC2B2 acts as a suppressor mutation in the absence of sufC1B1. In addition, the deletion of sufC1B1 and/or sufC2B2 did not affect the total Fe–S cluster content in M. acetivorans cells. Overall, these results reveal that the minimal SUF system is not required for Fe–S cluster biogenesis in M. acetivorans and challenge the universal role of SufBC in Fe–S cluster biogenesis in methanogens.