bluuebunny/crossref_metadata_2025 huggingface dataset:
High-repetition-rate strong-field terahertz source by optical rectification in DSTMS crystals
Authors: Zheng Zhuorui , Wang Kang , Li Hongyang , Meng Xianze , Tian Ye , Song Liwei
Published: November 2024

We present the generation of high-repetition-rate strong-field terahertz (THz) pulses from a thin 4-N,N-dimethylamino-4’-N’-methyl-stilbazolium 2,4,6-trimethylbenzenesulfonate (DSTMS) organic crystal pumped by an ytterbium-doped yttrium aluminum garnet laser. The generated THz pulse energy reaches 932.8 nJ at 1 kHz repetition rate, with a conversion efficiency of 0.19% and a peak electric field of 819 kV/cm. At a repetition rate of 10 kHz, it is able to maintain a peak electric field of 236 kV/cm and an average THz power of 0.77 mW. The high-repetition-rate, strong-field THz source provides a convenient tool for the study of THz matter manipulation and THz spectroscopy.
A Speechless Monarch: Early China’s Battle for Intellectual Authority
Authors: Pines Yuri
Published: November 2024

Although the earliest political text from early China, namely the Canon of Documents, comprises speeches attributed to ancient kings, for most of the Eastern Zhou period (770–255 BCE) monarchs remained conspicuously silent. This article surveys the instances of the rulers’ speeches in major historical collections and a sample of philosophical texts from the Warring States period. I demonstrate that the rulers’ voice in these texts is overwhelmingly confined to short questions, approval of proposed policies, or other insignificant uttering. I argue that this silence was deliberately built into the texts by their composers, so as to preserve the intellectual authority in the hands of the educated elite. It was only with the imperial unification of 221 BCE and the dramatic change in the balance of power between the emperors and the intellectuals that the royal speech regained its prominence and political importance.
Сircinaria ucrainica sp. nov., a new species from sand dunes of the Lower Dnipro valley (Ukraine)
Authors: Khodosovtsev Alexander , Darmostuk Valerii , Dembicz Iwona , Dengler Jürgen , Moysiyenko Ivan , Kuzemko Anna
Published: November 2024

During a recent expedition of the Eurasian Dry Grassland Group in the steppes of southern Ukraine, we discovered on sand dunes a new sterile crustose aspicilioid lichen with rhizomorphs. It is described here as new to science under the name Circinaria ucrainica (Megasporaceae). The new combination Circinaria reptans (Looman) Khodos. & Darmostuk is also proposed. Circinaria ucrainica is characterized by small grey areoles with a net of dark grey to brownish spicate prothalline tips and pale rhizomorphs. According to the phylogenetic analysis, the new species is closely related to the terricolous Circinaria reptans, but the latter has thicker rhizomorphs of 200–400 μm diameter, finely developed areoles and lacks spicate prothalline tips. Furthermore, we discuss the differences between the new species and other morphologically similar species with rhizomorphs, such as Aspicilia spicata, Circinaria crespiana and C. reptans. The ecological characters of soil and vegetation, including vascular plants, bryophytes and lichens, are provided for the habitat of C. ucrainica.
Statistical Properties of Quasi‐Periodic Electromagnetic Ion Cyclotron Waves: ULF Modulation Effects
Authors: Shahid Muhammad , Bashir M. Fraz , Artemyev A. V. , Zhang X.‐J. , Angelopoulos Vassilis , Murtaza G.
Published: November 2024

Electromagnetic ion cyclotron (EMIC) waves effectively scatter relativistic electrons in Earth's radiation belts and energetic ions in the ring current. Empirical models parameterizing the EMIC wave characteristics are important elements of inner magnetosphere simulations. Two main EMIC wave populations included in such simulations are the population generated by plasma sheet injections and another population generated by magnetospheric compression due to the solar wind. In this study, we investigate a third class of EMIC waves, generated by hot plasma sheet ions modulated by compressional ultra‐low frequency (ULF) waves. Such ULF‐modulated EMIC waves are mostly observed on the dayside, between magnetopause and the outer radiation belt edge. We show that ULF‐modulated EMIC waves are weakly oblique (with a wave normal angle ) and narrow‐banded (with a spectral width of of the mean frequency). We construct an empirical model of the EMIC wave characteristics as a function of ‐shell and MLT. The low ratio of electron plasma frequency to electron gyrofrequency around the EMIC wave generation region does not allow these waves to scatter energetic electrons. However, these waves provide very effective (comparable to strong diffusion) quasi‐periodic precipitation of plasma sheet protons.
Variation of the Altitude of Auroral Emission During a Substorm Cycle: Stereoscopic Optical Observations During the LAMP Rocket Experiment
Authors: Hosokawa K. , Miyoshi Y. , Mcharg M. , Ledvina V. , Hampton D. , Lessard M. , Shumko M. , Asamura K. , Sakanoi T. , Mitani T. , Namekawa T. , Nosé M. , Ogawa Y. , Jaynes A. , Halford A.
Published: November 2024

We estimated the altitude of aurora by combining data from all‐sky cameras at multiple places which were obtained during the LAMP sounding rocket experiment in Alaska on 5 March 2022. During the launch window of the rocket, three high‐speed all‐sky cameras were operative at three stations immediately below the trajectory of the rocket: Poker Flat, Venetie and Fort Yukon. The all‐sky cameras captured all‐sky images with a temporal resolution of 100 Hz (80 Hz for the Fort Yukon case). The method of altitude determination is based on analyses of time‐series of the optical intensity obtained from the all‐sky cameras in Venetie and Poker Flat covering the downrange area of the rocket trajectory. The estimated altitude of pulsating aurora during the rocket experiment was found to be consistent with that derived from the in‐situ observation of precipitating electrons with a model of optical emission, which confirms the feasibility of deriving the emission altitude through correlation analyses using time‐series. The estimated altitude of aurora decreased after the expansion onset of the substorm and stayed slightly below 100 km during the interval of pulsating aurora in the recovery phase. In particular, prompt and brief lowering of the auroral emission, well down to around 90 km, was detected during a transition of auroral form from discrete to diffuse which occurred ∼10 min after the onset. This result implies an existence of a process causing harder electron precipitation operative soon after the start of the expansion phase of auroral substorm.
LncRNA MALAT1 promotes Erastin-induced ferroptosis in the HBV-infected diffuse large B-cell lymphoma
Authors: Bai Xiaofei , Li Jianguo , Guo Xuecong , Huang Yinghui , Xu Xu , Tan Ailing , Jia Yisha , Sun Qiaoyi , Guo Xudong , Chen Jie , Kang Jiuhong
Published: November 2024

In a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX’s role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.
Cancer cells sense solid stress to enhance metastasis by CKAP4 phase separation-mediated microtubule branching
Authors: Sun Xing , Zhou Yangyang , Sun Shengjie , Qiu Siyuan , Peng Menglan , Gong Han , Guo Junxiao , Wen Chengcai , Zhang Yibin , Xie Yifang , Li Hui , Liang Long , Luo Guoyan , Wu Wencan , Liu Jing , Tan Weihong , Ye Mao
Published: November 2024

Solid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid–liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Cav1.2-dependent calcium influx, which collectively remodels microtubules. These findings reveal an unprecedented mechanism of how cancer cells sense solid stress for cancer malignancy and bridge the gap between cancer physics and cancer cell biology.
Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial
Authors: Baretti Marina , Danilova Ludmila , Durham Jennifer N. , Betts Courtney B. , Cope Leslie , Sidiropoulos Dimitrios N. , Tandurella Joseph A. , Charmsaz Soren , Gross Nicole , Hernandez Alexei , Ho Won Jin , Thoburn Chris , Walker Rosalind , Leatherman James , Mitchell Sarah , Christmas Brian , Saeed Ali , Gaykalova Daria A. , Yegnasubramanian Srinivasan , Fertig Elana J. , Coussens Lisa M. , Yarchoan Mark , Jaffee Elizabeth , Azad Nilofer S.
Published: November 2024

Pancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors to ICI therapy. This phase II study combined entinostat with nivolumab (PD1 inhibitor) in patients with advanced PDA (NCT03250273). Patients received entinostat 5 mg orally once weekly for 14-day lead-in, followed by entinostat and nivolumab. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. Secondary endpoints included safety, duration of response, progression free-survival and overall survival. Between November 2017 and November 2020, 27 evaluable patients were enrolled. Three showed partial responses (11% ORR, 95% CI, 2.4%-29.2%) with a median response duration of 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were, respectively, 1.89 (95% CI, 1.381-2.301) and 2.729 (95% CI, 1.841-5.622) months. Grade ≥3 treatment-related adverse events occurred in 19 patients (63%), including decreased lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. As exploratory analysis, peripheral and tumor immune profiles changes were assessed using CyTOF, mIHC, and RNA-seq. Entinostat increased dendritic cell activation and maturation. Gene expression analysis revealed an enrichment in inflammatory response pathways with combination treatment. Although the primary endpoint was not met, entinostat and nivolumab showed durable responses in a small subset of PDA patients. Myeloid cell immunomodulation supported the preclinical hypothesis, providing a basis for future combinatorial therapies to enhance clinical benefits in PDA.
Mechanically Tunable, Compostable, Healable and Scalable Engineered Living Materials
Authors: Manjula-Basavanna Avinash , Duraj-Thatte Anna M. , Joshi Neel S.
Published: November 2024

Advanced design strategies are essential to realize the full potential of engineered living materials, including their biodegradability, manufacturability, sustainability, and ability to tailor functional properties. Toward these goals, we present mechanically engineered living material with compostability, healability, and scalability – a material that integrates these features in the form of a stretchable plastic that is simultaneously flushable, compostable, and exhibits the characteristics of paper. This plastic/paper-like material is produced in scalable quantities (0.5–1 g L−1), directly from cultured bacterial biomass (40%) containing engineered curli protein nanofibers. The elongation at break (1–160%) and Young’s modulus (6-450 MPa) is tuned to more than two orders of magnitude. By genetically encoded covalent crosslinking of curli nanofibers, we increase the Young’s modulus by two times. The designed engineered living materials biodegrade completely in 15–75 days, while its mechanical properties are comparable to petrochemical plastics and thus may find use as compostable materials for primary packaging.
Sequence variants associated with BMI affect disease risk through BMI itself
Authors: Einarsson Gudmundur , Thorleifsson Gudmar , Steinthorsdottir Valgerdur , Zink Florian , Helgason Hannes , Olafsdottir Thorhildur , Rognvaldsson Solvi , Tragante Vinicius , Ulfarsson Magnus O. , Sveinbjornsson Gardar , Snaebjarnarson Audunn S. , Einarsson Hafsteinn , Aegisdottir Hildur M. , Jonsdottir Gudrun A. , Helgadottir Anna , Gretarsdottir Solveig , Styrkarsdottir Unnur , Arnason Hannes K. , Bjarnason Ragnar , Sigurdsson Emil , Arnar David O. , Bjornsson Einar S. , Palsson Runolfur , Bjornsdottir Gyda , Stefansson Hreinn , Thorgeirsson Thorgeir , Sulem Patrick , Thorsteinsdottir Unnur , Holm Hilma , Gudbjartsson Daniel F. , Stefansson Kari
Published: November 2024

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it’s unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk.
Leveraging ancient DNA to uncover signals of natural selection in Europe lost due to admixture or drift
Authors: Pandey Devansh , Harris Mariana , Garud Nandita R. , Narasimhan Vagheesh M.
Published: November 2024

Large ancient DNA (aDNA) studies offer the chance to examine genomic changes over time, providing direct insights into human evolution. While recent studies have used time-stratified aDNA for selection scans, most focus on single-locus methods. We conducted a multi-locus genotype scan on 708 samples spanning 7000 years of European history. We show that the G12 statistic, originally designed for unphased diploid data, can effectively detect selection in aDNA processed to create ‘pseudo-haplotypes’. In simulations and at known positive control loci (e.g., lactase persistence), G12 outperforms the allele frequency-based selection statistic, SweepFinder2, previously used on aDNA. Applying our approach, we identified 14 candidate regions of selection across four time periods, with half the signals detectable only in the earliest period. Our findings suggest that selective events in European prehistory, including from the onset of animal domestication, have been obscured by neutral processes like genetic drift and demographic shifts such as admixture.
Shareable artificial intelligence to extract cancer outcomes from electronic health records for precision oncology research
Authors: Kehl Kenneth L. , Jee Justin , Pichotta Karl , Paul Morgan A. , Trukhanov Pavel , Fong Christopher , Waters Michele , Bakouny Ziad , Xu Wenxin , Choueiri Toni K. , Nichols Chelsea , Schrag Deborah , Schultz Nikolaus
Published: November 2024

Databases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes from individual EHRs. However, patient privacy restrictions have historically precluded dissemination of these models beyond the centers at which they were trained. In this study, the vulnerability of text classification models trained directly on protected health information to membership inference attacks is confirmed. A teacher-student distillation approach is applied to develop shareable models for annotating outcomes from imaging reports and medical oncologist notes. ‘Teacher’ models trained on EHR data from Dana-Farber Cancer Institute (DFCI) are used to label imaging reports and discharge summaries from the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. ‘Student’ models are trained to use these MIMIC documents to predict the labels assigned by teacher models and sent to Memorial Sloan Kettering (MSK) for evaluation. The student models exhibit high discrimination across outcomes in both the DFCI and MSK test sets. Leveraging private labeling of public datasets to distill publishable clinical AI models from academic centers could facilitate deployment of machine learning to accelerate precision oncology research.
HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling
Authors: Erinjeri Annmary Paul , Wang Xunyan , Williams Rhianna , Chiozzi Riccardo Zenezini , Thalassinos Konstantinos , Labbadia Johnathan
Published: November 2024

Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways.
A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA
Authors: Li Yinglei , Zheng Ran , Jiang Lai , Yan Chenchao , Liu Ran , Chen Luyi , Jin Wenwen , Luo Yuanyuan , Zhang Xiafei , Tang Jun , Dai Zhe , Jiang Wei
Published: November 2024

Human genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression. Consistently, inducible FOXA2 overexpression could phenocopy the differentiation defect. More importantly, mice carrying risk-G exhibit abnormal pancreatic islet architecture and are more sensitive to streptozotocin or a high-fat diet to develop into diabetes eventually. This study not only identifies a causal noncoding variant in diabetes susceptibility but also dissects the underlying gain-of-function mechanism by recruiting stage-specific factors.
Sea-level rise and extreme Indian Ocean Dipole explain mangrove dieback in the Maldives
Authors: Carruthers Lucy , Ersek Vasile , Maher Damien , Sanders Christian , Tait Douglas , Soares Juliano , Floyd Matthew , Hashim Aminath Shaha , Helber Stephanie , Garnett Mark , East Holly , Johnson Jamie A. , Ponta Gheorghe , Sippo James Z.
Published: November 2024

Mangrove forests enhance Small Island Developing States’ resilience to climate change, yet in 2020, a mangrove dieback impacted ~ 25% of mangrove-containing islands in the Maldives. Using remote sensing, dendrology and sediment geochemistry, we document a significant decrease in mangrove health post-2020 (NDVI: 0.75 ± 0.09) compared to pre-2020 (0.85 ± 0.04; P < 0.0001). Dead trees showed reduced stomatal conductance (δ13C: − 26.21 ± 0.11 ‰) relative to living ones (− 27.66 ± 0.14 ‰), indicating salinity stress. Critically, sea-level rise (30.50 ± 23.30 mm/year) outpaced mangrove sediment accretion (6.40 ± 0.69 mm/year) five-fold between 2017 and 2020. We attribute this dieback to salinity stress driven by record-high sea levels in 2020, linked to an extreme positive Indian Ocean Dipole event. These findings reveal the vulnerability of mangrove ecosystems to rapid sea-level rise and highlights the urgent need for adaptive conservation strategies in Small Island Developing States.
Generating bat primary and immortalised cell-lines from wing biopsies
Authors: Alcock Dominic , Power Sarahjane , Hogg Bridget , Sacchi Carlotta , Kacprzyk Joanna , McLoughlin Sarah , Bertelsen Mads Frost , Fletcher Nicola F. , O’Riain Aidan , Teeling Emma C.
Published: November 2024

Bats are becoming recognised as new model species to study naturally evolved mammalian extended healthspan and disease tolerance. However, this research is limited by the lack of bat specific cellular resources. Here we describe an optimised protocol to develop both primary and immortalised fibroblast cell-lines from wing biopsy punches from the Egyptian fruit bat, Rousettus aegyptiacus. We show that the immortalised cell lines and primary cells show similar characteristics in their proliferative capacity and response to oxidative stress. They also exhibited a similar response in their NF-κB immune response to TLR agonists including SARS-CoV2. As wing punches can be acquired non-lethally, these methods can be used to develop primary and immortalised cells, from potentially any bat species, including those of conservation concern that cannot be sacrificed. This can expand the scope of bat species that can be studied in the future, and the development of key cellular resources required to functionally validate the regulators of bats’ unique longevity.
Correlative light and soft X-ray tomography of in situ mesoscale heterochromatin structure in intact cells
Authors: Gupta Rajshikhar , Goswami Yagyik , Yuan Luezhen , Roy Bibhas , Pereiro Eva , Shivashankar GV
Published: November 2024

Heterochromatin organization is critical to many genome-related programs including transcriptional silencing and DNA repair. While super-resolution imaging, electron microscopy, and multiomics methods have provided indirect insights into the heterochromatin organization, a direct measurement of mesoscale heterochromatin ultrastructure is still missing. We use a combination of correlative light microscopy and cryo-soft X-ray tomography (CLXT) to analyze heterochromatin organization in the intact hydrated state of human mammary fibroblast cells. Our analysis reveals that the heterochromatin ultra-structure has a typical mean domain size of approximately 80 nm and a mean separation of approximately 120 nm between domains. Functional perturbations yield further insights into the molecular density and alterations in the mesoscale organization of the heterochromatin regions. Furthermore, our polymer simulations provide a mechanistic basis for the experimentally observed size and separation distributions of the mesoscale chromatin domains. Collectively, our results provide direct, label-free observation of heterochromatin organization in the intact hydrated state of cells.
Nutritional education on health beliefs, metabolic profiles, and quality of life among high-risk pregnant women for gestational diabetes mellitus: a randomized controlled trial
Authors: Sharifat Robab , Borazjani Fatemeh , Araban Marzieh , Pakpour Amir H. , Angali Kambiz Ahmadi , Aiiashi Saleh
Published: November 2024

In recent years, nutrition has become increasingly important in treating and managing gestational diabetes mellitus. The Health Belief Model (HBM) is a conceptual framework in health behavior research used in some medical research. The present study aimed to evaluate the effect of glycemic index training based on the HBM on metabolic indicators and pregnant women’s health-related quality of life. In this open-label, parallel-controlled randomized trial, 90 pregnant women from primary health centers in Iran were recruited and randomly assigned to either the intervention group or the control group, using a block randomization method with a block size of six. The intervention group underwent 12 weeks of nutritional education on the glycemic index and load of foodstuff. The control group only received routine health care. Valid and reliable questionnaires included demographic and prenatal information, physical activity, three days of food records, quality of life (SF-12), and HBM constructs. Fasting blood samples were taken at baseline and end of the study, to assess fasting blood glucose (FBS), fasting insulin, hs-CRP, and lipids. Eighty-four pregnant women with an age mean of 30.12 ± 4.35 completed 12 weeks of intervention. At baseline, there were no significant differences between groups in the HBM subscales (P > 0.05). However, within the intervention group, there was an increase in perceived susceptibilities (mean change 1.45 ± 4.21; P = 0.03) and cue to action (mean change: 1.22 ± 3.38; P = 0.02). In the adjusted model, the General Health subscale of Quality of Life showed a significant increase in the comparison between groups (mean change 13.69 ± 29.83 vs. 0.00 ± 29.58; P = 0.04). Additionally, the adjusted model revealed a notable difference between the groups in serum hs-CRP level, (mean change -0.877 ± 3.47 vs. -0.067 ± 3.40; P = 0.01) and triglyceride level (mean change − 55.24 ± 111.21 vs. 40.92 ± 142.01; P = 0.001). However, in the adjusted model, the total cholesterol levels increased between groups (mean change 22.75 ± 66.17 vs. 30.12 ± 61.33; P = 0.01) at the end of the study. There was no significant difference in glycemic indices (P > 0.05). Participation in a nutrition education program might positively impact nutritional beliefs, behaviors, and some biochemical indicators among pregnant women. Future studies with larger sample sizes and longer follow-ups are warranted.

Trial registration number: IRCTID: IRCT20190227042858N1. Registration date: 2019-07-18.
Accuracy and reliability of accelerometer-based pedometers in step counts during walking, running, and stair climbing in different locations of attachment
Authors: Pan Jiahao , Wei Shutao
Published: November 2024

This study aimed to investigate the accuracy and reliability of accelerometer-based pedometers placed on the wrist, waist, and shoe’s midsole during walking, running, and stair climbing. Twenty healthy adults were recruited. Steps were recorded by the pedometers and visually assessed from simultaneously recorded video to evaluate the accuracy of each pedometer in different locations of attachment. One week later, steps were recorded again by the pedometers only to evaluate the reliability of each pedometer in different locations of attachment. The wrist-worn pedometer presented significantly greater error scores compared to the midsole-worn pedometer during walking (p < 0.001), running (p = 0.006), and stair climbing (p = 0.003). Additionally, mean absolute precent error and Bland-Altman plots indicated that the pedometer worn in the midsole was most accurate for running and stair climbing, followed by waist-worn and wrist-worn pedometers. Furthermore, the midsole-worn and waist-worn pedometers showed strong reliability during walking and running, but only the midsole-worn pedometer presented acceptable reliability during stair climbing. The pedometer’s position impacts the accuracy and reliability of step counts, especially for walking and stair climbing. Embedding the pedometer into the midsole seems an effective approach to improve the accuracy and reliability of step counts.
Prone positioning is associated with increased insulin requirements in mechanically ventilated patients with COVID-19
Authors: Griffiths Harry , Cardwell Amy , Richardson Max , Barne Meg , Petrisor Bogdan , Usman Ammara , Heales Laura , Latorre Julia Calvo , Bansiya Vishakha , Mahroof Razeen , Szakmany Tamas , Martin Daniel , Rostron Anthony , Morris Andrew Conway , Lockhart Sam
Published: November 2024

Stress hyperglycaemia is common in critical illness. We have previously observed that increasing severity of respiratory failure in patients with severe COVID-19 is associated with increased insulin demand. Given previously reported direct effects of hypoxia on insulin action, we reasoned that rapid improvements in oxygenation following prone positioning may improve insulin sensitivity and increase risk of hypoglycaemia. A retrospective multi-centre service evaluation comparing blood glucose and insulin administration in patients with COVID-19 pneumonitis receiving prone mechanical ventilation, comparing the 16 h pre-prone and 16 h post-prone time periods. 155 patients were included in this analysis. Oxygenation improved significantly following prone positioning (change in SpO2/FIO2 per hour prone: 3.01 ± 0.14, P < 0.0001). Glycaemic control was similar during the supine and prone study periods, and there were no hypoglycaemic events in the prone study period. Prone positioning was associated with an unexpected modest but significant increase in insulin requirements (mean difference in total insulin dose (IU): 8.32 ± 2.14, P < 0.001) that was robust to several sensitivity analyses, and could not be explained by changes in carbohydrate intake. We did not observe an increased rate of hypoglycaemia during prone ventilation and the adequacy of glycaemic control was comparable during the supine and prone study periods. Unexpectedly, prone ventilation was associated with an increase in insulin requirements despite significant improvement in hypoxaemia. Our findings support the safety of prone ventilation with respect to glycaemic control and identify a novel relationship between ventilation position and insulin requirements in critical illness.
Lineup position affects guessing-based selection but not culprit-presence detection in simultaneous and sequential lineups
Authors: Mayer Carolin , Bell Raoul , Menne Nicola Marie , Buchner Axel
Published: November 2024

The two-high threshold eyewitness identification model was applied to investigate the effects of lineup position on the latent cognitive processes underlying eyewitness responses in lineups. In two experiments with large sample sizes and random assignment of culprits and innocent suspects to all possible lineup positions, we examined how detection-based and non-detection-based processes vary across the positions of six-person photo lineups. Experiment 1 (N = 2586) served to investigate position effects in simultaneous lineups in which all photos were presented in a single row. Experiment 2 (N = 2581) was focused on sequential lineups. In both experiments, lineup position had no effect on the detection of the presence of the culprit. Guessing-based selection, in contrast, differed as a function of lineup position. Specifically, a lineup member placed in the first position in a lineup was significantly more likely to be selected based on guessing than lineup members placed in other positions. These results justify the practice of avoiding to place the suspect in the first position in a lineup, as this placement increases the suspect’s chance of being selected based on guessing.
Motion-induced blindness shows spatial anisotropies in conscious perception
Authors: Sárközy András , Robinson Jonathan E. , Kovács Gyula
Published: November 2024

Polar angle asymmetries (PAAs), the differences in perceptual experiences and performance across different regions of the visual field are present in various paradigms and tasks of visual perception. Currently, research in this area is sparse, particularly regarding the influence of PAAs during perceptual illusions, highlighting a gap in visual cognition studies. We aim to fill this gap by measuring PAAs across the visual field during an illusion applied to test conscious vision widely. Motion-induced blindness (MIB) is an illusion when a peripheral target disappears from consciousness as the result of a continuously moving background pattern. During MIB we separately measured the average disappearance time of peripheral targets in eight equidistant visual field positions. Our results indicate a significant variation in MIB disappearance times and frequencies as a function of target location. Specifically, we found shorter and fewer disappearances along the cardinal compared to oblique directions, and along the horizontal compared to the vertical meridian. Our results suggest specific consistencies between visual field asymmetries and conscious visual perception.
Liver transcriptomics-metabolomics integration reveals biological pathways associated with fetal programming in beef cattle
Authors: Polizel Guilherme Henrique Gebim , Fanalli Simara Larissa , Diniz Wellison J. S. , Cesar Aline Silva Mello , Cônsolo Nara Regina Brandão , Fukumasu Heidge , Cánovas Angela , Fernandes Arícia Christofaro , Prati Barbara Carolina Teixeira , Furlan Édison , Pombo Gabriela do Vale , Santana Miguel Henrique de Almeida
Published: November 2024

We investigated the long-term effects of prenatal nutrition on pre-slaughter Nelore bulls using integrative transcriptome and metabolome analyses of liver tissue. Three prenatal nutritional treatments were administered to 126 cows: NP (control, mineral supplementation only), PP (protein-energy supplementation in the third trimester), and FP (protein-energy supplementation throughout pregnancy). Liver samples from 22.5 ± 1-month-old bulls underwent RNA-Seq and targeted metabolomics. Weighted correlation network analysis (WGCNA) identified treatment-associated gene and metabolite co-expression modules, further analyzed using MetaboAnalyst 6.0 (metabolite over-representation analysis and transcriptome-metabolome integrative analysis) and Enrichr (gene over-representation analysis). We identified several significant gene and metabolite modules, as well as hub components associated with energy, protein and oxidative metabolism, regulatory mechanisms, epigenetics, and immune function. The NP transcriptome-metabolome analysis identified key pathways (aminoacyl t-RNA biosynthesis, gluconeogenesis, and PPAR signaling) and hub components (glutamic acid, SLC6A14). PP highlighted pathways (arginine and proline metabolism, TGF-beta signaling, glyoxylate and dicarboxylate metabolism) with arginine and ODC1 as hub components. This study highlights the significant impact of prenatal nutrition on the liver tissue of Nelore bulls, shedding light on critical metabolic pathways and hub components related to energy and protein metabolism, as well as immune system and epigenetics.
A statistical mechanics investigation of unfolded protein response across organisms
Authors: Luchetti Nicole , Smith Keith M. , Matarrese Margherita A. G. , Loppini Alessandro , Filippi Simonetta , Chiodo Letizia
Published: November 2024

Living systems rely on coordinated molecular interactions, especially those related to gene expression and protein activity. The Unfolded Protein Response is a crucial mechanism in eukaryotic cells, activated when unfolded proteins exceed a critical threshold. It maintains cell homeostasis by enhancing protein folding, initiating quality control, and activating degradation pathways when damage is irreversible. This response functions as a dynamic signaling network, with proteins as nodes and their interactions as edges. We analyze these protein-protein networks across different organisms to understand their intricate intra-cellular interactions and behaviors. In this work, analyzing twelve organisms, we assess how fundamental measures in network theory can individuate seed proteins and specific pathways across organisms. We employ network robustness to evaluate and compare the strength of the investigated protein-protein interaction networks, and the structural controllability of complex networks to find and compare the sets of driver nodes necessary to control the overall networks. We find that network measures are related to phylogenetics, and advanced network methods can identify main pathways of significance in the complete Unfolded Protein Response mechanism.
Facial Image expression recognition and prediction system
Authors: Talukder Animesh , Ghosh Surath
Published: November 2024

Facial expression recognition system is an advanced technology that allows machines to recognize human emotions based on their facial expressions. In order to develop a robust prediction model, this research work proposes three distinct architectural models to produce a facial expression prediction system that looks like this: The first model is on using a support vector machine to carry out a classification task. As a follow-up to the second model, an attempt was made to create a Convolution Neural Network (CNN) using the VGG-NET (Visual Geometry Group Network). Following analysis of the results, an attempt was made to enhance the outcome using the third model, which used convolutional sequential layers linked to seven distinct expressions, and an inference was drawn based on loss and accuracy metric behavior. We will use a dataset of human picture facial images in this research, which has more than 35500 facial photographs and represents seven different types of facial expressions. We will analyze our data and make every effort to remove as much noise as we can before feeding that information to our model. We use the confusion matrix to assess the model’s performance after it has been implemented effectively. To demonstrate the effectiveness of our model architecture, we will generate bar graphs and scatter plots for each model to display model loss and accuracy. The output of this model is visualized with actual class and predictive class and the result has a graphical representation for each and every output facial Images which makes our recognition system user-friendly.
Brain imaging and machine learning reveal uncoupled functional network for contextual threat memory in long sepsis
Authors: Strohl Joshua J. , Carrión Joseph , Huerta Patricio T.
Published: November 2024

Positron emission tomography (PET) utilizes radiotracers like [18F]fluorodeoxyglucose (FDG) to measure brain activity in health and disease. Performing behavioral tasks between the FDG injection and the PET scan allows the FDG signal to reflect task-related brain networks. Building on this principle, we introduce an approach called behavioral task–associated PET (beta-PET) consisting of two scans: the first after a mouse is familiarized with a conditioning chamber, and the second upon recall of contextual threat. Associative threat conditioning occurs between scans. Beta-PET focuses on brain regions encoding threat memory (e.g., amygdala, prefrontal cortex) and contextual aspects (e.g., hippocampus, subiculum, entorhinal cortex). Our results show that beta-PET identifies a biologically defined network encoding contextual threat memory and its uncoupling in a mouse model of long sepsis. Moreover, machine learning algorithms (linear logistic regression) and ordinal trends analysis demonstrate that beta-PET robustly predicts the behavioral defense response and its breakdown during long sepsis.
A comparative study to elucidate factors explaining willingness to use home-care robots in Japan, Ireland, and Finland
Authors: Ide Hiroo , Suwa Sayuri , Akuta Yumi , Kodate Naonori , Tsujimura Mayuko , Ishimaru Mina , Shimamura Atsuko , Kitinoja Helli , Donnelly Sarah , Hallila Jaakko , Toivonen Marika , Bergman-Kärpijoki Camilla , Takahashi Erika , Yu Wenwei
Published: November 2024

The implementation of home-care robots is sometimes unsuccessful. This study aimed to explore factors explaining people’s willingness to use home-care robots, particularly among care recipients and caregivers. Surveys were conducted in Japan, Ireland, and Finland. The survey questionnaire comprised four categories (familiarity with robots, important points about home-care robots, functions expected from home-care robots, and ethically acceptable uses), with 48 items assessing users’ willingness to use home-care robots. The responses from 525 Japanese, 163 Irish, and 170 Finnish respondents were analyzed to identify common and distinct factors influencing their willingness to use these robots. Common factors across the countries included “willingness to participate in research and development,” “interest in robot-related news,” and “having a positive impression of robots”. The distinct factors for each country were: “convenience” in Japan; “notifying family members and support personnel when an unexpected change occurs in an older person” in Ireland; and “design” in Finland. Therefore, developers should determine potential users’ willingness to participate in the research and development of home-care robots and consider a system that involves them in the development process.
Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages
Authors: Howard Laura , Ishikawa Yuki , Katayama Tomohiko , Park Sung-Joon , Hill Matthew J. , Blake Derek J. , Nishida Kohji , Hayashi Ryuhei , Quantock Andrew J.
Published: November 2024

The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period. We demonstrate a progression from pluripotency through to tissue specification and differentiation which encompasses both surface ectodermal and neuroectodermal ocular lineages and the generation of iPSC-derived components of the developing cornea, conjunctiva, lens, and retina. Our findings not only advance the understanding of ocular development in a stem cell-based system of human origin, but also establish a robust methodological paradigm for exploring cellular and molecular dynamics during SEAM formation at single-cell resolution and highlight the potential of hiPSC-derived systems as powerful platforms for modelling human eye development and disease.
Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii
Authors: Li Fei-Ju , Starrs Lora , Mathur Anukriti , Enosi Tuipulotu Daniel , Man Si Ming , Burgio Gaetan
Published: November 2024

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.
Dynamic processes determine precipitation variability in Eastern Central Europe since the Last Glacial Maximum
Authors: Warken Sophie F. , Riechelmann Dana F. C. , Fohlmeister Jens , Schröder-Ritzrau Andrea , Frank Norbert , Scholz Denis , Jochum Klaus P. , Mirea Ionuț-Cornel , Constantin Silviu , Spötl Christoph
Published: November 2024

The response of European precipitation variability to climate change is still poorly understood. Here we present a high-resolution speleothem record of Eastern Central European (ECE) autumn/winter precipitation to study decadal to centennial hydroclimatic variations in the European-Atlantic sector since the Last Glacial Maximum. The Cloşani Cave δ18O record shows that the reorganization of the North Atlantic jet following the demise of the Northern Hemispheric ice sheets lasted until c. 6000 to 5000 years before present. Trace element-derived semi-quantitative autumn/winter precipitation amount reveals that the late Glacial and the early to mid-Holocene experienced about 20–30% higher precipitation than present. During the deglaciation, we detect an increased decadal to centennial precipitation variability decoupled from millennial-scale North Atlantic temperature changes. The findings suggest that dynamic (rather than thermodynamic) processes determine regional precipitation variability and the probability of extreme precipitation events in ECE, highlighting the importance of understanding such dynamics for future predictions.