bluuebunny/crossref_metadata_2025 huggingface dataset:
DDCNN-F: double decker convolutional neural network 'F' feature fusion as a medical image classification framework
Authors: Veeramani Nirmala , Jayaraman Premaladha , Krishankumar Raghunathan , Ravichandran Kattur Soundarapandian , Gandomi Amir H.
Published: January 2024

Melanoma is a severe skin cancer that involves abnormal cell development. This study aims to provide a new feature fusion framework for melanoma classification that includes a novel ‘F’ Flag feature for early detection. This novel ‘F’ indicator efficiently distinguishes benign skin lesions from malignant ones known as melanoma. The article proposes an architecture that is built in a Double Decker Convolutional Neural Network called DDCNN future fusion. The network's deck one, known as a Convolutional Neural Network (CNN), finds difficult-to-classify hairy images using a confidence factor termed the intra-class variance score. These hirsute image samples are combined to form a Baseline Separated Channel (BSC). By eliminating hair and using data augmentation techniques, the BSC is ready for analysis. The network's second deck trains the pre-processed BSC and generates bottleneck features. The bottleneck features are merged with features generated from the ABCDE clinical bio indicators to promote classification accuracy. Different types of classifiers are fed to the resulting hybrid fused features with the novel 'F' Flag feature. The proposed system was trained using the ISIC 2019 and ISIC 2020 datasets to assess its performance. The empirical findings expose that the DDCNN feature fusion strategy for exposing malignant melanoma achieved a specificity of 98.4%, accuracy of 93.75%, precision of 98.56%, and Area Under Curve (AUC) value of 0.98. This study proposes a novel approach that can accurately identify and diagnose fatal skin cancer and outperform other state-of-the-art techniques, which is attributed to the DDCNN ‘F’ Feature fusion framework. Also, this research ascertained improvements in several classifiers when utilising the ‘F’ indicator, resulting in the highest specificity of + 7.34%.
Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice
Authors: de Assis Leonardo Vinicius Monteiro , Harder Lisbeth , Lacerda José Thalles , Parsons Rex , Kaehler Meike , Cascorbi Ingolf , Nagel Inga , Rawashdeh Oliver , Mittag Jens , Oster Henrik
Published: January 2024

Thyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. We explored these genes and created an expression panel that assesses liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH action under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state.
Pregnancy-induced remodeling of the murine reproductive tract: a longitudinal in vivo magnetic resonance imaging study
Authors: Suarez Aileen C. , Gimenez Clara J. , Russell Serena R. , Wang Maosen , Munson Jennifer M. , Myers Kristin M. , Miller Kristin S. , Abramowitch Steven D. , De Vita Raffaella
Published: January 2024

Mammalian pregnancy requires gradual yet extreme remodeling of the reproductive organs to support the growth of the embryos and their birth. After delivery, the reproductive organs return to their non-pregnant state. As pregnancy has traditionally been understudied, there are many unknowns pertaining to the mechanisms behind this remarkable remodeling and repair process which, when not successful, can lead to pregnancy-related complications such as maternal trauma, pre-term birth, and pelvic floor disorders. This study presents the first longitudinal imaging data that focuses on revealing anatomical alterations of the vagina, cervix, and uterine horns during pregnancy and postpartum using the mouse model. By utilizing advanced magnetic resonance imaging (MRI) technology, T1-weighted and T2-weighted images of the reproductive organs of three mice in their in vivo environment were collected at five time points: non-pregnant, mid-pregnant (gestation day: 9–10), late pregnant (gestation day: 16–17), postpartum (24–72 h after delivery) and three weeks postpartum. Measurements of the vagina, cervix, and uterine horns were taken by analyzing MRI segmentations of these organs. The cross-sectional diameter, length, and volume of the vagina increased in late pregnancy and then returned to non-pregnant values three weeks after delivery. The cross-sectional diameter of the cervix decreased at mid-pregnancy before increasing in late pregnancy. The volume of the cervix peaked at late pregnancy before shortening by 24–72 h postpartum. As expected, the uterus increased in cross-sectional diameter, length, and volume during pregnancy. The uterine horns decreased in size postpartum, ultimately returning to their average non-pregnant size three weeks postpartum. The newly developed methods for acquiring longitudinal in vivo MRI scans of the murine reproductive system can be extended to future studies that evaluate functional and morphological alterations of this system due to pathologies, interventions, and treatments.
A comparative study of language learners’ ICT attitudes and behavior pre- and post-COVID-19
Authors: Habók Anita , Nguyen Lan Anh Thuy
Published: January 2024

Along with the adoption of hybrid teaching and learning modes, the integration of ICT into language instruction in higher education during the COVID-19 pandemic has afforded teachers and students increased opportunities to engage with technology. This quantitative study uses a self-report questionnaire to examine language learners’ attitudes and behavior tied to the role of ICT in learning before and after the COVID-19 pandemic. Firstly, the study confirms the questionnaire’s validity for assessing ICT attitudes and behavior in the Hungarian educational context. Additionally, the measurement invariance and differential item functioning of the assessment tool pre- and post-COVID-19 show that attitudes and the frequency of ICT use remain consistent at both the construct and item levels. Overall, the results demonstrate significant variations between the two student groups in attitudes and behavior tied to the use of ICT tools in language learning. The findings show that the post-COVID-19 group exhibits higher attitudes, and an increased frequency of technology use is observed compared to the pre-COVID-19 period. Furthermore, the study indicates that attitudes before COVID-19 do not strongly influence habitual technology use for language learning, while the opposite is true for the post-COVID-19 period.
Quantifying motor adaptation in a sport-specific table tennis setting
Authors: Carius Daniel , Kaminski Elisabeth , Clauß Martina , Schewe Yannick , Ryk Lenja , Ragert Patrick
Published: January 2024

Studies on motor adaptation aim to better understand the remarkable, largely implicit capacity of humans to adjust to changing environmental conditions. So far, this phenomenon has mainly been investigated in highly controlled laboratory setting, allowing only limited conclusions and consequences for everyday life scenarios. Natural movement tasks performed under externally valid conditions would provide important support on the transferability of recent laboratory findings. Therefore, one major goal of the current study was to create and assess a new table tennis paradigm mapping motor adaptation in a more natural and sport-specific setting. High-speed cinematographic measurements were used to determine target accuracy in a motor adaptation table tennis paradigm in 30 right-handed participants. In addition, we investigated if motor adaptation was affected by temporal order of perturbations (serial vs. random practice). In summary, we were able to confirm and reproduce typical motor adaptation effects in a sport-specific setting. We found, according to previous findings, an increase in target errors with perturbation onset that decreased during motor adaptation. Furthermore, we observed an increase in target errors with perturbation offset (after-effect) that decrease subsequently during washout phase. More importantly, this motor adaptation phenomenon did not differ when comparing serial vs. random perturbation conditions.
Combination of high resolution MRI with 3D-printed needle guides for ex vivo myocardial biopsies
Authors: Reiss Simon , Thielmann Julien , Fischer Johannes , Lottner Thomas , Maier Alexander , Westermann Dirk , von zur Mühlen Constantin , Heidt Timo , Bock Michael
Published: January 2024

Magnetic resonance imaging (MRI) provides a multitude of techniques to detect and characterize myocardial infarction. To correlate MRI findings with histology, in most cases terminal animal studies are performed; however, precise extraction and spatial correlation of myocardial tissue samples to MRI image data is difficult. In this proof of concept study, we present a 3D-printing technique to facilitate the extraction of tissue samples from myocardial regions. Initially, seven pig hearts embedded in formaldehyde were imaged on a clinical 3 T system to define biopsy targets on high resolution ex vivo images. Magnitude images and R2*-maps acquired with a 3D multi-echo gradient echo sequence and 0.58 mm isotropic resolution were used to create digital models of the cardiac anatomy. Biopsy guides were 3D-printed to steer the extraction of myocardial samples. In total, 61 tissue samples were extracted with an average offset of the tissue sample location from the target location of 0.59 ± 0.36 mm. This offset was not dependent on the distance of the target point to the epicardial surface. Myocardial tissue could be extracted from all samples. The presented method enables extraction of myocardial tissue samples that are selected by ex vivo MRI with submillimeter precision.
Enhanced vegetable production in hydroponic systems using decontamination of closed circulating fluid
Authors: Perez Shirly Lara , Ferro Rafael Basilio , Corrêa Bruna , Casarin Rene , Corrêa Thaila Quatrini , Blanco Kate Cristina , Bagnato Vanderlei Salvador
Published: January 2024

While plant microorganisms can promote plants by producing natural antibiotics, they can also be vectors for disease transmission. Contamination from plant management practices and the surrounding environment can adversely affect plants, leading to infections and hindered growth due to microbial competition for nutrients. The recirculation of nutrient-rich fluids can facilitate the transport of microorganisms between vegetables in the hydroponic production system. This issue can be addressed through the application of the decontamination method in the hydroponic liquid. Ultraviolet light (UV-C) has been employed for microbiology, and its effects on lettuce were evaluated in this study. This study aims to assess the effectiveness of a decontamination system using UV-C in hydroponic solutions during nutrient recirculation in hydroponics. We evaluated the time required for lettuce plants to reach their maximum height, as well as their pigment content, phenolic compounds, antioxidant capacity, and micro and macronutrient levels. The evaluation was conducted under two photoperiods (18 and 20 hours) in lettuce samples exposed to UV-C in the hydroponic fluid, with control groups not exposed to UV-C. The application of the UV-C decontamination system in hydroponic circulation water containing nutrients accelerated plant growth while maintaining nutritional values equal to or higher than those in the control groups without such a system. The results of microorganism control highlight the potential application of this technique for enhancing and expediting vegetable production. This approach reduces production time and enhances nutrient absorption and the content of certain compounds and minerals.
Nonlinearity association between hyperuricemia and all-cause mortality in patients with chronic kidney disease
Authors: Liu Ya-Fei , Han Liang , Geng Yin-Hong , Wang Huan-Huan , Yan Jia-Hui , Tu Sheng-Hao
Published: January 2024

Controversy surrounds the role of serum uric acid and whether treatment intervention is favorable in retarding the progression of chronic kidney disease (CKD). The association of serum uric acid levels and CKD patient mortality risk needs to be further determined by large sample cohort studies. The National Health and Nutrition Examination Survey participants with CKD from 1998 to 2017 were enrolled in the study. Multivariable Cox regression models were used to reveal the association of serum uric acid concentrations and CKD mortality risks. A total of 9891 CKD patients were enrolled in the study, and 3698 individuals died during the follow-up. Increasing serum uric acid levels are independently relevant to higher mortality risks of CKD patients (HR per SD increase). A restricted cubic spline curve showed a nonlinear association between serum uric acid and CKD mortality risks (p for nonlinearity = 0.046). CKD patients with higher levels of serum uric acid (≥ 5.900 mg/dL) show a significant increase in mortality risks (HR = 1.102, 95% CI 1.043–1.165). Sensitivity analysis demonstrated that the results were stable and robust. High serum uric acid levels (≥ 5.900 mg/dL) may be associated with increased mortality risks in CKD patients.
Transcriptome-based biomarker prediction for Parkinson’s disease using genome-scale metabolic modeling
Authors: Abdik Ecehan , Çakır Tunahan
Published: January 2024

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Identification of PD biomarkers is crucial for early diagnosis and to develop target-based therapeutic agents. Integrative analysis of genome-scale metabolic models (GEMs) and omics data provides a computational approach for the prediction of metabolite biomarkers. Here, we applied the TIMBR (Transcriptionally Inferred Metabolic Biomarker Response) algorithm and two modified versions of TIMBR to investigate potential metabolite biomarkers for PD. To this end, we mapped thirteen post-mortem PD transcriptome datasets from the substantia nigra region onto Human-GEM. We considered a metabolite as a candidate biomarker if its production was predicted to be more efficient by a TIMBR-family algorithm in control or PD case for the majority of the datasets. Different metrics based on well-known PD-related metabolite alterations, PD-associated pathways, and a list of 25 high-confidence PD metabolite biomarkers compiled from the literature were used to compare the prediction performance of the three algorithms tested. The modified algorithm with the highest prediction power based on the metrics was called TAMBOOR, TrAnscriptome-based Metabolite Biomarkers by On–Off Reactions, which was introduced for the first time in this study. TAMBOOR performed better in terms of capturing well-known pathway alterations and metabolite secretion changes in PD. Therefore, our tool has a strong potential to be used for the prediction of novel diagnostic biomarkers for human diseases.
Continent-island boundary and environment-shaped evolution in the marine amphipod Ampithoe marcuzzii complex (Crustacea: Eumalacostraca: Ampithoidae)
Authors: Iwasa-Arai Tammy , Siqueira Silvana G. L. , Sobral-Souza Thadeu , Leite Fosca P. P. , Andrade Sónia C. S.
Published: January 2024

Marine amphipods are crustaceans that lack a larval phase and consequently have low dispersion rates. Despite that, these crustaceans present a remarkable ability to be transported by rafting on natural floating substrata, especially macroalgae, where they find shelter, food and a mating ground. The species Ampithoe marcuzzii is widely distributed throughout the western Atlantic Ocean. Here, it was used as a model to study seascape genomics and phylogeography in invertebrates with low dispersion capacities. We anticipated that the lineages would present isolation-by-distance patterns. However, surface currents and other abiotic variables could facilitate connectivity among distant sites. Based on mitochondrial and nuclear genes, SNPs, and environmental associations, we observed the presence of a species complex within A. marcuzzii, separating mainland and insular populations. Each species showed an independent evolutionary history, with a strong latitudinal population structure and evidence of isolation-by-distance and isolation-by-environment, characterizing the 'continent' species. Historical expansion and environmental variables were observed associated with the southeastern population, and ecological niche modeling corroborated the region as a paleorefuge. Conversely, populations from 'islands' presented complicated evolutionary histories, with closer localities genetically isolated and distant localities connected. These findings indicate that insular populations with low dispersion capacity might be more susceptible to spatial connectivity by floating substrata and to changes in surface currents. In contrast, mainland populations might be more vulnerable to local climate changes due to lack of gene flow.
β-Carboline (FG-7142) modulates fear but not anxiety-like behaviour in zebrafish
Authors: Scatterty Kale R. , Hamilton Trevor J.
Published: January 2024

The β-Carboline FG-7142 is a partial inverse agonist at the benzodiazepine allosteric site on the GABA-A receptor that induces anxiogenic, proconvulsant, and appetite-reducing effects in many species, including humans. Seizure-kindling effects have been well studied, however anxiogenic properties are relatively unexplored. This study aimed to investigate concentration-dependent effects of FG-7142 on anxiety-like behaviour and fear responses in zebrafish (Danio rerio) using the open-field test (OF) and novel object approach test (NOA). A U-shaped distribution was found with maximal responses in increased immobility and reduced distance moved at 10 µM in the NOA but not the OF. Follow up experiments demonstrated a lack of effect in repeated OF testing and no changes in opercular movements. Furthermore, the effect of FG-7142 was reversed with ethanol treatment. These results suggest that FG-7142 elicits a ‘freezing’ response in zebrafish via the introduction of novelty, suggesting fear-induction. These findings indicate that FG-7142 may act as an agent to promote acute fear responses in zebrafish.
Incidence and determinants of adverse events in individuals with HIV commencing Dolutegravir-based antiretroviral therapy in mainland Tanzania
Authors: Fimbo Adam , Mwalwisi Yonah H. , Mwamwitwa Kissa , Matiko Damas , Mfinanga Elirehema , Lyimo Johnson , Sabasaba Amon , Missago Seth , Bukundi Elias , Gotora Goodluck , Respick Dorice , Nkayamba Alex , Masunga Emmanuel , Mnkugwe Rajabu Hussein , Kunambi Peter P. , Munishi Castory , Musanhu Christine Chiedza , Minzi Omary M. S. , Mlugu Eulambius M.
Published: January 2024

Tanzania adopted a Dolutegravir (DTG)-based regimen as first-line treatment in 2019 following the World Health Organization recommendation. Data on the DTG safety profile from sub-Saharan Africa including Tanzania are limited. We investigated the incidence of DTG-related adverse events (AEs) and associated factors among people living with HIV (PLHIV) initiated on a DTG regimen. A prospective cohort study was conducted from 25 Care and Treatment Clinics in mainland Tanzania. PLHIV aged 12 years and above who were initiated on a DTG-based regimen were actively followed up for three months. The Cox regression model was used to determine the predictors of occurrence of AEs over time. A p-value of 0.05 was considered statistically significant. From January 2020 to June 2022, a cohort of 935 participants who were both newly diagnosed and ART-experienced who transitioned to a DTG-based regimen was enrolled. Out of 935 participants, 59 (6.3%) reported a total of 62 AEs. The most frequently experienced AE was skin itching and rashes (15/62; 24.2%). DTG-associated neuropsychiatric AEs were less common and included headache (6 [9.6%]) and sleep disturbances (3 [4.8%]). The overall incidence of occurrence of the first AEs was 96.7 per 1000 person-months [95% C.I: 74.4–125.7] with the highest incidence observed among the elderly (≥ 60 years). Individuals on WHO HIV Clinical Stage 2 had a 2.7 significantly higher risk of developing AEs (adjusted hazard ratio = 2.73, 95% CI = 1.46–5.12, p = 0.017). We report a low incidence of grade I (mild) and grade II (moderate) DTG-associated AEs suggesting that the regimen is generally safe in the population. Continued monitoring of DTG safety in the population is recommended.
Exploration of neuroprotective effect from Coriandrum sativum L. ethanolic seeds extracts on brain of obese rats
Authors: Hardiany Novi Silvia , Dewi Putri Krishna Kumara , Dewi Syarifah , Tejo Bimo A.
Published: January 2024

In this study, the potential neuroprotective ability of coriander seeds (Coriandrum sativum L.) ethanolic extract (CSES) as a neuroprotectant agent in the brains of high-fat diet-induced obese rats was analyzed. The study investigated how CSES impacts oxidative stress markers (i.e., malondialdehyde/MDA, glutathione/GSH and catalase), inflammation marker (i.e., Interleukin-6/IL-6), cellular senescence markers (i.e., senescence-associated β-galactoside/SA-β-Gal activity and p16), brain damage marker (i.e., Neuron-specific Enolase/NSE), and neurogenesis markers (i.e., mature Brain-derived Neurotropic Factor/BDNF, pro-BDNF, and mature/pro-BDNF ratio). Male adult Wistar rats were fed a high-fat diet and given CSES once daily, at 100 mg/kg body weight, for 12 weeks. CSES significantly reduced MDA concentration (p = < 0.001), SA-β-Gal activity (p = 0.010), and increased GSH concentration (p = 0.047) in the brain of obese rats; however, the decrease of IL-6, NSE, and p16 as well as the increase of catalase specific activity and BDNF expression were not significant. Moreover, the mature/pro-BDNF ratio was significantly higher in the brains of non-obese rats, both given the control diet and the high-fat diet compared to the control. Our results suggest that obese rats benefited from consuming CSES, showing improved oxidative stress levels, reduced cellular senescence and increased endogenous antioxidants, making CSES a potential neuroprotective agent.
Short-term wind speed prediction based on improved Hilbert–Huang transform method coupled with NAR dynamic neural network model
Authors: Chen Jian , Guo Zhikai , Zhang Luyao , Zhang Shanju
Published: January 2024

Wind energy, as a renewable energy source, offers the advantage of clean and pollution-free power generation. Its abundant resources have positioned wind power as the fastest-growing and most widely adopted method of electricity generation. Wind speed stands as a key characteristic when studying wind energy resources. This study primarily focuses on predictive models for wind speed in wind energy generation. The intense intermittency, randomness, and uncontrollability of wind speeds in wind power generation present challenges, leading to high development costs and posing stability challenges to power systems. Consequently, scientifically forecasting wind speed variations becomes imperative to ensure the safety of wind power equipment, maintain grid integration of wind power, and ensure the secure and stable operation of power systems. This holds significant guiding value and significance for power production scheduling institutions. Due to the complexity of wind speed, scientifically predicting its fluctuations is crucial for ensuring the safety of wind power equipment, maintaining wind power integration systems, and ensuring the secure and stable operation of power systems. This research aims to enhance the accuracy and stability of wind speed prediction, thereby reducing the costs associated with wind power generation and promoting the sustainable development of renewable energy. This paper utilizes an improved Hilbert–Huang transform (HHT) using complementary ensemble empirical mode decomposition (CEEMD) to overcome issues in the traditional empirical mode decomposition (EMD) method, such as component mode mixing and white noise interference. Such an approach not only enhances the efficiency of wind speed data processing but also better accommodates strong stochastic and nonlinear characteristics. Furthermore, by employing mathematical analytical methods to compute weights for each component, a dynamic neural network model is constructed to optimize wind speed time series modeling, aiming for a more accurate prediction of wind speed fluctuations. Finally, the optimized HHT-NAR model is applied in wind speed forecasting within the Xinjiang region, demonstrating significant improvements in reducing root mean square errors and enhancing coefficient of determination. This model not only showcases theoretical innovation but also exhibits superior performance in practical applications, providing an effective predictive tool within the field of wind energy generation.
Modulation of antioxidant defense and PSII components by exogenously applied acetate mitigates salinity stress in Avena sativa
Authors: Kappachery Sajeesh , AlHosani Mohamed , Khan Tanveer Alam , AlKharoossi Sara Nouh , AlMansoori Nemah , AlShehhi Sara Ali Saeed , AlMansoori Hamda , AlKarbi Maha , Sasi Shina , Karumannil Sameera , Elangovan Sampath Kumar , Shah Iltaf , Gururani Mayank Anand
Published: January 2024

Salinity stress has detrimental effects on various aspects of plant development. However, our understanding of strategies to mitigate these effects in crop plants remains limited. Recent research has shed light on the potential of sodium acetate as a mitigating component against salinity stress in several plant species. Here, we show the role of acetate sodium in counteracting the adverse effects on oat (Avena sativa) plants subjected to NaCl-induced salinity stress, including its impact on plant morphology, photosynthetic parameters, and gene expression related to photosynthesis and antioxidant capacity, ultimately leading to osmoprotection. The five-week experiment involved subjecting oat plants to four different conditions: water, salt (NaCl), sodium acetate, and a combination of salt and sodium acetate. The presence of NaCl significantly inhibited plant growth and root elongation, disrupted chlorophylls and carotenoids content, impaired chlorophyll fluorescence, and down-regulated genes associated with the plant antioxidant defense system. Furthermore, our findings reveal that when stressed plants were treated with sodium acetate, it partially reversed these adverse effects across all analyzed parameters. This reversal was particularly evident in the increased content of proline, thereby ensuring osmoprotection for oat plants, even under stressful conditions. These results provide compelling evidence regarding the positive impact of sodium acetate on various plant development parameters, with a particular focus on the enhancement of photosynthetic activity.
Evaluation of calcium carbide residue and fly ash as sustainable binders for environmentally friendly loess soil stabilization
Authors: Julphunthong Phongthorn , Joyklad Panuwat , Manprom Papantasorn , Chompoorat Thanakorn , Palou Martin-Tchingnabé , Suriwong Tawat
Published: January 2024

The incorporation of waste materials into cementitious binders serves as a strategy to diminish waste volume and lower carbon emissions. This study presents an in-depth evaluation of calcium carbide residue and coal fly ash as alternative binders. The assessment of raw materials emphasized their chemical composition and potential for pozzolanic reactions. Based on these factors, the optimal ratio of Ca/(SiO2 + Al2O3) in the raw materials was determined to be 1.5. Therefore, this study was designed to vary the raw material composition with a CaO/(SiO2 + Al2O3) ratio ranging from 1.7 to 0.9. Upon investigating the effect of the raw material proportion on the compressive strength of pastes and mortars, the composition yielding the highest compressive strength was selected for its potential application as a stabilizer for loess soil. A mixture of calcium carbide residue and coal fly ash with a Ca/(SiO2 + Al2O3) ratio of 1.5 resulted in the highest compressive strength at long curing periods in both pastes and mortars. Mineralogical and microstructural analyses revealed several products, beyond those formed from the pozzolanic reactions, that occurred and enhanced the compressive strength of samples. The highest performing mixture of carbide residue and coal fly ash was then used to stabilize loess soil at 10–25 wt%. The unconfined compressive strength, along with mass and strength loss due to wetting and drying cycles, was also studied. It was observed that the unconfined compressive strength of the stabilized soils remained consistent after six wet-dry cycles but decreased after twelve cycles due to microcracks. The findings suggest that carefully designed mixtures based on the chemical interactions of calcium carbide residue and coal fly ash can offer a sustainable, efficient approach for soil stabilization, potentially revolutionizing construction practices.
Unsupervised anomaly detection for earthquake detection on Korea high-speed trains using autoencoder-based deep learning models
Authors: Seo Jeonguk , Kim Yunu , Ha Jisung , Kwak Dongyoup , Ko Minsam , Yoo Mintaek
Published: January 2024

We propose a method for detecting earthquakes for high-speed trains based on unsupervised anomaly-detection techniques. In particular, we utilized autoencoder-based deep learning models for unsupervised learning using only normal training vibration data. Datasets were generated from South Korean high-speed train data, and seismic data were measured using seismometers nationwide. The proposed method is compared with the conventional Short Time Average over Long Time Average (STA/LTA) model, considering earthquake detection capabilities, focusing on a Peak Ground Acceleration (PGA) threshold of 0.07, a criterion for track derailment. The results show that the proposed model exhibit improved earthquake detection capabilities than STA/LTA for PGA of 0.07 or higher. Furthermore, the proposed model reduced false earthquake detections under normal operating conditions and accurately identified normal states. In contrast, the STA/LTA method demonstrated a high rate of false earthquake detection under normal operating conditions, underscoring its propensity for inaccurate detection in many instances. The proposed approach shows promising performance even in situations with limited seismic data and offers a viable solution for earthquake detection in regions with relatively few seismic events.
Autosurv: interpretable deep learning framework for cancer survival analysis incorporating clinical and multi-omics data
Authors: Jiang Lindong , Xu Chao , Bai Yuntong , Liu Anqi , Gong Yun , Wang Yu-Ping , Deng Hong-Wen
Published: January 2024

Accurate prognosis for cancer patients can provide critical information for optimizing treatment plans and improving life quality. Combining omics data and demographic/clinical information can offer a more comprehensive view of cancer prognosis than using omics or clinical data alone and can also reveal the underlying disease mechanisms at the molecular level. In this study, we developed and validated a deep learning framework to extract information from high-dimensional gene expression and miRNA expression data and conduct prognosis prediction for breast cancer and ovarian-cancer patients using multiple independent multi-omics datasets. Our model achieved significantly better prognosis prediction than the current machine learning and deep learning approaches in various settings. Moreover, an interpretation method was applied to tackle the “black-box” nature of deep neural networks and we identified features (i.e., genes, miRNA, demographic/clinical variables) that were important to distinguish predicted high- and low-risk patients. The significance of the identified features was partially supported by previous studies.
Paneth-like cells produced from OLFM4+ stem cells support OLFM4+ stem cell growth in advanced colorectal cancer
Authors: Sakahara Mizuho , Okamoto Takuya , Srivastava Upasna , Natsume Yasuko , Yamanaka Hitomi , Suzuki Yutaka , Obama Kazutaka , Nagayama Satoshi , Yao Ryoji
Published: January 2024

Tumor tissues consist of heterogeneous cells that originate from stem cells; however, their cell fate determination program remains incompletely understood. Using patient-derived organoids established from patients with advanced colorectal cancer (CRC), we evaluated the potential of olfactomedin 4 (OLFM4)+ stem cells to produce a bifurcated lineage of progenies with absorptive and secretory properties. In the early phases of organoid reconstruction, OLFM4+ cells preferentially gave rise to secretory cells. Additionally, we found that Paneth-like cells, which do not exist in the normal colon, were induced in response to Notch signaling inhibition. Video recordings of single OLFM4+ cells revealed that organoids containing Paneth-like cells were effectively propagated and that their selective ablation led to organoid collapse. In tumor tissues, Paneth-like cells were identified only in the region where tumor cells lost cell adhesion. These findings indicate that Paneth-like cells are directly produced by OLFM4+ stem cells and that their interaction contributes to tumor formation by providing niche factors. This study reveals the importance of the cell fate specification program for building a complete tumor cellular ecosystem, which might be targeted with novel therapeutics.
Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR
Authors: Novischi S. Y. Phoebe , Karoly-Lakatos Andrea , Chok Kerby , Bonifer Christian , Becker-Baldus Johanna , Glaubitz Clemens
Published: January 2024

The ABC transporter MsbA plays a critical role in Gram-negative bacteria in the regulation of the outer membrane by translocating core-LPS across the inner membrane. Additionally, a broad substrate specificity for lipophilic drugs has been shown. The allosteric interplay between substrate binding in the transmembrane domains and ATP binding and turnover in the nucleotide-binding domains must be mediated via the NBD/TMD interface. Previous studies suggested the involvement of two intracellular loops called coupling helix 1 and 2 (CH1, CH2). Here, we demonstrate by solid-state NMR spectroscopy that substantial chemical shift changes within both CH1 and CH2 occur upon substrate binding, in the ATP hydrolysis transition state, and upon inhibitor binding. CH2 is domain-swapped within the MsbA structure, and it is noteworthy that substrate binding induces a larger response in CH2 compared to CH1. Our data demonstrate that CH1 and CH2 undergo structural changes as part of the TMD-NBD cross-talk.
Curvature sensing lipid dynamics in a mitochondrial inner membrane model
Authors: Golla Vinaya Kumar , Boyd Kevin J. , May Eric R.
Published: January 2024

Membrane curvature is essential for many cellular structures and processes, and factors such as leaflet asymmetry, lipid composition, and proteins all play important roles. Cardiolipin is the signature lipid of mitochondrial membranes and is essential for maintaining the highly curved shapes of the inner mitochondrial membrane (IMM) and the spatial arrangement of membrane proteins. In this study, we investigate the partitioning behavior of various lipids present in the IMM using coarse-grained molecular dynamics simulations. This study explores curved bilayer systems containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CDL) in binary and ternary component mixtures. Curvature properties such as mean and Gaussian curvatures, as well as the distribution of lipids into the various curved regions of the cristae models, are quantified. Overall, this work represents an advance beyond previous studies on lipid curvature sensing by simulating these systems in a geometry that has the morphological features and scales of curvature consistent with regions of the IMM. We find that CDL has a stronger preference for accumulating in regions of negative curvature than PE lipids, in agreement with previous results. Furthermore, we find lipid partitioning propensity is dominated by sensitivity to mean curvature, while there is a weaker correlation with Gaussian curvature.
Suppressing MTERF3 inhibits proliferation of human hepatocellular carcinoma via ROS-mediated p38 MAPK activation
Authors: Zheng Zhihai , Zhao Youjuan , Yu Hongjia , Wang Tingting , Li Jinhai , Xu Liang , Ding Chunming , He Lan , Wu Lijun , Dong Zhixiong
Published: January 2024

Mitochondrial transcription termination factor 3 (MTERF3) negatively regulates mitochondrial DNA transcription. However, its role in hepatocellular carcinoma (HCC) progression remains elusive. Here, we investigate the expression and function of MTERF3 in HCC. MTERF3 is overexpressed in HCC tumor tissues and higher expression of MTERF3 positively correlates with poor overall survival of HCC patients. Knockdown of MTERF3 induces mitochondrial dysfunction, S-G2/M cell cycle arrest and apoptosis, resulting in cell proliferation inhibition. In contrast, overexpression of MTERF3 promotes cell cycle progression and cell proliferation. Mechanistically, mitochondrial dysfunction induced by MTERF3 knockdown promotes ROS accumulation, activating p38 MAPK signaling pathway to suppress HCC cell proliferation. In conclusion, ROS accumulation induced by MTERF3 knockdown inhibits HCC cell proliferation via p38 MAPK signaling pathway suggesting a promising target in HCC patients.
Characterizing immune variation and diagnostic indicators of preeclampsia by single-cell RNA sequencing and machine learning
Authors: Zhou Wenwen , Chen Yixuan , Zheng Yuhui , Bai Yong , Yin Jianhua , Wu Xiao-Xia , Hong Mei , Liang Langchao , Zhang Jing , Gao Ya , Sun Ning , Li Jiankang , Zhang Yiwei , Wu Linlin , Jin Xin , Niu Jianmin
Published: January 2024

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+monocytes and IFN+non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.
Antagonistic interactions safeguard mitotic propagation of genetic and epigenetic information in zebrafish
Authors: Lawir Divine-Fondzenyuy , Soza-Ried Cristian , Iwanami Norimasa , Siamishi Iliana , Bylund Göran O. , O´Meara Connor , Sikora Katarzyna , Kanzler Benoît , Johansson Erik , Schorpp Michael , Cauchy Pierre , Boehm Thomas
Published: January 2024

The stability of cellular phenotypes in developing organisms depends on error-free transmission of epigenetic and genetic information during mitosis. Methylation of cytosine residues in genomic DNA is a key epigenetic mark that modulates gene expression and prevents genome instability. Here, we report on a genetic test of the relationship between DNA replication and methylation in the context of the developing vertebrate organism instead of cell lines. Our analysis is based on the identification of hypomorphic alleles of dnmt1, encoding the DNA maintenance methylase Dnmt1, and pole1, encoding the catalytic subunit of leading-strand DNA polymerase epsilon holoenzyme (Pole). Homozygous dnmt1 mutants exhibit genome-wide DNA hypomethylation, whereas the pole1 mutation is associated with increased DNA methylation levels. In dnmt1/pole1 double-mutant zebrafish larvae, DNA methylation levels are restored to near normal values, associated with partial rescue of mutant-associated transcriptional changes and phenotypes. Hence, a balancing antagonism between DNA replication and maintenance methylation buffers against replicative errors contributing to the robustness of vertebrate development.
Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species
Authors: Rhoades Nicholas S. , Cinco Isaac R. , Hendrickson Sara M. , Prongay Kamm , Haertel Andrew J. , Flores Gilberto E. , Slifka Mark K. , Messaoudi Ilhem
Published: January 2024

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species. Finally, we compared the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance of unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.
Vibroscape analysis reveals acoustic niche overlap and plastic alteration of vibratory courtship signals in ground-dwelling wolf spiders
Authors: Choi Noori , Miller Pat , Hebets Eileen A.
Published: January 2024

To expand the scope of soundscape ecology to encompass substrate-borne vibrations (i.e. vibroscapes), we analyzed the vibroscape of a deciduous forest floor using contact microphone arrays followed by automated processing of large audio datasets. We then focused on vibratory signaling of ground-dwelling Schizocosa wolf spiders to test for (i) acoustic niche partitioning and (ii) plastic behavioral responses that might reduce the risk of signal interference from substrate-borne noise and conspecific/heterospecific signaling. Two closely related species - S. stridulans and S. uetzi - showed high acoustic niche overlap across space, time, and dominant frequency. Both species show plastic behavioral responses - S. uetzi males shorten their courtship in higher abundance of substrate-borne noise, S. stridulans males increased the duration of their vibratory courtship signals in a higher abundance of conspecific signals, and S. stridulans males decreased vibratory signal complexity in a higher abundance of S. uetzi signals.
Attachment performance of the ectoparasitic seal louse Echinophthirius horridus
Authors: Preuss Anika , Büscher Thies H. , Herzog Insa , Wohlsein Peter , Lehnert Kristina , Gorb Stanislav N.
Published: January 2024

Marine mammals host a great variety of parasites, which usually co-evolved in evolutionary arms races. However, little is known about the biology of marine mammal insect parasites, and even less about physical aspects of their life in such a challenging environment. One of 13 insect species that manage to endure long diving periods in the open sea is the seal louse, Echinophthirius horridus, parasitising true seals. Its survival depends on its specialised adaptations for enduring extreme conditions such as hypoxia, temperature changes, hydrostatic pressure, and strong drag forces during host dives. To maintain a grip on the seal fur, the louse’s leg morphology is equipped with modified snap hook claws and soft pad-like structures that enhance friction. Through techniques including CLSM, SEM, and histological staining, we have examined the attachment system’s detailed structure. Remarkably, the seal louse achieves exceptional attachment forces on seal fur, with safety factors (force per body weight) reaching 4500 in average measurements and up to 18000 in peak values, indicating superior attachment performance compared to other insect attachment systems. These findings underscore the louse’s remarkable adaptations for life in a challenging marine environment, shedding light on the relationship between structure and function in extreme ecological niches.
Multi-ancestry genome-wide meta-analysis identifies novel basal cell carcinoma loci and shared genetic effects with squamous cell carcinoma
Authors: Choquet Hélène , Jiang Chen , Yin Jie , Kim Yuhree , Hoffmann Thomas J. ,   23andMe Research Team, Aslibekyan Stella , Auton Adam , Babalola Elizabeth , Bell Robert K. , Bielenberg Jessica , Bryc Katarzyna , Bullis Emily , Coker Daniella , Partida Gabriel Cuellar , Dhamija Devika , Das Sayantan , Elson Sarah L. , Filshtein Teresa , Fletez-Brant Kipper , Fontanillas Pierre , Freyman Will , Gandhi Pooja M. , Heilbron Karl , Hicks Barry , Hinds David A. , Jewett Ethan M. , Jiang Yunxuan , Kukar Katelyn , Lin Keng-Han , Lowe Maya , McCreight Jey , McIntyre Matthew H. , Micheletti Steven J. , Moreno Meghan E. , Mountain Joanna L. , Nandakumar Priyanka , Noblin Elizabeth S. , O’Connell Jared , Petrakovitz Aaron A. , Poznik G. David , Schumacher Morgan , Shastri Anjali J. , Shelton Janie F. , Shi Jingchunzi , Shringarpure Suyash , Tran Vinh , Tung Joyce Y. , Wang Xin , Wang Wei , Weldon Catherine H. , Wilton Peter , Hernandez Alejandro , Wong Corinna , Tchakouté Christophe Toukam , Jorgenson Eric , Asgari Maryam M.
Published: January 2024

Basal cell carcinoma (BCC) is one of the most common malignancies worldwide, yet its genetic determinants are incompletely defined. We perform a European ancestry genome-wide association (GWA) meta-analysis and a Hispanic/Latino ancestry GWA meta-analysis and meta-analyze both in a multi-ancestry GWAS meta-analysis of BCC, totaling 50,531 BCC cases and 762,234 controls from four cohorts (GERA, Mass-General Brigham Biobank, UK Biobank, and 23andMe research cohort). Here we identify 122 BCC-associated loci, of which 36 were novel, and subsequently fine-mapped these associations. We also identify an association of the well-known pigment geneSLC45A2as well as associations atRCC2andCLPTM1Lwith BCC in Hispanic/Latinos. We examine these BCC loci for association with cutaneous squamous cell carcinoma (cSCC) in 16,407 SCC cases and 762,486 controls of European ancestry, and 33 SNPs show evidence of association. Our study findings provide important insights into the genetic basis of BCC and cSCC susceptibility.