bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancestral allele of DNA polymerase gamma modifies antiviral tolerance
Authors: Kang Yilin , Hepojoki Jussi , Maldonado Rocio Sartori , Mito Takayuki , Terzioglu Mügen , Manninen Tuula , Kant Ravi , Singh Sachin , Othman Alaa , Verma Rohit , Uusimaa Johanna , Wartiovaara Kirmo , Kareinen Lauri , Zamboni Nicola , Nyman Tuula Anneli , Paetau Anders , Kipar Anja , Vapalahti Olli , Suomalainen Anu 
Published: April 2024

AbstractMitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1–4. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5. Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms5, indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals6demonstrates enrichment of immunodeficient traits in carriers of thePOLG1p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.
Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia
Authors: Koeberl Dwight , Schulze Andreas , Sondheimer Neal , Lipshutz Gerald S. , Geberhiwot Tarekegn , Li Lerong , Saini Rajnish , Luo Junxiang , Sikirica Vanja , Jin Ling , Liang Min , Leuchars Mary , Grunewald Stephanie 
Published: April 2024

AbstractPropionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.
Structural basis of Integrator-dependent RNA polymerase II termination
Authors: Fianu Isaac , Ochmann Moritz , Walshe James L. , Dybkov Olexandr , Cruz Joseph Neos , Urlaub Henning , Cramer Patrick 
Published: April 2024

AbstractThe Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript1, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator–PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10–INTS13–INTS14–INTS15 module that may use its ‘sting’ to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator–PP2A complex in an inactive closed conformation2 reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements.
Mapping Road Surface Type of Kenya Using OpenStreetMap and High-resolution Google Satellite Imagery
Authors: Zhou Qi , Liu Zixian , Huang Zesheng 
Published: April 2024

AbstractIdentifying road surface types (paved or unpaved) can ensure road vehicle safety, reduce energy consumption, and promote economic development. Existing studies identified road surface types by using sensors mounted on mobile devices and high-resolution satellite images that are not openly accessible, which makes it difficult to apply them to large-scale (e.g., national or regional) study areas. Addressing this issue, this study developed a dataset of road surface types (paved and unpaved) for the national road network of Kenya, containing 1,267,818 road segments classified as paved or unpaved. To accomplish this, this study proposes a method that integrates crowdsourced geographic data (OpenStreetMap) and Google satellite imagery to identify road surface types. The accuracy, recall, and F1 score of the method were all above 0.94, validating the effectiveness of the method. The data sources of the method are freely available, and the method may be applied to other countries and regions. The dataset developed based on the method can provide data support and decision support for local governments to improve road infrastructure.
Strain-dependent grain boundary properties of n-type germanium layers
Authors: Igura Kota , Nozawa Koki , Ishiyama Takamitsu , Suemasu Takashi , Toko Kaoru 
Published: April 2024

AbstractPolycrystalline Ge thin films have attracted considerable attention as potential materials for use in various electronic and optical devices. We recently developed a low-temperature solid-phase crystallization technology for a doped Ge layer and achieved the highest electron mobility in a polycrystalline Ge thin film. In this study, we investigated the effects of strain on the crystalline and electrical properties of n-type polycrystalline Ge layers. By inserting a GeOx interlayer directly under Ge and selecting substrates with different coefficients of thermal expansion, we modulated the strain in the polycrystalline Ge layer, ranging from approximately 0.6% (tensile) to − 0.8% (compressive). Compressive strain enlarged the grain size to 12 µm, but decreased the electron mobility. The temperature dependence of the electron mobility clarified that changes in the potential barrier height of the grain boundary caused this behavior. Furthermore, we revealed that the behavior of the grain boundary barrier height with respect to strain is opposite for the n- and p-types. This result strongly suggests that this phenomenon is due to the piezoelectric effect. These discoveries will provide guidelines for improving the performance of Ge devices and useful physical knowledge of various polycrystalline semiconductor thin films.
Investigating the phase diagram-ionic conductivity isotherm relationship in aqueous solutions of common acids: hydrochloric, nitric, sulfuric and phosphoric acid
Authors: Al-Salih Hilal , Abu-Lebdeh Yaser 
Published: April 2024

AbstractThe relationship between phase diagram features around the solid–liquid equilibrium region and ionic conductivity in aqueous solutions is not well understood over the whole concentration range as is the case for acidic aqueous solutions. In this work, we have studied the ionic conductivity (κ) as a function of molar fraction (x) and temperature (T) for four acid/water solutions namely, monoprotic hydrochloric acid (HCl) and nitric acid (HNO3), diprotic sulfuric acid (H2SO4) and triprotic phosphoric acid (H3PO4) along with their binary phase diagrams. The connection between the main features of the phase diagrams and the trends in the ionic conductivity isotherms is established with a new insight on the two pertinent dominant conductivity mechanisms (hopping and vehicular). Ionic conductivity at different temperatures were collected from literature and fitted to reported isothermal (κ vs. x) and iso-compositional (κ vs. T) equations along with a novel semi-empirical equation (κ = f (x, T)) for diprotic and triprotic acids. This equation not only has the best fit for acids with different valency; but also contains four parameters, less than any other similar equation in literature. This work is one of few that advances the understanding of the intricate relationship between structure and ionic transport in various acidic aqueous solutions.
Design of a broadband circularly polarised uniplanar crossed-dipole antenna
Authors: Wang Heesu , Park Yong Bae , Park Ikmo 
Published: April 2024

AbstractThis study presents the design of a uniplanar crossed-dipole antenna with broadband characteristics. The antenna comprises a pair of identical crossed-dipole arms printed on the same plane of a dielectric substrate. The crossed-dipole arms are corner-cut fat dipoles that are perpendicular to each other and connected with a bent stripline to generate circularly polarised (CP) radiations. A wide dipole arm was used to improve impedance matching and widen the axial ratio (AR) bandwidth. Additionally, the corner of each dipole arm was cut into a triangular shape to broaden the impedance and AR bandwidths further. The antenna in free space is excited via a wideband microstrip-to-parallel stripline tapered balun to reduce the effect of leakage current on the coaxial cable. Experiments and full-wave electromagnetic simulations were employed to design, verify, and validate the antenna design. The antenna, having an overall size of 45 × 45 × 0.508 mm3 (0.4 × 0.4 × 0.0045 λL3 where λL is the lowest frequency in the 3-dB AR bandwidth), demonstrates the following measured performances: an |S11|< − 10 dB impedance bandwidth of 2.53–9.14 GHz (113.3%), a 3 dB AR bandwidth of 2.65–7.75 GHz (98.1%), and peak gain of 3.7 dBic at 6.6 GHz.
Real-time monitoring of CdTe quantum dots growth in aqueous solution
Authors: da Costa P. F. G. M. , Merízio L. G. , Wolff N. , Terraschke H. , de Camargo A. S. S. 
Published: April 2024

AbstractQuantum dots (QDs) are remarkable semiconductor nanoparticles, whose optical properties are strongly size-dependent. Therefore, the real-time monitoring of crystal growth pathway during synthesis gives an excellent opportunity to a smart design of the QDs luminescence. In this work, we present a new approach for monitoring the formation of QDs in aqueous solution up to 90 °C, through in situ luminescence analysis, using CdTe as a model system. This technique allows a detailed examination of the evolution of their light emission. In contrast to in situ absorbance analysis, the in situ luminescence measurements in reflection geometry are particularly advantageous once they are not hindered by the concentration increase of the colloidal suspension. The synthesized particles were additionally characterized using X-ray diffraction analysis, transition electron microscopy, UV-Vis absorption and infrared spectroscopy. The infrared spectra showed that 3-mercaptopropionic acid (MPA)-based thiols are covalently bound on the surface of QDs and microscopy revealed the formation of CdS. Setting a total of 3 h of reaction time, for instance, the QDs synthesized at 70, 80 and 90 °C exhibit emission maxima centered at 550, 600 and 655 nm. The in situ monitoring approach opens doors for a more precise achievement of the desired emission wavelength of QDs.
The high FKBP1A expression in WBCs as a potential screening biomarker for pancreatic cancer
Authors: Watcharanurak Papitchaya , Mutirangura Apiwat , Aksornkitti Vitavat , Bhummaphan Narumol , Puttipanyalears Charoenchai 
Published: April 2024

AbstractGiven the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The development of blood-based molecular biomarkers for pancreatic cancer screening and early detection which provide less-invasive, high-sensitivity, and cost-effective, is urgently needed. The goal of this study is to identify and validate the potential molecular biomarkers in white blood cells (WBCs) of pancreatic cancer patients. Gene expression profiles of pancreatic cancer patients from NCBI GEO database were analyzed by CU-DREAM. Then, mRNA expression levels of three candidate genes were determined by quantitative RT-PCR in WBCs of pancreatic cancer patients (N = 27) and healthy controls (N = 51). ROC analysis was performed to assess the performance of each candidate gene. A total of 29 upregulated genes were identified and three selected genes were performed gene expression analysis. Our results revealed high mRNA expression levels in WBCs of pancreatic cancer patients in all selected genes, including FKBP1A (p < 0.0001), PLD1 (p < 0.0001), and PSMA4 (p = 0.0002). Among candidate genes, FKBP1A mRNA expression level was remarkably increased in the pancreatic cancer samples and also in the early stage (p < 0.0001). Moreover, FKBP1A showed the greatest performance to discriminate patients with pancreatic cancer from healthy individuals than other genes with the 88.9% sensitivity, 84.3% specificity, and 90.1% accuracy. Our findings demonstrated that the alteration of FKBP1A gene in WBCs serves as a novel valuable biomarker for patients with pancreatic cancer. Detection of FKBP1A mRNA expression level in circulating WBCs, providing high-sensitive, less-invasive, and cost-effective, is simple and feasible for routine clinical setting that can be applied for pancreatic cancer screening and early detection.
Cross-correlations between currents and tunnel magnetoresistance in interacting double quantum dot-Majorana wire system
Authors: Wrześniewski Kacper , Weymann Ireneusz 
Published: April 2024

AbstractWe theoretically investigate the spin and charge transport properties of a double quantum dot coupled to distinct edges of the nanowire hosting Majorana zero-energy modes. The focus is on the analysis of the currents flowing through the left and right junctions and their cross-correlations. We show that the system reveals very different transport properties depending on the detuning protocol of the quantum dot energy levels. For the symmetric detuning, the current dependencies reveal only two maxima associated with resonant tunneling, and currents in the left and right arms of the system reveal weak positive cross-correlations. On the other hand, for antisymmetric detuning, the flow of electrons into drains is maximized and strongly correlated in one bias voltage direction, while for the opposite bias direction a spin blockade is predicted. Furthermore, we observe a suppression of the current cross-correlations at a highly symmetric detuning point, indicating the involvement of the Majorana zero-energy modes in the transport processes. To gain insight into the role of the spin polarization of the Majorana edge states, we analyze the spin-dependent transport characteristics by considering the relationship between the spin canting angle, which describes the coupling of the Majorana modes to the spin of the quantum dots, and the magnetic configurations of the ferromagnetic drains. Moreover, we examine the non-local zero bias anomaly in the differential conductance, detailed analysis of which revealed a specific operational mode of the device that can facilitate the identification of the Majorana presence in the quantum dot-Majorana wire system. Finally, we also consider the transport properties in different magnetic configurations of the system and discuss the behavior of the associated tunnel magnetoresistance.
Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer
Authors: Futoh Yurie , Miyato Hideyo , Yamaguchi Hironori , Matsumiya Misaki , Takahashi Rei , Kaneko Yuki , Kimura Yuki , Ohzawa Hideyuki , Sata Naohiro , Kitayama Joji , Hosoya Yoshinori 
Published: April 2024

AbstractThe vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.
Soil pore characteristics and the fate of new switchgrass-derived carbon in switchgrass and prairie bioenergy cropping systems
Authors: Kim Kyungmin , Juyal Archana , Kravchenko Alexandra 
Published: April 2024

AbstractMonoculture switchgrass and restored prairie are promising perennial feedstock sources for bioenergy production on the lands unsuitable for conventional agriculture. Such lands often display contrasting topography that influences soil characteristics and interactions between plant growth and soil C gains. This study aimed at elucidating the influences of topography and plant systems on the fate of C originated from switchgrass plants and on its relationships with soil pore characteristics. For that, switchgrass plants were grown in intact soil cores collected from two contrasting topographies, namely steep slopes and topographical depressions, in the fields in multi-year monoculture switchgrass and restored prairie vegetation. The 13C pulse labeling allowed tracing the C of switchgrass origin, which X-ray computed micro-tomography enabled in-detail characterization of soil pore structure. In eroded slopes, the differences between the monoculture switchgrass and prairie in terms of total and microbial biomass C were greater than those in topographical depressions. While new switchgrass increased the CO2 emission in depressions, it did not significantly affect the CO2 emission in slopes. Pores of 18–90 µm Ø facilitated the accumulation of new C in soil, while > 150 µm Ø pores enhanced the mineralization of the new C. These findings suggest that polyculture prairie located in slopes can be particularly beneficial in facilitating soil C accrual and reduce C losses as CO2.
Dihydrotanshinone I exhibits antitumor effects via β-catenin downregulation in papillary thyroid cancer cell lines
Authors: Molteni Elisabetta , Baldan Federica , Damante Giuseppe , Allegri Lorenzo 
Published: April 2024

AbstractThyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of β-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.
The application value of deep learning-based nomograms in benign–malignant discrimination of TI-RADS category 4 thyroid nodules
Authors: Zhang Xinru , Jia Cheng , Sun Meng , Ma Zhe 
Published: April 2024

AbstractThyroid nodules are a common occurrence, and although most are non-cancerous, some can be malignant. The American College of Radiology has developed the Thyroid Imaging Reporting and Data System (TI-RADS) to standardize the interpretation and reporting of thyroid ultrasound results. Within TI-RADS, a category 4 designation signifies a thyroid nodule with an intermediate level of suspicion for malignancy. Accurate classification of these nodules is crucial for proper management, as it can potentially reduce unnecessary surgeries and improve patient outcomes. This study utilized deep learning techniques to effectively classify TI-RADS category 4 thyroid nodules as either benign or malignant. A total of 500 patients were included in the study and randomly divided into a training group (350 patients) and a test group (150 patients). The YOLOv3 model was constructed and evaluated using various metrics, achieving an 84% accuracy in the classification of TI-RADS category 4 thyroid nodules. Based on the predictions of the model, along with clinical and ultrasound data, a nomogram was developed. The performance of the nomogram was superior in both the training and testing groups. Furthermore, the calibration curve demonstrated good agreement between predicted probabilities and actual outcomes. Decision curve analysis further confirmed that the nomogram provided greater net benefits. Ultimately, the YOLOv3 model and nomogram successfully improved the accuracy of distinguishing between benign and malignant TI-RADS category 4 thyroid nodules, which is crucial for proper management and improved patient outcomes.