bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do calcium channel blockers applied to cardiomyocytes cause increased channel expression resulting in reduced efficacy?
Authors: Jæger Karoline Horgmo , Charwat Verena , Wall Samuel , Healy Kevin E. , Tveito Aslak 
Published: March 2024

AbstractIn the initial hours following the application of the calcium channel blocker (CCB) nifedipine to microtissues consisting of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we observe notable variations in the drug’s efficacy. Here, we investigate the possibility that these temporal changes in CCB effects are associated with adaptations in the expression of calcium ion channels in cardiomyocyte membranes. To explore this, we employ a recently developed mathematical model that delineates the regulation of calcium ion channel expression by intracellular calcium concentrations. According to the model, a decline in intracellular calcium levels below a certain target level triggers an upregulation of calcium ion channels. Such an upregulation, if instigated by a CCB, would then counteract the drug’s inhibitory effect on calcium currents. We assess this hypothesis using time-dependent measurements of hiPSC-CMs dynamics and by refining an existing mathematical model of myocyte action potentials incorporating the dynamic nature of the number of calcium ion channels. The revised model forecasts that the CCB-induced reduction in intracellular calcium concentrations leads to a subsequent increase in calcium ion channel expression, thereby attenuating the drug’s overall efficacy. The data and fit models suggest that dynamic changes in cardiac cells in the presence of CCBs may be explainable by induced changes in protein expression, and that this may lead to challenges in understanding calcium based drug effects on the heart unless timings of applications are carefully considered.
Combinatorial selective ER-phagy remodels the ER during neurogenesis
Authors: Hoyer Melissa J. , Capitanio Cristina , Smith Ian R. , Paoli Julia C. , Bieber Anna , Jiang Yizhi , Paulo Joao A. , Gonzalez-Lozano Miguel A. , Baumeister Wolfgang , Wilfling Florian , Schulman Brenda A. , Harper J. Wade 
Published: March 2024

AbstractThe endoplasmic reticulum (ER) employs a diverse proteome landscape to orchestrate many cellular functions, ranging from protein and lipid synthesis to calcium ion flux and inter-organelle communication. A case in point concerns the process of neurogenesis, where a refined tubular ER network is assembled via ER shaping proteins into the newly formed neuronal projections to create highly polarized dendrites and axons. Previous studies have suggested a role for autophagy in ER remodelling, as autophagy-deficient neurons in vivo display axonal ER accumulation within synaptic boutons, and the membrane-embedded ER-phagy receptor FAM134B has been genetically linked with human sensory and autonomic neuropathy. However, our understanding of the mechanisms underlying selective removal of the ER and the role of individual ER-phagy receptors is limited. Here we combine a genetically tractable induced neuron (iNeuron) system for monitoring ER remodelling during in vitro differentiation with proteomic and computational tools to create a quantitative landscape of ER proteome remodelling via selective autophagy. Through analysis of single and combinatorial ER-phagy receptor mutants, we delineate the extent to which each receptor contributes to both the magnitude and selectivity of ER protein clearance. We define specific subsets of ER membrane or lumenal proteins as preferred clients for distinct receptors. Using spatial sensors and flux reporters, we demonstrate receptor-specific autophagic capture of ER in axons, and directly visualize tubular ER membranes within autophagosomes in neuronal projections by cryo-electron tomography. This molecular inventory of ER proteome remodelling and versatile genetic toolkit provide a quantitative framework for understanding the contributions of individual ER-phagy receptors for reshaping ER during cell state transitions.
Graph states of atomic ensembles engineered by photon-mediated entanglement
Authors: Cooper Eric S. , Kunkel Philipp , Periwal Avikar , Schleier-Smith Monika 
Published: March 2024

AbstractGraph states are a broad family of entangled quantum states, each defined by a graph composed of edges representing the correlations between subsystems. Such states constitute versatile resources for quantum computation and quantum-enhanced measurement. Their generation and engineering require a high level of control over entanglement. Here we report on the generation of continuous-variable graph states of atomic spin ensembles, which form the nodes of the graph. We program the entanglement structure encoded in the graph edges by combining global photon-mediated interactions in an optical cavity with local spin rotations. By tuning the entanglement between two subsystems, we either localize correlations within each subsystem or enable Einstein–Podolsky–Rosen steering—a strong form of entanglement that enables the extraction of precise information from one subsystem through measurements on the other. We further engineer a four-mode square graph state, highlighting the flexibility of our approach. Our method is scalable to larger and more complex graphs, laying groundwork for measurement-based quantum computation and advanced protocols in quantum metrology.
Biosorption of nickel and cadmium using Pachira aquatica Aubl. peel biochar
Authors: Nascimento Talita L. S. , Oliveira Karine F. S. , Junior Joemil O. D. , Pimenta Alexandre S. , Melo Dulce M. A. , Melo Marcus A. F. , Braga Renata M. 
Published: March 2024

AbstractThis study aimed to assess the value of Pachira aquatica Aubl. fruit peels by exploring their applicability in the biosorption process for the removal of Ni(II) and Cd(II) metal ions. The Pachira aquatica Aubl. fruit peel biochar (PAB) was extensively characterized through various techniques, including proximate analysis, helium pycnometer, XRD, SEM, point of zero charge determination, zeta potential measurement, and Boehm titration. Subsequently, kinetic, isotherm, and thermodynamic batch biosorption studies were conducted, followed by column biosorption tests. The characteristics of PAB, including low moisture content, a neutral point of zero charge, porosity, an irregular and heterogeneous structure, a negatively charged surface, and the presence of functional groups, indicate its remarkable capacity for efficiently binding with heavy metals. Biosorption equilibrium time was achieved at 300 min for both ions, fitting well with a pseudo second-order kinetic model and Langmuir isotherm model. These data suggest that the biosorption process occurred chemically in monolayer. The column C presented an exhaust volume of 1200 mL for Ni(II) and 1080 for Cd(II) and removal of 98% and 99% of removal for Ni(II) and Cd(II), respectively. In summary, PAB demonstrates substantial potential as a biosorbent for effectively removing heavy metals, making a valuable contribution to the valorization of this co-product and the mitigation of environmental pollution.
Evolution mechanism of water-conducting fractures in overburden under the influence of water-rich fault in underground coal mining
Authors: Zhengzheng Cao , Xiangqian Yang , Zhenhua Li , Feng Du 
Published: March 2024

AbstractBased on the 7618 working face in Yaoqiao coal mine of Datun mining area, the activation mechanism of water-rich faults and the development characteristics of water-conducting fractures in overlying strata under the influence of faults are studied by theoretical analysis, numerical simulation and field measurement in this paper. The research results show that Anderson model and Mohr–Coulomb strength criterion are combined to establish the fault failure mechanical model, and the fault activation criterion under the influence of mining is obtained. FLAC3D numerical simulation results show that with the advance of the working face, the fault begins to be affected by the mining effect of the working face at the distance of 20 ~ 30 m from the fault. Meanwhile, with the advance of the working face, the overburden shear failure range also expands, and the fault fracture gradually expands from top to bottom. The failure zone of the working face roof is connected with the fault fracture zone. Then the fault is "activated" and causes the fault to become a water gushing channel, and finally the water gushing disaster occurs. Through numerical simulation and comparative analysis, the development height of water-conducting fracture is 73.2 m in the absence of fault, and 73.7 m in the presence of fault, indicating that the fault has little influence on the maximum development height of water-conducting fracture. The actual development height of the water-conducting fracture zone in the 7618 working face is 73.97 m and the fracture production ratio is 13.7. The research results can provide theoretical reference for the safe mining of similar working faces across faults.
Glucose values from the same continuous glucose monitoring sensor significantly differ among readers with different generations of algorithm
Authors: Babaya Naru , Noso Shinsuke , Hiromine Yoshihisa , Taketomo Yasunori , Niwano Fumimaru , Yoshida Sawa , Yasutake Sara , Kawabata Yumiko , Maeda Norikazu , Ikegami Hiroshi 
Published: March 2024

AbstractContinuous glucose monitoring (CGM) values obtained from CGM systems using the same sensor but with different internal algorithms (the first- and third-generation FreeStyle Libre (1st-gen-libre and 3rd-gen-libre, respectively)) were compared. We used 19,819 paired and simultaneously measured CGM values of 13 patients with diabetes. The average CGM value was significantly higher (P < 0.0001) and the time below range (CGM value < 70 mg/dL) was significantly lower (P < 0.0001) with the 3rd-gen-libre than with the 1st-gen-libre. There was a significant correlation (P < 0.0001) between the CGM values of the 3rd-gen-libre (y-axis, mg/dL) and 1st-gen-libre (x-axis, mg/dL) using the following formula: y = 0.9728x + 10.024. On assessing the association between glycated hemoglobin (HbA1c (%), y-axis) and the average CGM values (x-axis, mg/dL) by applying the obtained equation to previously reported 1st-gen-libre data and converting it to 3rd-gen-libre data, we obtained the equation y = 0.02628x + 3.233, indicating that the glucose management indicator reported in the West may be underestimated compared with the laboratory-measured HbA1c in the Japanese population. Glucose values from the same sensor were found to be significantly different between readers with different algorithms, and the calculation of CGM-related indices may need to be individualized for each device.
Risk factors for Echinococcus multilocularis intestinal infections in owned domestic dogs in a North American metropolis (Calgary, Alberta)
Authors: Toews Emilie , Musiani Marco , Smith Anya , Checkley Sylvia , Visscher Darcy , Massolo Alessandro 
Published: March 2024

AbstractHuman alveolar echinococcosis is increasingly documented in Alberta, Canada. Its causative agent, Echinococcus multilocularis (Em), can be transmitted to humans by infected dogs. We assessed the prevalence and associated risk factors for Em infections in domestic dogs in Calgary, Alberta, Canada. In this cross-sectional study that coupled collection and assessment of dog feces with a survey on potential risk factors, 13 of 696 (Bayesian true prevalence, 2.4%; 95% CrI: 1.3–4.0%) individual dogs’ feces collected during August and September 2012 were qPCR positive for Em. Sequencing two of these cases indicated that both were from the same Em European strain responsible for human infections in Alberta. Likelihood of intestinal Em was 5.6-times higher in hounds than other breeds, 4.6-times higher in dogs leashed at dog parks than those allowed off-leash, 3.1-times higher in dogs often kept in the backyard during spring and summer months than those rarely in the yard, and 3.3-times higher in dogs living in neighbourhoods bordering Bowmont park than those in other areas of Calgary. This situation warrants surveillance of dog infections as a preventative measure to reduce infections in North America.
A novel difficult-to-segment samples focusing network for oral CBCT image segmentation
Authors: Hu Fengjun , Chen Zeyu , Wu Fan 
Published: March 2024

AbstractUsing deep learning technology to segment oral CBCT images for clinical diagnosis and treatment is one of the important research directions in the field of clinical dentistry. However, the blurred contour and the scale difference limit the segmentation accuracy of the crown edge and the root part of the current methods, making these regions become difficult-to-segment samples in the oral CBCT segmentation task. Aiming at the above problems, this work proposed a Difficult-to-Segment Focus Network (DSFNet) for segmenting oral CBCT images. The network utilizes a Feature Capturing Module (FCM) to efficiently capture local and long-range features, enhancing the feature extraction performance. Additionally, a Multi-Scale Feature Fusion Module (MFFM) is employed to merge multiscale feature information. To further improve the loss ratio for difficult-to-segment samples, a hybrid loss function is proposed, combining Focal Loss and Dice Loss. By utilizing the hybrid loss function, DSFNet achieves 91.85% Dice Similarity Coefficient (DSC) and 0.216 mm Average Symmetric Surface Distance (ASSD) performance in oral CBCT segmentation tasks. Experimental results show that the proposed method is superior to current dental CBCT image segmentation techniques and has real-world applicability.
An integrated model of the human cornea as a linear biaxial birefringent medium
Authors: Sobczak Marcelina , Jóźwik Agnieszka , Kurzynowski Piotr 
Published: March 2024

AbstractA novel model of human corneal birefringence is presented. The cornea is treated as a homogeneous biaxial linear birefringent medium in which the values of the binormal axes angle and organization of the main refractive indices vary continuously from the apex to the limbus. In its central part, the angle between binormal axes is 35°, and para centrally, it smoothly increases to 83.7°. The values of the main refractive indices (nx, ny, nz) change, as well as their order, from nx < nz < ny to nz < nx < ny. The transition between these two states was described with a normal distribution (μ = 0.45, σ = 0.1). The presented model corresponds with the experimental results presented in the literature. To our knowledge, it is the first model that presents the anisotropic properties’ distributions of the entire cornea. The presented model facilitates a better understanding of the corneal birefringence phenomenon directly related to its lamellar structure.
A case study on the early stage of Pinus nigra invasion and its impact on species composition and pattern in Pannonic sand grassland
Authors: Bakacsy László , Szepesi Ágnes 
Published: March 2024

AbstractAlien woody species are successful invaders, frequently used for afforestation in regions like semi-arid lands. Shrubs and trees create important microhabitats in arid areas. Understorey vegetation in these habitats has unique species composition and coexistence. However, the impact of solitary woody species on understorey vegetation is less understood. This study evaluated the effect of native (Juniperus communis) and invasive solitary conifers (Pinus nigra) on surrounding vegetation, where individuals were relatively isolated (referred to as solitary conifers). The field study conducted in Pannonic dry sand grassland in 2018 recorded plant and lichen species presence around six selected solitary conifers. Composition and pattern of understorey vegetation were assessed using 26 m belt transects with 520 units of 5 cm × 5 cm contiguous microquadrats. Compositional diversity (CD) and the number of realized species combinations (NRC) were calculated from the circular transects. Results showed native conifer J. communis created more complex, organized microhabitats compared to alien P. nigra. CD and NRC values were significantly higher under native conifers than invasive ones (p = 0.045 and p = 0.026, respectively). Native species also had more species with a homogeneous pattern than the alien species. Alien conifers negatively affected understorey vegetation composition and pattern: some species exhibited significant gaps and clusters of occurrences along the transects under P. nigra. Based on our study, the removal of invasive woody species is necessary to sustain habitat diversity.
The subseasonal predictability of the western North Pacific subtropical high and the 2020 record-breaking event
Authors: Tseng Kai-Chih , Ho Yun-Hsuan 
Published: March 2024

AbstractThe western North Pacific subtropical high (WNPSH), a prominent feature in the North Pacific during the boreal summer, exerts significant socioeconomic consequences by influencing hydrological extremes such as tropical cyclones, the Meiyu front, and summer heat waves over East Asia. Accurately forecasting the characteristics of the WNPSH over extended timescales is crucial, but subseasonal prediction in this specific context is still in its early stages due to the complex dynamics involved. In this study, we investigate the optimal predictable pattern of the WNPSH using linear stochastic dynamics. Our findings reveal that convection over the Philippine/South China Sea and Japan serves as key precursors, where a dipole vorticity pattern leads to maximum growth of the WNPSH on subseasonal timescales, providing a potential source of predictability. Additionally, we examine the role of optimal predictable patterns in the record-breaking 2020 WNPSH event, and we find that the cumulative effect of stochastic forcing helps explain the sustained features of this extreme case.
Germline determinants of aberrant signaling pathways in cancer
Authors: Dalfovo Davide , Scandino Riccardo , Paoli Marta , Valentini Samuel , Romanel Alessandro 
Published: March 2024

AbstractCancer is a complex disease influenced by a heterogeneous landscape of both germline genetic variants and somatic aberrations. While there is growing evidence suggesting an interplay between germline and somatic variants, and a substantial number of somatic aberrations in specific pathways are now recognized as hallmarks in many well-known forms of cancer, the interaction landscape between germline variants and the aberration of those pathways in cancer remains largely unexplored. Utilizing over 8500 human samples across 33 cancer types characterized by TCGA and considering binary traits defined using a large collection of somatic aberration profiles across ten well-known oncogenic signaling pathways, we conducted a series of GWAS and identified genome-wide and suggestive associations involving 276 SNPs. Among these, 94 SNPs revealed cis-eQTL links with cancer-related genes or with genes functionally correlated with the corresponding traits’ oncogenic pathways. GWAS summary statistics for all tested traits were then used to construct a set of polygenic scores employing a customized computational strategy. Polygenic scores for 24 traits demonstrated significant performance and were validated using data from PCAWG and CCLE datasets. These scores showed prognostic value for clinical variables and exhibited significant effectiveness in classifying patients into specific cancer subtypes or stratifying patients with cancer-specific aggressive phenotypes. Overall, we demonstrate that germline genetics can describe patients’ genetic liability to develop specific cancer molecular and clinical profiles.
Phosphorylation regulates tau’s phase separation behavior and interactions with chromatin
Authors: Abasi Lannah S. , Elathram Nesreen , Movva Manasi , Deep Amar , Corbett Kevin D. , Debelouchina Galia T. 
Published: March 2024

AbstractTau is a microtubule-associated protein often found in neurofibrillary tangles (NFTs) in the brains of patients with Alzheimer’s disease. Beyond this context, mounting evidence suggests that tau localizes into the nucleus, where it may play a role in DNA protection and heterochromatin regulation. The molecular mechanisms behind these observations are currently unclear. Using in vitro biophysical experiments, here we demonstrate that tau can undergo liquid-liquid phase separation (LLPS) with DNA, mononucleosomes, and reconstituted nucleosome arrays under low salt conditions. Low concentrations of tau promote chromatin compaction and protect DNA from digestion. While the material state of samples at physiological salt is dominated by chromatin oligomerization, tau can still associate strongly and reversibly with nucleosome arrays. These properties are driven by tau’s strong interactions with linker and nucleosomal DNA. In addition, tau co-localizes into droplets formed by nucleosome arrays and phosphorylated HP1α, a key heterochromatin constituent thought to function through an LLPS mechanism. Importantly, LLPS and chromatin interactions are disrupted by aberrant tau hyperphosphorylation. These biophysical properties suggest that tau may directly impact DNA and chromatin accessibility and that loss of these interactions could contribute to the aberrant nuclear effects seen in tau pathology.
Digital RNA sequencing using unique molecular identifiers enables ultrasensitive RNA mutation analysis
Authors: Luna Santamaría Manuel , Andersson Daniel , Parris Toshima Z. , Helou Khalil , Österlund Tobias , Ståhlberg Anders 
Published: March 2024

AbstractMutation analysis is typically performed at the DNA level since most technical approaches are developed for DNA analysis. However, some applications, like transcriptional mutagenesis, RNA editing and gene expression analysis, require RNA analysis. Here, we combine reverse transcription and digital DNA sequencing to enable low error digital RNA sequencing. We evaluate yield, reproducibility, dynamic range and error correction rate for seven different reverse transcription conditions using multiplexed assays. The yield, reproducibility and error rate vary substantially between the specific conditions, where the yield differs 9.9-fold between the best and worst performing condition. Next, we show that error rates similar to DNA sequencing can be achieved for RNA using appropriate reverse transcription conditions, enabling detection of mutant allele frequencies <0.1% at RNA level. We also detect mutations at both DNA and RNA levels in tumor tissue using a breast cancer panel. Finally, we demonstrate that digital RNA sequencing can be applied to liquid biopsies, analyzing cell-free gene transcripts. In conclusion, we demonstrate that digital RNA sequencing is suitable for ultrasensitive RNA mutation analysis, enabling several basic research and clinical applications.
Cooler Arctic surface temperatures simulated by climate models are closer to satellite-based data than the ERA5 reanalysis
Authors: Tian Tian , Yang Shuting , Høyer Jacob Lorentsen , Nielsen-Englyst Pia , Singha Suman 
Published: March 2024

AbstractMany climate models simulate near-surface air temperatures that are too low in the Arctic compared to the observation-based ERA5 reanalysis data, a bias that was noted in the Inter-governmental Panel on Climate Change Sixth Assessment Report (IPCC AR6). Here we present a high-resolution, satellite-derived dataset of near-surface air temperatures for the Arctic sea-ice region (1982–2020). We use it as a benchmark to reevaluate climate reanalyses and model simulations in CMIP6 (Coupled Model Intercomparison Project 6). We find that the CMIP6 simulations in the central Arctic, with generally thicker ice and snow, align well with satellite observations, with an annual mean bias of less than ± 1 °C over sea ice. By contrast, climate reanalyses like ERA5 exhibit widespread warm biases exceeding 2 °C in the same region. We conclude that reliance on ERA5 reanalysis as a reference may have led to an underestimation of climate model reliability in the Arctic region.