bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physicochemical stability of bortezomib solutions for subcutaneous administration
Authors: Gómez Ángela , Benéitez García Mª Cristina , Barrueco Nélida , Lucena-Campillo Mª Amparo , López-Lunar Elena , García-Díaz Benito , Vicario-de-la-Torre Marta , Escobar-Rodríguez Ismael , Gil-Alegre María Esther 
Published: April 2024

AbstractFor the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20–30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.
A data-driven global flood forecasting system for medium to large rivers
Authors: Palash Wahid , Akanda Ali S. , Islam Shafiqul 
Published: April 2024

AbstractLosses from catastrophic floods are driving intense efforts to increase preparedness and improve response to disastrous flood events by providing early warnings. Yet accurate flood forecasting remains a challenge due to uncertainty in modeling, calibrating, and validating a useful early warning system. This paper presents the Requisitely Simple (ReqSim) flood forecasting system that includes key variables and processes of basin hydrology and atmospheric forcing in a data-driven modeling framework. The simplicity of the modeling structure and data requirements of the system allows for customization and implementation in any medium to large rain-fed river basin globally, provided there are water level or discharge measurements at the forecast locations. The proposed system's efficacy is demonstrated in this paper through providing useful forecasts for various river basins around the world. This include 3–10-day forecasts for the Ganges and Brahmaputra rivers in South Asia, 2–3-day forecast for the Amur and Yangtze rivers in East Asia, 5–10-day forecasts for the Niger, Congo and Zambezi rivers in West and Central Africa, 6–8-day forecasts for the Danube River in Europe, 2–5-day forecasts for the Parana River in South America, and 2–7-day forecasts for the Mississippi, Missouri, Ohio, and Arkansas rivers in the USA. The study also quantifies the effect of basin size, topography, hydrometeorology, and river flow controls on forecast accuracy and lead times. Results indicate that ReqSim's forecasts perform better in river systems with moderate slopes, high flow persistence, and less flow controls. The simple structure, minimal data requirements, ease of operation, and useful operational accuracy make ReqSim an attractive option for effective real-time flood forecasting in medium and large river basins worldwide.
Ambulatory electrocardiographic longitudinal monitoring in a canine model for Duchenne muscular dystrophy identifies decreased very low frequency power as a hallmark of impaired heart rate variability
Authors: Barthélémy Inès , Su Jin Bo , Cauchois Xavier , Relaix Frédéric , Ghaleh Bijan , Blot Stéphane 
Published: April 2024

AbstractDuchenne muscular dystrophy (DMD) patients exhibit a late left ventricular systolic dysfunction preceded by an occult phase, during which myocardial fibrosis progresses and some early functional impairments can be detected. These latter include electrocardiographic (ECG) and heart rate variability (HRV) abnormalities. This longitudinal study aimed at describing the sequence of ECG and HRV abnormalities, using Holter ECG in the GRMD (Golden retriever muscular dystrophy) dog model, known to develop a DMD-like disease, including cardiomyopathy. Most of the known ECG abnormalities described in DMD patients were also found in GRMD dogs, including increased heart rate, prolonged QT and shortened PR intervals, ventricular arrhythmias, and several of them could be detected months before the decrease of fractional shortening. The HRV was impaired like in DMD patients, one of the earliest evidenced abnormalities being a decrease in the very low frequency (VLF) component of the power spectrum. This decrease was correlated with the further reduction of fractional shortening. Such decreased VLF probably reflects impaired autonomic function and abnormal vasomotor tone. This study provides new insights into the knowledge of the GRMD dog model and DMD cardiomyopathy and emphasizes the interest to monitor the VLF power in DMD patients, still unexplored in this disease, whilst it is highly predictive of deleterious clinical events in many other pathological conditions.
Somatic mutations of esophageal adenocarcinoma: a comparison between Black and White patients
Authors: Lim Hyeyeun , Gingras Marie-Claude , Zhao Jing , Byun Jinyoung , Castro Patricia D. , Tsavachidis Spiridon , Hu Jianhong , Doddapaneni Harshavardhan , Han Yi , Muzny Donna M. , Gibbs Richard A. , Amos Christopher I. , Thrift Aaron P. 
Published: April 2024

AbstractEsophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational signatures. Group 1 is associated with age and NTHL1 deficiency-related signatures. Group 2 occurs primarily in Black patients and is associated with signatures related to DNA damage from oxidative stress and NTHL1 deficiency-related signatures. Group 3 is associated with defective homologous recombination-based DNA often caused by BRCA mutation in White patients. We observed significantly mutated race related genes (LCE2B in Black, SDR39U1 in White) were (q-value < 0.1). Our findings underscore the possibility of distinct molecular mutation patterns in EAC among different races. Further studies are needed to validate our findings, which could contribute to precision medicine in EAC.
Genetic architecture of white striping in turkeys (Meleagris gallopavo)
Authors: Vanderhout Ryley J. , Abdalla Emhimad A. , Leishman Emily M. , Barbut Shai , Wood Benjamin J. , Baes Christine F. 
Published: April 2024

AbstractWhite striping (WS) is a myopathy of growing concern to the turkey industry. It is rising in prevalence and has negative consequences for consumer acceptance and the functional properties of turkey meat. The objective of this study was to conduct a genome-wide association study (GWAS) and functional analysis on WS severity. Phenotypic data consisted of white striping scored on turkey breast fillets (N = 8422) by trained observers on a 0–3 scale (none to severe). Of the phenotyped birds, 4667 genotypic records were available using a proprietary 65 K single nucleotide polymorphism (SNP) chip. The SNP effects were estimated using a linear mixed model with a 30-SNP sliding window approach used to express the percentage genetic variance explained. Positional candidate genes were those located within 50 kb of the top 1% of SNP windows explaining the most genetic variance. Of the 95 positional candidate genes, seven were further classified as functional candidate genes because of their association with both a significant gene ontology and molecular function term. The results of the GWAS emphasize the polygenic nature of the trait with no specific genomic region contributing a large portion to the overall genetic variance. Significant pathways relating to growth, muscle development, collagen formation, circulatory system development, cell response to stimulus, and cytokine production were identified. These results help to support published biological associations between WS and hypoxia and oxidative stress and provide information that may be useful for future-omics studies in understanding the biological associations with WS development in turkeys.
Temporal dynamics of public transportation ridership in Seoul before, during, and after COVID-19 from urban resilience perspective
Authors: Lee Sangwan , Kim Jooae , Cho Kuk 
Published: April 2024

AbstractWe delve into the temporal dynamics of public transportation (PT) ridership in Seoul, South Korea, navigating the periods before, during, and after the COVID-19 pandemic through a spatial difference-in-difference model (SDID). Rooted in urban resilience theory, the study employs micro-level public transportation card data spanning January 2019 to December 2023. Major findings indicate a substantial ridership decline during the severe COVID impact phase, followed by a period in the stable and post-COVID phases. Specifically, compared to the pre-COVID phase, PT ridership experienced a 32.1% decrease in Severe, followed by a reduced magnitude of 21.8% in Stable and 13.5% in post-COVID phase. Interestingly, the observed decrease implies a certain level of adaptability, preventing a complete collapse. Also, contrasting with findings in previous literature, our study reveals a less severe impact, with reductions ranging from 27.0 to 34.9%. Moreover, while the ridership in the post-COVID phase exhibits recovery, the ratio (Post/Pre) staying below 1.0 suggests that the system has not fully returned to its pre-pandemic state. This study contributes to the urban resilience discourse, illustrating how PT system adjusts to COVID, offering insights for transportation planning.
Convolutional neural networks develop major organizational principles of early visual cortex when enhanced with retinal sampling
Authors: da Costa Danny , Kornemann Lukas , Goebel Rainer , Senden Mario 
Published: April 2024

AbstractPrimate visual cortex exhibits key organizational principles: cortical magnification, eccentricity-dependent receptive field size and spatial frequency tuning as well as radial bias. We provide compelling evidence that these principles arise from the interplay of the non-uniform distribution of retinal ganglion cells, and a quasi-uniform convergence rate from the retina to the cortex. We show that convolutional neural networks outfitted with a retinal sampling layer, which resamples images according to retinal ganglion cell density, develop these organizational principles. Surprisingly, our results indicate that radial bias is spatial-frequency dependent and only manifests for high spatial frequencies. For low spatial frequencies, the bias shifts towards orthogonal orientations. These findings introduce a novel hypothesis about the origin of radial bias. Quasi-uniform convergence limits the range of spatial frequencies (in retinal space) that can be resolved, while retinal sampling determines the spatial frequency content throughout the retina.
Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV‑2 Mpro)
Authors: Azevedo Pedro Henrique R. de A. , Camargo Priscila G. , Constant Larissa E. C. , Costa Stephany da S. , Silva Celimar Sinézia , Rosa Alice S. , Souza Daniel D. C. , Tucci Amanda R. , Ferreira Vivian N. S. , Oliveira Thamara Kelcya F. , Borba Nathalia R. R. , Rodrigues Carlos R. , Albuquerque Magaly G. , Dias Luiza R. S. , Garrett Rafael , Miranda Milene D. , Allonso Diego , Lima Camilo Henrique da S. , Muri Estela Maris F. 
Published: April 2024

AbstractCOVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.
Imaging the top of the Earth’s inner core: a present-day flow model
Authors: Tkalčić Hrvoje , Belonoshko Anatoly B. , Muir Jack B. , Mattesini Maurizio , Moresi Louis , Waszek Lauren 
Published: April 2024

AbstractDespite considerable progress in seismology, mineral physics, geodynamics, paleomagnetism, and mathematical geophysics, Earth’s inner core structure and evolution remain enigmatic. One of the most significant issues is its thermal history and the current thermal state. Several hypotheses involving a thermally-convecting inner core have been proposed: a simple, high-viscosity, translational mode, or a classical, lower-viscosity, plume-style convection. Here, we use state-of-the-art seismic imaging to probe the outermost shell of the inner core for its isotropic compressional speed and compare it with recently developed attenuation maps. The pattern emerging in the resulting tomograms is interpreted with recent data on the viscosity of iron as the inner core surface manifestation of a thermally-driven flow, with a positive correlation among compressional speed and attenuation and temperature. Although the outer-core convection controls the heat flux across the inner core boundary, the internally driven inner-core convection is a plausible model that explains a range of observations for the inner core, including distinct anisotropy in the innermost inner core.
Adaptive immune responses to two-dose COVID-19 vaccine series in healthy Canadian adults ≥ 50 years: a prospective, observational cohort study
Authors: Gaultier Gabrielle N. , McMillan Brynn , Poloni Chad , Lo Mandy , Cai Bing , Zheng Jean J. , Baer Hannah M. , Shulha Hennady P. , Simmons Karen , Márquez Ana Citlali , Bartlett Sofia R. , Cook Laura , Levings Megan K. , Steiner Theodore , Sekirov Inna , Zlosnik James E. A. , Morshed Muhammad , Skowronski Danuta M. , Krajden Mel , Jassem Agatha N. , Sadarangani Manish 
Published: April 2024

AbstractTo evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.
TusDCB, a sulfur transferase complex involved in tRNA modification, contributes to UPEC pathogenicity
Authors: Sato Yumika , Takita Ayako , Suzue Kazutomo , Hashimoto Yusuke , Hiramoto Suguru , Murakami Masami , Tomita Haruyoshi , Hirakawa Hidetada 
Published: April 2024

AbstracttRNA modifications play a crucial role in ensuring accurate codon recognition and optimizing translation levels. While the significance of these modifications in eukaryotic cells for maintaining cellular homeostasis and physiological functions is well-established, their physiological roles in bacterial cells, particularly in pathogenesis, remain relatively unexplored. The TusDCB protein complex, conserved in γ-proteobacteria like Escherichia coli, is involved in sulfur modification of specific tRNAs. This study focused on the role of TusDCB in the virulence of uropathogenic E. coli (UPEC), a bacterium causing urinary tract infections. The findings indicate that TusDCB is essential for optimal production of UPEC's virulence factors, including type 1 fimbriae and flagellum, impacting the bacterium's ability to aggregate in bladder epithelial cells. Deletion of tusDCB resulted in decreased virulence against urinary tract infection mice. Moreover, mutant TusDCB lacking sulfur transfer activity and tusE- and mnmA mutants revealed the indispensability of TusDCB's sulfur transfer activity for UPEC pathogenicity. The study extends its relevance to highly pathogenic, multidrug-resistant strains, where tusDCB deletion reduced virulence-associated bacterial aggregation. These insights not only deepen our understanding of the interplay between tRNA sulfur modification and bacterial pathogenesis but also highlight TusDCB as a potential therapeutic target against UPEC strains resistant to conventional antimicrobial agents.
Memory type Bayesian adaptive max-EWMA control chart for weibull processes
Authors: A. Zaagan Abdullah , Khan Imad , Ayari-Akkari Amel , Raza Aamir , Ahmad Bakhtiyar 
Published: April 2024

AbstractThe simultaneous monitoring of both the process mean and dispersion has gained considerable attention in statistical process control, especially when the process follows the normal distribution. This paper introduces a novel Bayesian adaptive maximum exponentially weighted moving average (Max-EWMA) control chart, designed to jointly monitor the mean and dispersion of a non-normal process. This is achieved through the utilization of the inverse response function, particularly suitable for processes conforming to a Weibull distribution. To assess the effectiveness of the proposed control chart, we employed the average run length (ARL) and the standard deviation of run length (SDRL). Subsequently, we compared the performance of our proposed control chart with that of an existing Max-EWMA control chart. Our findings suggest that the proposed control chart demonstrates a higher level of sensitivity in detecting out-of-control signals. Finally, to illustrate the effectiveness of our Bayesian Max-EWMA control chart under various Loss Functions (LFs) for a Weibull process, we present a practical case study focusing on the hard-bake process in the semiconductor manufacturing industry. This case study highlights the adaptability of the chart to different scenarios. Our results provide compelling evidence of the exceptional performance of the suggested control chart in rapidly detecting out-of-control signals during the hard-bake process, thereby significantly contributing to the improvement of process monitoring and quality control.
Computed tomography-based automated measurement of abdominal aortic aneurysm using semantic segmentation with active learning
Authors: Kim Taehun , On Sungchul , Gwon Jun Gyo , Kim Namkug 
Published: April 2024

AbstractAccurate measurement of abdominal aortic aneurysm is essential for selecting suitable stent-grafts to avoid complications of endovascular aneurysm repair. However, the conventional image-based measurements are inaccurate and time-consuming. We introduce the automated workflow including semantic segmentation with active learning (AL) and measurement using an application programming interface of computer-aided design. 300 patients underwent CT scans, and semantic segmentation for aorta, thrombus, calcification, and vessels was performed in 60–300 cases with AL across five stages using UNETR, SwinUNETR, and nnU-Net consisted of 2D, 3D U-Net, 2D-3D U-Net ensemble, and cascaded 3D U-Net. 7 clinical landmarks were automatically measured for 96 patients. In AL stage 5, 3D U-Net achieved the highest dice similarity coefficient (DSC) with statistically significant differences (p < 0.01) except from the 2D–3D U-Net ensemble and cascade 3D U-Net. SwinUNETR excelled in 95% Hausdorff distance (HD95) with significant differences (p < 0.01) except from UNETR and 3D U-Net. DSC of aorta and calcification were saturated at stage 1 and 4, whereas thrombus and vessels were continuously improved at stage 5. The segmentation time between the manual and AL-corrected segmentation using the best model (3D U-Net) was reduced to 9.51 ± 1.02, 2.09 ± 1.06, 1.07 ± 1.10, and 1.07 ± 0.97 min for the aorta, thrombus, calcification, and vessels, respectively (p < 0.001). All measurement and tortuosity ratio measured − 1.71 ± 6.53 mm and − 0.15 ± 0.25. We developed an automated workflow with semantic segmentation and measurement, demonstrating its efficiency compared to conventional methods.