bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoproteogenomic stratification of the missense variant cysteinome
Authors: Desai Heta , Andrews Katrina H. , Bergersen Kristina V. , Ofori Samuel , Yu Fengchao , Shikwana Flowreen , Arbing Mark A. , Boatner Lisa M. , Villanueva Miranda , Ung Nicholas , Reed Elaine F. , Nesvizhskii Alexey I. , Backus Keriann M. 
Published: October 2024

AbstractCancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics—a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues—with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.
Tailoring smart hydrogels through manipulation of heterogeneous subdomains
Authors: Yang Haoqing , Liu Tengxiao , Jin Lihua , Huang Yu , Duan Xiangfeng , Sun Hongtao 
Published: October 2024

AbstractThe mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film. These subdomains arise from the distinct mechanical responses of the pattern and film domains under applied mechanical forces. Unlike previous studies that incorporate reinforced inclusions into soft matrices to tailor material properties, our method manipulates the localization, integration, and interaction of these subdomain building blocks within the soft film. This enables extensive tuning of both local and global behaviors. Notably, we introduce a subdomain-interface mechanism that allows for the concurrent customization and decoupling of mechanical properties and shape transformations within a single material system—an achievement rarely accomplished with current synthetic soft materials. Additionally, our use of in-situ imaging characterizations, including full-field strain mapping via digital imaging correlation and reciprocal-space patterns through fast Fourier transform analysis of real-space pattern domains, provides rapid real-time monitoring tools to uncover the underlying principles governing tailored multiscale heterogeneities and intricate behaviors.
Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial
Authors: Garety Philippa A. , Edwards Clementine J. , Jafari Hassan , Emsley Richard , Huckvale Mark , Rus-Calafell Mar , Fornells-Ambrojo Miriam , Gumley Andrew , Haddock Gillian , Bucci Sandra , McLeod Hamish J. , McDonnell Jeffrey , Clancy Moya , Fitzsimmons Michael , Ball Hannah , Montague Alice , Xanidis Nikos , Hardy Amy , Craig Thomas K. J. , Ward Thomas 
Published: October 2024

AbstractDistressing voices are a core symptom of psychosis, for which existing treatments are currently suboptimal; as such, new effective treatments for distressing voices are needed. AVATAR therapy involves voice-hearers engaging in a series of facilitated dialogues with a digital embodiment of the distressing voice. This randomized phase 2/3 trial assesses the efficacy of two forms of AVATAR therapy, AVATAR-Brief (AV-BRF) and AVATAR-Extended (AV-EXT), both combined with treatment as usual (TAU) compared to TAU alone, and conducted an intention-to-treat analysis. We recruited 345 participants with psychosis; data were available for 300 participants (86.9%) at 16 weeks and 298 (86.4%) at 28 weeks. The primary outcome was voice-related distress at both time points, while voice severity and voice frequency were key secondary outcomes. Voice-related distress improved, compared with TAU, in both forms at 16 weeks but not at 28 weeks. Distress at 16 weeks was as follows: AV-BRF, effect −1.05 points, 96.5% confidence interval (CI) = −2.110 to 0, P = 0.035, Cohen’s d = 0.38 (CI = 0 to 0.767); AV-EXT −1.60 points, 96.5% CI = −3.133 to −0.058, P = 0.029, Cohen’s d = 0.58 (CI = 0.021 to 1.139). Distress at 28 weeks was: AV-BRF, −0.62 points, 96.5% CI = −1.912 to 0.679, P = 0.316, Cohen’s d = 0.22 (CI = −0.247 to 0.695); AV-EXT −1.06 points, 96.5% CI = −2.700 to 0.586, P = 0.175, Cohen’s d = 0.38 (CI = −0.213 to 0.981). Voice severity improved in both forms, compared with TAU, at 16 weeks but not at 28 weeks whereas frequency was reduced in AV-EXT but not in AV-BRF at both time points. There were no related serious adverse events. These findings provide partial support for our primary hypotheses. AV-EXT met our threshold for a clinically significant change, suggesting that future work should be primarily guided by this protocol. ISRCTN registration: ISRCTN55682735.
SMARTINI3 parametrization of multi-scale membrane models via unsupervised learning methods
Authors: Soleimani Alireza , Risselada Herre Jelger 
Published: October 2024

AbstractIn this study, we utilize genetic algorithms to develop a realistic implicit solvent ultra-coarse-grained (ultra-CG) membrane model comprising only three interaction sites. The key philosophy of the ultra-CG membrane model SMARTINI3 is its compatibility with realistic membrane proteins, for example, modeled within the Martini coarse-grained (CG) model, as well as with the widely used GROMACS software for molecular simulations. Our objective is to parameterize this ultra-CG model to accurately reproduce the experimentally observed structural and thermodynamic properties of Phosphatidylcholine (PC) membranes in real units, including properties such as area per lipid, area compressibility, bending modulus, line tension, phase transition temperature, density profile, and radial distribution function. In our example, we specifically focus on the properties of a POPC membrane, although the developed membrane model could be perceived as a generic model of lipid membranes. To optimize the performance of the model (the fitness), we conduct a series of evolutionary runs with diverse random initial population sizes (ranging from 96 to 384). We demonstrate that the ultra-CG membrane model we developed exhibits authentic lipid membrane behaviors, including self-assembly into bilayers, vesicle formation, membrane fusion, and gel phase formation. Moreover, we demonstrate compatibility with the Martini coarse-grained model by successfully reproducing the behavior of a transmembrane domain embedded within a lipid bilayer. This facilitates the simulation of realistic membrane proteins within an ultra-CG bilayer membrane, enhancing the accuracy and applicability of our model in biophysical studies.
Presenting a model for estimating the cube compressive strength of self-compacting concrete in cast in-situ piles using GEP
Authors: Maleki Toulabi Hossein , Hosseini Seyed Azim 
Published: October 2024

AbstractThe cast in-situ pile is a widely used type of deep foundations which its execution in civil projects is increasing daily. The use of ordinary concrete in this type of piles causes technical and executive problems, a decrease in the compressive strength (CS) of concrete, and an increase in the permeability under the ground level. But use of the self-compacting concrete in the cast in-situ piles while increasing the CS of concrete ensures proper compaction, increase in the execution speed, and easy placing of concrete. In this article, utilizing the data obtained from the laboratory results and also the application of soft computing techniques, predicting the degree of CS of self-compacting concrete (SCC) in concrete piles was investigated. To estimate the CS of SCC, a total number of 7 inputs were implemented. Then, using gene expression programming (GEP) a model was presented for estimating the CS of SCC in the cast in-situ piles. The results of the neural network showed a precision of 99.98% which exhibits the high accuracy of the model. The use of this model could greatly help persons, companies, and research centers in the preparation and construction of self-compacting concrete with the desired CS.
A bioanalytically validated RP-HPLC method for simultaneous quantification of rivaroxaban, paracetamol, and ceftriaxone in human plasma: a combination used for COVID-19 management
Authors: Ismail Reham A. , Ayad Miriam F. , Hussein Lobna A. , Trabik Yossra A. 
Published: October 2024

AbstractRivaroxaban is a direct oral anticoagulant medication that has been found to be beneficial for the management of thromboembolic events linked to the Corona virus disease 2019 (COVID-19) pandemic, which has resulted in more than 6 million deaths worldwide. Hence, a sensitive, selective, and green bioanalytically validated method was developed using RP-HPLC coupled with DAD for the simultaneous determination of rivaroxaban in human plasma, and two co-administered drugs, namely, paracetamol, an analgesic, and ceftriaxone, an antibiotic, that are used in the management of COVID-19. An Exsil 100 ODS C18 column (250 × 4.6 mm, 5 μm) was used as the stationary phase, and acetonitrile: water: methanol at a ratio of 60:30:10 (v/v/v) was used in isocratic mode as the mobile phase with a flow rate of 0.7 ml/min. The method was validated over a concentration range of 0.1–10.0 µg/mL for rivaroxaban, and 1.0–15.0 µg/mL for paracetamol and ceftriaxone. The lower limits of detection (LLODs) were found to be 0.03, 0.32, and 0.32 µg/ml for rivaroxaban, paracetamol, and ceftriaxone, respectively. Moreover, the lower limits of quantitation (LLOQs) were found to be 0.1, 0.96, and 0.98 µg/ml. The developed method showed excellent accuracy and precision for the determination of the aforementioned drugs. Four metrics were used to evaluate the greenness of the developed method. The results revealed that the suggested method is green, with values of 81 and 0.6 for the analytical eco-scale and analytical greenness assessment (AGREE), respectively.
Analysis of ventricular repolarization parameters and heart rate variability in obesity: a comparative study
Authors: Tomar Akash , Ahluwalia Himani , Isser H. S. , Gulati Sameer , Kumar Puneet , Yadav Indrajeet 
Published: October 2024

AbstractObesity is associated with dysfunctional electrocardiographic and cardiac autonomic parameters, which may lead to increased cardiovascular morbidity. Novel electrocardiographic repolarization markers such as Tpeak-Tend (Tpe) interval have not yet been deeply studied in obese patients. We aimed to investigate the association between ventricular repolarization parameters and heart rate variability (HRV) and how they are affected by changes occurring in the cardiac autonomic nervous system. Ninety subjects categorized by Southeast Asian BMI (kg/m2) standards - normal (18-22.9), overweight (23-24.9), and obese (> 24.9), underwent assessment of ventricular repolarization parameters and HRV. Linear correlation between different parameters was also conducted. Obese subjects exhibited longer QTc and Tpe intervals compared to normal-weight subjects (p-value < 0.001, 0.026 respectively). The QTc interval showed a significant correlation (p < 0.05) with all HRV parameters by linear correlation, while the Tpe interval did not. Anthropometric parameters (BMI, WC, and WHR) were also correlated to both ventricular repolarization variables and HRV. While changes in the QTc interval may be due to obesity and/or autonomic changes occurring in the obese state, the Tpe interval does not show a relation with autonomic parameters. Thus, implicating that a change in the Tpe interval is primarily due to the direct effect of either cardiac or visceral obesity. The observed associations between ECG parameters, obesity indices, and HRV parameters suggest a role for ECG in screening for cardiovascular morbidity.
Simplified shielded MEG-MRI multimodal system with scalar-mode optically pumped magnetometers as MEG sensors
Authors: Ito Yosuke , Ueda Hiroyuki , Oida Takenori , Moriya Takahiro , Saito Akinori , Suyama Motohiro 
Published: October 2024

AbstractMagnetoencephalography (MEG) conventionally operates within high-performance magnetic shields due to the extremely weak magnetic field signals from the measured objects and the narrow dynamic range of the magnetic sensors employed for detection. This limitation results in elevated equipment costs and restricted usage. Additionally, the information obtained from MEG is functional images, and to analyze from which part of the brain the signals are coming, it is necessary to capture morphological images separately. When MEG and morphological imaging devices are separate, despite their individual high measurement accuracies, discrepancies in positional information may arise. In response, we have developed a low-field magnetic resonance imaging system that incorporates scalar-mode optically pumped magnetometers with a wide dynamic range and exceptionally high measurement sensitivity as sensors for MEG. Operating at low magnetic fields eliminates the need for superconducting coils in magnetic resonance imaging and the high-performance magnetic shields essential for MEG, promising a substantial cost reduction compared to traditional approaches. We achieved a noise level of about $${16.7}\,\hbox {pT/Hz}^{1/2}$$

16.7

pT/Hz

1
/
2

with a single channel magnetometer, and reached a noise level of $${367}\,\hbox {fT/cm/Hz}^{1/2}$$

367

fT/cm/Hz

1
/
2

with a baseline of 1 cm through differential measurements. We employed this system to conduct sequential OPM-based magnetic field measurements and MRI imaging, successfully demonstrating the compatibility of high OPM sensitivity with clear MRI acquisition.
Hydrothermal synthesis of rGO and MnCoS composite for enhanced supercapacitor application
Authors: Manikandan M. , Prasankumar T. , Manikandan E. , Papanasam E. , Ramesh K. , Ramesh S. 
Published: October 2024

AbstractNanostructured materials incorporating transition metal sulfides have demonstrated considerable potential across various applications, particularly in the realms of energy production and storage. Sulfide-based material preparation is a challenging and costly procedure that requires a high temperature and reducing atmosphere. This work reports that manganese cobalt sulfide (MCS) and reduced graphene oxide composite manganese cobalt sulfide (rMCS) were successfully prepared through a hydrothermal method. Various characterization techniques were employed to analyze the prepared materials, including X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller analysis, and X-ray photoelectron spectroscopy. In a three-electrode system, MCS and rMCS electrodes exhibit an excellent specific capacitance of 1695 and 1925 F g−1 at 1 A g−1 current density respectively. MCS delivers the capacitance retention of 99% and rMCS exhibits the capacitance retention of 100% capacitance retention over 5000 consecutive cycles. The constructed asymmetric supercapacitor electrode (rMCS//rGO) exhibits the energy and power density of 64 Wh kg−1 at 799 W kg−1, respectively with outstanding cyclic stability of 97.4% even after 10,000 cycles. The exceptional electrochemical properties of MCS with rGO composite electrode indicate that they would make an outstanding electrode material for cutting-edge energy storage devices.
Structural behaviour of built-up I-shaped CFS columns
Authors: Hussein Ardalan B. 
Published: October 2024

AbstractThe utilization of cold-formed thin-walled members as structural members has gained significant popularity due to their advantages in fabrication, cost-effectiveness, and transportation convenience. However, the reduced thickness of the used sections poses challenges such as global, local, and distortional member buckling, leading to a decrease in their axial strength. This study focuses on addressing these challenges by connecting the channels together using screws as an alternative to welding, considering the cost, time, and ease of implementation. Conducting finite element analysis on structural columns built-up from cold-formed double C steel channels and subjected to axial loads, this paper verifies the numerical models used against experimental tests known from the literature. A comparison of experimental results with nonlinear FEA and AISI & AS/NZ standards reveals commendable agreement, particularly in predicting the buckling behavior of the built-up I-shaped CFS columns. While the results of the finite element analysis show an overestimation of approximately 3.6% compared to the experimental tests, the AISI and AS/NZS standards demonstrate a conservatism of about 3.0%. Furthermore, the current study investigates the influence of screw spacing on axial strength of built-up cold-formed steel columns. The findings are derived from 175 finite element experiments, evaluating seven different cross-sectional profiles with twelve distinct screw spacings. These spacings correspond to the half-wavelength of local, distortional, and global buckling, divided by values ranging from one to four. The screw spacing determined by half the local buckling half-wavelength along the webs’ centerline resulted in enhancements of 22%, 7%, 13%, and 11% in the critical elastic local, distortional, and global column buckling loads, as well as the nominal axial strength, respectively. These increases were even more pronounced for double-lane fasteners with the same spacing, yielding improvements of 25%, 46%, 17%, and 12%, respectively. For economic considerations, it is advisable to utilize single-lane fasteners with a half-wavelength equal to half the local buckling half-wavelength.
Developmental cues are encoded by the combinatorial phosphorylation of Arabidopsis RETINOBLASTOMA-RELATED protein RBR1
Authors: Zamora-Zaragoza Jorge , Klap Katinka , Sánchez-Pérez Jaheli , Vielle-Calzada Jean-Philippe , Willemsen Viola , Scheres Ben 
Published: October 2024

AbstractRETINOBLASTOMA-RELATED (RBR) proteins orchestrate cell division, differentiation, and survival in response to environmental and developmental cues through protein–protein interactions that are governed by multisite phosphorylation. Here we explore, using a large collection of transgenic RBR phosphovariants to complement protein function in Arabidopsis thaliana, whether differences in the number and position of RBR phosphorylation events cause a diversification of the protein’s function. While the number of point mutations influence phenotypic strength, phosphosites contribute differentially to distinct phenotypes. RBR pocket domain mutations associate primarily with cell proliferation, while mutations in the C-region are linked to stem cell maintenance. Both phospho-mimetic and a phospho-defective variants promote cell death, suggesting that distinct mechanisms can lead to similar cell fates. We observed combinatorial effects between phosphorylated T406 and phosphosites in different protein domains, suggesting that specific, additive, and combinatorial phosphorylation events fine-tune RBR function. Suppression of dominant phospho-defective RBR phenotypes with a mutation that inhibits RBR interacting with LXCXE motifs, and an exhaustive protein–protein interaction assay, not only revealed the importance of DREAM complex members in phosphorylation-regulated RBR function but also pointed to phosphorylation-independent RBR roles in environmental responses. Thus, combinatorial phosphorylation defined and separated developmental, but not environmental, functions of RBR.
Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches
Authors: Nuyttens Louise , Vandewalle Jolien , Libert Claude 
Published: October 2024

AbstractSepsis is a heterogeneous syndrome resulting from a dysregulated host response to infection. It is considered as a global major health priority. Sepsis is characterized by significant metabolic perturbations, leading to increased circulating metabolites such as lactate. In mammals, pyruvate is the primary substrate for lactate production. It plays a critical role in metabolism by linking glycolysis, where it is produced, with the mitochondrial oxidative phosphorylation pathway, where it is oxidized. Here, we provide an overview of all cytosolic and mitochondrial enzymes involved in pyruvate metabolism and how their activities are disrupted in sepsis. Based on the available data, we also discuss potential therapeutic strategies targeting these pyruvate-related enzymes leading to enhanced survival.
Preliminary Exploration of Variations in Measures of Pharyngeal Area During Nonswallowing Tasks
Authors: Steele Catriona M. , Mancopes Renata , Barrett Emily , Panes Vanessa , Peladeau-Pigeon Melanie , Simmons Michelle M. , Smaoui Sana 
Published: October 2024

Purpose:

Age- and disease-related changes in oropharyngeal anatomy and physiology may be identified through quantitative videofluoroscopic measures of pharyngeal area and dynamics. Pixel-based measures of nonconstricted pharyngeal area (PhAR) are typically taken during oral bolus hold tasks or on postswallow rest frames. A recent study in 87 healthy adults reported mean postswallow PhAR of 62%(C2–4)
2
, (range: 25%–135%), and significantly larger PhAR in males. The fact that measures were taken after initial bolus swallows without controlling for the presence of subsequent clearing swallows was identified as a potential source of variation. A subset of study participants had completed a protocol including additional static nonswallowing tasks, enabling us to explore variability across those tasks, taking sex differences into account.

Method:

Videofluoroscopy still shots were analyzed for 20 healthy adults (10 males, 10 females,
M
age
= 26 years) in head-neutral position, chin-down and chin-up positions, a sustained /a/ vowel vocalization, and oral bolus hold tasks (1-cc, 5-cc). Trained raters used ImageJ software to measure PhAR in %(C2–4)
2
units. Measures were compared to previously reported mean postswallow PhAR for the same participants: (a) explorations of sex differences; (b) pairwise linear mixed-model analyses of variance (ANOVAs) of PhAR for each nonswallowing task versus postswallow measures, controlling for sex; and (c) a combined mixed-model ANOVA to confirm comparability of the subset of tasks showing no significant differences from postswallow measures in Step 2.

Results:

Overall, PhAR measures were significantly larger in male participants; however, most pairwise task comparisons did not differ by sex. No significant differences from postswallow measures were seen for 5-cc bolus hold, chin-down and chin-up postures, and the second (but not the first) of two repeated head neutral still shots. PhAR during a 5-cc bolus hold was most similar to postswallow measures: mean ± standard deviation of 51 ± 13%(C2–4)
2
in females and 64 ± 16%(C2–4)
2
in males.

Conclusions:
PhAR is larger in men than in women. Oral bolus hold tasks with a 5-cc liquid bolus yield similar measures to those obtained from postswallow rest frames.