bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomics-based functional outcome prediction in acute single subcortical infarction
Authors: Yang Tang , Ming Yue , Cheng Yajun , Jiang Shuai , Yan Yuying , Hu Yi , Ye Chen , Pan Ruosu , Sun Jiayu , Wu Bo 
Published: July 2024

AbstractBackgroundClinical outcomes vary considerably among patients with acute single subcortical infarction (SSI). We aimed to construct a model incorporating radiomic features and clinical factors to predict functional outcomes in patients with acute SSI.MethodsWe enrolled patients who experienced acute SSI within 14 days of stroke onset and randomly divided them into training (n=118) and test (n=30) cohorts. Unfavorable functional outcome was defined as a modified Rankin Scale score >1 at 3 months. We extracted and selected radiomics features from baseline diffusion-weighted imaging and perfusion-weighted imaging to develop a radiomics model. Multivariate logistic regression was performed to construct a clinical model using clinical factors and imaging features. Finally, a combined model was built using both clinical and radiomics features. Receiver operating characteristic curves were used to evaluate the discriminatory ability of these models.ResultsThe radiomics model, encompassing 13 radiomics features, exhibited good predictive performance for unfavorable functional outcomes with area under the curve (AUC) values of 0.774 and 0.824 in the training and test cohorts, respectively. The combined model, which included clinical factors (early neurological deterioration, hypertension, baseline National Institutes of Health Stroke Scale score, infarct volume, and summary cerebral small vessel disease score) and radiomics features, improved performance in the training (AUC = 0.915) and test (AUC = 0.846) cohorts.ConclusionsThe clinical-radiomics model provided improved accuracy for the prognostic prediction of SSI, which may help clinicians in the decision-making process and improve long-term outcomes in patients with SSI.
Spinal Cord Infarction Outcomes with a Focus on Thrombolysis: A Nationwide Database Study
Authors: Al-Salahat Ali , Dilsaver Danielle B. , Jabbar Ali Bin Abdul , Bawaneh Saif , Singh Abhishek 
Published: July 2024

AbstractBackgroundSpinal cord infarction (SCI) is a rare and challenging condition to diagnose. The literature lacks large studies examining the characteristics and outcomes of SCI. Treatments, such as thrombolysis, which are considered standard of care in cerebral stroke, have not been previously studied in SCI. The primary aim was to determine outcomes of hospitalizations with SCI in the United States (US) by assessing inpatient mortality and all-cause 30-day and 90-day readmissions. After adjusting for age and comorbidity burden, we analyzed if these outcomes differed based on thrombolysis, and the most common concomitant conditions, such as aneurysms, dissections and sepsis.MethodsHospitalizations of patients over 18 years of age with SCI were abstracted from the 2016-2021 Nationwide Readmissions Database (NRD). We estimated logistic and lognormal regression models to evaluate whether outcomes differed based on thrombolysis, or concomitant aneurysm, dissection, or sepsis. Multivariable models adjusted for age and comorbidity burden.ResultsAn estimated 12,548 hospitalizations involved patients diagnosed with SCI; of those, 21.43% were specifically for SCI. Other common reasons for SCI hospitalization included aneurysms or dissections (22.22%) and sepsis (9.11%). The average LOS was 13.09 days (95% CI: 12.61-13.59), with an inpatient mortality rate of 14.66% (95% CI: 13.74-15.59). Age and comorbidity burden significantly impacted inpatient mortality, LOS, and hospital costs. Hospitalizations of patients with SCI were predominately at large bed size facilities (72.36%, Weighted N: 9,079) and metropolitan teaching hospitals (86.57%, Weighted N: 10,862). Thrombolysis was associated with lower odds of 90-day readmissions (adjusted OR=0.35, p-value= 0.009) and no significant difference in mortality. Concomitant sepsis significantly increased mortality, LOS, cost, and readmission odds.ConclusionsThis study highlights factors that impact the outcomes of SCI on a large scale. Additionally, the findings uncover the association between thrombolysis and better long-term outcomes in SCI. This paves the way for further investigation into the role of thrombolysis in SCI.
Discovery and pharmacological characterization of nanobodies acting as potent positive allosteric modulators of the calcium-sensing receptor
Authors: Mos Iris , Zögg Thomas , Wohlkönig Alexandre , Egholm Anne Mette Helmich , Rahman Sabrina N. , Pardon Els , Steyaert Jan , Bräuner-Osborne Hans , Mathiesen Jesper M. 
Published: July 2024

AbstractThe calcium-sensing receptor (CaSR) is responsible for sustaining a stable blood calcium concentration. Consequently, genetic and acquired changes in this G protein-coupled receptor can give rise to various calcium homeostasis disorders. Synthetic positive allosteric modulators targeting CaSR are currently used to treat hypercalcemia, but their usage is highly limited due to the high risk of severe hypocalcemia and gastrointestinal intolerance. In this study, we aimed to generate pharmacologically active CaSR-specific nanobodies that could be employed as a new generation of pharmacological tools to investigate the receptor function and potentially serve as a new drug modality for effective treatment of CaSR-related disorders.Nanobodies were generated by immunization of a llama with CHO cells recombinantly overexpressing a myc-epitope-tagged human CaSR. Following construction of a phage display library representing the repertoire of nanobody genes, nanobodies binding to the CaSR were isolated by FACS of whole HEK293 cells recombinantly overexpressing HA-epitope-tagged human CaSR. Based on sequence comparison, 37 nanobodies from 25 different sequence families were purified and subsequent characterized in vitro for modulation of CaSR signaling. The nanobodies were screened for agonist, as well as positive and negative allosteric modulators activity inin vitrocellular assays downstream of CaSR activation. We identified eight pharmacologically active nanobodies acting as positive allosteric modulators that could be divided into five main families based on their sequence identity. The most potent nanobody (Nb4) binding to the extracellular domain of CaSR was slightly more potent than the reference small molecule PAM NPS R-568.This study describes the discovery and pharmacological characterization of nanobodies acting as potent CaSR positive allosteric modulators. These nanobodies are a new class of pharmacological research tools for the CaSR, which potentially can be developed into new therapeutics in the treatment of CaSR-related disorders.
Casein Kinases 2-dependent phosphorylation of the placental ligand VAR2CSA regulates Plasmodium falciparum-infected erythrocytes cytoadhesion
Authors: Dorin-Semblat Dominique , Semblat Jean-Philippe , Hamelin Romain , Srivastava Anand , Tetard Marilou , Matesic Graziella , Doerig Christian , Gamain Benoit 
Published: July 2024

AbstractPlacental malaria is characterized by the massive accumulation and sequestration of infected erythrocytes in the placental intervillous blood spaces, causing severe birth outcomes. The variant surface antigen VAR2CSA is associated withPlasmodium falciparumsequestration in the placenta via its capacity to adhere to chondroitin sulfate A. We have previously shown that the extracellular region of VAR2CSA is phosphorylated on several residues and that the phosphorylation enhances the adhesive properties of CSA-binding infected erythrocytes. Here, we aimed to identify the kinases mediating this phosphorylation. Here, we report that human andPlasmodium falciparumCasein Kinase 2α are involved in the phosphorylation of the extracellular region of VAR2CSA. We notably show that both CK2α can phosphorylate the extracellular region of recombinant and immunoprecipitated VAR2CSA. Mass spectrometry analysis of recombinant VAR2CSA phosphorylated by recombinant Human andP. falciparumCK2α combined with site-directed mutagenesis led to the identification of residue S1068 in VAR2CSA, which is phosphorylated by both enzymes and is associated with CSA binding. Furthermore, using CRISPR/Cas9 we generated a parasite line in which phosphoresidue, S1068, was changed to alanine. This mutation strongly impairs infected erythrocytes adhesion by abolishing VAR2CSA translocation to the surface of infected erythrocytes. We also report that two specific CK2 inhibitors reduce infected erythrocytes adhesion to CSA and decrease the phosphorylation of the recombinant extracellular region of VAR2CSA using either infected erythrocytes lysates as a source of kinases or recombinant Human andP. falciparumcasein kinase 2.Taken together, these results undoubtedly demonstrate that host andP. falciparumCK2α phosphorylate the extracellular region of VAR2CSA and that this post-translational modification is important for VAR2CSA trafficking and for infected erythrocytes adhesion to CSA.
MICROBIOTA AT THE CROSS ROAD OF DIET AND HEALTH: HOW DIETARY FATS SHAPE BACTERIAL LAND-SCAPE AND INFLUENCE GLOBAL HEALTH
Authors: Portela Néstor D. , Eberhardt Natalia , Bergero Gastón , Mazzocco Yanina L. , Aoki Maria P. , Galván Cristian A. , Cano Roxana C. , Pesoa Susana A. 
Published: July 2024

AbstractHost-gut microbiota (GM) interactions play a pivotal role in shaping the delicate balance between health and disease within the human body. The impact of dietary factors, specifically high fat content diets on GM composition has been widely demonstrated. We have previously shown that the constant and sustained administration of Omega-3 fatty acids induced specific changes in GM composition, modulating the immune metabolic response of visceral adipose tissue (VAT) in our mouse model of obesity. We now set out to determine if this effect is Omega-3 dose-dependent. To achieve this, C57BL/6J(B6) mice were fed for 24 weeks with three diets, two with medium content total fat, but different Omega-3 content and a control diet.GM composition, metabolic biomarkers and immune cells in VAT were analyzed. A distinctive segregation of GM composition, a significantly higher proportion of regulatory T cells (CD45+CD4+FoxP3+), Omega-3 dose dependent and increased levels of leptin and cholesterol with no differences in adiponectin values were found in fat fed groups. Simple mediation analyses revealed significant associations between the microbial profile and immunometabolic regulation. To remark is the capacity ofLachnospiraceae UCG- 001to modulate levels of leptin, glucose, and cholesterol through the stimulation of CD45+CD4+FOXP3+IL10+ cells. Our findings suggest a modulatory effect of omega-3 fatty acids on the microbiota, the metabolism, and the immunoregulatory capacity of VAT, supporting the hypothesis that alteration of the GM composition by omega-3 fatty acids may be a promising approach in managing obesity and associated metabolic diseases.
Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins
Authors: Beyer Jenna N. , Serebrenik Yevgeniy V. , Toy Kaitlyn , Najar Mohd. Altaf , Raniszewski Nicole R. , Shalem Ophir , Burslem George M. 
Published: July 2024

AbstractThe ability to study proteins in a cellular context is crucial to our understanding of biology. Here, we report a new technology for “intracellular protein editing”, drawing from intein- mediated protein splicing, genetic code expansion, and endogenous protein tagging. This protein editing approach enables us to rapidly and site specifically install residues and chemical handles into a protein of interest. We demonstrate the power of this protein editing platform to edit cellular proteins, inserting epitope peptides, protein-specific sequences, and non-canonical amino acids (ncAAs). Importantly, we employ an endogenous tagging approach to apply our protein editing technology to endogenous proteins with minimal perturbation. We anticipate that the protein editing technology presented here will be applied to a diverse set of problems, enabling novel experiments in live mammalian cells and therefore provide unique biological insights.
Cerebellar output neurons impair non-motor behaviors by altering development of extracerebellar connectivity
Authors: Lee Andrew S. , Arefin Tanzil M. , Gubanova Alina , Stephen Daniel N. , Liu Yu , Lao Zhimin , Krishnamurthy Anjana , De Marco García Natalia V. , Heck Detlef H. , Zhang Jiangyang , Rajadhyaksha Anjali M. , Joyner Alexandra L. 
Published: July 2024

AbstractThe capacity of the brain to compensate for insults during development depends on the type of cell loss, whereas the consequences of genetic mutations in the same neurons are difficult to predict. We reveal powerful compensation from outside the cerebellum when the excitatory cerebellar output neurons are ablated embryonically and demonstrate that the minimum requirement for these neurons is for motor coordination and not learning and social behaviors. In contrast, loss of the homeobox transcription factors Engrailed1/2 (EN1/2) in the cerebellar excitatory lineage leads to additional deficits in adult learning and spatial working memory, despite half of the excitatory output neurons being intact. Diffusion MRI indicates increased thalamo-cortico-striatal connectivity inEn1/2mutants, showing that the remaining excitatory neurons lackingEn1/2exert adverse effects on extracerebellar circuits regulating motor learning and select non-motor behaviors. Thus, an absence of cerebellar output neurons is less disruptive than having cerebellar genetic mutations.
FapR regulates HssRS-mediated heme homeostasis inBacillus anthracis
Authors: Pi Hualiang , Carlin Sophia M. , Beavers William N. , Hillebrand Gideon H. , Krystofiak Evan S. , Stauff Devin L. , Skaar Eric P. 
Published: July 2024

ABSTRACTBacillus anthracis, a Gram-positive facultative anaerobe and the causative agent of anthrax, multiplies to extraordinarily high numbers in vertebrate blood, resulting in considerable heme exposure. Heme is an essential nutrient and the preferred iron source for bacteria during vertebrate colonization, but its high redox potential makes it toxic in excess. To regulate heme homeostasis, many Gram-positive bacteria, includingB. anthracis, rely on the two-component signaling system HssRS. HssRS comprises the heme sensing histidine kinase HssS, which modulates the activity of the HssR transcription factor to enable bacteria to circumvent heme toxicity. However, the regulation of the HssRS system remains unclear. Here we identify FapR, the transcriptional regulator of fatty acid biosynthesis, as a key factor in HssRS function. FapR plays an important role in maintaining membrane integrity and the localization of the histidine kinase HssS. Specifically, disruption offapRleads to increased membrane rigidity, which hinders the penetration of HssRS inducers, resulting in the inactivation of HssRS. Furthermore, deletion offapRaffects the loading of HssS onto the cell membrane, compromising its heme sensing function and subsequently reducing endogenous heme biosynthesis. These findings shed light on the molecular mechanisms governing bacterial adaptation to heme stress and provide potential targets for antimicrobial intervention strategies.IMPORTANCEUnderstanding the mechanisms by whichB. anthracisregulates heme homeostasis is crucial for developing new strategies to combat anthrax, a serious disease affecting both humans and animals. This study uncovers the role of the transcriptional regulator FapR in maintaining membrane integrity and facilitating the proper function of the HssRS two-component signaling system, which is essential for managing heme toxicity inB. anthracis, as well as other Gram-positive pathogens. By elucidating the connection between FapR and HssRS, our findings provide new insights into the molecular adaptation of bacteria to heme stress and expand our knowledge of bacterial physiology and pathogenicity. More importantly, targeting the regulatory pathways involved in heme sensing and homeostasis presents a promising approach for developing novel therapeutics against anthrax and potentially other bacterial infections that rely on similar mechanisms.
Performance of Advanced Large Language Models (GPT-4o, GPT-4, Gemini 1.5 Pro, Claude 3 Opus) on Japanese Medical Licensing Examination: A Comparative Study
Authors: Liu Mingxin , Okuhara Tsuyoshi , Dai Zhehao , Huang Wenbo , Okada Hiroko , Furukawa Emi , Kiuchi Takahiro 
Published: July 2024

AbstractPurposeThis study aims to evaluate the accuracy of medical knowledge in the most advanced LLMs (GPT-4o, GPT-4, Gemini 1.5 Pro, and Claude 3 Opus) as of 2024. It is the first to evaluate these LLMs using a non-English medical licensing exam. The insights from this study will guide educators, policymakers, and technical experts in the effective use of AI in medical education and clinical diagnosis.MethodAuthors inputted 790 questions from Japanese National Medical Examination into the chat windows of the LLMs to obtain responses. Two authors independently assessed the correctness. Authors analyzed the overall accuracy rates of the LLMs and compared their performance on image and non-image questions, questions of varying difficulty levels, general and clinical questions, and questions from different medical specialties. Additionally, authors examined the correlation between the number of publications and LLMs’ performance in different medical specialties.ResultsGPT-4o achieved highest accuracy rate of 89.2% and outperformed the other LLMs in overall performance and each specific category. All four LLMs performed better on non-image questions than image questions, with a 10% accuracy gap. They also performed better on easy questions compared to normal and difficult ones. GPT-4o achieved a 95.0% accuracy rate on easy questions, marking it as an effective knowledge source for medical education. Four LLMs performed worst on “Gastroenterology and Hepatology” specialty. There was a positive correlation between the number of publications and LLM performance in different specialties.ConclusionsGPT-4o achieved an overall accuracy rate close to 90%, with 95.0% on easy questions, significantly outperforming the other LLMs. This indicates GPT-4o’s potential as a knowledge source for easy questions. Image-based questions and question difficulty significantly impact LLM accuracy. “Gastroenterology and Hepatology” is the specialty with the lowest performance. The LLMs’ performance across medical specialties correlates positively with the number of related publications.
Additive effects of cerebrovascular disease functional connectome phenotype and plasma p-tau181 on longitudinal neurodegeneration and cognitive outcomes
Authors: Chong Joanna Su Xian , Ji Fang , Hilal Saima , Chong Joyce Ruifen , Lau Jia Ming , Tong Nathanael Ren Jie , Tan Boon Yeow , Venketasubramanian Narayanaswamy , Lai Mitchell Kim Peng , Chen Christopher Li-Hsian , Zhou Juan Helen 
Published: July 2024

ABSTRACTINTRODUCTIONWe investigated the effects of multiple cerebrovascular disease (CeVD) neuroimaging markers on brain functional connectivity (FC), and how such CeVD-related FC changes interact with plasma p-tau181 (Alzheimer’s disease (AD) marker) to influence downstream neurodegeneration and cognitive changes.METHODSMultivariate associations between four CeVD markers and whole-brain FC in 529 participants across the dementia spectrum were examined using partial least squares correlation. Interactive effects of CeVD-related FC patterns and p-tau181 on longitudinal grey matter volume and cognitive changes were investigated using linear mixed-effects models.RESULTSWe identified a brain FC phenotype associated with high CeVD burden across all markers. Further, expression of this general CeVD-related FC phenotype and p-tau181 contributed additively, but not synergistically, to baseline and longitudinal grey matter volumes and cognitive changes.DISCUSSIONOur findings suggest that CeVD exerts global effects on the brain connectome and highlight the additive nature of AD and CeVD on neurodegeneration and cognition.
Quantum algorithm for solving the advection equation using Hamiltonian simulation
Authors: Brearley Peter , Laizet Sylvain 
Published: July 2024

A quantum algorithm for solving the advection equation by embedding the discrete time-marching operator into Hamiltonian simulations is presented. One-dimensional advection can be simulated directly since the central finite-difference operator for first-order derivatives is anti-Hermitian. Here this is extended to industrially relevant multidimensional flows with realistic boundary conditions and arbitrary finite-difference stencils. A single copy of the initial quantum state is required and the circuit depth grows linearly with the required number of time steps, the sparsity of the time-marching operator, and the inverse of the allowable error. State-vector simulations of a scalar transported in a two-dimensional channel flow and lid-driven cavity configuration are presented as a proof of concept of the proposed approach.

Published by the American Physical Society
2024
Categorizing
SU(3)f
representations of scalar mesons by
J/ψ
decays
Authors: Geng Chao-Qiang , Liu Chia-Wei , Yu Xiao , Zhou Ao-Wen 
Published: July 2024

The scalar mesons have been established for a long time, but their nature is still an open question. In this paper, we investigate the potential of categorizing their SU(3)f representations via J/ψ→SV and γS, offering a criterion that may illuminate this issue. Here, S (V) denotes scalar (vector) mesons. Using the SU(3)f symmetry with the current data, we find that f0(500) and f0(980) are mostly made of singlet and octet SU(3)f representations, respectively, with the singlet-octet mixing angle of θ=(82.9±4.4)°. This conclusion is consistent with the caculations of the quark-antiquark (qq¯) hypothesis. For the scalar mesons in the range of 1–2 GeV, we discuss the mixings between qq¯ and glueballs. Our numerical results suggest that f0(1710) is likely composed of the scalar glueball. We urge our experimental colleagues to measure J/ψ→ρa0(980,1450,1710), K*(892)±K*(700,1430,1950)∓, and ωf0(500), which provide useful information in the SU(3)f analysis.

Published by the American Physical Society
2024
Toward extracting the scattering phase shift from integrated correlation functions. II. A relativistic lattice field theory model
Authors: Guo Peng 
Published: July 2024

In the present work, a relativistic relation that connects the difference of interacting and noninteracting integrated two-particle correlation functions in finite volume to infinite volume scattering phase shift through an integral is derived. We show that the difference of integrated finite volume correlation functions converges rapidly to its infinite volume limit as the size of the periodic box is increased. The fast convergence of our proposed formalism is illustrated by analytic solutions of a contact interaction model, the perturbation theory calculation, and also the Monte Carlo simulation of a complex ϕ4 lattice field theory model.

Published by the American Physical Society
2024