bluuebunny/crossref_metadata_2025 huggingface dataset:
Household level insecticide deployments (micro-mosaics) for insecticide resistance management: Evaluating deliberate and accidental deployments
Authors: Hobbs Neil Philip , Hastings Ian Michael
Published: July 2024

Mixtures of two insecticides in a single formulation at full-dose are frequently evaluated as the “best” insecticide resistance (IRM) strategy in public health. However, this requires both insecticides to be mixed together in a single formulation which may not be possible or practical. Deploying different insecticides in different households (“micro-mosaics”) may allow for mosquitoes to encounter different insecticides in subsequent gonotrophic cycles obtaining a “temporal mixture”. We evaluate micro-mosaics considering their deliberate use and their accidental use using a mathematical model assuming polygenic resistance. Deliberate micro-mosaics are evaluated against rotations and mixtures (full-dose or half-dose) over a range of scenarios allowing for cross resistance and insecticide decay on their ability to slow the development of resistance. Accidental micro-mosaics are evaluated to understand the implication of mixture insecticide-treated nets (ITNs) and standard (pyrethroid only) ITNs being deployed alongside one another on the development of resistance across a range of initial resistance scenarios. Deliberate micro-mosaics are found to not differ substantially in their IRM capability from either rotations or half-dose mixtures. When micro-mosaics do outperform rotations or half-dose mixtures the benefit is often small. Micro-mosaics are found to perform worse than full-dose mixtures. Accidental micro-mosaics are found to reduce the ability of mixtures to slow the development of resistance. The deployment of deliberate micro-mosaics was found to not be beneficial versus rotations or mixtures indicating this strategy should not be pursued. Micro-mosaics occurring accidentally due to multiple distribution channels inhibits the effectiveness of mixture ITNs in slowing the development of resistance. Where mixture ITNs are used keep the coverage of the mixture high relative to standard (pyrethroid-only) ITNs is key.
Advancing Thalamic Nuclei Segmentation: The Impact of Compressed Sensing and FastSurfer on MRI Processing
Authors: Hübner Sebastian , Tambalo Stefano , Novello Lisa , Hilbert Tom , Kober Tobias , Jovicich Jorge
Published: July 2024

The thalamus is a collection of gray matter nuclei that play a crucial role in sensorimotor processing and modulation of cortical activity. Characterizing thalamic nuclei non-invasively with structural MRI is particularly relevant for patient populations with Parkinson’s disease, epilepsy, dementia, and schizophrenia. However, severe head motion in these populations poses a significant challenge for in vivo mapping of thalamic nuclei. Recent advancements have leveraged the compressed sensing (CS) framework to accelerate structural MRI acquisition times in MPRAGE sequence variants, while fast segmentation tools like FastSurfer have reduced processing times in neuroimaging research.

In this study, we evaluated thalamic nuclei segmentations derived from six different MPRAGE variants with varying degrees of CS acceleration (from about 9 to about 1 minute acquisitions), using both FreeSurfer and FastSurfer for segmentation. Our findings show minimal sequence effects with no systematic bias, and low volume variability across sequences for the whole thalamus and major thalamic nuclei. Notably, CS-accelerated sequences produced less variable volumes compared to non-CS sequences. Additionally, segmentations of thalamic nuclei by FreeSurfer and FastSurfer were highly comparable.

We provide first evidence supporting that a good segmentation quality of thalamic nuclei with compressed sensing T1-weighted image acceleration in a clinical 3T MRI system is possible. Our findings encourage future applications of fast T1-weighted MRI to study deep gray matter. CS-accelerated sequences and rapid segmentation methods are promising tools for future studies aiming to characterize thalamic nuclei in vivo at 3T in both healthy individuals and clinical populations.
Sleep and circadian rhythm activity alterations during adolescence in a mouse model of neonatal fentanyl withdrawal syndrome
Authors: Williams Benjamin R. , Gamble Mackenzie C. , Singh Navsharan , Bryant Camron D. , Logan Beth A. , Logan Ryan W.
Published: July 2024

Purpose

Fentanyl, a highly potent synthetic opioid, is a major contributor to the ongoing opioid epidemic. During adulthood, fentanyl is known to induce pronounced sleep and circadian disturbances during use and withdrawal. Children exposed to opioidsin uteroare likely to develop neonatal opioid withdrawal syndrome, and display sleep disturbances after birth. However, it is currently unknown how neonatal opioid withdrawal from fentanyl impacts sleep and circadian rhythms in mice later in life.

Methods

To model neonatal opioid withdrawal syndrome, mice were treated with fentanyl from postnatal days 1 through 14, analogous to the third trimester of human gestation. After weaning, fentanyl and saline treated mice underwent non-invasive sleep and circadian rhythm monitoring during adolescence postnatal days 23 through 30.

Results

Neonatal fentanyl exposure led to reduced duration of wake and a decrease in the number of bouts of non-rapid eye movement sleep. Further, neonatally exposed mice displayed an increase in the average duration of rapid eye movement sleep bouts, reflecting an overall increase in the percent time spent in rapid eye movement sleep across days.

Conclusions

Neonatal fentanyl exposure leads to altered sleep-wake states during adolescence in mice.
Exploring The Association of Student Perceptions of Their Teachers’ Science Instruction and Emotional Engagement and The Variance between Grade Level
Authors: Xia Xin , Tai Robert H.
Published: July 2024

Abstract

Previous research has consistently shown students have higher learning interests attitudes, and motivation toward science in elementary compared to middle and high school. However, the key predictors behind the observed differences in engagement levels across grade levels remain unclear. This study aims to identify the association between students’ perceptions of science instruction and their emotional engagement, as well as examine the differences across various educational stages. A multilevel random effect model was employed to investigate this association. In addition, the analysis examined whether the associations vary between grade levels. A sample of 6465 students from 25 schools participated in the study.

This study shows that students in higher grades have significantly lower emotional engagement compared to third-grade students. Similarly, students in higher grades have significantly lower values on perceptions of science instruction of interesting science and understandable science decrease compared to third grade. Findings reveal significant associations between students’ perceptions of science instruction, both in perceiving interesting science instruction and understandable science instruction, and their emotional engagement in science learning. The interaction term (Perception of Interesting Science Instruction × Grade) of Grades four, six through eight, and grade 12 are statistically significantly related to emotional engagement, indicating that more positive slopes correspond to high-grade level than third-grade students. The increase in students’ perception of interesting science has the steepest slope of improvement in students’ emotional engagement in 6thgrade. We find no statistically significant difference between grades in students’ perception of understandable science and emotional engagement.

Interesting and understandable science classes have positive correlations with students’ emotional engagement in science learning. For future studies, it is worth exploring science instruction during transition grades to better address and mitigate the observed difference in emotional engagement.
A Portrait of a Young Fish: Redescription ofPteronisculus gunnari(Nielsen, 1942) from a juvenile specimen from the Early Triassic of East Greenland, with implications for ontogenetic development in early actinopterygians
Authors: Cavicchini Iacopo , Argyriou Thodoris , Fernandez Vincent , Dollman Katheen , Giles Sam
Published: July 2024

The Early–Middle Triassic actinopterygian genusPteronisculus(White, 1933) is part of the Triassic Early Fish Fauna (TEFF), a cosmopolitan group of taxa that thrived in the aftermath of the end-Permian mass extinction.Pteronisculusis considered an important non-neopterygian outgroup taxon in many works dealing with the interrelationships of early crown actinopterygians, but the phylogenetic relationships of many of TEFF genera are debated, with the topology of the lineages giving rise to crown actinopterygians consequently unclear. This is despite exceptional, three-dimensionally preservation of an abundance of fossils associated with TEFF fishes.P. gunnari, from the Induan (Early Triassic) Kap Stosch Formation, East Greenland, is known in less detail than other species of the genus. Here, we use X-ray micro-computed tomography to comprehensively redescribe the three-dimensionally preserved holotype ofP. gunnari, including a detailed description of the internal anatomy. The specimen shows morphological features previously undescribed for the genus, including paired premaxillae, medially-directed teeth on the palate, canals for the buccohypophysial canal and internal carotids piercing the parasphenoid, and numerous parotic toothplates. Scale covering is complete, but the braincase and palatoquadrate are ossified as multiple elements, indicating that the specimen was not fully mature and allowing new insights into ossification patterns and ontogenetic development of non-neopterygian actinopterygians. These new anatomical data enrich our understanding of both the morphological complexity and the interrelationships of actinopterygians from the Triassic Early Fish Fauna.
Beta-frequency sensory stimulation enhances gait rhythmicity through strengthened coupling between striatal networks and stepping movement
Authors: Sridhar Sudiksha , Lowet Eric , Gritton Howard J. , Freire Jennifer , Zhou Chengqian , Liang Florence , Han Xue
Published: July 2024

Stepping movement is delta (1-4 Hz) rhythmic and depends on sensory inputs. In addition to delta rhythms, beta (10-30 Hz) frequency dynamics are also prominent in the motor circuits and are coupled to neuronal delta rhythms both at the network and the cellular levels. Since beta rhythms are broadly supported by cortical and subcortical sensorimotor circuits, we explore how beta-frequency sensory stimulation influences delta-rhythmic stepping movement, and dorsal striatal circuit regulation of stepping. We delivered audiovisual stimulation at 10 Hz or 145 Hz to mice voluntarily locomoting, while simultaneously recording stepping movement, striatal cellular calcium dynamics and local field potentials (LFPs). We found that 10 Hz, but not 145 Hz stimulation prominently entrained striatal LFPs. Even though sensory stimulation at both frequencies promoted locomotion and desynchronized striatal network, only 10 Hz stimulation enhanced the delta rhythmicity of stepping movement and strengthened the coupling between stepping and striatal LFP delta and beta oscillations. These results demonstrate that higher frequency sensory stimulation can modulate lower frequency dorsal striatal neural dynamics and improve stepping rhythmicity, highlighting the translational potential of non-invasive beta-frequency sensory stimulation for improving gait.
Coordination of transcription-coupled repair and repair-independent release of stalled RNA polymerase II in response to transcription-blocking lesions
Authors: Zhu Yongchang , Zhang Xiping , Gao Meng , Huang Yanchao , Tan Yuanqing , Parnas Avital , Wu Sizhong , Zhan Delin , Adar Sheera , Hu Jinchuan
Published: July 2024

Transcription-blocking lesions (TBLs) stall elongating RNA polymerase II (PolII), which then initiates transcription-coupled repair (TCR) to remove TBLs and allow transcription recovery. In the absence of TCR, eviction of lesion-stalled PolII is required for alternative pathways to address the damage, but the mechanism is unclear. This study, utilizing Protein-Associated DNA Damage Sequencing (PADD-seq), reveals that the p97-proteasome pathway can evict lesion-stalled PolII independently of repair. Both TCR and repair-independent eviction require CSA and ubiquitination. However, p97 is dispensable for TCR and PolII eviction in TCR-proficient cells, highlighting repair’s prioritization over repair-independent eviction. Moreover, ubiquitination of RPB1-K1268 is important for both pathways, with USP7’s deubiquitinase activity promoting TCR without abolishing repair-independent PolII release. In summary, this study elucidates the fate of lesion-stalled PolII, and may shed light on the molecular basis of genetic diseases caused by the defects of TCR genes.
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

Background

Clinical 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.

Methods

We 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.

Results

The 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.

Conclusions

The 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

Background

Spinal 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.

Methods

Hospitalizations 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.

Results

An 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.

Conclusions

This 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

The 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

Placental 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

Host-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

The 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

The 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

Bacillus 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.

IMPORTANCE

Understanding 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

Purpose

This 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.

Method

Authors 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.

Results

GPT-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.

Conclusions

GPT-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

INTRODUCTION

We 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.

METHODS

Multivariate 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.

RESULTS

We 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.

DISCUSSION

Our findings suggest that CeVD exerts global effects on the brain connectome and highlight the additive nature of AD and CeVD on neurodegeneration and cognition.
Accurate estimation of pathway activity in single cells for clustering and differential analysis
Authors: Davis Daniel , Wizel Avishai , Drier Yotam
Published: July 2024

Inferring which and how biological pathways and gene sets change is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer SiPSiC, a new method to infer pathway activity in every single cell. This allows more sensitive differential analysis and utilization of pathway scores to cluster cells and compute UMAP or other similar projections. We apply our method to COVID-19, lung adenocarcinoma and glioma data sets, and demonstrate its utility. SiPSiC analysis results are consistent with findings reported in previous studies in many cases, but SiPSiC also reveals the differential activity of novel pathways, enabling us to suggest new mechanisms underlying the pathophysiology of these diseases and demonstrating SiPSiC's high accuracy and sensitivity in detecting biological function and traits. In addition, we demonstrate how it can be used to better classify cells based on activity of biological pathways instead of single genes and its ability to overcome patient-specific artifacts.
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
Entanglement entropy of (
2+1
)-dimensional SU(2) lattice gauge theory on plaquette chains
Authors: Ebner Lukas , Schäfer Andreas , Seidl Clemens , Müller Berndt , Yao Xiaojun
Published: July 2024

We study the entanglement entropy of Hamiltonian SU(2) lattice gauge theory in 2+1 dimensions on linear plaquette chains and show that the entanglement entropies of both ground and excited states follow Page curves. The transition of the subsystem size dependence of the entanglement entropy from the area law for the ground state to the volume law for highly excited states is found to be described by a universal crossover function. Quantum many-body scars in the middle of the spectrum, which are present in the electric flux truncated Hilbert space, where the gauge theory can be mapped onto an Ising model, disappear when higher electric field representations are included in the Hilbert space basis. This suggests the continuum (2+1)-dimensional SU(2) gauge theory does not have such scarred states.

Published by the American Physical Society
2024
U(1) fields from qubits: An approach via D-theory algebra
Authors: Berenstein David , Kawai Hiroki , Brower Richard
Published: July 2024

A new quantum link microstructure was proposed for the lattice quantum chromodynamics (QCD) Hamiltonian, replacing the Wilson gauge links with a bilinear of fermionic qubits, later generalized to D-theory. This formalism provides a general framework for building lattice field theory algorithms for quantum computing. We focus mostly on the simplest case of a quantum rotor for a single compact U(1) field. We also make some progress for non-Abelian setups, making it clear that the ideas developed in the U(1) case extend to other groups. These in turn are building blocks for 1+0-dimensional (1+0-D) matrix models, 1+1-D sigma models and non-Abelian gauge theories in 2+1 and 3+1 dimensions. By introducing multiple flavors for the U(1) field, where the flavor symmetry is gauged, we can efficiently approach the infinite-dimensional Hilbert space of the quantum O(2) rotor with increasing flavors. The emphasis of the method is on preserving the symplectic algebra exchanging fermionic qubits by sigma matrices (or hard bosons) and developing a formal strategy capable of generalization to a SU(3) field for lattice QCD and other non-Abelian 1+1-D sigma models or 3+1-D gauge theories. For U(1), we discuss briefly the qubit algorithms for the study of the discrete 1+1-D sine-Gordon equation.

Published by the American Physical Society
2024
Probing the sterile neutrino dipole portal with SN1987A and low-energy supernovae
Authors: Chauhan Garv , Horiuchi Shunsaku , Huber Patrick , Shoemaker Ian M.
Published: July 2024

Beyond the Standard Model electromagnetic properties of neutrinos may lead to copious production of sterile neutrinos in the hot and dense core of a core-collapse supernova. In this work, we focus on the active-sterile transition magnetic moment portal for heavy sterile neutrinos. Firstly, we revisit the SN1987A cooling bounds for dipole portal using the integrated luminosity method, which yields more reliable results (especially in the trapping regime) compared to the previously explored via emissivity loss, also known as the Raffelt criterion. Secondly, we obtain strong bounds on the dipole coupling strength reaching as low as 10−11  GeV−1 from energy deposition, i.e., constrained from the observation of explosion energies of underluminous Type IIP supernovae. In addition, we find that sterile neutrino production from Primakoff upscattering off of a proton dominates over scattering off of an electron for low sterile neutrino masses.

Published by the American Physical Society
2024
Accumulating hints for flavor-violating Higgs bosons at the electroweak scale
Authors: Crivellin Andreas , Iguro Syuhei
Published: July 2024

We show that supplementing the Standard Model by only a second Higgs doublet, a combined explanation of h→eτ, h→μτ, b→sℓ+ℓ−, the W mass and R(D(*)) as well as the excess in t→bH+(130  GeV)→bb¯c is possible. While this requires flavor violating couplings, the stringent bounds from, e.g., μ→eγ, τ→μγ, Bs−B¯s mixing, b→sγ, low mass dijet, and pp→H+H−→τ+τ−νν¯ searches can be avoided. However, the model is very constrained; it inevitably predicts a shift in the SM Higgs coupling strength to tau leptons as well as a nonzero t→hc rate, as indeed preferred by recent measurements. We study three benchmark points providing such a simultaneous explanation and calculate their predictions, including collider signatures which can be tested with upcoming LHC run-3 data.

Published by the American Physical Society
2024
Effects of squared four-fermion operators of the standard model effective field theory on meson mixing
Authors: Vale Silva Luiz
Published: July 2024

The standard model effective field theory (SMEFT) is a universal way of parametrizing new physics (NP) manifesting as new, heavy particle interactions with the Standard Model (SM) degrees of freedom, that respect the SM gauged symmetries. Higher order terms in the NP interactions possibly lead to sizable effects, mandatory for meaningful phenomenological studies, such as contributions to neutral meson mixing, which typically pushes the scale of NP to energy scales much beyond the reach of direct searches in colliders. I discuss the leading-order renormalization of double-insertions of dimension-6 four-fermion operators that change quark flavor by one unit (i.e., |ΔF|=1, F=strange-, charm-, or bottom-flavor), by dimension-8 operators relevant to meson mixing (i.e., |ΔF|=2) in SMEFT. Then, I consider the phenomenological implications of contributions proportional to large Yukawas, setting bounds on the Wilson coefficients of operators of dimension-6 via the leading logarithmic contributions. Given the underlying interest of SMEFT to encode full-fledged models at low energies, this work stresses the need to consider dimension-8 operators in phenomenological applications of dimension-6 operators of SMEFT.

Published by the American Physical Society
2024
Analytical formula for signal optimization in stimulated photon-photon scattering setup with three laser pulses
Authors: Berezin A. V. , Fedotov A. M.
Published: July 2024

We consider a setup to detect stimulated photon-photon scattering using high-power lasers. Signal photons are emitted from an overlap of the incoming intense laser pulses focused in vacuum from three sides. We derive and justify a general approximate analytical formula for the angular distribution and total yield of such signal photons in terms of the parameters of the incoming pulses, including their intensity, carrier frequencies, durations, focusing, polarizations, mutual orientation and overlap. Using the obtained formula a parametric study of the signal is carried out and optimization is performed.

Published by the American Physical Society
2024
Prediction of the bubble wall velocity for a large jump in degrees of freedom
Authors: Sanchez-Garitaonandia Mikel , van de Vis Jorinde
Published: July 2024

The bubble expansion velocity is an important parameter in the prediction of gravitational waves from first-order phase transitions. This parameter is difficult to compute, especially in phase transitions in strongly coupled theories. In this work, we present a method to estimate the wall velocity for phase transitions with a large enthalpy jump, valid for weakly and strongly coupled theories. We find that detonations are disfavored in this limit, but wall velocities are not necessarily small. We also investigate the effect of two other features in the equation of state: nonconformal sound speeds and a limited range of temperatures for which the phases exist. We find that the former can increase the wall velocity for a given nucleation temperature, and the latter can restrict the wall velocities to small values. To test our approach, we use holographic phase transitions, which typically display these three features. We find excellent agreement with numerically obtained values of the wall velocity. We also demonstrate that the implications for gravitational waves can be significant.

Published by the American Physical Society
2024
Higher-curvature gravity in
AdS3
, holographic
c
-theorems, and black hole microstates
Authors: Chernicoff M. , Giribet G. , Moreno J. , Oliva J. , Rojas R. , Torres C. Ramirez de Arellano
Published: July 2024

We construct higher-derivative gravity theories in three dimensions that admit holographic c-theorems and exhibit a unique maximally symmetric vacuum, at arbitrary order n in the curvature. We show that these theories exhibit special properties, the most salient ones being the decoupling of ghost modes around anti–de Sitter (AdS) space, the enhancement of symmetries at linearized level, and the existence of a one-parameter generalization of the Bañados-Teitelboim-Zanelli (BTZ) black hole that, while being asymptotically AdS, is not of constant curvature but rather exhibits a curvature singularity. For such black holes, we provide a holographic derivation of their thermodynamics. This gives a microscopic picture of black hole thermodynamics for nonsupersymmetric solutions, of nonconstant curvature in higher-derivative theories of arbitrary order in the curvature.

Published by the American Physical Society
2024
Toward higher-spin symmetry breaking in the bulk
Authors: Didenko V. E. , Korybut A. V.
Published: July 2024

We present a new vacuum of the bosonic higher-spin gauge theory in d+1 dimensions, which has leftover symmetry of the Poincaré algebra in d dimensions. Its structure is very simple: the space-time geometry is that of anti–de Sitter space, while the only nonzero field is a scalar. The scalar extends along the Poincaré radial coordinate z and is shown to be linearly exact for an arbitrary mixture of its two Δ=2 and Δ=d−2 conformal branches. The obtained vacuum breaks the global higher-spin symmetry, leading to a broken phase that lives in the Minkowski space-time.

Published by the American Physical Society
2024
Inhomogeneous Kinetic Equation for Mixed Neutrinos: Tracing the Missing Energy
Authors: Fiorillo Damiano F. G. , Raffelt Georg G. , Sigl Günter
Published: July 2024

Flavor-dependent neutrino transport is described by a well-known kinetic equation for occupation-number matrices in flavor space. However, in the context of fast flavor conversion, we identify an unforeseen predicament: the pivotal self-induced exponential growth of small inhomogeneities strongly violates conservation of neutrino-neutrino refractive energy. We prove that it is traded with the huge reservoir of neutrino kinetic energy through gradients of neutrino flavor coherence (the off-diagonal piece of the flavor density matrix) and derive the missing gradient terms. The usual equations remain sufficient to describe flavor evolution, at the cost of renouncing energy conservation, which cannot play any role in explaining the numerically observed final state.

Published by the American Physical Society
2024