bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of the expansion of the Personal Assistance Service Program on the uptake of the National Health Screening in people with severe disability
Authors: Kim Woorim , Choi Mingee , Shin Jaeyong
Published: October 2024

Background

Korea operates the Personal Assistance Service (PAS) program, a social service program that assists with the daily activities and coping needs of individuals with disabilities. In January 2013, the eligibility to enroll in the PAS program was expanded to include all individuals with severe disabilities.

Objective

As supporting individuals with disabilities is important in reducing disparities related to the uptake of health screening, this study investigated whether eligibility expansion of the PAS program was associated with increased participation in the National Health Screening Program (NHSP) among adults with severe disabilities.

Methods

Nationwide data from Korea that included 24 701 individuals were used. The treatment group included individuals with severe disabilities, while the control group included those with mild disabilities. The difference-in-difference approach was used to estimate differences in participation in the NHSP between the two groups before and after the intervention period. A negative binomial distribution model was applied in the analysis with adjustment for all independent variables.

Results

The expansion of the PAS program was directly related to an increase in NHSP uptake by people with severe disabilities (increase by 0.044 times compared to the control group following the implementation of the policy).

Conclusions

Expanding the eligibility for the PAS program was associated with an increase in NHSP participation among individuals with severe disabilities. These findings suggest the importance of supporting individuals with disabilities by increasing participation in health screenings to reduce potential related health disparities.
Isotopic steady state or non-steady state transpiration? Insights from whole-tree chambers
Authors: Harwood Richard , Cernusak Lucas A , Drake John E , Barton Craig V M , Tjoelker Mark G , Barbour Margaret M
Published: October 2024

Unravelling the complexities of transpiration can be assisted by understanding the oxygen isotope composition of transpired water vapour (δE). It is often assumed that δE is at steady state, thereby mirroring the oxygen isotope composition of source water (δsource), but this assumption has never been tested at the whole-tree scale. This study utilized the unique infrastructure of 12 whole-tree chambers enclosing Eucalyptus parramattensis E.C.Hall trees to measure δE along with concurrent temperature and gas exchange data. Six chambers tracked ambient air temperature and six were exposed to an ambient +3 °C warming treatment. Day time means for δE were within 1.2‰ of δsource (−3.3‰) but varied considerably throughout the day. Our observations show that E. parramattensis trees are seldom transpiring at isotopic steady state over a diel period, but transpiration approaches source water isotopic composition over longer time periods.
Assessment of Radiotherapy as a Standalone Treatment Following Neoadjuvant Chemotherapy in Nonmetastatic Breast Cancer
Authors: Loap Pierre , Kirova Youlia
Published: October 2024

Objectives:

Traditional breast cancer management involves surgery followed by systemic therapies. However, advancements in neoadjuvant chemotherapy (NACT) raise questions about the necessity of surgery in cases with an excellent response to NACT. This study investigates the outcomes of radiotherapy without surgery in selected patients with nonmetastatic breast cancer after a complete or substantial response to NACT.

Methods:

A retrospective study was conducted using the SEER database, reviewing records from 2010 to 2020 for patients with nonmetastatic breast cancer who received NACT, associated with a clinical response, followed by radiotherapy alone. The population included 123 patients, stratified into complete clinical response (cCR) and non-cCR (partial or unspecified clinical response) cohorts. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier and Cox proportional hazards models.

Results:

The median follow-up was 41 months. Among the patients, 17 (13.82%) achieved cCR. The 5-year OS and CSS for the entire cohort were 65.8% and 71%, respectively, with the cCR group achieving 100% rates for both. Age above 60 and larger tumor size (T3 to T4) were associated with lower OS. The non-cCR group showed a 5-year OS of 61.5% and CSS of 67.1%.

Conclusions:

This study indicates that omitting surgery in patients with a cCR to NACT may be feasible, as evidenced by this subgroup's 100% OS and CSS rates at 5 and 10 years. These promising results support further research into less invasive breast cancer management. However, prospective studies must validate these findings and identify suitable patients for nonsurgical approaches.
Coronary artery injury in pulsed field ablation
Authors: Higuchi Satoshi , Gerstenfeld Edward P.
Published: October 2024

Purpose of review

Although pulsed field ablation (PFA) has emerged as an innovative nonthermal catheter ablation modality, recent reports raise concerns about its potential impact on nearby coronary arteries. This review provides a comprehensive overview of the current understanding and future directions regarding the effects of PFA on or near coronary arteries.

Recent findings

Clinical studies have demonstrated the risks of acute transient vasospasm after delivery of PFA, especially with ablation of structures in proximity to the coronary arteries, such as the cavotricuspid and mitral isthmuses. The clinical incidence has been reported to be approximately 0.14%, according to the largest multicenter registry. Nitroglycerin pretreatment has been demonstrated to mitigate vasospastic events. However, early preclinical models indicate that chronic neointimal hyperplasia, tunica media fibrosis and mild coronary artery narrowing may occur, suggesting long-term coronary injury after delivering PFA near coronary arteries.

Despite reducing collateral tissue damage compared with thermal methods, PFA near coronary arteries may require careful procedural planning and proactive use of nitroglycerin to reduce coronary vasospasm. Further research is essential to elucidate the mechanisms underlying PFA-induced coronary spasm, optimize catheter design and placement, and assess the long-term coronary health implications.
Effects of a Smartphone App-Based Intervention on Rheumatoid Arthritis Self-Management Efficacy: A Randomized Controlled Trial
Authors: SHAO Jung-Hua , YU Kuang-Hui , KAO Yi-Chun , LIANG Yen-Chiu , CHEN Su-Hui
Published: October 2024

Background

Self-management programs can help patients with rheumatoid arthritis develop strategies to address their disease-related problems. However, accessibility to traditional self-management programs is often limited.

Purpose

This study was developed to assess the effectiveness, feasibility, and acceptability of a smartphone-delivered self-management program application (app) for adults with rheumatoid arthritis.

Methods

A two-arm (intervention vs. control) randomized controlled trial was used. Adult patients with rheumatoid arthritis were recruited from the rheumatology departments of a medical center. Study enrollment capabilities were limited by current pandemic restrictions. The patients who met the inclusion criteria and agreed to participate (N = 46) were enrolled as participants and randomly assigned either to the intervention group (n = 25), which received instructions on the use of a smartphone app designed to facilitate the self-management of rheumatoid arthritis, or to the control group (n = 21), which received instructions on related self-management only. The outcome variables were assessed at baseline and at 8 and 12 weeks. Differences in between-group outcomes over time were analyzed using generalized estimating equations. Feasibility and acceptability were also evaluated. Data were collected between August 1, 2020, and July 31, 2022.

Results

At baseline, no differences were detected between the two groups in terms of the demographic and disease characteristics of concern. Outcome measures for the intervention group improved significantly more than the control group for self-efficacy of pain at 8 weeks (B = 6.39, p < .05) and for both of self-efficacy of pain and self-management behavior at 12 weeks (B = 9.16, p < .05, and B = 4.25, p < .001, respectively). Factors related to app ease of use included limiting pop-ups and windows and having no time restrictions. Most of the participants reported the app as acceptable and easy to use, although challenges relating to using technology limited the usability of the app for some.

Conclusions/Implications for Practice

The smartphone app was shown to improve self-efficacy of pain and self-management behaviors. However, an accurate assessment of the effectiveness of the app and generalizability of the findings is limited by the smaller-than-desired sample size due to the COVID-19 pandemic and technological challenges. A greater understanding of how to overcome technological challenges is needed to optimize the delivery of self-management programs via smartphone-based apps. Studies reevaluating this app on a larger sample size should be conducted.
Insights into Overuse: Ergonomic Trends and Pain Prevalence Among Orthotics and Prosthetics Practitioners in the United States
Authors: Sherman Jeremy , Gregg Keelan , Parker Taylor
Published: October 2024

Introduction

The field of orthotics and prosthetics (O&P) combines patient care and craftsmanship, with professionals working in a physically challenging atmosphere. Despite studies in related health care professions, there is a lack of research on ergonomics within O&P in the United States.

Methods

A 45-question survey was developed with questions focusing on demographics, pain locations, ergonomic setup, and daily ergonomic demands. Respondents included certified orthotists, prosthetists, pedorthists, technicians, fitters, residents, students, and educators.

Results

A total of 152 completed responses were analyzed, with 62.50% of O&P professionals reporting chronic, acute, or both types of pain. Younger and less experienced professionals were more likely to report pain. Pain was commonly experienced in the lumbar and cervical spines and the right upper limb. Activities like fabrication work, computer-based tasks, and frequent reaching above shoulder height correlated with the presence of pain.

Conclusions

The study highlights the prevalence of pain among US O&P professionals, emphasizing the need for targeted ergonomic interventions. Diverse body positions during tasks indicate a lack of standardized ergonomic approaches in O&P clinics. In addition, the presence of clinic amenities such as adjustable-height patient beds did not have an effect on the presence of pain. This suggests that, in addition to new interventions, the implementation of existing ergonomic solutions must be revisited. Maintaining ergonomic principles, such as maintaining ideal working height and neutral postures, is crucial for mitigating the risk of overuse injuries.

Clinical Relevance

The study indicates a high prevalence of pain among O&P professionals, which disproportionately affects those who are younger and less experienced. This suggests practice guidelines and interventions should be designed to address the needs of this demographic, potentially focusing on standardizing procedures, optimizing work processes, and minimizing prolonged exposure to physically demanding tasks.
The diagnostic value of combining preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging in preoperative resectability of pancreatic cancer
Authors: Yang Shuli , Ma Ruixue , Wu Jing
Published: October 2024

Objective

Pancreatic cancer is an increasing cause of cancer-related mortality, with persistently low survival rates. We investigated the clinical diagnostic value of the combination of preoperative serum carbohydrate antigen 19-9 (CA19-9), albumin–bilirubin (ALBI) score, and 18F-fluoro-2-deoxy-d-glucose PET integrated with computed tomography (18F-FDG PET/CT) imaging in pancreatic cancer preoperative resectability.

Methods

This study included 143 pancreatic cancer patients, including 68 preoperative resectable and 75 preoperative unresectable pancreatic cancer patients. Meanwhile, 67 patients with non-pancreatic cancer were included as the control group. The clinical data were collected. Serum CA19-9 level was measured by ELISA. The levels of total bilirubin and albumin were determined using a biochemical analyzer, with the ALBI score calculated. All patients underwent 18F-FDG PET/CT imaging. The consistency of the diagnosis was evaluated by the Kappa test. Logistic univariate and multivariate regression analyses were performed. The diagnostic efficacy of these parameters was evaluated using receiver operating characteristic (ROC) curves, and the optimal ROC curve thresholds were obtained using the Youden index.

Results

The preoperative serum CA19-9 and ALBI score of patients with preoperative resectable pancreatic cancer were increased, which helped diagnose preoperative resectable pancreatic cancer. 18F-FDG PET/CT imaging had diagnostic value for preoperative resectable pancreatic cancer. Preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging were independent influencing factors for pancreatic cancer preoperative resectability, and their combination had higher diagnostic value for preoperative resectable pancreatic cancer than any single of these indexes.

Conclusion

The combination of preoperative serum CA19-9, ALBI score, and 18F-FDG PET/CT imaging had high diagnostic value for pancreatic cancer preoperative resectability.
Retrospective Data-Driven Motion Correction of 18F-FDG Brain PET
Authors: Maurer Alexander , Spangler-Bickell Matthew G. , Mader Cäcilia E. , Kotasidis Fotis , Huellner Martin W.
Published: October 2024

A 51-year-old man with severe multifactorial neurocognitive disorders subsequent to delirium, benzodiazepine withdrawal, and preexisting psychiatric illness was referred for 18F-FDG PET/CT brain imaging in order to rule out an underlying neurodegenerative cause of the symptoms, particularly frontotemporal lobar degeneration. Imaging was impaired by severe motion artifacts, leading to a false-positive result. However, utilizing retrospective data-driven motion correction facilitated a change in diagnosis, ruling out the presence of neurodegenerative disease. The implementation of motion correction of the 18F-FDG PET dataset proved crucial for the patient, as the exclusion of frontotemporal lobar degeneration formed the basis for continuing psychiatric and psychotherapeutic treatment.
Upper bill bending as an adaptation for nectar feeding in hummingbirds
Authors: Rico-Guevara Alejandro , Sustaita Diego , Hurme Kristiina J. , Hanna Jenny E. , Jung Sunghwan , Field Daniel J.
Published: October 2024

Observations of maxillary (upper bill) bending in hummingbirds have been considered an optical illusion, yet a recent description of out-of-phase opening and closing between their bill base and tip suggests a genuine capacity for bill bending. We investigate bill kinematics during nectar feeding in six species of hummingbirds. We employed geometric morphometrics to identify bending zones and combined these data with measurements of bill flexural rigidity from microCT scans to better understand the flexing mechanism. We found that the mandible remains in place throughout the licking cycle, while the maxilla undergoes significant shape deformation, such that the distal portion of the upper bill bends upwards. We propose that bill bending is a key component of the drinking mechanism in hummingbirds, allowing the coordination of bill function (distal wringing and basal expansion) and tongue function (raking/squeegeeing) during intraoral transport. We present a fluid analysis that reveals a combination of pressure-driven (Poiseuille) and boundary-driven (Couette) flows, which have previously been thought to represent alternative drinking mechanisms. Bill bending allows for separation of the bill tips while maintaining a tightly closed middle section of the bill, enabling nectar exploitation in long and narrow flowers that can exclude less efficient pollinators.
Leveraging genomic large language models to enhance causal genotype-brain-clinical pathways in Alzheimer’s disease
Authors: Liu Qiao , Zeng Wanwen , Zhu Hongtu , Li Lexin , Wong Wing Hung ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2024

Genome-wide association studies (GWAS) have identified numerous Alzheimer’s disease (AD)- associated variants. However, how these variants contribute to the etiology of AD remains largely elusive. Recent advances in genomic large language models (LLMs) offer new opportunities to interpret the genetic variation observed in personal genome. In this study, we propose epiBrainLLM, a novel computational framework that leverages genomic LLM to enhance our understanding of the causal pathways from genotypes to brain measures to AD-related clinical phenotypes. epiBrainLLM will first convert the personal DNA sequence into a diverse set of genomic and epigenomic features using a pretrained genomic LLM and then use these features to further predict phenotypes. Across various experimental settings, epiBrainLLM significantly improves causal analysis compared to traditional genotype association approach. We conclude that epiBrainLLM provides a novel perspective for understanding the regulatory mechanisms underlying the AD disease etiology, potentially offering insights into complex disease mechanisms beyond AD.
VITRUVIUS: A conversational agent for real-time evidence based medical question answering
Authors: Villa Maria Camila , Llano Isabella , Castano-Villegas Natalia , Martinez Julian , Guevara Maria Fernanda , Zea Jose , Velásquez Laura
Published: October 2024

Background

The application of Large Language Models (LLMs) to create conversational agents (CAs) that can aid health professionals in their daily practice is increasingly popular, mainly due to their ability to understand and communicate in natural language. Conversational agents can manage enormous amounts of information, comprehend and reason with clinical questions, extract information from reliable sources and produce accurate answers to queries. This presents an opportunity for better access to updated and trustworthy clinical information in response to medical queries.

Objective

We present the design and initial evaluation of Vitruvius, an agent specialized in answering queries in healthcare knowledge and evidence-based medical research.

Methodology

The model is based on a system containing 5 LLMs; each is instructed with precise tasks that allow the algorithms to automatically determine the best search strategy to provide an evidence-based answer. We assessed our system’s comprehension, reasoning, and retrieval capabilities using the public clinical question-answer dataset MedQA-USMLE. The model was improved accordingly, and three versions were manufactured.

Results

We present the performance assessment for the three versions of Vitruvius, using a subset of 288 QA (Accuracy V1 86%, V2 90%, V3 93%) and the complete dataset of 1273 QA (Accuracy V2 85%, V3 90.3%). We also evaluate intra-inter-class variability and agreement. The final version of Vitruvius (V3) obtained a Cohen’s kappa of 87% and a state-of-the-art (SoTA) performance of 90.26%, surpassing current SoTAs for other LLMs using the same database.

Conclusions

Vitruvius demonstrates excellent performance in medical QA compared to standard database responses and other popular LLMs. Future investigations will focus on testing the model in a real-world clinical environment. While it enhances productivity and aids healthcare professionals, it should not be utilized by individuals unqualified to reason with medical data to ensure that critical decision-making remains in the hands of trained professionals.
Exploring the trade-off between deep-learning and explainable models for brain-machine interfaces
Authors: Cubillos Luis H. , Revach Guy , Mender Matthew J. , Costello Joseph T. , Temmar Hisham , Hite Aren , Zutshi Diksha , Wallace Dylan M. , Ni Xiaoyong , Kelberman Madison M. , Willsey Matthew S. , van Sloun Ruud J.G. , Shlezinger Nir , Patil Parag , Draelos Anne , Chestek Cynthia A.
Published: October 2024

People with brain or spinal cord-related paralysis often need to rely on others for basic tasks, limiting their independence. A potential solution is brain-machine interfaces (BMIs), which could allow them to voluntarily control external devices (e.g., robotic arm) by decoding brain activity to movement commands. In the past decade, deep-learning decoders have achieved state-of-the-art results in most BMI applications, ranging from speech production to finger control. However, the ‘black-box’ nature of deep-learning decoders could lead to unexpected behaviors, resulting in major safety concerns in real-world physical control scenarios. In these applications, explainable but lower-performing decoders, such as the Kalman filter (KF), remain the norm. In this study, we designed a BMI decoder based on KalmanNet, an extension of the KF that augments its operation with recurrent neural networks to compute the Kalman gain. This results in a varying “trust” that shifts between inputs and dynamics. We used this algorithm to predict finger movements from the brain activity of two monkeys. We compared KalmanNet results offline (pre-recorded data,n= 13 days) and online (real-time predictions,n= 5 days) with a simple KF and two recent deep-learning algorithms with state-of-the-art results: tcFNN and LSTM. KalmanNet achieved comparable or better results than other deep learning models in offline and online modes, relying on the dynamical model for stopping while depending more on neural inputs for initiating movements. We further validated this mechanism by implementing a heteroscedastic KF that used the same strategy, and it also approached state-of-the-art performance while remaining in the explainable domain of standard KFs. However, we also see two downsides to KalmanNet. KalmanNet shares the limited generalization ability of existing deep-learning decoders, and its usage of the KF as an inductive bias limits its performance in the presence of unseen noise distributions. Despite this trade-off, our analysis successfully integrates traditional controls and modern deep-learning approaches to motivate high-performing yet still explainable BMI designs.
Mechanobiological cues to bone cells during early metastasis drive later osteolysis: a computational mechanoregulation framework prediction
Authors: Verbruggen Anneke S.K. , McCarthy Elan C. , Dwyer Roisin , McNamara Laoise M.
Published: October 2024

Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.
Gene-by-environment interactions and adaptive body size variation in mice from the Americas
Authors: Mack Katya L. , Landino Nico P. , Tertyshnaia Mariia , Longo Tiffany C. , Vera Sebastian A. , Crew Lilia A. , McDonald Kristi , Phifer-Rixey Megan
Published: October 2024

The relationship between genotype and phenotype is often mediated by the environment. Moreover, gene-by-environment (GxE) interactions can contribute to variation in phenotypes and, in turn, fitness. Nevertheless, understanding the impact of GxE interactions in wild systems remains challenging. In the last 500 years, house mice have invaded the Americas. Despite their short residence time, there is evidence of rapid climate adaptation, including shifts in body size and aspects of metabolism with latitude. Previous studies in this system have identified candidate genes for metabolic adaptation using selection scans, however, environmental variation in diet as well as GxE interactions affecting metabolism are likely important factors in shaping body mass variation in wild populations. Here, we investigate the role of the environment and GxE interactions in shaping adaptive phenotypic variation with an experimental manipulation of diet. Using new locally adapted inbred strains from North and South America, we evaluated response to a high-fat diet, finding that sex, strain, diet, and the interaction between strain and diet contribute significantly to variation in aspects of body size. We also found that transcriptional response to diet is largely strain-specific, indicating that GxE interactions affecting gene expression are pervasive. Next, we used crosses between strains from contrasting climates (New York x Brazil and New York x Florida) to characterize gene expression regulatory divergence on a standard breeder diet and on a high-fat diet. We found that gene regulatory divergence is often condition-specific, particularly fortrans-acting changes. Finally, we find evidence for lineage-specific selection oncis-regulatory variation involved in diverse processes, including lipid metabolism. Overlap with scans for selection identified candidate genes for environmental adaptation with diet-specific effects. Together, our results underscore the importance of environmental variation and GxE interactions to adaptive variation in complex traits.
3D Reconstruction Enables High-Throughput Phenotyping and Quantitative Genetic Analysis of Phyllotaxy
Authors: Davis Jensina M. , Gaillard Mathieu , Tross Michael C. , Shrestha Nikee , Ostermann Ian , Grove Ryleigh J. , Li Bosheng , Benes Bedrich , Schnable James C.
Published: October 2024

Differences in canopy architecture play a role in determining both the light and water use efficiency. Canopy architecture is determined by several component traits, including leaf length, width, number, angle, and phyllotaxy. Phyllotaxy may be among the most difficult of the leaf canopy traits to measure accurately across large numbers of individual plants. As a result, in simulations of the leaf canopies of grain crops such as maize and sorghum, this trait is frequently approximated as alternating 180° angles between sequential leaves. We explore the feasibility of extracting direct measurements of the phyllotaxy of sequential leaves from 3D reconstructions of individual sorghum plants generated from 2D calibrated images and test the assumption of consistently alternating phyllotaxy across a diverse set of sorghum genotypes. Using a voxel-carving-based approach, we generate 3D reconstructions from multiple calibrated 2D images of 366 sorghum plants representing 236 sorghum genotypes from the sorghum association panel. The correlation between automated and manual measurements of phyllotaxy is only modestly lower than the correlation between manual measurements of phyllotaxy generated by two different individuals. Automated phyllotaxy measurements exhibited a repeatability ofR2= 0.41 across imaging timepoints separated by a period of two days. A resampling based genome wide association study (GWAS) identified several putative genetic associations with lower-canopy phyllotaxy in sorghum. This study demonstrates the potential of 3D reconstruction to enable both quantitative genetic investigation and breeding for phyllotaxy in sorghum and other grain crops with similar plant architectures.
Pathological PNPase variants with altered RNA binding and degradation activity affect the phenotype of bacterial and human cell models
Authors: Pizzoccheri R. , Falchi F. A. , Alloni A. , Caldarulo M. , Camboni T. , Zambelli F. , Pavesi G. , Visentin C. , Camilloni C. , Sertic S. , Briani F.
Published: October 2024

Human PNPase (hPNPase) is an essential RNA exonuclease located in mitochondria, where it contributes to RNA import from the cytoplasm, degradation of mitochondrial RNA, and R-loop homeostasis. Biallelic mutations in the hPNPasePNPT1gene cause different genetic diseases, ranging from hereditary hearing loss to Leigh syndrome. In this work, we used anEscherichia colimodel we recently developed to test the effects of four pathologicalPNPT1mutations associated with diseases of different severity. Moreover, we generated a new human cell model by introducingPNPT1mutations into 293T cells via CRISPR-Cas editing. Notably, the bacterial cells expressing the different mutant alleles exhibited similar phenotypes consistent with hPNPase loss of function. In contrast, the human cell model responded differently to the two mutations tested, with responses correlating with the severity of the respective pathologies. We interpreted the data derived from both models in the light of thein vitroRNA binding and degradation activity of the purified wild-type and mutated hPNPase variants. We found that all pathogenic mutations tested caused defects in protein assembly and affected the degradation and RNA binding efficiency to varying degrees. However, the severity of the conditions caused by different mutations did not correlate with the catalytic activity of the mutant proteins. Also, we demonstrated that human PNPase, like its bacterial orthologue, is capable of trimming ssDNA and some mutations inhibit such activity.
Accurate genotyping of three major respiratory bacterial pathogens with ONT R10.4.1 long-read sequencing
Authors: Zidane Nora , Rodrigues Carla , Bouchez Valérie , Rethoret-Pasty Martin , Passet Virginie , Brisse Sylvain , Crestani Chiara
Published: October 2024

High-throughput massive parallel sequencing has significantly improved bacterial pathogen genomics, diagnostics, and epidemiology. Despite its high accuracy, short-read sequencing struggles with complete genome reconstruction and assembly of extrachromosomal elements such as plasmids. Long-read sequencing with Oxford Nanopore Technologies (ONT) presents an alternative that offers benefits like real-time sequencing and cost-efficiency, particularly useful in resource-limited settings. However, the higher error rates of ONT have so far limited its application in high-precision genomic typing. The recent release of ONT’s R10.4.1 chemistry, with significantly improved raw read accuracy (Q20+), offers a potential solution to this problem.

The aim of this study was to evaluate the performance of ONT’s latest chemistry for bacterial genomic typing against the gold standard Illumina technology, focusing on three respiratory pathogens of public health importance,Klebsiella pneumoniae, Bordetella pertussis, andCorynebacterium diphtheriae, and their related species. Using the Rapid Barcoding Kit V14, we generated and analyzed genome assemblies with different basecalling tools and models, at different simulated depths of coverage. ONT assemblies were compared to the Illumina reference for completeness and core genome multilocus sequence typing (cgMLST) accuracy (number of allelic mismatches).

Our results show that genomes obtained from raw data basecalled with Dorado (with both simplex and duplex reads) SUP v0.7.1, assembled with Flye, and with a minimum coverage depth of 30×, optimized the accuracy for all bacterial species tested. The error rates were consistently below 1% of each cgMLST scheme, indicating that ONT R10.4.1 data is suitable for high-resolution genomic typing applied to outbreak investigations and public health surveillance.
Cross-species orthology detection of long non-coding RNAs (lncRNA) through 13 species using genomic and functional annotations
Authors: Degalez Fabien , Allain Coralie , Lagoutte Laetitia , Lecerf Frédéric , Lagarrigue Sandrine
Published: October 2024

Long non-coding RNAs (lncRNAs), defined by a length of over 200 nucleotides and limited protein-coding potential, have emerged as key regulators of gene expression. However, their evolutionary conservation and functional roles remain largely unexplored. Comparative genomics, particularly through sequence conservation analysis, offers a promising approach to infer lncRNA functions. Traditional methods focusing on protein-coding genes (PCGs) fall short due to the rapid evolutionary divergence of lncRNA sequences. To address this, a workflow combining syntenic methods and motif analysis via the Mercator- Pecan genome alignment was developed and applied across 13 vertebrate species, from zebrafish to various amniotes and birds. Further analyses to infer functionality revealed co-expression patterns through 17 shared tissues between human and chicken but also functional short-motif enrichment across the 13 species using the LncLOOM tool, exemplified by the human OTX2-AS1 and its counterparts in other species. The study expanded the catalog of conserved lncRNAs, providing insights into their evolutionary conservation and information related to potential functions. The workflow presented serves as a robust tool for investigating lncRNA conservation across species, supporting future research in molecular biology to elucidate the roles of these enigmatic transcripts.
Unraveling Integration-Segregation Imbalances in Schizophrenia Through Topological High-Order Functional Connectivity
Authors: Li Qiang , Huang Wei , Qiao Chen , Chen Huafu
Published: October 2024

Background

The occurrence of brain disorders correlates with detectable dysfunctions in the specialization of brain connectomics. While extensive research has explored this relationship, there is a lack of studies specifically examining the statistical correlation between the integration and segregation of psychotic brain networks using high-order networks, given the limitations of low-order networks. Moreover, these dysfunctions are believed to be linked to information imbalances in brain functions. However, our understanding of how these imbalances give rise to specific psychotic symptoms remains limited.

Methods

This study aims to address this gap by investigating variations at the topological high-order level of the system with regard to specialization in both healthy individuals and those diagnosed with schizophrenia. By employing graph-theoretic brain network analysis, we systematically examine information integration and segregation to delineate system-level differences in the connectivity patterns of brain networks.

Results

The findings indicate that topological high-order functional connectomics highlight differences in the connectome between healthy controls and schizophrenia, demonstrating increased cingulo-opercular task control and salience interactions, while the interaction between subcortical and default mode networks, dorsal attention and sensory/somatomotor mouth decreases in schizophrenia. Furthermore, we observed a reduction in the segregation of brain systems in healthy controls compared to individuals with schizophrenia, which means the balance between segregation and integration of brain networks is disrupted in schizophrenia, suggesting that restoring this balance may aid in the treatment of the disorder. Additionally, the increased segregation and decreased integration of brain systems in schizophrenia patients compared to healthy controls may serve as a novel indicator for early schizophrenia diagnosis.

Conclusion

We discovered that topological high-order functional connectivity highlights brain network interactions compared to low-order functional connectivity. Furthermore, we observed alterations in specific brain regions associated with schizophrenia, as well as changes in brain network information integration and segregation in individuals with schizophrenia.
Sustainable Regeneration of 20 Aminoacyl-tRNA Synthetases in a Reconstituted System Toward Self-Synthesizing Artificial Systems
Authors: Hagino Katsumi , Masuda Keiko , Shimizu Yoshihiro , Ichihashi Norikazu
Published: October 2024

In vitro construction of self-reproducible artificial systems is a major challenge in bottom-up synthetic biology. Here, we developed a reconstituted system capable of sustainably regenerating all 20 aminoacyl-tRNA synthetases (aaRSs), which are major components of the translation system. To achieve this, we needed five types of improvements: 1) optimization of aaRS sequences for efficient translation, 2) optimization of the composition of the translation system to enhance translation, 3) employment of another bacterial AlaRS and SerRS to improve each aminoacylation activity, 4) diminishing the translational inhibition caused by certain aaRS sequences by codon optimization and EF-P addition, and 5) balancing the DNA concentrations of 20 aaRSs to match each requirement. After these improvements, we succeeded in the sustainable regeneration of all 20 aaRSs for up to 20 cycles of 2.5-fold serial dilutions. These methodologies and results provide a substantial advancement toward the realization of self-reproducible artificial systems.
AI-Driven Analysis of Telehealth Effectiveness in Youth Mental Health Services: Insights from SAMHSA Data
Authors: Mansoor Masab A. , Grindem David J.
Published: October 2024

Background

The rapid adoption of telehealth services for youth mental health care necessitates a comprehensive evaluation of its effectiveness. This study aimed to analyze the impact of telehealth on youth mental health outcomes using artificial intelligence techniques applied to large-scale public health data.

Methods

We conducted an AI-driven analysis of data from the National Survey on Drug Use and Health (NSDUH) and other SAMHSA datasets. Machine learning techniques, including Random Forest models, K-means clustering, and time series analysis, were employed to evaluate telehealth adoption patterns, predictors of effectiveness, and comparative outcomes with traditional in-person care. Natural language processing was used to analyze sentiment in user feedback.

Results

Telehealth adoption among youth increased significantly, with usage rising from 2.3 sessions per year in 2019 to 8.7 in 2022. Telehealth showed comparable effectiveness to in-person care for depressive disorders and superior effectiveness for anxiety disorders. Session frequency, age, and prior diagnosis were identified as key predictors of telehealth effectiveness. Four distinct user clusters were identified, with socioeconomic status and home environment strongly associated with positive outcomes. States with favorable reimbursement policies saw a 15% greater increase in youth telehealth utilization and a 7% greater improvement in mental health outcomes.

Conclusions

Telehealth demonstrates significant potential in improving access to and effectiveness of mental health services for youth. However, addressing technological barriers and socioeconomic disparities is crucial to maximize its benefits.
Density functional Bogoliubov-de Gennes theory for superconductors implemented in the SIESTA code
Authors: Reho R. , Wittemeier N. , Kole A. H. , Ordejón P. , Zanolli Z.
Published: October 2024

We present SIESTA-BdG, an implementation of the simultaneous solution of the Bogoliubov-de Gennes (BdG) and density functional theory (DFT) problem in SIESTA, a first-principles method and code for material simulations which uses pseudopotentials and a localized basis set. This unified approach describes both conventional and unconventional superconducting states, and enables a description of inhomogeneous superconductors and heterostructures. We demonstrate the validity, accuracy, and efficiency of SIESTA-BdG by computing physically relevant quantities (superconducting charge density, band structure, superconducting gap features, density of states) for conventional singlet (Nb, Pb) and unconventional (FeSe) superconductors. We find excellent agreement with experiments and results obtained within the KKR-BdG computational framework. SIESTA-BdG forms the basis for modeling quantum transport in superconducting devices and including—in an approximate fashion—the superconducting DFT potential of Oliveira, Gross, and Kohn.

Published by the American Physical Society
2024
Quantum spin systems: Toroidal classification and geometric duality
Authors: Azimi-Mousolou Vahid , Bergman Anders , Delin Anna , Eriksson Olle , Pereiro Manuel , Thonig Danny , Sjöqvist Erik
Published: October 2024

We demonstrate a toroidal classification for quantum spin systems, revealing an intrinsic geometric duality within this structure. Through our classification and duality, we reveal that various bipartite quantum features in magnon systems can manifest equivalently in both bipartite ferromagnetic and antiferromagnetic materials, based upon the availability of relevant Hamiltonian parameters. Additionally, the results highlight the antiferromagnetic regime as an ultrafast dual counterpart to the ferromagnetic regime, both exhibiting identical capabilities for quantum spintronics and technological applications. Concrete illustrations are provided, demonstrating how splitting and squeezing types of two-mode magnon quantum correlations can be realized across ferro- and antiferromagnetic regimes.

Published by the American Physical Society
2024
Nonperturbative RG for the weak interaction corrections to the magnetic moment
Authors: Mastropietro Vieri
Published: October 2024

We analyze, by rigorous renormalization group methods, a Fermi model for weak forces with a single family of leptons, one massless and the other with mass m=Me−β, with M the gauge boson mass, a quartic nonlocal interaction with coupling λ2, and a momentum cutoff Λ. The magnetic moment is written as a series in λ2, with n-th coefficients bounded by Cn(m2M2)β2n(Λ2M2)(1+0+)(n−1) if C is a constant; this implies convergence and provides nonperturbative bounds on the higher order contributions. The fact that the magnetic moment is associated with a dimensionally irrelevant quantity requires the implementation of cancellations in the multiscale analysis.

Published by the American Physical Society
2024
Unconventional Crystal Structure of the High-Pressure Superconductor
La3Ni2O7
Authors: Puphal P. , Reiss P. , Enderlein N. , Wu Y.-M. , Khaliullin G. , Sundaramurthy V. , Priessnitz T. , Knauft M. , Suthar A. , Richter L. , Isobe M. , van Aken P. A. , Takagi H. , Keimer B. , Suyolcu Y. E. , Wehinger B. , Hansmann P. , Hepting M.
Published: October 2024

The discovery of high-temperature superconductivity in La3Ni2O7 at pressures above 14 GPa has spurred extensive research efforts. Yet, fundamental aspects of the superconducting phase, including the possibility of a filamentary character, are currently subjects of controversial debates. Conversely, a crystal structure with NiO6 octahedral bilayers stacked along the c-axis direction was consistently posited in initial studies on La3Ni2O7. Here, we reassess this structure in optical floating zone-grown La3Ni2O7 single crystals that show signs of filamentary superconductivity. Employing scanning transmission electron microscopy and single-crystal x-ray diffraction under high pressures, we observe multiple crystallographic phases in these crystals, with the majority phase exhibiting alternating monolayers and trilayers of NiO6 octahedra, signifying a profound deviation from the previously suggested bilayer structure. Using density functional theory, we disentangle the individual contributions of the monolayer and trilayer structural units to the electronic band structure of

La

3

Ni

2

O

7

, providing a firm basis for advanced theoretical modeling and future evaluations of the potential of the monolayer-trilayer structure for hosting superconductivity.

Published by the American Physical Society
2024
Magnetic interactions in the cooperative paramagnet
Tb2Ti2O7
Authors: Roll A. , Balédent V. , Robert J. , Ollivier J. , Decorse C. , Guitteny S. , Mirebeau I. , Petit S.
Published: October 2024

For about two decades, Tb2Ti2O7 has remained an enigma in condensed matter physics and frustrated magnetism. This material evades long-range order down to temperature as low as 20 mK, and, as in spin ice, its ground state exhibits puzzling diffuse magnetic scattering. To shed light on this issue, we present spin dynamics measurements by inelastic neutron scattering, which we confront with random phase approximation calculations (RPA) to determine exchange couplings capable of reproducing the dispersion of the first excited crystal electric field level. These couplings suggest that Tb2Ti2O7 lives at the boundary between several phases, in particular the spin ice and planar antiferromagnetic ones.

Published by the American Physical Society
2024
Optical induction of monopoles, knots, and skyrmions in quantum gases
Authors: Annala Toni , Mikkonen Tommi , Möttönen Mikko
Published: October 2024

Single topological defects and related structures have been experimentally created inside clouds of Bose-Einstein condensates. However, a practical protocol for creating multiple defects inside a single cloud—a prerequisite for studying defect interactions—has been lacking. Here we propose, and theoretically analyze, a practical protocol for the creation of configurations of topological monopoles, quantum knots, and skyrmions in Bose-Einstein condensates by employing fictitious magnetic fields induced by the interaction of the atomic cloud with coherent light fields. It is observed that a single coherent field is not enough for this purpose, but instead we find incoherent superpositions of several coherent fields that introduce topological point charges. We numerically estimate the experimentally achievable strengths and gradients of the induced fictitious magnetic fields and find them to be adjustable at will to several orders of magnitude greater than those of the physical magnetic fields employed in previous experimental studies. This property together with ultrafast control of the optical fields paves the way for advanced engineering of topological defects in quantum gases.

Published by the American Physical Society
2024
Controlling
4f
antiferromagnetic dynamics via itinerant electronic susceptibility
Authors: Lee Sang-Eun , Windsor Yoav William , Zahn Daniela , Kraiker Alexej , Kummer Kurt , Kliemt Kristin , Krellner Cornelius , Schüßler-Langeheine Christian , Pontius Niko , Staub Urs , Vyalikh Denis V. , Ernst Arthur , Rettig Laurenz
Published: October 2024

Optical manipulation of magnetism holds promise for future ultrafast spintronics, especially with lanthanides and their huge, localized 4f magnetic moments. These moments interact indirectly by spin polarizing the conduction electrons (the Ruderman-Kittel-Kasuya-Yosida exchange interaction), influenced by interatomic orbital overlap, and the conduction electron's susceptibility around the Fermi level. Here, we study this influence in a series of 4f antiferromagnets, GdT2Si2 (T = Co, Rh, Ir), using ultrafast resonant x-ray diffraction. We observe a twofold increase in the ultrafast intersublattice angular momentum transfer rate between the materials, originating from modifications in the conduction electron susceptibility, as confirmed by first-principles calculations.

Published by the American Physical Society
2024