bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study about the public's perception of primary care providers
Authors: Gillette Chris , Ostermann Jan , Garvick Sarah , Everett Christine M. , Valente Jessica , Aguilar Aylin Aguilar , Lacci-Reilly Kandice 
Published: November 2024

ABSTRACT

Objective:
With the growth of physician associates/assistants (PAs) and NPs providing primary care services, we sought to understand the public's perception of the different types of healthcare providers (HCPs) they might encounter in a clinical setting, such as primary care.

Objectives:
This study aimed to evaluate public perceptions about various types of primary care providers (PCPs), identify public preferences for PCPs in relation to experience and training, and examine public preferences for PCP credentials.

Methods:
We conducted semistructured interviews with adults, and used inductive and deductive coding and reflexive thematic analysis to analyze the data.

Results:
We reached thematic saturation after 12 completed interviews. Participants reported confusion about the types of HCPs they might encounter in a primary care setting (for example, physician, PA, NP). Participants who reported a preference for a physician valued more years in training and their role in the hierarchy of medicine; those who reported a preference for a PA or NP indicated that compassion, patience, and longer clinic visit times were most important to them.

Conclusions:
Previous reports suggested that the public might be confused by the different types of HCPs they might encounter during a primary care visit. Participants identified specific characteristics that are important when they are choosing their PCP. A direct, coordinated marketing campaign may be needed to educate the public and reduce confusion about different types of PCPs, how they contribute to safe and high-quality care, and ensure preference-concordant care.
Associations Between Vestibular Perception and Cognitive Performance in Healthy Adults
Authors: Kobel Megan J. , Wagner Andrew R. , Merfeld Daniel M. 
Published: November 2024

Objectives:
A growing body of evidence has linked vestibular function to the higher-order cognitive ability in aging individuals. Past evidence has suggested unique links between vestibular function and cognition on the basis of end-organ involvement (i.e., otoliths versus canals). However, past studies have only assessed vestibular reflexes despite the diversity of vestibular pathways. Thus, this exploratory study aimed to assess associations between vestibular perception and cognition in aging adults to determine potential relationships.

Design:
Fifty adults (21 to 84 years; mean = 52.9, SD = 19.8) were included in this cross-sectional study. All participants completed a vestibular perceptual threshold test battery designed to target perception predominantly mediated by each end-organ pair and intra-vestibular integration: 1 Hz y-translation (utricle), 1 Hz z-translation (saccule), 2 Hz yaw rotation (horizontal canals), 2 Hz right anterior, left posterior (RALP), and left anterior, right posterior (LARP) tilts (vertical canals), and 0.5 Hz roll tilt (canal-otolith integration). Participants also completed standard assessments of cognition and path integration: Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and the Gait Disorientation Test (GDT). Associations were assessed using Spearman rank correlation, and multivariable regression analyses.

Results:
For correlation analyses, DSST correlated to RALP/LARP tilt, roll tilt, and z-translation. TMT-A only correlated to z-translation, and TMT-B correlated to roll tilt and z-translation after correcting for multiple comparisons. GDT correlated to RALP/LARP tilt and y-translation. In age-adjusted regression analyses, DSST and TMT-B were associated with z-translation thresholds and GDT was associated with y-translation thresholds.

Conclusions:
In this cross-sectional study, we identified associations between vestibular perceptual thresholds with otolith contributions and standard measures of cognition. These results are in line with past results suggesting unique associations between otolith function and cognitive performance.
Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model–Derived Tapering Strategies for Patients With Rheumatoid Arthritis
Authors: Hooijberg Femke , van den Berg Stefan P. H. , Layegh Zohra , Leeuw Maureen , Elkayam Ori , de Vries Annick , Nurmohamed Mike , Rispens Theo , Dorlo Thomas P. C. , Wolbink Gertjan 
Published: November 2024

Background:
Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy.

Methods:
A population pharmacokinetic model of intravenous tocilizumab was developed using data from a randomized controlled trial of dose tapering in patients with RA. Subsequent population-level Monte Carlo and individual Bayesian simulations were performed to create tapering strategies involving dose reduction and interval extension. The target trough concentration of tocilizumab was 5 mg/L. Finally, the drug savings were compared between the 2 methods.

Results:
The pharmacokinetic of tocilizumab was described with a 2-compartment model with parallel linear (CL 0.20 L/d) and nonlinear (VM 5.2 mg/d, KM 0.19 mg/L) elimination. The linear clearance rate and central volume of distribution increased with lean body mass, and men exhibited higher clearance rates than women. The simulated concentration–time profiles demonstrated that, owing to nonlinear clearance, drug concentrations decreased more than dose-proportionally with lower doses. Tapering based on an individual Bayesian approach emerged as the most promising strategy, yielding a 39% reduction in drug use across virtual populations.

Conclusions:
Tapering strategies were developed for intravenous tocilizumab, offering potential application in patients with RA who have reached low disease activity or remission, pending clinical validation. The developed strategies demonstrate that the tapering of tocilizumab should be approached more carefully and in smaller steps than that of TNFi.
Chronic low back pain caused by metastatic adenocarcinoma of unknown origin in a young man: a case report
Authors: Hodaifa Yara , Hodaifa Amr , Kudsi Maysoun 
Published: November 2024

Introduction and importance:
Low back pain (LBP) is one of the most common complaints and sacroiliac joint dysfunction is the third cause of this chronic burden. Sacroiliitis might be a primary sign of axial spondylarthritis, although it might be found in other diseases, and malignancies, either primary tumors or metastases, meanwhile, this is a rare case that is described as sacroiliitis with adenocarcinoma of unknown origin.

Case presentation:
A 24-year-old male presented at the hospital with fever and urinary retention. He had a history of progressively worsening chronic LBP, with increased curvature in the dorsal vertebrae. Physical examination revealed fever (39°C), a dorsal kyphosis with an absence of lumbar lordosis. Strength was low in the proximal and distal muscles of the lower limbs, with hyperreflexia in the left lower limb and paresthesia limbs in the whole lower and lower region of the abdomen. Laboratory studies revealed normocytic anemia, high ESR and CRP levels, and hypercalcemia with low PTH. The radiology study showed sacroiliitis, many lytic bone lesions, and a collapse in the 4th lumbar vertebral, and increased lung density. Biopsy from a lytic lesion showed metastatic poorly differentiated adenocarcinoma of unknown origin with features suggestive of pancreatic primary. Palliative radiotherapy was started; unfortunately, he died after 4 months.

Clinical discussion:
Cancer is an additional risk factor for the development of sacroiliac joint pain and disorder. A lot of tumors and metastases can be associated with sacroiliitis. Many patients present with bone lytic metastases of unknown origin as a first manifest. The association between metastatic adenocarcinoma and sacroiliitis was reported three cases in the literature; meanwhile, this was a rare case that described sacroiliitis with adenocarcinoma of unknown origin.

Conclusion:
Low back pain is one of the most common complaints, but it may be an initial symptom of serious conditions. Awareness of clinical clues can prevent faulty or delayed diagnoses. Although sacroiliitis is usually associated with axial spondylarthritis in adult patients, it can be the first manifestation of adenocarcinoma.
Pediatric acquired demyelinating syndromes: updates in diagnosis, testing, and management
Authors: Mirchi Amytice , Hopkins Sarah 
Published: November 2024

Purpose of review
To highlight the clinical presentation, diagnostic approach, and management of acquired inflammatory demyelinating syndromes in children.

Recent findings
The identification of myelin oligodendrocyte glycoprotein antibody-associated disease in 2017 and evolving evidence regarding best practices for management has had a significant impact on pediatric neuroimmunology, as has the shift in treatment of pediatric-onset multiple sclerosis, with the use of high-efficacy disease-modifying therapies early in the disease course.

Summary
With expanding awareness and growing interest in pediatric onset neuroinflammatory conditions, the number of children diagnosed with acquired demyelinating syndromes is rising. It is critical to refine our understanding of the underlying pathophysiological mechanisms in these disorders to provide the most effective care. Much of our practice continues to be modeled on adult care, and further large-scale pediatric studies are necessary to explore the natural history and assess the safety and efficacy of immunotherapies in childhood-onset demyelinating diseases.
Eliminating Error in Central Line Scheduling and Placement Using Quality Improvement Methods
Authors: Roach Jonathan P , Linton Anna , Tchou Michael J , Riess Laurel , Adamson Leanne , Garrington Timothy P , Younoszai Adel , Anstett Tyler J 
Published: November 2024

Background:
The Joint Commission defines a sentinel event as “surgery or other invasive procedure performed at the wrong site, on the wrong patient, or that is the wrong (unintended) procedure for a patient regardless of the type of procedure or the magnitude of the outcome.” At our institution, we observed a low but consistent rate of incorrect surgical line placement for pediatric patients with cancer.

Study Design:
Following quality improvement methodology and using the resources available on a large academic medical campus we designed and implemented a new multi-factorial process to schedule and place surgical central lines for pediatric patients with cancer. Changes included re-defining responsibilities, adding staff, and redesigning the process with workflows supported by modifications to the electronic medical record. Our primary outcome measures were incorrect central line placement or near miss event per quarter and days between these events.

Results:
After implementation the rate of incorrect line placement and near miss events was reduced to zero with 1018 days since the last incorrect line placement.

Conclusions:
As a result of our multi-factorial quality improvement initiative in the scheduling and placement of central lines, we were able to eliminate surgical line placement sentinel events and improve care for pediatric patients with cancer.
Dynamics of N-genes and T-genes in cancer
Authors: Gil Gabriel , Gonzalez Augusto 
Published: November 2024

AbstractThe normal-tissue and tumor attractors are far apart in gene-expression space[1,2]. As a consequence, there are genes with specific gene-expression intervals characteristic only of normal tissues or tumors[3]. We call them N-genes and T-genes, respectively. They are not only perfect markers, but are also responsible of anchoring the state in the vicinity of the corresponding attractor. According to the higher degree of disorder of tumors[4,5], there are 10-times more T-genes than N-genes[3]. Carcinogenesis, which is the progressive motion from the N-attractor to the T-attractor, can also be viewed as a process of deactivating the N-genes marking and holding the normal tissue and setting new T-markers and anchors for the tumor. In prostate, for example, the process starts with around 500 activated N-genes in any healthy normal tissue that may be dramatically reduced to a few N-genes before the transition to the tumor occurs. The available gene expression data[6,7]shows that even 2 or 3 active N-genes are enough for holding the normal state condition (at least from a pathological perspective). The process is expected to evolve in the form of consecutive deregulation cascades[8], in which a few initial cascades inactivate most of the active N-genes, and a final cascade inactivates the remaining N-markers and sets the new T-markers for the tumor. The whole process shares similarities with the multistep model of cancer[9].
Treading lightly: Quantitative estimates of seafloor contact for longline trap and hook fishing gear
Authors: Doherty Beau , Lacko Lisa , Kronlund Allen R , Alexander Kenyon , Cox Sean P. 
Published: November 2024

AbstractDespite increasing calls for sustainability and ecosystem objectives to manage fishing gear interactions with bottom habitats there are few quantitative approaches for assessing risks from bottom contact fishing. Risk assessments for bottom longline fisheries are particularly challenging due to a lack of information for estimating bottom contact areas from longline gear. In this paper, we demonstrate how data sensors and video cameras deployed on fishing gear can be used to quantify the bottom contact area for longline trap and hook fishing gear from the British Columbia Sablefish fishery. Our bottom contact estimates indicate that Sablefish fishing risks to bottom habitat are low in the majority of fishing areas, since 91.8% of the area fished is expected to have had zero bottom contact over the last 17 years. For the other 8.2% of Sablefish fishing areas that experience some contact from fishing gear, the majority are only contacted once. This indicates that most habitats contacted by Sablefish gear can be expected to have a minimum of 17 years to recover between subsequent bottom contact events. We demonstrate an approach for estimating fisheries bottom contact that can be widely implemented across longline fisheries. Our findings address key data gaps in bottom impacts research for longline gear fisheries, allowing fishing risks to be quantified over fine spatial scales. Such quantitative approaches for habitat risk assessment can provide essential information for management decisions aimed at determining acceptable trade-offs between habitat preservation and fishery benefits.
A fish frontier? Itatiaia expedition and biodiversity repositories reveal gaps in fish occurrences in Brazil’s high-altitude aquatic ecosystems
Authors: Soares Guedes Gustavo Henrique , Pacheco da Luz Carlos Henrique , de Jesus Souza Victória , Araújo Francisco Gerson 
Published: November 2024

AbstractBrazil harbors one of the greatest diversities of freshwater fish in the world; however, the presence or absence of fish in high-altitude aquatic ecosystems remains largely unknown. This study aims to investigate fish occurrence on the Itatiaia Plateau (Itatiaia National Park) at altitudes ranging from 2,140 to 2,543 meters, marking one of the highest-altitude fish surveys conducted in Brazil. Additionally, it analyzes gaps in fish distribution above 2,000 meters in Brazil by compiling approximately 1 million occurrence records from digital biodiversity repositories (SpeciesLink, Salve, SIBBr). Results from the Itatiaia expedition and biodiversity repositories converge to indicate a lack of fish records in high-altitude aquatic ecosystems (> 2,000 m) in Brazil.Psalidodon scabripinnis(Jenyns 1842) is the species with the highest recorded altitude (∼1,944 m). Challenging climatic conditions, physical barriers to dispersal, isolation, historical absence, sampling gaps, and repository biases may be associated with this lack of fish occurrences. This study highlights gaps in knowledge of fish distribution and the potential for future research to discover previously unknown species or species adapted to high altitudes in Brazil.
Bidirectional Peptide Conformation Prediction for MHC Class II using PANDORA
Authors: Rademaker Daniel T. , Parizi Farzaneh M. , van Vreeswijk Marieke , Eerden Sanna , Marzella Dario F. , Xue Li C. 
Published: November 2024

AbstractRecent discoveries have transformed our understanding of peptide binding in Major Histocompatibility Complex (MHC) molecules, showing that peptides, for some MHC class II alleles, can bind in a reverse orientation (C-terminus to N-terminus) and can still effectively activate CD4+ T cells. These finding challenges established concepts of immune recognition and suggests new pathways for therapeutic intervention, such as vaccine design.We present an updated version of PANDORA, which, to the best of our knowledge, is the first tool capable of modeling reversed-bound peptides. Modeling these peptides presents a unique challenge due to the limited structural data available for these orientations in existing databases. PANDORA has overcome this challenge through integrative modeling using algorithmically reversed peptides as templates.We have validated the new PANDORA feature through a series of experiments, achieving an average backbone binding-core L-RMSD value of 0.63 Å. Notably, it maintained low RMSD values even when using templates from different alleles and peptide sequences. Our results suggest that PANDORA will be an invaluable resource for the immunology community, aiding in the development of targeted immunotherapies and vaccine design.AvailabilitySource code and data is freely available athttps://github.com/X-lab-3D/PANDORA; Contact:Li.Xue@radboudumc.nl
Asymmetric gene flow maintains an abundant range center
Authors: Hancock Zachary B. , Adams Nicole E. , Wood Perry L. , Bradburd Gideon S. 
Published: November 2024

ABSTRACTThe abundant center hypothesis postulates that population density is the highest in the center of the range and declines towards the periphery. While many evolutionary hypotheses have been offered to explain what generates this pattern, ecologically it’s assumed the pattern emerges due to increasing distance from a species ideal niche with edge populations occupying a “marginal” niche of low suitability. However, the ubiquity of the abundant center pattern has recently been questioned. Furthermore, it has proven difficult to assess both the pattern of the abundant center and the potential generative scenarios (e.g., gene swamping, migration limitation) due to the inherent complexity of species ranges. In this study, we evaluate the suitability of the abundant center hypothesis to explain patterns of genetic diversity and inbreeding in shovel bugs – small, sand-burrowing coastal crustaceans. In addition, we evaluate potential biases in migration direction due to the dominant current regimes in the North Atlantic using a common method for querying the site frequency spectrum, the directionality index (𝜓). While patterns of genetic diversity are consistent with an abundant center, we find a strong signature of recent central colonization from the range periphery. Using simulations, we evaluate the performance of 𝜓 under different migration regimes, finding that, in the presence of asymmetric migration, it strongly infers an edge-to-center colonization dynamic. We conclude that asymmetric migration towards the center can lead to signatures of an abundant center without necessarily implying a reduction in niche quality towards the range periphery.
Assessing Structures and Conformational Ensembles of Apo and Holo Protein States Using Randomized Alanine Sequence Scanning Combined with Shallow Subsampling in AlphaFold2 : Insights and Lessons from Predictions of Functional Allosteric Conformations
Authors: Raisinghani Nishank , Parikh Vedant , Foley Brandon , Verkhivker Gennady 
Published: November 2024

AbstractProteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2 that combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms. Using several well-established datasets of structurally diverse apo-holo protein pairs, the proposed approach enables robust predictions of apo and holo structures and conformational ensembles, while also displaying notably similar dynamics distributions. These observations are consistent with the view that the intrinsic dynamics of allosteric proteins is defined by the structural topology of the fold and favors conserved conformational motions driven by soft modes. Our findings support the notion that AlphaFold2 approaches can yield reasonable accuracy in predicting minor conformational adjustments between apo and holo states, especially for proteins with moderate localized changes upon ligand binding. However, for large, hinge-like domain movements, AlphaFold2 tends to predict the most stable domain orientation which is typically the apo form rather than the full range of functional conformations characteristic of the holo ensemble. These results indicate that robust modeling of functional protein states may require more accurate characterization of flexible regions in functional conformations and detection of high energy conformations. By incorporating a wider variety of protein structures in training datasets including both apo and holo forms, the model can learn to recognize and predict the structural changes that occur upon ligand binding.
Investigating the causal network of dementia by employing a causal discovery approach combined with natural language processing models
Authors: Yu Xinzhu , Lophatananon Artitaya , Holmes Vivien , Muir Kenneth R. , Guo Hui 
Published: November 2024

AbstractINTRODUCTIONComprehensively studying modifiable risk factors altogether to explore how they contribute to dementia mechanism is imperative for effective interventions.METHODSThis study utilized natural language processing (NLP) models to pre-select candidate risk factors of dementia from 5,505 variables in the UK Biobank. We then took a holistic machine learning approach, fast causal inference in combination with mixed graphical models, to explore the complex causal mechanisms underlying dementia from 120 imputed variables.RESULTSThe identified causal network highlighted eight risk factors which may directly or indirectly contribute to dementia. In particular, mental disorders due to brain damage and dysfunction and to physical disease were identified as direct causes as well as mediators on the causal pathways to dementia. Evidence for a direct causal impact of phenotypic age on dementia was less pronounced.DISCUSSIONOur study offered valuable insights into the mechanisms of dementia. Beyond direct connections to nerve or brain disorders, the potential direct link with biological age highlights its possible value in dementia management. Moreover, the use of NLP models for variable pre-selection introduced an innovative application to medical research. Our study added weight to the accruing evidence that machine learning has a promising future for exploring complex disease mechanisms from high-dimensional data.