bluuebunny/crossref_metadata_2025_split huggingface dataset:
Women's perceptions and preferences for cervical cancer screening in light of updated guidelines
Authors: Bustamante Gabriela , Liebermann Erica , McNair Katelyn , Fontenot Holly B. 
Published: July 2023

ABSTRACT

Background:
Updated risk-based guidelines for cervical cancer screening (CCS) allow for individualized screening that minimizes unnecessary testing. However, these guidelines are complex and may not be easily understandable to patients.

Purpose:
To describe women's perceptions and preferences about CCS in light of recent guideline changes.

Methodology:
This qualitative study conducted in February 2020 used online, text-based focus groups with a sample of US women (n = 49) ages 27–45. After participants completed a short demographic survey, an experienced moderator used a semistructured guide to solicit participants' perceptions of routine gynecologic care and CCS. We summarized survey data using descriptive statistics. Two authors analyzed transcripts using conventional content analysis and met with other team members to resolve discrepancies and determine final themes.

Results:
Most participants were non-Hispanic White (65%), had health insurance (90%), and reported having a routine gynecologic examination in the past year (70%). We identified four common themes: (1) low perceived risk of human papillomavirus (HPV) coupled with low knowledge about HPV as a causative factor for cervical cancer, (2) confusion about—and mistrust of—recent individual risk-based guidelines that determine the indicated timing and type of CCS test (Pap or HPV testing), (3) mixed opinions about performing a self-swab for HPV testing, and (4) conflicting perceptions of trust toward providers and the health care industry.

Conclusions:
Findings highlight women's uncertainty and hesitancy about updated CCS guidelines.

Implications:
Provider–patient communication strategies should consider women's gaps in knowledge about HPV, include the rationale for guidelines and types of tests, and build trust between patients and providers.
Treatment of hyperhidrosis with Botox (onabotulinumtoxinA): Development, insights, and impact
Authors: Lowe Nicholas , Naumann Markus , Eadie Nina 
Published: July 2023

Hyperhidrosis (chronic excessive sweating) may substantially affect an individual’s emotional and social well-being. Therapies available before onabotulinumtoxinA were generally topical, with limited effectiveness, application-site skin reactions, and frequent, time-consuming treatments. Intradermal injection of onabotulinumtoxinA to treat sweat glands arose as a novel therapeutic approach. To develop this treatment, appropriate dosing needed to be established, and training on administration was required. Further, no previous scale existed to measure the effects of hyperhidrosis on patients’ lives, leading Allergan to develop and validate the 4-point Hyperhidrosis Disease Severity Scale (HDSS), which measures the disease’s impact on daily activities.
The onabotulinumtoxinA clinical development program for hyperhidrosis included 2 double-blind, placebo-controlled pivotal trials, immunogenicity studies, long-term studies of safety and efficacy, and quality of life assessments. In Europe and North America, the primary efficacy measures were, respectively, axillary sweat production measured gravimetrically and HDSS improvement. Compared with placebo, onabotulinumtoxinA treatment significantly reduced axillary sweat production and axillary hyperhidrosis severity, as measured by a 2-point or greater reduction on the HDSS. The effects of onabotulinumtoxinA occurred rapidly, within 1 week after injection, and lasted ≥6 months. Treatment with onabotulinumtoxinA was associated with significant quality of life improvements based on Short Form-12 physical and mental component scores. The Hyperhidrosis Impact Questionnaire also indicated greater treatment satisfaction, reduced negative impact on aspects of daily life, and improved emotional well-being with onabotulinumtoxinA versus placebo. The clinical development program and subsequent clinical experience showed that onabotulinumtoxinA treatment for hyperhidrosis was well tolerated with no new safety signals, and led to greater disease awareness.
Fatigue and Physical Activity Patterns in Children With Inflammatory Bowel Disease
Authors: Bevers Nanja , Van de Vijver Els , Hanssen Adrienne , Aliu Arta , Vande Velde Saskia , Roelant Ella , Rezazadeh Ardabili Ashkan , Rosias Philippe , Stapelbroek Janneke , Maartens Imke Bertrams , van de Feen Cathelijne , Escher Johanna , Oudshoorn Annemarie , Teklenburg-Roord Sarah , Vreugdenhil Anita , Pierik Marie , van Rheenen Patrick 
Published: July 2023

Objectives:
Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view.

Methods:
A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <−2.0. Non-fatigued children had a z score ≥−2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated.

Results:
Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008).

Conclusion:
Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life.
Predictors of Outcomes in 900 Alveolar Bone Grafts
Authors: Padwa Bonnie L. , Tio Pauline , Garkhail Prakriti , Nuzzi Laura C. 
Published: July 2023

Background:
Significant discrepancies exist in the reported variables influencing alveolar bone graft outcomes. The purpose of this study was to evaluate graft success and identify outcome predictors in a large patient cohort using an objective cone beam computed tomography assessment tool.

Methods:
Consecutive patients with cleft lip/palate who underwent alveolar bone grafting by 1 surgeon were included. Predictor variables were age at graft, oronasal fistula, canine position, concurrent premaxillary osteotomy, size of cleft, presence of bony palatal bridge, history of failed graft, location of primary repair, and surgeon experience. The outcome variable was graft success, determined using a cone beam computed tomography assessment tool and defined as a score of 3 or 4 (out of 4) in the following domains: vertical bone level, labiopalatal thickness, and nasal piriform symmetry.

Results:
The sample included 900 alveolar cleft sites (median graft age, 9.9 years). The success rate was 94.6%. Presence of an erupted canine, large cleft defect, or premaxillary osteotomy were independent predictors of graft failure; presence of a bony palatal bridge was associated with graft success (P < 0.05).

Conclusions:
Presence of an erupted canine, large bony defect, or premaxillary osteotomy increase the risk of failure, and a bony palatal bridge portends success. Age 12 years or older, visible oronasal fistula, history of failed graft, primary cleft repaired at outside institution, and surgeon experience were associated with higher graft failure, but were not independent predictors when controlling for covariates. Surgeons should be aware that these factors in combination increase the odds of graft failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Convergent Validity of 2 Widely Used Methodologies for Calculating the Hospital Standardized Mortality Ratio in Flanders, Belgium
Authors: Cox Bianca , Van Wilder Astrid , De Ridder Dirk , Tambeur Wim , Maertens Pieter , Stijnen Pieter , Voorspoels Wouter , Vanden Boer Guy , Bruyneel Luk , Vanhaecht Kris 
Published: July 2023

Objectives
To assess their construct validity, we compared results from 2 models used for estimating hospital standardized mortality ratios (HSMRs) in Belgium. The method of the Flemish Hospital Network (FHN) is based on a logistic regression for each of the 64 All Patient Refined Diagnosis-Related Groups that explain 80% of mortality and uses the Elixhauser score to correct for comorbidities. (H)SMRs published on the 3M-Benchmark-Portal are calculated by a simpler indirect standardization for All Patient Refined Diagnosis-Related Groups and risk of mortality (ROM) at discharge.

Methods
We used administrative data from all eligible hospital admissions in 22 Flemish hospitals between 2016 and 2019 (FHN, n = 682,935; 3M, n = 2,122,305). We evaluated model discrimination and accuracy and assessed agreement in estimated HSMRs between methods.

Results
The Spearman correlation between HSMRs generated by the FHN model and the standard 3M model was 0.79. Although 2 of 22 hospitals showed opposite classification results, that is, an HSMR significantly <1 according to the FHN method but significantly >1 according to the 3M model, classification agreement between methods was significant (agreement for 59.1% of hospitals, κ = 0.45). The 3M model (c statistic = 0.96, adjusted Brier score = 26%) outperformed the FHN model (0.87, 17%). However, using ROM at admission instead of at discharge in the 3M model significantly reduced model performance (c statistic = 0.94, adjusted Brier score = 21%), but yielded similar HSMR estimates and eliminated part of the discrepancy with FHN results.

Conclusions
Results of both models agreed relatively well, supporting convergent validity. Whereas the FHN method only adjusts for disease severity at admission, the ROM indicator of the 3M model includes diagnoses not present on admission. Although diagnosis codes generated by complications during hospitalization have the tendency to increase the predictive performance of a model, these should not be included in risk adjustment procedures.
Safety, Tolerability, and Pharmacokinetics of a Novel Macrocyclic Gadolinium-Based Contrast Agent, HNP-2006, in Healthy Subjects
Authors: Huh Ki Young , Chung Woo Kyung , Lee Heejeong , Choi Seung Hong , Yu Kyung-Sang , Lee SeungHwan 
Published: July 2023

Objectives
Gadolinium-based contrast agents (GBCAs) are indispensable in contrast-enhanced magnetic resonance imaging. A higher risk of gadolinium deposition in linear GBCAs required the introduction of macrocyclic GBCAs with a stable molecular structure. We conducted the first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (PKs) of HNP-2006, a novel macrocyclic GBCA, in healthy male subjects.

Materials and Methods
A randomized, placebo-controlled, double-blind, single-ascending dose study was conducted. Subjects received either a single intravenous bolus injection of HNP-2006 or its matching placebo with a treatment-to-placebo ratio of 6:2 at the dose level of 0.02, 0.05, 0.1, 0.2, and 0.3 mmol/kg. Safety was assessed through routine clinical assessments. Blood sampling and urine collection were performed up to 72 hours postdose for PK assessments. Noncompartmental methods were used to calculate PK parameters, and a population PK model was constructed.

Results
Overall, 40 subjects completed the study. Fourteen subjects reported 22 treatment-emergent adverse events (TEAEs). The severity of all TEAEs was mild, and the HNP-2006 dose was associated with the incidence of TEAEs. The most common TEAEs included nausea and dizziness, which occurred within an hour of administration. HNP-2006 was rapidly eliminated by urinary excretion with a half-life of 1.8–2.0 hours and showed a dose-proportional PK. A 2-compartment model had the best fit with the population PK analysis.

Conclusions
A single intravenous dose of HNP-2006 was well-tolerated and safe up to 0.30 mmol/kg. HNP-2006 was rapidly excreted in urine and exhibited dose-independent PK profiles.
Sequential colonization events with restricted gene flow in a widespread European carnation species
Authors: Kaczmarek T. , Chen X. , Fior S. , Venon A. , Roman A. , Ursu T. , Giraud T. , Mezhenskyj V. , Koupilova K. , Hood M.E. , Widmer A. , Cornille A. 
Published: July 2023

AbstractThe key questions relating to the evolutionary processes underlying plant colonization success pertain to the geographic origin of the source population(s), the location of the migration routes, the extent to which genetic diversity is reduced via founder effects, and the extent of gene flow among populations during expansion. However, these questions must still be addressed for perennial herbaceous plants with large geographic distributions. We investigated the colonization history ofDianthus carthusianorum(the Carthusian Pink), one of the most widespread European carnation species. We called genome-wide 236,964 SNPs from a large sample across theD. carthusianorumdistribution range, and used up-to-date population genomics approaches (approximate Bayesian computation Random-Forest method, ABC-RF) to infer population demographic history. Spatial genetic structure and diversity analyses and demographic inferences indicated successive East-West colonization events by the Carthusian Pink. ABC-RF also revealed gene flow during colonization, but only among geographically close populations. This study provides important insights into the colonization processes of herbaceous perennial species belonging to one of Europe’s most diverse plant genera.
MLOsMetaDB, a meta-database to centralize the information on Liquid-liquid phase separation proteins and Membraneless organelles
Authors: Orti Fernando , Fernández María Laura , Marino-Buslje Cristina 
Published: July 2023

AbstractOver the past few years, there has been a focus on proteins that create separate liquid phases in the intracellular liquid environment, known as membraneless organelles (MLO). These organelles allow for the spatiotemporal associations of macromolecules that dynamically exchange within the cellular milieu. They provide a form of compartmentalization crucial for organizing key functions in many cells. Metabolic processes and signaling pathways in both the cytoplasm and nucleus are among the functions performed by MLOs, which are facilitated by diverse combinations of proteins and nucleic acids. However, disruptions in these liquid-liquid phase separation processes (LLPS) may lead to several diseases, such as neurodegenerative disorders and cancer, among others.To foster the study of this process and MLOs function, we presentMLOsMetaDB(http://mlos.leloir.org.ar), a comprehensive resource of information on MLO and LLPS related proteins. Our database integrates and centralizes available information for every protein involved in MLOs, which is otherwise disseminated across a plethora of different databases.Our manuscript outlines the development and features of MLOsMetaDB which provides an interactive and user-friendly environment with modern biological visualizations and easy and quick access to proteins based on LLPS role, MLO location, and organisms. Additionally, it offers an advanced search for making complex queries to generate customized information.Furthermore, MLOsMetaDB provides evolutionary information by collecting the orthologs of every protein in the same database.This is a crucial resource for transferring knowledge to other species because the LLPS protein databases are highly biased towards human proteins and, to a lesser extent, a few other well-studied or model organisms. Overall, MLOsMetaDB is a valuable resource as a starting point for researchers studying the many processes driven by LLPS proteins and membraneless organelles.
Cell Surface β-Lactamase Recruitment: A Facile Selection to Identify Protein-Protein Interactions
Authors: Hinmon Jordan A. , King Jade M. , Mayo Latrina J. , Faries Cierra R. , Street Ya’hnis T. , Crawford David W. , Beardslee Patrick C. , Hendricks Alexander , McNaughton Brian R. 
Published: July 2023

AbstractProtein-protein interactions are central to many cellular processes, and the identification of novel protein-protein interactions is a critical step in the discovery of protein therapeutics. Simple methods to identify naturally existing or laboratory evolved protein-protein interactions are therefore valuable research tools. We have developed a facile selection that links protein-protein interaction-dependent β-lactamase recruitment on the surface of E. coli with resistance to ampicillin. Bacteria displaying a protein which form a complex with a specific protein-β-lactamase fusion are protected from ampicillin-dependent cell death. In contrast, bacteria that do not recruit β-lactamase to the cell surface are killed by ampicillin. Given its simplicity and tunability, we anticipate this selection will be a valuable addition to the palette of methods for illuminating and interrogating protein-protein interactions.
Shrew evolution in hybrid zones: a meiotic undecavalent as an exclusive chromosomal supermultivalent and its weak effect on fertility
Authors: Matveevsky Sergey , Kolomiets Oxana , Shchipanov Nikolay A. , Pavlova Svetlana V. 
Published: July 2023

AbstractHybrid zones are “natural laboratories” for studying speciation. In the common shrewSorex araneus, the hybrid zone between extremely divergent in karyotypes the Moscow and Seliger chromosomal races is unique, because complex heterozygotes (interracial hybrids) form the longest meiotic configuration consisting of 11 chromosomes with monobrachial homology (undecavalent or chain-of-eleven – CXI). Different studies suggested that such a multivalent would negatively affect meiotic progression and, in general, would significantly reduce fertility. In this work, using immunocytochemical and electron microscopy methods, we investigated chromosome synapsis, recombination, and meiotic silencing in pachytene spermatocytes carrying undecavalent. Despite some abnormalities detected in spermatocytes, such as single associations of chromosomes, stretched centromeres in the multivalent, shifted recombinational peak towards distal parts of chromosomal arms of superchain, heterozygous shrews were able to form a large number of morphologically normal and active spermatozoa. Possible low stringency of pachytene checkpoints, proper segregation of homologous chromosomes, and the ability of hybrids to form mature germ cells imply rapid evolutionary fixation and circulation of Rb chromosomes within shrew populations, leading to a variety of chromosomal races.
Multi-modal representation of the size of space in the human brain
Authors: Lee Jaeeun , Park Soojin 
Published: July 2023

ABSTRACTTo estimate the size of an indoor space, we must analyze the visual boundaries that limit the spatial extent and acoustic cues from reflected interior surfaces. We used fMRI to examine how the brain processes geometric size of indoor scenes when various types of sensory cues are presented individually or together. Specifically, we asked whether the size of space is represented in a modality-specific way or in an integrative way that combines multimodal cues. In a block-design study, images or sounds that depict small and large sized indoor spaces were presented. Visual stimuli were real-world pictures of empty spaces that were small or large. Auditory stimuli were sounds convolved with different reverberation. By using a multi-voxel pattern classifier, we asked whether the two sizes of space can be classified in visual, auditory, and visual-auditory combined conditions. We identified both sensory specific and multimodal representations of the size of space. To further investigate the nature of the multimodal region, we specifically examined whether it contained multimodal information in a coexistent or integrated form. We found that AG and the right IFG pars opercularis had modality-integrated representation, displaying sensitivity to the match in the spatial size information conveyed through image and sound. Background functional connectivity analysis further demonstrated that the connection between sensory specific regions and modality-integrated regions increase in the multimodal condition compared to single modality conditions. Our results suggest that the spatial size perception relies on both sensory specific and multimodal representations, as well as their interplay during multimodal perception.
Discovering genetic biomarkers for targeted cancer therapeutics with eXplainable AI
Authors: Chakraborty Debaditya , Gutierrez-Chakraborty Elizabeth , Rodriguez-Aguayo Cristian , Başağaoğlu Hakan , Lopez-Berestein Gabriel , Amero Paola 
Published: July 2023

AbstractExplainable Artificial Intelligence (XAI) enables a holistic understanding of the complex and nonlinear relationships between genes and prognostic outcomes of cancer patients. In this study, we focus on a distinct aspect of XAI – to generate accurate and biologically relevant hypotheses and provide a shorter and more creative path to advance medical research. We present an XAI-driven approach to discover otherwise unknown genetic biomarkers as potential therapeutic targets in high-grade serous ovarian cancer, evidenced by the discovery of IL27RA, which leads to reduced peritoneal metastases when knocked down in tumor-carrying mice given IL27-siRNA-DOPC nanoparticles.SummaryExplainable Artificial Intelligence is amenable to generating biologically relevant testable hypotheses despite their limitations due to explanations originating from post hoc realizations.
tidysdm: leveraging the flexibility oftidymodelsfor Species Distribution Modelling in R
Authors: Leonardi Michela , Colucci Margherita , Pozzi Andrea Vittorio , Scerri Eleanor M. L. , Manica Andrea 
Published: July 2023

ABSTRACTIn species distribution modelling (SDM), it is common practice to explore multiple machine-learning algorithms and combine their results into ensembles. This is no easy task in R: different algorithms were developed independently, with inconsistent syntax and data structures. Specialised SDM packages integrate multiple algorithms by creating a complex interface between the user (providing a unified input and receiving a unified output), and the back-end code (that tackles the specific needs depending on the algorithm). This requires a lot of work to create and maintain the right interface, and it prevents an easy integration of other methods that may become available.Here we presenttidysdm, an R package that solves this problem by taking advantage of thetidymodelsuniverse. Being part of thetidyverse, (i) it has standardised grammar and data structures providing a coherent interface for modelling, (ii) includes packages designed for fitting, tuning, and validating various models, and (iii) allows easy integration of new algorithms and methods.tidysdmallows easy, flexible and quick species distribution modelling by supporting standard algorithms, including additional SDM-oriented functions, and giving the opportunity of using any algorithm or procedure to fit, tune and validate a large number of different models. Additionally, it provides further functions to easily fit models based on paleo/time-scattered data.The package includes two vignettes detailing standard procedures for present-day and time-scattered data. These vignettes also showcase the integration withpastclim(Leonardiet al. 2023) to allow easier access to palaeoclimatic data series, if needed, but users can bring in their own climatic data in standard formats.