bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, efficacy and safety of a novel fibrinogen concentrate in pediatric patients with congenital afibrinogenemia
Authors: Khayat Claudia Djambas , Navarro-Puerto Jordi , Ross Cecil Reuben , Subramanian Kannan , Kalappanavar Nijalingappa K. , Rucker Karen , Liang Wei , Mondou Elsa 
Published: December 2022

Introduction
Congenital afibrinogenemia treatment with plasma-derived fibrinogen concentrates in pediatric patients is limited. This study investigated the pharmacokinetics, surrogate efficacy, and safety of a plasma-derived fibrinogen concentrate (FIB Grifols) in pediatric patients with congenital afibrinogenemia.

Methods
Patients aged <18 years old diagnosed with congenital afibrinogenemia were included in this prospective, multinational, phase 1–2, single-arm study. After a single dose of a plasma-derived fibrinogen concentrate (70 mg/kg body weight), pharmacokinetic parameters were determined from plasma fibrinogen activity (Clauss method) and antigen method (ELISA), and calculated by noncompartmental and population pharmacokinetic (popPK) models. Patients were followed up over 14 days. Efficacy variables were the mean change on thromboelastographic variables (maximum clot firmness [MCF], alpha angle [α]) and coagulation tests (prothrombin time, activated partial thromboplastin time, and thrombin time) 1 h postinfusion. Safety parameters were assessed.

Results
Eleven patients with a median (range) age 8.80 (3.7–12.7) years were treated with the plasma-derived fibrinogen concentrate. Using the popPK modeling, fibrinogen activity reached a mean (standard deviation) C
max of 1.3 (0.225) g/l, half-life (t
1/2) of 60.6 (4.48) h and incremental in vivo recovery (IVR) of 1.86 (0.322) (mg/dl)/(mg/kg). Surrogate efficacy was demonstrated by significant increase in MCF (9.23 [3.94] mm; P < 0.001; 95% confidence interval 6.58, 11.87). All coagulation times were significantly shortened after fibrinogen concentrate infusion. Adverse events were mild or moderate in severity, and unrelated to fibrinogen concentrate.

Conclusions
In pediatric patients with congenital afibrinogenemia, plasma-derived fibrinogen concentrate revealed a favorable and specific pharmacokinetic profile, demonstrated efficacy in coagulation and was safe and well tolerated.
Exploring the potential cost-effectiveness of a novel platelet assay for guiding dual antiplatelet therapy duration in acute coronary syndrome patients following percutaneous coronary intervention
Authors: Vilain Katherine A. , DiBattiste Peter M. , Schneider David J. , Cohen David J. 
Published: December 2022

Objective
Duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) influences ischemic and bleeding events. Platelet expression of constant fragment of immunoglobulin, low affinity IIa, receptor (FcγRIIa) independently predicts risk of ischemic complications and is proposed as a tool to guide individualized care.

Methods
We used a Markov model to predict lifetime ischemic and bleeding events and healthcare costs in acute myocardial infarction (MI) patients treated with PCI and DAPT and to project cost-effectiveness of platelet FcγRIIa-assay-guided care (30:3 months DAPT for patients at high: low ischemic risk) versus current standard care (12 months DAPT) from the perspective of the US healthcare system. Model inputs included assay sensitivity and specificity, ischemic and bleeding event rates, and impacts on quality of life, mortality, and costs. Assay cost was $90. Sensitivity analyses were conducted over a range of plausible clinical and cost assumptions.

Results
Under base case assumptions, platelet FcγRIIa-assay-guided DAPT duration was projected to increase lifetime costs by $19 versus standard care, with an associated incremental cost-effectiveness ratio (ICER) of $436 per quality-adjusted life-year (QALY) gained. Assay-guided DAPT duration was consistent with high-value care (ICER < $50 000/QALY gained) over a broad range of alternative assumptions.

Conclusion
Based on a decision-analytic model, for patients with MI treated with PCI, the additional costs of the platelet FcγRIIa assay for guiding DAPT duration would be largely offset by reductions in downstream event-related costs, and assay-guided care would be highly cost-effective by current standards. These findings require confirmation in prospective studies and in a randomized clinical trial of assay-guided versus nonassay-guided DAPT duration.
Prevalence of low-attenuation plaques and statin therapy in plaque rupture type of acute coronary syndrome
Authors: Kashiwagi Manabu , Taruya Akira , Kuroi Akio , Katayama Yosuke , Terada Kosei , Wada Teruaki , Takahata Masahiro , Shiono Yasutsugu , Tanimoto Takashi , Tanaka Atsushi 
Published: December 2022

Background
We sought to investigate the differences in coronary plaque morphology on coronary computed tomography angiography (CCTA) and medical therapy between acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD). We also explored the relationship between plaque morphology on CCTA at the initial phase and lesion morphology in the acute phase of ACS.

Methods
In 5967 patients who underwent invasive coronary angiography, 58 ACS and 91 SIHD patients who had prior CCTA imaging of the culprit lesion and denied ischemic heart disease at CCTA scanning were enrolled.

Results
Although the prevalence of positive remodeling was not different (P = 0.27), low-attenuation plaques (LAP) on prior CCTA were significantly higher in ACS than in SIHD (52% vs. 24%, P < 0.01). The frequency of coronary stenosis grading did not differ between the two groups (P = 0.14). In ACS patients, the frequencies of plaque rupture and lipid-rich plaque assessed by optical coherence tomography (OCT) were significantly higher in LAP than in non-LAP (73% vs. 23%, P < 0.01; 82% and 23%, P < 0.01). Multivariate regression analysis revealed that statin use and LAP on prior CCTA were predictors of future ACS events (P < 0.01, and P < 0.05, respectively).

Conclusions
LAP on CCTA, not positive arterial remodeling, and lack of statin therapy were associated with ACS development. In addition, LAP more frequently led to the development of the plaque rupture type of ACS compared with non-LAP. Lipid-lowering therapy with statins might be useful to prevent plaque rupture in patients with LAP regardless of coronary stenosis.
Tips and tricks for management of the dysfunctional maxillary sinus
Authors: Chung Sei Y. , Halderman Ashleigh A. 
Published: December 2022

Purpose of the review
To review the various factors associated with the most common cause of maxillary sinus dysfunction; recalcitrant chronic maxillary sinusitis (RCMS). In addition, available medical and surgical management options are discussed along with various tips and tricks for optimal management.

Recent findings
Defects in mucociliary clearance, immunodeficiency, anatomic factors, and infectious etiologies have been implicated in dysfunction of the maxillary sinus leading to RCMS. Medical management including oral antibiotics or topical drugs have shown varying degrees of success. Endoscopic modified medial maxillectomy (EMMM) has been shown to significantly improve symptoms in patients with RCMS.

Summary
A dysfunctional maxillary sinus presents a clinical challenge. A thorough evaluation of any potential contributing factors must be done in addition to an assessment of the adequacy of prior surgical treatment of the maxillary sinus. Beyond the middle meatal antrostomy, EMMM can be used to effectively address RCMS. In cases that fail EMMM, removal of the condemned mucosa to encourage auto-obliteration of the sinus can be considered.
Interprofessional Naloxone Student Training to Manage Suspected Opioid Overdose
Authors: Riley Elizabeth , Trotter Stephanie , Dayer Lindsey , Teigen Amber , Nagel Corey , Stickley Kimberly , LaBorde Pamela , Richardson Leah , McFerguson Rochelle , Ward Nicole , Anders Michael 
Published: December 2022

Purpose
The study purpose was to examine the effect of interprofessional naloxone training on students' knowledge, confidence, and interprofessional collaboration competency. The overarching goal was to decrease mortality related to opioid overdoses.

Design/Methods
A training session for interprofessional students consisted of a lecture presentation, demonstration, and hands-on practice regarding appropriate administration of naloxone for suspected opioid overdose. A questionnaire elicited baseline and change in knowledge, confidence, and interprofessional collaboration competency scores at pretraining and posttraining. In addition, changes in knowledge and confidence were also measured 3 weeks after the training. Thematic analysis explored training components that students perceived as valuable or needing improvement.

Results
Participants (N = 100) were nursing (n = 33), physician assistant (n = 37), and pharmacy (n = 30) students. Pretraining and posttraining comparison demonstrated increased knowledge (P < .001), confidence (P < .001), and collaboration scores (P < .001). At 3 weeks, knowledge and confidence remained higher than pretraining (P < .001). Knowledge was trending downward compared with posttraining (P = .09). Thematic analysis identified 4 themes: (a) indications for administration of different naloxone types, (b) learning modalities, (c) knowledge application, and (d) improvements.

Conclusions
An interprofessional naloxone administration training resulted in increased knowledge, confidence, and interprofessional teamwork. Educators can adapt this training for a variety of future or current healthcare professionals to improve immediate intervention and outcomes in suspected opioid overdoses.
What the Joint Commission Medication Management Titration Standards Mean to Quality Care for Complex Patients
Authors: Chechel Laura , McLean Barbara , Slazinski Theresa , Rincon Teresa 
Published: December 2022

Abstract
The Joint Commission (TJC), the nation’s largest healthcare accreditor, was founded in the 1950s. Its Standards for Medication Management (MM) of titratable medications focused on prescriptive ordering practices versus reliance on nurse clinical decision making. The use of measurable endpoints to guide nurse decision making regarding medication titration has been the standard of care since the inception of TJC. Evidence to support altering these practice patterns is lacking. Using the 6 aims for the healthcare system (safe, timely, effective, efficient, equitable, and patient-centered) from the National Academy of Medicine, formerly the Institute of Medicine, and the American Association of Critical-Care Nurses Healthy Work Environment essential standards (skilled communication, true collaboration, effective decision making, appropriate staffing, meaningful recognition, authentic leadership), this article examines the impact of TJC MM standards on system design in critical care environments.
A new era of HIV care for age-associated multimorbidity
Authors: Collini Paul , Mawson Rebecca L. 
Published: December 2022

Purpose of review
The management of people with HIV has shifted focus from acute AIDS-defining illness towards improving detection of chronic disease and reducing impact of multimorbidity. In this review, we explore this shifting paradigm of HIV care and the evidence for alternative models proposed to provide integrated holistic services for people with HIV (PWH) with multimorbidity.

Recent findings
Despite 25 years of the antiretroviral treatment (ART) era an increased incidence of noncommunicable disease (NCD) and multimorbidity in PWH persists. As the world moves closer to universal ART coverage this phenomenon is now reported in low- and middle-income settings. Multimorbidity affects PWH disproportionately compared to the general population and results in reduced health related quality of life (HRQoL), greater hospitalization and higher mortality. There is evidence that NCD care provision and outcomes may be inferior for PWH than their HIV negative counterparts. Various models of integrated multimorbidity care have developed and are grouped into four categories; HIV specialist clinics incorporating NCD care, primary care services incorporating HIV care, community NCD clinics offering integrated HIV care, and multidisciplinary care integrated with HIV in secondary care. Evidence is limited as to the best way to provide multimorbidity care for PWH.

Summary
A new era of HIV care for an ageing population with multimorbidity brings challenges for health providers who need to develop holistic patient focused services which span a range of coexisting conditions.
Coronary Artery Calcium Evaluation Using New Generation Photon-counting Computed Tomography Yields Lower Radiation Dose Compared With Standard Computed Tomography
Authors: Schwartz Fides R. , Daubert Melissa A. , Molvin Lior , Ramirez-Giraldo Juan C. , Samei Ehsan , Marin Daniele , Tailor Tina D. 
Published: December 2022

Abstract:
Prospective head-to-head comparison of coronary calcium scores between standard computed tomography (CT) and photon-counting CT show no significant differences, while photon-counting CT administers substantially lower radiation dose.
Factors associated with support-seeking behavior among AIAN women survivors of IPV
Authors: Park Susanna Y 
Published: December 2022

AbstractObjectivesTo understand how Native women seek support as survivors of intimate partner violence by examining factors associated with seeking formal support (e.g., medical, police), informal support (e.g., family, friends), or both types of support.MethodsData from the 2010 National Intimate and Sexual Violence Survey were analyzed among the AIAN oversamples. Descriptive statistics and odds ratio analyses were conducted to observe significant factors that are associated with adult Native women survivors seeking support.ResultsSurvivors have higher odds of seeking informal supports than formal supports. Formal support is not often sought, however survivors had significantly higher odds of seeking therapy. Conclusions. While there are various avenues in which survivors may seek support, not all types of support are helpful to the survivor’s needs. However, this study is still valuable in distinguishing factors related to support-seeking and observing general relationships. Focused and intentional public health research on support for AIAN women survivors is needed to further understand how programs and policies can be improved.
Habitat edges affect tree diversity more than biomass regeneration in a reforested wet neotropical timber plantation
Authors: Medina Nicholas , Capetz Emma , Johnson Andrea , Mendoza Agustín , Villalobos Max 
Published: December 2022

AbstractAbout half of all forests are tropical and secondary, making tropical forest regeneration integral to future forests. Tree stand biomass and taxonomic richness can recover in a few decades, but relative abundances may lag indefinitely. Since most forests are within a km of a habitat edge, edge effects likely affect community composition regeneration. However, most studies assess how degraded edges affect intact forests, leaving it unclear whether higher-quality edges could facilitate regeneration of nearby degraded forests. Notably, higher quality edges near intact forests could promote processes like dispersal and wood biomass accumulation that effectively accelerate succession, leading to better performance of shade-tolerant taxa compared to pioneer taxa in the early stages of forested plantation regeneration. This study addressed how wet tropical forested plantation regeneration was affected by distance to adjacent intact forest edge. It was hypothesized that old timber plantations facilitate regeneration by increasing available shade, favoring the presence and biomass of later-successional taxa, ultimately changing community composition overall. A wet neotropical timber plantation reforested after 20 years and adjacent to primary forest was censused for trees along a 300 m edge distance gradient, and analysis matched identified taxa to broad dispersal mode and wood density traits using relevant literature.As distance from primary forest edge increased, stem and wood density tended to increase significantly, with ~10% variation explained, while biomass and canopy light surprisingly tended to stay the same. Stand tree richness also tended to increase significantly, but diversity decreased steeply and non-linearly, explained in part by wood density, and taxonomic composition varied notably. Finally, tree taxa associated with both early and late successional stages decreased significantly, as well as genus Ficus, but biomass by dispersal mode did not tend to change. Overall this study supports that stand composition is less resilient and more subject to edge effects than biomass and richness, suggesting that global forests will likely be distinctly new assemblages in the future, with timber and biodiversity trade-offs occurring based on local and regional management activity.
ModelCIF: An extension of PDBx/mmCIF data representation for computed structure models
Authors: Vallat Brinda , Tauriello Gerardo , Bienert Stefan , Haas Juergen , Webb Benjamin M. , Žídek Augustin , Zheng Wei , Peisach Ezra , Piehl Dennis W. , Anischanka Ivan , Sillitoe Ian , Tolchard James , Varadi Mihaly , Baker David , Orengo Christine , Zhang Yang , Hoch Jeffrey C. , Kurisu Genji , Patwardhan Ardan , Velankar Sameer , Burley Stephen K. , Sali Andrej , Schwede Torsten , Berman Helen M. , Westbrook John D. 
Published: December 2022

ABSTRACTModelCIF (github.com/ihmwg/ModelCIF) is a data information framework developed for and by computational structural biologists to enable delivery ofFindable, Accessible, Interoperable, andReusable(FAIR) data to users worldwide. It is an extension of the Protein Data Bank Exchange / macromolecular Crystallographic Information Framework (PDBx/mmCIF), which is the global data standard for representing experimentally-determined, three-dimensional (3D) structures of macromolecules and associated metadata. ModelCIF provides an extensible data representation for deposition, archiving, and public dissemination of predicted 3D models of proteins. The PDBx/mmCIF framework and its extensions (e.g., ModelCIF) are managed by the Worldwide Protein Data Bank partnership (wwPDB,wwpdb.org) in collaboration with relevant community stakeholders such as the wwPDB ModelCIF Working Group (wwpdb.org/task/modelcif). This semantically rich and extensible data framework for representing computed structure models (CSMs) accelerates the pace of scientific discovery. Herein, we describe the architecture, contents, and governance of ModelCIF, and tools and processes for maintaining and extending the data standard. Community tools and software libraries that support ModelCIF are also described.
The energetic and allosteric landscape for KRAS inhibition
Authors: Weng Chenchun , Faure Andre J. , Lehner Ben 
Published: December 2022

AbstractThousands of proteins have now been genetically-validated as therapeutic targets in hundreds of human diseases. However, very few have actually been successfully targeted and many are considered ‘undruggable’. This is particularly true for proteins that function via protein-protein interactions: direct inhibition of binding interfaces is difficult, requiring the identification of allosteric sites. However, most proteins have no known allosteric sites and a comprehensive allosteric map does not exist for any protein. Here we address this shortcoming by charting multiple global atlases of inhibitory allosteric communication in KRAS, a protein mutated in 1 in 10 human cancers. We quantified the impact of >26,000 mutations on the folding of KRAS and its binding to six interaction partners. Genetic interactions in double mutants allowed us to perform biophysical measurements at scale, inferring >22,000 causal free energy changes, a similar number of measurements as the total made for proteins to date. These energy landscapes quantify how mutations tune the binding specificity of a signalling protein and map the inhibitory allosteric sites for an important therapeutic target. Allosteric propagation is particularly effective across the central beta sheet of KRAS and multiple surface pockets are genetically-validated as allosterically active, including a distal pocket in the C-terminal lobe of the protein. Allosteric mutations typically inhibit binding to all tested effectors but they can also change the binding specificity, revealing the regulatory, evolutionary and therapeutic potential to tune pathway activation. Using the approach described here it should be possible to rapidly and comprehensively identify allosteric target sites in many important proteins.
Spatial and Spectral Components of the BOLD Global Signal in Rat Resting-State Functional MRI
Authors: Anumba Nmachi , Maltbie Eric , Pan Wen-Ju , LaGrow Theodore J. , Xu Nan , Keilholz Shella 
Published: December 2022

ABSTRACTIn resting-state fMRI (rs-fMRI), the global signal average captures widespread fluctuations related to unwanted sources of variance such as motion and respiration, and has long been used as a regressor to reduce noise during data preprocessing. However, coherent neural activity in spatially-extended functional networks can also contribute to the global signal. The relative contributions of neural and non-neural sources to the global signal remain poorly understood. This study sought to tackle this problem through the comparison of the blood oxygenation level dependent (BOLD) global signal to an adjacent non-brain tissue signal from the same scan in rs-fMRI obtained from anesthetized rats. In this dataset motion was minimal and ventilation was phase-locked to image acquisition to minimize respiratory fluctuations. In addition to contrasting the spatial and spectral components of these two signals, we also observed these differences across the use of three different anesthetics: isoflurane, dexmedetomidine, and a combination of dexmedetomidine and light isoflurane. Here, we report differences in the spectral composition of the two signals as evaluated by a power spectral density (PSD) estimate and a fractional amplitude of low-frequency fluctuations (fALFF) calculation. Additionally, we show spatial selectivity for specific brain structures that show an increased correlation to the global signal both statically and dynamically, through Pearson’s correlation and co-activation pattern analysis, respectively. All of the observed differences between the BOLD global signal and the adjacent non-brain tissue signal were maintained across all three anesthetic conditions, showing that the global signal is distinct from the noise contained in the tissue signal. This study provides a unique perspective to the contents of the global signal and their origins.