bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Rapid Qualitative Screen for Anticoagulant Presence
Authors: Wong Selena , Slingerland Jenna , Dickerson Jane A , Pak Jennifer , Roach Gavin D , Saifee Nabiha H 
Published: December 2023

Abstract

Background
Direct oral anticoagulants (DOACs) and fondaparinux with stable pharmacokinetics are commonly used anticoagulants for outpatient care. Due to the lack of monitoring requirements, drug-specific assays are not available in most hospital laboratories, but drug levels are needed in some urgent/emergency situations. This study describes the development of a qualitative screen for the presence of DOAC or fondaparinux using coagulation tests found in most laboratories.

Methods
The DOAC screen is composed of a heparin anti-Xa activity assay and thrombin time (TT) assay. The STA®-Liquid-Anti-Xa assay calibrated with Stago Multi Hep® and STA®-TT were run on STA-R Max® analyzers. The anti-Xa activity and TT assays were repeated 5 times in samples of commercially available calibrators and controls for each drug: fondaparinux, dabigatran, rivaroxaban, apixaban, and edoxaban. Statistical analysis and correlations were performed for anti-Xa activity and TT results for each drug and pooled normal plasma.

Results
A significant correlation was found between heparin-calibrated anti-Xa levels and fondaparinux, rivaroxaban, apixiban, and edoxaban (r2 = 0.99–1.0). Dabigatran showed a strong linear correlation (r2 = 0.99) with TT. Anti-Xa levels &gt;0.3 IU/mL and TT &gt;25 seconds were determined as cutoffs at our lab for the detection of clinically relevant drug levels of factor Xa inhibitor and direct thrombin inhibitor, respectively.

Conclusions
Our study demonstrates that commonly available heparin anti-Xa activity and TT assays can be used to qualitatively detect DOACs and fondaparinux and provides a method to establish a qualitative interpretation.
Explainable Machine Learning Models for Rapid Risk Stratification in the Emergency Department: A Multicenter Study
Authors: van Doorn William P T M , Helmich Floris , van Dam Paul M E L , Jacobs Leo H J , Stassen Patricia M , Bekers Otto , Meex Steven J R 
Published: December 2023

Abstract

Background
Risk stratification of patients presenting to the emergency department (ED) is important for appropriate triage. Diagnostic laboratory tests are an essential part of the workup and risk stratification of these patients. Using machine learning, the prognostic power and clinical value of these tests can be amplified greatly. In this study, we applied machine learning to develop an accurate and explainable clinical decision support tool model that predicts the likelihood of 31-day mortality in ED patients (the RISKINDEX). This tool was developed and evaluated in four Dutch hospitals.

Methods
Machine learning models included patient characteristics and available laboratory data collected within the first 2 h after ED presentation, and were trained using 5 years of data from consecutive ED patients from the Maastricht University Medical Center (Maastricht), Meander Medical Center (Amersfoort), and Zuyderland Medical Center (Sittard and Heerlen). A sixth year of data was used to evaluate the models using area under the receiver-operating-characteristic curve (AUROC) and calibration curves. The Shapley additive explanations (SHAP) algorithm was used to obtain explainable machine learning models.

Results
The present study included 266 327 patients with 7.1 million laboratory results available. Models show high diagnostic performance with AUROCs of 0.94, 0.98, 0.88, and 0.90 for Maastricht, Amersfoort, Sittard and Heerlen, respectively. The SHAP algorithm was utilized to visualize patient characteristics and laboratory data patterns that underlie individual RISKINDEX predictions.

Conclusions
Our clinical decision support tool has excellent diagnostic performance in predicting 31-day mortality in ED patients. Follow-up studies will assess whether implementation of these algorithms can improve clinically relevant end points.
The Role of Artificial Intelligence for Providing Scientific Content for Laboratory Medicine
Authors: Wu Alan H B , Jaffe Allan S , Peacock William Franklin , Kavsak Pete , Greene Dina , Christenson Robert H 
Published: December 2023

Abstract

Background
Artificial intelligence (AI) promises to become an important tool in the practice of laboratory medicine. AI programs are available online that can provide concise medical and laboratory information within seconds after a question is submitted.

Methods
We posed the following contemporary and relevant question for clinical chemists using an AI program: “Should labs eliminate CK-MB testing?” The results of this inquiry were critically reviewed by a cardiologist, emergency department physician, and clinical laboratorians for accuracy and appropriateness.

Results
An AI report answering this question was generated within 15 s. The experts felt that the information was inaccurate with the statements that CK-MB results are released earlier than cardiac troponin (cTn), and are more useful for detection of myocardial injury in patients with renal insufficiencies. The summary omitted discussion on the ongoing debate for periprocedural detection of acute myocardial infarction (MI), the perceived value for detection of reinfarction, the value in risk stratification compared to cTn, the economic justification for testing both CK-MB and cTn, and medicolegal aspects of testing when results are discordant.

Conclusions
At this time, AI does not appear to be ready to be used by clinical laboratories for answering important practice questions.
Implementing Next-Generation Sequencing Process Changes to Increase Capacity and Improve Timeliness of Molecular Biomarker Profiling for Lung Cancer Patients
Authors: Semenuk Laura J , Kartolo Baskoro A , Feilotter Harriet E , Lee Shawna M , Savage Colleen A , Boag Alexander H , Digby Geneviève C , Mates Mihaela 
Published: December 2023

Abstract

Background
Faced with expansion of molecular tumor biomarker profiling, the molecular genetics laboratory at Kingston Health Science Centre experienced significant pressures to maintain the provincially mandated 2-week turnaround time (TAT) for lung cancer (LC) patients. We used quality improvement methodology to identify opportunities for improved efficiencies and report the impact of the initiative.

Methods
We set a target of reducing average TAT from accessioning to clinical molecular lab report for LC patients. Process measures included percentage of cases reaching TAT within target and number of cases. We developed a value stream map and used lean methodology to identify baseline inefficiencies. Plan-Do-Study-Act cycles were implemented to streamline, standardize, and automate laboratory workflows. Statistical process control (SPC) charts assessed for significance by special cause variation.

Results
A total of 257 LC cases were included (39 baseline January–May 2021; 218 post-expansion of testing June 2021). The average time for baseline TAT was 12.8 days, peaking at 23.4 days after expansion of testing, and improved to 13.9 days following improvement interventions, demonstrating statistical significance by special cause variation (nonrandom variation) on SPC charts.

Conclusions
The implementation of standardized manual and automated laboratory processes improved timeliness of biomarker reporting despite the increasing volume of testing at our center.
Merlin/NF2 regulates SLC7A11/xCT expression and cell viability under glucose deprivation at high cell density in glioblastoma cells
Authors: Yamaguchi Itsuki , Katoh Hironori 
Published: December 2023

Abstract
The cystine/glutamate transporter SLC7A11/xCT is highly expressed in many cancer cells and plays an important role in antioxidant activity by supplying cysteine for glutathione synthesis. Under glucose-depleted conditions, however, SLC7A11-mediated cystine uptake causes oxidative stress and cell death called disulfidptosis, a new form of cell death. We previously reported that high cell density (HD) promotes lysosomal degradation of SLC7A11 in glioblastoma cells, allowing them to survive under glucose-depleted conditions. In this study, we found that the neurofibromatosis type 2 gene, Merlin/NF2 is a key regulator of SLC7A11 in glioblastoma cells at HD. Deletion of Merlin increased SLC7A11 protein level and cystine uptake at HD, leading to promotion of cell death under glucose deprivation. Furthermore, HD significantly decreased SLC7A11 mRNA level, which was restored by Merlin deletion. This study suggests that Merlin suppresses glucose deprivation-induced cell death by downregulating SLC7A11 expression in glioblastoma cells at HD.
Sprouting of afferent and efferent inputs to pelvic organs after spinal cord injury
Authors: Zhao Shunyi , Tang Chuanxi , Weinberger Jeremy , Gao Dianshuai , Hou Shaoping 
Published: December 2023

Abstract
Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo similar morphological changes. Using a rat spinal cord transection model, we conducted immunohistochemistry to investigate afferent and efferent innervations to the kidney, colon, and bladder. Approximately 3–4 weeks after injury, immunostaining demonstrated that tyrosine hydroxylase (TH)-labeled postganglionic sympathetic fibers and calcitonin gene-related peptide (CGRP)-immunoreactive sensory terminals sprout in the renal pelvis and colon. Morphologically, sprouted afferent or efferent projections showed a disorganized structure. In the bladder, however, denser CGRP-positive primary sensory fibers emerged in rats with SCI, whereas TH-positive sympathetic efferent fibers did not change. Numerous CGRP-positive afferents were observed in the muscle layer and the lamina propria of the bladder following SCI. TH-positive efferent inputs displayed hypertrophy with large diameters, but their innervation patterns were sustained. Collectively, afferent or efferent inputs sprout widely in the pelvic organs after SCI, which may be one of the morphological bases underlying functional adaptation or maladaptation.
Easier In than Out: Lessons Learned from the Termination of the Iraq Sanctions Regime
Authors: Grauvogel Julia , Attia Hana 
Published: December 2023

Abstract
Sanctions senders respond to the abrupt escalation of crises, such as the Iraqi invasion of Kuwait in 1990 or the Russian invasion of Ukraine in February 2022. To react quickly, they often decide on coercive measures without a long-term exit strategy in mind. Similarly, research has long prioritized questions of sanctions onset and effectiveness, while studies on their termination remain scarce. In response, we reconstruct previously neglected debates about ending sanctions for the “watershed case” of the UN embargo against Iraq. Based on a conceptual framework that emphasizes a more process-oriented and signaling perspective on sanctions termination, we analyze archival data as well as governmental and UN documents. We find that the United States depicted the lifting of sanctions as an all-or-nothing question, which impeded a more gradual approach toward ending the measures. We show that senders significantly disagreed over the requirements for ending sanctions and over whether possibly signaling the end of Iraq’s isolation was politically desirable. In the second step, we then draw implications from the case of Iraq to study contemporary sanctions termination. We use novel data on the termination of all EU, UN, and US sanctions from 1990 to 2018 to explore whether the Iraq case inspired changes in senders’ approaches. We find that the use of review provisions and sunset clauses significantly increased post-Iraq. Finally, we discuss whether disagreements over termination requirements in the case of Russia risk the repetition of past pitfalls when it comes to the process of ending sanctions.
Self-perceived leadership and entrepreneurship skills: profiling healthcare professionals
Authors: Sacre Hala , Iskandar Katia , Haddad Chadia , Shahine Mayssam , Hajj Aline , Zeenny Rony M , Akel Marwan , Salameh Pascale 
Published: December 2023

Abstract

Background
Healthcare is a complex system with overarching challenges that arise from the different hierarchically organized structures and the diversity of people interacting and communicating in the same environment. This complexity can be addressed by strengthening healthcare professional leadership and entrepreneurship competencies. This study aims to evaluate the self-perception of healthcare professionals regarding these skills and their association with demographic characteristics and university attributes.

Method
A cross-sectional survey conducted online from July to December 2021 recruited 245 Lebanese health professionals from different health-related institutions (hospitals, pharmaceutical industry, health professions universities, and others) using snowball sampling. A cluster analysis was performed based on the socio-demographic and work characteristics of the participants to classify their profiles. Bivariate and multivariate analyses were performed after ensuring the adequacy of the models. Significance was set at a P value &lt; 0.05.

Results
Cluster analysis showed two distinct profiles, reflected by Cluster 1 for older individuals with moderate/high management versus Cluster 2 for younger people with low management profiles. The logistic regression showed that Cluster 1 was significantly associated with higher leadership with administrative, interpersonal, and conceptual skills. The interpersonal skills represented best Cluster 1 (ORa = 7.47), followed by the conceptual skills (ORa = 4.40). Linear regression analysis showed that Cluster 1 was significantly associated with higher decision-making (β = 0.69) and higher tolerance of ambiguity (β = 1.01). No association was found between other subscales, total entrepreneurship scales, and belonging to any cluster (P &gt; 0.05).

Conclusion
Although most healthcare professionals showed moderate to high perceptions related to their leadership and entrepreneurship, younger ones were aware of the need to develop these skills to meet the challenges of the complex dynamic health system. Educating students and training professionals to acquire these skills would create value in emerging health services while fostering innovation, creativity, and quality improvement in the workplace.
Implementation and Perceived Effectiveness of Prospective Audit and Feedback and Preauthorization by US Pediatric Antimicrobial Stewardship Programs
Authors: Manice Christina S , Muralidhar Nivedita , Campbell Jeffrey I , Nakamura Mari M 
Published: December 2023

Abstract

Background
Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs’ perceptions of how these choices affected attainment of stewardship goals.

Methods
We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid. We asked open-ended questions about organization, staffing, and operation of these strategies, as well as rationales for and perceived advantages and disadvantages of these choices. We used applied thematic analysis to analyze transcripts, organizing coded text into themes and categories. We formulated a conceptual model for how the design and performance of PAF and preauthorization affect stewardship goals and stewards’ work experiences.

Results
Eighteen physicians and 14 pharmacists from 24 hospitals participated in five focus groups. Stewards described myriad advantages and limitations of PAF and preauthorization that support or detract from stewardship goals. For example, PAF uncovered institutional trends in antibiotic use and fostered relationship building but was time-consuming. Preauthorization efficiently reduced broad-spectrum antimicrobial use, yet offered limited educational opportunities. How these strategies facilitated or impeded appropriate antimicrobial use in turn affected stewards’ professional satisfaction, creating a feedback loop that could reinforced positive or negative outcomes.

Conclusions
ASPs reported differing emphasis on and implementation of PAF and preauthorization. Each strategy entailed contrasting benefits and trade-offs for steward satisfaction and perceived efficacy, suggesting that a hybrid approach could enable ASPs to maximize strengths of each to mitigate drawbacks of the other.
Identification and estimation of causal peer effects using double negative controls for unmeasured network confounding
Authors: Egami Naoki , Tchetgen Tchetgen Eric J 
Published: December 2023

AbstractIdentification and estimation of causal peer effects are challenging in observational studies for two reasons. The first is the identification challenge due to unmeasured network confounding, for example, homophily bias and contextual confounding. The second is network dependence of observations. We establish a framework that leverages a pair of negative control outcome and exposure variables (double negative controls) to non-parametrically identify causal peer effects in the presence of unmeasured network confounding. We then propose a generalised method of moments estimator and establish its consistency and asymptotic normality under an assumption about ψ-network dependence. Finally, we provide a consistent variance estimator.
Unveiling hidden variability components in accreting X-ray binaries using both the Fourier power and cross-spectra
Authors: Méndez Mariano , Peirano Valentina , García Federico , Belloni Tomaso , Altamirano Diego , Alabarta Kevin 
Published: December 2023

ABSTRACT
We present a novel method for measuring the lags of (weak) variability components in neutron-star and black-hole low-mass X-ray binaries (LMXBs). For this we assume that the power and cross-spectra of these sources consists of a number of components that are coherent in different energy bands, but are incoherent with one another. The technique is based on fitting simultaneously the power spectrum (PS) and the Real and Imaginary parts of the cross-spectrum (CS) with a combination of Lorentzian functions. We show that, because the PS of LMXBs is insensitive to signals with a large Imaginary part and a small Real part in the CS, this approach allows us to uncover new variability components that are only detected in the CS. We also demonstrate that, contrary to earlier claims, the frequency of the type-C quasi-periodic oscillation (QPO) in the black-hole binary GRS 1915+105 does not depend on energy. Rather, the apparent energy dependence of the QPO frequency can be explained by the presence of a separate QPO component with a slightly higher frequency than that of the QPO, whose rms amplitude increases faster with energy than the rms amplitude of the QPO. From all the above we conclude that, as in the case of the PS, the CS of black-hole and neutron-star binaries can be fitted by a combination of Lorentzian components. Our findings provide evidence that the frequency-dependent part of the transfer function of these systems can be described by a combination of responses, each of them acting over relatively well-defined time-scales. This conclusion challenges models that assume that the main contribution to the lags comes from a global, broadband, transfer function of the accreting system.
H3 K27M-altered glioma and diffuse intrinsic pontine glioma: Semi-systematic review of treatment landscape and future directions
Authors: van den Bent Martin , Saratsis Amanda M , Geurts Marjolein , Franceschi Enrico 
Published: December 2023

AbstractH3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on www.clinicaltrials.gov evaluating novel therapeutics in this population. Current clinical trials were identified using clinicaltrials.gov, and studies qualifying for this analysis were active or ongoing interventional trials that evaluated a therapy in at least 1 treatment arm or cohort comprised exclusively of patients with DIPG and H3 K27M-mutant glioma. Forty-one studies met these criteria, including trials evaluating H3 K27M vaccination, chimeric antigen receptor T-cell therapy, and small molecule inhibitors. Ongoing evaluation of novel therapeutics is necessary to identify safe and effective interventions in this underserved patient population.
Effects of intermittent fasting combined with physical exercise on cardiometabolic outcomes: systematic review and meta-analysis of clinical studies
Authors: Kazeminasab Fatemeh , Baharlooie Maryam , Karimi Bahareh , Mokhtari Khatereh , Rosenkranz Sara K , Santos Heitor O 
Published: December 2023

Abstract

Context
Different intermittent fasting (IF) protocols have been proven to be efficient in improving cardiometabolic markers, but further research is needed to examine whether or not combining IF regimens plus physical exercise is superior to control diets (ie, nonfasting eating) plus physical exercise in this setting.

Objective
The aim of this study was to determine whether or not combining IF plus exercise interventions is more favorable than a control diet plus exercise for improving cardiometabolic health outcomes.

Data Source
PubMed, Scopus, and Web of Science were comprehensively searched until April 2023.

Data Extraction
Electronic databases were searched for clinical trials that determined the effect of IF plus exercise vs a control diet plus exercise on body weight, lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol), and systolic and diastolic blood pressure (SBP and DBP, respectively). Analyses were conducted for IF plus exercise vs a nonfasting diet plus exercise to calculate weighted mean differences (WMDs).

Data Analysis
The meta-analysis included a total of 14 studies, with a total sample of 360 adults with or without obesity. The duration ranged from 4 to 52 weeks. IF plus exercise decreased body weight (WMD = –1.83 kg; P = 0.001), LDL (WMD = –5.35 mg/dL; P = 0.03), and SBP (WMD = –2.99 mm Hg; P = 0.003) significantly more than a control diet plus exercise. HDL (WMD = 1.57 mg/dL; P = 0.4) and total cholesterol (WMD = –2.24 mg/dL; P = 0.3) did not change significantly for IF plus exercise vs a control diet plus exercise, but there was a trend for reducing triglycerides (WMD = –13.13 mg/dL; P = 0.07) and DBP (WMD = 2.13 mm Hg; P = 0.05), which shows clinical magnitude.

Conclusion
IF plus exercise improved some cardiometabolic outcomes (body weight, blood pressure, and lipid profile) compared with a control diet plus exercise.

Systematic Review Registration
PROSPERO registration no. CRD42023423878.