bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing Referral Laboratory Testing Governance and Addressing “Miscellaneous” Test Orders across an Academic Health System
Authors: Chambliss Allison B , Deignan Joshua L , Isip Charlemagne , Trinh Monique , Werre William , Ziman Alyssa 
Published: January 2025

Abstract

Background
Referral (send-out) laboratories support clinical needs but may cause issues for hospitals or health systems related to regulations and governance, specimen logistics, test result availability, and cost and reimbursement. The use of a “miscellaneous” referral test order can increase risks of specimen collection or processing errors, result delays, and repeat testing.

Methods
We established an approved referral laboratory test list and a digital form for providers to request new referral tests. We collated laboratory stewardship committee decisions over a 20-month period. Separately, we retrospectively reviewed referral tests ordered as miscellaneous across our health system over 1 year. Subject matter experts identified appropriate tests to build as discretely orderable in the electronic health record. Following targeted provider notification of the new tests, we assessed their uptake and impact on result turnaround times for the first 5 built tests over 6 months.

Results
Our laboratory stewardship committee approved 16 of 27 provider requests to build new referral tests over the first 20 months following implementation of the new request process. In addition, 37 of the 100 most frequently ordered miscellaneous tests were recommended to be built as discrete orders. Uptake of the first 5 built tests (relative to providers continuing to use miscellaneous orders) averaged 64% over the first 6 months. Result turnaround times improved by an average of 1.1 days when the discrete orders were used.

Conclusions
We successfully established oversight of referral laboratory testing across our health system, pivoted orders away from miscellaneous, and observed improvements in turnaround times.
Teaching the Laboratory’s Role in Diagnostic Stewardship: Engaging Pathology Residents in a Quality Initiative to Improve Autoverification Rates
Authors: Maggiore Jack A , Kanakis Constantine E , Gant Kanegusuku Anastasia , Kahn Stephen E 
Published: January 2025

Abstract

Background
Our institution involves our pathology residents in departmental quality initiatives and in identifying needs for operational improvements. The solutions achieved by these projects have effects beyond the laboratory, and ultimately help to improve diagnostic stewardship by supporting the clinician’s ability to obtain necessary biochemical information at the right time. A project highlighting a successful venture is described here in which our investment in new total laboratory automation was not meeting our goals for autoverification rates, resulting in less than expected improvements to turnaround times (TAT).

Methods
To improve efficiency of the new laboratory automation, our third-year pathology residents examined the limitations to the verification process and current delta checks. They performed a literature review for the most updated evidence-based practices, examined clinical metrics such as TAT. The residents assessed their findings combined with the laboratory’s quality goals, and contributed to updating middleware rule modifications. Several chemistry analyte software rules were revised while others were eliminated.

Results
After implementation of the modifications autoverification rates improved from 78% to 89% within 2 months of rule revisions. Average TAT for STAT basic metabolic profile improved from 51 to 46 minutes.

Conclusions
This study demonstrates the benefits of involving pathology residents in quality improvement initiatives. Residents are skilled resources capable of evaluating laboratory workflow processes in the context of clinical need. In this process, the residents experience the responsibilities of laboratory administration and learn the role of the laboratory in diagnostic stewardship.
Increasing the Diagnostic Utility of Heparin-Induced Thrombocytopenia (HIT) Testing: An Academic Medical Center’s Utilization Analysis and Intervention
Authors: Parsons Meredith G , Hobbs Ryan A , Schmidt Julie , Merrill Anna E 
Published: January 2025

Abstract

Background
Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse drug reaction with numerous diagnostic challenges. Diagnosis of HIT begins with 4T score clinical assessment, followed by laboratory testing for those not deemed low risk. Laboratory testing for HIT includes screening [enzyme-linked immunosorbent assay (ELISA)] and confirmatory [serotonin release assay (SRA)] assays, wherein SRA testing can be pursued following a positive ELISA result. These tests aid diagnosis of HIT, but also introduce interpretive challenges, additional costs, and delays in clinical intervention.

Methods
A retrospective review of 1011 HIT ELISA and 169 SRA tests performed over 5 years was conducted. ELISA percent inhibition and ELISA low-heparin optical density (OD) were evaluated for positive predictive value (PPV). Based on these findings, HIT ELISA reporting and management algorithm changes were implemented and metrics compared for 5 months pre- and post-intervention to assess intervention success.

Results
Equivocal and positive HIT ELISA interpretation showed poor PPV based on percent inhibition (0.20 and 0.32, respectively). However, rising low-heparin OD correlated with increasing PPV (PPV of 0.00 for OD values 0.40–1.00, 0.29 for values 1.00–1.99, and 0.91 for values &gt;2.00). Data-driven intervention decreased ELISA positivity rates (13% to 5%), decreased rates of SRA confirmatory testing overall (13% to 9%), decreased SRA testing rates for patients with non-negative ELISAs (78% to 43%), and increased heparin resumption (20% to 57%). Hematology consults remained relatively stable (78% and 86%).

Conclusions
Low-heparin OD-based HIT ELISA interpretation yielded enhanced PPV compared with percent inhibition-based interpretation. Implementation of data-driven changes improved testing stewardship and clinical management for patients with non-negative ELISAs.
Blood Culture Contamination and Diagnostic Stewardship: From a Clinical Laboratory Quality Monitor to a National Patient Safety Measure
Authors: Bunn Jake D , Cornish Nancy E 
Published: January 2025

Abstract
Laboratory analysis of blood cultures is vital to the accurate and timely diagnosis of bloodstream infections. However, the reliability of the test depends on clinical compliance with standard operating procedures that limit the risk of inconclusive or incorrect results. False-negative blood culture results due to inadequate volumes of blood can result in misdiagnosis, delay therapy, and increase patients’ risk of developing or dying from bloodstream infections. Likewise, commonly occurring bacteria or fungi on human skin (i.e., commensal organisms) can contaminate the blood culture during collection and increase the risk of false positives, compromising care and leading to unnecessary antibiotic therapy and prolonged hospitalization.
In December 2022, a Centers for Medicare & Medicaid Services (CMS) consensus-based entity (CBE) endorsed the Centers for Disease Control and Prevention’s (CDC) proposal for a new patient safety measure to address these concerns. CDC developed this quality measure to promote the standardization of blood culture best practices and improve laboratory diagnosis of bloodstream infections nationally. This special report will emphasize the importance of standardizing blood culture collection and describe the need for a national patient safety measure, new quality tools, and next steps.
Diagnostic Laboratory Stewardship in a Growing Integrated Delivery Network
Authors: Wilhelms Kelly W , Braun Derek A , Mochon A Brian , Lainhart William D , Porter Sheelagh M , Beuthin Brandie M A , Blasko Diane M , Shapiro Meghan J , Proytcheva Maria A 
Published: January 2025

Abstract

Background
Many organizations institute laboratory diagnostic stewardship (DS) programs to improve the utilization of laboratory resources.

Methods
In this paper, we describe the road to implementing laboratory DS in a large, not-for-profit integrated delivery network located in the western United States.

Results
Program structure, projects, challenges, and future opportunities are discussed, providing tactics and opportunities that facilities can employ to maximize their initial foray into the DS landscape.

Conclusions
With effective planning and organization, laboratory DS can be implemented by any organization to realize resource optimization and financial benefits while maintaining high levels of patient care.
Financial Analytics for Laboratory Stewardship: Using Data and Informatics to Increase Financial Returns for Labs and Decrease Financial Harm to Patients
Authors: Ibrahim Khalda A , Astion Michael L 
Published: January 2025

Abstract

Background
As clinical laboratories struggle to maintain their financial footing and as patients face mounting out-of-pocket expenses for diagnostic testing, being able to perform financial analysis of laboratory stewardship efforts has become an increasingly important skill.

Content
Understanding the revenue cycle as it relates to diagnostic testing is fundamental to selecting, designing, implementing, and evaluating laboratory stewardship interventions for maximum financial return. Leveraging the data and processes driving the revenue cycle can inform informatics-based interventions (such as clinical decision support) and allow deliberate financial analyses of stewardship-focused projects. For labs striving not only to ensure their own financial health but also to help their patients avoid financial toxicity, the most effective strategies often depend on developing productive partnerships with key players along the revenue cycle.

Summary
Financial laboratory analytics is an emerging skill set that can power laboratory stewardship efforts and whose benefits accrue to patients, clinicians, laboratories, and health systems.
The substance-exposed birthing person-infant/child dyad and health information exchange in the United States
Authors: Bourgeois Fabienne C , Sinha Amrita , Tuli Gaurav , Harper Marvin B , Robbins Virginia K , Jeffrey Sydney , Brownstein John S , Jilani Shahla M 
Published: January 2025

Abstract

Objective
Timely access to data is needed to improve care for substance-exposed birthing persons and their infants, a significant public health problem in the United States. We examined the current state of birthing person and infant/child (dyad) data-sharing capabilities supported by health information exchange (HIE) standards and HIE network capabilities for data exchange to inform point-of-care needs assessment for the substance-exposed dyad.

Material and Methods
A cross-map analysis was performed using a set of dyadic data elements focused on pediatric development and longitudinal supportive care for substance-exposed dyads (70 birthing person and 110 infant/child elements). Cross-mapping was conducted to identify definitional alignment to standardized data fields within national healthcare data exchange standards, the United States Core Data for Interoperability (USCDI) version 4 (v4) and Fast Healthcare Interoperability Resources (FHIR) release 4 (R4), and applicable structured vocabulary standards or terminology associated with USCDI. Subsequent survey analysis examined representative HIE network sharing capabilities, focusing on USCDI and FHIR usage.

Results
91.11% of dyadic data elements cross-mapped to at least 1 USCDI v4 standardized data field (87.80% of those structured) and 88.89% to FHIR R4. 75% of the surveyed HIE networks reported supporting USCDI versions 1 or 2 and the capability to use FHIR, though demand is limited.

Discussion
HIE of clinical and supportive care data for substance-exposed dyads is supported by current national standards, though limitations exist.

Conclusion
These findings offer a dyadic-focused framework for electronic health record-centered data exchange to inform bedside care longitudinally across clinical touchpoints and population-level health.
Aristotle’s dilemma
Authors: Kapsner Andreas 
Published: January 2025

Abstract
The contra-classicality of connexive logics presents a challenge to classical logic that is interestingly different from other non-classical logics, and discussions of that difference have been a main feature of the literature around connexive logic. Seldom, if ever, however, is the following question addressed: is this challenge more severe or less severe than the one presented by sub-classical logics (i.e. almost all other non-classical projects)? This paper will aim to show that, in fact, the connexive project, suitably unpacked, contains a charge that is not only different, but qualitatively more weighty than other non-classical logics. In order to make that argument, I introduce a new principle I call Aristotle’s Dilemma that is, I argue, closely related to the connexive axioms, and that gives an answer to this question. It also suggests an answer to a second question, namely why connective logics are not better known in philosophical logical circles, or, to the extent that they are, why it has taken so long. In part, I suggest, this is down to the unusual formal guise in which the connexive cause is normally voiced. Aristotle’s Dilemma offers a remedy to this.
Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection
Authors: Gaensbauer James T , Reves Randall R , Katz Dolly , Ahmed Amina , Venkatappa Thara 
Published: January 2025

Abstract

Introduction
Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values.

Methods
Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar’s Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results.

Results
Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P &lt; .001). This difference was noted for all age categories except &lt;2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL.

Conclusions
In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.
Sex-Specific Effects in Acute Nicotine Vapor Exposure on Binge Drinking and Activity in the Central Amygdala and Ventral Tegmental Area
Authors: Echeveste Sanchez Maria , Guerry Hayley , Grady Shyenne , Herman Melissa 
Published: January 2025

Abstract

Introduction
The increasing prevalence of electronic nicotine delivery systems and alcohol drinking has led to increases in nicotine and alcohol co-use. However, the impact of ENDs on brain activity and binge drinking behavior is not fully understood.

Aims and Methods
We subjected female and male C57BL/6J mice to a voluntary drinking and electronic nicotine vapor exposure paradigm. We first established baseline drinking using a drinking-in-the-dark paradigm. In the third week, mice were exposed to 3 hours sessions of electronic nicotine vapor prior to ethanol access, and ethanol and water drinking levels were measured. Following the last nicotine vapor and drinking session we measured blood alcohol levels (BAL) and collected tissue to measure brain activity by cFos expression.

Results
Nicotine vapor exposure decreased both alcohol and water intake in males, only reduced ethanol intake in females, and did not alter binge alcohol intake in either sex. Nicotine and alcohol increased activity in the central amygdala in females but had no effect in males. In the ventral tegmental area (VTA) nicotine increased activity in females but alcohol did not produce any additional increases. Nicotine and alcohol-exposed males had significantly lower BAL as compared to females, suggesting sex differences in drinking patterns where males appeared to “front-load” and females drank more throughout the end of the session.

Conclusions
These results highlight important sex differences in the impact of nicotine and alcohol co-exposure and underscore the importance of further investigating the neurobiological effects of alcohol and nicotine on brain activity and metabolism in males and females.

Implications
With increasing nicotine and alcohol use, it is imperative to understand the neurobiological and behavioral consequences of co-use with a focus on sex differences. Using passive nicotine vapor inhalation and a binge drinking paradigm, we investigated the effects of nicotine and alcohol co-use in mice. We found sex differences in alcohol intake and brain activity from this poly-substance use approach. Nicotine decreased alcohol and water intake in males, only reduced alcohol intake in females, and did not change binge alcohol drinking. Alcohol and nicotine produced sex-specific increases in the central amygdala and only nicotine increased VTA activity.
Can Equity Option Returns Be Explained by a Factor Model? IPCA Says Yes
Authors: Goyal Amit , Saretto Alessio 
Published: January 2025

Abstract
A number of delta-hedged equity option strategies exhibit very large average returns. We show that much of the profitability of these strategies can be explained by an IPCA factor model. The economic magnitude of the return-adjustment produced by IPCA is impressive: even before transaction costs, the average IPCA alpha of 46 long-short trading strategies constructed on previously discovered signals, is close to zero and contrasts with average realized returns of over 80 basis points per month. Our IPCA model can be used as a benchmark for assessing the performance of other option portfolios.
Gut barrier integrity disruption in atopic dermatitis: truth or myth—a case–control study
Authors: El Sayed Naglaa M , Riad Merna A , Taleb Raghda S Z , El Morsy Eman H 
Published: January 2025

Abstract

Background
Gut dysbiosis has been linked to the onset and progression of various diseases, including atopic dermatitis, by disrupting the intestinal barrier integrity. In turn, it allows the translocation of microbes and toxins into the systemic circulation, which triggers an immune response.

Objectives
To measure serum levels of the gut integrity markers claudin 3 and intestinal fatty acid-binding protein in patients with atopic dermatitis.

Methods
This prospective study was conducted on 43 patients with atopic dermatitis. Healthy volunteers (n = 35) served as controls. The serum level of claudin 3 and intestinal fatty acid-binding protein were measured using an enzyme-linked immunosorbent assay for all participants.

Results
There were no significant differences in serum levels of claudin 3 and intestinal fatty acid-binding protein between patients with atopic dermatitis and the control group (P = 0.61 and 0.81, respectively). In addition, there was no significant correlation between the two markers, and different clinical and laboratory parameters (onset of disease, eczema area severity index, other allergic manifestations and serum IgE).

Conclusion
Alterations in the intestinal barrier may be absent in the ethnically distinct group of patients with atopic dermatitis included in our study. Nevertheless, our findings might have been influenced by factors such as the duration of the disease, diet and characteristics of the study population. Further studies are needed to investigate additional biomarkers or mechanisms that may be involved in atopic dermatitis pathogenesis, especially those related to the gut–skin axis.
Single-cell RNA-seq reveals that granulosa cells are a target of phthalate toxicity in the ovary
Authors: Mattson Erik , Warner Genoa R 
Published: January 2025

Abstract
Phthalates are known endocrine-disrupting chemicals and ovarian toxicants that are used widely in consumer products. Phthalates have been shown to exert ovarian toxicity on multiple endpoints, altering transcription of genes responsible for normal ovarian function. However, the molecular mechanisms by which phthalates act on the ovary are not well understood. In this study, we hypothesized that phthalates specifically target granulosa cells within the ovarian follicle. To test our hypothesis, we cultured whole mouse antral follicles for 96 h in the presence of vehicle or 10 µg/ml of a phthalate metabolite mixture. At the end of the culture period, follicles were dissociated into single-cell suspensions and subjected to single-cell RNA-sequencing. We used markers from published studies to identify cell-type clusters, the largest of which were granulosa and theca/stroma cells. We further identified subpopulations of granulosa, theca, and stromal cells and analyzed differentially expressed genes between the phthalate treatment and control. Granulosa cells, specifically mural granulosa cells, had the most differentially expressed genes. Pathway analysis of differentially expressed genes from the overall granulosa cell cluster revealed disruption of cell cycle and mitosis, whereas pathway analysis of the mural granulosa cell subcluster identified terms related to translation, ribosome, and endoplasmic reticulum. Our findings suggest that phthalates have both broad impacts on cell types and specific impacts on cellular subtypes, emphasizing the complexity of phthalate toxicity and highlighting how bulk sequencing can mask effects on vulnerable cell types.
Haemotoxicity of snakes: a review of pathogenesis, clinical manifestations, novel diagnostics and challenges in management
Authors: Alvitigala Bhawani Yasassri , Dissanayake Harsha A , Weeratunga Praveen N , Padmaperuma P A Chanya D , Gooneratne Lallindra Viranjan , Gnanathasan Christeine Ariaranee 
Published: January 2025

Abstract
Haemotoxicity is the most common complication of systemic envenoming following snakebite, leading to diverse clinical syndromes ranging from haemorrhagic to prothrombotic manifestations. Key haematological abnormalities include platelet dysfunction, venom-induced consumption coagulopathy, anticoagulant coagulopathy and organ-threatening thrombotic microangiopathy. Diagnostic methods include the bedside whole blood clotting test, laboratory coagulation screening and other advanced methods such as thromboelastogram and clot strength analysis. The primary management strategies are venom neutralisation with antivenom and correction of coagulopathy with blood component transfusions, while options such as plasma exchange are utilised in certain cases. Recent advancements in understanding the pathogenesis of haemotoxicity have facilitated the development of new diagnostic and treatment modalities. This review summarises current knowledge on the pathogenesis, diagnosis, clinical and laboratory manifestations and treatment of the haematological effects of snake envenoming. Furthermore, it highlights important challenges concerning diagnosis and management. Addressing these challenges is crucial for achieving the WHO's goal of reducing deaths and disabilities caused by snakebites by 2030.