bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural resilience of climate regime in the global conflicts
Authors: Guan Chuanjing , Meng Jialian , Xu Qinyi
Published: January 2025

The intensification of geopolitical tensions and great power rivalries have disrupted global climate actions. In the era of global conflicts, the effectiveness of current climate regime has been questioned. How to measure the stability of the climate regime under diverse shocks? The article finds that global climate actions have formed an institutional network that involves the basic (state-dominated), central (UNFCCC centered) and extended (non-climate multilateral organization) layers of climate governance. We argue that the measurement towards the resilience of such structure shall be based on the evaluation of the ‘three-layer stability’. As proposed in the article, the three-layer structure in the global climate governance system is more resilient to shocks, presented with the two features of institutional redundancy and structural heterogeneity. Due to structural heterogeneity, shocks have performed differentiated effects across layers that allows certain autonomy to exist within layers. Based on structural redundancy, the extended layer is reinforced by the steady increase in climate reform and institutionalization in international organizations to sustain the system while the central layer is experiencing turbulence in international affairs. The evaluations of climate finance and renewable energy investment data are presented in the article to test the function of three-layered institutional complex that mitigates shocks.
Impact of obtaining prescriptions upon discharge on hospital readmissions in a large healthcare system
Authors: Robarts Ethan , McGinnis Brandy , Nguyen Brian , Pan Neil , Ong Emily
Published: January 2025

Purpose

To evaluate the impact of a discharge pharmacy program on hospital readmission rates among adult patients.

Methods

A multicenter, retrospective cohort study was conducted across 4 hospitals and their partnered discharge pharmacy for the period from July 2022 to July 2023. Adult patients aged 18 years or older who were discharged from an inpatient hospital unit and had their prescriptions sent to an Ascension Seton hospital-based discharge pharmacy before leaving the hospital were compared to those whose prescriptions were sent elsewhere. This comparison was conducted to assess the impact of an integrated healthcare delivery approach. Baseline characteristics, such as the number of discharge medications, index admission diagnoses, and discharge unit, were collected for comparison. The primary endpoint was the rate of 30-day hospital readmission, with secondary endpoints including the readmission rate within 31 to 60 days and reasons for 30-day readmission.

Results

A total of 15,690 patients were included in the study (3,376 in the Ascension Seton hospital-based discharge pharmacy group and 12,314 in the control group). The rate of hospital readmission within 30 days from the index visit was 3.31% (95% confidence interval [CI], 2.99% to 3.63%) in the non–Ascension Seton pharmacy group compared to 2.10% (95% CI, 1.62% to 2.58%) in the Ascension Seton pharmacy group. The difference in 30-day hospital readmission rate was statistically significant (P = 0.01), with an absolute difference of 1.21%.

Conclusion

A statistically significant decrease in 30-day hospital readmission rate was seen in the Ascension Seton hospital-based discharge pharmacy group compared to the study group that had their discharge prescriptions sent to a pharmacy other than an Ascension Seton hospital-based discharge pharmacy.
Prospective study on time-to-tertiary care in alcohol-associated hepatitis: space–time coordinates as prognostic tool and therapeutic target
Authors: Skladaný Ľubomír , Žilinčanová Daniela , Kubánek Natália , Selčanová Svetlana Adamcová , Havaj Daniel , Laffers Lukáš , Žilinčan Michal , Islam Alvi H , Arab Juan Pablo , Koller Tomáš
Published: January 2025

Background and aims

Alcohol-associated hepatitis (AH) frequently triggers acute decompensation (AD) in cirrhosis, with severe AH linked to high short-term mortality, especially in acute-on-chronic liver failure. Current corticosteroid treatments have limited efficacy, highlighting the need for new therapies. We hypothesized that severe AH outcomes are influenced by early specialized care; thus, we examined the impact of time-to-tertiary care (TTTc).

Methods

Adults with cirrhosis or advanced chronic liver disease were enrolled (RH7, NCT04767945). AH was diagnosed using National Institute on Alcohol Abuse and Alcoholism criteria. Primary admission site, TTTc, and adverse outcomes (death or liver transplantation) were analyzed. Patients admitted directly to tertiary care were assigned a TTTc of zero.

Results

Of 221 AD-AH patients, 107 were transferred from secondary care to tertiary care (TTTc >0) and 114 were admitted directly (TTTc = 0). TTTc >0 patients were younger (48.3 vs. 52 years, P = .008) and had more severe disease, as shown by model for end-stage liver disease scores (25.5 vs. 20.8, P < .001) and Maddrey’s discriminant function (59.3 vs. 40.6, P < .001). Propensity-score matching yielded 49 case pairs. The Cox model showed that transfer from secondary care was not associated with increased risk, but delayed transfer (days, hazard ratio = 1.03, 95% confidence interval 1.01–1.05) independently predicted adverse outcomes.

Conclusions

Delayed initiation of specialized care adversely impacts outcomes in AD-AH. If validated, timely care bundles could improve AH survival, similar to sepsis or vascular syndromes.

Highlights

AD-AH is a common syndrome associated with high short-term mortality. There is an unmet need for new prognosis-modifying therapies for AH. Currently, in real-life hepatology, refining the existing bundle of care is the only practical option to improve the prognosis of AD-AH. Past experience with acute coronary syndromes, stroke, and sepsis, emphasizing symptoms-to-intervention duration, combined with the recent COVID-19 lockdown finding of increased mortality due to skewed access to specialized liver care indicates that focusing on timely specialized care might be key to improved outcome in certain liver conditions. In this line, we set out to track the number of days elapsing between admission to SC and referral to TC, coining this interval as “time-to-tertiary care” (TTTc). We examined TTTc as a potential compound surrogate that might influence the prognosis in AD-AH. After correcting for important baseline differences, we conclude that the delay of transfer to the tertiary care hospital was independently associated with a worse prognosis with each additional day in TTTc increasing adverse outcomes by nearly 3%.
From inconsistency to coherence: examining the SGCA’s quest for a comprehensive approach to determining pre-award arbitrability
Authors: Bhukya Kanishka
Published: January 2025

This article critically examines the Singapore Court of Appeal’s (SGCA) innovative ‘composite’ approach to determining pre-award arbitrability, as established in Anupam Mittal v Westbridge Ventures II Investment Holdings [2023]. The SGCA’s two-tiered approach considers both the law governing the arbitration agreement and the law of the seat. While this method attempts to balance party autonomy with public policy considerations, the article identifies several challenges, including conceptual tensions with public policy principles, potential paradoxes in application, and conflicts with established arbitration frameworks. The author proposes a comprehensive reform centred on a ‘Materially Close Connection’ test, to be applied consistently at both pre-award and post-award stages. This proposal includes revising the UNCITRAL Model Law to incorporate this test, aiming to create a more unified and coherent framework for arbitrability determinations in international arbitration. The article argues that this approach would promote consistency, accommodate diverse international disputes, and balance party autonomy with legitimate public policy interests.
The beak shape variation of Neotropical passerines is explained more by body size than diet
Authors: Brodt Michele S C , Cáceres Nilton C
Published: January 2025

Beak morphology in birds is often linked to diet. In this study, we aimed to analyse whether diet or other drivers, such as allometry or species relatedness, explain the morphological beak variation of Neotropical passerines and whether there are specific predictors for beak shape variation for the two passerine suborders, Oscines and Suboscines. We analysed beak measurements (length, width, and depth) as response variables and body size, diet, and phylogenetic distance as predictor variables. After controlling for allometry which had major impact on beack shape, beak length and depth exhibited significant differences across diet categories and between suborders. Compared with Oscines, the beak shape of Suboscines is more influenced by species relatedness, probably owing to niche conservatism. Our findings suggest an adaptive convergence between the two passerine suborders in the Neotropics, driven mainly by allometric constraints rather than by the trophic niche.
Method Validation for Estimation of Imidacloprid and its Metabolites in Maize and Soil by LCMS-MS
Authors: Kaur Sandeep , Sharma Smriti , Kang Balpreet K
Published: January 2025

Validation of Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method was performed for estimation of imidacloprid (IM) and its metabolites in maize leaves, immature kernels, mature kernels, stalk, and soil using liquid chromatograph tandem mass spectrometry, coupled with electrospray ionization. The extraction in different matrices of maize and soil was performed using acetonitrile +0.1% formic acid followed by clean-up with primary secondary amine sorbent and anhydrous magnesium sulfate. The method was validated in terms of selectivity, linearity, limit of detection, limit of quantification, matrix effect, ion ratios, quality control, robustness, accuracy, and precision. The validation of all parameters was done in accordance with European Commission's Directorate-General for Health and Food Safety (DG SANTE) guidelines. A linear relationship with high correlation coefficients R2 > 0.99 was obtained for solvents and different matrices viz., maize leaves, immature kernels, mature kernels, stalk, and soil. The recovery and relative standard deviations were ˃78% and ˂5.4%, respectively. This method permits a simple, sensitive, accurate, cost-effective, precise, and rapid extraction of IM and its metabolites from maize leaves, immature kernels, mature kernels, stalks, and soil. This can help the residue analysts to address effective residue estimation, regular monitoring of residues and can also aid in the regulatory and food safety concerns about the usage of IM in maize.
Incidental Detection of Maternal Cancer Following Cell-Free DNA Screening for Fetal Aneuploidies
Authors: Goldlust Ian S , Bianchi Diana W
Published: January 2025

Background

Prenatal cell-free DNA (cfDNA) screening is a success story of clinical genomics that has translated to and transformed obstetric care. It is a highly sensitive and specific method of screening for the most common fetal aneuploidies, including trisomies 13, 18, and 21. While primarily designed to detect fetal chromosomal abnormalities, the test also analyzes maternal cfDNA, which can complicate interpretation of results. Occasionally, abnormalities in cfDNA that do not align with fetal aneuploidy may indicate benign or malignant maternal disease states, presenting unique diagnostic challenges and opportunities.

Content

This review explores the methods and implications of incidental cancer detection through prenatal cfDNA screening. Early case reports noted instances in which abnormal cfDNA results, initially suggestive of fetal aneuploidies, led to post-pregnancy diagnoses of maternal cancers. Subsequent large retrospective studies have established significant correlations between atypical prenatal cfDNA results and undiagnosed maternal malignancies. Abnormal cfDNA profiles, particularly those indicating multiple aneuploidies, first require fetal diagnostic tests, such as amniocentesis. If the fetal studies are normal, further investigation into a maternal source should proceed. Clinical management of these findings may involve a multidisciplinary approach, incorporating advanced imaging techniques and genetic counseling to ensure timely and accurate maternal diagnoses.

The integration of genome-wide analysis and innovative bioinformatics tools into prenatal cfDNA screening has enhanced its ability to identify potential cancer cases. Developing standardized guidelines for reporting and managing incidental findings is crucial to optimizing patient outcomes and mitigating psychological impacts on expectant persons and their partners.
Economic and equity evaluation of age restrictions on over-the-counter diet pills and muscle-building supplements
Authors: Tschampl Cynthia A , Tabata-Kelly Masami , Lee Mary R , Soranno Elena , Barman Upanita , Raffoul Amanda , Austin S Bryn
Published: January 2025

Over-the-counter diet pills and muscle-building supplements are linked to increased eating disorder diagnoses, especially among youth. With limited regulatory oversight, minors may unknowingly consume harmful substances leading to other adverse effects. Massachusetts has proposed restricting sales to individuals under 18 years. However, concerns about health equity and unintended consequences arise when proposing new policies. We conducted a cost-effectiveness analysis of the proposed age-restriction policy compared to the status quo, focusing on 2 closed cohorts of males and females aged 0-17 years in Massachusetts over a 30-year time horizon. We evaluated the impact from both societal and health systems’ perspectives and further assessed equity implications by modeling 3 racial/ethnic subgroups. The policy is projected to prevent 57 034 eating disorder cases and over 46 000 additional adverse medical events (eg, liver injuries). It would yield 51 749 quality-adjusted life years and generate healthcare savings of $14 million and societal savings of $30 million annually. The Latine subpopulation would see the highest per capita health benefits followed by Black and White residents, respectively. Restricting the sale of these supplements to minors offers both health and economic benefits. These findings underscore the policy's effectiveness, fiscal responsibility, and positive equity impacts, providing confidence for policymakers and the public.
Regulation of storage organ formation by long-distance tuberigen signals in potato
Authors: Bao Xinru , Zhu Yunke , Li Guangcun , Liu Lu
Published: January 2025

Potatoes are valued as reliable crops due to their high carbohydrate content and relatively low farming demands. Consequently, significant attention has been directed towards understanding and controlling the life cycle of potato tubers in recent years. Notably, recent studies have identified SELF PRUNING 6A (StSP6A) as a key component of the tuberigen, the mobile signal for tuber formation, produced in leaves and then transported underground to induce tuber formation in potatoes. Recent progress in comprehending the signaling mechanisms that regulate StSP6A by photoperiod and ambient temperature components, its long-distance transport into underground tissue, and its involvement in regulating stolon tuberization has advanced significantly. Consequently, the modulation of StSP6A and other possible tuberigen signals, along with their regulatory pathways, significantly impacts potato domestication and crop yield. This progress highlights the differential regulation of tuberigen signals and their potential functions in promoting tuber formation.
Cefiderocol AST in a real-life Klebsiella pneumoniae collection: challenges in the ATU range
Authors: Castillo-Polo Juan Antonio , Hernández-García Marta , Maruri-Aransolo Ainhize , Morosini María-Isabel , Ruiz-Garbajosa Patricia , Cantón Rafael
Published: January 2025

Objectives

FDC susceptibility testing is challenging as none of the commercial tests have been proven to accurately determine the susceptibility in the area of technical uncertainty (ATU). Here, we evaluated the performance of different FDC testing methods on Klebsiella pneumoniae isolates around this range.

Methods

A challenging collection of 104 K. pneumoniae isolates with different FDC susceptibility was designed, including high representation (70%) of the 2024-ATU (21–23 mm) ± 1 mm. MICs were determined by broth-microdilution (BMD) reference method, commercial BMD (ComASP®, EUMDROXF®), MIC-gradient strips (Liofilchem) and disk-diffusion (DD) (Liofilchem, ThermoFisher). MIC devices evaluation was performed following ISO 20776-2:2021, calculating essential agreement (EA) and bias. DD results were evaluated following 2023 and 2024-EUCAST-guidelines, calculating major errors (ME) and very major errors. Categorical agreement (CA) was determined for all the methods.

Results

Overall, EUMDROXF® and ComASP® showed 81.7% (95% CI = 72.9–88.6) and 88.5% (95% CI = 80.8–93.9) EA, +2.6% and +27.9% bias and 99.0% (95% CI = 94.7–99.9) and 98.1% (95% CI = 93.3–99.8) CA, respectively. Liofilchem MIC-gradient strips exhibited 47.1% (95% CI = 37.2–57.1) EA, +2.9% bias and 93.3% (95% CI = 86.7–97.3) CA. In DD, variability between manufacturers was elevated. CA lowered and ME increased more than 10% with 2024-EUCAST-breakpoints modification.

Conclusions

DD performance was insufficient to assess FDC resistance in K. pneumoniae and modification of EUCAST-breakpoints did not solve the problem. ComASP® panel fulfilled ISO criteria and could be used as MIC-confirmatory method, at least in K. pneumoniae. However, EUMDROXF®, even close, did not fulfil the EA criterion. MIC-gradient strips exhibited major limitations.
A Committee-Based Diagnostic Stewardship Model for Pathogen Metagenomic Sequencing in Children
Authors: Allen Brian S , Kidd Mehgan , Sue Paul K , Filkins Laura M
Published: January 2025

Background

Metagenomic next-generation sequencing (mNGS) for pathogen detection offers the potential for broad pathogen detection directly from clinical specimens. However, the yield and impact of testing is variable, financial cost is high, and questions surrounding its optimal use remain. Our pediatric institution used a clinical committee-based approach to discuss and approve or deny mNGS test requests. In this study, we evaluate the patient characteristics for which mNGS testing was considered, test yield, and clinical impact of mNGS results when employing this model of diagnostic stewardship.

Methods

Patients for which plasma cell-free DNA mNGS testing was requested and assessed by the clinical committee between August 1, 2018, and April 30, 2021, were included. The committee discussion emails were used to evaluate reasons for making the test request and treatment plans. Patient characteristics and additional clinical information were gathered by chart review. For approved cases, the clinical impact of the mNGS results were retrospectively adjudicated by infectious disease and clinical microbiology experts.

Results

Twelve requests for plasma cell-free DNA mNGS were evaluated and 9 were approved. mNGS results led to a positive clinical management change in 55% of approved requests. Negative clinical impact of mNGS testing did not occur during the study. The patients for which testing requests were denied had resolution of symptoms without further intervention.

Conclusions

This committee-based test request approval diagnostic stewardship model has the potential to support high-yield mNGS testing while using healthcare resources responsibly.
Cost-Effective Drug Testing: Analytical Methodology, Best Practices, and Clinical Utility
Authors: Chenoweth James A , LaValley Clayton K , Eberhardt Cara S , Colby Daniel K , Albertson Timothy E , Tran Nam K
Published: January 2025

Background

Drug overdose-related deaths continue to increase globally. Testing demands have likewise increased, prompting healthcare facilities to adopt a range of methods, from simple point-of-care immunoassays to comprehensive chromatographic and mass spectrometry-based techniques. Each of these testing methods has trade-offs related to cost, performance, speed, and convenience, requiring healthcare facilities to carefully determine the best options to meet their clinical needs. Unfortunately, current testing practices may result in unnecessary costs and certain methods, such as immunoassays, have significant limitations that affect their clinical utility. As such, the goal of this review is to frame the current state of drug testing and related cost-effectiveness and patient centered approaches to address this evolving public health challenge.

Content

This review discusses the current state of substance use mortality/morbidity, the economic impact of substance use disorders, provides an overview of testing methods and their relative cost-benefit, solutions to improve test utilization and cost-effectiveness, and finally, future threats and new opportunities that can improve the clinical utility of these tests.

The cost-effectiveness of drugs of abuse testing revolves around proper test utilization, including understanding what test is being ordered, its limitations, understanding results, and ordering testing when it can provide actionable information. Fundamental principles of test utilization such as education, clinical informatics, and optimizing test panels remain essential. Future threats in this space include new compounds and regulatory changes. However, novel solutions such as new noninvasive sample types, automation, and artificial intelligence can play a significant role in improving overall test utilization practices.
One Size Fits Small: The Narrow Utility for Plasma Metagenomics
Authors: Graf Erin H , Bryan Andrew , Bowers Michael , Grys Thomas E
Published: January 2025

Metagenomic sequencing of plasma has been advertised by Karius, Inc. as a way to diagnose a variety of infectious syndromes. Due to the lack of robust evidence of clinical utility, our laboratory began actively stewarding Karius testing. Microbiology Directors recommended cancelation of Karius orders when certain criteria were identified. We set out to review Karius test requests in a 52-month period of stewardship, during which we recommended cancellation on 21 of 57 orders (37%). Of Karius tests sent on samples with negative conventional testing, only 3 (7%) had positive results for Karius with plausible explanatory etiologies. Of these three cases, two were empirically covered for the positive finding without improvement and one case was never treated. Twelve (29%) had positive results that were noted by infectious diseases (ID) to reflect insignificant detections. Given the 4-fold higher detection of insignificant Karius results, we set out to systematically analyze the literature for the experience of insignificant detections at other centers. When we compared studies that included healthy controls or had clinical adjudication of positive Karius findings by ID physicians, we found a median of 17.5% of individual patients that had positive insignificant detections of potential pathogenic bacteria or fungi. The most frequently detected species were as likely to be clinically adjudicated to be insignificant as they were to be significant within the same studies. Overall, these findings highlight limited utility of Karius testing and a need for careful stewardship, not only to ensure it is sent on patients who may benefit, but also to ensure results of potential pathogens are interpreted cautiously.
Screening with Metoclopramide Test to Reduce Unnecessary Pituitary Magnetic Resonance Studies in Moderate Hyperprolactinemia
Authors: Moreno Ana , Deza Sara , Salvador Javier , Galofre Juan C , González Álvaro , Alegre Estibaliz
Published: January 2025

Background

In prolactinoma diagnosis, current guidelines recommend prolactin (PRL) assessment, considering values exceeding 200 ng/mL highly suggestive of prolactinoma. However, subtler hyperprolactinemia is more common, and to rule out potential prolactinomas, pituitary resonance magnetic imaging (MRI) studies are necessary. These present limitations in terms of availability, costs, and delays in diagnosis. We aimed to evaluate the screening utility of the metoclopramide (MCP) test in identifying patients with moderate hyperprolactinemia for whom MRI studies might be unnecessary.

Methods

We retrospectively selected patients with moderate hyperprolactinemia, with an MCP test and a pituitary MRI within the same assistance, and with no interfering pharmacological treatment. Increases in PRL (ΔPRLMax) and thyrotropin (ΔTSHMax) after MCP infusion were compared according to MRI findings: patients with microadenoma (<10 mm; n = 23), with macroadenoma (≥10 mm; n = 5), or without adenoma (n = 39).

Results

ΔPRLMax exceeds baseline PRL capability to identify patients with an adenoma (area under the curve = 0.872 vs 0.776). ΔPRLMax below 220% identifies 100% of these patients with 71% of specificity. This screening would have avoided 42% of MRI, resulting in a cost savings of 34%. Analysis of ΔTSHMax only slightly increased specificity when considered as a secondary criterion. Test duration can be shortened to 30 min without compromising its screening capability.

Conclusions

A short MCP test is a useful and cost-effective screening tool to avoid unnecessary MRI. Its simplicity allows its performance in almost any clinical facility to easily rule out prolactinoma in an important percentage of patients, something of upmost importance especially in regions where MRI facilities or their access are limited.
Developing Benchmarking Metrics for Appropriate Ordering of Vitamin D, Thyroid Testing, and Iron Workups
Authors: Liao Hsuan-Chieh , Saitman Alec , Dickerson Jane
Published: January 2025

Background

Laboratory stewardship programs are increasingly adopted to enhance test utilization and improve patient care. Despite their potential, implementation within complex healthcare systems remains challenging. Benchmarking metrics helps institutions compare their performance against peers or best practices. However, the application in laboratory stewardship is underrepresented in the literature.

Methods

The PLUGS (Patient-centered Laboratory Utiliazation Guidance Services) Informatics Working Group developed guidelines to address common test utilization issues. Metrics were based on data that are easily retrievable and calculable. Three key benchmarks were chosen for a pilot study: the ratio of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D test orders, the ratio of thyroid-stimulating hormone (TSH) to free thyroxine (FT4) test orders, and the percentage of iron workup orders after an initial low mean corpuscular volume (MCV). Institutions analyzed their own data and we established optimal benchmarks through inter-laboratory comparisons.

Results

Nine laboratories evaluated vitamin D testing, with 2 implementing stewardship interventions beforehand. A benchmark of 50:1 was established, where a higher ratio indicates intentional ordering of 1,25-dihydroxyvitamin D. Nine laboratories evaluated thyroid testing, with 3 implementing interventions. The benchmark of 3.5:1 was established, with a higher ratio suggesting judicious TSH ordering. Seven laboratories evaluated iron workups, proposing a benchmark of 50% as a starting metric. Intervention guidelines were provided for laboratories below the benchmarks to promote improvement.

Conclusions

Benchmarking metrics provide a standardized framework for assessing and enhancing test utilization practices across multiple laboratories. Continued collaboration and refinement of benchmarking methodologies is essential in maximizing the impact of laboratory stewardship programs on patient safety and resource utilization.
What Is Diagnostic Stewardship?
Authors: Claeys Kimberly C , Coffey K C , Morgan Daniel J
Published: January 2025

Background

Diagnostic stewardship is a set of clinically based changes to the ordering, processing, and reporting of diagnostic tests designed to improve patient outcomes (through decreased inappropriate testing, and reduced patient harm from wrong, delayed, or missed diagnosis). It shares a common philosophy with laboratory stewardship but has some key differences.

Content

Laboratory stewardship focuses primarily on pre- and post-analytical components of the testing process. Laboratory stewardship encourages laboratorians to engage clinical partners in discussion around the impact of pre- and post-analytical components of testing. Diagnostic stewardship extends laboratory stewardship into clinical medicine as it considers the clinician’s interaction and experience with the ordering system and attempts to modify clinical thinking, even before a test is ordered. Diagnostic stewardship then goes beyond the post-analytic laboratory interpretation of results to contextualize those results in evidence-based best practice recommendations. Compared to laboratory stewardship, diagnostic stewardship is clinician led vs laboratorian led, utilizes clinician-focused terminology rather than laboratory-specific language, and incorporates clinician decision support and behavioral economics to drive behavior change.

There are many complementary principles and activities between laboratory and diagnostic stewardship, and collaboration allows both programs to grow and improve patient overall quality of care.
The Use of Social Media to Promote Lab Medicine to Students, Patients, and the General Public
Authors: Wu Alan H B , Camargo Diana
Published: January 2025

Background

The clinical laboratory provides critical information by which medical decisions are made. However, few understand the effort and support required to deliver high-quality results. This has led to unfavorable federal legislation that threatens the ability of laboratorians to be innovative and advance the field.

Methods

A social media campaign was launched in late 2023 in an attempt to educate the general public as to the value of the clinical lab in hopes of reversing this trend. Featured topics include clinical chemistry, microbiology, toxicology, molecular diagnostics, and clinical microbiology.

Results

To date, 26 posts have been made via a popular social media site. Each of these videos is between 2 and 3 minutes long and features an individual who endures a medical condition or medicolegal situation where clinical laboratory results are central to the outcome of the case. Using social media vernacular, the popularity of these videos is reflected by the number of “views,” “likes,” and “followers.” To date, these values are 5 million, 86 000, and 44 000, respectively. It is difficult if not impossible to objectively document the long-term impact of this social media campaign on the profession.

Conclusions

An alternative means of promoting the field of laboratory medicine is required if the field is to be adequately funded and staffed to meet current and future testing goals.
Opioid hair concentrations using retrospective prescription data from a United States workplace testing population
Authors: Stowe G. Neil , Paulsen Ryan B , Schaffer Michael I
Published: January 2025

Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, Psychemedics frequently encounters questions from clients/Medical Review Officers regarding opioid hair concentrations in relation to the amount of opioids taken as part of a prescription. In this article, we have analyzed a large number of real-world examples of opioid hair concentrations following self-reported consumption of an opioid prescription regimen. This dataset provides a reference point of opioid hair concentrations after an extensive aqueous wash that likely corresponds to consumption of an opioid prescription regimen. Practitioners in the field could use this reference to make decisions on the opioid concentration of a hair sample in relation to a client-provided prescription.
Profiling translation in the nervous system
Authors: Ichinose Toshiharu , Tanimoto Hiromu
Published: January 2025

Regulation at the level of translation is critical in the nervous system, such as for the formation of cell-type-specific proteomes or plastic changes in neural circuits. Whilst current knowledge of the translatome is relatively limited compared to transcriptome, a growing array of tools to analyse translation is becoming available. In this review, we discuss techniques for profiling translation on a genome-wide scale with a special emphasis on cell-type-specific analyses in the nervous system. This includes polysome-profiling-seq, Translating Ribosome Affinity Purification (TRAP)-seq and ribosome profiling (Ribo-seq). We review recent advances to achieve spatial resolution of translatome analysis, such as genetic labelling of the targeted cells and cell sorting, and discuss the biological implications of translational regulation in the brain and potential future extensions.
Impact of seasonal flooding on Jaguar (Panthera onca) home range and movements
Authors: de Brito Marcos Roberto Monteiro , Alvarenga Guilherme Costa , Oliveira-Santos Luiz Gustavo Rodrigues , Maranhão Louise , Pinto dos Santos Lázaro , Gomes dos Santos Railgler , Menezes Jorge Fernando Saraiva , Ramalho Emiliano Esterci
Published: January 2025

Movement is an integral part of animal foraging and survival. Thus, conditions that hamper animal movement should cause significant shifts in their ecology, especially in traits directly related to movement such as home range, displacement, and site fidelity. Using jaguars (Panthera onca) as our model species, we measured the effect of reduced mobility in a unique natural experiment. The Amazonian varzeas of the Mamirauá Reserve have such a prevalent and intense flooding that jaguars in the region adopt a semiaquatic and arboreal lifestyle during the wet season. We hypothesized that Jaguar space use would change substantially between seasons with decreasing home ranges, core areas, and displacements during the high-water periods. Given previously documented sex-based differences in Jaguar space use and movement we also evaluated sex-based differences in movement parameters in our study system. We measured seasonal home ranges and core areas using autocorrelated kernel density estimation, with the 95% contour for home ranges and 50% for core areas. Displacement was calculated as the velocity of movement in meters per second in each given step comprised of locations every 6 h. Our results indicated that home range area remained constant between seasons, but displacement decreased during high-water periods as expected. We discuss the possibility that jaguars switch to an ambushing form of predation, which is made possible by the large number of prey in the region. This ambushing tactic would allow jaguars to retain a large home range despite low mobility and larger movement costs.
International Merger Control: How Long Does it Take and How Much Does it Cost? An Empirical Study Based on the Brazilian Case Law
Authors: Burnier da Silveira Paulo , Maiolino Isabela
Published: January 2025

This paper analyses both the duration and the expenses resulting from notification fees in relation to international merger control proceedings in Brazil. For this purpose, the research relies on a dataset of 192 cases reviewed by the Brazilian Competition Authority between 2013 and 2022. The dataset indicates that an international merger requires in average 103 days for time review in Brazil, eight notifications to competition authorities around the globe and €175,794.00 in expenses with notification fees. In addition, the 192 cases revealed a total of 1,562 merger notifications worldwide involving 73 jurisdictions. The research provides a descriptive overview of the statistics and a correlation analysis between the duration of the international merger reviews and key factors (i.e. geographic scope of transaction, number of jurisdictions notified, existence of international cooperation, number of relevant markets, type of decisions, number of staff, and expenses with notification fees). The paper concludes with a summary of the key findings and suggestions for future work.
Tree models for assessing covariate-dependent method agreement with an application to physical activity measurements
Authors: Karapetyan Siranush , Zeileis Achim , Henriksen André , Hapfelmeier Alexander
Published: January 2025

Method comparison studies assess agreement between different measurement methods. In the present work, we are interested in comparing physical activity measurements using two different accelerometers. However, a potential issue arises with the popular Bland–Altman analysis, as it assumes that differences between measurements are identically distributed across all observational units. In the case of the physical activity measurements, agreement might depend on sex, height, weight, or age of the person wearing the accelerometers, among others. To capture this potential dependency, we introduce the concept of conditional method agreement, which defines subgroups with heterogeneous agreement in dependence of covariates. We propose several tree-based models that can detect such a dependency and incorporate it into the model by splitting the data into subgroups, showing that the agreement of the activity measurements is conditional on the participant’s age. Simulation studies also showed that all models were able to detect subgroups with high accuracy as the sample size increased. We call the proposed modelling approach conditional method agreement trees and make them publicly available through the R package coat.
Penile suspensory ligament: anatomy, function, and clinical perspectives of its repair
Authors: Liu Wen , Calopedos Ross , Blecher Gideon , Love Christopher
Published: January 2025

Background

The penile suspensory ligament (PSL) plays a significant role in penile support and erection and its injury or congenital absence may result in functional impairment of erectile function.

Aim

To describe the diagnosis and surgical repair technique for PSL abnormalities and overall outcomes.

Methods

A comprehensive review of the literature was performed to understand the anatomic relevance of the PSL and historical management of PSL defects. A contemporary method for PSL repair is described using a transverse infrapubic incision with placement of midline anchoring (non-absorbable braided) sutures between the tunica albuginea (TA) and symphysis pubis to correct penile position and instability.

Outcomes

Surgical success defined as degree of penile curvature and penile stability for sexual intercourse as well as patient and partner satisfaction rates were reviewed.

Results

Though limited in number, available case series in the literature indicate a success rate between 85-100%, and more recent reviews fall in the 85-91% range. Patient satisfaction rates vary from 82-88%, but some series included patients with penile dysmorphic disorder and Peyronie’s disease, which are known to have higher dissatisfaction rates related to the underlying etiology itself. In patients with venogenic erectile dysfunction (ED), resolution was 100% but de novo ED occurred in 3-5%; these cases were all successfully managed medically.

Clinical Implications

This review addresses the diagnosis of PSL abnormalities and demonstrates a simple but effective repair technique to significantly improve erectile stability in men with acceptable risk.

Strengths and Limitations

This is a comprehensive review of the available research on PSL abnormalities that outlines its diverse patient presentation and a systematic method to diagnosis and repair PSL defects. The patient satisfaction rates are reasonably high but given the relatively rarity of this entity, larger longitudinal multi-institutional studies are required to further elucidate risks of de novo ED, penile shortening, and functional outcomes over the long-term.

Conclusion

PSL repair using permanent anchoring sutures or a fascial graft between the pubic symphysis and the TA of the corpora cavernosa is a safe and efficacious way to restore an important part of the penile suspensory apparatus that helps stabilize the penis during erection for normal sexual function.
Transcriptional regulation of daily sleep amount by TCF4–HDAC4–CREB complex in mice
Authors: Zhou Rui , Zhang Chaodong , Gan Rui , Yin Xin , Wang Meng , Shi Bihan , Chen Lin , Wu Chongyang , Li Qi , Liu Qinghua
Published: January 2025

Histone deacetylase HDAC4/5 cooperates with cAMP response element-binding protein (CREB) in the transcriptional regulation of daily sleep amount downstream of LKB1-SIK3 kinase cascade in mice. Here, we report a significant enrichment of the E-box motifs for the basic loop–helix–loop (bHLH) proteins near the CREB- and HDAC4-binding sites in the mouse genome. Adeno-associated virus-mediated expression of class I bHLH transcription factors, such as TCF4, TCF3, or TCF12, across the mouse brain neurons reduces the duration of rapid eye movement sleep (REMS) and non-REMS (NREMS). TCF4 requires its bHLH domain to regulate REMS or NREMS amount, of which the latter is mostly independent of the E-box-binding activity. Consistent with that TCF4 interacts with CREB and HDAC4 via the bHLH domain, TCF4 relies on CREB and partly on HDAC4 to regulate NREMS/REMS amount. Conversely, the ability of CREB to regulate sleep duration also requires its binding to TCF4 and HDAC4. Together, these results indicate that TCF4, HDAC4, and CREB could function cooperatively in the transcriptional regulation of daily sleep amount in mice.
Financial assistance for snakebite envenoming by OECD nations
Authors: Rae Richenda J
Published: January 2025

Background

The World Health Organization re-established snakebite as a neglected tropical disease in 2017. An overview is provided on snakebite financial assistance in relation to the policy landscape change.

Methods

The Organisation for Economic Co-operation and Development Creditor Reporting System database was searched and 184 results obtained from 1999 to 2022 underwent simple Excel analysis.

Results

Contributions increased from $0.05 million in 1999 to a peak of $100.8 million in 2020. Most assistance was directed towards treatment research.

Conclusions

Contributions increased since snakebite was reprioritised by global health stakeholders, aligning with policy landscape changes. Financial reprioritisation of strategic priorities beyond treatment research may be required for established goals to be met.
Determinants of seeking or foregoing allopathic treatment after snakebite: a population-based study from rural Sri Lanka
Authors: Jayawardana Subashini , Chang Thashi , Gnanathasan Ariaranee , Arambepola Carukshi
Published: January 2025

Background

Despite the availability of antivenom, not all snakebite victims choose to seek allopathic care. This choice of care is likely to be determined by unexplored personal and external factors. We studied the factors influencing the choice of treatment and first aid measures among snakebite victims.

Methods

We conducted a population-based study integrating quantitative and qualitative research methods among snakebite victims in the preceding 12 months, selected from 8707 residents in Ampara District, representing typical rural Sri Lanka with a high snakebite burden. Interviewers collected data using questionnaires and in-depth interviews. Logistic regression and thematic analysis were performed.

Results

Among the 153 victims, 57.5% were farmers. As first aid, 19.6% practiced the application of tourniquets. The treatment choices were allopathic medicine (65.4%), ayurvedic/traditional (26.1%), faith healing (3.3%), self-medication (2.0%) and none (3.3%). Visible ambient light at the time of bite (adjusted odds ratio [aOR] 2.3 [95% confidence interval {CI} 1.1 to 4.7]), absence of local swelling (aOR 2.5 [95% CI 1.1 to 5.3]) and prolonged bleeding (aOR 8.6 [95% CI 1.9 to 33.3]) determined failure to seek allopathic treatment, while personal characteristics showed no influence. Qualitative inquiry revealed that the treatment choice was influenced by the ability of the victim or others to recognize envenoming features and the snake as venomous and awareness of the facilities available in hospitals.

Conclusions

The time of snakebite, recognition of the snake/envenoming and awareness of accessible medical services determined the treatment choice following snakebite.
Local swelling in snakebite envenomation: Are we missing something for want of a name?
Authors: Kadhiravan Tamilarasu
Published: January 2025

Envenomations caused by viperid and some elapid snakebites are typically accompanied by local swelling and signs of inflammation that appear within a few hours of bite and spread centripetally for a few days. Often these changes are mistaken for signs of infection and are misdiagnosed as ‘cellulitis’. This potentially results in unwarranted use of antibiotics. There are important clinical differences between the swelling caused by local envenomation vis-à-vis cellulitis. The term venom-induced spreading sterile inflammation (VISSI) is more appropriate as a diagnosis name for the local swelling caused by snakebite envenomation.
Proteogenomic approaches for snake venom protein-based drug development: current trends and challenges
Authors: Jhade Sandeep Kumar , Kalidoss Karthik , Pathak Poonam Kumari , Shrivastava Rahul
Published: January 2025

Snake venom proteins have long been recognized for their therapeutic potential. Proteogenomic strategies, integrating transcriptomics and proteomics, have emerged as powerful tools for identifying and characterizing venom proteins for the development of novel therapeutic agents. Analytical techniques like mass spectrometry and next-generation sequencing enable comprehensive analysis, identifying key venom components and their variants. Recent studies unveil the diversity and complexity of snake venom, highlighting species-specific variations in toxin composition. Structural biology techniques, including x-ray crystallography and cryo-electron microscopy, provide insights into venom enzyme structures and mechanisms of action, facilitating drug design. Bioinformatics tools aid in data analysis and prediction of venom protein functions, enhancing drug discovery efforts. Despite advancements, challenges persist, including toxicity, formulation stability and clinical validation. This review describes the current as well as future options for research and development and emphasizes the critical role of proteogenomic techniques in developing snake venom protein-based drugs.