bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-077: High-throughput 3D-spheroid invasion assay: A powerful tool to identify novel drugs targeting tumor micro-environment in HNSCC
Authors: Karve Kunal , Poon Stephanie , Prinos Panagiotis , Ailles Laurie 
Published: September 2023

Abstract
Cancer metastasis is a complex cascade that involves activation of cancer cell invasion and migration. This activation is greatly attributed by multiple factors, including the tumor-microenvironment (TME). Cancer-associated fibroblasts (CAF), a prominent cell type within the TME, have been shown to promote cancer cell invasion and migration, causing metastasis in various cancers including head and neck squamous cell carcinoma (HNSCC). The molecular mechanisms of how CAFs promote HNSCC invasion remain elusive. Our research goal is to understand how CAFs influence HNSCC cells to become invasive and potentially metastatic. Using a top-down research approach, our aim is to identify novel therapeutic chemical probe/drug regimens that potentially target CAF-dependent HNSCC cancer cell-invasion. In-order to perform high-throughput small molecule screens, we have established a 384-well format, three-dimensional (3D) spheroid invasion assay, as a powerful tool to study CAF-dependent HNSCC cancer cell invasion. This platform is currently being used to screen small molecule libraries and identify putative molecular targets, providing insights into underlying mechanisms of CAF-induced cancer cell invasion and candidate therapeutic strategies.
Citation Format: Kunal Karve, Stephanie Poon, Panagiotis Prinos, Laurie Ailles. High-throughput 3D-spheroid invasion assay: A powerful tool to identify novel drugs targeting tumor micro-environment in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-077.
Which Small Molecule? Selecting Chemical Probes for Use in Cancer Research and Target Validation
Authors: Mader Mary M. , Rudolph Joachim , Hartung Ingo V. , Uehling David , Workman Paul , Zuercher William 
Published: September 2023

Abstract

Small-molecule chemical “probes” complement the use of molecular biology techniques to explore, validate, and generate hypotheses on the function of proteins in diseases such as cancer. Unfortunately, the poor selection and use of small-molecule reagents can lead to incorrect conclusions. Here, we illustrate examples of poor chemical tools and suggest best practices for the selection, validation, and use of high-quality chemical probes in cancer research. We also note the complexity associated with tools for novel drug modalities, exemplified by protein degraders, and provide advice and resources to facilitate the independent identification of appropriate small-molecule probes by researchers.

Significance:
Validation of biological targets and pathways will be aided by a shared understanding of the criteria of potency, selectivity, and target engagement associated with small-molecule reagents (“chemical probes”) that enable that work. Interdisciplinary collaboration between cancer biologists, medicinal chemists, and chemical biologists and the awareness of available resources will reduce misleading data generation and interpretation, strengthen data robustness, and improve productivity in academic and industrial research.
From Global to Local: The Development of Heavy Water in International Nuclear Programs (1945–1970)
Authors: Sanz-Lafuente Gloria 
Published: September 2023

Abstract
Because of how heavy water is produced and used, it has a unique business history and structure. In the late 1940s and 1950s, heavy-water reactors offered the dream of nearly inexhaustible quantities of nuclear power generation. This was because they could operate using natural uranium and also produce plutonium that could be used as fuel in breeder reactors (and also as fissile material for nuclear weapons). Several of the processes and materials used in synthetic fertilizer production could also be used, in somewhat modified form, in the production of heavy water. Yet the production costs for heavy water are exceedingly high, requiring copious amounts of electricity and the infrastructure of an advanced chemical industry. This article suggests that in several countries the fertilizer and heavy-water industries had a close relationship. The governments in those countries, seeking to increase the national trade in fertilizers and to develop domestic nuclear programs, supported both industries. The case of the Spanish Nuclear Board and Energía e Industrias Aragonesas in Sabiñanigo is instructive in this regard.
Loanwords in the Fiery Furnace
Authors: Gvaryahu Amit 
Published: September 2023

Abstract
This article is a discussion of two Greek loanwords found in the Rabbinic text Song of Songs Rabbah. It shows that these words are best identified and explained through a comparison with a Stoic theory of fire, described and refuted by Philo of Alexandria. That these words, both hapax legomena in Rabbinic literature, are used in the Midrash show that at least some rabbis were conversant in Greek scientific terminology—and perhaps specifically with a version of this Stoic dispute. The uses to which these terms were put show that the rabbis deployed their vast, specialized knowledge where it was most important to them: interpreting the scriptures.
Reference intervals for deconjugated urine metanephrines by Bhattacharya analysis
Authors: Li Bobby , King Richard , Sies Christiaan , Thompson Simon , Florkowski Chris 
Published: September 2023

Background Urine metanephrines are used to screen for phaeochromocytoma or paraganglioma (PPGL). Current reference intervals (RI) derived in healthy individuals are not age or sex-stratified, and lower than in hypertensive patients, leading to high false positive rates. This study aims to determine age and sex-stratified RI from a contingent screening population. Methods Patients with 24-h deconjugated urine metanephrines from 3/6/2010 to 27/8/2022 were included (2936 males, 5285 females), initially by liquid chromatography-electrochemical detection (LC-ECD) then liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bhattacharya analysis was used after log transformation to determine age and sex-stratified RI for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios. Results Normetanephrine excretion increases with age (RI: males: 18–<30 years: <3.4 µmol/24 h, 30–<40 years: <3.7 µmol/24 h, 40+ years: <5.3 µmol/24 h; females: 18–<30 years: <2.7 µmol/24 h, 30–<40 years: <3.1 µmol/24 h, 40+ years: <3.7 µmol/24 h), while metanephrine excretion was consistent across adulthood (RI: males: 18+ years: <1.8 µmol/24 h; females: 18+ years: <1.2 µmol/24 h). However, normetanephrine/creatinine and metanephrine/creatinine increase steadily with age after early adulthood, likely due to a decrease in muscle mass, with females having higher normetanephrine/creatinine and metanephrine/creatinine ratios. Conclusions Age and sex-stratified RI were derived for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios. This is expected to reduce false positives while flagging most PPGL.
A Real-World Comparison of Apixaban and Rivaroxaban in Obese and Morbidly Obese Patients With Nonvalvular Atrial Fibrillation
Authors: Burnham Kevin T. , Yang Tianrui , Wooster Jessica 
Published: September 2023

Background: Contemporary guidelines for managing nonvalvular atrial fibrillation (NVAF) include apixaban and rivaroxaban as first-line anticoagulation treatment options. Minimal guidance is available regarding selecting anticoagulants for patients with class I-III obesity. Objective: This study aims to evaluate the comparative effectiveness and safety of apixaban and rivaroxaban in both obese and morbidly obese patients with NVAF. Methods: A retrospective cohort study was conducted at an outpatient cardiovascular clinic after Institutional Review Board approval. Patients were eligible if they were ≥18 years of age, had a BMI ≥30 kg/m2, and took apixaban or rivaroxaban for NVAF for ≥3 months. The primary endpoint was the composite rate of stroke, transient ischemic attack (TIA), myocardial infarction (MI), or presence of atrial thrombosis. Bleeding events were evaluated as the primary safety endpoint. Results: Combined, the cohorts consisted of 303 obese or morbidly obese patients. The primary composite endpoint occurred in 3.8% of patients taking apixaban and 1.7% of patients taking rivaroxaban ( P = .28). Both clinically relevant, non-major and major bleeding occurred more often in the apixaban arm, but this difference was not statistically significant; however, bleeding risk may have been skewed due to differences in baseline characteristics. Conclusion and Relevance: For obese and morbidly obese patients prescribed either apixaban or rivaroxaban for NVAF, rates of stroke, TIA, MI, and atrial thrombosis did not differ. The preferred DOAC for patients with class I-III obesity remains elusive, but current data points to a patient-centered approach for anticoagulant selection.
Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes
Authors: Campbell Ashley M. , Pae Elizabeth , Lee Eunice , Jacisin Timothy , Price Alina , DeAngelo Jessica 
Published: September 2023

Background: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. Objective: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. Methods: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, “underdosed”) were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. Results: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) “underdosed.” The 147 “underdosed” patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). Conclusion and Relevance: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.
Epidemiology of podoconiosis in sub-Saharan Africa: A systematic review and meta-analysis
Authors: Abiso Temesgen Lera , Abebe Kerbo Amene , Wolka Woticha Eskinder 
Published: September 2023

Objective: Podoconiosis, one of the neglected tropical diseases (NTDs), affects barefoot people in impoverished regions and contributes to poverty by having negative impacts on economic output, education, and disability. People who have the disease waste nearly half of all of their productive workdays. There is limited evidence available on prevalence of podoconiosis in sub-Saharan Africa (SSA). Therefore, the aim of this research was to determine the pooled prevalence of podoconiosis in the SSA over the last 10 years. Methods: Studies were retrieved from PubMed, Embase, Web of Science, Scopus, Google Scholar, and Google by using a combination of search terms with Boolean operators. All authors independently assessed each study’s quality using the modified Newcastle–Ottawa Scale for cross-sectional studies. STATA Version 14 was used to conduct the statistical analysis. The random-effect approach of meta-analysis was used. To test for heterogeneity, I-Squared ( I2) statistics were employed and sensitivity analysis with a leave-one-out was done. Result: In this systematic review and meta-analysis, a total of 16 publications with 2,195,722 individuals were included. The pooled prevalence of podoconiosis was 2.66 (95% confidence interval (CI): 2.24, 3.10) with heterogeneity index ( I2) of 99.9%. Walking barefoot adjusted odd ratio (AOR) 5.35 (95% CI: 1.65, 9.05), p = 0.001, not washing feet with soap and water regularly AOR 2.8 (95% CI: 1.16, 4.44, p = 0.001), and an increased age AOR 2.23 (95% CI: 1.25, 5.58) were factors significantly associated with the prevalence of podoconiosis. Conclusion: This study revealed that pooled prevalence of podoconiosis was considerable in SSA. Age, being barefoot, and failing to wash one’s feet with soap and water have been identified to be factors that were significantly associated with the prevalence of podoconiosis. Therefore, creating awareness on shoe wearing and providing shoes in communication with supporting organizations in podoconiosis prevalent areas, and early diagnosis based on family history are needed for the prevention of podoconiosis
Co-occurring implementation strategies: The effects of academic detailing for opioid use disorder campaign on the advancing pharmacological treatments for opioid use disorder (ADaPT-OUD) study
Authors: Miller Wendy A. , Gordon Adam J. , Clothier Barbara A. , Ackland Princess E. , Bounthavong Mark , Garcia Carla , Kenny Marie E. , Noorbaloochi Siamak , Hagedorn Hildi J. 
Published: September 2023

Background Barriers at the system, clinician, and patient level limit access to medications for opioid use disorder (MOUD). The Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD) study implemented an external facilitation strategy within the Veterans Health Administration (VHA) aimed at facility-level barriers to improve uptake of MOUD. During ADaPT-OUD, an independent Academic Detailing Services Opioid Agonist Treatment of OUD Campaign was co-occurring and aimed to increase evidence-based practice for OUD at the clinician level. While both these initiatives aim to increase MOUD reach, they address different barriers and did not intentionally collaborate. Thus, understanding the interaction between these two independent implementation initiatives and their effect on MOUD reach will further inform and mold future implementation efforts of MOUD. Methods This was a secondary analysis of the ADaPT-OUD study that included 35 VHA facilities in the lowest quartile of MOUD reach; eight received the ADaPT-OUD external facilitation and 27 matched sites received implementation as usual. The number of academic detailing (AD) visits during ADaPT-OUD was used as a proxy for the intensity of Academic Detailing for OUD Campaign activity. The interaction between external facilitation status and AD intensity was evaluated by comparing the change in facility-level MOUD reach. Results There was a general increase in the number of AD visits, in both external facilitation and implementation as usual sites, over the course of ADaPT-OUD's implementation period. A non-statistically significant, positively sloped, linear relationship was observed between average number of AD visits per quarter and change in MOUD reach in facilities also receiving ADaPT-OUD external facilitation that was not observed in the implementation as usual sites. Conclusion Co-occurring initiatives focusing on different barriers to MOUD access have the potential to further increase MOUD in low-performing facilities, but further research into timing, quality, and collaboration between initiatives are warranted.
Polymer–lipid hybrid nanoparticles as potential lipophilic anticancer drug carriers
Authors: Salel Sedef , Iyisan Banu 
Published: September 2023

AbstractNanocarrier systems are widely used for drug delivery applications, but limitations such as the use of synthetic surfactants, leakage of toxic drugs, and a poor encapsulation capacity remain as challenges. We present a new hybrid nanocarrier system that utilizes natural materials to overcome these limitations and improve the safety and efficacy of drug delivery. The system comprises a biopolymeric shell and a lipid core, encapsulating the lipophilic anticancer drug paclitaxel. Bovine serum albumin and dextran, in various molecular weights, are covalently conjugated via Maillard reaction to form the shell which serves as a stabilizer to maintain nanoparticle integrity. The properties of the system, such as Maillard conjugate concentration, protein/polysaccharide molar ratio, and polysaccharide molecular weight, are optimized to enhance nanoparticle size and stability. The system shows high stability at different pH conditions, high drug loading capacity, and effective in vitro drug release through the trigger of enzymes and passive diffusion. Serine proteases are used to digest the protein portion of the nanoparticle shell to enhance the drug release. This nanocarrier system represents a significant advancement in the field of nanomedicine, offering a safe and effective alternative for the delivery of lipophilic drugs.
Graphical abstract
Evaluation of the DBP formation potential of biocides and identification of knowledge gaps in environmental risk assessment
Authors: Usman Muhammad , Hüben Michael , Hahn Stefan , Wieck Stefanie , Kehrer-Berger Anja , Linnemann Volker , Wintgens Thomas 
Published: September 2023

AbstractDisinfectants and preservatives used as biocides may contain or release active substances (a.s.) that can form by-products with the surrounding matrices during their application which may be released into the environment. Over the past 40 years, several hundred of these so-called disinfection by-products (DBPs) have been detected after applications of biocides used for disinfection. Due to intensive research and further development of analytical capabilities, many new DBP classes, such as iodinated DBPs (I-DBPs), halonitromethanes (HNMs), haloacetamides (HaAms), or halomethanesulfonic acids were detected worldwide in various matrices and applications. Due to the possible hazards and risks for humans and the environment, frequently occurring DBP classes, such as trihalomethanes (THM), haloacetic acids (HAA) and nitrosamines (NDMA), have already been included in many legislations and given limit values. In the European Union, biocides are assessed under the Biocidal Products Regulation 528/2012 (BPR) regarding their efficacy, potential hazards, and risks to human health and the environment. However, the available guidance for the environmental risk assessment (ERA) of DBPs remains vague. To identify knowledge gaps and to further develop the assessment scheme for the ERA of DBPs, a literature search on the multiple uses of biocides and their formation potential of DBPs was performed and the existing process for ERA was evaluated. The results show knowledge gaps on the formation of DBP in non-aqueous systems and DBP formation by non-halogen-based biocidal active substances. Based on the literature research on biocides, a possible proposal of grouping a.s. to consider their DBP formation potential is presented to simplify future ERAs. However, this also requires further research. Until then, a pragmatic approach considering the DBPs formation potential of the active substances and the identified knowledge gaps need to be established for the environmental risk assessment of DBPs in the EU.
Graphical Abstract
A unique case of a fulminant clonal CD8-positive T-cell lymphoproliferative disorder with CNS involvement
Authors: Mesbah-Oskui Lia , Alabkal Jarrah , Alduaij Waleed , Dhawan Priya S. 
Published: September 2023

Abstract
Background
This is a unique case that describes the presentation, investigations, and disease trajectory of a fatal, clonal CD8-positive T-cell lymphoproliferative disorder in an otherwise healthy and immunocompetent patient with Epstein-Barr virus seronegative status. Central nervous system involving T-cell lymphoproliferative disorders are rare and typically encountered in the setting of immunocompromise. These disorders are often associated with aggressive cytomorphological features and characteristic magnetic resonance imaging patterns, which were not seen in this case.

Case presentation
Here we describe a case of a 65 year-old male presenting with neuropsychiatric symptoms, truncal ataxia, and falls who’s bone marrow, cerebrospinal fluid, and brain biopsy were consistent with a clonal CD8-positive T-cell lymphoproliferative disorder that did not meet existing World Health Organization criteria for classification as T-cell lymphoma. The patient was treated with intrathecal methotrexate resulting in transient improvement of his symptoms followed by disease progression and death related to aspiration.

Conclusions
This case highlights the importance of urgent and comprehensive work-up in patients with clinical features suggestive of lymphoma with central nervous system involvement, despite atypical imaging features and lack of cytomorphological features satisfying current World Health Organization classification criteria.
Leptomeningeal neuraxis relapse in glioblastoma is an uncommon but not rare event associated with poor outcome
Authors: Wegener Eric , Horsley Patrick , Wheeler Helen , Jayamanne Dasantha , Kastelan Marina , Guo Linxin , Brown Chris , Back Michael 
Published: September 2023

Abstract
Background
Spinal neuraxis leptomeningeal metastasis (LM) relapse in glioblastoma is an uncommon event that is challenging to manage. This study aims to determine the incidence, associated factors, and outcome of LM relapse in patients with glioblastoma managed with radical intent.

Methods
Patients managed for glioblastoma using the EORTC-NCIC (Stupp) Protocol from 2007 to 2019 were entered into a prospective ethics-approved database. Follow-up included routine cranial MRI surveillance with further imaging as clinically indicated. LM relapse was determined by MRI findings and/or cerebrospinal fluid analysis. The chi-square test of independence was used to evaluate clinico-pathologic factors associated with increased risk of subsequent LM relapse. Median survival post-LM relapse was calculated using Kaplan-Meier technique.

Results
Four-hundred-and-seven patients were eligible, with median follow-up of 60 months for surviving patients. Eleven (2.7%) had LM at first relapse and in total 21 (5.1%) experienced LM in the entire follow-up period. Sites of LM relapse were 8 (38%) focal spinal, 2 (10%) focal brainstem medulla and 11 (52%) diffuse spinal. Median overall survival from initial diagnosis for the entire cohort was 17.6 months (95% CI 16.7–19.0). Median survival from LM relapse to death was 39 days (95% CI: 19–107). Factors associated with LM relapse were age less than 50 years (p < 0.01), initial disease located in the temporal lobe (p < 0.01) and tumours lacking MGMT promoter methylation (p < 0.01).

Conclusions
LM relapse is an uncommon but not rare event in patients managed radically for glioblastoma. It is associated with poor outcome with the majority of patients deceased within two months of recognition.