bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of carvedilol on pharmacokinetics of sofosbuvir and its metabolite GS-331007: role of P-glycoprotein
Authors: Fahmy Salma N , Khedr Lobna H , Wahdan Sara A , Menze Esther T , Azab Samar S , El-Demerdash Ebtehal 
Published: June 2024

Abstract
Sofosbuvir (SOF) is a P-glycoprotein (P-gp) substrate, and carvedilol (CAR) is an inhibitor of P-gp, suggesting that it may affect the oral pharmacokinetics and safety of SOF. The current study investigated the pharmacokinetic interaction of CAR with SOF and its metabolite, GS-331007, and the possible consequent toxicities in rats. To assess the pharmacokinetics of SOF and GS-331007, rats were divided into three groups; all received a single oral dose of SOF preceded with saline (SAL), verapamil (VER) as a standard P-gp inhibitor, or CAR, respectively. The serosal, plasma, and hepatic tissue contents of SOF and GS-331007 were assessed using LC-MS/MS. Renal and hepatic toxicities were assessed using biochemical and histopathological tests. Serosal and plasma concentrations of SOF and GS-331007 were increased in the presence of CAR, suggesting a significant inhibitory effect of CAR on intestinal P-gp. Simultaneously, the pharmacokinetic profile of SOF showed a significant increase in the Cmax, AUC(0-t), AUC (0-∞), t1/2, and a reduction in its apparent oral clearance. While the pharmacokinetic profile of GS-331007 was not significantly affected. However, this notable elevation in drug oral bioavailability was corroborated by a significant alteration in renal functions. Hence, further clinical investigations are recommended to ensure the safety and dosing of CAR/SOF combination.
Randomized Phase 1b CROSSWALK-a and Phase 2a CROSSWALK-c Trials Crovalimab for SCD
Authors: Hsia Allison W , Salvino Marco Aurélio , Antmen Bulent , Asirwa Fredrick Chite , Chonat Satheesh , de Franceschi Lucia , Eleftheriou Perla , Inati Adlette , Mahlangu Johnny , Nur Erfan , Payán-Pernía Salvador , Charania Asad , Gradinaru Diana , Luder Yves , Perretti Thomas , Sreckovic Sasha , Bartolucci Pablo 
Published: June 2024

Abstract

Presentation Date: 6/9/2024
Presentation Start Time: 1:33:00 PM

Background
In sickle cell disease (SCD), a beta-globin gene single point mutation results in hemoglobin S (HbS) production, which can polymerize upon deoxygenation. Polymerization distorts the red blood cell membrane, generating sickled red blood cells and contributing to microvascular occlusions, which may present as acute, painful vaso-occlusive episodes (VOEs). Among patients with SCD, 70% of emergency department visits and 90% of hospitalizations are VOE-related.1,2 Despite the availability of treatments for VOE prevention, considerable morbidity and mortality remain. Due to a lack of targeted therapies, acute VOE treatment is limited to supportive care.
Nonclinical data suggest a multimodal role for complement dysregulation in the pathophysiology of SCD, including in vaso-occlusion, hemolysis, inflammation, endothelial activation, thrombogenicity, and end-organ damage.3 Crovalimab is a novel, engineered, anti-complement C5 monoclonal antibody that allows for small-volume subcutaneous injection after an initial intravenous loading dose.4 Here, we describe the design of two randomized, double-blind, placebo-controlled trials evaluating crovalimab in patients with SCD: CROSSWALK-a (Phase 1b; NCT04912869) and CROSSWALK-c (Phase 2a; NCT05075824).

Methods
CROSSWALK-a evaluates the safety of crovalimab in managing acute uncomplicated VOEs. CROSSWALK-c evaluates the efficacy and safety of crovalimab as adjunct therapy in preventing VOEs.
Patients between 12 and 55 years of age, weighing ≥40 kg, having a confirmed diagnosis of sickle cell anemia (homozygous HbSS or heterozygous HbS/β0 thalassemia), and N. meningitidis, H. influenzae type B and S. pneumoniae vaccinations are eligible (Fig. 1 and 2). Concurrent SCD-directed therapies are allowed.

Conclusions
CROSSWALK-a and CROSSWALK-c are currently actively enrolling patients with SCD in 6 and 7 countries, respectively.
References
1. Ballas et al, Am J Hematol 2005; 79:17–25.
2. Lanzkron et al, Am J Hematol 2010; 85:797–799.
3. Roumenina et al, Am J Hematol 2020; 95:456–464.
4. Röth et al, Blood 2020; 135:912–920.
© American Society of Hematology (2023). Reused with permission.
Point-of-care Diagnostic for Foetal Haemoglobin in Kids for Sickle Cell Disease in Ghana
Authors: Segbefia Catherine , Dei-Adomakoh Yvonne , Mensah Enoch , Thota Priya , Odame Isaac 
Published: June 2024

Abstract

Presentation Date: 6/9/2024
Presentation Start Time: 2:30:00 PM

Background
Sickle cell disease (SCD) is an inherited blood disorder which causes acute and chronic complications and can result in early death. About three-fourth of patients with SCD live in sub-Saharan Africa; in Ghana, 1 in 50 newborns are affected with SCD. Foetal hemoglobin (Hb F) level is a strong modifier of SCD severity. High levels of Hb F inhibit sickling and hemolysis and reduce disease morbidity and mortality. Hb F monitoring is also used to assess adherence and response to disease modifying therapy such as hydroxyurea. Standard hemoglobin electrophoretic techniques are unable to quantify Hb F. In resource-limited settings like Ghana, the use of high-performance liquid chromatography (HPLC) for Hb F quantification is often challenging due to cost and logistic constraints such limited availability of adequate technology and appropriately trained personnel. In this study, we assessed the performance of a low-cost, point-of-care (POC), microchip based cellulose acetate electrophoresis “GazelleTM” compared to HPLC for Hb F quantification in children with SCD in Ghana. GazelleTM is a fast ( &lt; 8 minutes), easy-to-use test which can be performed by minimally trained end-users using only a finger-prick volume of blood.

Methods
This cross-sectional study was conducted at the paediatric SCD Clinic in Korle Bu Teaching Hospital, Accra, Ghana. Study participants were children of ages ≥ 1 year to 16 years who were known to have sickle cell disease and were about to commence or were on hydroxyurea therapy and followed at the SCD clinic.

Results
A total of 532 children were included in the analysis. Gazelle showed a correlation of 0.98 (Pearson correlation) when compared to HPLC.

Conclusions
Haemoglobin variants are quantified by Gazelle offering the ability to monitor disease modifying therapy in SCD such as hydroxyurea, where quantification of Hb F levels is important in assessing treatment adherence and determining response to therapy. Gazelle has the potential to be utilized as a POC test for quantification of Hb F levels in monitoring hydroxyurea therapy for children with SCD, especially in limited-resource settings.
Diagnostic Potential of Platelet-Neutrophil Ratio (PNR) for Stroke Risk in SCD Children
Authors: Efobi Chilota Chibuife , Nri-Ezedi Chisom A , Hyppolite Regine , Darbari Deepika S , Campbell Andrew D 
Published: June 2024

Abstract

Presentation Date: 6/9/2024
Presentation Start Time: 3:00:00 PM

Background
Sickle cell disease (SCD) presents a formidable healthcare challenge, with stroke being a significant complication. The gold standard for stroke risk assessment is transcranial doppler ultrasound (TCD). However, resource constraints often limit TCD availability. This study explores the potential of the platelet-neutrophil ratio (PNR) as a cost-effective and an additional tool for assessing stroke risk in SCD patients.

Methods
This was a retrospective study conducted on 144 SCD HbSS children from Children’s National Hospital, Washington DC, USA as part of the CNH Natural History Study of SCD. TCD values were categorized (based on the STOP Study) as normal, abnormal, or conditional. PNR was calculated from routine complete blood count tests. Statistical analyses were employed to evaluate the association between the platelet-neutrophil ratio and stroke risk.

Results
The platelet-neutrophil ratio (PNR) demonstrated distinctive values across stroke risk categories: 83.83 (58.15-127.65) for normal, 75.69 (64.89-88.6) for conditional, and 62.57 (28.12-64.47) for abnormal (p = 0.031). Following adjustments for age and hydroxyurea intake, a unit increase in PNR was significantly associated with a decreased risk of stroke (OR = 0.975, 95% CI: 0.953-0.998, p = 0.0345). PNR showed superior discriminative performance for stroke risk compared to neutrophils and platelets, with AUC values of 0.81, 0.57, and 0.19, respectively.

Conclusions
This research unveils a promising avenue for more equitable healthcare in SCD management by introducing the platelet-neutrophil ratio (PNR) as a cost-effective and additional tool to assess for stroke risk in poor resource settings. A larger study is needed to validate these findings.
Hyperhemolysis Syndrome in Child with Sickle Cell Disease: Case Report and Literature Review
Authors: Arcara Catherine , Morgan Epley , Sinha Shabnum , Ahmed Rafat , Ostrowicki Renata , Eddington K Allen , Gao Yuanzheng Andrew 
Published: June 2024

Abstract

Presentation Date: 6/8/2024
Presentation Start Time: 6:00:00 PM

Background
Worsening anemia in the setting of various sickle cell disease sequelae is often treated with packed red blood cell (pRBC) transfusion. Hyperhemolysis syndrome (HHS) is a rare and life-threatening complication of transfusion. HHS is the destruction of host RBC and transfused RBC in the absence of red cell antibodies. This is evidenced by declining hemoglobin (Hb) and reticulocyte counts following transfusion, with negative antibody testing. The pathophysiology of HHS continues to be investigated. Proposed mechanisms include bystander hemolysis, erythropoiesis suppression, and macrophage mediated destruction. Hyperhemolysis is typically treated with IVIG and steroids. Goals of treatment include improving Hb and reticulocyte count.

Objective
Describe a case of a 15 year old male with sickle cell SS disease with acute chest syndrome (ACS) complicated by hyperhemolysis syndrome.

Methods
Single case report and literature review

Results
15 year old male with sickle cell disease type SS and history of delayed transfusion reactions who initially presented with right sided chest pain and shortness of breath. Patient found to have acute hypoxic respiratory failure with new infiltrates on chest x-ray consistent with right sided pneumonia progressing to ACS requiring increasing respiratory support and antibiotics. Patient noted to have significant anemia, requiring pRBC transfusions. After PRBC transfusion, he experienced worsening clinical status with increasing oxygen requirements, anemia, reticulocytopenia, thrombocytopenia, and leukocytosis with negative Direct Coombs test, raising concern for acute HHS. Patient demonstrated cyclical pattern of significant anemia necessitating transfusions with expected increase in hemoglobin followed by significant thrombocytopenia, reticulocytopenia, and anemia within 48-72 hours of transfusion. Given history of transfusion reactions and suspected HHS, patient was initiated on IV glucocorticoids with demonstrated resolution of anemia, thrombocytopenia, and reticulocytopenia.

Conclusions
While the exact underlying cause of this patient’s hyperhemolysis remains unknown, he responded immediately to the administration of IV steroids. Both steroids and IVIG together are standard treatment, however this case supports that IV steroids alone are sufficient to treat HHS. IV steroids are more cost effective than IVIG. Furthermore, there is evidence of IVIG induced hemolytic anemia, which would exacerbate the underlying pathologic process in HHS. Being familiar with the presentation of HHS is important to be able to recognize the condition and provide timely treatment.
The Role of Endothelial Cells in Sickle Cell Hemoglobin Clearance: What Do We Know So Far?
Authors: Pradhan-Sundd Tirthadipa , Kaminski Tomasz , Zhang Hong 
Published: June 2024

Abstract

Presentation Date: 6/8/2024
Presentation Start Time: 6:00 PM

Background
Sickle cell disease (SCD) is a monogenic disorder that affects 100,000 African Americans and millions of people worldwide. Intra-erythrocytic polymerization of sickle hemoglobin (HbS) promotes erythrocyte sickling, impaired rheology, ischemia and hemolysis, leading to the development of progressive organ injury in SCD. Liver resident Kupffer cells and monocytes are known to enable the clearance of HbS, however, the role of liver sinusoidal endothelial cells (LSECs) in HbS clearance and liver injury in SCD remains unknown.

Methods
We used real-time intravital imaging, flow cytometry analysis, and confocal imaging of human and mouse primary endothelial cells to investigate their potential function in hemoglobin clearance.

Results
We show for the first time that LSECs are capable of HbS clearance. Hb uptake by LSECs was mediated by micropinocytosis. We show that accumulation of HbS in LSECs promotes endothelial senescence. Hepatic monocytes were observed to attenuate LSEC senescence by accelerating HbS clearance in the liver of SCD mice, however, this protection was impaired in P-selectin-deficient SCD mice secondary to reduced monocyte recruitment in the liver.

Conclusions
These findings are the first to suggest that LSECs contribute to HbS clearance and HbS induced LSEC-senescence promotes progressive liver injury in SCD mice. Our results provide a novel insight into the pathogenesis of hemolysis induced chronic liver injury in SCD caused by LSEC senescence. Identifying the regulators of LSEC mediated HbS clearance may lead to new therapies to prevent the progression of liver injury in SCD.
“The heavens, the earth and all their hosts” (Gen 2,1). The inventory of the supernatural entities in the Hebrew Bible created with the Elyonim veTachtonim system
Authors: Kosior Wojciech 
Published: June 2024

Abstract
Elyonim veTachtonim is a system of quantitative and qualitative analysis of the traditions involving supernatural entities and, in this article, I showcase its implementation to the construction of the biblical inventory. I start with a review of the printed and electronic resources and recognize their advantages and limitations which informed and motivated the production of the database. Next, I summarize the theoretical and methodological fundamentals of the endeavor and then scrutinize the development process emphasizing the quantitative and qualitative specificities of the biblical inventory. Finally, I sketch out the possible applications of the database and its prospective developments.
Challenges of Providing Optimal and Safe Intrapartum Analgesia in Patients With HELLP Syndrome: A Case Report and Literature Review
Authors: Crane Anise A , Russo Christopher M , Wands Kayla , Gafner Jeffrey L , Burch Robert H 
Published: June 2024

ABSTRACT
HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) Syndrome is a rare but serious complication of pregnancy that can lead to disseminated intravascular coagulation, pulmonary edema, respiratory failure, hepatic and renal injury, and death if not recognized and treated promptly. A 36-year-old nulligravid (G0) active duty Marine at 36 weeks and 1 day gestation with dichorionic diamniotic twins presented to triage for routine cervical examination found to have elevated blood pressures and symptomatic thrombocytopenia, with a suspected diagnosis of HELLP. A multidisciplinary decision was made by anesthesiology, obstetrics and gynecology, and pediatrics to deliver the twins to avoid any further complications. The twins were in cephalic presentation and the patient desired to attempt a vaginal delivery. Due to the patient’s thrombocytopenia, neuraxial anesthesia (spinal and/or epidural) left the patient at a high risk of developing catastrophic complications such as an epidural hematoma, and the subsequent motor block/weakness would likely lessen the patient’s ability to participate in active labor for a vaginal delivery. A Cesarean section under general anesthesia was also to be avoided as the patient’s elevated risk of catastrophic hemorrhage would be worsened by volatile anesthetic agents which cause significant uterine vascular relaxation and reduced uterine muscular tone. Ultimately, the decision was made to provide analgesia through a remifentanil PCA (patient-controlled analgesia) for labor and a ketamine bolus for delivery. The mother delivered both twins vaginally in the operating room without perioperative complication. This case demonstrates the safety of alternate forms of anesthesia for delivery when neuraxial anesthesia is contraindicated.
The Dreaded 3-Minute Wait: Does It Really Prevent Operating Room Fires? The IGNITE Trial
Authors: Keenan Corey , Danis Hillary , Fraley Jim , Roets Jack , Spitzer Holly , Grasso Samuel 
Published: June 2024

ABSTRACT

Introduction
Operating room fires can have devastating consequences and as such must be prevented. There exists a paucity of literature requiring further elucidation regarding manufacturer recommendations of a predefined waiting period prior to patient draping after using alcohol-based surgical antiseptics, in order to reduce the risk of operating room fires.

Methods
This was further investigated by exposing two common alcohol-based surgical antiseptics to electrosurgery and open flames at various power settings and time intervals in an ex vivo porcine model. The simulated surgical site was prepped following manufacturer recommendations and exposed to monopolar electrosurgery at low and high power, using both PURE CUT and COAGULATION modes, and open flame, at 15-s increments after application.

Results
While using PURE CUT mode at both low and high power, no ignition was observed on hairless surgical sites prepped with ChloraPrep® at any time point. However, use of COAGULATION mode at both low and high powers resulted in ignition consistently out to 1-min post-application. Additionally, if the prepped area subjectively appeared wet, especially with pooling of the antiseptic, both COAGULATION mode and open flame caused ignition. Dry time was found to be about 59 s for both prep solutions. It was also observed that the amount of pressure directly correlated with the amount of prep dispersed and increased dry times.

Conclusion
In conclusion, our data suggest an average dry time of less than 1-min, with ignition only observed when the antiseptic was visibly wet. Ignition did not occur on hairless skin with electrocautery on CUT mode using ChloraPrep at any time point. Additionally, ignition on hair-bearing skin was not observed past 3 min, with current manufacturer recommendations stating 1 h wait time for hair-bearing skin. Arbitrarily waiting a specific predetermined dry time until patient draping, as recommended by the manufacturers, may be unnecessary and lead to hours’ worth of time wasted each year. Ongoing research will further investigate the utility of drying the antiseptic after application and its affect on not only preventing ignition but also antimicrobial efficacy.
Understanding stellar populations in thin and thick discs of edge-on galaxies with MUSE – I. The case of the reignited S0 galaxy ESO 544-27
Authors: Somawanshi Devang , Bhattacharya Souradeep , Kataria Manish , Kobayashi Chiaki 
Published: June 2024

ABSTRACT
Edge-on galaxies act as the best laboratories to understand the origin of thin and thick discs in galaxies. Measurement of spatially resolved stellar population properties in such galaxies, particularly age, metallicity, and [α/Fe], are crucial to understanding the formation and evolution of disc galaxies. Such measurements are made possible from stellar population model fits to deep integral field spectroscopic (IFU) observations of resolved galaxies. We utilize archival MUSE IFU observations of the edge-on galaxy ESO 544-27 to uncover the formation history of its thin and thick discs through its stellar populations. We find the thin disc of the galaxy is dominated by an old (&gt;9 Gyr) low [α/Fe] metal-rich stellar population. Its outer thick disc is dominated by an old (&gt;9 Gyr) high [α/Fe] metal-rich component that should have formed with higher star formation efficiency than the Milky Way thick disc. We thus find [α/Fe] dichotomy in ESO 544-27 with its thin and thick discs dominated by low and high [α/Fe] stellar populations, respectively. However, we also find a metal-rich younger (&lt;2 Gyr old) stellar population in ESO 544-27. The galaxy was nearly quenched until its star formation was reignited recently first in the outer and inner thick disc (∼1 Gyr ago) and then in the thin disc (∼600 Myr ago). We thus find that both the low [α/Fe] thin and high [α/Fe] thick discs of ESO 544-27 are inhabited primarily by similarly old metal-rich stellar populations, a contrast to that of other galaxies with known thin and thick disc stellar population properties.
Longitudinal filtering, sponge layers, and equatorial jet formation in a general circulation model of gaseous exoplanets
Authors: Christie D A , Mayne N J , Zamyatina M , Baskett H , Evans-Soma T M , Wood N , Kohary K 
Published: June 2024

ABSTRACT
General circulation models are a useful tool in understanding the three dimensional structure of hot Jupiter and sub-Neptune atmospheres; however, understanding the validity of the results from these simulations requires an understanding of the artificial dissipation required for numerical stability. In this paper, we investigate the impact of the longitudinal filter and vertical ‘sponge’ used in the Met Office’s unified model when simulating gaseous exoplanets. We demonstrate that excessive dissipation can result in counter-rotating jets and a catastrophic failure to conserve angular momentum. Once the dissipation is reduced to a level where a super-rotating jet forms, however, the jet and thermal structure are relatively insensitive to the dissipation, except in the nightside gyres where temperatures can vary by $\sim 100\, \mathrm{K}$. We do find, however, that flattening the latitudinal profile of the longitudinal filtering alters the results more than a reduction in the strength of the filtering itself. We also show that even in situations where the temperatures are relatively insensitive to the dissipation, the vertical velocities can still vary with the dissipation, potentially impacting physical processes that depend on the local vertical transport.
Unveiling the properties of asteroids: linking photopolarimetry to spectral classification
Authors: Prasad B , Das H S 
Published: June 2024

ABSTRACT
This paper attempts to present a comprehensive analysis of the photopolarimetric properties of asteroids. In light of the limitations identified in several previously employed empirical formulae, this paper introduces a new formula that offers a reliable fit for the phase-polarization curve of asteroids. The validity of the new empirical formula is confirmed by analysing polarimetric data for lunar soil samples across a wide range of phase angles and various spectral bands. Notably, this investigation reveals a strong negative correlation between $P_{\mathrm{ max}}$ and wavelength ($\lambda$) for lunar soil samples. Furthermore, the examination of key features of the phase-polarization curve of asteroids, such as the polarization minimum ($P_{\mathrm{ min}}$), polarization maximum ($P_{\mathrm{ max}}$), and the slope (h) at the inversion angle, allows us to explore their correlations with the geometric albedo (A) of asteroids. We have investigated whether our photopolarimetric studies could corroborate the existing classification scheme for asteroids, which divides them into three major composition classes: Chondrite (C), Metallic (M), and Stony (S)-types, based on spectral analysis. Our findings have revealed a good agreement with the existing classification. Each class is characterized by a specific combination of geometric albedo (A) and polarimetric properties ($P_{\mathrm{ min}}$, $P_{\mathrm{ max}}$, and h) observed in asteroids, represented by four distinct regions. Interestingly, besides the three main types (C-, M-, and S-), we have found an overlapping region containing both M- and S-type asteroids.