bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects
Authors: Menachem Assaf , Alteber Zoya , Cojocaru Gady , Fridman Kfir Tal , Blat Dan , Leiderman Olga , Galperin Moran , Sever Lital , Cohen Nadav , Cohen Keren , Granit Roy Z. , Vols Sandra , Frenkel Masha , Soffer Liron , Meyer Karin , Menachem Keren , Galon Tilleman Hadas , Morein Dina , Borukhov Itamar , Toporik Amir , Perpinial Shahor Michal , Tatirovsky Evgeny , Mizrachi Aviram , Levy-Barda Adva , Sadot Eran , Strenov Yulia , Eitan Ram , Jakobson-Setton Ariella , Yanichkin Natalia , Ferre Pierre , Ophir Eran 
Published: April 2024

Abstract
Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment (TME) in response to IFNγ upregulation in a negative feedback mechanism. In this study, we found that IL18 is upregulated in the TME compared with the periphery across multiple human tumors and most of it is bound to IL18BP. Bound IL18 levels were largely above the amount required for T-cell activation in vitro, implying that releasing IL18 in the TME could lead to potent T-cell activation. To restore the activity of endogenous IL18, we generated COM503, a high-affinity anti-IL18BP that blocks the IL18BP:IL18 interaction and displaces precomplexed IL18, thereby enhancing T- and NK-cell activation. In vivo, administration of a surrogate anti-IL18BP, either alone or in combination with anti-PD-L1, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, the anti-IL18BP induced pronounced TME-localized immune modulation including an increase in polyfunctional nonexhausted T- and NK-cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL18BP using an Ab is a promising approach to harness cytokine biology for the treatment of cancer.
Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J. 
Published: April 2024

Abstract

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the β1+β2-agonist isoproterenol and administering β1 or β1+β2 antagonists prior to exercise revealed these effects to be β2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, β2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies.

Significance:
Exercise mobilizes effector γδ T-cells to blood via β2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.
Discordance Between Very Low‐Density Lipoprotein Cholesterol and Low‐Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort
Authors: Seehusen Kristina E. , Remaley Alan T. , Sampson Maureen , Meeusen Jeffrey W. , Larson Nicholas B. , Decker Paul A. , Killian Jill M. , Takahashi Paul Y. , Roger Véronique L. , Manemann Sheila M. , Lam Reyna , Bielinski Suzette J. 
Published: April 2024

Background
Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low‐density lipoprotein cholesterol (VLDL‐C) and lipid discordance could be contributors to the residual risk of ASCVD.

Methods and Results

Cardiovascular disease–free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low‐density lipoprotein cholesterol (LDL‐C) and VLDL‐C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow‐up. The association of LDL‐C and VLDL‐C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL‐C and VLDL‐C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL‐C (per 10‐mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05–1.09];
P
<0.001]) after adjustment for traditional risk factors. The interaction between LDL‐C and VLDL‐C was not statistically significant (
P
=0.11). Discordant individuals with high VLDL‐C and low LDL‐C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person‐years, during follow‐up.

Conclusions
VLDL‐C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.
Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction
Authors: Christersson Malin , Gustafsson Stefan , Lampa Erik , Almstedt Matilda , Cars Thomas , Bodegård Johan , Arefalk Gabriel , Sundström Johan 
Published: April 2024

Background
Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%–49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high.

Methods and Results
We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within‐person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within‐person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later.

Conclusions
LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.
Speaking “Mouth to Mouth” (Num 12:8)
Authors: Berman Joshua 
Published: April 2024

Abstract
The phrase פה אל פה אדבר בו in Num 12:8a is generally taken to mean to speak with Moses “face to face.” However, commentators have noted that this understanding presents grammatical difficulties. In this study I propose a new understanding of the idiom and argue that it refers to oral transmission, from one speaking agent to the next in a linear chain. This idiomatic use of the phrase “mouth to mouth” is found in ancient Egyptian texts and widely across many cultures. This understanding of the idiom פה אל פה is animated further by a re-examination of four pieces of textual data: a) the meaning of the phrase בכל ביתי נאמן הוא in Num 12:7, and specifically an interpretation widespread in rabbinic commentary, but absent from modern exegesis; b) the meanings and diffusion of the prepositional verb דבר ב; c) the morphologies of various פה-פה expressions found in 2 Kings, Jeremiah, and Ezra; d) the structural and thematic similarities of Num 11 and Num 12.
Species Diversity of the Leafhopper Tribe Paralimnini Distant (Hemiptera: Cicadellidae: Deltocephalinae) from Pakistan, with Description of Two New Genera
Authors: Naveed Hassan , Hassan Muhammad Asghar , Zhang Yalin , Chen Keping 
Published: April 2024

Abstract
Paralimnini Distant, 1908, is a notable leafhopper tribe that exhibits a wide distribution across all biogeographical regions, namely the Palearctic, Nearctic, Afrotropical, Oriental, Neotropical, and Australian regions. Among these, the Oriental region demonstrates the highest diversity of Paralimnini, with a significant portion of this diversity remaining unexplored according to recent investigations. This study focuses on examining 10 species under seven genera of the Paralimnini leafhopper tribe found in Pakistan. A comprehensive morphological study is conducted, which includes the description of two new genera, Paralimnolus gen. nov. and Lalianlus gen. nov., with P. bicolor sp. nov. and L. bifurcates sp. nov. within the tribe. The study meticulously describes and provides illustrations of all the taxa based on careful observations of specimens obtained from Pakistan. Additionally, the study furnishes an updated checklist and a key to facilitate the identification of known and new Pakistani genera belonging to the tribe Paralimnini. The present findings shed light on the diversity and distribution patterns of the Paralimnini tribe in Pakistan, particularly emphasizing the junction of the Oriental and Palearctic regions in the northern parts, as these parts of the country serve as a significant reservoir of undocumented species. The thorough documentation and available identification resources provided in this study serve as valuable references for future investigations and contribute to our knowledge of the leafhopper fauna in Pakistan.
Sensitivities of the West Greenland Current to Greenland Ice Sheet Meltwater in a Mesoscale Ocean/Sea Ice Model
Authors: Morrison Theresa J. , McClean Julie L. , Gille Sarah T. , Maltrud Mathew E. , Ivanova Detelina P. , Craig Anthony P. 
Published: April 2024

Abstract
Meltwater from the Greenland Ice Sheet can alter the continental shelf/slope circulation and cross-shelf freshwater fluxes and limit deep convection in adjacent basins through surface freshening. We explore the impacts on the West Greenland Current and eastern Labrador Sea with different vertical distributions of the meltwater forcing. In this study, we present the results from global coupled ocean/sea ice simulations, forced with atmospheric reanalysis, that are mesoscale eddy-active (∼2–3-km horizontal spacing) and eddy-permitting (∼6–7-km horizontal spacing) in the study region. We compare the West Greenland Current in mesoscale eddy-active and eddy-permitting without meltwater to highlight the role of small-scale features. The mesoscale eddy-active configuration is then used to assess the change in the eastern Labrador Sea when meltwater is added to the surface or vertically distributed to account for mixing within fjords. In both simulations with meltwater, the West Greenland and West Greenland Coastal Currents are faster than in the simulation with no meltwater; their mean surface speeds are the highest in the vertical distribution case. In the latter case, there is enhanced baroclinic conversion at the shelf break compared to the simulation with no meltwater. When meltwater is vertically distributed, there is an increase in baroclinic conversion at the shelf break associated with increased eddy kinetic energy. In addition, in the eastern Labrador Sea, the salinity is lower and the meltwater volume is greater when meltwater is vertically distributed. Therefore, the West Greenland Current is sensitive to how meltwater is added to the ocean with implications for the freshening of the Labrador Sea.

Significance Statement
Our goal is to understand how the flux of freshwater across the West Greenland continental slope into the Labrador Sea is modified by meltwater from the Greenland Ice Sheet. We compare the simulations of the ocean that capture key dynamics along the West Greenland continental slope that have no meltwater, meltwater added to the ocean surface, and meltwater distributed vertically to represent the mixing within fjords. When meltwater is added, the currents along the continental slope are faster, with the greatest increase when meltwater is vertically distributed. In that case, there is enhanced freshening of the Labrador Sea because modified density gradients generate more eddies. Proper representation of the vertical structure of meltwater is important for projecting the impact of freshwater on the subpolar North Atlantic.
Eddy Detection Inverted from Argo Profiles to Surface Altimetry
Authors: Chen Xiaoyan , Quartly Graham D. , Chen Ge 
Published: April 2024

Abstract
Argo floats are widely used to characterize vertical structures of ocean eddies, yet their capability to invert sea surface features of eddies, especially those overlooked by available altimeters, has not been explored. In this paper, we propose an “interior-to-surface” inversion algorithm to effectively expand the capacity of eddy detection by estimating altimeter-missed eddies’ surface attributes from their Argo-derived potential density anomaly profiles, given that the interior property and surface signature of eddies are highly correlated. An altimeter-calibrated machine learning ensemble is employed for the inversion training based on the joint altimeter–Argo eddy data and shows promising performance with mean absolute errors of 5.4 km, 0.5 cm, and 14.3 cm2 s−2 for eddy radius, amplitude, and kinetic energy, respectively. Then, the trained ensemble model is applied to independently invert the properties of eddies captured by an Argo-alone detection scheme, which yields high spatiotemporal consistency with their altimeter-captured counterparts. In particular, a portion of Argo-alone eddies is ∼25% smaller than altimeter-derived ones, indicating Argo’s unique capability of profiling weaker submesoscale eddies. Sea surface temperature and chlorophyll data are further applied to validate the reliability of eddies identified and characterized by the Argo-only algorithm. This new methodology effectively complements that of altimetry in eddy detection and can be expanded to estimate other physical/biochemical eddy variables from a variety of in situ observations.

Significance Statement
Despite thousands of eddies being routinely identified on a daily basis, it has been recognized that a substantial portion of eddies may still be missed due to inadequate sampling of altimeter constellations. Taking advantage of eddy’s correlation between surface and interior, a considerable number of eddies are discovered for the first time through an Argo-based eddy identification scheme. Here, we propose a new methodology to independently infer these recaptured eddies’ surface properties from their vertical signals through an “interior-to-surface” inversion process. The inferred eddy properties are verified by the spatiotemporal consistency with those derived from altimetry. Since Argo is capable of profiling smaller and weaker eddies, the proposed methodology significantly complements and expands that of altimetry in eddy observation.
Evaluating Aboriginal and Torres Strait Islander Social and Emotional Wellbeing services: A collective case study in Far North Queensland
Authors: Furst Mary Anne , McDonald Tina , McCalman Janya , Salinas-Perez Jose , Fagan Ruth , Lee Hong Anita , Nona Merrissa , Saunders Vicki , Salvador-Carulla Luis 
Published: April 2024

Background: Access to a coordinated range of strengths-based, culturally appropriate community-led primary mental health and Social and Emotional Wellbeing services is critical to the mental health and wellbeing of young Aboriginal and Torres Strait Islander people, and is a policy commitment of the Australian government. However, complex and fragmented service networks and a lack of standardised service data are barriers in identifying what services are available and what care they provide. Method: A standardised service classification tool was used to assess the availability and characteristics of Social and Emotional Wellbeing services for young Aboriginal and Torres Strait Islander people in two regions in Queensland, Australia. Results: We identified a complex pattern of service availability and gaps in service provision. Non-Indigenous non-governmental organisations provided a significant proportion of services, particularly ‘upstream’ support, while Aboriginal Community Controlled Organisations were more likely to provide ‘downstream’ crisis type care. Most services provided by the public sector were through Child Safety and Youth Justice departments. Conclusions: Our findings demonstrate the complexity of current networks, and show that non-Indigenous organisations are disproportionately influential in the care received by young Aboriginal and Torres Strait Islander people, despite community goals of self-determination, and government commitment to increasing capacity of Aboriginal Community Controlled Organisations to support their local communities. These findings can be used to support decision making and planning.
Economic Policy Uncertainty and Household Consumer Confidence: Evidence from Indian Household Data
Authors: Rooj Debasis , Banerjee Anurag , Sengupta Reshmi 
Published: April 2024

This article aims to analyse how economic policy uncertainty (EPU) affects consumer confidence in India. The study uses unit-level observations on consumer confidence from the Reserve Bank of India’s Consumer Confidence Survey from June 2016 to May 2021. Exploring the variations in consumer confidence across several cities in India, the regression exercise shows how India-specific EPU and global EPU impact consumer confidence. Findings from the study show that EPU has a negative and significant impact on consumers’ perceptions and outlook about the economy. The results also show that the effect of global EPU is stronger, compared to India-specific EPU. A disaggregated analysis is also conducted to analyse the impact of EPU on several consumer confidence indicators, such as the perception and the outlook on household income, spending, employment and general price levels. Contrary to the current literature, this study uses individual-level responses on consumer confidence from survey data and examines the role of EPU on consumer sentiments. Overall, the findings suggest that news-based economic policy-related uncertainty shocks negatively affect households’ sentiments. Moreover, a disaggregated analysis is also conducted for several consumer confidence indicators such as perception and outlook on household income, spending, employment and general price levels. JEL Codes: E66, E71, H31
Dual Language Education and Academic Growth
Authors: Johnson Angela 
Published: April 2024

Background or Context: Dual language education aims to foster the development of bilingualism, biliteracy, sociocultural competence, and academic skills in all school subjects. Early correlational research suggests that participation in dual language education is associated with higher achievement. Recent studies leveraged more comprehensive sets of baseline characteristics and found that dual language students improved their achievement status more than other students. A major limitation to these studies is their lack of ability to model within-student growth. Thus, we lack evidence on the relationship between dual language education and growth trajectories within and across grades. Purpose: This paper reports academic achievement and growth in grades 2 through 8 for Hispanic participants and nonparticipants of a Spanish–English dual language program. It extends the literature by providing novel evidence on seasonal patterns of learning for multilingual students across the elementary and middle grades. Research Design: Applying a piecewise multilevel model to rich assessment data on a large sample of Hispanic students in a district in the Midwest, I compare the math and English reading growth rates of participants to nonparticipants of a dual language (DL) program. By separately specifying growth terms for each school year and summer, I test whether any differences in growth rates between DL and non-DL students expand, stay the same, or diminish across grade levels. Conclusion: Dual language participants started second grade with lower achievement than nonparticipants. In math, dual language participants grew more than nonparticipants during each year in grades 2 to 5 but lost more learning during summers. In English reading, dual language participants grew more during some school years. These findings suggest summer learning opportunities are crucial for addressing achievement disparities.
Is ultrafiltration volume a predictor of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass?
Authors: Gerami Hamid , Sajedianfard Javad , Ghasemzadeh Bahram , AnsariLari Maryam 
Published: April 2024

Introduction Intraoperative ultrafiltration (UF) is a procedure used during cardiopulmonary bypass (CPB) to reduce haemodilution and prevent excessive blood transfusion. However, the effect of UF volume on acute kidney injury (AKI) is not well established, and the results are conflicting. Additionally, there are no set indications for applying UF during CPB. Methods This retrospective study analysed 641 patients who underwent coronary artery bypass graft (CABG) surgery with CPB. Perioperative parameters were extracted from the patients’ records, and the UF volume was recorded. Acute Kidney Injury Network classification was used to define AKI. Univariable and multivariable logistic regression models were used to predict AKI while controlling for confounding factors. Results The study enrolled patients with a mean age of 58.8 ± 11.1 years, 39.2% of whom were female. AKI occurred in 22.5% of patients, with 16.1% (103) experiencing stage I and 6.4% (41) experiencing stage II. The results showed a significant association between UF volume and the risk of developing AKI, with higher UF volumes associated with a higher risk of AKI. In the multivariable analysis, the other predictors of AKI included age, lowest mean arterial pressure (MAP), and red blood cell (RBC) transfusion during CPB. Conclusion The predictors of postoperative AKI in coronary CABG patients were the volume of UF, age, MAP, and blood transfusion during CPB.