bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer effects of ikarugamycin and astemizole identified in a screen for stimulators of cellular immune responses
Authors: Zhang Shuai , Zhao Liwei , Guo Mengfei , Liu Peng , Li Sijing , Xie Wei , Tian Ai-Ling , Pol Jonathan G , Chen Hui , Pan Hui , Mao Misha , Li Yumei , Zitvogel Laurence , Jin Yang , Kepp Oliver , Kroemer Guido 
Published: July 2023

BackgroundMost immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations.MethodFor immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature precursors present MHC (major histocompatibility complex) class I-restricted antigen to a T-cell hybridoma that then secretes interleukin-2 (IL-2).ResultsThe screening of three drug libraries relevant to known signaling pathways, FDA (Food and Drug Administration)-approved drugs and neuroendocrine factors yielded two major hits, astemizole and ikarugamycin. Mechanistically, ikarugamycin turned out to act on DCs to inhibit hexokinase 2, hence stimulating their antigen presenting potential. In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. Astemizole induced the production of IL-2 and interferon-γ (IFN-γ) by CD4+and CD8+T cells both in vitro and in vivo. Both ikarugamycin and astemizole improved the anticancer activity of the immunogenic chemotherapeutic agent oxaliplatin in a T cell-dependent fashion. Of note, astemizole enhanced the CD8+/Foxp3+ratio in the tumor immune infiltrate as well as IFN-γ production by local CD8+T lymphocytes. In patients with cancer, high H1R1 expression correlated with low infiltration by TH1 cells, as well as with signs of T-cell exhaustion. The combination of astemizole and oxaliplatin was able to cure the majority of mice bearing orthotopic non-small cell lung cancers (NSCLC), then inducing a state of protective long-term immune memory. The NSCLC-eradicating effect of astemizole plus oxaliplatin was lost on depletion of either CD4+or CD8+T cells, as well as on neutralization of IFN-γ.ConclusionsThese findings underscore the potential utility of this screening system for the identification of immunostimulatory drugs with anticancer effects.
Self-evidence-based digital care programme improves health-related quality of life in adults with a variety of autoimmune diseases and long COVID: a retrospective study
Authors: Bundy Nicole , De Jesus Mackenzie , Lytle Millennia , Calabrese Leonard , Gobin Christina , Dyhrberg Mette 
Published: July 2023

ObjectiveTo retrospectively investigate the feasibility and impact on health-related quality of life (HRQoL) of a digital care programme (DCP) designed to guide personalised diet and integrative interventions in a variety of autoimmune diseases and long COVID.MethodsAdults who participated in the DCP between April 2020 and June 2022, and for whom baseline (BL) and end-of-programme (EOP) Patient-Reported Outcomes Measurement Information System (PROMIS) scores were available, were included in this retrospective study. Changes from BL to EOP were calculated using standardised T-scores.ResultsTwo hundred two adults between 17 and 82 years old were included. Diagnoses included: rheumatoid arthritis (20.1%); long COVID (14.9%); psoriatic arthritis (10.9%); psoriasis (8.9%); systemic lupus erythematosus (6.4%); inflammatory bowel disease (5.9%); multiple sclerosis (5.9%); ankylosing spondylitis (5.4%) and other (23.3%). On average, individuals entered observations 7.6 times/day on 86% of programme days, attended 14 coach sessions and completed the programme in an average of 17.2 weeks. Statistically significant improvements were seen in all 10 PROMIS domains analysed. Individuals with higher severity of compromise at BL experienced greater average improvements than all-comers in all 10 PROMIS domains included.ConclusionAn evidence-based DCP that uses patient data to help identify hidden symptom triggers and guide personalised dietary and other non-pharmacological interventions was associated with a high level of engagement and adherence and statistically significant, clinically meaningful improvements in HRQoL. Those with the least favourable PROMIS scores at BL experienced the greatest improvements.
Comment on “Noether symmetry analysis in Chameleon field cosmology”
Authors: Paliathanasis Andronikos 
Published: July 2023

We review the Noether symmetry analysis for the Chameleon cosmology presented in R. Bhaumik, S. Dutta and S. Chakraborty, Int. J. Mod. Phys. A 37, 2250018 (2022). We show that the classification problem for the field equations in Chameleon cosmology is still open.
Computational predictions of CeO2 using HSE03: An ab initio investigation
Authors: Tse Geoffrey 
Published: July 2023

In this paper, the structural, electronic, optical, and mechanical properties of the hexagonal Ceria CeO2 have been studied with hybrid functionals. The rare-earth oxide compound exhibits a [Formula: see text] indirect bandgap, with a bandgap energy of 2.706 eV. The electronic bandstructure has been described in detail in terms of orbital states. The rare-earth Ce f orbital contributes to the conduction band and transitional Ce d, O s electron orbitals to the valence bands. Our optical spectra also fully explain the structural and electronic properties of the material. (i.e. atomic-bonding, density or capacity inside Cerium oxide system, and the excitation of electrons to transfer from valence O 2p to conduction Ce f orbitals, leading to orbital hybridizations, etc.). Finally, our elastic coefficients verify the mechanical stability of our Ceria system. Our bandgap energy found is in excellent agreement with the experimental data. A high optical absorption coefficient of up to [Formula: see text] cm[Formula: see text] is found, indicating a good material absorption within the ultraviolet C (UVC) range. The findings of this work would be beneficial to both theoretical and experimental research works to explore the potential applications of CeO2 in optoelectronics devices.
Modeling the Landscape of Histone-Mutant Pediatric High-Grade Gliomas: A Study in Partner Alterations
Authors: Lubanszky Evan , Hawkins Cynthia 
Published: July 2023

Summary:Pediatric high-grade gliomas represent a group of deadly, heterogeneous tumors, often driven by histone mutations and the accumulation of clonal mutations, correlating with different tumor types, locations, and age of onset. In this study, McNicholas and colleagues present 16 in vivo models of histone-driven gliomas to investigate subtype-specific tumor biology and treatment options.See related article by McNicholas et al., p. 1592 (7).
Characterizing the Immune Microenvironment and Neoantigen Landscape of Hürthle Cell Carcinoma to Identify Potential Immunologic Vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald , Xu Bin , Morris Luc G.T. , Chan Timothy A. 
Published: July 2023

Hürthle cell carcinoma (HCC) is a rare type of thyroid cancer with high rates of distant metastasis and recurrence. Along with the scarcity of effective systemic therapies for HCC, these factors contribute to poor clinical outcomes. The immunologic features of HCC are poorly defined and response rates with immune checkpoint blockade have not been reported. A more comprehensive understanding of the immune landscape and factors that predict response to checkpoint inhibitors is needed.
We performed RNA sequencing on 40 tumors to characterize the neoantigen landscape and immune microenvironment of HCC. We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction and correlated these to genetic features such as tumor mutation burden, neoantigen burden, mitochondrial mutations, and LOH from chromosomal uniparental disomy. Finally, immune profiles of patients with recurrence were compared with those of patients without recurrence.
HCC tumors exhibited low levels of immune infiltration, with the more aggressive widely invasive phenotype associated with more immune depletion. There was a negative correlation between tumor mutation burden, neoantigen burden, programmed cell death ligand 1 (PD-L1) expression, and the immune infiltration score. HCC tumors that exhibited a global LOH from chromosomal uniparental disomy or haploidization had the lowest level of immune infiltration. HCC tumors that recurred displayed an immune-depleted microenvironment associated with global LOH and aerobic glycolysis.
These findings offer new insights into the functional immune landscapes and immune microenvironment of HCC. Our data identify potential immunologic vulnerabilities for these understudied and often fatal cancers.

Significance:
The immune landscape of HCC is poorly defined and response rates to immunotherapy have not been reported. The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.
Expanding knowledge of American Cerambycidae (Coleoptera): new species, new records, and morphological variations
Authors: Bezark Larry G. , Santos-Silva Antonio 
Published: July 2023

Four new species are described: Xystochroma luteotarsis sp. nov. (Cerambycinae, Callichromatini), from Ecuador; Psyrassa tysoni sp. nov. (Cerambycinae, Elaphidiini), from Guatemala; Bisaltes (Bisaltes) lateralis sp. nov. (Lamiinae, Apomecynini), from Ecuador; and Nagma hovorei sp. nov. (Lamiinae, Calliini), from Ecuador. A key to species of Xystochroma Schmidt, 1924 is provided and Psyrassa tysoni sp. nov. is included in a previous key. Variation in the pubescent pattern of Rosalba strandi (Breuning, 1943) is reported and the species is newly recorded for Paraguay. Chromatic variation in Cyrtinus umbus Martins & Galileo, 2009 (Lamiinae, Cyrtinini) is provided and the species is redescribed based on a dark specimen; a new province record (Puntarenas, Costa Rica) and a new country record (Panama) are included. Chromatic variation and sexual dimorphism in Phaea quadrimaculata Wappes & Santos-Silva, 2021 (Lamiinae, Tetraopini) is reported, and a new Mexican state record (Oaxaca) is provided.
Background Medical Therapy and Clinical Outcomes From the VICTORIA Trial
Authors: Ezekowitz Justin A. , McMullan Ciaran J. , Westerhout Cynthia M. , Piña Ileana L. , Lopez-Sendon Jose , Anstrom Kevin J. , Hernandez Adrian F. , Lam Carolyn S.P. , O’Connor Christopher M. , Pieske Burkert , Ponikowski Piotr , Roessig Lothar , Voors Adriaan A. , Koglin Joerg , Armstrong Paul W. , Butler Javed ,   for the VICTORIA Study Group
Published: July 2023

BACKGROUND:
We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo.

METHODS:

We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dose-corrected adherence (indication-corrected adherence+≥50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and
P
interaction
are reported.

RESULTS:
Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indication-corrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity.

CONCLUSIONS:
Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02861534.
Funding High-poverty School Districts: Federal Policy Tools and the Limits of Incentives
Authors: Gordon Nora , Reber Sarah 
Published: July 2023

Abstract
What can the federal government do to help ensure that the public schools attended by children living in poverty have enough resources to serve their students? In this brief, we describe existing federal efforts to support education spending in high-poverty districts, discuss their limitations, and suggest alternative approaches for federal policy. We focus especially on the Education Finance Incentive Grant (EFIG) formula—a part of the compensatory Title I grant program designed to encourage changes to state school finance policy—and show that the incentives embedded in the formula are in fact negligible; revising the formula to be more effective would be difficult. Further, any attempt to incentivize desirable state policy faces a fundamental trade-off: Such policy can reinforce inequality because districts in states that do not respond to the incentives by adopting desirable policies also do not receive (as much) federal funding. We argue that federal policy should be more attentive to state fiscal capacity because it is an important determinant of district-level school spending, and the federal government is uniquely positioned to address between-state inequality.
How to Start a Request? A Contrastive Study of Alerters in Spanish by Speakers of L1 Spanish and L1 French
Authors: Marsily Aurélie , De Cock Barbara 
Published: July 2023

Abstract
The formulation of requests has been widely studied in pragmatics, both within a (variety of) language and from a contrastive perspective. In this study, we will show the specific role of alerters (elements that precede the request head act and that serve to get the attention of the hearer on the request) in request formulation, comparing L1 speakers of Spanish and L2 speakers of Spanish with L1 French in Discourse Completion Tests and Naturalised Interactions. In doing so, we contribute to the contrastive pragmatic study of both languages. Our data reveal that there are statistically significant differences in the use of alerters from Spanish L1 and L2 speakers in the DCTs but not in the Naturalised Interactions. Alerters occur with rather similar frequencies in both groups, but there are qualitative differences as to which forms are adopted. At the methodological level, we highlight that data obtained from both groups’ DCTs vs. Naturalised Interactions show different results, thus underlining the importance of combined methods for contrastive pragmatics research.
Sutureless valves versus aortic root enlargement for aortic valve replacement in small aortic annulus: A systematic review and pooled analysis
Authors: Agarwal Rajat , Arnav Amiy , Ranjan Ashis , Mudgal Shiv , Singh Dharmendra 
Published: July 2023

Background Very few studies provide direct comparisons between aortic root enlargement and sutureless valve implantation in patients with a small aortic annulus who underwent aortic valve replacement. This study aims to provide comparative outcomes between the two in such a subset of patients, through a systematic review and pool analysis. Methods The PubMed, Scopus and Embase databases were searched using the appropriate terms. The data from original articles mentioning aortic root enlargement and sutureless valves in a single or comparative study with another group of patients with a small aortic annulus were pooled and analyzed using descriptive statistics. Results Both cardiopulmonary bypass (68.4 vs. 125.03 min, p < 0.001) and aortic cross-clamp times were significantly shorter in the sutureless valve group, along with a concomitantly higher number of minimally invasive surgeries. The incidence of permanent pacemaker implantation (9.76% vs. 3.16%, p < 0.00001), patient prosthesis mis-match and paravalvular leak was significantly higher in the sutureless valve group. In comparison, the incidence of re-exploration for bleeding was higher in the aortic root enlargement group (5.27% vs. 3.16%, p < 0.02). The two groups had no differences in the duration of hospital stays or mortality. Conclusions Sutureless valves demonstrated a comparable hemodynamic outcome with aortic root enlargement in patients with a small aortic annulus. In addition to this, it greatly facilitated minimally invasive surgery. However, the high incidence of pacemaker implantation is still a concern for the widespread recommendation of sutureless valves, especially in young patients with a small aortic annulus.
Henri Maldiney dans les pas de François Cheng. La tradition de l'esthétique chinoise et la phénoménologie de l’art
Authors: Chen Jing , Ducard Dominique 
Published: July 2023

Résumé Comment et pourquoi le philosophe Henri Maldiney a puisé dans les textes de la tradition esthétique chinoise issue de la philosophie du Daoïsme et du Chan dans son approche phénoménologique de l’art. En quoi les ouvrages de l’écrivain et essayiste François Cheng, traducteur et médiateur, de par sa double culture, ont constitué pour lui une ressource textuelle et une source de réflexion. Notre article place ainsi le premier dans les pas du second pour montrer d’une part la mise en œuvre, par des opérations de citation, paraphrase, reformulation et corrélation, d’une lecture active et interprétative, d’autre part pour mettre en évidence le rapprochement effectué entre les deux conceptions théoriques. Au final il en ressort un éclairage mutuel des catégories de la pensée chinoise et des concepts phénoménologiques, qui renouvelle la compréhension des unes comme des autres.
Bioactivity Screening of Thirty Black Turmeric (Curcuma caesia Roxb.) Essential Oils Against Free Radicals and MDR Isolates
Authors: Khuntia Snehalata , Lenka Jyotirmayee , Dash Manaswini , Sahoo Bhaskar Chandra , Kar Basudeba , Sahoo Suprava 
Published: July 2023

Background Curcuma caesia Roxb. (Black turmeric) is a perennial medicinal herb belonging to the Zingiberaceae family that is endangered in Southeast Asia. It is treasured for its high-quality essential oil with tremendous medicinal and aromatic properties. In the present scenario, C. caesia Roxb. is an unexplored plant for drug discovery. Objectives The present study was undertaken to compare the bioactivities of Thirty C. caesia rhizomes and leaf oils collected from various eco-regions of Eastern India. Materials and Methods The comparative antioxidant and antimicrobial activities of leaf and rhizome essential oils from different eco-regions of Eastern India were assessed. The antioxidant activities were evaluated against standards like butylated hydroxytoluene (BHT) and ascorbic acid by the 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. Moreover, the essential oils were also evaluated for their antimicrobial activity using the broth micro-dilution assay for minimum inhibitory concentrations (MIC) against multidrug resistant strains. Results Leaf essential oils exhibited a considerable level of antioxidant potential as compared to rhizome essential oils and standard BHT. Furthermore, the essential oils also possessed a significant level of inhibitory activity against three multidrug-resistant (MDR) strains, such as Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae. The rhizome essential oils had shown the most effective antimicrobial activity against A. baumannii (MIC: 0.09 to 6.25 µg/mL) when compared with the positive control, ampicillin (MIC: 25 µg/mL). Conclusion The variability in bioactivities was greatly influenced by geographical origin. The identified accessions of C. caesia, that is, Cc 26 with better bioactivity potential, might be useful for formulating drugs in the future.
Projected health and economic outcomes of extending public funding of pharmacy services to include administration of Pneu23 and Td/Tdap immunizations by pharmacy practitioners in New Brunswick
Authors: Folkins Chris , Gorman-Asal Madeleine , Brewster Clark , Foster Rebecca , Gulliver Adrienne , Thomson Emily , Singh Paramdeep , Miah Pablo , Magalhaes Sandra , McDonald J. Ted 
Published: July 2023

Background: Although legislation permits New Brunswick pharmacy professionals to administer a wide range of immunizations, public funding for these services is currently limited to immunizations against influenza and COVID-19 and was recently extended to include pneumococcal immunization (Pneu23) in individuals aged 65 years or older. We used administrative data to project health and economic outcomes associated with the current Pneu23 program and with extension of public funding to include: 1) younger adults aged 19 years or older in the Pneu23 program, and 2) tetanus boosters (Td/Tdap). Methods: Two model scenarios were compared: a Physician-Only model in which physicians remain the only practitioners to administer publicly funded Pneu23 and Td/Tdap, and a Blended model in which this service is also provided by pharmacy professionals. Immunization rates by practitioner type were projected based on physician billing data accessed via the New Brunswick Institute for Research, Data and Training in conjunction with trends observed with influenza immunization by pharmacists. These projections were used along with published data to estimate health and economic outcomes under each model. Results: Public funding of Pneu23 (65+), Pneu23 (19+) and Td/Tdap (19+) administration by pharmacy professionals is projected to yield increased immunization rates and physician time savings compared with the Physician-Only model. Public funding of Pneu23 and Td/Tdap administration by pharmacy professionals in those aged ≥19 years would result in cost savings, owing primarily to productivity losses avoided in the working age population. Discussion: Increased immunization rates, physician time savings and cost savings may be realized if public funding were extended to include administration of Pneu23 in younger adults and Td/Tdap, by pharmacy practitioners.