bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilisation and barriers of social health protection program among its enrolled population of federally administrative areas, Pakistan
Authors: Farooqui Marium Amir , Nabeel Ali Khizar , Riaz Sonia 
Published: May 2024

ObjectivesThe objective of this research is to analyse the extent of utilisation and identify the barriers faced by individuals in the Federally Administrative Area of Pakistan concerning the Social Health Protection Programme.MethodsA cross-sectional study was carried out, enrolling permanent residents from Islamabad, Gilgit-Baltistan and Azad Kashmir. The sampling frame was provided by the Sehat Sahulat Programme (SSP) office in Islamabad, using a simple random sampling method. The study used the ‘WHO Health Survey 2002’ tool, which is validated, to assess the utilisation and barriers of the Social Health Protection Programme.ResultsThe study findings indicated that approximately 12% of the participants used the Social Health Protection Programme, while 6.5% experienced barriers in utilisation. The identified barriers were further classified into seeking (3%), reaching (0.25%) and receiving care (3.25%) barriers. A χ2test of association revealed significant statistical associations between card utilisation and sociodemographic factors such as age and level of education (p value <0.001). Additionally, statistically significant associations were observed with hospitalisation in the last year, duration and frequency of hospitalisation (p value <0.001). However, no statistically significant association was found between the utilisation of SSP and utilisation barriers.ConclusionThe SSP had a low utilisation ratio due to the fact that half of the enrolled households were satisfied with their health conditions and did not feel the need for hospitalisation.
Distinguishability of binary extreme-mass-ratio inspirals in low frequency band
Authors: Jiang Ye , Han Wen-Biao , Zhong Xing-Yu , Shen Ping , Luo Zi-Ren , Wu Yue-Liang 
Published: May 2024

AbstractThe inspiral of compact stellar objects into massive black holes are one of the main astrophysical sources for the Laser Interferometer Space Antenna (LISA) and Taiji. These extreme-mass-ratio inspirals (EMRIs) have great potential for cosmology and fundamental physics. A binary extreme-mass-ratio inspiral (b-EMRI) describes the case where binary black holes (BBHs) are captured by a supermassive black hole. The b-EMRIs serve as multi-band gravitational wave sources and provide insights into the dynamics of nuclei and tests of general relativity. However, if the b-EMRIs can be distinguished from the normal EMRIs or not is still not clear. In this work, with a few of assumptions, and using the Teukolsky equation, we calculate the approximate gravitational waves of b-EMRIs and assess their detectability by space-based detectors. We also decouple the secondary object information from the Teukolsky equation, enabling us to calculate the energy fluxes and generate the waveforms more conveniently. Variations in the quadrupole of the binary result in small but non-negligible changes in energy fluxes and waveforms, making it possible to distinguish b-EMRI signals with data analysis. This opens up the potential of using b-EMRIs to test gravity theories and for further astrophysical studies.
Terrorism: Interpol Global Policing Goals and SDGs
Authors: Mordeson John N. , Mathew Sunil 
Published: May 2024

In this paper, we determined how well an OECD country is achieving the Received Interpol goals with respect to the SDGs pertinent to them. We found that the Scandinavian countries were at the top in the achievement. In combatting terrorism in general, we found that the Scandinavian countries were at the top. We also show that the fuzzy similarity measure of the ranking of countries used by the SDGs relevant to terrorism compared with SDG 16 alone was high. Let [Formula: see text] and [Formula: see text] be rankings of a set [Formula: see text] and [Formula: see text] and [Formula: see text] the associated fuzzy subsets, respectively. Consider the similarity measures [Formula: see text] and [Formula: see text] [J. N. Mordeson and S. Mathew, Journal of Mahani Mathematical Research 13(1) (2024) 279–291]. Suppose that [Formula: see text] and [Formula: see text] are known, but [Formula: see text] is unknown. It is shown in the reference by J. N. Mordeson and S. Mathew [Mathematics of Uncertainty for Coping with World Challenges, Climate Change, World Hunger, Modern Slavery, Coronavirus, Human Trafficking (Springer, 2021)] that if [Formula: see text] is near [Formula: see text] then [Formula: see text] is near [Formula: see text] In this paper, a similar result for [Formula: see text] is shown.
A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors
Authors: Li Junyao , Luo Lanqing , He Jia , Yu Jinchao , Li Xinyan , Shen Xueying , Zhang Junxia , Li Sai , Karp Jeffrey M. , Kuai Rui 
Published: May 2024

Abstract
Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)–based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid–based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNβ than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy.
Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors.
Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Cocozaki Alexis , Chuong Edward B. , Bitler Benjamin G. 
Published: May 2024

Abstract
Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.
Long Noncoding RNA MSL3P1 Regulates CUL3 mRNA Cytoplasmic Transport and Stability and Promotes Lung Adenocarcinoma Metastasis
Authors: Shao Ming-Ming , Li Xin , Wei Rui-Qi , Chen Qing-Yu , Zhang Xin , Qiao Xin , Li Hui 
Published: May 2024

Abstract
Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long noncoding RNAs (lncRNA) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, an lncRNA referred to as a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrant expression of MSL3P1. Mechanistically, owing to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway and promotes tumor invasion and metastasis.
Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.
First record of Pyrgotidae (Diptera, Tephritoidea) from Uruguay with two new synonyms in the genus Leptopyrgota Hendel
Authors: Mello Ramon Luciano 
Published: May 2024

Pyrgotidae are a small family of Tephritoidea of worldwide distribution, whose larvae are known to be endoparasites in the abdomen of adult Scarabaeidae beetles. This study presents the first record of the family from Uruguay, represented by the Leptopyrgota albitarsis Aczél, 1956 from Treinta y Tres, Quebrada de los Cuervos. Based on the study of holotypes, the following synonymy is proposed: Leptopyrgota albitarsis Aczél, 1956 = Leptopyrgota definienda Bernardi, 1991, new synonym and L. liae Bernardi, 1991 new synonym. Photos of the holotypes of the three studied species are presented, for the first time.
Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis
Authors: Mukherjee Monica , Strom Jordan B. , Afilalo Jonathan , Hu Mo , Beussink-Nelson Lauren , Kim Jiwon , Addetia Karima , Bertoni Alain G. , Gottdiener John S. , Michos Erin D. , Gardin Julius M. , Shah Sanjiv J. , Freed Benjamin H. 
Published: May 2024

BACKGROUND:
Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions.

METHODS:
In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis.

RESULTS:
The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities.

CONCLUSIONS:
Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.
Overexpressed Trophoblast Glycoprotein Contributes to Preeclampsia Development by Inducing Abnormal Trophoblast Migration and Invasion Toward the Uterine Spiral Artery
Authors: Sun Lu , Shi Meiting , Wang Jian , Han Xiaoxue , Wei Jiachun , Huang Zhengrui , Yang Xiaofeng , Ding Yuzhen , Zhang Ping , He Andong , Liu Mengyuan , Yan Ruiling , Yang Xuesong , Li Ruiman , Wang Guang 
Published: May 2024

BACKGROUND:
Preeclampsia is a significant pregnancy disorder with an unknown cause, mainly attributed to impaired spiral arterial remodeling.

METHODS:
Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein). Pregnant rats were injected with TPBG-carrying adenovirus to detect preeclamptic features. HTR-8/SVneo cells transfected with a TPBG overexpression lentiviral vector were used in cell function experiments. The downstream molecular mechanisms of TPBG were explored using RNA sequencing and single-cell RNA sequencing data. TPBG expression was knocked down in the lipopolysaccharide-induced preeclampsia-like rat model to rescue the preeclampsia features. We also assessed TPBG’s potential as an early preeclampsia predictor using clinical plasma samples.

RESULTS:
TPBG emerged as a crucial differentially expressed gene, expressed specifically in syncytiotrophoblasts and extravillous trophoblasts. Subsequently, we established a rat model with preeclampsia-like phenotypes by intravenously injecting TPBG-expressing adenoviruses, observing impaired spiral arterial remodeling, thus indicating a causal correlation between TPBG overexpression and preeclampsia. Studies with HTR-8/SVneo cells, chorionic villous explants, and transwell assays showed TPBG overexpression disrupts trophoblast/extravillous trophoblast migration/invasion and chemotaxis. Notably, TPBG knockdown alleviated the lipopolysaccharide-induced preeclampsia-like rat model. We enhanced preeclampsia risk prediction in early gestation by combining TPBG expression with established clinical predictors.

CONCLUSIONS:
These findings are the first to show that TPBG overexpression contributes to preeclampsia development by affecting uterine spiral artery remodeling. We propose TPBG levels in maternal blood as a predictor of preeclampsia risk. The proposed mechanism by which TPBG overexpression contributes to the occurrence of preeclampsia via its disruptive effect on trophoblast and extravillous trophoblast migration/invasion on uterine spiral artery remodeling, thereby increasing the risk of preeclampsia.
Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study
Authors: Meng Xia , Li Shuya , Dai Hongguo , Lu Guozhi , Wang Weiwei , Che Fengyuan , Geng Yu , Sun Minghui , Li Xiyan , Wang Yongjun 
Published: May 2024

Background
Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset.

Methods
This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China.

Results
The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90.

Conclusions
It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China.

Clinical Trial Registration Information

NCT04915729 (
https://clinicaltrials.gov/study/NCT04915729
)
Edible insects as a sustainable protein source: a meta-analysis
Authors: Nasir S.Q. , Palupi E. , Nasution Z. , Ploeger A. , Susanto I. , Setiawan B. , Rimbawan R. , Jayanegara A. 
Published: May 2024

Abstract
With the global population set to reach 9.7 billion by 2050, posing a potential 75% increase in food demand, this study examined the viability of edible insects as a sustainable protein source compared with beef. Employing a meta-analysis approach, data were synthesized from studies conducted over the past 13 years, using Hedges’ d effect size and mixed model methods. The parameter values included the nutritional, environmental, and economic aspects of edible insects. Out of 10,119 articles screened, 222 were selected for analysis, revealing 135 different species. Subsequently, 10 species were selected, based on the most comprehensive data available, for mixed model analysis. Although the protein content of these 10 edible insect species was generally lower than that of beef, certain species exhibited amino acid scores surpassing those of beef. Edible insects also exhibited significantly higher calcium, iron, and zinc content compared with beef. Environmental aspects may enhance the value of edible insects as they exhibited greater advantages compared with beef. Despite some identified risks in incorporating edible insects into the diets of humans and animals, there remain potential areas for further investigation and development, such as addressing fat content, indigestible carbohydrate, availability, and sustainability aspects. Further research is required to promote local edible insect products as nutritious food and feed.
Effect of Turbulence on the Collision Rate between Settling Ice Crystals and Droplets
Authors: Sheikh M. Z. , Gustavsson K. , Lévêque E. , Mehlig B. , Pumir A. , Naso A. 
Published: May 2024

Abstract
In mixed-phase clouds, graupel forms by riming, a process whereby ice crystals and supercooled water droplets settling through a turbulent flow collide and aggregate. We consider here the early stage of the collision process of small ice crystals with water droplets and determine numerically the geometric collision kernel in turbulent flows (therefore neglecting all interactions between the particles and assuming a collision efficiency equal to unity), over a range of energy dissipation rate 1–250 cm2 s−3 relevant to cloud microphysics. We take into account the effect of small, but nonzero fluid inertia, which is essential since it favors a biased orientation of the crystals with their broad side down. Since water droplets and ice crystals have different masses and shapes, they generally settle with different velocities. Turbulence does not play any significant role on the collision kernel when the difference between the settling velocities of the two sets of particles is larger than a few millimeters per second. The situation is completely different when the settling speeds of droplets and crystals are comparable, in which case turbulence is the main cause of collisions. Our results are compatible with those of recent experiments according to which turbulence does not clearly increase the growth rate of tethered graupel in a flow transporting water droplets.
Quantifying Environmental Degradation through Renewable Energy, Financial Development and Economic Sustainability: Insights from Panel Quantile Regression Analysis
Authors: Mehmood Saqib , Kaewsaeng-on Rudsada 
Published: May 2024

The degradation of the environment is a global concern that needs serious attention, including the environmental Kuznets curve (EKC) hypothesis. This article examines the effects of renewable energy, financial development and economic sustainability on the environmental quality of newly industrialized countries (NICs) from 1998 to 2021 in light of the increasing severity of environmental problems associated with industrialization. This study utilized different panel cointegration estimation techniques and panel quantile regression (PQR) estimates to obtain robust findings by examining the variance of each quantile. The results of the cointegration tests confirm the long-run relationship among the variables. Nevertheless, the outcomes from the PQR unveiled that renewable energy negatively and significantly influences CO2 emissions in NICs, namely in the lower and middle quantiles (20th–50th). Financial development showed heterogeneity in the results of all the quantiles. It results in an increase in CO2 emissions from the 70th to 90th quantiles in NICs. The EKC hypothesis is relevant to these findings as this study presents the economic sustainability index, which postulates that when NICs achieve sustainability, they give greater importance to environmental preservation and sustainability. This shift is characterized by reduced emissions throughout all quantiles, ranging from the 10th to the 90th. Economic sustainability corresponds to the falling part of the U-shaped curve of the EKC, wherein sustainability gets priority, resulting in reduced CO2 emissions. Analogous results have been confirmed by comparing heterogeneous panel estimators; nonetheless, there was a significant variation in the intensity of their parameters. Moreover, the robustness analysis through quantile slope equality and symmetric quantiles tests proved legitimate results. The study’s findings offer policymakers with valuable policy recommendations. JEL Codes: C1, F36, F43, O44, Q56