bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐world safety of neurohormonal antagonist initiation among older adults following a heart failure hospitalization
Authors: Goyal Parag , Zullo Andrew R. , Gladders Barbara , Onyebeke Chukwuma , Kwak Min Ji , Allen Larry A. , Levitan Emily B. , Safford Monika M. , Gilstrap Lauren 
Published: February 2023

AbstractAimsTo optimize guideline‐directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established.Methods and resultsWe conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008–2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time‐varying exposure) and all‐cause mortality, all‐cause rehospitalization, and fall‐related adverse events over the 90 day period following hospitalization. We calculated inverse probability‐weighted hazard ratios (IPW‐HRs) with 95% confidence intervals (CIs) comparing initiation of 1, 2, or 3 NHAs vs. 0. The IPW‐HRs for mortality were 0.80 [95% CI (0.78–0.83)] for 1 NHA, 0.70 [95% CI (0.66–0.75)] for 2, and 0.94 [95% CI (0.83–1.06)] for 3. The IPW‐HRs for readmission were 0.95 [95% CI (0.93–0.96)] for 1 NHA, 0.89 [95% CI (0.86–0.91)] for 2, and 0.96 [95% CI (0.90–1.02)] for 3. The IPW‐HRs for fall‐related adverse events were 1.13 [95% CI (1.10–1.15)] for 1 NHA, 1.25 [95% CI (1.21–1.30)] for 2, and 1.64 [95% CI (1.54–1.76)] for 3.ConclusionsInitiating 1–2 NHAs among older adults within 90 days of HFrEF hospitalization was associated with lower mortality and lower readmission. However, initiating 3 NHAs was not associated with reduced mortality or readmission and was associated with a significant risk for fall‐related adverse events.
Comparison of the Sensitivity of Tetragonisca angustula (Apidae-Meliponini) and Apis mellifera (Apidae-Apini) to Three Insecticides (Malathion, Imidacloprid, and Fipronil) Used in Costa Rica
Authors: Mena Freylan , Berrocal Silvia , Solano Karla , Herrera Eduardo , Gallardo Mario , Jiménez Katherine , Aguilar Ingrid , Pinnock-Branford Margaret 
Published: February 2023

Abstract
The decline of insect pollinators is a significant concern within the current biodiversity crisis. The paradox between the benefits that these animals represent to humans and the evidence of human activities driving their extinction calls for the urgent protection of bees. To address the role of chemical pollution in this scenario, we assessed the acute toxicity as well as four biomarker responses (cholinesterase [ChE], glutathione S-transferase, catalase, and lipid peroxidation [LPO]) elicited by dietary 24-h exposure to three insecticides (malathion, imidacloprid, and fipronil) on the stingless neotropical bee Tetragonisca angustula and the honeybee Apis mellifera. Malathion was the most toxic substance to both species, with 48-h median lethal doses (LD50s) of 0.25 ng/bee to A. mellifera and 0.02 ng/bee to T. angustula. Fipronil was also highly toxic and presented a similar toxicity to both species, with 48-h LD50s of 0.5 ng/bee (A. mellifera) and 0.4 ng/bee (T. angustula). Imidacloprid had the lowest acute toxicity with a 48-h LD50 of 29 ng/bee for A. mellifera, whereas T. angustula tolerated exposure higher than 35 ng/bee. Apparent biomarker responses were observed in bees of both species that survived exposure to higher concentrations of malathion (ChE inhibition) and fipronil (increased LPO). Our results suggest that specific sensitivity to insecticides varies greatly among compounds and pollinator species, but the use of different representative species can facilitate the prioritization of substances regarding their risk to pollinators. Further research is necessary to better characterize the risk that pesticides represent in neotropical agricultural landscapes. Environ Toxicol Chem 2023;42:1022–1031. © 2023 SETAC
Variation in the Chemical Sensitivity of Earthworms from Field Populations to Imidacloprid and Copper
Authors: Duque Tomás , Nuriyev Rufat , Römbke Jörg , Schäfer Ralf B. , Entling Martin H. 
Published: February 2023

Abstract
The chemical risk of pesticides for nontarget soil macroorganisms has mainly been assessed using the compost earthworm Eisenia fetida. However, E. fetida does not occur in agroecosystems, and it is generally less sensitive than other earthworm species. Thus, the extrapolation of its response to pesticides to other earthworm species may lead to uncertainties in risk assessment. Because toxicity data for other earthworms are scarce, we assessed the chemical sensitivity of five species (Allolobophora chlorotica, Aporrectodea caliginosa, Aporrectodea longa, Aporrectodea rosea, and Lumbricus rubellus) from different habitats (forests, wetlands, and grasslands), as well as E. fetida, to imidacloprid and copper in single-species acute toxicity tests. In addition, we examined the relationship between earthworm traits (ecotype and weight), habitat characteristics (ecosystem type and soil pH), and chemical sensitivity. The lower limits of the hazardous concentration affecting 5% (HC5) of species were 178.99 and 0.32 mg active ingredient/kg dry weight for copper and imidacloprid, respectively. Some concentrations that have been measured in European agroecosystems for both pesticides were above the HC5s, indicating toxic risks for these organisms. Furthermore, soil pH from the sampling habitat played a significant role, with earthworms sampled from extremely acidic soils being less sensitive to copper than earthworms from neutral soils. In addition, endogeic earthworms were more sensitive to imidacloprid than epigeic earthworms. This may translate to changes in soil functions such as bioturbation, which is mainly carried out by endogeic earthworms. Our results suggest that risk assessment should include a wider range of earthworms covering different habitats and ecosystem functions to achieve a better protection of the biological functions carried out by these key soil organisms. Environ Toxicol Chem 2023;42:939–947. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Financial development, institutions, and economic growth nexus: A spatial econometrics analysis using geographical and institutional proximities
Authors: Ahmad Mahyudin , Law Siong Hook 
Published: February 2023

AbstractThis paper investigates the nexus between financial development (FD), institutions, and economic growth using a spatial autoregressive model on a panel dataset of 82 countries from 1990 to 2019. We measure the dependence between countries through geographical and institutional proximity. The latter has not been widely explored in the finance‐growth literature. The concept of institutional proximity proposes that countries with similar institutions will have similar levels of economic growth and larger spillovers once spatial effects of FD and institutional quality are controlled. Overall, our findings support this proposition, as FD and political institutions are shown to have significant positive effects on growth. However, the growth‐effect of FD becomes negative beyond a certain threshold. We also find significant positive spatial lag growth in the model, indicating the presence of indirect spillover effects of FD and institutions on the growth of neighbouring countries in both geographical and institutional spheres. Furthermore, the spatial growth model with the institutional proximity matrix exhibits a higher rate of convergence and larger size of spillover than the model with geographical proximity. These findings are robust to various model specifications, and the paper concludes with some policy recommendations.
2‐Deoxy‐D‐glucose simultaneously targets glycolysis and Wnt/β‐catenin signaling to inhibit cervical cancer progression
Authors: Su Min , Shan Shidong , Gao Yang , Dai Mengyuan , Wang Hua , He Can , Zhao Mengna , Liang Ziyan , Wan Shimeng , Yang Junyuan , Cai Hongbing 
Published: February 2023

AbstractCervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2‐Deoxy‐D‐glucose (2‐DG) is a glycolysis inhibitor that acts on hexokinase, the first rate‐limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2‐DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa. Cell function experiments revealed that 2‐DG significantly inhibited cell growth, migration, and invasion, and induced G0/G1 phase arrest at non‐cytotoxic concentrations. In addition, we found that 2‐DG down‐regulated Wingless‐type (Wnt)/β‐catenin signaling. Mechanistically, 2‐DG accelerated the degradation of β‐catenin protein, which resulted in the decrease of β‐catenin expression in both nucleus and cytoplasm. The Wnt agonist lithium chloride and β‐catenin overexpression vector could partially reverse the inhibition of malignant phenotype by 2‐DG. These data suggested that 2‐DG exerted its anti‐cancer effects on cervical cancer by co‐targeting glycolysis and Wnt/β‐catenin signaling. As expected, the combination of 2‐DG and Wnt inhibitor synergistically inhibited cell growth. It is noteworthy that, down‐regulation of Wnt/β‐catenin signaling also inhibited glycolysis, indicating a similar positive feedback regulation between glycolysis and Wnt/β‐catenin signaling. In conclusion, we investigated the molecular mechanism by which 2‐DG inhibits the progression of cervical cancer in vitro, elucidated the interregulation between glycolysis and Wnt/β‐catenin signaling, and preliminarily explored the effect of combined targeting of glycolysis and Wnt/β‐catenin signaling on cell proliferation, which provides more possibilities for the formulation of subsequent clinical treatment strategies.
Porous honeycomb film membranes enhance endothelial barrier integrity in human vascular wall bilayer model compared to standard track‐etched membranes
Authors: Ebrahim Neven A. , Mwizerwa Olive N. , Ekwueme Emmanuel C. , Muss Tessa E. , Ersland Erik E. , Oba Takahiro , Oku Keisuke , Nishino Masafumi , Hikimoto Daichi , Miyoshi Hayato , Tomotoshi Kimihiko , Neville Craig M. , Sundback Cathryn A. 
Published: February 2023

AbstractIn vitro vascular wall bilayer models for drug testing and disease modeling must emulate the physical and biological properties of healthy vascular tissue and its endothelial barrier function. Both endothelial cell (EC)‐vascular smooth muscle cell (SMC) interaction across the internal elastic lamina (IEL) and blood vessel stiffness impact endothelial barrier integrity. Polymeric porous track‐etched membranes (TEM) typically represent the IEL in laboratory vascular bilayer models. However, TEM stiffness exceeds that of diseased blood vessels, and the membrane pore architecture limits EC‐SMC interaction. The mechanical properties of compliant honeycomb film (HCF) membranes better simulate the Young's modulus of healthy blood vessels, and HCFs are thinner (4 vs. 10 μm) and more porous (57 vs. 6.5%) than TEMs. We compared endothelial barrier integrity in vascular wall bilayer models with human ECs and SMCs statically cultured on opposite sides of HCFs and TEMs (5 μm pores) for up to 12 days. Highly segregated localization of tight junction (ZO‐1) and adherens junction (VE‐cadherin) proteins and quiescent F‐actin cytoskeletons demonstrated superior and earlier maturation of interendothelial junctions. Quantifying barrier integrity based on transendothelial electrical resistance (TEER), membranes showed only minor but significant TEER differences despite enhanced junctional protein localization on HCF. Elongated ECs on HCF likely experienced greater paracellular diffusion than blocky ECs on TEM. Also, larger populations of plaques of connexin 43 subunit‐containing gap junctions suggested enhanced EC‐SMC communication across the more porous, thinner HCF. Compared with standard TEMs, engineered vascular wall bilayers cultured on HCFs better replicate physiologic endothelial barrier integrity.
GalaxyDock2‐HEME: Protein–ligand docking for heme proteins
Authors: Lee Changsoo , Yang Jinsol , Kwon Sohee , Seok Chaok 
Published: February 2023

AbstractPrediction of protein–ligand binding poses is an essential component for understanding protein–ligand interactions and computer‐aided drug design. Various proteins involve prosthetic groups such as heme for their functions, and adequate consideration of the prosthetic groups is vital for protein–ligand docking. Here, we extend the GalaxyDock2 protein–ligand docking algorithm to handle ligand docking to heme proteins. Docking to heme proteins involves increased complexity because the interaction of heme iron and ligand has covalent nature. GalaxyDock2‐HEME, a new protein–ligand docking program for heme proteins, has been developed based on GalaxyDock2 by adding an orientation‐dependent scoring term to describe heme iron‐ligand coordination interaction. This new docking program performs better than other noncommercial docking programs such as EADock with MMBP, AutoDock Vina, PLANTS, LeDock, and GalaxyDock2 on a heme protein–ligand docking benchmark set in which ligands are known to bind iron. In addition, docking results on two other sets of heme protein–ligand complexes in which ligands do not bind iron show that GalaxyDock2‐HEME does not have a high bias toward iron binding compared to other docking programs. This implies that the new docking program can distinguish iron binders from noniron binders for heme proteins.
Efficacy and safety of saroglitazar in real‐world patients of non‐alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience
Authors: Chaudhuri Sujit , Dutta Agnibha , Chakraborty Sunil Baran Das 
Published: February 2023

AbstractBackground and AimSaroglitazar, a dual PPAR α/γ agonist, is useful in management of NAFLD and diabetic dyslipidemia. Here, we report the safety and efficacy of saroglitazar in NAFLD patients with or without diabetes including compensated cirrhosis.MethodsPatients, started on saroglitazar 4 mg were prospectively evaluated for 52 weeks in a tertiary care center in Eastern India. Effectiveness was measured in terms of anthropometric measurements, fasting blood glucose, LFT, lipid profile, HbA1c, and elastography parameters (LSM and CAP) measured at baseline, 24, and 52 weeks. Adverse drug reactions were monitored.ResultsA total of 112 patients were enrolled in the study, of whom 63 patients were taken up for per‐protocol analysis. Mean age was 49.11 ± 11.09 years and 46(73%) were male. Thirty‐four (54%) were nondiabetic. Eleven patients had compensated cirrhosis. There was significant improvement of LSM from baseline (11.03 ± 7.19 kPa) to 24‐week (9.29 ± 6.39 kPa) and 52‐week (8.59 ± 6.35 kPa) values respectively (P < 0.001). Significant reduction was also seen in CAP values, ALT, AST, HbA1c, LDL, total cholesterol, and triglyceride values. There was no significant weight change along the study interval. Pruritus occurred in one patient who required treatment discontinuation and another patient had mild symptomatic loose motion.ConclusionsSaroglitazar is effective and safe in improving biochemical parameters and LSM and CAP values irrespective of weight reduction. It may be used in compensated cirrhotics with close monitoring for side effects.
Improved bounds for the oriented radius of mixed multigraphs
Authors: Babu Jasine , Benson Deepu , Rajendraprasad Deepak 
Published: February 2023

AbstractA mixed multigraph is an ordered pair with a set of vertices, a multiset of unordered and ordered pairs of vertices, respectively, called undirected and directed edges. An orientation of a mixed multigraph is an assignment of exactly one direction to each undirected edge of . A mixed multigraph can be oriented to a strongly connected digraph if and only if is bridgeless and strongly connected. For each , let denote the smallest number such that any strongly connected bridgeless mixed multigraph with radius can be oriented to a digraph of radius at most . We improve the current best upper bound of on to . Our upper bound is tight up to a multiplicative factor of 1.5 since, for every positive integer , there exists an undirected bridgeless graph of radius such that every orientation of it has a radius at least . We prove a marginally better lower bound, , for mixed multigraphs. While this marginal improvement does not help with asymptotic estimates, it clears a natural suspicion that, like, undirected graphs, may be equal to even for mixed multigraphs. En route, we show that if each edge of lies in a cycle of length at most , then the oriented radius of is at most . All our proofs are constructive and lend themselves to polynomial‐time algorithms.
Reducing the use of nil per os past midnight for inpatient diagnostic and therapeutic procedures: A quality improvement initiative
Authors: Hommel Erin , Sissoho Fatoumatta B. , Chang Karen , Suthar Krishna 
Published: February 2023

AbstractBackgroundPre‐procedural fasting (nil per os [NPO]) is a commonly implemented protocol to prevent aspiration during certain diagnostic and therapeutic procedures. However, evidence suggests aspiration risk is quite low. Current guidelines support a reduced fasting duration before procedures necessitating anesthesia or sedation, but many health systems persist in the use of NPO past midnight.ObjectiveWe aimed to reduce the use of NPO p MN before inpatient diagnostic and therapeutic procedures necessitating anesthesia or sedation by 50% within 6 months.Design, Setting and ParticipantsWe performed a quality improvement initiative at a single academic health system in Southeast Texas. We include the experience of patients of all ages across 4 affiliated hospitals (one main academic hospital and three community satellite hospitals).InterventionAn interprofessional team was convened to review best practices and oversee this quality improvement initiative. Diagnostic imaging protocols previously requiring NPO were amended to reflect evidence‐based fasting requirements. A pre‐procedure clear liquid diet was also implemented.Main Outcome and MeasuresWe describe the steps to implementation, feasibility of implementation as described through key process measures, and the safety of implementation (balancing measures).ResultsNPO requirements were removed from 70% of existing diagnostic imaging and therapeutic orders. After these amended protocols and the implementation of a pre‐procedure clear liquid diet, we displayed an immediate 50% reduction in NPO past midnight usage. Further stakeholder engagement/education and targeted interventions reduced NPO past midnight usage to only 33% of pre‐procedural diet orders. Surgery remains the most common indication for continued use of NPO. Aspiration events and procedural delays were rare.
Quantitative analysis of phthalates using a pyrolyzer gas chromatography/mass spectrometry method
Authors: Lee Donghyo , Kwon Jungmin , Choi Choongryul , Jeon Jinkyung , Lee Gyeonghweon 
Published: February 2023

AbstractA pyrolyzer gas chromatography/mass spectrometry (GC/MS) method eliminates toxic solvents that burden our environment and can address the crucial problem of the solvent extraction GC/MS method. The purpose of this study is to establish an efficient quantitative analysis method for 10 phthalates that are regulated by the several governments. A change of concentrations over time for phthalates and internal standards was measured to verify the feasibility of using an auto sampler that facilitates analyzing multiple samples. Both standards maintained constant concentrations over the appropriate time for analysis. A certified reference material under the auspices of the Korea Research Institute of Standards and Science was used to verify the calibration curve obtained by the pyrolyzer GC/MS method, and a deviation was considered similar to the solvent extraction GC/MS method. Then, the limit of detection and limit of quantitation values were confirmed for various consumer products. To verify the reliability of the method, a comparative test with several accredited testing institutes was conducted, and the results were within the standard deviations of the results provided by the institutes. These results indicate that the pyrolyzer GC/MS method can be used in not only screening but also in accurate quantitative analysis.
Localization of cyclopropyl groups and alkenes within glycerophospholipids using gas‐phase ion/ion chemistry
Authors: Shenault De'Shovon M. , McLuckey Scott A. , Franklin Elissia T. 
Published: February 2023

AbstractShotgun lipid analysis using electrospray ionization tandem mass spectrometry (ESI‐MS/MS) is a common approach for the identification and characterization of glycerophohspholipids GPs. ESI‐MS/MS, with the aid of collision‐induced dissociation (CID), enables the characterization of GP species at the headgroup and fatty acyl sum compositional levels. However, important structural features that are often present, such as carbon–carbon double bond(s) and cyclopropane ring(s), can be difficult to determine. Here, we report the use of gas‐phase charge inversion reactions that, in combination with CID, allow for more detailed structural elucidation of GPs. CID of a singly deprotonated GP, [GP − H]−, generates FA anions, [FA − H]−. The fatty acid anions can then react with doubly charged cationic magnesium tris‐phenanthroline complex, [Mg(Phen)3]2+, to form charge inverted complex cations of the form [FA − H + MgPhen2]+. CID of the complex generates product ion spectral patterns that allow for the identification of carbon–carbon double bond position(s) as well as the sites of cyclopropyl position(s) in unsaturated lipids. This approach to determining both double bond and cyclopropane positions is demonstrated with GPs for the first time using standards and is applied to lipids extracted from Escherichia coli.
High‐Affinity Adsorbent with Honeycomb Structure for Efficient Acteoside Separation
Authors: Xiong Feng , Hao Yanyan , Xu Helin , Li Xueqin , Sun Yu , Liu Jiaxing , Chen Xi , Wei Zhong 
Published: February 2023

AbstractIn this study, a series of adsorbents with honeycomb structure that hyperbranched polyethyleneimine (PEI) functionalized carboxymethyl chitosan (CMC/PEI) are successfully designed for acteoside (ACT) separation. The microstructures of adsorbents are adjusted to optimum by changing the molecular weight and addition amount of PEI. The scanning electron microscope (SEM) and N2 adsorption‐desorption experiment results show that CMC/PEI‐70000‐4.5g presents the honeycomb structure with the highest specific surface area and the largest pore volume. The honeycomb structure has the multiple internal cavities, which provide sufficient space for accommodating and adsorbing ACT molecules, improving the adsorption capacity. Furthermore, this work introduces PEI on the inner and outer surface of pores and forms an amino layer, which has high‐affinity for ACT molecules and realizes the excellent selectivity. Therefore, CMC/PEI‐70000‐4.5g shows the highest adsorption capacity of 125.67 mg g−1 and selectivity of 5.38. The adsorption process of ACT can be fitted by pseudo‐second‐order kinetics, intraparticle diffusion, and Langmuir isotherm models. High‐affinity (hydrogen bond, hydrophilic attraction, and Van der Waals force) is proposed as the main driving forces for adsorption between CMC/PEI‐70000‐4.5g and ACT. This work provides a strategy to synthesize the adsorbents with honeycomb structure for bioactive components separation from natural products.