bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Sweep Experiments on a Heterogeneous Phase Composite System Based on Branched-Preformed Particle Gel in High Water-Cut Reservoirs after Polymer Flooding
Authors: Zhang Xianmin , Zhang Yiming , Liu Haicheng , Li Shanshan , Liu Lijie
Published: April 2023

Heterogeneous phase composite (HPC) flooding technology that is based on branched-preformed particle gel (B-PPG) is an important technology for enhancing oil recovery in high water-cut reservoirs. In this paper, we conducted a series of visualization experiments under the condition of developed high-permeability channels after polymer flooding, with respect to well pattern densification and adjustment, and HPC flooding and its synergistic regulation. The experiments show that for polymer-flooded reservoirs, HPC flooding can significantly reduce the water cut and increase oil recovery, but that the injected HPC system mainly advances along the high-permeability channel with limited sweep expansion. Furthermore, well pattern densification and adjustment can divert the original mainstream direction, which has a positive effect on HPC flooding, and can effectively expand the sweeping range under the synergistic effect of residual polymers. Due to the synergistic effect of multiple chemical agents in the HPC system, after well pattern densification and adjustment, the production time for HPC flooding with the water cut lower than 95% was significantly prolonged. In addition, conversion schemes, in which the original production well is converted into the injection well, are better than non-conversion schemes in terms of expanding sweep efficiency and enhancing oil recovery. Therefore, for well groups with obvious high-water-consuming channels after polymer flooding, the implementation of HPC flooding can be combined with well pattern conversion and intensification in order to further improve oil displacement.
A New Assessment of Robust Capuchin Monkey (Sapajus) Evolutionary History Using Genome-Wide SNP Marker Data and a Bayesian Approach to Species Delimitation
Authors: Martins Amely Branquinho , Valença-Montenegro Mônica Mafra , Lima Marcela Guimarães Moreira , Lynch Jessica W. , Svoboda Walfrido Kühl , Silva-Júnior José de Sousa e , Röhe Fábio , Boubli Jean Philippe , Fiore Anthony Di
Published: April 2023

Robust capuchin monkeys, Sapajus genus, are among the most phenotypically diverse and widespread groups of primates in South America, with one of the most confusing and often shifting taxonomies. We used a ddRADseq approach to generate genome-wide SNP markers for 171 individuals from all putative extant species of Sapajus to access their evolutionary history. Using maximum likelihood, multispecies coalescent phylogenetic inference, and a Bayes Factor method to test for alternative hypotheses of species delimitation, we inferred the phylogenetic history of the Sapajus radiation, evaluating the number of discrete species supported. Our results support the recognition of three species from the Atlantic Forest south of the São Francisco River, with these species being the first splits in the robust capuchin radiation. Our results were congruent in recovering the Pantanal and Amazonian Sapajus as structured into three monophyletic clades, though new morphological assessments are necessary, as the Amazonian clades do not agree with previous morphology-based taxonomic distributions. Phylogenetic reconstructions for Sapajus occurring in the Cerrado, Caatinga, and northeastern Atlantic Forest were less congruent with morphology-based phylogenetic reconstructions, as the bearded capuchin was recovered as a paraphyletic clade, with samples from the Caatinga biome being either a monophyletic clade or nested with the blond capuchin monkey.
LncRNA-SNPs in a Brazilian Breast Cancer Cohort: A Case-Control Study
Authors: Mathias Carolina , Marin Anelis , Kohler Ana , Sanchuki Heloisa , Sukow Natalie , Beltrame Marcia , Baal Suelen , Sebastião Ana , de Souza Fonseca Ribeiro Enilze , Gradia Daniela , Aoki Mateus , Carvalho de Oliveira Jaqueline
Published: April 2023

Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs that contain more than 200 nucleotides and exhibit a versatile regulatory capacity. Genomic alterations in lncRNAs have already been investigated in several complex diseases, including breast cancer (BC). BC is a highly heterogeneous disease and is the most prevalent cancer type among women worldwide. Single nucleotide polymorphisms (SNPs) in lncRNA regions appear to have an important role in BC susceptibility; however, little is known about lncRNA-SNPs in the Brazilian population. This study used Brazilian tumor samples to identify lncRNA-SNPs with a biological role in BC development. We applied a bioinformatic approach intersecting lncRNAs that are differentially expressed in BC tumor samples using The Cancer Genome Atlas (TCGA) cohort data and looked for lncRNAs with SNPs associated with BC in the Genome Wide Association Studies (GWAS) catalog. We highlight four lncRNA-SNPs—rs3803662, rs4415084, rs4784227, and rs7716600—which were genotyped in Brazilian BC samples in a case-control study. The SNPs rs4415084 and rs7716600 were associated with BC development at higher risk. These SNPs were also associated with progesterone status and lymph node status, respectively. The rs3803662/rs4784227 haplotype GT was associated with BC risk. These genomic alterations were also evaluated in light of the lncRNA’s secondary structure and gain/loss of miRNA binding sites to better understand its biological functions. We emphasize that our bioinformatics approach could find lncRNA-SNPs with a potential biological role in BC development and that lncRNA-SNPs should be more deeply investigated in a highly heterogeneous disease population.
Positive Regulation of Splicing of Cellular and Viral mRNA by Intragenic RNA Elements That Activate the Stress Kinase PKR, an Antiviral Mechanism
Authors: Kaempfer Raymond
Published: April 2023

The transient activation of the cellular stress kinase, protein kinase RNA-activated (PKR), by double-helical RNA, especially by viral double-stranded RNA generated during replication, results in the inhibition of translation via the phosphorylation of eukaryotic initiation factor 2 α-chain (eIF2α). Exceptionally, short intragenic elements within primary transcripts of the human tumor necrosis factor (TNF-α) and globin genes, genes essential for survival, can form RNA structures that strongly activate PKR and thereby render the splicing of their mRNAs highly efficient. These intragenic RNA activators of PKR promote early spliceosome assembly and splicing by inducing phosphorylation of nuclear eIF2α, without impairing the translation of the mature spliced mRNA. Unexpectedly, excision of the large human immunodeficiency virus (HIV) rev/tat intron was shown to require activation of PKR by the viral RNA and eIF2α phosphorylation. The splicing of rev/tat mRNA is abrogated by viral antagonists of PKR and by trans-dominant negative mutant PKR, yet enhanced by the overexpression of PKR. The TNFα and HIV RNA activators of PKR fold into compact pseudoknots that are highly conserved within the phylogeny, supporting their essential role in the upregulation of splicing. HIV provides the first example of a virus co-opting a major cellular antiviral mechanism, the activation of PKR by its RNA, to promote splicing.
Staff Successes and Challenges with Telecommunications-Facilitated Patient Care in Hybrid Hospital-at-Home during the COVID-19 Pandemic
Authors: Zawada Stephanie K. , Sweat Jeffrey , Paulson Margaret R. , Maniaci Michael J.
Published: April 2023

Technology-enhanced hospital-at-home (H@H), commonly referred to as hybrid H@H, became more widely adopted during the COVID-19 pandemic. We conducted focus group interviews with Mayo Clinic staff members (n = 14) delivering hybrid H@H in three separate locations—a rural community health system (Northwest Wisconsin), the nation’s largest city by area (Jacksonville, FL), and a desert metropolitan area (Scottsdale, AZ)—to understand staff experiences with implementing a new care delivery model and using new technology to monitor patients at home during the pandemic. Using a grounded theory lens, transcripts were analyzed to identify themes. Staff reported that hybrid H@H is a complex care coordination and communication initiative, that hybrid H@H faces site-specific challenges modulated by population density and state policies, and that many patients are receiving uniquely high-quality care through hybrid H@H, partly enabled by advances in technology. Participant responses amplify the need for additional qualitative research with hybrid H@H staff to identify areas for improvement in the deployment of new models of care enabled by modern technology.
Mobile Health Interventions to Improve Health Behaviors and Healthcare Services among Vietnamese Individuals: A Systematic Review
Authors: Nguyen Anna , Eschiti Valerie , Bui Thanh C. , Nagykaldi Zsolt , Dwyer Kathleen
Published: April 2023

The purpose of this review is to summarize the feasibility, acceptability, and efficacy of interventions that utilize mobile health (mHealth) technology to promote health behavior changes or improve healthcare services among the Vietnamese population. Ovid MEDLINE, CINAHL, EMBASE, Scopus, and Web of Science were used to identify studies published from 2011–2022. Studies utilizing mHealth to promote behavior change and/or improve healthcare services among Vietnamese were included. Studies that included Vietnamese people among other Asians but did not analyze the Vietnamese group separately were excluded. Three independent researchers extracted data using Covidence following PRISMA guidelines. Measures of feasibility, acceptability, and efficacy were synthesized. The ROBINS-I and RoB2 tools were used to evaluate methodological quality. Fourteen articles met inclusion criteria and included 5660 participants. Participants rated high satisfaction, usefulness, and efficacy of mHealth interventions. Short message service was most frequently used to provide health education, support smoking cessation, monitor chronic diseases, provide follow-up, and manage vaccination. Measures of feasibility, acceptability, and efficacy varied across studies; overall findings indicated that mHealth is promising for promoting lifestyle behavior change and improving healthcare services. Cost effectiveness and long-term outcomes of mHealth interventions among the Vietnamese population are unknown and merit further research. Recommendations to integrate mHealth interventions are provided to promote the health of Vietnamese people.
Potentially Avoidable Hospitalizations by Asthma and COPD in Switzerland from 1998 to 2018: A Cross-Sectional Study
Authors: Gouveia Alexandre , Mauron Charlène , Marques-Vidal Pedro
Published: April 2023

Potentially avoidable hospitalizations (PAH) are commonly used as an indicator for healthcare quality and primary care performance. However, data are usually presented in a restricted timeframe and for a specific region, limiting the identification of trends and national patterns. We aimed in this study to calculate rates, identify clinical determinants, and estimate costs of PAH for two frequent lung diseases (asthma and COPD) in Switzerland between 1998 and 2018 using hospital discharge data available for patients aged ≥20 years. PAH were defined according to the Health Care Quality Indicators Project (HCQIP) from the Organisation for Economic Co-operation and Development (OECD). The distribution of PAH in seven administrative regions (Leman, Mittelland, Northwest, Zurich, Eastern, Central, and Ticino) was calculated, along with PAH-associated total hospital days and Diagnosis-Related Group (DRG) estimated costs. Totals of 25,260 PAH for asthma and 135,069 PAH for COPD were identified in the 20-year period. The standardized rates of PAH per 100,000 people for asthma fluctuated from 18.7 in 1998 to 22.5 on 2018. The standardized rates of PAH per 100,000 people from COPD almost doubled from 77.4 in 1998 to 142.7 in 2018. In 2018, the estimated total costs of PAH amounted to 7.7 million CHF for asthma and 91.2 million CHF for COPD. We conclude that PAH for asthma and COPD represent a significant and unnecessary burden and costs of hospitalizations in Switzerland.
Modernism in the Mediterranean: Omiš, Croatia, Urban and Architectural Development of the Dalmatian City in the Second Half of the 20th Century
Authors: Barišić Marenić Zrinka , Perković Jović Vesna
Published: April 2023

Omiš is characterised by an exceptional layering of its natural environment and historical architecture, which is why its modern achievements have not been fully researched so far. The aim of this scientific paper is a more comprehensive study of the modern architecture of Omiš of the second half of the 20th century. Its architectural corpus has remained in the shadow of modern architectural realisations of the nearby city of Split, which belongs to the same prominent protagonists of modernity. Work methods in this paper have included the analysis of primary and secondary sources and research of the current situation in the field. This work, for the first time, gives a systematic presentation of the modern architecture of this picturesque town while the elements of the author’s expression integrate features of modern architecture and reinterpret the tradition of life in the Mediterranean.
The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals
Authors: Almuraikhy Shamma , Anwardeen Najeha , Doudin Asmma , Sellami Maha , Domling Alexander , Agouni Abdelali , Al Thani Asmaa A. , Elrayess Mohamed A.
Published: April 2023

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20–30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.
Peptidases: Role and Function in Health and Disease
Authors: Kos Janko
Published: April 2023

Peptidases represent a large family of hydrolases present in all living organisms, which catalyze the degradation of peptide bonds in different biological processes
Nutri-PEITC Jelly Significantly Improves Progression-Free Survival and Quality of Life in Patients with Advanced Oral and Oropharyngeal Cancer: A Blinded Randomized Placebo-Controlled Trial
Authors: Lam-Ubol Aroonwan , Sukhaboon Jirasak , Rasio Withee , Tupwongse Peerawitch , Tangshewinsirikul Thapana , Trachootham Dunyaporn
Published: April 2023

TP53 mutation is associated with cancer progression. Novel strategies to reboot p53 are required to stabilize the disease and improve survival. This randomized placebo-controlled trial investigated safety and efficacy of Nutri-PEITC Jelly (a texture-modified nutritious diet fortified with β-phenethyl isothiocyanate (PEITC) on oral cancer. Seventy-two patients with advanced-staged oral or oropharyngeal cancer were randomly assigned to study and control groups, who consumed 200 g of Nutri-Jelly with and without 20 mg of PEITC, respectively, 5 days/week for 12 weeks. Outcomes, including adverse events, health-related quality of life (HRQOL), progression-free survival (PFS), tumor response, serum p53, and cytochrome c, were measured at 0, 1, and 3 months. Results show that the study group had a higher proportion of participants with improved HRQOL, stable disease, and increased serum p53 levels than those in the control group (p < 0.001). The PFS time in the study group was significantly longer than that of the control group (p < 0.05). Serum cytochrome c levels were non-significantly decreased in the study group. No serious intervention-related adverse events occurred in either group. In conclusion, Nutri-PEITC Jelly intake for 3 months is safe, stabilizes the disease, improves quality of life and progression-free survival, and might re-activate p53 in advanced-stage oral and oropharyngeal cancer patients.
Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions
Authors: Smith-Cortinez Natalia , Tan A. Katherine , Stokroos Robert J. , Versnel Huib , Straatman Louise V.
Published: April 2023

Sensorineural hearing loss is caused by damage to sensory hair cells and/or spiral ganglion neurons. In non-mammalian species, hair cell regeneration after damage is observed, even in adulthood. Although the neonatal mammalian cochlea carries regenerative potential, the adult cochlea cannot regenerate lost hair cells. The survival of supporting cells with regenerative potential after cochlear trauma in adults is promising for promoting hair cell regeneration through therapeutic approaches. Targeting these cells by manipulating key signaling pathways that control mammalian cochlear development and non-mammalian hair cell regeneration could lead to regeneration of hair cells in the mammalian cochlea. This review discusses the pathways involved in the development of the cochlea and the impact that trauma has on the regenerative capacity of the endogenous progenitor cells. Furthermore, it discusses the effects of manipulating key signaling pathways targeting supporting cells with progenitor potential to promote hair cell regeneration and translates these findings to the human situation. To improve hearing recovery after hearing loss in adults, we propose a combined approach targeting (1) the endogenous progenitor cells by manipulating signaling pathways (Wnt, Notch, Shh, FGF and BMP/TGFβ signaling pathways), (2) by manipulating epigenetic control, and (3) by applying neurotrophic treatments to promote reinnervation.
Essential Involvement of Neutrophil Elastase in Acute Acetaminophen Hepatotoxicity Using BALB/c Mice
Authors: Ishida Yuko , Zhang Siying , Kuninaka Yumi , Ishigami Akiko , Nosaka Mizuho , Harie Isui , Kimura Akihiko , Mukaida Naofumi , Kondo Toshikazu
Published: April 2023

Intense neutrophil infiltration into the liver is a characteristic of acetaminophen-induced acute liver injury. Neutrophil elastase is released by neutrophils during inflammation. To elucidate the involvement of neutrophil elastase in acetaminophen-induced liver injury, we investigated the efficacy of a potent and specific neutrophil elastase inhibitor, sivelestat, in mice with acetaminophen-induced acute liver injury. Intraperitoneal administration of 750 mg/kg of acetaminophen caused severe liver damage, such as elevated serum transaminase levels, centrilobular hepatic necrosis, and neutrophil infiltration, with approximately 50% mortality in BALB/c mice within 48 h of administration. However, in mice treated with sivelestat 30 min after the acetaminophen challenge, all mice survived, with reduced serum transaminase elevation and diminished hepatic necrosis. In addition, mice treated with sivelestat had reduced NOS-II expression and hepatic neutrophil infiltration after the acetaminophen challenge. Furthermore, treatment with sivelestat at 3 h after the acetaminophen challenge significantly improved survival. These findings indicate a new clinical application for sivelestat in the treatment of acetaminophen-induced liver failure through mechanisms involving the regulation of neutrophil migration and NO production.
Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions
Authors: Bure Irina V. , Nemtsova Marina V.
Published: April 2023

Chromatin remodeling is the one of the main epigenetic mechanisms of gene expression regulation both in normal cells and in pathological conditions. In recent years, a growing number of investigations have confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. Genes encoding protein subunits of chromatin remodeling complexes are often mutated and change their expression in diseases, as well as non-coding RNAs (ncRNAs). Moreover, different mechanisms of their mutual regulation have already been described. Further understanding of these processes may help apply their clinical potential for establishment of the diagnosis, prognosis, and treatment of the diseases. The therapeutic targeting of the chromatin structure has many limitations because of the complexity of its regulation, with the involvement of a large number of genes, proteins, non-coding transcripts, and other intermediary molecules. However, several successful strategies have been proposed to target subunits of chromatin remodeling complexes and genes encoding them, as well as the ncRNAs that regulate the operation of these complexes and direct them to the target gene regions. In our review, we focus on chromatin remodeling complexes and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application.
Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review
Authors: Amati Francesco , Stainer Anna , Polelli Veronica , Mantero Marco , Gramegna Andrea , Blasi Francesco , Aliberti Stefano
Published: April 2023

Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.
In Vitro Approaches to Determine the Potential Carcinogenic Risk of Environmental Pollutants
Authors: Barguilla Irene , Maguer-Satta Veronique , Guyot Boris , Pastor Susana , Marcos Ricard , Hernández Alba
Published: April 2023

One important environmental/health challenge is to determine, in a feasible way, the potential carcinogenic risk associated with environmental agents/exposures. Since a significant proportion of tumors have an environmental origin, detecting the potential carcinogenic risk of environmental agents is mandatory, as regulated by national and international agencies. The challenge mainly implies finding a way of how to overcome the inefficiencies of long-term trials with rodents when thousands of agents/exposures need to be tested. To such an end, the use of in vitro cell transformation assays (CTAs) was proposed, but the existing prevalidated CTAs do not cover the complexity associated with carcinogenesis processes and present serious limitations. To overcome such limitations, we propose to use a battery of assays covering most of the hallmarks of the carcinogenesis process. For the first time, we grouped such assays as early, intermediate, or advanced biomarkers which allow for the identification of the cells in the initiation, promotion or aggressive stages of tumorigenesis. Our proposal, as a novelty, points out that using a battery containing assays from all three groups can identify if a certain agent/exposure can pose a carcinogenic risk; furthermore, it can gather mechanistic insights into the mode of the action of a specific carcinogen. This structured battery could be very useful for any type of in vitro study, containing human cell lines aiming to detect the potential carcinogenic risks of environmental agents/exposures. In fact, here, we include examples in which these approaches were successfully applied. Finally, we provide a series of advantages that, we believe, contribute to the suitability of our proposed approach for the evaluation of exposure-induced carcinogenic effects and for the development of an alternative strategy for conducting an exposure risk assessment.
Editorial of Special Issue “Synthesis and Molecular Applications of Metal-Organic Frameworks (MOFs)”
Authors: Khrizanforov Mikhail
Published: April 2023

This Special Issue is dedicated to exploring various approaches and techniques for the preparation and modification of metal–organic frameworks (MOFs), as well as their applications, with a specific focus on molecular research [...]
Attacking Cancer Progression and Metastasis
Authors: Hunáková Ľuba
Published: April 2023

This Special Issue, focused on a collection of papers on “attacking cancer progression and metastasis”, is devoted to communicating current knowledge about the cellular and molecular mechanisms involved in cancer progression and metastasis, as well as suggesting new targets for possible future therapeutic interventions [...]
A Facile Synthesis and Molecular Characterization of Certain New Anti-Proliferative Indole-Based Chemical Entities
Authors: Al-Wabli Reem I. , Issa Iman S. , Al-mutairi Maha S. , Almomen Aliyah A. , Attia Mohamed I.
Published: April 2023

Cancer cells frequently develop drug resistance, which leads to chemotherapeutic treatment failure. Additionally, chemotherapies are hindered by their high toxicity. Therefore, the development of new chemotherapeutic drugs with improved clinical outcomes and low toxicity is a major priority. Several indole derivatives exhibit distinctive anti-cancer mechanisms which have been associated with various molecular targets. In this study, target compounds 4a–q were obtained through the reaction of substituted benzyl chloride with hydrazine hydrate, which produces benzyl hydrazine. Subsequently, the appropriate substituted benzyl hydrazine was allowed to react with 1H-indole-2-carboxylic acid or 5-methoxy-1H-indole-2-carboxylic acid using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a coupling agent. All compounds exhibited cytotoxicity in three cell lines, namely, MCF-7, A549, and HCT. Compound 4e exhibited the highest cytotoxicity, with an average IC50 of 2 µM. Moreover, a flow cytometry study revealed a significantly increased prevalence of Annexin-V and 7-AAD positive cell populations. Several derivatives of 4a–q showed moderate to high cytotoxicity against the tested cell lines, with compound 4e having the highest cytotoxicity, indicating that it may possess potential apoptosis-inducing capabilities.
Universal Evolution of Fickian Non-Gaussian Diffusion in Two- and Three-Dimensional Glass-Forming Liquids
Authors: Rusciano Francesco , Pastore Raffaele , Greco Francesco
Published: April 2023

Recent works show that glass-forming liquids display Fickian non-Gaussian Diffusion, with non-Gaussian displacement distributions persisting even at very long times, when linearity in the mean square displacement (Fickianity) has already been attained. Such non-Gaussian deviations temporarily exhibit distinctive exponential tails, with a decay length λ growing in time as a power-law. We herein carefully examine data from four different glass-forming systems with isotropic interactions, both in two and three dimensions, namely, three numerical models of molecular liquids and one experimentally investigated colloidal suspension. Drawing on the identification of a proper time range for reliable exponential fits, we find that a scaling law λ(t)∝tα, with α≃1/3, holds for all considered systems, independently from dimensionality. We further show that, for each system, data at different temperatures/concentration can be collapsed onto a master-curve, identifying a characteristic time for the disappearance of exponential tails and the recovery of Gaussianity. We find that such characteristic time is always related through a power-law to the onset time of Fickianity. The present findings suggest that FnGD in glass-formers may be characterized by a “universal” evolution of the distribution tails, independent from system dimensionality, at least for liquids with isotropic potential.
Cell Programming for Cardiovascular Disease Modeling and Therapy
Authors: David Robert
Published: April 2023

Cardiovascular diseases have a high mortality due to a very limited regenerative potential of lost cardiomyocytes and therefore are one of the leading causes of death in developed countries [...]
Two-Dimensional Mixed-Ligand Metal–Organic Framework Constructed from Bridging Bidentate V-Shaped Ligands
Authors: Zhong Wen-Wu , Dehghani Firuzabadi Fahimeh , Hanifehpour Younes , Zeng Xue , Feng Yuan-Jiao , Liu Kuan-Guan , Joo Sang Woo , Morsali Ali , Retailleau Pascal
Published: April 2023

A two-dimensional and bifunctional pillar-layered metal–organic framework (MOF)—with the molecular formula [Zn(cba)(bpdb)]·DMF (2DTMU-1), H2cba = 4,4′-methylenedibenzoic acid, bpdb = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene—was obtained via the reaction of zinc(II) nitrate with H2cba as the carboxylate linker and bpdb as the N-donor pillar. 2DTMU-1 is based on a binuclear paddlewheel Zn(II) unit complexed by four bridging bidentate (dicarboxylate) V-shaped ligands, which combine to from H2cba; this tetragonal array, which is connected by bpdb with a bridging azine group, presents a pore size of 18 × 12 Å2.
Copper-Coordinated Thiazoles and Benzothiazoles: A Perfect Alliance in the Search for Compounds with Antibacterial and Antifungal Activity
Authors: Colorado-Peralta Raúl , Olivares-Romero José Luis , Rosete-Luna Sharon , García-Barradas Oscar , Reyes-Márquez Viviana , Hernández-Romero Delia , Morales-Morales David
Published: April 2023

Throughout human history, bacteria and fungi have caused infections that are difficult to combat. For this reason, countless research groups have developed novel compounds to solve this problem. Thiazole and benzothiazole are present in different structures with interesting biological effects and are used to develop new effective antimicrobial agents. Moreover, nitrogen atoms that are present in this heterocycle allow for coordination with various metals, forming metal complexes that enhance the biological activity of organic ligands that are often used as commercial drugs. This bibliographical review summarizes the copper complexes that use thiazole and benzothiazole as ligands and that report efficient antimicrobial activity against different bacteria and fungi.
Exploring the Hydrogen Sorption Capabilities of a Novel Ti-V-Mn-Zr-Nb High-Entropy Alloy
Authors: Bouzidi Anis , Perrière Loïc , Elkaim Erik , Laversenne Laetitia , Nassif Vivian , Vaughan Gavin , Zlotea Claudia
Published: April 2023

Hydrogen is considered as a clean energy carrier able to achieve the decarbonization of the economy, but its compact, safe, and efficient storage represents an important challenge. Among many materials forming hydrides, this work reports the study of hydrogen sorption properties of a novel bcc high-entropy alloy, Ti0.30V0.25Mn0.10Zr0.10Nb0.25, synthesized by arc melting. In less than 60 s, the alloy fully absorbs hydrogen at room temperature, reaching a capacity of 2.0 H/M (2.98 wt.%). A two-step reaction with hydrogen is confirmed by pressure-composition isotherms, synchrotron X-ray and neutron diffraction: bcc solid solution ↔ bcc monohydride ↔ fcc dihydride. For the second step transformation, the calculated thermodynamic values indicate the formation of a very stable dihydride, with ΔHabs = −97 kJ/molH2. Moreover, the pair distribution function analysis of high-energy synchrotron X-ray scattering data validates a completely random distribution of metal atoms in the fcc dihydride phase, without noticeable lattice strain nor elemental segregation. In situ synchrotron X-ray and neutron diffraction, performed during hydrogen desorption by heating under vacuum, demonstrated full reversibility of the reaction with hydrogen. On the basis of these results, tuning the chemical composition of high-entropy alloys may have great implications in terms of hydrogen sorption properties.
Effect of CaO-TiO2-SiO2 on the Microstructure and Mechanical Properties of Ceramic Corundum Abrasives
Authors: Zhao Quanbao , Li Zhihong , Zhu Yumei
Published: April 2023

Ceramic corundum abrasives were prepared using pseudo-boehmite as a raw material via the sol-gel method. Additives can significantly change the microscopic morphology of abrasives and improve mechanical properties. When 2 wt% CaO-TiO2-SiO2 with a molar ratio of 3:4:9 was added, samples with the best morphology and mechanical properties were obtained. Single-particle compressive strength, density, Vickers hardness, and average grain size were 51.45 N, 3.94 g·cm−3, 16.43 GPa, and 0.98 μm, respectively. We compared the same additive system with abrasives prepared by ball milling, and found that ball milling was beneficial for obtaining denser and smaller grain size abrasives. On the other hand, abrasives obtained without ball milling had relatively higher single-particle compressive strength. Additionally, the additives are non-precious metal oxides, which can reduce the cost of the synthesis process. In addition, there has been discussion of the connection between microstructure and mechanical characteristics.
Transcatheter Aortic Valve Replacement Prognostication with Augmented Mean Arterial Pressure
Authors: Chao Chieh-Ju , Agasthi Pradyumna , Seri Amith R. , Barry Timothy , Shanbhag Anusha , Wang Yuxiang , Eleid Mackram F. , Fortuin David , Sweeney John P. , Pollak Peter , El Sabbagh Abdallah , Lester Steven J. , Freeman William K. , Naqvi Tasneem Z. , Holmes David R. , Appleton Christopher P. , Arsanjani Reza
Published: April 2023

Background: Post-transcatheter aortic valve replacement (TAVR) patient outcome is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure (AugMAP)) derived from blood pressure and aortic valve gradients. Methods: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between 1 January 2012 and 30 June 2017 were identified to retrieve baseline clinical, echocardiographic and mortality data. AugSBP, AugMAP and valvulo-arterial impedance (Zva) (Zva) were evaluated using Cox regression. Receiver operating characteristic curve analysis and the c-index were used to assess the model performance against the Society of Thoracic Surgeons (STS) risk score. Results: The final cohort contained 974 patients with a mean age of 81.4 ± 8.3 years old, and 56.6% were male. The mean STS risk score was 8.2 ± 5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Both univariate and multivariate Cox regression showed that AugSBP and AugMAP parameters were independent predictors for intermediate-term post-TAVR mortality (all p < 0.0001). AugMAP1 < 102.5 mmHg was associated with a 3-fold-increased risk of all-cause mortality 1-year post-TAVR (hazard ratio 3.0, 95%confidence interval 2.0–4.5, p < 0.0001). A univariate model of AugMAP1 surpassed the STS score model in predicting intermediate-term post-TAVR mortality (area under the curve: 0.700 vs. 0.587, p = 0.005; c-index: 0.681 vs. 0.585, p = 0.001). Conclusions: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis.
Patterns of Cognitive Impairment in Hemodialysis Patients and Related Factors including Depression and Anxiety
Authors: Golenia Aleksandra , Żołek Norbert , Olejnik Piotr , Żebrowski Paweł , Małyszko Jolanta
Published: April 2023

Introduction: Hemodialysis patients are at higher risk of developing cognitive impairment, but the pattern of affected cognitive domains is still undetermined. Little is also known about the symptoms of depression and anxiety in hemodialysis patients. Methods: In this cross-sectional study, we included 74 consecutive adult patients undergoing hemodialysis. Cognitive functions were assessed using the Addenbrooke Cognitive Test III. In addition, all patients were screened for symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale. Results: The mean age of hemodialysis patients was 65.69 ± 14 years. Among the patients, there were 27% and 31% of patients with mild cognitive impairment and suspected dementia, respectively. In the group of patients with suspected dementia, all cognitive functions had significantly lower values compared to these functions in incognitively unimpaired and mild cognitive impairment patients. The most impaired domain was verbal fluency, which reflects impairments in executive function. Depression and anxiety symptoms were observed in 28% and 22% of patients, respectively. Patients with anxiety symptoms had higher levels of endogenous creatinine, parathyroid hormone, and hemoglobin, as well as decreased creatinine clearance, being younger and less educated. No factors contributing to the occurrence of depressive symptoms were found. Conclusion: Cognitive dysfunction is a significant problem in hemodialysis patients. Our study showed that the prevalence of cognitive impairment and depression and anxiety symptoms in hemodialysis patients was high. The domain of executive functions was most affected. Furthermore, creatinine, parathyroid hormone, hemoglobin levels, creatinine clearance, and education affected the anxiety scale score.
Anesthesia Analysis of Compound Lidocaine Cream Alone in Adult Male Device-Assisted Circumcision
Authors: Zheng Zhihuan , Ding Ke , Tang Zhengyan , Wu Ziqiang , Li Zhongyi , Wang Guilin , Fan Benyi , Wang Zhao
Published: April 2023

Objective: to evaluate the anesthetic effect among adult male patients with the single use of compound lidocaine cream in device-assisted circumcision, hoping to provide an anesthetic method for the simplification of the surgical process. Methods: Male adult patients undergoing device-assisted circumcision through prepuce local anesthesia using lidocaine cream in Xiangya Hospital of Central South University from December 2020 to August 2021 were selected. According to different age groups and different surgical procedures, the anesthetic effect of compound lidocaine cream was analyzed considering the aspects of anesthetic cost, anesthetic time, anesthetic duration, anesthetic effect, anesthetic side effects and anesthetic satisfaction. Results: In the study, 99.1% of 649 patients needed only 1 application of compound lidocaine cream to complete the operation. The time taken for anesthesia was short; the whole anesthesia process only required approximately 2–5 min. However, for patients with severe phimosis, the time to complete the anesthesia procedure was correspondingly longer. The pain degree caused by anesthesia was low, and the patients with a pain score of ≤3 points accounted for 96.7%. The anesthetic effect lasted for a sufficiently long period, and the time of algesia recovery from local anesthesia was almost 1 h after surgery. The anesthesia effect was sufficient, and patients with an intraoperative pain score of ≤3 accounted for 98.7%, which could meet the surgical requirements. There were few side effects of the anesthesia. The overwhelming majority of patients were pleased with the anesthesia, and 98.9% of patients had an anesthesia satisfaction score of ≥7. Conclusion: The compound lidocaine cream, as a local anesthetic, is safe and effective for most adult male device-assisted circumcisions. More useful information needs to be corroborated by more advanced evidence, especially for severe phimosis.
Hypertensive Heart Disease—The Imaging Perspective
Authors: Ismail Tevfik F. , Frey Simon , Kaufmann Beat A. , Winkel David J. , Boll Daniel T. , Zellweger Michael J. , Haaf Philip
Published: April 2023

Hypertensive heart disease (HHD) develops in response to the chronic exposure of the left ventricle and left atrium to elevated systemic blood pressure. Left ventricular structural changes include hypertrophy and interstitial fibrosis that in turn lead to functional changes including diastolic dysfunction and impaired left atrial and LV mechanical function. Ultimately, these changes can lead to heart failure with a preserved (HFpEF) or reduced (HFrEF) ejection fraction. This review will outline the clinical evaluation of a patient with hypertension and/or suspected HHD, with a particular emphasis on the role and recent advances of multimodality imaging in both diagnosis and differential diagnosis.
Uncovering the Benefits of the Ketamine–Dexmedetomidine Combination for Procedural Sedation during the Italian COVID-19 Pandemic
Authors: Riccardi Alessandro , Serra Sossio , De Iaco Fabio , Fabbri Andrea , Shiffer Dana , Voza Antonio
Published: April 2023

This retrospective observational study evaluated the safety and efficacy of the ketamine and dexmedetomidine combination (keta-dex) compared to ketamine or dexmedetomidine alone for sedation of patients with acute respiratory distress due to COVID-19 pneumonia who require non-invasive ventilation. The following factors were assessed: tolerance to the ventilation, sedation level on the Richmond Agitation-Sedation Scale (RASS), hemodynamic and saturation profile, adverse effects, and discontinuation or mortality during ventilation. The study included 66 patients who underwent sedation for non-invasive ventilation using keta-dex (KETA-DEX group, n = 22), ketamine (KET group, n = 22), or dexmedetomidine (DEX group, n = 22). The DEX group showed a slower sedation rate and a significant reduction in blood pressure compared to the KETA-DEX group (p < 0.05). An increase in blood pressure was recorded more frequently in the KET group. No reduction in oxygen saturation and no deaths were observed in any of the groups. None of the patients discontinued ventilation due to intolerance. The mean duration of sedation was 28.12 h. No cases of delirium were observed in any of the groups. Overall, keta-dex was associated with faster sedation rates and better hemodynamic profiles compared to dexmedetomidine alone. Keta-dex is effective and safe for sedation of uncooperative patients undergoing non-invasive ventilation.
Clinical Update on Congenital Adrenal Hyperplasia: Recommendations from a Multidisciplinary Adrenal Program
Authors: Uslar Thomas , Olmos Roberto , Martínez-Aguayo Alejandro , Baudrand René
Published: April 2023

Congenital adrenal hyperplasia (CAH) is a common genetic disorder in endocrinology, especially its milder clinical presentation, often caused by a partial or total deficiency of the 21-hydroxylase enzyme located in the adrenal cortex. CAH is characterized by the overproduction of androgen, along with variable degrees of cortisol and aldosterone deficiency. The age at diagnosis can provide some information about underlying mutations, with those diagnosed at birth/early infancy more likely to have severe enzymatic defects, which may include adrenal insufficiency, sexual development disorders, short stature in adulthood, hirsutism, and a higher risk for metabolic syndrome and infertility. Non-classic CAH, a milder form of CAH, is usually manifested later in life and is a common differential diagnosis of Polycystic Ovary Syndrome and should be actively evaluated during initial studies of clinical or biochemical hyperandrogenism. The main goals of CAH treatment are hormone supplementation for severe cases, controlling adrenal androgen overproduction to minimize long-term side effects, managing fertility and genetic counseling, and optimizing patients’ quality of life.
Prophylactic Treatment with Vedolizumab in the Prevention of Postoperative Recurrence (POR) in High-Risk Crohn’s Patients
Authors: Frieri Giuseppe , Valvano Marco , Frassino Sara , Faenza Susanna , Cesaro Nicola , Amicucci Gianfranco , Manetta Rosa , Viscido Angelo , Latella Giovanni
Published: April 2023

About 50% of Crohn’s Disease (CD) patients undergo an intestinal resection during their lifetime. Although the patients experience a fairly long period of well-being after the intestinal resection, they presented a postoperative recurrence (POR) in 40% of cases within 5 years. In this case series, we aimed to evaluate the incidence of POR in CD patients with high risk for early POR, prophylactically treated with Vedolizumab. All consecutive CD patients (followed from 2017 to 2020) who underwent ileocolonic resection after the loss of response at anti-Tumor Necrosis Factor α (anti-TNFα) and with one or more risk factors for early POR were included. POR was defined as a Rutgeerts score (Ri) > 1 at the colonoscopic evaluation. All the included patients underwent a Magnetic resonance enterography (MRE) at least one year after the surgical resection. Six patients (4 Female; 2 Males) were included. At the first endoscopic evaluation, all patients were in endoscopic remission (5 patients Ri 0; 1 patient Ri 1). No stenosis nor other intestinal wall changes or complications were observed at MRE. Five patients underwent colonoscopy over two years of follow-up (median: 32 months; range 25–33). The Ri score was 0 in four patients, while the fifth patient showed severe endoscopic relapse. The same patient presented a clinical relapse (Harvey-Bradshaw index = 10) with a flare of disease in the colonic mucosa. These data suggest that early post-operative treatment with Vedolizumab could be a valuable strategy to be submitted to a prospective controlled trial for preventing POR.