bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength Assessment of Water–Glass Sand Mixtures
Authors: Motohashi Toshiyuki , Sasahara Shigeo , Inazumi Shinya
Published: October 2023

For years, the chemical injection process has aided construction works by increasing the strength and water-sealing efficiency of sandy soil. Despite its growing popularity in projects, such as seismic strengthening and liquefaction mitigation, a unified understanding of how chemically treated soil develops its strength, especially under static conditions, remains elusive. Some studies have proposed that strength is derived from the tensile effects of dilatancy, where shearing of the sandy soil causes expansion, creating tension in the interstitial hydrogel and resulting in negative pressure that consolidates the soil particles. Other studies, however, attribute this strength development to the volumetric shrinkage of the hydrogel, which the authors argue confines and compresses the sandy soil particles. Challenges are encountered with this theory, particularly with respect to the consistency of the volumetric shrinkage measurements and the timing of these measurements in relation to changes in soil strength. The aim of the current research is to shed light on this mechanism by using consolidation drainage triaxial compression (CD) tests to measure the cohesive strength and internal friction angle of chemically enhanced soil. By eliminating the dilatancy-induced negative pressure effects and coupling this with an analysis of the molecular structure of the hydrogel, the present study provides an in-depth look at the strength development mechanism and its durability. This holistic approach not only fills in the existing gaps in the understanding of this mechanism, but also paves the way for optimized construction techniques.
Polyelectrolyte-Complex-Based Hydrogel Inserts for Vaginal Delivery of Posaconazole and Probiotics
Authors: Deshkar Sanjeevani , Yeole Purva , Mahore Jayashri , Shinde Ankita , Giram Prabhanjan
Published: October 2023

Worldwide, 40 to 50% of women suffer from reproductive tract infections. Most of these infections are mixed infections, are recurrent and difficult to treat with antimicrobials or antifungals alone. For symptomatic relief of infections, oral antimicrobial therapy must be combined with topical therapy. The purpose of this work is to optimize and develop a polyelectrolyte complex (PEC) of chitosan/anion for the formulation of posaconazole- and probiotic-loaded vaginal hydrogel inserts with prolonged release and significant mucoadhesion. PECs were prepared using chitosan as cationic and carrageenan, pectin and polycarbophil as anionic polymers via a lyophilization technique. PEC formation was confirmed by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry, by observing changes in its surface, physical and thermal properties. The probiotic, Lactobacillus casei, was added to the PEC during the lyophilization process and the effect on the probiotic viability was studied. The PECs were further compressed along with posaconazole to form hydrogel inserts and optimized using a 32 full-factorial design. The hydrogel inserts were assessed for swelling behavior, drug release, in vitro mucoadhesion and in vitro antifungal activity. The chitosan–pectin hydrogel insert demonstrated excellent mucoadhesion (1.25 N), sustained drug release (88.2 ± 2.4% in 8 h) and a swelling index of 154.7%. The efficacy of hydrogel inserts was evaluated using in vitro study with a co-culture of Lactobacillus casei and Candida albicans. This study revealed an increase in Lactobacilli casei count and a significant drop in the viable count of Candida albicans (4-log reduction in 24 h), indicating the effectiveness of hydrogel inserts in alleviating the fungal infection. Overall, our study demonstrated the potential of the hydrogel insert for preventing vaginal infection and restoring normal vaginal microbiota.
(N-Alkyloxalamido)-Amino Acid Amides as the Superior Thixotropic Phase Selective Gelators of Petrol and Diesel Fuels
Authors: Vujičić Nataša Šijaković , Makarević Janja , Popović Jasminka , Štefanić Zoran , Žinić Mladen
Published: October 2023

(N-Alkyloxalamido)-amino acid amides 9–12 exhibit excellent gelation capacities toward some lipophilic solvents as well as toward the commercial fuels, petrol and diesel. Gelator 10 exhibits an excellent phase-selective gelation (PSG) ability and also possesses the highest gelation capacity toward petrol and diesel known to date, with minimum gelation concentration (MGC) values (%, w/v) as low as 0.012 and 0.015, respectively. The self-assembly motif of 10 in petrol and toluene gel fibres is determined from xerogel X-ray powder diffraction (XRPD) data via the simulated annealing procedure (SA) implemented in the EXPO2014 program and refined using the Rietveld method. The elucidated motif is strongly supported by the NMR (NOE and variable temperature) study of 10 toluene-d8 gel. It is shown that the triple unidirectional hydrogen bonding between gelator molecules involving oxalamide and carboxamide groups, together with their very low solubility, results in the formation of gel fibres of a very high aspect ratio (d = 10–30 nm, l = 0.6–1.3 μm), resulting in the as-yet unprecedented capacity of gelling commercial fuels. Rheological measurements performed at low concentrations of 10 confirmed the strength of the self-assembled network with the desired thixotropic properties that are advantageous for multiple applications. Instantaneous phase-selective gelation was obtained at room temperature through the addition of the 10 solution to the biphasic mixture of diesel and water in which the carrier solvent was congealed along with the diesel phase. The superior gelling properties and PSG ability of 10 may be used for the development of more efficient marine and surface oil spill recovery and waste water treatment technologies as well as the development of safer fuel storage and transport technologies.
Role of pH and Crosslinking Ions on Cell Viability and Metabolic Activity in Alginate–Gelatin 3D Prints
Authors: Souza Andrea , Parnell Matthew , Rodriguez Brian J. , Reynaud Emmanuel G.
Published: October 2023

Alginate–gelatin hydrogels are extensively used in bioengineering. However, despite different formulations being used to grow different cell types in vitro, their pH and its effect, together with the crosslinking ions of these formulations, are still infrequently assessed. In this work, we study how these elements can affect hydrogel stability and printability and influence cell viability and metabolism on the resulting 3D prints. Our results show that both the buffer pH and crosslinking ion (Ca2+ or Ba2+) influence the swelling and degradation rates of prints. Moreover, buffer pH influenced the printability of hydrogel in the air but did not when printed directly in a fluid-phase CaCl2 or BaCl2 crosslinking bath. In addition, both U2OS and NIH/3T3 cells showed greater cell metabolic activity on one-layer prints crosslinked with Ca2+. In addition, Ba2+ increased the cell death of NIH/3T3 cells while having no effect on U2OS cell viability. The pH of the buffer also had an important impact on the cell behavior. U2OS cells showed a 2.25-fold cell metabolism increase on one-layer prints prepared at pH 8.0 in comparison to those prepared at pH 5.5, whereas NIH/3T3 cells showed greater metabolism on one-layer prints with pH 7.0. Finally, we observed a difference in the cell arrangement of U2OS cells growing on prints prepared from hydrogels with an acidic buffer in comparison to cells growing on those prepared using a neutral or basic buffer. These results show that both pH and the crosslinking ion influence hydrogel strength and cell behavior.
Discovering Genomic Regions Associated with Reproductive Traits and Frame Score in Mexican Simmental and Simbrah Cattle Using Individual SNP and Haplotype Markers
Authors: Calderón-Chagoya René , Vega-Murillo Vicente Eliezer , García-Ruiz Adriana , Ríos-Utrera Ángel , Martínez-Velázquez Guillermo , Montaño-Bermúdez Moisés
Published: October 2023

Reproductive efficiency stands as a critical determinant of profitability within beef production systems. The incorporation of molecular markers can expedite advancements in reproductive performance. While the use of SNPs in association analysis is prevalent, approaches centered on haplotypes can offer a more comprehensive insight. The study used registered Simmental and Simbrah cattle genotyped with the GGP Bovine 150 k panel. Phenotypes included scrotal circumference (SC), heifer fertility (HF), stayability (STAY), and frame score (FS). After quality control, 105,129 autosomal SNPs from 967 animals were used. Haplotype blocks were defined based on linkage disequilibrium. Comparison between haplotypes and SNPs for reproductive traits and FS was conducted using Bayesian and frequentist models. 23, 13, 7, and 2 SNPs exhibited associations with FS, SC, HF, and STAY, respectively. In addition, seven, eight, seven, and one haplotypes displayed associations with FS, SC, HF, and STAY, respectively. Within these delineated genomic segments, potential candidate genes were associated.
Genome-Wide Identification and Expression Analysis of the Cucumber FKBP Gene Family in Response to Abiotic and Biotic Stresses
Authors: Yang Dekun , Li Yahui , Zhu Mengdi , Cui Rongjing , Gao Jiong , Shu Yingjie , Lu Xiaomin , Zhang Huijun , Zhang Kaijing
Published: October 2023

The FKBP (FK506-binding protein) gene family is an important member of the PPlase protease family and plays a vital role during the processes of plant growth and development. However, no studies of the FKBP gene family have been reported in cucumber. In this study, 19 FKBP genes were identified in cucumber, which were located on chromosomes 1, 3, 4, 6, and 7. Phylogenetic analysis divided the cucumber FKBP genes into three subgroups. The FKBP genes in the same subgroup exhibited similar structures and conserved motifs. The cis-acting elements analysis revealed that the promoters of cucumber FKBP genes contained hormone-, stress-, and development-related cis-acting elements. Synteny analysis of the FKBP genes among cucumber, Arabidopsis, and rice showed that 12 kinds of syntenic relationships were detected between cucumber and Arabidopsis FKBP genes, and 3 kinds of syntenic relationships were observed between cucumber and rice FKBP genes. The tissue-specific expression analysis showed that some FKBP genes were expressed in all tissues, while others were only highly expressed in part of the 10 types of tissues. The expression profile analysis of cucumber FKBP genes under 13 types of stresses showed that the CsaV3_1G007080 gene was differentially expressed under abiotic stresses (high temperature, NaCl, silicon, and photoperiod) and biotic stresses (downy mildew, green mottle mosaic virus, Fusarium wilt, phytophthora capsica, angular leaf spot, and root-knot nematode), which indicated that the CsaV3_1G007080 gene plays an important role in the growth and development of cucumber. The interaction protein analysis showed that most of the proteins in the FKBP gene family interacted with each other. The results of this study will lay the foundation for further research on the molecular biological functions of the cucumber FKBP gene family.
Current State of Genomics in Nursing: A Scoping Review of Healthcare Provider Oriented (Clinical and Educational) Outcomes (2012–2022)
Authors: Thomas Joanne , Keels Jordan , Calzone Kathleen A. , Badzek Laurie , Dewell Sarah , Patch Christine , Tonkin Emma T. , Dwyer Andrew A.
Published: October 2023

In the 20 years since the initial sequencing of the human genome, genomics has become increasingly relevant to nursing. We sought to chart the current state of genomics in nursing by conducting a systematic scoping review of the literature in four databases (2012–2022). The included articles were categorized according to the Cochrane Collaboration outcome domains/sub-domains, and thematic analysis was employed to identify key topical areas to summarize the state of the science. Of 8532 retrieved articles, we identified 232 eligible articles. The articles primarily reported descriptive studies from the United States and other high-income countries (191/232, 82%). More than half (126/232, 54.3%) aligned with the “healthcare provider oriented outcomes” outcome domain. Three times as many articles related to the “knowledge and understanding” sub-domain compared to the “consultation process” subdomain (96 vs. 30). Five key areas of focus were identified, including “nursing practice” (50/126, 40%), “genetic counseling and screening” (29/126, 23%), “specialist nursing” (21/126, 17%), “nurse preparatory education” (17/126, 13%), and “pharmacogenomics” (9/126, 7%). Only 42/126 (33%) articles reported interventional studies. To further integrate genomics into nursing, study findings indicate there is a need to move beyond descriptive work on knowledge and understanding to focus on interventional studies and implementation of genomics into nursing practice.
Making Words—The Unconscious in Translation: Philosophical, Psychoanalytical, and Philological Approaches
Authors: Kasper Judith
Published: October 2023

The topic of the article is the status of translation and homophony in philosophy, psychoanalysis and philology. The article focuses on the question of how translation is carried out using the basic principle of equivalence of meaning by homophony and what effects this can produce. The analysis of two case studies by Freud and Lacan shows that homophonic transfer from one language to another can be extremely productive for the subjective traversal of a phantasm. It is then shown that this is not, however, of purely subjective interest. Werner Hamacher has sketched the future of philology starting from such homophonic translations; Lacan has tried to advance to another theory of language through homophonic formations.
A Study on the Monitoring of Toxocara spp. in Various Children’s Play Facilities in the Republic of Korea (2016–2021)
Authors: Oh Young-Hwan , Sohn Hae-Jin , Choi Mi-Yeon , Hyun Min-Woo , Hong Seok-Ho , Lee Ji-Su , Ryu Ah-Reum , Kim Jong-Hyun , Shin Ho-Joon
Published: October 2023

Toxocara spp. is a zoonotic soil-transmitted parasite that infects canids and felids, which causes toxocariasis in humans, migrating to organ systems, including the lungs, the ocular system, and the central nervous system. Since Toxocara spp. is usually transmitted through soil, children tend to be more susceptible to infection. In order to monitor contamination with Toxocara spp. in children’s play facilities in the Republic of Korea, we investigated 11,429 samples of soil from daycare centers, kindergartens, elementary schools, and parks across the country from January 2016 to December 2021. Since the Environmental Health Act in the Republic of Korea was enacted in March 2008, there have been sporadic reports of contamination by Toxocara spp. in children’s activity zones. In this study, soil from children’s play facilities in regions across the Republic of Korea was monitored according to the Korean standardized procedure to use it as basic data for preventive management and public health promotion. The national average positive rate was 0.16% (18/11,429), and Seoul showed a higher rate of 0.63% (2/318) than any other regions while Incheon, Daegu, Ulsan, Kangwon-do, Jeollabuk-do, and Jeollanam-do were negative (p < 0.05). The positive rates were as follows: 0.37% (4/1089) in daycare centers, 0.13% (3/2365) in kindergartens, 0.2% (7/4193) in elementary schools, 0.09% (1/1143) in apartments, and 0.14% (3/2198) in parks. In addition, it was confirmed that 0.2% (1/498) of elementary schools and 1.17% (2/171) of parks were re-contaminated among play facilities managed with the establishment of a regular inspection cycle. Consequently, there is an essential need for continuous monitoring of Toxocara spp. contamination and regular education for preschool and school children in order to prevent soil-borne parasite infections.
Preventing Zoonoses: Testing an Intervention to Change Attitudes and Behaviors toward More Protective Actions
Authors: Stel Marielle , Banach Nicole
Published: October 2023

Zoonotic outbreaks are considered one of the most important threats to public health. Therefore, it is important to educate people on how to prevent zoonotic infections. The purpose of this research was to investigate an intervention aimed at changing people’s attitudes and behaviors toward more protective actions. In two studies (NStudy1 = 402; NStudy2 = 706), participants received an intervention based on previous literature in which knowledge about zoonoses, protective actions they could take, and a fear appeal were provided. In the control condition, no intervention was given. Subsequently, we measured participants’ risk knowledge, attitudes and behavioral intentions to reduce zoonotic risks, and fear. The results showed that the intervention heightened participants’ zoonotic knowledge and affected their attitudes and behavioral intentions (Studies 1 and 2) and a behavioral decision (Study 2) to reduce zoonotic risks. Moreover, our designed intervention proved more effective than the World Health Organization informative message on zoonoses (Study 2). In terms of theory, this is the first experimental demonstration that a general zoonotic risk communication message changed attitudes and behaviors toward more protective actions. In terms of policy, this research showed that a basic information message for the broader public has the potential to reduce zoonotic risks.
Synergistic Enhancement of Protein Recruitment and Retention via Implant Surface Microtopography and Superhydrophilicity in a Computational Fluid Dynamics Model
Authors: Kitajima Hiroaki , Hirota Makoto , Iwai Toshinori , Mitsudo Kenji , Saruta Juri , Ogawa Takahiro
Published: October 2023

The exact mechanisms by which implant surface properties govern osseointegration are incompletely understood. To gain insights into this process, we examined alterations in protein and blood recruitment around screw implants with different surface topographies and wettability using a computational fluid dynamics (CFD) model. Compared with a smooth surface, a microrough implant surface reduced protein infiltration from the outer zone to the implant thread and interface zones by over two-fold. However, the microrough implant surface slowed blood flow in the interface zone by four-fold. As a result, compared with the smooth surface, the microrough surface doubled the protein recruitment/retention index, defined as the mass of proteins present in the area per unit time. Converting implant surfaces from hydrophobic to superhydrophilic increased the mass of protein infiltration 2–3 times and slowed down blood flow by up to two-fold in the implant vicinity for both smooth and microrough surfaces. The protein recruitment/retention index was highest at the implant interface when the implant surface was superhydrophilic and microrough. Thus, this study demonstrates distinct control of the mass and speed of protein and blood flow through implant surface topography, wettability, and their combination, significantly altering the efficiency of protein recruitment. Although microrough surfaces showed both positive and negative impacts on protein recruitment over smooth surfaces, superhydrophilicity was consistently positive regardless of surface topography.
Genomic and Reverse Translational Analysis Discloses a Role for Small GTPase RhoA Signaling in the Pathogenesis of Schizophrenia: Rho-Kinase as a Novel Drug Target
Authors: Tanaka Rinako , Yamada Kiyofumi
Published: October 2023

Schizophrenia is one of the most serious psychiatric disorders and is characterized by reductions in both brain volume and spine density in the frontal cortex. RhoA belongs to the RAS homolog (Rho) family and plays critical roles in neuronal development and structural plasticity via Rho-kinase. RhoA activity is regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). Several variants in GAPs and GEFs associated with RhoA have been reported to be significantly associated with schizophrenia. Moreover, several mouse models carrying schizophrenia-associated gene variants involved in RhoA/Rho-kinase signaling have been developed. In this review, we summarize clinical evidence showing that variants in genes regulating RhoA activity are associated with schizophrenia. In the last half of the review, we discuss preclinical evidence indicating that RhoA/Rho-kinase is a potential therapeutic target of schizophrenia. In particular, Rho-kinase inhibitors exhibit anti-psychotic-like effects not only in Arhgap10 S490P/NHEJ mice, but also in pharmacologic models of schizophrenia (methamphetamine- and MK-801-treated mice). Accordingly, we propose that Rho-kinase inhibitors may have antipsychotic effects and reduce cognitive deficits in schizophrenia despite the presence or absence of genetic variants in small GTPase signaling pathways.
The Toxicity Differences of Fluralaner against the Red Imported Fire Ant (Solenopsis invicta) at Different Developmental Stages
Authors: Shao Leyi , Wang Wei , Gong Xin , Yu Yinghao , Xue Junao , Zeng Xinnian , Liu Jiali
Published: October 2023

The red imported fire ant (RIFA), Solenopsis invicta, is an invasive pest that causes damage to agricultural and ecological environments worldwide. Fluralaner is a new isoxazoline pesticide with the potential to become a control agent against RIFA. However, it is not clear whether S. invicta responds the same way to fluralaner at different reproductive stages. The present study firstly evaluated the toxicity of fluralaner to S. invicta at different developmental stages, finding that fourth instar larvae (LD50, 1744.23 mg/kg) and worker ants (LD50, 8.62 mg/kg) were differently susceptible to fluralaner, while the mortality rate of fourth instar larvae was significantly lower at the same concentration of 10 mg/L (5.56 ± 3.14%) than that of worker ants (62.22 ± 3.14%), demonstrating a greater tolerance to fluralaner. Subsequently, the metabolic responses of worker and larval ants to fluralaner stress (10 mg/L) were investigated using non-targeted metabolomics, which indicated that the amount of differential metabolites and the KEGG metabolic pathways enriched were different between workers and larvae when exposed to the same dose (10 mg/L) of fluralaner. Differential metabolites of larvae and worker ants under fluralaner stress were mainly concentrated in organic acids and their derivatives, lipids and lipid-like molecules, nucleosides, nucleotides, and analogues, combined with the enriched metabolic pathways, revealed that the differential metabolic responses of larvae and worker ants were mainly in energy metabolism, detoxification metabolism, and neurotransmitter ligands. Workers consumed more substrates in the arginine synthesis pathway (l-glutamic acid, l-aspartic acid, and fumaric acid) to provide energy for the detoxification (glutathione) of pesticides when exposed to fluralaner stress, and the high accumulation of l-aspartic acid induced excitotoxicity in the worker ants. Larval ants consumed more arachidonic acid to synthesize PG D2, and changes in the metabolism of antioxidants such as catechins, hesperidin, and l-ascorbic acid suggested that larvae were more capable of scavenging the ROS response than worker ants. The results of non-targeted metabolomics successfully revealed differences in the sensitivity of larvae and workers to fluralaner agents, providing insights into the fluralaner control of Solenopsis invicta.
Fitness Trade-Offs between Phage and Antibiotic Sensitivity in Phage-Resistant Variants: Molecular Action and Insights into Clinical Applications for Phage Therapy
Authors: Fujiki Jumpei , Nakamura Keisuke , Nakamura Tomohiro , Iwano Hidetomo
Published: October 2023

In recent decades, phage therapy has been overshadowed by the widespread use of antibiotics in Western countries. However, it has been revitalized as a powerful approach due to the increasing prevalence of antimicrobial-resistant bacteria. Although bacterial resistance to phages has been reported in clinical cases, recent studies on the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy. This strategy aims to restore the antibiotic susceptibility of antimicrobial-resistant bacteria, even if phage-resistant variants develop. Here, we summarize the basic virological properties of phages and their applications within the context of antimicrobial resistance. In addition, we review the occurrence of phage resistance in clinical cases, and examine fitness trade-offs between phage and antibiotic sensitivity, exploring the potential of an evolutionary fitness cost as a countermeasure against phage resistance in therapy. Finally, we discuss future strategies and directions for phage-based therapy from the aspect of fitness trade-offs. This approach is expected to provide robust options when combined with antibiotics in this era of phage ‘re’-discovery.
Global Proteomics for Identifying the Alteration Pathway of Niemann–Pick Disease Type C Using Hepatic Cell Models
Authors: Miyoshi Keitaro , Hishinuma Eiji , Matsukawa Naomi , Shirasago Yoshitaka , Watanabe Masahiro , Sato Toshihiro , Sato Yu , Kumondai Masaki , Kikuchi Masafumi , Koshiba Seizo , Fukasawa Masayoshi , Maekawa Masamitsu , Mano Nariyasu
Published: October 2023

Niemann–Pick disease type C (NPC) is an autosomal recessive disorder with progressive neurodegeneration. Although the causative genes were previously identified, NPC has unclear pathophysiological aspects, and patients with NPC present various symptoms and onset ages. However, various novel biomarkers and metabolic alterations have been investigated; at present, few comprehensive proteomic alterations have been reported in relation to NPC. In this study, we aimed to elucidate proteomic alterations in NPC and perform a global proteomics analysis for NPC model cells. First, we developed two NPC cell models by knocking out NPC1 using CRISPR/Cas9 (KO1 and KO2). Second, we performed a label-free (LF) global proteomics analysis. Using the LF approach, more than 300 proteins, defined as differentially expressed proteins (DEPs), changed in the KO1 and/or KO2 cells, while the two models shared 35 DEPs. As a bioinformatics analysis, the construction of a protein–protein interaction (PPI) network and an enrichment analysis showed that common characteristic pathways such as ferroptosis and mitophagy were identified in the two model cells. There are few reports of the involvement of NPC in ferroptosis, and this study presents ferroptosis as an altered pathway in NPC. On the other hand, many other pathways and DEPs were previously suggested to be associated with NPC, supporting the link between the proteome analyzed here and NPC. Therapeutic research based on these results is expected in the future.
Effects of Catecholamine Stress Hormones Norepinephrine and Epinephrine on Growth, Antimicrobial Susceptibility, Biofilm Formation, and Gene Expressions of Enterotoxigenic Escherichia coli
Authors: Niu Lingdi , Gao Mingchun , Wen Shanshan , Wang Fang , Shangguan Haikun , Guo Zhiyuan , Zhang Runxiang , Ge Junwei
Published: October 2023

Enterotoxigenic Escherichia coli (ETEC) is a significant contributor to diarrhea. To determine whether ETEC-catecholamine hormone interactions contribute to the development of diarrhea, we tested the effects of catecholamine hormones acting on ETEC in vitro. The results showed that in the presence of norepinephrine (NE) and epinephrine (Epi), the growth of 9 out of 10 ETEC isolates was promoted, the MICs of more than 60% of the isolates to 6 antibiotics significantly increased, and the biofilm formation ability of 10 ETEC isolates was also promoted. In addition, NE and Epi also significantly upregulated the expression of the virulence genes feaG, estA, estB, and elt. Transcriptome analysis revealed that the expression of 290 genes was affected by NE. These data demonstrated that catecholamine hormones may augment the diarrhea caused by ETEC.
Postnatal Maturation of the Blood–Brain Barrier in Senescence-Accelerated OXYS Rats, Which Are Prone to an Alzheimer’s Disease-like Pathology
Authors: Rudnitskaya Ekaterina , Kozlova Tatiana , Burnyasheva Alena , Peunov Daniil , Tyumentsev Michail , Stefanova Natalia , Kolosova Nataliya
Published: October 2023

Alzheimer’s disease (AD) is an old-age neurodegenerative disorder; however, AD predisposition may arise early in life. Vascular dysfunction makes a big contribution to AD development. Nonetheless, the possible role of early-life vascular dysfunction in AD development is still poorly investigated. Here, using OXYS rats as a suitable model of the most common (sporadic) type of AD, we investigated maturation of the blood–brain barrier (BBB) in the hippocampus and frontal cortex in the first 3 weeks of life. Using RNA-Seq data, we found an altered expression of BBB-associated genes in the middle of the first and second weeks of life in OXYS rats compared to control rats (Wistar strain). Moreover, by immunohistochemistry and electronic microscopy, we revealed a delay of vascularization and of subsequent pericyte coating of blood vessels in OXYS rats. These specific features were accompanied by an accelerated decrease in BBB permeability estimated using Evans blue dye. Notably, almost all of the observed differences from Wistar rats disappeared on postnatal day 20. Nonetheless, the observed features, which are characteristic of the postnatal period, may have long-term consequences and contribute to neurovascular dysfunction observed in OXYS rats late in life, thereby promoting early development of AD signs.
Effective Local and Secondary Protein Structure Prediction by Combining a Neural Network-Based Approach with Extensive Feature Design and Selection without Reliance on Evolutionary Information
Authors: Milchevskiy Yury V. , Milchevskaya Vladislava Y. , Nikitin Alexei M. , Kravatsky Yury V.
Published: October 2023

Protein structure prediction continues to pose multiple challenges despite outstanding progress that is largely attributable to the use of novel machine learning techniques. One of the widely used representations of local 3D structure—protein blocks (PBs)—can be treated in a similar way to secondary structure classes. Here, we present a new approach for predicting local conformation in terms of PB classes solely from amino acid sequences. We apply the RMSD metric to ensure unambiguous future 3D protein structure recovery. The selection of statistically assessed features is a key component of the proposed method. We suggest that ML input features should be created from the statistically significant predictors that are derived from the amino acids’ physicochemical properties and the resolved structures’ statistics. The statistical significance of the suggested features was assessed using a stepwise regression analysis that permitted the evaluation of the contribution and statistical significance of each predictor. We used the set of 380 statistically significant predictors as a learning model for the regression neural network that was trained using the PISCES30 dataset. When using the same dataset and metrics for benchmarking, our method outperformed all other methods reported in the literature for the CB513 nonredundant dataset (for the PBs, Q16 = 81.01%, and for the DSSP, Q3 = 85.99% and Q8 = 79.35%).
Clavulanic Acid Improves Memory Dysfunction and Anxiety Behaviors through Upregulating Glutamatergic Transporters in the Nucleus Accumbens of Mice Repeatedly Exposed to Khat Extract
Authors: Arab Amal O. , Alasmari Fawaz , Albaker Awatif B. , Alhazmi Hassan A. , Alameen Alaa Alnoor , Alagail Naser M. , Alwaeli Saleh A. , Rizwan Ahamad Syed , AlAsmari Abdullah F. , AlSharari Shakir D.
Published: October 2023

Khat (Catha edulis) is an evergreen shrub whose buds and leaves give a state of delight and euphoria when chewed. Cathinone, an amphetamine-like stimulant that is among the active ingredients in khat, is able to downregulate glutamate transporter subtype I (GLT-1). Neurobehavioral dysfunctions such as altered locomotor activity, anorexia, and nociception have been observed in animals exposed to cathinone. Interestingly, treatment with a β-lactam antibiotic such as ceftriaxone, which upregulates GLT-1, normalizes cathinone-induced conditioned place preference, and alters repetitive movements in rats. However, little is known about the role of the glutamatergic system in memory dysfunction and anxiety-like behaviors in mice exposed to khat. We found here that clavulanic acid, a β-lactam-containing compound and GLT-1 upregulator, would modulate the neurobehavioral changes, including memory impairment and anxiety-like behaviors, associated with repeated exposure of mice to khat. Our data supported that clavulanic acid could improve memory impairment and anxiety-like behaviors through upregulating GLT-1 in the nucleus accumbens (NAc), an effect abolished with a selective GLT-1 blocker. This upregulation was associated with restored glutamate/cystine antiporter expression in the NAc using a Western blotting assay. Cathine and cathinone were identified in khat extract using the gas chromatography technique. Our work provides preclinical insight into the efficacy of β-lactam-containing compounds for the attenuation of neurobehavioral changes induced by khat exposure.
The Role of Longevity Assurance Homolog 2/Ceramide Synthase 2 in Bladder Cancer
Authors: Garcia-Vallicrosa Clara , Falcon-Perez Juan M. , Royo Felix
Published: October 2023

The human CERS2 gene encodes a ceramide synthase enzyme, known as CERS2 (ceramide synthase 2). This protein is also known as LASS2 (LAG1 longevity assurance homolog 2) and TMSG1 (tumor metastasis-suppressor gene 1). Although previously described as a tumor suppressor for different types of cancer, such as prostate or liver cancer, it has also been observed to promote tumor growth in adenocarcinoma. In this review, we focus on the influence of CERS2 in bladder cancer (BC), approaching the existing literature about its structure and activity, as well as the miRNAs regulating its expression. From a mechanistic point of view, different explanations for the role of CERS2 as an antitumor protein have been proposed, including the production of long-chain ceramides, interaction with vacuolar ATPase, and its function as inhibitor of mitochondrial fission. In addition, we reviewed the literature specifically studying the expression of this gene in both BC and biopsy-derived tumor cell lines, complementing this with an analysis of public gene expression data and its association with disease progression. We also discuss the importance of CERS2 as a biomarker and the presence of CERS2 mRNA in extracellular vesicles isolated from urine.
Identification of MicroRNAs Associated with Prediabetic Status in Obese Women
Authors: Kovac Leona , Speckmann Thilo , Jähnert Markus , Gottmann Pascal , Fritsche Louise , Häring Hans-Ulrich , Birkenfeld Andreas L. , Fritsche Andreas , Schürmann Annette , Ouni Meriem
Published: October 2023

MicroRNAs (miRNAs) recently emerged as means of communication between insulin-sensitive tissues to mediate diabetes development and progression, and as such they present a valuable proxy for epigenetic alterations associated with type 2 diabetes. In order to identify miRNA markers for the precursor of diabetes called prediabetes, we applied a translational approach encompassing analysis of human plasma samples, mouse tissues and an in vitro validation system. MiR-652-3p, miR-877-5p, miR-93-5p, miR-130a-3p, miR-152-3p and let-7i-5p were increased in plasma of women with impaired fasting glucose levels (IFG) compared to those with normal fasting glucose and normal glucose tolerance (NGT). Among these, let-7i-5p and miR-93-5p correlated with fasting blood glucose levels. Human data were then compared to miRNome data obtained from islets of Langerhans and adipose tissue of 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and liver fat content. Similar to human plasma, let-7i-5p was increased in adipose tissue and islets of Langerhans of diabetes-prone mice. As predicted by the in silico analysis, overexpression of let-7i-5p in the rat β-cell line INS-1 832/12 resulted in downregulation of insulin signaling pathway components (Insr, Rictor, Prkcb, Clock, Sos1 and Kcnma1). Taken together, our integrated approach highlighted let-7i-5p as a potential regulator of whole-body insulin sensitivity and a novel marker of prediabetes in women.
Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
Authors: Carrero Laura , Antequera Desireé , Alcalde Ignacio , Megias Diego , Ordoñez-Gutierrez Lara , Gutierrez Cristina , Merayo-Lloves Jesús , Wandosell Francisco , Municio Cristina , Carro Eva
Published: October 2023

Alzheimer’s disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-β (Aβ) accumulation that can directly interfere with the regulation of the circadian cycle. Although the cause of AD pathology is poorly understood, one of the main risk factors for AD is female gender. Here, we found that female APP/PS1 mice at 6- and 12-months old display severe circadian rhythm disturbances and retinal pathological hallmarks, including Aβ deposits in retinal layers. Since brain Aβ transport is facilitated by aquaporin (AQP)4, the expression of AQPs were also explored in APP/PS1 retina to investigate a potential correlation between retinal Aβ deposits and AQPs expression. Important reductions in AQP1, AQP4, and AQP5 were detected in the retinal tissue of these transgenic mice, mainly at 6-months of age. Taken together, our findings suggest that abnormal transport of Aβ, mediated by impaired AQPs expression, contributes to the retinal degeneration in the early stages of AD.
AI Chatbots in Digital Mental Health
Authors: Balcombe Luke
Published: October 2023

Artificial intelligence (AI) chatbots have gained prominence since 2022. Powered by big data, natural language processing (NLP) and machine learning (ML) algorithms, they offer the potential to expand capabilities, improve productivity and provide guidance and support in various domains. Human–Artificial Intelligence (HAI) is proposed to help with the integration of human values, empathy and ethical considerations into AI in order to address the limitations of AI chatbots and enhance their effectiveness. Mental health is a critical global concern, with a substantial impact on individuals, communities and economies. Digital mental health solutions, leveraging AI and ML, have emerged to address the challenges of access, stigma and cost in mental health care. Despite their potential, ethical and legal implications surrounding these technologies remain uncertain. This narrative literature review explores the potential of AI chatbots to revolutionize digital mental health while emphasizing the need for ethical, responsible and trustworthy AI algorithms. The review is guided by three key research questions: the impact of AI chatbots on technology integration, the balance between benefits and harms, and the mitigation of bias and prejudice in AI applications. Methodologically, the review involves extensive database and search engine searches, utilizing keywords related to AI chatbots and digital mental health. Peer-reviewed journal articles and media sources were purposively selected to address the research questions, resulting in a comprehensive analysis of the current state of knowledge on this evolving topic. In conclusion, AI chatbots hold promise in transforming digital mental health but must navigate complex ethical and practical challenges. The integration of HAI principles, responsible regulation and scoping reviews are crucial to maximizing their benefits while minimizing potential risks. Collaborative approaches and modern educational solutions may enhance responsible use and mitigate biases in AI applications, ensuring a more inclusive and effective digital mental health landscape.
A Comparative Assessment of Myocardial Work Performance during Spontaneous Rhythm, His Bundle Pacing, and Left Bundle Branch Area Pacing: Insights from the EMPATHY Study
Authors: Azzolini Giorgia , Bianchi Nicola , Vitali Francesco , Malagù Michele , Balla Cristina , De Raffele Martina , Bertini Matteo
Published: October 2023

Background: Physiological pacing has gained significant interest due to its potential to achieve optimal hemodynamic response. This study aimed to assess left ventricular performance in terms of electrical parameters, specifically QRS duration and mechanical performance, evaluated as myocardial work. We compared His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP) to evaluate their effects. Methods: Twenty-four patients with class I or IIa indications for pacing were enrolled in this study, with twelve patients undergoing HBP implantation and another twelve undergoing LBBAP implantation. A comprehensive analysis of myocardial work was conducted. Results: Our findings indicate that there were no major differences in terms of spontaneous and HBP activation in myocardial work, except for global wasted work (217 mmHg% vs. 283 mmHg%; p 0.016) and global work efficiency (87 mmHg% vs. 82 mmHg%; p 0.049). No significant differences were observed in myocardial work between spontaneous activation and LBBAP. Similarly, no significant differences in myocardial work were found between HBP and LBBAP. Conclusions: Both pacing modalities provide physiological ventricular activation without significant differences when compared to each other. Moreover, there were no significant differences in QRS duration between HBP and LBBAP. However, LBBAP demonstrated advantages in terms of feasibility, as it achieved better lead electrical parameters compared to HBP (threshold@0.4 ms 0.6 V vs. 1 V; p = 0.045—sensing 9.4 mV vs. 2.4 mV; p < 0.001). Additionally, LBBAP required less fluoroscopy time (6 min vs. 13 min; p = 0.010) and procedural time (81 min vs. 125 min; p = 0.004) compared to HBP.
Percutaneous Tibial Nerve Stimulation in the Treatment of Refractory Idiopathic Overactive Bladder Syndrome: A Retrospective Cohort Study
Authors: Frey Janine Nicole , Vidal Angela , Krebs Jörg , Christmann Corina
Published: October 2023

Background: Overactive bladder (OAB) is a syndrome defined as urinary urgency, accompanied by increased frequency and nocturia with or without urge incontinence, in the absence of urinary tract infection or other obvious pathology. The standard therapies are anticholinergic agents, selective beta-3 adrenoreceptor agonists, or intradetrusor injections of botulinum toxin (BTX-A). For patients with contraindications for BTX-A or drug therapies, percutaneous tibial nerve stimulation (PTNS) may be used. PTNS shows fewer side effects than anticholinergic drugs and costs less than BTX-A. The primary outcome of this study was to assess the efficacy of PTNS in women with refractory OAB. Methods: Women with refractory OAB undergoing PTNS at our tertiary referral center from 2017 to 2019 were included. The validated German Female Pelvic Floor Questionnaire and a micturition protocol were filled out before and after PTNS. PTNS was applied weekly for 12 weeks. Results: Improvements in OAB symptoms were seen in daily micturition frequency, urgency, and urgency incontinence from pre- to post-PTNS (p < 0.006). Impairments to quality of daily life were significantly (p < 0.0002) less severe after PTNS. There was a significant reduction in daytime voiding frequency from a median of nine to five (p < 0.0001). Conclusions: Substantial reductions in OAB symptoms, daily micturition frequency, urgency, and urgency incontinence were found in patients with refractory OAB after PTNS.
Postoperative Discharge Destination Impacts 30-Day Outcomes: A National Surgical Quality Improvement Program Multi-Specialty Surgical Cohort Analysis
Authors: Riveros Carlos , Ranganathan Sanjana , Shah Yash B. , Huang Emily , Xu Jiaqiong , Geng Michael , Melchiode Zachary , Hu Siqi , Miles Brian J. , Esnaola Nestor , Kaushik Dharam , Jerath Angela , Wallis Christopher J. D. , Satkunasivam Raj
Published: October 2023

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes.
Single Lung Transplant for Secondary Pulmonary Hypertension: The Right Option for the Right Patient
Authors: Housman Brian , Laskey Daniel , Dawodu Gbalekan , Scheinin Scott
Published: October 2023

Introduction: The optimal treatment for Secondary Pulmonary Hypertension from End-Stage Lung Disease remains controversial. Double Lung Transplantation is widely regarded as the treatment of choice as it eliminates all diseased parenchyma and introduces a large volume of physiologically normal allograft. By comparison, the role of single lung transplantation for pulmonary hypertension (PAH) is less clear. The remaining diseased lung will limit clinical improvements and permit downstream sequelae; including residual cough, recurrent infection, and continued pulmonary hypertension. But not every patient can undergo DLT. Advanced age, frailty, co-morbid conditions, and limited availability of organs will all affect surgical candidacy and can offset the benefits of double lung procedures. Studies that compare SLT and DLT do not commonly explore the utility of single lung procedures even though multiple theoretical advantages exist; including reduced waiting times, less waitlist mortality, fewer surgical complications, and lower operative mortality. Worse, multiple forms of publication and selection bias may favor DLT in registry-based studies. In this review, we present the prevailing literature on single and double lung transplants in patients with secondary pulmonary hypertension and clarify the potential utility of these procedures. Materials and Methods: A PubMed search for English-language articles exploring single and double lung transplants in the setting of secondary pulmonary hypertension was conducted from 1990 to 2023. Key words included “single lung transplant”, “double lung transplant”, “pulmonary hypertension”, “rejection”, “complications”, “extracorporeal membranous oxygenation”, “death”, and all appropriate Boolean operators. We prioritized research from retrospective studies that evaluated clinical outcomes from single centers. Conclusions: The question is not whether DLT is better at resolving lung disease; instead, we must ask if SLT is an acceptable form of therapy in a select group of high-risk patients. Further research should focus on how best to identify recipients that may benefit from each type of procedure, and the clinical utility of perioperative VA ECMO.