bluuebunny/crossref_metadata_2025 huggingface dataset:
Trifluoromethoxylation of Arynes Using 2,4‐Dinitro‐1‐(trifluoromethoxybenzene) as Trifluoromethoxide Anion Source
Authors: Wisson L. , Hanquet G. , Toulgoat F. , Billard T. , Panossian A. , Leroux F. R.
Published: May 2024

The trifluoromethoxy moiety, an emerging fluorinated group, shows interesting properties for pharmaceutical and agrochemical applications. However, only few methods have been reported for the direct introduction of this group on molecules with high efficiency, safety and low cost. Indeed, most of direct trifluoromethoxylation reagents are either expensive, hazardous or require preliminary synthesis before their use. Here we describe the use of 2,4‐dinitro‐1‐(trifluoromethoxy)benzene (DNTFB) as an easy‐to‐handle, safe, commercially available and cheap source of trifluoromethoxide anion for the trifluoromethoxylation of arynes.
Changes in CpG Methylation of the Vitellogenin 1 Promoter in Adult Male Zebrafish after Exposure to 17α-Ethynylestradiol
Authors: Kolli Ramya T. , Glenn Travis C. , Bringolf Robert B. , Henderson Matthew , Cummings Brian S. , Kenneke John F.
Published: May 2024

Numerous pharmaceutical and industrial chemicals are classified as endocrine-disrupting chemicals (EDCs) that interfere with hormonal homeostasis, leading to developmental disorders and other pathologies. The synthetic estrogen 17α-ethynylestradiol (EE2) is used in oral contraceptives and other hormone therapies. EE2 and other estrogens are inadvertently introduced into aquatic environments through municipal wastewater and agricultural effluents. Exposure of male fish to estrogens increases expression of the egg yolk precursor protein vitellogenin (Vtg), which is used as a molecular marker of exposure to estrogenic EDCs. The mechanisms behind Vtg induction are not fully known, and we hypothesized that it is regulated via DNA methylation. Adult zebrafish were exposed to either dimethyl sulfoxide or 20 ng/L EE2 for 14 days. Messenger RNA (mRNA) expression and DNA methylation were assessed in male zebrafish livers at 0, 0.25, 0.5, 1, 4, 7, and 14 days of exposure; and those of females were assessed at 13 days (n ≥ 4/group/time point). To test the persistence of any changes, we included a recovery group that received EE2 for 7 days and did not receive any for the following 7 days, in the total 14-day study. Methylation of DNA at the vtg1 promoter was assessed with targeted gene bisulfite sequencing in livers of adult male and female zebrafish. A significant increase in vtg1 mRNA was observed in the EE2-exposed male fish as early as 6 h. Interestingly, DNA methylation changes were observed at 4 days. Decreases in the overall methylation of the vtg1 promoter in exposed males resulted in levels comparable to those in female controls, suggesting feminization. Importantly, DNA methylation levels in males remained significantly impacted after 7 days post–EE2 removal, unlike mRNA levels. These data identify an epigenetic mark of feminization that may serve as an indicator of not only estrogenic exposure but also previous exposure to EE2. Environ Toxicol Chem 2024;43:1547–1556. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Impact of oxygen scavenger, temperature, and packaging materials on freshness quality of packaged green teas during storage
Authors: Fan Fangyuan , Wang Zipei , Chen Xiaogan , Yu Qiuwen , Yang Xiufang , Su Xiaoqin , Zhang Xu , Wang Jiawei , Xu Yingxin , Chen Ping , Chu Qiang , Guo Haowei , Gong Shuying
Published: May 2024

Green tea is renowned for its exceptional freshness; nevertheless, preserving its freshness poses a formidable challenge during storage due to its susceptibility to environmental factors. However, the effect of storage factors on freshness quality of green tea remains unclear, particularly with a lack of research studies regarding aroma quality and associated volatiles. In this study, we investigated the effects of oxygen scavenger, temperature, and packaging materials on freshness quality of packaged green teas during storage. The sensory freshness and corresponding volatile metabolites of the samples were investigated; the sensory‐chemical changes among packaged green teas during storage under different treatments were further explored. The freshness preservation in packaged green teas can be effectively achieved through the implementation of low‐temperature storage, packaging with oxygen scavenger and utilizing packaging with minimal oxygen permeability. A total of 151 volatile compounds were detected in all samples, among which 104 volatiles were identified as key contributors for distinguishing sample groups under 3 different treatments. The presence of volatiles with green, spicy, minty, and vegetable notes was found to be positively correlated with high freshness quality observed in packaged green tea. Conversely, an increase in volatiles characterized by fruity, sweet, fatty, and alkane notes was associated with the freshness deterioration. The volatiles changes that lead to freshness deterioration occurred especially under conditions of elevated temperature and increased oxygen levels, predominantly involving fat degradation, lipid oxidation, the Maillard reaction, carotenoids degradation, and dehydration reactions. The findings provide a theoretical foundation for the advancement of storage technology in packaged green teas.
Directionally‐split volume‐of‐fluid technique for front propagation under curvature flow
Authors: Fakhreddine Ali , Alamé Karim , Mahesh Krishnan
Published: May 2024

A directionally‐split volume‐of‐fluid (VOF) methodology for evolving interfaces under curvature‐dependent speed is devised. The interface is reconstructed geometrically and the volume fraction is advected with a technique to incorporate a topological volume conservation constraint. The proposed approach uses the idea that the role of curvature in a speed function is analogous to the role of viscosity in the corresponding hyperbolic conservation law to propagate complex interfaces where singularities may exist. The approach has the advantage of simple implementation and straightforward extension to more complex multiphase systems by formulating the interface evolution problem using energy functionals to derive an expression for the interface‐advecting velocity. The numerical details of the volume‐of‐fluid based formulation are discussed with emphasis on the importance of curvature estimation. Finally, canonical curves and surfaces traditionally investigated by the level set (LS) method are tested with the devised approach and the results are compared with existing work in LS.
Inhibition of phosphodiesterase 4 attenuates aquaporin 4 expression and astrocyte swelling following cerebral ischemia/reperfusion injury
Authors: Chen Kechun , Xu Bingtian , Qiu Shuqin , Long Lu , Zhao Qian , Xu Jiangping , Wang Haitao
Published: May 2024

We have previously shown that phosphodiesterase 4 (PDE4) inhibition protects against neuronal injury in rats following middle cerebral artery occlusion/reperfusion (MCAO/R). However, the effects of PDE4 on brain edema and astrocyte swelling are unknown. In this study, we showed that inhibition of PDE4 by Roflumilast (Roflu) reduced brain edema and brain water content in rats subjected to MCAO/R. Roflu decreased the expression of aquaporin 4 (AQP4), while the levels of phosphorylated protein kinase B (Akt) and forkhead box O3a (FoxO3a) were increased. In addition, Roflu reduced cell volume and the expression of AQP4 in primary astrocytes undergoing oxygen and glucose deprivation/reoxygenation (OGD/R). Consistently, PDE4B knockdown showed similar effects as PDE4 inhibition; and PDE4B overexpression rescued the inhibitory role of PDE4B knockdown on AQP4 expression. We then found that the effects of Roflu on the expression of AQP4 and cell volume were blocked by the Akt inhibitor MK2206. Since neuroinflammation and astrocyte activation are the common events that are observed in stroke, we treated primary astrocytes with interleukin‐1β (IL‐1β). Astrocytes treated with IL‐1β showed decreased AQP4 and phosphorylated Akt and FoxO3a. Roflu significantly reduced AQP4 expression, which was accompanied by increased phosphorylation of Akt and FoxO3a. Furthermore, overexpression of FoxO3a partly reversed the effect of Roflu on AQP4 expression. Our findings suggest that PDE4 inhibition limits ischemia‐induced brain edema and astrocyte swelling via the Akt/FoxO3a/AQP4 pathway. PDE4 is a promising target for the intervention of brain edema after cerebral ischemia.
Ethnic Variation and Structure‐Function Analysis of Tauopathy‐Associated PERK Alleles
Authors: Park Goonho , Galdamez Angela , Song Keon‐Hyoung , Le Masako , Kim Kyle , Lin Jonathan H.
Published: May 2024

EIF2AK3, also known as PERK, plays a pivotal role in cellular proteostasis, orchestrating the Unfolded Protein Response (UPR) and Integrated Stress Response (ISR) pathways. In addition to its central position in intracellular stress regulation, human GWAS identify EIF2AK3 as a risk factor in tauopathies, neurodegenerative diseases caused by aberrant tau protein accumulation. Guided by these genomic indicators, our investigation systematically analyzed human PERK variants, focusing on those with potential tauopathy linkages. We assembled a comprehensive data set of human PERK variants associated with Wolcott Rallison Syndrome (WRS), tauopathies, and bioinformatically predicted loss‐of‐function, referencing the gnomAD, Ensembl, and NCBI databases. We found extensive racial/ethnic variation in the prevalence of common PERK polymorphisms linked to tauopathies. Using SWISS‐MODEL, we identified structural perturbations in the ER stress‐sensing luminal domain dimers/oligomers of tauopathy‐associated PERK variants, Haplotypes A and B, in combination with another tauopathy‐linked R240H mutation. Recombinant expression of disease‐associated variants in vitro revealed altered PERK signal transduction kinetics in response to ER stress compared to the predominant non‐disease variant. In summary, our data further substantiates that human PERK variants identified in tauopathy genetic studies negatively impact PERK structure, function, and downstream signaling with significant variations in prevalence among different racial and ethnic groups.
Family cumulative risk, life satisfaction, and anxiety and depression in adolescents: A developmental cascades model
Authors: Xiong Junmei , Fang Xuebing , Wang Jiawei , Xie Weiwei , Liu Meiqi , Niu Gengfeng
Published: May 2024

Introduction

Family cumulative risk (FCR) is predominantly regarded as an antecedent for adolescent mental health, as the prevailing perspective continues to emphasize the influential role of parents, despite recognizing the child's influence. To identify the interplay between family adversity (FCR, process‐related FCR, and sociodemographic‐related FCR), life satisfaction (LS), and anxiety and depression (AD), this study examined the cascade effects among these constructs.

Method

Participants (N = 707; 52.9% male; grades 10 and 11) from four high schools in Wuhan, China, were recruited to participate, and they completed the measures in October 2018, April 2019, and November 2019. Family sociodemographic risk (e.g., single parenthood) and family process risk (e.g., low family cohesion) were simulated in the models for FCR, sociodemographic‐related FCR, and process‐related FCR.

Results

The random intercept cross‐lagged panel models (RI‐CLPMs) revealed a lagged effect from LS to FCR; lagged effects from LS and AD to process‐related FCR at the within‐person level; and significant associations between LS, AD, and family adversity at the between‐person level.

Conclusions

The lagged effects provide evidence for the influential child perspective and suggest that FCR and family process risk are sensitive to adolescent well‐being and psychopathological symptoms. School mental health prevention and intervention programs that take a complete mental health approach to enhance children's well‐being and alleviate symptoms would help prevent increases in family risk.
Synthesis and study of organo‐modified silica based hydrogels: Rheological properties and drug release kinetics
Authors: Parfenyuk Elena V. , Dolinina Ekaterina S. , Kraev Anton S.
Published: May 2024

The method of synthesis of unmodified and organo‐modified silica hydrogels and their composites with orotic acid as a model drug was developed. The hydrogels had a pH of 6.5–7.8. The particulate nature and highly porous structures of the hydrogel materials were revealed using scanning electron and optical microscopy methods. The content of aqueous phase in the hydrogels was 99% or more. In order to evaluate the possibility of their application as a basis for development of novel soft drug formulations and cosmetic compositions, rheological properties of the hydrogels and in vitro release kinetics of the drug were studied. The effects of synthesis conditions (increasing concentration of catalyst of silica sol formation, drug loading) and the silica matrix modification with various organic groups on the indicated properties were investigated. It was found that all synthesized hydrogels exhibited pseudoplasticity, thixotropy and controlled release of the drug, which are important for their potential application. However, in general, the indicated effects led to worsening the properties of the hydrogel materials in comparison with the unmodified silica hydrogels.
A systematic DFT study of structure and electronic properties of titanium dioxide
Authors: Marzouk Asma , Papavasileiou Konstantinos D. , Peristeras Loukas D. , Bezemer Leendert , van Bavel Alexander P. , Shenai Prathamesh M. , Economou Ioannis G.
Published: May 2024

DFT functionals are of paramount importance for an accurate electronic and structural description of transition metal systems. In this work, a systematic analysis using some well‐known and commonly used DFT functionals is performed. A comparison of the structural and energetic parameters calculated with the available experimental data is made in order to find the adequate functional for an accurate description of the TiO2 bulk and surface of both anatase and rutile structures. In the absence of experimental data on the surface energy, the theoretical predictions obtained using the high‐accuracy HSE06 functional were used as a reference to compare against the surface energy values calculated with the other DFT functionals. A clear improvement in the electronic description of both anatase and rutile was observed by introducing the Hubbard U correction term to PBE, PW91, and OptPBE functionals. The OptPBE‐U4 functional was found to offer a good compromise between accurately describing the structural and electronic properties of titania.
TRPM2 channels are essential for regulation of cytokine production in lung interstitial macrophages
Authors: Rajan Suhasini , Shalygin Alexey , Gudermann Thomas , Chubanov Vladimir , Dietrich Alexander
Published: May 2024

Interstitial macrophages (IMs) are essential for organ homeostasis, inflammation, and autonomous immune response in lung tissues, which are achieved through polarization to a pro‐inflammatory M1 and an M2 state for tissue repair. Their remote parenchymal localization and low counts, however, are limiting factors for their isolation and molecular characterization of their specific role during tissue inflammation. We isolated viable murine IMs in sufficient quantities by coculturing them with stromal cells and analyzed mRNA expression patterns of transient receptor potential (TRP) channels in naïve and M1 polarized IMs after application of lipopolysaccharide (LPS) and interferon γ. M‐RNAs for the second member of the melastatin family of TRP channels, TRPM2, were upregulated in the M1 state and functional channels were identified by their characteristic currents induced by ADP‐ribose, its specific activator. Most interestingly, cytokine production and secretion of interleukin‐1α (IL‐1α), IL‐6 and tumor necrosis factor‐α in M1 polarized but TRPM2‐deficient IMs was significantly enhanced compared to WT cells. Activation of TRPM2 channels by ADP‐ribose (ADPR) released from mitochondria by ROS‐produced H2O2 significantly increases plasma membrane depolarization, which inhibits production of reactive oxygen species by NADPH oxidases and reduces cytokine production and secretion in a negative feedback loop. Therefore, TRPM2 channels are essential for the regulation of cytokine production in M1‐polarized murine IMs. Specific activation of these channels may promote an anti‐inflammatory phenotype and prevent a harmful cytokine storm often observed in COVID‐19 patients.
Establishing the short course in transferable skills training program
Authors: Lindsey Merry L. , Harris Brandon J. , Dahm Lauren E. , Woods Letha
Published: May 2024

While PhD programs prepare graduate students to perform biomedical research, a defined systematic training program for transferable skills is generally lacking. When provided, this training is often informal, unstructured, or inconsistent. Therefore, there is a need to provide critical skills in marketing, relationship building, project management, and budgeting to prepare trainees to navigate into a productive, engaging, and rewarding biomedical research career. To address this gap in training, the School of Graduate Studies at Meharry Medical College has developed the SHort Course In transFerable skills Training (SHIFT) Program, a 1‐year professional development program accessible to graduate students in the United States who are enrolled in graduate biomedical research related programs. The SHIFT Program has been launched to equip trainees with skills essential for success in all biomedical science careers. PhD students will be taught the primary constituents of career management through the use of four training modules. In Module I, students complete self‐assessments and are assigned to a small peer‐mentoring team with mentors. Module II consists of a 5‐day workshop that encompasses instruction on the transferable skills identified as essential for career success. Module III entails monthly interactive discussions over a 6‐month period involving case study review and mentor‐guided discussions to further reinforce skills learned. In Module IV, students compile the information learned from Modules I‐III to develop an Individual Development Plan that incorporates 3–5 specific, measurable, attainable, relevant, and time‐based career goals. Collectively, the SHIFT Program will allow participants to train, practice, and refresh skills, empowering them to navigate career transitions and obtain success in the career of their choice.
Effects of Lake Erie dredged material on microbiomes in a farm soil of northwestern Ohio
Authors: Gautam Jyotshana , Ebersole Wolfgang , Brigham Russell , Shang Junfeng , Vázquez‐Ortega Angélica , Xu Zhaohui
Published: May 2024

Dredged materials are often considered as candidates for replenishing lost topsoils in the watersheds of rivers and lakes. This study aimed to investigate the impacts of Lake Erie dredged material on the microbial community in a farm soil of northwestern Ohio. Dredged material from the Toledo Harbor, OH was mixed with a local farm soil at ratios of 0:100, 10:90, 20:80, and 100:0 for soybean growth in a greenhouse for 123 days and was subject to 16S rRNA gene sequencing. α‐Diversity analysis revealed that although the original dredged material hosted a highly diverse microbiome, soils blended with the dredged material had similar levels of bacterial diversity to 100% farm soil throughout the experiment. β‐Diversity analysis demonstrated that, given the same plant status, that is, with or without soybean, blended soils had similar bacterial communities to 100% farm soil during the experiment. Furthermore, by the end of the experiment, all soils with soybeans merged into one cluster distinctive from those without the plants, indicating that the growth of plants played a dominating role in defining the structure of soil microbiomes. The majority (73.8%) of the operational taxonomy units that were unique to the original dredged material were not detected by the end of the experiment. This study demonstrates that up to 20% of the dredged material can be safely blended into the farm soil without distorting the microbial communities of the latter, implying a potential beneficial use of the dredged material for topsoil restoration.
Recyclization of 3‐substituted‐6,8‐dimethylchromones with some heterocyclic enamines: Spectroscopic, quantum calculations (HOMO–LUMO, MEP, NLO), biological evaluation, and ADME investigation
Authors: Badran Al‐Shimaa , Ibrahim Magdy A.
Published: May 2024

The chemical reactivity of some 6,8‐dimethylchromones was studied toward certain heterocyclic enamines. Treatment of carboxaldehyde 1a with the certain enamines proceeded via condensation with concomitant γ‐pyrone ring opening. Reaction of carbonitrile 1b with enamine derivatives proceeded through opening of γ‐pyrone moiety associated with cycloaddition into the nitrile function. A novel angular chromenopyrazolopyridine and chromenopyridopyrimidines were efficiently synthesized from reacting carboxamide 1c with the current enamines. Moreover, frontier molecular orbitals analysis, electronegativity, global hardness, global softness, ionization energy, and HOMO‐LUMO energy gap were calculated by using DFT/B3LYP/6‐311++G(d,p) level. Using the GIAO approach, the 1H and 13C NMR spectra were calculated and showed good agreement with the experimental values. Additionally, the nonlinear optical (NLO) properties of the prepared compounds were found higher than urea. MEP was utilized to ascertain reactive sites within the molecules. The produced compounds exhibited varying degrees of inhibitory effect when tested for their antimicrobial and anticancer properties. The evaluation of ADME (absorption, distribution, metabolism, and excretion) parameters indicated good drug‐like properties of all the investigated compounds.
Global and regional burden of vaccine‐associated facial paralysis, 1967–2023: Findings from the WHO international pharmacovigilance database
Authors: Jeong Yi Deun , Lee Kyeongmin , Lee Sooji , Park Jaeyu , Kim Hyeon Jin , Lee Jinseok , Kang Jiseung , Jacob Louis , Smith Lee , Rahmati Masoud , López Sánchez Guillermo F. , Dragioti Elena , Son Yejun , Kim Soeun , Yeo Seung Geun , Lee Hayeon , Yon Dong Keon
Published: May 2024

The scarce and conflicting data on vaccine‐associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine‐associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine‐associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine‐associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine‐associated facial paralysis from 49 537 reports of all‐cause facial paralysis. Vaccine‐associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID‐19) pandemic, which is attributable to the COVID‐19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID‐19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60–29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella‐zoster, meningococcal, Ad‐5 vectored COVID‐19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole‐virus COVID‐19 vaccines. Concerning age‐ and sex‐specific risks, vaccine‐associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine‐associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine‐induced facial paralysis, primarily owing to COVID‐19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine‐associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
High‐risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects
Authors: Lo Cigno Irene , Calati Federica , Girone Carlo , Catozzo Marta , Gariglio Marisa
Published: May 2024

Human papillomaviruses (HPVs) are double‐stranded DNA (dsDNA) tumor viruses causally associated with 5% of human cancers, comprising both anogenital and upper aerodigestive tract carcinomas. Despite the availability of prophylactic vaccines, HPVs continue to pose a significant global health challenge, primarily due to inadequate vaccine access and coverage. These viruses can establish persistent infections by evading both the intrinsic defenses of infected tissues and the extrinsic defenses provided by professional innate immune cells. Crucial for their evasion strategies is their unique intraepithelial life cycle, which effectively shields them from host detection. Thus, strategies aimed at reactivating the innate immune response within infected or transformed epithelial cells, particularly through the production of type I interferons (IFNs) and lymphocyte‐recruiting chemokines, are considered viable solutions to counteract the adverse effects of persistent infections by these oncogenic viruses. This review focuses on the complex interplay between the high‐risk HPV oncoproteins E6 and E7 and the innate immune response in epithelial cells and HPV‐associated cancers. In particular, it details the molecular mechanisms by which E6 and E7 modulate the innate immune response, highlighting significant progress in our comprehension of these processes. It also examines forward‐looking strategies that exploit the innate immune system to ameliorate existing anticancer therapies, thereby providing crucial insights into future therapeutic developments.
Alternative point‐wise metrics for tropical cyclone risks
Authors: Gil Eunhee , Kang Namyoung
Published: May 2024

To minimize the risks from tropical cyclones (TCs), the quantification and regular monitoring of TC activities are strongly needed. While the accumulated cyclone energy (ACE) (Bell et al., 2000, Climate assessment for 1999. Bulletin of the American Meteorological Society, 81, S1–S50) has been widely used for examining the level of basin‐wide TC activities, the conventional ACE does not discriminate the regional characteristics of TC risks. By introducing a point‐wise version of ACE, this paper proposes a geographical approach to the risk map for TCs. Here, the alternative metric is named the localized ACE (LACE), which interprets the TC risk directly felt by the local residents. Annual LACE at a geographical point measures TC activity by merging the quantities of frequency, intensity and duration factors, which contribute to the local TC activity in a year. In conjunction with LACE, a concept of LACE partial contribution (LACEP) is also proposed. The LACEP enables quantitative comparison of the contribution by each factor to the LACE, and thereby identifies the characteristics of the regional TC risks. To demonstrate the efficacy of the indices, that is, LACE and LACEP, this paper provides the response of the local TC activities to El Niño–Southern Oscillation in the western North Pacific and confirms the value of these indices.
1H and 13C NMR spectra of infinitene and the ring current effect of the aromatic molecule
Authors: Kleinpeter Erich , Koch Andreas
Published: May 2024

The spatial magnetic properties (through‐space NMR shieldings—TSNMRSs—actually the ring current effect in 1H NMR spectroscopy) of the recently synthesized infinitene (the helically twisted [12]circulene) have been calculated using the GIAO perturbation method employing the nucleus‐independent chemical shift (NICS) concept and visualized as iso‐chemical‐shielding surfaces (ICSS) of various size and direction. Both 1H and 13C chemical shifts of infinitene and the aromaticity of this esthetically very appealing molecule have been studied subject to the ring current effect thus obtained. This spatial magnetic response property of TSNMRSs dominates the different magnitude of 1H and 13C chemical shifts, especially in the cross‐over section of infinitene, which is unequivocally classified as an aromatic molecule based on the deshielding belt of its ring current effect. Differences in aromaticity of infinitene compared with isolated benzene can also be qualified and quantified on the magnetic criterion.
Proteomic diversification of spermatostyles among six species of whirligig beetles
Authors: Gomez R. Antonio , Dallai Romano , Sims‐West Dylan J. , Mercati David , Sinka Rita , Ahmed‐Braimah Yasir , Pitnick Scott , Dorus Steve
Published: May 2024

Seminal fluid protein composition is complex and commonly assumed to be rapidly divergent due to functional interactions with both sperm and the female reproductive tract (FRT), both of which evolve rapidly. In addition to sperm, seminal fluid may contain structures, such as mating plugs and spermatophores. Here, we investigate the evolutionary diversification of a lesser‐known ejaculate structure: the spermatostyle, which has independently arisen in several families of beetles and true bugs. We characterized the spermatostyle proteome, in addition to spermatostyle and FRT morphology, in six species of whirligig beetles (family Gyrinidae). Spermatostyles were enriched for proteolytic enzymes, and assays confirmed they possess proteolytic activity. Sperm‐leucylaminopeptidases (S‐LAPs) were particularly abundant, and their localization to spermatostyles was confirmed by immunohistochemistry. Although there was evidence for functional conservation of spermatostyle proteomes across species, phylogenetic regressions suggest evolutionary covariation between protein composition and the morphology of both spermatostyles and FRTs. We postulate that S‐LAPs (and other proteases) have evolved a novel structural role in spermatostyles and discuss spermatostyles as adaptations for delivering male‐derived materials to females.
Association between embryo morphokinetic development and intracytoplasmic sperm injection with epididymal sperm via time‐lapse imaging
Authors: Borges Edson , Braga Daniela , Provenza Rodrigo , Iaconelli Assumpto , Setti Amanda
Published: May 2024

The objective of this study was to investigate the impact of sperm source on embryo morphokinetics and the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles by considering the clustering of data (multiple embryos per patient that share a comparable developmental timing). This matched cohort study was performed at a private university–affiliated in vitro fertilization center. Women who underwent ICSI with epididymal sperm between January 2019 and December 2020 (the percutaneous epididymal sperm aspiration group, n = 32 cycles) were matched with women who underwent ICSI with ejaculated sperm because of idiopathic male factor infertility (the male factor infertility [MFI] group, n = 32 cycles) or female infertility (the control group, n = 32 cycles). Embryos were cultured in a time‐lapse imaging incubator, and morphokinetic development was recorded and compared among the groups. Significantly slower divisions were observed in embryos derived from epididymal sperm than in those derived from the MFI and control groups. Embryos derived from epididymal sperm had a significantly lower KIDScore (3.1 ± 0.2) than did those derived from ejaculated spermatozoa from the MFI (5.4 ± 0.1) and control (5.6 ± 0.2, p < 0.001) groups. Epididymal sperm‐derived embryos showed a significantly greater occurrence of multinucleation (23.2%) than did those derived from ejaculated sperm from the MFI and control groups (2.8% and 3.7%, p < 0.001, respectively). Epididymal sperm‐derived embryos were significantly more likely to undergo direct or reverse cleavage (11.1%) than ejaculated sperm‐derived embryos in the control group (4.3%, p = 0.001). In conclusion, delayed cell cleavage and increased incidences of blastomere multinucleation and abnormal cleavage patterns are observed when epididymal‐derived sperm are used for ICSI.
The impact of facility and staff characteristics on infection control of COVID‐19: Perceptions of elder care home managers in Stockholm, Sweden
Authors: Liljas Ann E. M. , Morath Lenke P. , Burström Bo , Schön Pär , Agerholm Janne
Published: May 2024

Aim

To examine the perceptions of managers of elder care homes on the impact of facility and staff characteristics on infection control of COVID‐19.

Design

Case study.

Methods

Six purposively sampled care home managers in the city of Stockholm were interviewed. Through content analysis, three categories and nine subcategories were identified.

Results

According to the interviewed care home managers, a home‐like environment that allows for isolation of residents and possibilities for staff to get changed and store personal protective equipment outside each resident's room was considered ideal. Experienced employees were reported as invaluable when facing an infectious outbreak. A mix of permanent and temporary staff was considered essential although some thought that temporary staff who work in multiple care homes might negatively influence the spread of infection. Language barriers among staff were considered an obstacle when trying to disseminate information.
Nursing diagnoses and hospital readmission of patients with respiratory diseases: Findings from a case–control study
Authors: Suárez‐González Paloma , Suárez‐Elosegui Ane , Arias‐Fernández Lucía , Pérez‐Regueiro Irene , Jimeno‐Demuth Francisco J. , Lana Alberto
Published: May 2024

Aim

The rate of readmission after hospitalisation for respiratory diseases has become a common and challenging clinical problem. Social and functional patient variables could help identify cases at high risk of readmission. The aim was to identify the nursing diagnoses that were associated with readmission after hospitalisation for respiratory disease in Spain.

Design

Case‐control study within the cohort of patients admitted for respiratory disease during 2016–19 in a tertiary public hospital in Spain (n = 3781).

Methods

Cases were patients who were readmitted within the first 30 days of discharge, and their controls were the remaining patients. All nursing diagnoses (n = 130) were collected from the electronic health record. They were then grouped into 29 informative diagnostic categories. Clinical confounder‐adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression models.

Results

The readmission rate was 13.1%. The nursing diagnoses categories ‘knowledge deficit’ (OR: 1.61; 95%CI: 1.13–2.31), ‘impaired skin integrity and risk of ulcer infection’ (OR: 1.45; 95%CI: 1.06–1.97) and ‘activity intolerance associated with fatigue’ (OR: 1.56; 95%CI: 1.21–2.01) were associated with an increased risk of suffering an episode of hospital readmission rate at 30% after hospital discharge, and this was independent of sociodemographic background, care variables and comorbidity.

Patient or public contribution

The nursing diagnoses assigned as part of the care plan of patients during hospital admission may be useful for predicting readmissions.
Cost‐effectiveness of the McGill interactive pediatric oncogenetic guidelines in identifying Li–Fraumeni syndrome in female patients with osteosarcoma
Authors: Rios Juan David , Simbulan Frances , Reichman Lara , Caswell Kimberly , Tachdjian Melissa , Malkin David , Cotton Cecilia , Nathan Paul C. , Goudie Catherine , Pechlivanoglou Petros
Published: May 2024

Background

Li–Fraumeni syndrome (LFS) is a penetrant cancer predisposition syndrome (CPS) associated with the development of many tumor types in young people including osteosarcoma and breast cancer (BC). The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) decision‐support tool provides a standardized approach to identify patients at risk of CPSs.

Methods

We conducted a cost–utility analysis, from the healthcare payer perspective, to compare MIPOGG‐guided, physician‐guided, and universal genetic testing strategies to detect LFS in female patients diagnosed at an age of less than 18 years with osteosarcoma. We developed a decision tree and discrete‐event simulation model to simulate the clinical and cost outcomes of the three genetic referral strategies on a cohort of female children diagnosed with osteosarcoma, especially focused on BC as subsequent cancer. Outcomes included BC incidence, quality‐adjusted life‐years (QALYs), healthcare costs, and incremental cost–utility ratios (ICURs). We conducted probabilistic and scenario analyses to assess the uncertainty surrounding model parameters.

Results

Compared to the physician‐guided testing, the MIPOGG‐guided strategy was marginally more expensive by $105 (−$516; $743), but slightly more effective by 0.003 (−0.04; 0.045) QALYs. Compared to MIPOGG, the universal testing strategy was $1333 ($732; $1953) more costly and associated with 0.011 (−0.043; 0.064) additional QALYs. The ICUR for the MIPOGG strategy was $33,947/QALY when compared to the physician strategy; the ICUR for universal testing strategy was $118,631/QALY when compared to the MIPOGG strategy.

Discussion

This study provides evidence for clinical and policy decision‐making on the cost‐effectiveness of genetic referral strategies to identify LFS in the setting of osteosarcoma. MIPOGG‐guided strategy was most likely to be cost‐effective at a willingness‐to‐pay threshold value of $50,000/QALY.
Pediatric pulmonary embolism: Unveiling clinical manifestations, diagnostic challenges, and outcomes in Southwest China
Authors: Zhao Dandong , Xiong Qiang , Lv Ying , Ting Gong , Lu Shuya , Luo Jian , Xie Xiaohong , Zhang Mingxiang , He Linli , Yang Tian , Tian Daiyin
Published: May 2024

Pulmonary embolism (PE) leads to obstruction of pulmonary circulation, resulting in increased pulmonary vascular resistance, elevated pulmonary arterial pressure, and increased right heart load. In severe cases, it can lead to cardiac decompensation and life‐threatening conditions. However, clinical studies on PE in children are limited, with many diagnostic and treatment guidelines derived from adult populations. We retrospectively analyzed the clinical manifestations, risk factors, co‐morbidity, and outcomes of PE patients admitted to a large children's hospital in southwest China. A total of 24 children with PE participated, 9 boys (37.5%), aged 0.1–14.6, (median: 8.15 years old). Except for two asymptomatic cases, the duration from symptom onset to the diagnosis of PE varied from 2 to 45 days (median: 12 days). Among these children, 13 (54.2%) patients experienced a delayed diagnosis exceeding 10 days. A total of 7 children died from underlying diseases, and no one met the outcome of recurrent PE or PE‐related death. Among the 17 survivors, complete resolution of PE was in 11 (64.7%) children, partial resolution who progressed to chronic PE was in 3 (17.7%) children, and no follow‐up computed tomography pulmonary angiography was performed in the remaining 3 (17.7%) children. This study revealed that the majority of pediatric PE cases presented with respiratory symptoms, with a considerable proportion initially misdiagnosed as pneumonia, and emphasized the importance of early recognition and appropriate management strategies in improving outcomes for the affected children. Further research is warranted to elucidate the pathophysiology, refine diagnostic algorithms, and establish standardized treatment protocols tailored to the pediatric population.
Medication‐related incidents in acute care hospitals among different age groups: An analysis of national patient safety report data
Authors: Han Ji Min , Heo Kyu‐Nam , Kim A Jeong , Lee Ah Young , Min Sangil , Ah Young‐Mi , Lee Ju‐Yeun
Published: May 2024

Purpose

This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups.

Methods

We analyzed medication‐related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed.

Results

Among a total of 5071 medication‐related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long‐term, permanent, and fatal harm. The proportion of medication‐related incidents that resulted in harm was the highest among the <1‐year‐old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication‐related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20–64‐year age group (256 cases, 11.7%) was ‘antibacterials for systemic use’, whereas ‘contrast media’ (236 cases, 11.6%) and ‘blood substitutes and perfusion solutions’ (98 cases, 19.3%) were the most prevalent drug classes in the ≥65‐ and <20‐year‐old age groups, respectively.

Conclusions

It is necessary to establish guidelines for the prevention of medication‐related incidents according to the medication use process and patient age group.
Assessment of Puccinia polliniicola as a potential biological control agent for Microstegium vimineum
Authors: Tan Min , Fang Yanxia , Zhang Yuanhe , Qiang Sheng
Published: May 2024

BACKGROUND

Microstegium vimineum (Trin.) A. Camus, commonly called stiltgrass, is a dominant weed in the United States and China. Although a lot of control approaches have been attempted, an economic, effective and practical measure has not been available to control the weed so far.

RESULTS

A serious rust disease of Microstegium vimineum was observed in three regions of Wenzhou city in China, from 2019 to 2021, with a disease incidence ranging from 82% to 97%. Typical rust disease symptoms on Microstegium vimineum were prominently visible during the early monsoon season (June–July), with chlorotic spots on the leaf surfaces. The morphological characterization of the strain WZ‐1 which was isolated from the diseased leaves was consistent with Puccinia polliniicola. The virulence tests showed that the average disease index of Microstegium vimineum plants could reach 35% at 10 days post‐inoculation. The host specificity of Puccinia polliniicola was tested on 64 plant species from 12 families and it did not cause any diseased symptoms on 24 major crops and 36 weeds, but slightly infected four gramineous weeds, Arthraxon hispidus, Polypogon fugax, Cynodon dactylon, and Microstegium ciliatum. However, newly‐produced urediniospores were not observed on the slightly infected plants. The urediniospores of strain WZ‐1 infected the Microstegium vimineum leaves by two main approaches: mycelium or appressorium invaded the stoma; and mycelium or appressorium directly invaded intercellular spaces. Field experiments showed that the rust disease naturally prevailed among Microstegium vimineum populations, causing severe rust disease symptoms on the leaf surface. The rust epidemic effectively controlled all of the target plants in the closed plot where the rust was released.

CONCLUSION

Puccinia polliniicola strain WZ‐1 has great potential to be used as a classical biological control agent against Microstegium vimineum. © 2024 Society of Chemical Industry.
Determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat by ultrahigh‐performance liquid chromatography–tandem mass spectrometry
Authors: Xu Liwei , Zha Andong , Xiong Xia , Sun Dehui
Published: May 2024

Rationale

Succinic acid and lactic acid have been associated with diarrhea in weaned piglets. The level of succinic acid and lactic acid in serum, meat, and intestinal contents is important to elucidate the mechanism of diarrhea in weaned piglets.

Methods

A facile method was developed for the quantification of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat using ultrahigh‐performance liquid chromatography–tandem mass spectrometry (UHPLC/MS/MS). The serum samples underwent protein precipitation with methanol. The meat and intestinal contents were freeze‐dried and homogenized using a tissue grinding apparatus. Methanol–water mixture (80:20, v/v) was used for homogenizing the meat, while water was used for homogenizing the intestinal contents. An additional step of protein precipitation with acetonitrile was required for the intestinal contents. The resulting solution was diluted with water before being analyzed by UHPLC/MS/MS. Separation of succinic acid and lactic acid could be achieved within 3 min using a Kinetic XB‐C18 column.

Results

The coefficients of variation for peak areas of succinic acid and lactic acid were less than 5.0%. The established method demonstrated good linearity as indicated by correlation coefficients exceeding 0.996. Additionally, satisfactory recoveries ranging from 88.58% to 108.8% were obtained. The detection limits (RS/N = 3) for succinic acid and lactic acid were determined to be 0.75 ng/mL and 0.02 μg/mL, respectively.

Conclusion

This method exhibited high sensitivity, simplicity in operation, and small sample weight, making it suitable for quantitative determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat. The method developed will provide valuable technical support in studying the metabolic mechanisms of succinic acid and lactic acid in pigs.
SARS‐CoV‐2, periodontal pathogens, and host factors: The trinity of oral post‐acute sequelae of COVID‐19
Authors: Schwartz Joel , Capistrano Kristelle J. , Gluck Joseph , Hezarkhani Armita , Naqvi Afsar R.
Published: May 2024

COVID‐19 as a pan‐epidemic is waning but there it is imperative to understand virus interaction with oral tissues and oral inflammatory diseases. We review periodontal disease (PD), a common inflammatory oral disease, as a driver of COVID‐19 and oral post‐acute‐sequelae conditions (PASC). Oral PASC identifies with PD, loss of teeth, dysgeusia, xerostomia, sialolitis‐sialolith, and mucositis. We contend that PD‐associated oral microbial dysbiosis involving higher burden of periodontopathic bacteria provide an optimal microenvironment for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. These pathogens interact with oral epithelial cells activate molecular or biochemical pathways that promote viral adherence, entry, and persistence in the oral cavity. A repertoire of diverse molecules identifies this relationship including lipids, carbohydrates and enzymes. The S protein of SARS‐CoV‐2 binds to the ACE2 receptor and is activated by protease activity of host furin or TRMPSS2 that cleave S protein subunits to promote viral entry. However, PD pathogens provide additional enzymatic assistance mimicking furin and augment SARS‐CoV‐2 adherence by inducing viral entry receptors ACE2/TRMPSS, which are poorly expressed on oral epithelial cells. We discuss the mechanisms involving periodontopathogens and host factors that facilitate SARS‐CoV‐2 infection and immune resistance resulting in incomplete clearance and risk for ‘long‐haul’ oral health issues characterising PASC. Finally, we suggest potential diagnostic markers and treatment avenues to mitigate oral PASC.