bluuebunny/crossref_metadata_2025 huggingface dataset:
While You Are Sleeping: Marital Ambivalence and Blunted Nocturnal Blood Pressure
Authors: Birmingham Wendy C. , Herr Raphael M. , Cressman Mikel , Patel Neha , Hung Man
Published: June 2024

Marital relationships offer health benefits, including a lower risk of cardiovascular disease (CVD). However, quality of the relationship matters; ambivalent behaviors may increase CVD risk by affecting blunted nocturnal blood pressure (BP) dipping. This study tracked daytime and nocturnal SBP and DBP in 180 normotensive individuals (90 couples; participant mean age 25.04; 91.58% white) over a 24 h period using ambulatory blood pressure monitors to explore the impact of martial quality. Results showed that perceptions of spousal ambivalence were associated with blunted nocturnal BP dipping. Perceptions of one’s own behavior as ambivalent also showed blunted nocturnal dipping. When in an ambivalent relationship, a gender interaction was found such that women were most likely to have blunted SBP dipping, but men were more likely to have blunted nocturnal DBP dipping. Overall, this study found an association between ambivalence and BP dipping, thus uncovering one virtually unexplored pathway by which marital relationships may have adverse effects on health.
Preferences for Follow-Up Procedures among Patients Lost to Follow-Up after Smoking Cessation Intervention among Therapists—An Interview Study
Authors: Wärjerstam Sanne , Dew-Hattens Camilla , Rasmussen Mette , Heitmann Berit Lilienthal , Raffing Rie , Tønnesen Hanne
Published: June 2024

Achieving high follow-up rates after smoking cessation interventions (SCIs) is a general challenge. The aim of this study was to identify preferences among patients and therapists for improving follow-up rates and to assess smoking status at 6 months among patients lost to follow-up. From the Danish STOPbase for Tobacco and Nicotine, which collects data on SCI across health care, 20 representative patients lost to follow-up by routine procedures were identified together with 11 therapists. All participated in individual semi-structured phone interviews, which for patients also included 6-month smoking status. Deductive and inductive analyses were performed. Four themes emerged from the analyses with several subthemes, all regarding contacts. Both patients and therapists preferred to intensify the follow-up process by boosting it with additional attempts and using voice messages, e-mail and/or SMS, calling at specified times of the day and avoiding calls from unknown numbers. In addition, some patients mentioned that they were busy or were not carrying their mobile devices at the time of a call as a barrier. Some therapists mentioned that barriers could include an expectation of relapse, but also a poor mental state, the time of day and patient fear of public systems. Among the patients originally lost to follow-up, 35% (95% CI 16%–59%) experienced continuous smoking cessation for 6 months, and the overall national rate was 22% (21.6–23.3%). In conclusion, both patients and therapists preferred intensified follow-up. The 6-month smoking status for patients lost to follow-up seemed to be similar to that of the routinely followed-up patients. These findings will be examined experimentally in a larger study.
The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy
Authors: Kiełbowski Kajetan , Bakinowska Estera , Procyk Grzegorz , Ziętara Marta , Pawlik Andrzej
Published: June 2024

Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder associated with muscle wasting and degeneration. The disease is caused by mutations in the gene that encodes dystrophin, a protein that links the cytoskeleton with cell membrane proteins. The current treatment methods aim to relieve the symptoms of the disease or partially rescue muscle functionality. However, they are insufficient to suppress disease progression. In recent years, studies have uncovered an important role for non-coding RNAs (ncRNAs) in regulating the progression of numerous diseases. ncRNAs, such as micro-RNAs (miRNAs), bind to their target messenger RNAs (mRNAs) to suppress translation. Understanding the mechanisms involving dysregulated miRNAs can improve diagnosis and suggest novel treatment methods for patients with DMD. This review presents the available evidence on the role of altered expression of miRNAs in the pathogenesis of DMD. We discuss the involvement of these molecules in the processes associated with muscle physiology and DMD-associated cardiomyopathy.
The Bloody Crossroads: Interactions between Periodontitis and Hematologic Diseases
Authors: Łobacz Michał , Mertowska Paulina , Mertowski Sebastian , Kozińska Aleksandra , Kwaśniewski Wojciech , Kos Marek , Grywalska Ewelina , Rahnama-Hezavah Mansur
Published: June 2024

Periodontitis is a common oral condition that can have a significant impact on the overall health of the body. In recent years, attention has been paid to potential relationships between periodontitis and various hematological disorders. This publication aims to present information available in the literature on this relationship, focusing on examples of red blood cell disorders (such as aplastic anemia and sickle cell anemia) and white blood cell disorders (such as cyclic neutropenia, maladaptive trained immunity, clonal hematopoiesis, leukemia, and multiple myeloma). Understanding these associations can help physicians and dentists better diagnose, monitor, and treat patients associated with both groups of conditions, highlighting the need for interdisciplinary care for patients with oral disorders and hematologic diseases.
Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments
Authors: Hovis Gabrielle , Chandra Neha , Kejriwal Nidhi , Hsieh Kaleb Jia-Yi , Chu Alison , Yang Isaac , Wadehra Madhuri
Published: June 2024

Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.
Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation
Authors: Kwon Mi-Ri , Park Ji-Soo , Ko Eun-Jung , Park Jin , Ju Eun-Jin , Shin Seol-Hwa , Son Ga-Won , Lee Hye-Won , Park Yun-Yong , Kang Myoung-Hee , Kim Yeon-Joo , Kim Byeong-Moon , Lee Hee-Jin , Kim Tae-Won , Kim Chong-Jai , Song Si-Yeol , Park Seok-Soon , Jeong Seong-Yun
Published: June 2024

Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.
Next-Generation Sequencing of the Human Aqueous Humour Microbiome
Authors: Schlunck Günther , Maier Philip , Maier Barbara , Maier Wolfgang , Strempel Sebastian , Reinhard Thomas , Heinzelmann Sonja
Published: June 2024

The microbiome of the ocular surface has been characterised, but only limited information is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed next-generation sequencing (NGS) of 16S rDNA genes in the aqueous humour. The aqueous humour was sampled from three patients during cataract surgery. Air swabs, conjunctival swabs from patients as well as from healthy donors served as controls. Following DNA extraction, the V3 and V4 hypervariable regions of the 16S rDNA gene were amplified and sequenced followed by denoising. The resulting Amplicon Sequence Variants were matched to a subset of the Ribosomal Database Project 16S database. The deduced bacterial community was then statistically analysed. The DNA content in all samples was low (0–1.49 ng/µL) but sufficient for analysis. The main phyla in the samples were Acinetobacteria (48%), Proteobacteria (26%), Firmicutes (14%), Acidobacteria (8%), and Bacteroidetes (2%). Patients’ conjunctival control samples and anterior chamber fluid showed similar patterns of bacterial species containing many waterborne species. Non-disinfected samples showed a different bacterial spectrum than the air swab samples. The data confirm the existence of an ocular surface microbiome. Meanwhile, a distinct intraocular microbiome was not discernible from the background, suggesting the absence of an intraocular microbiome in normal eyes.
Study on the Structure and Properties of Silk Fibers Obtained from Factory All-Age Artificial Diets
Authors: Pan Mengyao , Jiang Kexin , Jin Yuwei , Mao Ying , Lu Wangyang , Jiang Wenbin , Chen Wenxing
Published: June 2024

The traditional production mode of the sericulture industry is no longer suitable for the development requirements of modern agriculture; to facilitate the sustainable development of the sericulture industry, factory all-age artificial diet feeding came into being. Understanding the structural characteristics and properties of silk fibers obtained from factory all-age artificial diet feeding is an important prerequisite for application in the fields of textiles, clothing, biomedicine, and others. However, there have been no reports so far. In this paper, by feeding silkworms with factory all-age artificial diets (AD group) and mulberry leaves (ML group), silk fibers were obtained via two different feeding methods. The structure, mechanical properties, hygroscopic properties, and degradation properties were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Structurally, no new functional groups appeared in the AD group. Compared with the ML group, the structure of the two groups was similar, and there was no significant difference in mechanical properties and moisture absorption. The structure of degummed silk fibers is dominated by crystalline regions, but α-chymotrypsin hydrolyzes the amorphous regions of silk proteins, so that after 28 d of degradation, the weight loss of both is very small. This provides further justification for the feasibility of factory all-age artificial diets for silkworms.
The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis
Authors: Wang Chenyang , Oishi Kyosuke , Kobayashi Tadahiro , Fujii Ko , Horii Motoki , Fushida Natsumi , Kitano Tasuku , Maeda Shintaro , Ikawa Yuichi , Komuro Akito , Hamaguchi Yasuhito , Matsushita Takashi
Published: June 2024

The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription–polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.
mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process
Authors: Marafie Sulaiman K. , Al-Mulla Fahd , Abubaker Jehad
Published: June 2024

The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging. Given its extensive biological impact, mTOR signaling is a prime therapeutic target for addressing these complex conditions. The development of mTOR inhibitors has proven advantageous in numerous research domains. This review delves into the significance of mTOR signaling, highlighting the critical components of this intricate network that contribute to disease. Additionally, it addresses the latest findings on mTOR inhibitors and their clinical implications. The review also emphasizes the importance of developing more effective next-generation mTOR inhibitors with dual functions to efficiently target the mTOR pathways. A comprehensive understanding of mTOR signaling will enable the development of effective therapeutic strategies for managing diseases associated with mTOR dysregulation.
NaV1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model
Authors: Hartmann Nico , Knierim Maria , Maurer Wiebke , Dybkova Nataliya , Zeman Florian , Hasenfuß Gerd , Sossalla Samuel , Streckfuss-Bömeke Katrin
Published: June 2024

The sodium channel NaV1.8, encoded by the SCN10A gene, has recently emerged as a potential regulator of cardiac electrophysiology. We have previously shown that NaV1.8 contributes to arrhythmogenesis by inducing a persistent Na+ current (late Na+ current, INaL) in human atrial and ventricular cardiomyocytes (CM). We now aim to further investigate the contribution of NaV1.8 to human ventricular arrhythmogenesis at the CM-specific level using pharmacological inhibition as well as a genetic knockout (KO) of SCN10A in induced pluripotent stem cell CM (iPSC-CM). In functional voltage-clamp experiments, we demonstrate that INaL was significantly reduced in ventricular SCN10A-KO iPSC-CM and in control CM after a specific pharmacological inhibition of NaV1.8. In contrast, we did not find any effects on ventricular APD90. The frequency of spontaneous sarcoplasmic reticulum Ca2+ sparks and waves were reduced in SCN10A-KO iPSC-CM and control cells following the pharmacological inhibition of NaV1.8. We further analyzed potential triggers of arrhythmias and found reduced delayed afterdepolarizations (DAD) in SCN10A-KO iPSC-CM and after the specific inhibition of NaV1.8 in control cells. In conclusion, we show that NaV1.8-induced INaL primarily impacts arrhythmogenesis at a subcellular level, with minimal effects on systolic cellular Ca2+ release. The inhibition or knockout of NaV1.8 diminishes proarrhythmic triggers in ventricular CM. In conjunction with our previously published results, this work confirms NaV1.8 as a proarrhythmic target that may be useful in an anti-arrhythmic therapeutic strategy.
Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle
Authors: Schwarzer Evelin , Skorokhod Oleksii
Published: June 2024

Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis. Phosphorylation, acetylation, methylation, lipidation and lipoxidation, glycosylation, ubiquitination and sumoylation, nitrosylation and glutathionylation, all of which occur in malarial parasites, are reviewed. We provide information regarding the biological significance of these modifications along all phases of the complex life cycle of Plasmodium spp. Importantly, not only the parasite, but also the host and vector protein PTMs are often crucial for parasite growth and development. In addition to metabolic regulations, protein PTMs can result in epitopes that are able to elicit both innate and adaptive immune responses of the host or vector. We discuss some existing and prospective results from antimalarial drug discovery trials that target various PTM-related processes in the parasite or host.
Endogenous Hormone Levels and Transcriptomic Analysis Reveal the Mechanisms of Bulbil Initiation in Pinellia ternata
Authors: Mou Lan , Zhang Lang , Qiu Yujie , Liu Mingchen , Wu Lijuan , Mo Xu , Chen Ji , Liu Fan , Li Rui , Liu Chen , Tian Mengliang
Published: June 2024

Pinellia ternata is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil initiation remain unclear. Here, we characterized bulbil development via histological, transcriptomic, and targeted metabolomic analyses to unearth the intricate relationship between hormones, genes, and bulbil development. The results show that the bulbils initiate growth from the leaf axillary meristem (AM). In this stage, jasmonic acid (JA), abscisic acid (ABA), isopentenyl adenosine (IPA), and salicylic acid (SA) were highly enriched, while indole-3-acetic acid (IAA), zeatin, methyl jasmonate (MeJA), and 5-dexoxystrigol (5-DS) were notably decreased. Through OPLS-DA analysis, SA has emerged as the most crucial factor in initiating and positively regulating bulbil formation. Furthermore, a strong association between IPA and SA was observed during bulbil initiation. The transcriptional changes in IPT (Isopentenyltransferase), CRE1 (Cytokinin Response 1), A-ARR (Type-A Arabidopsis Response Regulator), B-ARR (Type-B Arabidopsis Response Regulator), AUX1 (Auxin Resistant 1), ARF (Auxin Response Factor), AUX/IAA (Auxin/Indole-3-acetic acid), GH3 (Gretchen Hagen 3), SAUR (Small Auxin Up RNA), GA2ox (Gibberellin 2-oxidase), GA20ox (Gibberellin 20-oxidase), AOS (Allene oxide synthase), AOC (Allene oxide cyclase), OPR (Oxophytodienoate Reductase), JMT (JA carboxy l Methyltransferase), COI1 (Coronatine Insensitive 1), JAZ (Jasmonate ZIM-domain), MYC2 (Myelocytomatosis 2), D27 (DWARF27), SMAX (Suppressor of MAX2), PAL (Phenylalanine Ammonia-Lyase), ICS (Isochorismate Synthase), NPR1 (Non-expressor of Pathogenesis-related Genes1), TGA (TGACG Sequence-specific Binding), PR-1 (Pathogenesis-related), MCSU (Molybdenium Cofactor Sulfurase), PP2C (Protein Phosphatase 2C), and SnRK (Sucrose Non-fermenting-related Protein Kinase 2) were highly correlated with hormone concentrations, indicating that bulbil initiation is coordinately controlled by multiple phytohormones. Notably, eight TFs (transcription factors) that regulate AM initiation have been identified as pivotal regulators of bulbil formation. Among these, WUS (WUSCHEL), CLV (CLAVATA), ATH1 (Arabidopsis Thaliana Homeobox Gene 1), and RAX (Regulator of Axillary meristems) have been observed to exhibit elevated expression levels. Conversely, LEAFY demonstrated contrasting expression patterns. The intricate expression profiles of these TFs are closely associated with the upregulated expression of KNOX(KNOTTED-like homeobox), suggesting a intricate regulatory network underlying the complex process of bulbil initiation. This study offers a profound understanding of the bulbil initiation process and could potentially aid in refining molecular breeding techniques specific to P. ternata.
Infection vs. Reinfection: The Immunomodulation of Erythropoiesis
Authors: Pêgo Ana Catarina , Lima Illyane Sofia , Martins Ana Catarina , Sá-Pereira Inês , Martins Gracelino , Gozzelino Raffaella
Published: June 2024

Severe malarial anemia (SMA) increases the morbidity and mortality of Plasmodium, the causative agent of malaria. SMA is mainly developed by children and pregnant women in response to the infection. It is characterized by ineffective erythropoiesis caused by impaired erythropoietin (EPO) signaling. To gain new insights into the pathogenesis of SMA, we investigated the relationship between the immune system and erythropoiesis, conducting comparative analyses in a mouse model of malaria. Red blood cell (RBC) production was evaluated in infected and reinfected animals to mimic endemic occurrences. Higher levels of circulating EPO were observed in response to (re)infection. Despite no major differences in bone marrow erythropoiesis, compensatory mechanisms of splenic RBC production were significantly reduced in reinfected mice. Concomitantly, a pronounced immune response activation was observed in erythropoietic organs of reinfected animals in relation to single-infected mice. Aged mice were also used to mimic the occurrence of malaria in the elderly. The increase in symptom severity was correlated with the enhanced activation of the immune system, which significantly impaired erythropoiesis. Immunocompromised mice further support the existence of an immune-shaping regulation of RBC production. Overall, our data reveal the strict correlation between erythropoiesis and immune cells, which ultimately dictates the severity of SMA.
Chitosan/Polyvinyl Alcohol-Based Biofilms Using Ternary Deep Eutectic Solvents towards Innovative Color-Stabilizing Systems for Anthocyanins
Authors: de Souza Hiléia K. S. , Guimarães Marta , Mateus Nuno , de Freitas Victor , Cruz Luís
Published: June 2024

Anthocyanins are amazing plant-derived colorants with highly valuable properties; however, their chemical and color instability issues limit their wide application in different food industry-related products such as active and intelligent packaging. In a previous study, it was demonstrated that anthocyanins could be stabilized into green plasticizers namely deep eutectic solvents (DESs). In this work, the fabrication of edible films by integrating anthocyanins along with DESs into biocompatible chitosan (CHT)-based formulations enriched with polyvinyl alcohol (PVA) and PVA nanoparticles was investigated. CHT/PVA-DES films’ physical properties were characterized by scanning electron microscopy, water vapor permeability, swelling index, moisture sorption isotherm, and thermogravimetry analysis. Innovative red-to-blue formulation films were achieved for CHT/PVA nanoparticles (for 5 min of sonication) at a molar ratio 1:1, and with 10% of ternary DES (TDES)-containing malvidin-3-glucoside (0.1%) where the physical properties of films were enhanced. After immersion in solutions at different pH values, films submitted to pHs 5–8 were revealed to be more color stable and resistant with time than at acidic pH values.
Synthesis and Study of Building Blocks with Dibenzo[b,f]oxepine: Potential Microtubule Inhibitors
Authors: Tobiasz Piotr , Borys Filip , Kucharska Marta , Poterała Marcin , Krawczyk Hanna
Published: June 2024

The synthesis of biphenylmethoxydibenzo[b,f]oxepine or photoswitchable fluorinated dibenzo[b,f]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[b,f]oxepine skeleton. An analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light.
Endothelial-to-Mesenchymal Transition in an Hereditary Hemorrhagic Telangiectasia-like Pediatric Case of Multiple Pulmonary Arteriovenous Malformations
Authors: Lorente-Herraiz Laura , Cuesta Angel M. , Recio-Poveda Lucía , Botella Luisa M. , Albiñana Virginia
Published: June 2024

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connections between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5000/8000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-β pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8-year-old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case under study follows a molecular pattern which is HHT-like. Therefore, molecular- biological and cellular-functional analyses have been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial-to-mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.
Acute Management of Paroxysmal Atrial Fibrillation with Intravenous Flecainide plus Oral Beta-Blockers
Authors: Kartalis Athanasios , Afendoulis Dimitrios , Voutas Petros , Moutafi Maria , Papagiannis Nikolaos , Garoufalis Stefanos , Kartalis Nikolaos , Smyrnioudis Nikolaos , Ziakas Antonios , Didagelos Matthaios
Published: June 2024

Background: Intravenous (IV) flecainide is recommended for the pharmacological cardioversion of recent-onset atrial fibrillation (AF). The aim of this study was to study the efficacy and safety of IV flecainide, co-administered with oral b-blockers, for the cardioversion of paroxysmal AF. Methods: Single-center registry, initiated in the “Skylitseion” General Hospital of Chios in January 2020. The main inclusion criterion was IV flecainide administration plus oral b-blocker for recent-onset AF (≤48 h). The primary outcome was conversion to sinus rhythm at 2 h. Results: A total of 121 (73 males and 48 females, with mean age 61.4 years) consecutive, unselected patients who complied with the study protocol were included. A successful conversion to sinus rhythm at 2 h was achieved in 99 patients (success rate: 81.8%). The median conversion time was 11.7 min (varied from 3 to 23 min). Duration of hospitalization was significantly shorter in patients who were successfully cardioverted with IV flecainide (10.9 vs. 30.7 h, p < 0.001). No serious adverse events were recorded. Conclusion: This is one of the largest registries worldwide, evaluating the effectiveness and safety of IV flecainide co-administered with a b-blocker in the acute management of recent-onset AF. The successful conversion rate at 2 h is very high and quick with no serious adverse events.
A Peer Mentoring Program for Faculty Development in Presentation Skills
Authors: Smith Jeremy , Goldberger Zachary D. , Zakowski Laura J.
Published: June 2024

Junior faculty are often called upon to deliver high-stakes large-group presentations. Training in the skills needed to do this effectively is often lacking. We devised a 1.25 h coaching program. The coach analyzed a practice run of the presentation using a locally developed assessment tool. Areas covered included public speaking skills, promoting learner understanding and retention, creating a dynamic learning climate, and optimal use of slides. COVID-19 necessitated a switch to virtual coaching, and we studied the impact of virtual vs. in-person coaching. We added two additional coaches and studied the transferability of the coaching component. There was high uptake of the offered coaching. Participant surveys showed improved comfort levels with large-group presentations; had a sense that their presentation skills had improved; showed an increased likelihood of volunteering for future speaking opportunities; and were likely to recommend the program. Comparisons between virtual and in-person coaching showed no statistical difference, and there was little difference between the original coach and the subsequent two coaches. Qualitative assessments revealed broad areas in which faculty felt the program had been most impactful. The coaching program was well-received and resulted in concrete positive changes in presenter behavior. Conducting the coaching in a virtual manner may increase the feasibility of the intervention, as would expanding the coach pool.
Generative AI, Research Ethics, and Higher Education Research: Insights from a Scientometric Analysis
Authors: Qadhi Saba Mansoor , Alduais Ahmed , Chaaban Youmen , Khraisheh Majeda
Published: June 2024

In the digital age, the intersection of artificial intelligence (AI) and higher education (HE) poses novel ethical considerations, necessitating a comprehensive exploration of this multifaceted relationship. This study aims to quantify and characterize the current research trends and critically assess the discourse on ethical AI applications within HE. Employing a mixed-methods design, we integrated quantitative data from the Web of Science, Scopus, and the Lens databases with qualitative insights from selected studies to perform scientometric and content analyses, yielding a nuanced landscape of AI utilization in HE. Our results identified vital research areas through citation bursts, keyword co-occurrence, and thematic clusters. We provided a conceptual model for ethical AI integration in HE, encapsulating dichotomous perspectives on AI’s role in education. Three thematic clusters were identified: ethical frameworks and policy development, academic integrity and content creation, and student interaction with AI. The study concludes that, while AI offers substantial benefits for educational advancement, it also brings challenges that necessitate vigilant governance to uphold academic integrity and ethical standards. The implications extend to policymakers, educators, and AI developers, highlighting the need for ethical guidelines, AI literacy, and human-centered AI tools.
Effect of Ephestia kuehniella Eggs on Development and Transcriptome of the Ladybird Beetle Propylea japonica
Authors: Li Guannan , Chen Pei-Tao , Chen Mei-Lan , Chen Tuo-Yan , Huang Yu-Hao , Lü Xin , Li Hao-Sen , Pang Hong
Published: June 2024

The eggs of the Mediterranean flour moth, Ephestia kuehniella, are frequently utilized as alternative diets and have demonstrated promising outcomes when consumed by various insects. Nonetheless, the specific reasons for their effectiveness remain unclear. In our study, we assessed the developmental performance of the ladybird Propylea japonica when fed E. kuehniella eggs, alongside 12 factitious prey or artificial diets. Our findings revealed that ladybirds fed E. kuehniella eggs displayed a performance comparable to those fed the natural prey Megoura crassicauda. Transcriptome profiling of larvae raised on E. kuehniella eggs and M. crassicauda revealed that genes upregulated in the former group were enriched in metabolic pathways associated with carbohydrates, lipids, and other essential nutrients. This suggests that E. kuehniella eggs may have a higher nutrient content compared to natural prey. Furthermore, a notable downregulation in the expression of immune effector genes, such as Attacin and Coleoptericin, was observed, which might be attributed to the lower microbial content in E. kuehniella eggs compared to M. crassicauda. We suggest that the difference between E. kuehniella eggs and M. crassicauda as food sources for P. japonica lies in their nutrient and microbial contents. These findings provide valuable insights for the advancement of innovative artificial breeding systems for natural enemies.
A Maximum Dose Bioassay to Assess Efficacy of Spinetoram against Cowpea Thrip Megalurothrips usitatus in China
Authors: Yu Huailiang , Wu Mingyue , Li Shaoka , Li Jin , Zou Xiang , Guo Zhaojiang , Wu Qingjun , Zhang Youjun , Kong Xiangyi , Xie Wen
Published: June 2024

The bean flower thrip Megalurothrips usitatus (Bagnall) is a severe pest on cowpeas and causes a 20–30% reduction in cowpeas in Hainan, China, with even complete crop failure in severe cases. Spinetoram is currently the most important pesticide against M. usitatus in cowpea production. In the main producing areas of cowpeas in Hainan, however, the efficacy of spinetoram against M. usitatus is not well known. In the present study, we employed the maximum dose bioassay to evaluate the efficacy of the mortality rates of adult thrips at F0 in spinetoram, freshly collected from 212 field populations of M. usitatus collected from 20 villages in the Yazhou District of Hainan. Our results showed that the mortality rates of these thrip populations exposed to spinetoram were from 3.31% to 100%. Among them, the mortality rates of 66.98% (142/212) of the populations exceeded 80%, while that of 33.96% (72/212) of the populations surpassed 90%. Only a small proportion of 0.47% (1/212) the populations exhibited a mortality rate below 10%, and 4.72% (10/212) displayed rates below 50%. Furthermore, significant differences were also observed in the mortality rates of thrips among different villages. Taken together, the maximum dosage bioassay method is a rapid and easily implemented approach providing valuable insights into the field efficacy of insecticides and offers guidance in determining the optimal dosage required in the field. Spinetoram is still effective against M. usitatus in the main producing areas of cowpeas in Hainan, but caution should be exercised in its combined use with other methods to reduce potential resistance.
Criticality of Spray Solvent Choice on the Performance of Next Generation, Spray-Based Ambient Mass Spectrometric Ionization Sources: A Case Study Based on Synthetic Cannabinoid Forensic Evidence
Authors: Mukta Shahnaz , Bondzie Ebenezer H. , Bell Sara E. , Deberry Chase , Mulligan Christopher C.
Published: June 2024

Mass spectrometry (MS) is a highly selective and sensitive analytical tool with a myriad of applications, but such techniques are typically used in laboratory settings due to the handling and preparations that are necessary. The merging of two streams of robust research, portable MS systems and next-generation ambient ionization methods, now provides the ability to perform high-performance chemical screening in an on-site and on-demand manner, with natural applications in disciplines such as forensic science, where samples of interest are typically found in field environments (i.e., traffic stops, crime scenes, etc.). Correspondingly, investigations regarding the suitability and robustness of these methodologies when they are utilized for authentic forensic evidence processing are prudent. This work reports critical insights into the role that choice of spray solvent system plays regarding analytical performance of two spray-based ambient ionization sources, paper spray ionization (PSI) and filter cone spray ionization (FCSI), when employed for evidence types containing emerging synthetic cannabinoids. The systematic characterization studies reported herein show that the applied spray solvent can dramatically affect both spectral intensity and signal duration, and in some circumstances, yield deleterious false negative responses. Overall, acetonitrile-based systems are shown to strike a balance between analyte solubility concerns and spray ionization dynamics of the novel ion sources employed on portable MS systems.
Win Statistics in Observational Cancer Research: Integrating Clinical and Quality-of-Life Outcomes
Authors: Chiaruttini Maria Vittoria , Lorenzoni Giulia , Spolverato Gaya , Gregori Dario
Published: June 2024

Background: Quality-of-life metrics are increasingly important for oncological patients alongside traditional endpoints like mortality and disease progression. Statistical tools such as Win Ratio, Win Odds, and Net Benefit prioritize clinically significant outcomes using composite endpoints. In randomized trials, Win Statistics provide fair comparisons between treatment and control groups. However, their use in observational studies is complicated by confounding variables. Propensity score (PS) matching mitigates confounding variables but may reduce the sample size, affecting the power of win statistics analyses. Alternatively, PS matching can stratify samples, preserving the sample size. This study aims to assess the long-term impact of these methods on decision making, particularly in colorectal cancer patients. Methods: A motivating example involves a cohort of patients from the ReSARCh observational study (2016–2021) with locally advanced adenocarcinoma of the rectum, situated up to 12 cm from the anal verge. These patients underwent either a watch-and-wait approach (WW) or trans-anal local excision (LE). Win statistics compared the effects of WW and LE on a composite outcome (overall survival, recurrence, presence of ostomy, and rectum excision). For matched win statistics, we used robust inference techniques proposed by Matsouaka et al. (2022), and for stratified win statistics, we applied the method proposed by Dong et al. (2018). A simulation study assessed the coverage probability of matched and stratified win statistics in balanced and unbalanced groups, calculating how often the confidence intervals included the true values of WR, NB, and WO across 1000 simulations. Results: The results suggest a better efficacy of the LE approach when considering efficacy outcomes alone (WR: 0.47 (0.01 to 1.14); NB: −0.16 (−0.34 to 0.02); and WO: 0.73 (0.5 to 1.05)). However, when QoL outcomes are included in the analyses, the estimates are closer to 1 (WR: 0.87 (0.06 to 2.06); WO: 0.93 (0.61 to 1.4)) and to 0 (NB: −0.04 (−0.25 to 0.17)), indicating a negative impact of the treatment effect of LE regarding the presence of ostomy and the excision of the rectum. Moreover, based on the simulation study, our findings underscore the superior performance of matched compared to stratified win statistics in terms of coverage probability (matched WR: 97% vs. stratified WR: 33.3% in a high-imbalance setting; matched WR: 98% vs. stratified WR: 34.4% in a medium-imbalance setting; and matched WR: 99.2% vs. stratified WR: 37.4% in a low-imbalance setting). Conclusions: In conclusion, our study sheds light on the interpretation of the results of win statistics in terms of statistical significance, providing insights into the application of pairwise comparison in observational settings, promoting its use to improve outcomes for cancer patients.
Minimally Invasive Approach for Replacement of the Ascending Aorta towards the Proximal Aortic Arch
Authors: Helms Florian , Deniz Ezin , Krüger Heike , Zubarevich Alina , Schmitto Jan Dieter , Poyanmehr Reza , Hinteregger Martin , Martens Andreas , Weymann Alexander , Ruhparwar Arjang , Schmack Bastian , Popov Aron-Frederik
Published: June 2024

Objectives: In recent years, minimally invasive approaches have been used with increasing frequency, even for more complex aortic procedures. However, evidence on the practicability and safety of expanding minimally invasive techniques from isolated operations of the ascending aorta towards more complex operations such as the hemiarch replacement is still scarce to date. Methods: A total of 86 patients undergoing elective surgical replacement of the ascending aorta with (n = 40) or without (n = 46) concomitant proximal aortic arch replacement between 2009 and 2023 were analyzed in a retrospective single-center analysis. Groups were compared regarding operation times, intra- and postoperative complications and long-term survival. Results: Operation times and ventilation times were significantly longer in the hemiarch replacement group. Despite this, no statistically significant differences between the two groups were observed for the duration of the ICU and hospital stay and postoperative complication rates. At ten-year follow-up, overall survival was 82.6% after isolated ascending aorta replacement and 86.3% after hemiarch replacement (p = 0.441). Conclusions: Expanding the indication for minimally invasive aortic surgery towards the proximal aortic arch resulted in comparable postoperative complication rates, length of hospital stay and overall long-term survival compared to the well-established minimally invasive isolated supracommissural ascending aorta replacement.
Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?
Authors: Makarov Igor , Voronkina Daria , Gurshchenkov Alexander , Ryzhkov Anton , Starshinova Anna , Kudlay Dmitry , Mitrofanova Lubov
Published: June 2024

Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12–14 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.
A Retrospective Cohort Analysis of Transarterial Chemoembolization for Hepatocellular Cancer at a Tertiary Center in Switzerland
Authors: Haak Fabian , Karli Tobias , Takes Martin , Zech Christoph J. , Kollmar Otto , Soysal Savas D.
Published: June 2024

Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan–Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15–6.78). Complications occurred after TACE procedures: Clavien–Dindo I + II = 30, Clavien–Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm.
Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers
Authors: Asmundo Luigi , Rizzetto Francesco , Blake Michael , Anderson Mark , Mojtahed Amirkasra , Bradley William , Shenoy-Bhangle Anuradha , Fernandez-del Castillo Carlos , Qadan Motaz , Ferrone Cristina , Clark Jeffrey , Ambrosini Valentina , Picchio Maria , Mapelli Paola , Evangelista Laura , Leithner Doris , Nikolaou Konstantin , Ursprung Stephan , Fanti Stefano , Vanzulli Angelo , Catalano Onofrio Antonio
Published: June 2024

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.