bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Health for Migrants, Ethnic and Cultural Minorities and the Role of Participatory Development: A Scoping Review
Authors: Radu Irina , Scheermesser Mandy , Spiess Martina Rebekka , Schulze Christina , Händler-Schuster Daniela , Pehlke-Milde Jessica
Published: October 2023

Digital health interventions (DHIs) are increasingly used to address the health of migrants and ethnic minorities, some of whom have reduced access to health services and worse health outcomes than majority populations. This study aims to give an overview of digital health interventions developed for ethnic or cultural minority and migrant populations, the health problems they address, their effectiveness at the individual level and the degree of participation of target populations during development. We used the methodological approach of the scoping review outlined by Tricco. We found a total of 2248 studies, of which 57 were included, mostly using mobile health technologies, followed by websites, informational videos, text messages and telehealth. Most interventions focused on illness self-management, mental health and wellbeing, followed by pregnancy and overall lifestyle habits. About half did not involve the target population in development and only a minority involved them consistently. The studies we found indicate that the increased involvement of the target population in the development of digital health tools leads to a greater acceptance of their use.
The Effects of Chronological Age on the Chondrogenic Potential of Mesenchymal Stromal Cells: A Systematic Review
Authors: Vogt Antonia , Kapetanos Konstantinos , Christodoulou Neophytos , Asimakopoulos Dimitrios , Birch Mark A. , McCaskie Andrew W. , Khan Wasim
Published: October 2023

Tissue engineering and cell therapy for regenerative medicine have great potential to treat chronic disorders. In musculoskeletal disorders, mesenchymal stromal cells (MSCs) have been identified as a relevant cell type in cell and regenerative strategies due to their multi-lineage potential, although this is likely to be a result of their trophic and immunomodulatory effects on other cells. This PRISMA systematic review aims to assess whether the age of the patient influences the chondrogenic potential of MSCs in regenerative therapy. We identified a total of 3027 studies after performing a search of four databases, including Cochrane, Web of Science, Medline, and PubMed. After applying inclusion and exclusion criteria, a total of 14 papers were identified that were reviewed, assessed, and reported. Cell surface characterization and proliferation, as well as the osteogenic, adipogenic, and chondrogenic differentiation, were investigated as part of the analysis of these studies. Most included studies suggest a clear link between aged donor MSCs and diminished clonogenic and proliferative potential. Our study reveals a heterogeneous and conflicting range of outcomes concerning the chondrogenic, osteogenic, and adipogenic potential of MSCs in relation to age. Further investigations on the in vitro effects of chronological age on the chondrogenic potential of MSCs should follow the outcomes of this systematic review, shedding more light on this complex relationship.
Molecular Mechanisms for the Regulation of Nuclear Membrane Integrity
Authors: Lee Ga-Eun , Byun Jiin , Lee Cheol-Jung , Cho Yong-Yeon
Published: October 2023

The nuclear membrane serves a critical role in protecting the contents of the nucleus and facilitating material and signal exchange between the nucleus and cytoplasm. While extensive research has been dedicated to topics such as nuclear membrane assembly and disassembly during cell division, as well as interactions between nuclear transmembrane proteins and both nucleoskeletal and cytoskeletal components, there has been comparatively less emphasis on exploring the regulation of nuclear morphology through nuclear membrane integrity. In particular, the role of type II integral proteins, which also function as transcription factors, within the nuclear membrane remains an area of research that is yet to be fully explored. The integrity of the nuclear membrane is pivotal not only during cell division but also in the regulation of gene expression and the communication between the nucleus and cytoplasm. Importantly, it plays a significant role in the development of various diseases. This review paper seeks to illuminate the biomolecules responsible for maintaining the integrity of the nuclear membrane. It will delve into the mechanisms that influence nuclear membrane integrity and provide insights into the role of type II membrane protein transcription factors in this context. Understanding these aspects is of utmost importance, as it can offer valuable insights into the intricate processes governing nuclear membrane integrity. Such insights have broad-reaching implications for cellular function and our understanding of disease pathogenesis.
Photosynthesis Response and Transcriptional Analysis: Dissecting the Role of SlHB8 in Regulating Drought Resistance in Tomato Plants
Authors: Yang Yinghua , Zhang Xinyue , Zhong Qiuxiang , Liu Xiaojuan , Guan Hongling , Chen Riyuan , Hao Yanwei , Yang Xiaolong
Published: October 2023

Deciphering drought resistance in crops is crucial for enhancing water productivity. Previous studies have highlighted the significant role of the transcription factor SlHB8 in regulating developmental processes in tomato plants but its involvement in drought resistance remains unclear. Here, gene overexpression (SlHB8-OE) and gene knockout (slhb8) tomato plants were utilized to study the role of SlHB8 in regulating drought resistance. Our findings showed that slhb8 plants exhibited a robust resistant phenotype under drought stress conditions. The stomata of slhb8 tomato leaves displayed significant closure, effectively mitigating the adverse effects of drought stress on photosynthetic efficiency. The slhb8 plants exhibited a decrease in oxidative damage and a substantial increase in antioxidant enzyme activity. Moreover, slhb8 effectively alleviated the degree of photoinhibition and chloroplast damage caused by drought stress. SlHB8 regulates the expression of numerous genes related to photosynthesis (such as SlPSAN, SlPSAL, SlPSBP, and SlTIC62) and stress signal transduction (such as SlCIPK25, SlABA4, and SlJA2) in response to drought stress. Additionally, slhb8 plants exhibited enhanced water absorption capacity and upregulated expression of several aquaporin genes including SlPIP1;3, SlPIP2;6, SlTIP3;1, SlNIP1;2, and SlXIP1;1. Collectively, our findings suggest that SlHB8 plays a negative regulatory role in the drought resistance of tomato plants.
Comparative Transcriptomic Analysis Revealed Potential Differential Mechanisms of Grass Carp Reovirus Pathogenicity
Authors: Kong Weiguang , Ding Guangyi , Yang Peng , Li Yuqing , Cheng Gaofeng , Cai Chang , Xiao Jun , Feng Hao , Xu Zhen
Published: October 2023

Grass carp reovirus (GCRV), one of the most serious pathogens threatening grass carp (Ctenopharyngodon idella), can lead to grass carp hemorrhagic disease (GCHD). Currently, GCRV can be divided into three genotypes, but the comparison of their pathogenic mechanisms and the host responses remain unclear. In this study, we utilized the Ctenopharyngodon idella kidney (CIK) model infected with GCRV to conduct comparative studies on the three genotypes. We observed a cytopathic effect (CPE) in the GCRV-I and GCRV-III groups, whereas the GCRV-II group did not show any CPE. Moreover, a consistent trend in the mRNA expression levels of antiviral-related genes across all experimental groups of CIK cells was detected via qPCR and further explored through RNA-seq analysis. Importantly, GO/KEGG enrichment analysis showed that GCRV-I, -II, and -III could all activate the immune response in CIK cells, but GCRV-II induced more intense immune responses. Intriguingly, transcriptomic analysis revealed a widespread down-regulation of metabolism processes such as steroid biosynthesis, butanoate metabolism, and N-Glycan biosynthesis in infected CIK cells. Overall, our results reveal the CIK cells showed unique responses in immunity and metabolism in the three genotypes of GCRV infection. These results provide a theoretical basis for understanding the pathogenesis and prevention and control methods of GCRV.
GSK3 as a Master Regulator of Cellular Processes
Authors: Lichtinghagen Ralf , Huber René
Published: October 2023

Since its initial purification and characterization as an enzyme negatively regulating glycogen synthase activity [...]
Myocardial Fibrosis and Steatosis in Patients with Aortic Stenosis: Roles of Myostatin and Ceramides
Authors: Zoico Elena , Giani Anna , Saatchi Tanaz , Rizzatti Vanni , Mazzali Gloria , Fantin Francesco , Benfari Giovanni , Onorati Francesco , Urbani Silvia , Zamboni Mauro
Published: October 2023

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S’, global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets.
Targeted Mass Spectrometry Reveals Interferon-Dependent Eicosanoid and Fatty Acid Alterations in Chronic Myeloid Leukaemia
Authors: Scott Hannah C. , Draganov Simeon D. , Yu Zhanru , Kessler Benedikt M. , Pinto-Fernández Adán
Published: October 2023

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, the detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography–dynamic multiple reaction monitoring–targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of chronic myeloid leukaemia (CML), we found that the levels of intra- and extracellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), extracellular Prostaglandin F2α (PGF2α), extracellular 5-Hydroxyeicosatetraenoic acid (5-HETE), extracellular Palmitic acid (PA, C16:0) and extracellular Stearic acid (SA, C18:0), were altered in response to immunomodulation by type I interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism, with potential relevance in the context of cancer inflammation and CML.
Neuroblastoma Patients’ Outcome and Chromosomal Instability
Authors: Ognibene Marzia , De Marco Patrizia , Amoroso Loredana , Fragola Martina , Zara Federico , Parodi Stefano , Pezzolo Annalisa
Published: October 2023

Chromosomal instability (CIN) induces a high rate of losses or gains of whole chromosomes or parts of chromosomes. It is a hallmark of most human cancers and one of the causes of aneuploidy and intra-tumor heterogeneity. The present study aimed to evaluate the potential prognostic role of CIN in NB patients at diagnosis. We performed array comparative genomic hybridization analyses on 451 primary NB patients at the onset of the disease. To assess global chromosomal instability with high precision, we focused on the total number of DNA breakpoints of gains or losses of chromosome arms. For each tumor, an array-CGH-based breakpoint instability index (BPI) was assigned which defined the total number of chromosomal breakpoints per genome. This approach allowed us to quantify CIN related to whole genome disruption in all NB cases analyzed. We found differences in chromosomal breakages among the NB clinical risk groups. High BPI values are negatively associated with survival of NB patients. This association remains significant when correcting for stage, age, and MYCN status in the Cox model. Stratified analysis confirms the prognostic effect of BPI index in low-risk NB patients with non-amplified MYCN and with segmental chromosome aberrations.
Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032
Authors: Eedara Basanth Babu , Manivannan Bhagyashree , Alabsi Wafaa , Sun Bo , Curiel-Lewandrowski Clara , Zhang Tianshun , Bode Ann M. , Mansour Heidi M.
Published: October 2023

Nonmelanoma skin cancers (NMSC) are the most common skin cancers, and about 5.4 million people are diagnosed each year in the United States. A newly developed T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor, HI-TOPK-032, is effective in suppressing colon cancer cell growth, inducing the apoptosis of colon cancer cells and ultraviolet (UV) light-induced squamous cell carcinoma (SCC). This study aimed to investigate the physicochemical properties, permeation behavior, and cytotoxicity potential of HI-TOPK-032 prior to the development of a suitable topical formulation for targeted skin drug delivery. Techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRPD), Karl Fisher (KF) coulometric titration, Raman spectrometry, confocal Raman microscopy (CRM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and Fourier transform infrared microscopy were used to characterize HI-TOPK-032. The dose effect of HI-TOPK-032 on in vitro cell viability was evaluated using a 2D cell culture of the human skin keratinocyte cell line (HaCaT) and primary normal human epidermal keratinocytes (NHEKs). Transepithelial electrical resistance (TEER) at the air–liquid interface as a function of dose and time was measured on the HaCAT human skin cell line. The membrane permeation behavior of HI-TOPK-032 was tested using the Strat-M® synthetic biomimetic membrane with an in vitro Franz cell diffusion system. The physicochemical evaluation results confirmed the amorphous nature of the drug and the homogeneity of the sample with all characteristic chemical peaks. The in vitro cell viability assay results confirmed 100% cell viability up to 10 µM of HI-TOPK-032. Further, a rapid, specific, precise, and validated reverse phase-high performance liquid chromatography (RP-HPLC) method for the quantitative estimation of HI-TOPK-032 was developed. This is the first systematic and comprehensive characterization of HI-TOPK-032 and a report of these findings.
Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives
Authors: Wang Jiaxin , Ren Lida , Liu Xinqi , Liu Jihong , Ling Qing
Published: October 2023

Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as “a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span”. Despite the widespread prevalence of UAB/DU, there are significant gaps in our understanding of its pathophysiological mechanisms, diagnosis, and treatment compared with overactive bladder (OAB) and detrusor overactivity (DO). These gaps are such that clinicians regard UAB/DU as an incurable condition. In recent years, the understanding of UAB has increased. The definition of UAB has been clarified, and the diagnostic criteria for DU have been considered more comprehensively. Meanwhile, a number of non-invasive diagnostic methods have also been reported. Clinical trials involving novel drugs, electrical stimulation, and stem cell therapy have shown promising results. Therefore, this review summarizes recent reports on UAB and DU and highlights the latest advances in their diagnosis and treatment.
ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization
Authors: Lu Tu , Xie Fangfang , Huang Chuangxin , Zhou Lijun , Lai Kunbei , Gong Yajun , Li Zijing , Li Longhui , Liang Jiandong , Cong Qifeng , Li Weihua , Ju Rong , Zhang Sarah X. , Jin Chenjin
Published: October 2023

Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.
Artemisia annua Extract Attenuate Doxorubicin-Induced Hepatic Injury via PI-3K/Akt/Nrf-2-Mediated Signaling Pathway in Rats
Authors: El-Said Karim Samy , Haidyrah Ahmed S. , Mobasher Maysa A. , Khayyat Arwa Ishaq A. , Shakoori Afnan , Al-Sowayan Noorah Saleh , Barnawi Ibrahim Omar , Mariah Reham A.
Published: October 2023

Doxorubicin (DOX), which is used to treat cancer, has harmful effects that limit its therapeutic application. Finding preventative agents to thwart DOX-caused injuries is thus imperative. Artemisia annua has numerous biomedical uses. This study aims to investigate the attenuative effect of Artemisia annua leaf extract (AALE) treatment on DOX-induced hepatic toxicity in male rats. A phytochemical screening of AALE was evaluated. Forty male rats were used; G1 was a negative control group, G2 was injected with AALE (150 mg/kg) intraperitoneally (i.p) daily for a month, 4 mg/kg of DOX was given i.p to G3 once a week for a month, and G4 was injected with DOX as G3 and with AALE as G2. Body weight changes and biochemical, molecular, and histopathological investigations were assessed. The results showed that AALE contains promising phytochemical constituents that contribute to several potential biomedical applications. AALE mitigated the hepatotoxicity induced by DOX in rats as evidenced by restoring the alterations in the biochemical parameters, antioxidant gene expression, and hepatic histopathological alterations in rats. Importantly, the impact of AALE against the hepatic deterioration resulting from DOX treatment is through activation of the PI-3K/Akt/Nrf-2 signaling, which in turn induces the antioxidant agents.
Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases
Authors: Videla Luis Alberto , Valenzuela Rodrigo , Del Campo Andrea , Zúñiga-Hernández Jessica
Published: October 2023

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.
ZNF714 Supports Pro-Oncogenic Features in Lung Cancer Cells
Authors: Oleksiewicz Urszula , Machnik Marta , Sobocińska Joanna , Molenda Sara , Olechnowicz Anna , Florczak Anna , Smolibowski Mikołaj , Kaczmarek Mariusz
Published: October 2023

Despite the ongoing progress in diagnosis and treatments, cancer remains a threat to more than one-third of the human population. The emerging data indicate that many Krüppel-associated box zinc finger proteins (KRAB-ZNF) belonging to a large gene family may be involved in carcinogenesis. Our previous study identified Zinc Finger Protein 714 (ZNF714), a KRAB-ZNF gene of unknown function, as being commonly overexpressed in many tumors, pointing to its hypothetical oncogenic role. Here, we harnessed The Cancer Genome Atlas (TCGA)-centered databases and performed functional studies with transcriptomic and methylomic profiling to explore ZNF714 function in cancer. Our pan-cancer analyses confirmed frequent ZNF714 overexpression in multiple tumors, possibly due to regional amplification, promoter hypomethylation, and Nuclear Transcription Factor Y Subunit Beta (NFYB) signaling. We also showed that ZNF714 expression correlates with tumor immunosuppressive features. The in vitro studies indicated that ZNF714 expression positively associates with proliferation, migration, and invasion. The transcriptomic analysis of ZNF714 knocked-down cells demonstrated deregulation of cell adhesion, migration, proliferation, apoptosis, and differentiation. Importantly, we provided evidence that ZNF714 negatively regulates the expression of several known TSGs indirectly via promoter methylation. However, as ZNF714 did not show nuclear localization in our research model, the regulatory mechanisms exerted by ZNF714 require further investigation. In conclusion, our results reveal, for the first time, that ZNF714 may support pro-oncogenic features in lung cancer cells.
Transcriptome Analysis Revealed Potential Genes of Skeletal Muscle Thermogenesis in Mashen Pigs and Large White Pigs under Cold Stress
Authors: Li Wenxia , Chen Yufen , Zhang Yunting , Zhao Ning , Zhang Wanfeng , Shi Mingyue , Zhao Yan , Cai Chunbo , Lu Chang , Gao Pengfei , Guo Xiaohong , Li Bugao , Kim Sung-Woo , Yang Yang , Cao Guoqing
Published: October 2023

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a four-day cold (4 °C) or normal temperature (25 °C) environment. We recorded phenotypic changes and collected blood and longissimus dorsi muscle for transcriptome sequencing. Finally, the PRSS8 gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency, were observed. However, the MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. The LW pigs primarily responded to cold stress by regulating their heat production and glycolipid energy metabolism. The MS pigs exhibited a distinct response to cold stress, involving the regulation of heat production, energy metabolism pathways, and robust mitochondrial activity, as well as a stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed that it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.
Iridescent Features Correlating with Periodic Assemblies in Custom-Crystallized Arylate Polyesters
Authors: Rahmayanti Widyantari , Nagarajan Selvaraj , Sun Ya-Sen , Woo Eamor M.
Published: October 2023

In this study, five different aryl polyesters, i.e., poly(ethylene terephthalate) (PET), poly(trimethylene terephthalate) (PTT), poly(octamethylene terephthalate) (POT), poly(nonamethylene terephthalate) (PNT), and poly(decamethylene terephthalate) (PDT), upon crystallization at a suitable temperature range, all exhibit ring-banded spherulites with universal characteristics. Previous research has revealed some fundamental mechanisms underlying the formation of periodic hierarchical structures. Additionally, this study further explored correlations among micro/nanocrystal assemblies in the top surface and internal grating architectures and the structural iridescent properties. The interior lamellar assembly of arylate polyesters’ banded spherulites is shown to exhibit periodic birefringence patterns that are highly reminiscent of those found in a variety of biological structures, with the capacity for iridescence from light interference. A laser diffraction analysis was also used to support confirmation of this condition, which could result in an arc diffraction pattern indicative of the presence of ringed spherulites. Among the five arylate polyesters, only PET is incapable of regularly producing ring-banded morphology, and thus cannot produce any iridescent color.
Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function—Preclinical Studies
Authors: Balsa André , Adão Rui , Brás-Silva Carmen
Published: October 2023

Pulmonary hypertension (PH) is a progressive condition that affects the pulmonary vessels, but its main prognostic factor is the right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate to clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and improved RV structure and function in PAB animals. PH models and PAB animals frequently exhibited similar results (73.1% concordance). Macitentan, sildenafil, and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Results are frequently not consistent with other studies, possibly due to the methodology, which greatly varied. Some research groups start treating the animals immediately, and others wait up to 4 weeks from model induction. Treatment duration and choice of anaesthetic are other important differences. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. However, a uniformization of methods may increase comparability between studies and, thus, improve translation to clinical trials.
Side-Chain Modified [99mTc]Tc-DT1 Mimics: A Comparative Study in NTS1R-Positive Models
Authors: Kanellopoulos Panagiotis , Nock Berthold A. , Rouchota Maritina , Loudos George , Krenning Eric P. , Maina Theodosia
Published: October 2023

Radiolabeled neurotensin analogs have been developed as candidates for theranostic use against neurotensin subtype 1 receptor (NTS1R)-expressing cancer. However, their fast degradation by two major peptidases, neprilysin (NEP) and angiotensin-converting enzyme (ACE), has hitherto limited clinical success. We have recently shown that palmitoylation at the ε-amine of Lys7 in [99mTc]Tc-[Lys7]DT1 (DT1, N4-Gly-Arg-Arg-Pro-Tyr-Ile-Leu-OH, N4 = 6-(carboxy)-1,4,8,11-tetraazaundecane) led to the fully stabilized [99mTc]Tc-DT9 analog, displaying high uptake in human pancreatic cancer AsPC-1 xenografts but unfavorable pharmacokinetics in mice. Aiming to improve the in vivo stability of [99mTc]Tc-DT1 without compromising pharmacokinetics, we now introduce three new [99mTc]Tc-DT1 mimics, carrying different pendant groups at the ε-amine of Lys7: MPBA (4-(4-methylphenyl)butyric acid)—[99mTc]Tc-DT10; MPBA via a PEG4-linker—[99mTc]Tc-DT11; or a hydrophilic PEG6 chain—[99mTc]Tc-DT12. The impact of these modifications on receptor affinity and internalization was studied in NTS1R-positive cells. The effects on stability and AsPC-1 tumor uptake were assessed in mice without or during NEP/ACE inhibition. Unlike [99mTc]Tc-DT10, the longer-chain modified [99mTc]Tc-DT11 and [99mTc]Tc-DT12 were significantly stabilized in vivo, resulting in markedly improved tumor uptake compared to [99mTc]Tc-DT1. [99mTc]Tc-DT11 was found to achieve the highest AsPC-1 tumor values and good pharmacokinetics, either without or during NEP inhibition, qualifying for further validation in patients with NTS1R-positive tumors using SPECT/CT.
An Integrated GIS-Based Reinforcement Learning Approach for Efficient Prediction of Disease Transmission in Aquaculture
Authors: Karras Aristeidis , Karras Christos , Sioutas Spyros , Makris Christos , Katselis George , Hatzilygeroudis Ioannis , Theodorou John A. , Tsolis Dimitrios
Published: October 2023

This study explores the design and capabilities of a Geographic Information System (GIS) incorporated with an expert knowledge system, tailored for tracking and monitoring the spread of dangerous diseases across a collection of fish farms. Specifically targeting the aquacultural regions of Greece, the system captures geographical and climatic data pertinent to these farms. A feature of this system is its ability to calculate disease transmission intervals between individual cages and broader fish farm entities, providing crucial insights into the spread dynamics. These data then act as an entry point to our expert system. To enhance the predictive precision, we employed various machine learning strategies, ultimately focusing on a reinforcement learning (RL) environment. This RL framework, enhanced by the Multi-Armed Bandit (MAB) technique, stands out as a powerful mechanism for effectively managing the flow of virus transmissions within farms. Empirical tests highlight the efficiency of the MAB approach, which, in direct comparisons, consistently outperformed other algorithmic options, achieving an impressive accuracy rate of 96%. Looking ahead to future work, we plan to integrate buffer techniques and delve deeper into advanced RL models to enhance our current system. The results set the stage for future research in predictive modeling within aquaculture health management, and we aim to extend our research even further.
Antiparasitic Activity of Oxindolimine–Metal Complexes against Chagas Disease
Authors: Portes Marcelo Cecconi , Ribeiro Grazielle Alves , Sabino Gustavo Levendoski , De Couto Ricardo Alexandre Alves , Vieira Leda Quércia , Alves Maria Júlia Manso , Da Costa Ferreira Ana Maria
Published: October 2023

Some copper(II) and zinc(II) complexes with oxindolimine ligands were tested regarding their trypanocidal properties. These complexes have already shown good biological activity in the inhibition of tumor cell proliferation, having DNA and mitochondria as main targets, through an oxidative mechanism, and inducing apoptosis. Herein, we demonstrate that they also have significant activity against the infective trypomastigote forms and the intracellular amastigote forms of T. cruzi, modulated by the metal ion as well as by the oxindolimine ligand. Selective indexes (LC50/IC50) determined for both zinc(II) and copper(II) complexes, are higher after 24 or 48 h incubation with trypomastigotes, in comparison to traditional drugs used in clinics, such as benznidazole, and other metal-based compounds previously reported in the literature. Additionally, tests against amastigotes indicated infection index <10% (% of infected macrophages/average number of amastigotes per macrophage), after 24 or 48 h in the presence of zinc(II) (60–80 µM) or analogous copper(II) complexes (10–25 µM). The copper complexes exhibit further oxidative properties, being able to damage DNA, proteins and carbohydrates, in the presence of hydrogen peroxide, with the generation of hydroxyl radicals. This redox reactivity could explain its better performance towards the parasites in relation to the zinc analogs. However, both copper and zinc complexes display good selective indexes, indicating that the influence of the ligand is also crucial, and is probably related to the inhibition of some crucial proteins.
Trends in Atrial Fibrillation Management—Results from a National Multi-Center Urgent Care Network Registry
Authors: Lebovitz Shalom , Estryk Menachem , Zimmerman Deena R. , Pollak Arthur , Luria David , Amir Offer , Biton Yitschak
Published: October 2023

Background: Atrial fibrillation (AF) is a common diagnosis in patients presenting to urgent care centers (UCCs), yet there is scant research regarding treatment in these centers. While some of these patients are managed within UCCs, some are referred for further care in an emergency department (ED). Objectives: We aimed to identify the rate of patients referred to an ED and define predictors for this outcome. We analyzed the rates of AF diagnosis and hospital referral over the years. Finally, we described trends in patient anticoagulation (AC) medication use. Methods: This retrospective study included 5873 visits of patients over age 18 visiting the TEREM UCC network with a diagnosis of AF over 11 years. Multivariate analysis was used to identify predictors for ED referral. Results: In a multivariate model, predictors of referral to an ED included vascular disease (OR 1.88 (95% CI 1.43–2.45), p < 0.001), evening or night shifts (OR 1.31 (95% CI 1.11–1.55), p < 0.001; OR 1.68 (95% CI 1.32–2.15), p < 0.001; respectively), previously diagnosed AF (OR 0.31 (95% CI 0.26–0.37), p < 0.001), prior treatment with AC (OR 0.56 (95% CI 0.46–0.67), p < 0.001), beta blockers (OR 0.63 (95% CI 0.52–0.76), p < 0.001), and antiarrhythmic medication (OR 0.58 (95% CI 0.48–0.69), p < 0.001). Visits diagnosed with AF increased over the years (p = 0.030), while referrals to an ED decreased over the years (p = 0.050). The rate of novel oral anticoagulant prescriptions increased over the years. Conclusions: The rate of referral to an ED from a UCC over the years is declining but remains high. Referrals may be predicted using simple clinical variables. This knowledge may help to reduce the burden of hospitalizations.
Glenohumeral Pathologies following Primary Anterior Traumatic Shoulder Dislocation—Comparison of Magnetic Resonance Arthrography and Arthroscopy
Authors: Holub Oliver , Schanda Jakob E. , Boesmueller Sandra , Tödtling Marion , Talaska Alexander , Kinsky Rudolf M. , Mittermayr Rainer , Fialka Christian
Published: October 2023

Background: We assessed intraarticular injuries in patients after primary anterior traumatic shoulder dislocation by comparing magnetic resonance arthrography (MRA) results with concomitant arthroscopic findings. Methods: All patients with primary traumatic shoulder dislocation who underwent arthroscopic surgery between 2001 and 2020 with preoperative MRA were included in this study. MRA was retrospectively compared with arthroscopic findings. Postoperative shoulder function was prospectively assessed using the Disabilities of Arm, Shoulder and Hand score (quick DASH), the Oxford Shoulder Score (OSS), the Subjective Shoulder Value (SSV), as well as the rate of return to sports. Results: A total of 74 patients were included in this study. A Hill–Sachs lesion was consistently found in the corresponding shoulders on MRA and arthroscopy in 35 cases (p = 0.007), a Bankart lesion in 37 shoulders (p = 0.004), and a superior labrum from anterior to posterior (SLAP) lesion in 55 cases (p = 0.581). Of all cases, 32 patients were available for a clinical and functional follow-up evaluation. A positive correlation was found between the level of sport practiced and the Oxford Shoulder Score (redislocation subset) (p = 0.032) and between the age at the time of surgery and the follow-up SSV (p = 0.036). Conversely, a negative correlation was observed between the age at the time of surgery and the Oxford Instability Score (redislocation subset) (p = 0.038). Conclusions: The results of this study show a good correlation between MRA and arthroscopy. Therefore, MRA is a valid tool for the detection of soft tissue pathologies after primary anterior traumatic shoulder dislocation and can aid in presurgical planning.
Mobility Assessment Using Multi-Positional MRI in Children with Cranio-Vertebral Junction Anomalies
Authors: Grenier-Chartrand Flavie , Taverne Maxime , James Syril , Guida Lelio , Paternoster Giovanna , Loiselet Klervie , Beccaria Kevin , Dangouloff-Ros Volodia , Levy Raphaël , de Saint Denis Timothée , Blauwblomme Thomas , Khonsari Roman Hossein , Boddaert Nathalie , Benichi Sandro
Published: October 2023

Objective: This study aimed to assess the relevance of using multi-positional MRI (mMRI) to identify cranio-vertebral junction (CVJ) instability in pediatric patients with CVJ anomalies while determining objective mMRI criteria to detect this condition. Material and Methods: Data from children with CVJ anomalies who underwent a mMRI between 2017 and 2021 were retrospectively reviewed. Mobility assessment using mMRI involved: (1) morphometric analysis using hierarchical clustering on principal component analysis (HCPCA) to identify clusters of patients by considering their mobility similarities, assessed through delta (Δ) values of occipito-cervical parameters measured on mMRI; and (2) morphological analysis based on dynamic geometric CVJ models and analysis of displacement vectors between flexion and extension. Receiver operating characteristics (ROC) curves were generated for occipito-cervical parameters to establish instability cut-off values. (3) Additionally, an anatomical qualitative analysis of the CVJ was performed to identify morphological criteria of instability. Results: Forty-seven patients with CVJ anomalies were included (26 females, 21 males; mean age: 10.2 years [3–18]). HCPCA identified 2 clusters: cluster №1 (stable patients, n = 39) and cluster №2 (unstable patients, n = 8). ΔpB-C2 (pB-C2 line delta) at ≥2.5 mm (AUC 0.98) and ΔBAI (Basion-axis Interval delta) ≥ 3 mm (AUC 0.97) predicted instability with 88% sensibility and 95% specificity and 88% sensitivity and 85% specificity, respectively. Geometric CVJ shape analysis differentiated patients along a continuum, from a low to a high CVJ motion that was characterized by a subluxation of C1 in the anterior direction. Qualitative analysis found correlations between instability and C2 anomalies, including fusions with C3 (body p = 0.032; posterior arch p = 0.045; inferior articular facets p = 0.012; lateral mass p = 0.029). Conclusions: We identified a cluster of pediatric patients with CVJ instability among a cohort of CVJ anomalies that were characterized by morphometric parameters with corresponding cut-off values that could serve as objective mMRI criteria. These findings warrant further validation through prospective case–control studies.
Anterolateral Thigh Chimeric Flap: An Alternative Reconstructive Option to Free Flaps for Large Soft Tissue Defects
Authors: Lee Yoon Jae , Kim Junnyeon , Lee Chae Rim , Kim Jun Hyeok , Oh Deuk Young , Jun Young Joon , Moon Suk-Ho
Published: October 2023

The anterolateral thigh (ALT) skin flap provides abundant, thin, pliable skin coverage with adequate pedicle length and calibre, and tolerable donor site morbidity. However, coverage of relatively large defects using the ALT flap alone is limited. We present our experience of using the ALT flap coupled with the vastus lateralis (VL) flap supplied by the same pedicle for large defect reconstruction. Between 2016 and 2020, ten patients with extensive lower-extremity or trunk defects were treated using the ALT/VL chimeric flap. The ALT portion was used to cover the cutaneous and joint defect while the VL part was used to resurface remnant defects, and a skin graft was performed. All flaps were based on the common descending pedicle, and branches to separate the components were individually dissected. All defects were successfully reconstructed using the ALT/VL chimeric flap. No surgery-related acute complications were observed, and the patients had no clinical issues with ambulation or running activities during the long-term follow-up period. With the separate components supplied by a common vascular pedicle, the ALT/VL chimeric flap allows us to reconstruct extensive defects with joint involvement or posterior trunk lesions. Thus, the ALT/VL chimeric flap may be a suitable alternative for extensive tissue defect reconstruction.
Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration
Authors: Kozan Natalie G. , Caswell Sean , Patel Milan , Grasman Jonathan M.
Published: October 2023

Volumetric muscle loss (VML) is a traumatic injury where at least 20% of the mass of a skeletal muscle has been destroyed and functionality is lost. The standard treatment for VML, autologous tissue transfer, is limited as approximately 1 in 10 grafts fail because of necrosis or infection. Tissue engineering strategies seek to develop scaffolds that can regenerate injured muscles and restore functionality. Many of these scaffolds, however, are limited in their ability to restore muscle functionality because of an inability to promote the alignment of regenerating myofibers. For aligned myofibers to form on a scaffold, myoblasts infiltrate the scaffold and receive topographical cues to direct targeted myofiber growth. We seek to determine the optimal pore size for myoblast infiltration and differentiation. We developed a method of tuning the pore size within collagen scaffolds while inducing longitudinal alignment of these pores. Significantly different pore sizes were generated by adjusting the freezing rate of the scaffolds. Scaffolds frozen at −20 °C contained the largest pores. These scaffolds promoted the greatest level of cell infiltration and orientation in the direction of pore alignment. Further research will be conducted to induce higher levels of myofiber formation, to ultimately create an off-the-shelf treatment for VML injuries.
Nuclear-Localized Fluorescent Proteins Enable Visualization of Nuclear Behavior in the Basidiomycete Schizophyllum commune Early Mating Interactions
Authors: Raudaskoski Marjatta , Butler-Hallissey Ciarán
Published: October 2023

Spinning disc confocal microscopical research was conducted on living mating hyphae of the tetrapolar basidiomycete Schizophyllum commune. Haploid strains with either the same or different A and B mating-type genes and expressing differently labelled histone 2B were confronted. In the haploid hyphae histone 2B mCherry and histone 2B EGFP were visualized as red and green nuclei, respectively. In hyphae with the same A but different B genes, the red and green nuclei were observed next to each other. This indicated that nuclear migration between strains, regulated by the B mating type, had taken place. The compatible mating with different A and B genes produced a high number of mixed EFGP/mCherry, yellow nuclei. The mixed nuclei resulted from nearby divisions of nuclei encoding different histones and mating-type genes. During this process, the histones with the different labels were incorporated in the same nuclei, along with the heterodimerized transcription factors encoded by the different A mating-type genes and present around the nuclei. This led to the activation of the A-regulated pathway and indicated that different A genes are important to the cell cycle activation of a compatible mating. Consequently, a yellow nuclear pair stuck together, divided synchronously and proceeded in the migration hyphae towards the colony periphery, where the dikaryotization was promoted by branch formation from the migration hyphae.
Validity of Diagnostic Support Model for Attention Deficit Hyperactivity Disorder: A Machine Learning Approach
Authors: Chu Kuo-Chung , Huang Hsin-Jou , Huang Yu-Shu
Published: October 2023

An accurate and early diagnosis of attention deficit hyperactivity disorder can improve health outcomes and prevent unnecessary medical expenses. This study developed a diagnostic support model using a machine learning approach to effectively screen individuals for attention deficit hyperactivity disorder. Three models were developed: a logistic regression model, a classification and regression tree (CART), and a neural network. The models were assessed by using a receiver operating characteristic analysis. In total, 74 participants were enrolled into the disorder group, while 21 participants were enrolled in the control group. The sensitivity and specificity of each model, indicating the rate of true positive and true negative results, respectively, were assessed. The CART model demonstrated a superior performance compared to the other two models, with region values of receiver operating characteristic analyses in the following order: CART (0.848) > logistic regression model (0.826) > neural network (0.67). The sensitivity and specificity of the CART model were 78.8% and 50%, respectively. This model can be applied to other neuroscience research fields, including the diagnoses of autism spectrum disorder, Tourette syndrome, and dementia. This will enhance the effect and practical value of our research.