bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Medical Physical Training and a Structured Personalized Exercise Training Program on Hemodynamic Parameters and Arterial Stiffness in Pregnant Women
Authors: Petre Izabella , Iurciuc Stela , Buleu Florina , Petre Ion , Moleriu Radu , Popa Daian , Turi Vladiana , Bordianu Anca , Tasdemir Rabia , Craciun Laura , Marc Luciana , Barna Flavia , Iurciuc Mircea
Published: May 2024

Introduction: In developed countries, heart disease is the primary cause of maternal mortality during pregnancy. Arterial stiffness, an independent risk factor for atherosclerosis and a predictor of cardiovascular complications, can be assessed using the augmentation index (AIx) and pulse wave velocity (PWV). In this prospective study, we aimed to evaluate diverse hemodynamic parameters and arterial stiffness in pregnant women before and after participating in a structured, personalized exercise training program. Materials and methods: Forty healthy pregnant women, non-smokers, who agreed to participate daily for 12 weeks in a physical exercise training program under the supervision of a team made up of an obstetrician, a cardiologist, and a physiotherapist were included. Anthropometric characteristics, arterial function, and physical activity data were collected from the participants at two different time points: at the beginning of the exercise training program (T0) and at the end, after 12 weeks (T1). Results: Upon conducting a statistical analysis, it was discovered that there were noteworthy disparities (p = 0.05) in body mass index, brachial AIx, systolic blood pressure, and pulse pressure values between the two time points. The regression analysis for the AIx brachial values and the PWVao values from Trim II (T0) and Trim III (T1) showed major differences between these two time points; the association between the AIx brachial values in the second and third trimesters of pregnancy revealed a strong direct significant correlation (p < 0.001), and the correlation between the PWVao values in the second (T0) and third trimester (T1) of pregnancy was weak and insignificant (p = 0.12). Conclusions: The findings of our study indicate that a personalized exercise training program positively impacts the physical and psychological well-being of pregnant women, leading to a reduction in PWV.
Point-of-Care Serum Proenkephalin as an Early Predictor of Mortality in Patients Presenting to the Emergency Department with Septic Shock
Authors: Verras Christos , Bezati Sofia , Bistola Vasiliki , Ventoulis Ioannis , Matsiras Dionysis , Tsiodras Sotirios , Parissis John , Polyzogopoulou Effie
Published: May 2024

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.
Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms
Authors: Fuchs Christina , Silveira Sarita , Meindl Thomas , Musil Richard , Austerschmidt Kim Laura , Eilert Dirk W. , Müller Norbert , Möller Hans-Jürgen , Engel Rolf , Reiser Maximilian , Driessen Martin , Beblo Thomas , Hennig-Fast Kristina
Published: May 2024

Background: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others’ mental states (overmentalizing). Methods: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. Results: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. Conclusions: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.
Research on the Value of Rayleigh Damping Parameter in Explicit and Implicit Integrals for Dynamic Analysis of Large Structures
Authors: Chen Yan , Wang Haitao , Wang Yougang , Zhang Junhong , Bao Zitong , Li Jianbo , Chen Miaomiao , Xu Peng
Published: May 2024

Rayleigh damping is proportional to the combination of the structural mass matrix and stiffness matrix and is widely used in structural seismic analysis. The accuracy of seismic analysis of nuclear power structures directly depends on the value of the Rayleigh damping parameters. However, the stiffness component of Rayleigh damping is not included in the explicit integral, so the Rayleigh damping in the explicit and implicit integrals needs to be handled differently. LS-DYNA R11.1.0 software provides various calculation methods for the value of the Rayleigh damping parameter in the explicit integral. To investigate the influence of the value of the Rayleigh damping parameter in the explicit and implicit integrals on the results of the dynamic analysis of a nuclear power plant, the AP1000 nuclear island plant is taken as an example, and the explicit and implicit dynamic calculation are carried out respectively for the nuclear power plant, considering the soil–structure interaction. The results show that the Rayleigh damping parameter calculated by different methods in the explicit integral has a large influence on the results of seismic analysis of nuclear power plants. The mass component of Rayleigh damping in the explicit and implicit integrals takes the same value, and the stiffness component of Rayleigh damping in the explicit integrals is taken as the negative of the stiffness component in the implicit integrals. Thus, the results of the two dynamic analyses can be in good agreement. The results provide a reference for the application of Rayleigh damping in the explicit integral for the seismic analysis of nuclear power structures.
Development of Virtual Tours for Understanding the Built Environment of an Educational Building
Authors: Li Simon , Say Winson , Rao Sumiran
Published: May 2024

Though we spend a significant amount of time in indoor and built environments as general occupants of residential or commercial spaces, we do not necessarily know how the heating, cooling, and ventilation services work in our occupied spaces. As the mechanical systems of buildings become more complex for energy saving and better indoor air quality, it is beneficial for occupants to learn more their built environment so that they can cooperate effectively for the building’s performance. In this context, the purpose of this research is to develop and evaluate how virtual reality (VR) technology can support occupants in understanding their built environment. An educational building on campus was selected for the development as it provides familiar spaces for potential participants in this research. This research was carried out in two stages. In Stage One, we, as researchers in mechanical engineering, explored the workflow for VR development and developed VR tours for four spaces: a classroom, an auditorium, a conference room, and a mechanical room. In Stage Two, we conducted a survey study to examine the VR experience from the perspective of users. In this survey study, we recruited 34 participants from engineering students/graduates, industry participants, and a sustainability group. The participants generally indicated a positive experience with the VR tours, although the quiz scores on the VR content were weak. From our reflection, we consider that positive and effective VR experiences for the education of the built environment require collaboration from three domains: (1) mechanical systems of buildings, (2) VR technology, and (3) pedagogy.
Open Innovation Inspired Framework to Support Business Internationalisation: A Cross-Sector and Cross-National Approach
Authors: Jiménez-Portaz María , Macias Aragonés Marta , Ureña Mayenco Macarena , Carvajal Juliana , Borejko Weronika , Beaume Nolwenn
Published: May 2024

In recent years, the business environment has experienced a fast-paced change due to issues such as geopolitics or COVID-19. Accordingly, business internationalisation has been accelerated while the approaches followed for such an end have been improved to maintain companies’ competitiveness. Within this context, this paper presents a new framework for the internationalisation of Earth Observation SMEs in two target countries: Australia and Chile. Internationalisation can be an effective strategy for SMEs to grow and expand, but it requires careful research, analysis and agile adaptation to markets and cultures through an integrative and innovative methodology. Secondly, a series of preparatory actions and several internationalisation strategies have been developed, including online bilateral meetings and online trade missions. This work is an innovation driver for the internationalisation of European SMEs, helping them to make the leap into two markets of great interest and in two very attractive sectors, agriculture and maritime, with remote sensing as the nexus.
Intersectionality, BRCA Genetic Testing, and Intrafamilial Communication of Risk: A Qualitative Study
Authors: Hesse-Biber Sharlene , Seven Memnun , Shea Hannah , Dwyer Andrew A.
Published: May 2024

Significant health disparities exist in relation to pathogenic variants in BRCA1/2. This study aimed to better understand the barriers and facilitators to BRCA1/2 genetic testing and intrafamilial communication of risk in racially and ethnically diverse individuals. We conducted qualitative interviews with non-Hispanic White (n = 11) and Black, Indigenous, People of Color (BIPOC) individuals (n = 14) who underwent testing for pathogenic BRCA1/2 variants. We employed template analysis, case study analysis, and comparative case study analysis to examine healthcare experiences related to genetic testing as well as intrafamilial communication of risk. Applying an intersectional lens, we sought to inform more person-centered approaches to precision healthcare and help dismantle disparities in genomic healthcare. Template analysis revealed salient factors at the individual (psychosocial well-being), interpersonal/familial, and healthcare system levels. A two-part case study analysis provided insights into how race/ethnicity, cultural norms, and socioeconomic status interact with systemic and structural inequities to compound disparities. These findings underscore the need for person-centered, tailored, and culturally sensitive approaches to understanding and addressing the complexities surrounding testing and the communication of BRCA risk. Applying an intersectional lens can inform more person-centered approaches to precision healthcare and may help to surmount existing disparities.
Susceptibility of Melanoma Cells to Targeted Therapy Correlates with Protection by Blood Neutrophils
Authors: Wendlinger Simone , Wohlfarth Jonas , Siedel Claudia , Kreft Sophia , Kilian Teresa , Junker Sarah , Schmid Luisa , Sinnberg Tobias , Dischinger Ulrich , Heppt Markus V. , Wistuba-Hamprecht Kilian , Meier Friedegund , Erpenbeck Luise , Neubert Elsa , Goebeler Matthias , Gesierich Anja , Schrama David , Kosnopfel Corinna , Schilling Bastian
Published: May 2024

Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell–cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection.
Preparation of Oxygen Reduction Catalyst Electrodes by Electrochemical Acidification and Synergistic Electrodeposition
Authors: Zhou Liheng , Guo Yongjian , Xu Yu , Li Ping , Zhang Qi
Published: May 2024

A proton exchange membrane fuel cell (PEMFC) is an efficient and environmentally friendly power production technology that uses hydrogen energy. The cathodic oxygen reduction electrode is a critical component in the development of PEMFC. Most techniques deposit catalyst nanoparticles in areas that are inaccessible for catalytic processes, reducing platinum utilization. The substrate used in this study was carbon paper (CP) with a self-supporting structure. First, electrochemical acidification technology was employed to modify the CP’s surface, followed by nanoparticle manufacturing and fixation on the CP in a single step by electrodeposition. The Pt/C0.5V2.24CP catalyst electrode demonstrated high-quality activity in the oxygen reduction reaction (ORR), with a homogeneous particle dispersion and particle size of around 50 nm. The mass activity and electrochemical active surface area (ECSA) of the Pt/C0.5V2.24CP catalyst electrode were 1.74 and 3.98 times higher than those of the Pt/C/CP-1 electrodes made with commercial catalysts, respectively. After 5000 cycles of accelerated durability testing (ADT), the mass activity and ECSA were 1.28 times and 6.16 times more than Pt/C/CP-1. This paper successfully proved the viability of electrodepositing Pt nanoparticles on CP following acidification, and that the electrochemical acidification methods have a positive influence on improving electrode ORR activity.
New Trends in the Use of Catalysts for Biofuel and Bioproduct Generation
Authors: Encinar Martín José María , Nogales-Delgado Sergio
Published: May 2024

Green technologies are gaining a vital role in the energy and industrial fields, as society faces challenges such as geopolitical conflicts and pollution related to the exploitation of petroleum resources [...]
Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair
Authors: Zhang Fenglin , Clair Andrew J. , Dankert John F. , Lee You Jin , Campbell Kirk A. , Kirsch Thorsten
Published: May 2024

Background: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.
Dissecting Genetic Mechanisms of Differential Locomotion, Depression, and Allodynia after Spinal Cord Injury in Three Mouse Strains
Authors: Yang Wendy W. , Matyas Jessica J. , Li Yun , Lee Hangnoh , Lei Zhuofan , Renn Cynthia L. , Faden Alan I. , Dorsey Susan G. , Wu Junfang
Published: May 2024

Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.
JAK/STAT Inhibition Normalizes Lipid Composition in 3D Human Epidermal Equivalents Challenged with Th2 Cytokines
Authors: Flori Enrica , Cavallo Alessia , Mosca Sarah , Kovacs Daniela , Cota Carlo , Zaccarini Marco , Di Nardo Anna , Bottillo Grazia , Maiellaro Miriam , Camera Emanuela , Cardinali Giorgia
Published: May 2024

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism.
Impaired Remodeling of White Adipose Tissue in Obesity and Aging: From Defective Adipogenesis to Adipose Organ Dysfunction
Authors: Iacobini Carla , Vitale Martina , Haxhi Jonida , Menini Stefano , Pugliese Giuseppe
Published: May 2024

The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders.
Novel Inositol 1,4,5-Trisphosphate Receptor Inhibitor Antagonizes Hepatic Stellate Cell Activation: A Potential Drug to Treat Liver Fibrosis
Authors: Smith-Cortinez Natalia , Heegsma Janette , Podunavac Masa , Zakarian Armen , Cardenas J. César , Faber Klaas Nico
Published: May 2024

Liver fibrosis, characterized by excessive extracellular matrix (ECM) deposition, can progress to cirrhosis and increases the risk of liver cancer. Hepatic stellate cells (HSCs) play a pivotal role in fibrosis progression, transitioning from a quiescent to activated state upon liver injury, wherein they proliferate, migrate, and produce ECM. Calcium signaling, involving the inositol 1,4,5-trisphosphate receptor (IP3R), regulates HSC activation. This study investigated the efficacy of a novel IP3R inhibitor, desmethylxestospongin B (dmXeB), in preventing HSC activation. Freshly isolated rat HSCs were activated in vitro in the presence of varying dmXeB concentrations. The dmXeB effectively inhibited HSC proliferation, migration, and expression of fibrosis markers without toxicity to the primary rat hepatocytes or human liver organoids. Furthermore, dmXeB preserved the quiescent phenotype of HSCs marked by retained vitamin A storage. Mechanistically, dmXeB suppressed mitochondrial respiration in activated HSCs while enhancing glycolytic activity. Notably, methyl pyruvate, dimethyl α-ketoglutarate, and nucleoside supplementation all individually restored HSC proliferation despite dmXeB treatment. Overall, dmXeB demonstrates promising anti-fibrotic effects by inhibiting HSC activation via IP3R antagonism without adverse effects on other liver cells. These findings highlight dmXeB as a potential therapeutic agent for liver fibrosis treatment, offering a targeted approach to mitigate liver fibrosis progression and its associated complications.
The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells
Authors: Velasquez Carlos , Gutierrez Olga , Carcelen Maria , Fernandez-Luna Jose L.
Published: May 2024

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA–ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38β MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38β MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF–EGFR pathway for novel therapeutic approaches.
From the Gut to the Brain: Is Microbiota a New Paradigm in Parkinson’s Disease Treatment?
Authors: Vilela Cristiana , Araújo Bruna , Soares-Guedes Carla , Caridade-Silva Rita , Martins-Macedo Joana , Teixeira Catarina , Gomes Eduardo D. , Prudêncio Cristina , Vieira Mónica , Teixeira Fábio G.
Published: May 2024

Parkinson’s disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiota in the etiology and pathophysiology of PD. The establishment of a brain–gut microbiota axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiota. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiota on PD and whether this may be a new paradigm for treating this devastating disease.
Small-Molecule Inhibitors of TIPE3 Protein Identified through Deep Learning Suppress Cancer Cell Growth In Vitro
Authors: Chen Xiaodie , Lu Zhen , Xiao Jin , Xia Wei , Pan Yi , Xia Houjun , Chen Youhai H. , Zhang Haiping
Published: May 2024

Tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3 or TIPE3) functions as a transfer protein for lipid second messengers. TIPE3 is highly upregulated in several human cancers and has been established to significantly promote tumor cell proliferation, migration, and invasion and inhibit the apoptosis of cancer cells. Thus, inhibiting the function of TIPE3 is expected to be an effective strategy against cancer. The advancement of artificial intelligence (AI)-driven drug development has recently invigorated research in anti-cancer drug development. In this work, we incorporated DFCNN, Autodock Vina docking, DeepBindBC, MD, and metadynamics to efficiently identify inhibitors of TIPE3 from a ZINC compound dataset. Six potential candidates were selected for further experimental study to validate their anti-tumor activity. Among these, three small-molecule compounds (K784-8160, E745-0011, and 7238-1516) showed significant anti-tumor activity in vitro, leading to reduced tumor cell viability, proliferation, and migration and enhanced apoptotic tumor cell death. Notably, E745-0011 and 7238-1516 exhibited selective cytotoxicity toward tumor cells with high TIPE3 expression while having little or no effect on normal human cells or tumor cells with low TIPE3 expression. A molecular docking analysis further supported their interactions with TIPE3, highlighting hydrophobic interactions and their shared interaction residues and offering insights for designing more effective inhibitors. Taken together, this work demonstrates the feasibility of incorporating deep learning and MD simulations in virtual drug screening and provides inhibitors with significant potential for anti-cancer drug development against TIPE3−.
Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia
Authors: Michel Zachary , Raborn Layne N. , Spencer Tiahna , Pan Kristen S. , Martin Daniel , Roszko Kelly L. , Wang Yan , Robey Pamela G. , Collins Michael T. , Boyce Alison M. , de Castro Luis Fernandez
Published: May 2024

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
The Long Non-Coding RNA Gene AC027288.3 Plays a Role in Human Endometrial Stromal Fibroblast Decidualization
Authors: Thapa Rupak , Marmo Kevin , Ma Liang , Torry Donald S. , Bany Brent M.
Published: May 2024

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role.
Mesenchymal Stem Cells and Their Role in Neurodegenerative Diseases
Authors: Mattei Vincenzo , Delle Monache Simona
Published: May 2024

Mesenchymal stem cells (MSCs) have garnered significant interest in the field of regenerative medicine for their ability to potentially treat various diseases, especially neurodegenerative disorders [...]
Actin Cytoskeleton Remodeling Accompanied by Redistribution of Adhesion Proteins Drives Migration of Cells in Different EMT States
Authors: Ilnitskaya Alla S. , Litovka Nikita I. , Rubtsova Svetlana N. , Zhitnyak Irina Y. , Gloushankova Natalya A.
Published: May 2024

Epithelial–mesenchymal transition (EMT) is a process during which epithelial cells lose epithelial characteristics and gain mesenchymal features. Here, we used several cell models to study migratory activity and redistribution of cell–cell adhesion proteins in cells in different EMT states: EGF-induced EMT of epithelial IAR-20 cells; IAR-6-1 cells with a hybrid epithelial–mesenchymal phenotype; and their more mesenchymal derivatives, IAR-6-1-DNE cells lacking adherens junctions. In migrating cells, the cell–cell adhesion protein α-catenin accumulated at the leading edges along with ArpC2/p34 and α-actinin. Suppression of α-catenin shifted cell morphology from fibroblast-like to discoid and attenuated cell migration. Expression of exogenous α-catenin in MDA-MB-468 cells devoid of α-catenin drastically increased their migratory capabilities. The Y654 phosphorylated form of β-catenin was detected at integrin adhesion complexes (IACs). Co-immunoprecipitation studies indicated that α-catenin and pY654-β-catenin were associated with IAC proteins: vinculin, zyxin, and α-actinin. Taken together, these data suggest that in cells undergoing EMT, catenins not participating in assembly of adherens junctions may affect cell migration.
Sprayable Diacetylene-Containing Amphiphile Coatings for Visual Detection of Gas-Phase Hydrogen Peroxide
Authors: Shiveshwarkar Priyanka , Jaworski Justyn
Published: May 2024

Colorimetric chemical sensing of target gases, such as hydrogen peroxide vapors, is an evolving area of research that implements responsive materials that undergo molecule-specific interaction, resulting in a visible color change. Due to the intuitive nature of an observable color change, such sensing systems are particularly desirable as they can be widely deployed at low cost and without the need for complex analytical instrumentation. In this work, we describe our development of a new spray-on sensing material that can provide a colorimetric response to the presence of a gas-phase target, specifically hydrogen peroxide vapor. By providing a cumulative response over time, we identified that part per million concentrations of hydrogen peroxide vapor can be detected. Specifically, we make use of iron chloride-containing formulations to enable the catalysis of hydrogen peroxide to hydroxyl radicals that serve to initiate polymerization of the diacetylene-containing amphiphile, resulting in a white to blue color transition. Due to the irreversible nature of the color change mechanism, the cumulative exposure to hydrogen peroxide over time is demonstrated, enabling longitudinal assessment of target exposure with the same coatings. The versatility of this approach in generating a colorimetric response to hydrogen peroxide vapor may find practical applications for environmental monitoring, diagnostics, or even industrial safety.
A Critical Analysis of Morocco’s Green Hydrogen Roadmap: A Modelling Approach to Assess Country Readiness from the Energy Trilemma Perspective
Authors: Caillard Amandine , Yeganyan Rudolf , Cannone Carla , Plazas-Niño Fernando , Howells Mark
Published: May 2024

Morocco, despite its heavy reliance on imported fossil fuels, which made up 68% of electricity generation in 2020, has recognised its significant renewable energy potential. The Nationally Determined Contribution (NDC) commitment is to reduce emissions by 45.5% from baseline levels with international assistance and abstain from constructing new coal plants. Moreover, the Green Hydrogen Roadmap aims to export 10 TWh of green hydrogen by 2030, as well as use it for local electricity storage. This paper critically analyses this Roadmap and Morocco’s readiness to reach its ambitious targets, focusing specifically on an energy trilemma perspective and using OSeMOSYS (Open-Source energy Modelling System) for energy modelling. The results reveal that the NDC scenario is only marginally more expensive than the least-cost scenario, at around 1.3% (approximately USD 375 million), and facilitates a 23.32% emission reduction by 2050. An important note is the continued reliance on existing coal power plants across all scenarios, which challenges both energy security and emissions. The assessment of the Green Hydrogen Scenarios highlights that it could be too costly for the Moroccan government to fund the Green Hydrogen Roadmap at this scale, which leads to increased imports of polluting fossil fuels for cost reduction. In fact, the emission levels are 39% higher in the green hydrogen exports scenario than in the least-cost scenario. Given these findings, it is recommended that the Green Hydrogen Roadmap be re-evaluated, with a suggestion for a postponement and reduction in scope.
Impact of Silver Nanoparticles on Arbuscular Mycorrhizal Fungi and Glomalin-Related Soil Proteins in the Rhizosphere of Maize Seedlings
Authors: Zhao Haiying , Liu Zhiyuan , Han Yu , Cao Jiling
Published: May 2024

Glomalin-related soil protein (GRSP), an important arbuscular mycorrhizal (AM) fungal by-product, plays a key role in preserving or sequestrating soil organic carbon (C). Silver nanoparticles (AgNPs) have become an emerging contaminant and their impacts on soil ecosystems attract increasing concerns. The dynamics of AM fungi and GRSP could therefore form the basis for an in-depth exploration of the influences of AgNPs on soil ecosystems. This study investigated the effects of AgNPs on mycorrhizal growth and AM fungal communities, as well as the GRSP contents in maize (Zea mays L.) soils, with a pot experiment. The contributions of GRSP to soil organic C and the correlations of GRSP with soil organic C were also evaluated. The results indicated that AgNPs decreased the mycorrhizal colonization, AM fungal biomass, and diversity indices, and strongly shifted the community composition of AM fungi with a reduction in Acaulosporaceae and an enrichment in Glomeraceae. Additionally, AgNPs also decreased the soil’s easily extractable (EE) GRSP and total (T) GRSP contents, resulting in lower contributions of EE-GRSP-C and T-GRSP-C to the soil organic C. Linkage analyses revealed that AM fungal abundances have positive correlations with EE- and T-GRSP, and EE- and T-GRSP also positively correlated with soil organic C, indicating that the negative effects of AgNPs on AM fungal abundances and communities were extended to AM-fungal-associated C processes. Altogether, our study found that AgNPs decreased the AM fungal abundances shaped AM fungal communities, and reduced the soil GRSP content, which might subsequently be unfavorable for soil C storage.
Correction: Raymann, J.; Rajalakshmi, R. GAR-Net: Guided Attention Residual Network for Polyp Segmentation from Colonoscopy Video Frames. Diagnostics 2023, 13, 123
Authors: Raymann Joel , Rajalakshmi Ratnavel
Published: May 2024

There was an error in the original publication [...]
Obscure Bleeding from a Metastatic Small Bowel Tumor Diagnosed Using Motorized Spiral Enteroscopy: A Case Study and a Literature Review
Authors: Banciu Christian , Munteanu Andreea , Aprotosoaie Adrian , Fabian Ramona , Dobrescu Amadeus , Vaduva Adrian , Fabian Antonio , Soica Irina , Ivan Viviana , Sima Laurentiu
Published: May 2024

Small bowel tumors are relatively rare, representing only around 5% of all gastrointestinal neoplasms, with a progressively increasing incidence. Currently, there are no established guidelines for diagnostic approaches, screening procedures, or management strategies for small bowel tumors. We present here the case of a patient with a rare type of metastatic tumor of the small bowel originating from primary lung adenocarcinoma who presented with abdominal pain, severe iron-deficiency anemia, and melena. The initial investigations, gastroscopy and colonoscopy, failed to identify the bleeding source. The obscure bleeding source and diagnosis were achieved through power motorized spiral enteroscopy (MSE), which allowed the visualization and biopsy of the tumor. Histopathological examination established the presence of a poorly differentiated non-mucinous adenocarcinoma originating from the lung. This case is reported to provide evidence of the efficiency of MSE in the diagnosis of small bowel tumors, with the method providing higher insertion depth in a reduced amount of time.
Case Report: A Sudden Thyroid-Related Death of a 15-Year-Old Girl
Authors: Rácz Kálmán , Simon Gábor , Kurucz Andrea , Harsányi Gergő Tamás , Török Miklós , Herczeg László Tamás , Gergely Péter Attila
Published: May 2024

A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.
Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer
Authors: Souza da Silva Ricella , Pina Maria João , Cirnes Luís , Gouveia Luís , Albergaria André , Schmitt Fernando
Published: May 2024

Pancreatic cancer is one of the deadliest malignancies, characterized by late-stage diagnosis and limited treatment options. Comprehensive genomic profiling plays an important role in understanding the molecular mechanisms underlying the disease and identifying potential therapeutic targets. Cell blocks (CBs), derived from EUS-FNA, have become valuable resources for diagnosis and genomic analysis. We examine the molecular profile of pancreatic ductal adenocarcinoma (PDAC) using specimens obtained from CB EUS-FNA, across a large gene panel, within the framework of next-generation sequencing (NGS). Our findings revealed that over half (55%) of PDAC CB cases provided adequate nucleic acid for next-generation sequencing, with tumor cell percentages averaging above 30%. Despite challenges such as low DNA quantification and degraded DNA, sequencing reads showed satisfactory quality control statistics, demonstrating the detection of genomic alterations. Most cases (84.6%) harbored at least one gene variant, including clinically significant gene mutation variants such as KRAS, TP53, and CDKN2A. Even at minimal concentrations, as long as the extracted DNA is of high quality, performing comprehensive molecular profiling on PDAC samples from cell blocks has remained feasible. This strategy has yielded valuable information about the diagnosis, genetic landscape, and potential therapeutic targets, aligning closely with a precision cytopathology approach.
The Impact of Diagnosis of Human Papillomavirus (HPV) Infection and Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia 3 (CIN3) on Women’s Sexual Lives
Authors: Bruno Maria Teresa , Caruso Giuseppe , Torrisi Elena , Grimaldi Raffaela , Abate Biagio , Luciani Francesco Saverio , Basile Susanna , Panella Marco Marzio
Published: May 2024

The aim of the study was to assess sexual health in women who underwent Loop Electrosurgical Excisional Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia 3 (CIN 3). One hundred thirty-one women were enrolled, and the Female Sexual Function Index (FSFI) questionnaire was administered before LEEP and 6 months after the procedure. In almost all of the participants, data revealed a statistically significant worsening in sexual quality of life after LEEP. Therefore, clinicians should be aware of these possible negative effects on sexual behavior, and provide women with appropriate, wide-ranging, and detailed counseling. The data obtained in the present study should help to plan appropriate counseling from communicating HPV diagnosis and medical treatment to CIN3 surgical procedure.