bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of CircRNAs Roles and Mechanisms in Liver Fibrosis
Authors: Wang Gaiping , Tong Jiahui , Li Yingle , Qiu Xianglei , Chen Anqi , Chang Cuifang , Yu Guoying
Published: June 2023

Liver fibrosis represents the reversible pathological process with the feature of the over-accumulation of extracellular matrix (ECM) proteins within the liver, which results in the deposition of fibrotic tissues and liver dysfunction. Circular noncoding RNAs (CircRNAs) have the characteristic closed loop structures, which show high resistance to exonuclease RNase, making them far more stable and recalcitrant against degradation. CircRNAs increase target gene levels by playing the role of a microRNA (miRNA) sponge. Further, they combine with proteins or play the role of RNA scaffolds or translate proteins to modulate different biological processes. Recent studies have indicated that CircRNAs play an important role in the occurrence and progression of liver fibrosis and may be the potential diagnostic and prognostic markers for liver fibrosis. This review summarizes the CircRNAs roles and explores their underlying mechanisms, with a special focus on some of the latest research into key CircRNAs related to regulating liver fibrosis. Results in this work may inspire fruitful research directions and applications of CircRNAs in the management of liver fibrosis. Additionally, our findings lay a critical theoretical foundation for applying CircRNAs in diagnosing and treating liver fibrosis.
Long-Time Dynamics of Selected Molecular-Motor Components Using a Physics-Based Coarse-Grained Approach
Authors: Liwo Adam , Pyrka Maciej , Czaplewski Cezary , Peng Xubiao , Niemi Antti J.
Published: June 2023

Molecular motors are essential for the movement and transportation of macromolecules in living organisms. Among them, rotatory motors are particularly efficient. In this study, we investigated the long-term dynamics of the designed left-handed alpha/alpha toroid (PDB: 4YY2), the RBM2 flagellum protein ring from Salmonella (PDB: 6SD5), and the V-type Na+-ATPase rotor in Enterococcus hirae (PDB: 2BL2) using microcanonical and canonical molecular dynamics simulations with the coarse-grained UNRES force field, including a lipid-membrane model, on a millisecond laboratory time scale. Our results demonstrate that rotational motion can occur with zero total angular momentum in the microcanonical regime and that thermal motions can be converted into net rotation in the canonical regime, as previously observed in simulations of smaller cyclic molecules. For 6SD5 and 2BL2, net rotation (with a ratcheting pattern) occurring only about the pivot of the respective system was observed in canonical simulations. The extent and direction of the rotation depended on the initial conditions. This result suggests that rotatory molecular motors can convert thermal oscillations into net rotational motion. The energy from ATP hydrolysis is required probably to set the direction and extent of rotation. Our findings highlight the importance of molecular-motor structures in facilitating movement and transportation within living organisms.
Plasma Osteopontin Reflects Tissue Damage in Acute Pancreatitis
Authors: Wirestam Lina , Nyberg Pernilla Benjaminsson , Dzhendov Todor , Gasslander Thomas , Sandström Per , Sjöwall Christopher , Björnsson Bergthor
Published: June 2023

Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, but the significance of OPN in AP has not yet been established. We aimed to evaluate plasma levels of OPN in relation to the severity of AP. In 39 individuals with confirmed AP, plasma was collected on the day of admission and consecutively for three days thereafter. Sex- and age-matched healthy blood donors (n = 39) served as controls. Plasma OPN was measured by a commercial enzyme-linked immunosorbent assay. At admission, patients with AP displayed higher OPN, 156.4 ng/mL (IQR 111.8–196.2) compared to controls, 37.4 ng/mL (IQR 11.7–65.7) (p < 0.0001). However, OPN levels on admission could not discriminate between mild and moderate-to-severe disease (132.6 ng/mL vs. 163.4 ng/mL). Nevertheless, the changes in OPN within 24 h of admission and Day 2/3 were higher among patients with moderate/severe AP (33.7%) compared to mild AP (−8.1%) (p = 0.01). This indicates that OPN is a relevant biomarker reflecting tissue injury in AP. The increase in OPN over time suggests that serial OPN measurements could contribute to the early detection of at-risk patients. Prospective studies assessing OPN in relation to outcome in AP are warranted.
Functional and Morphological Characteristics of the Retina of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus Treated with Hydroxychloroquine: A Retrospective Study
Authors: Kitay Alice M. , Hanson James V. M. , Hasan Nasiq , Driban Matthew , Chhablani Jay , Barthelmes Daniel , Gerth-Kahlert Christina , Al-Sheikh Mayss
Published: June 2023

Purpose: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). Methods: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. Results: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. Conclusions: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG.
Clinical Impact and Safety of Non-Target Punctures (NTP) during Portal Vein Access in TIPS Procedure
Authors: Feinggumloon Sasikorn , Haber Zachary , Saab Sammy , Kaldas Fady , Eghbalieh Navid , Luong Thanh T. , McWilliams Justin P. , Lee Edward Wolfgang
Published: June 2023

Background: Although non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures. Methods: A retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed. We identified inadvertent NTPs, including biliary, hepatic artery, lymphatic and capsular punctures. Next, the medical records and images were reviewed and analyzed to assess the safety and clinical outcomes of these cohorts. Results: A total of 71 NTPs were identified in 56 patients (15.18% of 369 patients). Of 369 TIPS patients, there were (1) 28 biliary punctures (7.6%), (2) 16 extracapsular punctures (4.3%), (3) 15 lymphatic punctures (4.1%) and (4) 12 hepatic artery punctures (3.3%). The overall complication rate was 2.2% (8/369). Based on the Clavien–Dindo classification, three patients (0.8%) had a minor complication. In addition, five patients (1.4%) experienced grade II–V major complications, such as symptomatic hemoperitoneum, arterio-biliary fistula or hemorrhagic shock leading to death. Mortality (0.5%) was only caused by extracapsular puncture combined with other NTP. Conclusions: NTPs during the portal access of TIPS procedures are associated with low complication risk. However, when extracapsular punctures are combined with other NTPs, a more severe complication, including mortality, can occur. Nevertheless, all patients with NTP should be closely monitored at a higher level of care after TIPS placement.
High-Accuracy ncRNA Function Prediction via Deep Learning Using Global and Local Sequence Information
Authors: Orro Alessandro , Trombetti Gabriele A.
Published: June 2023

The prediction of the biological function of non-coding ribonucleic acid (ncRNA) is an important step towards understanding the regulatory mechanisms underlying many diseases. Since non-coding RNAs are present in great abundance in human cells and are functionally diverse, developing functional prediction tools is necessary. With recent advances in non-coding RNA biology and the availability of complete genome sequences for a large number of species, we now have a window of opportunity for studying non-coding RNA biology. However, the computational methods used to predict the non-coding RNA functions are mostly either scarcely accurate, when based on sequence information alone, or prohibitively expensive in terms of computational burden when a secondary structure prediction is needed. We propose a novel computational method to predict the biological function of non-coding RNA genes that is based on a collection of deep network architectures utilizing solely ncRNA sequence information and which does not rely on or require expensive secondary ncRNA structure information. The approach presented in this work exhibits comparable or superior accuracy to methods that employ both sequence and structural features, at a much lower computational cost.
Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence
Authors: Butranova Olga I. , Ushkalova Elena A. , Zyryanov Sergey K. , Chenkurov Mikhail S. , Baybulatova Elena A.
Published: June 2023

Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets. The objective of this review is to perform a structure of evidence on the age-related changes contributing to the alteration of pharmacokinetic parameters in the elderly.
Pathogenesis, Intervention, and Current Status of Drug Development for Sarcopenia: A Review
Authors: Jang Jung Yoon , Kim Donghwan , Kim Nam Deuk
Published: June 2023

Sarcopenia refers to the loss of muscle strength and mass in older individuals and is a major determinant of fall risk and impaired ability to perform activities of daily living, often leading to disability, loss of independence, and death. Owing to its impact on morbidity, mortality, and healthcare expenditure, sarcopenia in the elderly has become a major focus of research and public policy debates worldwide. Despite its clinical importance, sarcopenia remains under-recognized and poorly managed in routine clinical practice, partly owing to the lack of available diagnostic testing and uniform diagnostic criteria. Since the World Health Organization and the United States assigned a disease code for sarcopenia in 2016, countries worldwide have assigned their own disease codes for sarcopenia. However, there are currently no approved pharmacological agents for the treatment of sarcopenia; therefore, interventions for sarcopenia primarily focus on physical therapy for muscle strengthening and gait training as well as adequate protein intake. In this review, we aimed to examine the latest information on the epidemiology, molecular mechanisms, interventions, and possible treatments with new drugs for sarcopenia.
Combined Pulmonary Fibrosis and Emphysema: Comparative Evidence on a Complex Condition
Authors: Calaras Diana , Mathioudakis Alexander G. , Lazar Zsofia , Corlateanu Alexandru
Published: June 2023

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical syndrome characterized by upper lobe emphysema and lower lobe fibrosis manifested by exercise hypoxemia, normal lung volumes, and severe reduction of diffusion capacity of carbon monoxide. It has varying prevalence worldwide with a male predominance, and with smoking history of more than 40 pack-years being a common risk factor. The unique imaging features of CPFE emphasize its distinct entity, aiding in the timely detection of pulmonary hypertension and lung cancer, both of which are common complications. High-resolution computed tomography (HRCT) is an important diagnostic and prognostic tool, while lung cancer is an independent factor that alters the prognosis in CPFE patients. Treatment options for CPFE are limited, but smoking cessation, usual treatments of pulmonary fibrosis and emphysema, and avoidance of environmental exposures are encouraged.
Targeting Store-Operated Calcium Entry Regulates the Inflammation-Induced Proliferation and Migration of Breast Cancer Cells
Authors: Alqinyah Mohammed , Alhamed Abdullah S. , Alnefaie Hajar O. , Algahtani Mohammad M. , Badr Amira M. , Albogami Abdullah M. , Mohany Mohamed , Alassmrry Yasseen A. , Alghaith Adel F. , Alhamami Hussain N. , Alhazzani Khalid , Alanazi Ahmed Z. , Alsaidan Omar Awad
Published: June 2023

Persistent challenges complicating the treatment of breast cancer remain, despite some recent undeniable successes. Sufficient evidence currently exists demonstrating the crucial role of inflammation, characterized by the enhanced activation of Toll-like receptor 4 (TLR4) and the COX-2/PGE2 pathway, in the migration and proliferation of breast cancer cells. Interestingly, the store-operated calcium entry (SOCE) pathway was shown to be essential for the TLR4 activity and COX-2 expression in immune cells such as macrophages and microglia. However, whether SOCE influences inflammatory signaling and the inflammation-induced proliferation and migration of breast cancer cells is still unknown. Thus, the current study intended to delineate the role of SOCE in the TLR4-induced inflammation, migration, and proliferation of breast cancer cells. To this end, MDA-MB-231 breast cancer cells were treated with lipopolysaccharide (LPS) to activate TLR4, BTP2 to inhibit SOCE, and Thapsigargin to induce SOCE. Following these treatments, several experiments were conducted to evaluate the proliferation and migration rates of the MDA-MB-231 cells and the expression of several inflammatory and oncogenic genes, including COX-2, PGE2, IL-6, IL-8, and VEGF. Different techniques were used to achieve the aims of this study, including qRT-PCR, Western blotting, ELISA, MTT, and wound healing assays. This study shows that SOCE inhibition using BTP2 suppressed the LPS-induced migration and proliferation of breast cancer cells. Additionally, treatment with LPS caused approximately six- and three-fold increases in COX-2 mRNA and protein expression, respectively, compared to the controls. The LPS-induced elevations in the COX-2 mRNA and protein levels were suppressed by BTP2 to the control levels. In addition to its effect on COX-2, BTP2 also suppressed the LPS-induced productions of PGE2, IL-6, IL-8, and VEGF. Conversely, SOCE induction using Thapsigargin enhanced the LPS-induced inflammation, migration, and proliferation of breast cancer cells. Collectively, these results provide evidence for the potentially important role of SOCE in inflammation-induced breast cancer progression processes. Thus, we argue that the current study may provide novel targets for designing new therapeutic approaches for the treatment of breast cancer.
Serine/Threonine Protein Phosphatases 1 and 2A in Lung Endothelial Barrier Regulation
Authors: Patil Rahul S. , Kovacs-Kasa Anita , Gorshkov Boris A. , Fulton David J. R. , Su Yunchao , Batori Robert K. , Verin Alexander D.
Published: June 2023

Vascular barrier dysfunction is characterized by increased permeability and inflammation of endothelial cells (ECs), which are prominent features of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and sepsis, and a major complication of the SARS-CoV-2 infection and COVID-19. Functional impairment of the EC barrier and accompanying inflammation arises due to microbial toxins and from white blood cells of the lung as part of a defensive action against pathogens, ischemia-reperfusion or blood product transfusions, and aspiration syndromes-based injury. A loss of barrier function results in the excessive movement of fluid and macromolecules from the vasculature into the interstitium and alveolae resulting in pulmonary edema and collapse of the architecture and function of the lungs, and eventually culminates in respiratory failure. Therefore, EC barrier integrity, which is heavily dependent on cytoskeletal elements (mainly actin filaments, microtubules (MTs), cell-matrix focal adhesions, and intercellular junctions) to maintain cellular contacts, is a critical requirement for the preservation of lung function. EC cytoskeletal remodeling is regulated, at least in part, by Ser/Thr phosphorylation/dephosphorylation of key cytoskeletal proteins. While a large body of literature describes the role of phosphorylation of cytoskeletal proteins on Ser/Thr residues in the context of EC barrier regulation, the role of Ser/Thr dephosphorylation catalyzed by Ser/Thr protein phosphatases (PPases) in EC barrier regulation is less documented. Ser/Thr PPases have been proposed to act as a counter-regulatory mechanism that preserves the EC barrier and opposes EC contraction. Despite the importance of PPases, our knowledge of the catalytic and regulatory subunits involved, as well as their cellular targets, is limited and under-appreciated. Therefore, the goal of this review is to discuss the role of Ser/Thr PPases in the regulation of lung EC cytoskeleton and permeability with special emphasis on the role of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) as major mammalian Ser/Thr PPases. Importantly, we integrate the role of PPases with the structural dynamics of the cytoskeleton and signaling cascades that regulate endothelial cell permeability and inflammation.
Change in Cartilage Status of Medial Compartment after Open-Wedge High Tibial Osteotomy without Cartilage Regeneration Procedure: Second Look Arthroscopic Assessment
Authors: Lee Sung-Sahn , Oh Juyong , Lee Dae-Hee
Published: June 2023

This study investigated the rate of cartilage regeneration after an open-wedge high tibial osteotomy (HTO) without cartilage regeneration by second-look arthroscopy. This study included patients who underwent an open-wedge HTO between July 2014 and March 2019. A total of 65 patients were enrolled. Pre- and postoperative (second-look arthroscopy) hip–knee–ankle (HKA) angle and tibial slope were measured. All patients underwent arthroscopic examination prior to osteotomy. Medial femoral condyle (MFC) and medial tibial plateau (MTP) articular cartilage were evaluated according to the International Cartilage Repair Society (ICRS) grading system. After 26.5 months, second-look arthroscopy was performed with plate removal to identify the cartilage status of the MFC and MTP. The preoperative HKA angle (6.4° ± 2.7°) was well corrected postoperatively (−2.7° ± 2.7°, p < 0.001). In terms of MFC on second-look arthroscopy, 29 patients (44.6%) showed an improved ICRS grade, 31 patients (47.7%) were maintained, and 5 patients (7.7%) showed a worse ICRS grade since the prior operation. In the MTP group, 19 patients (29.2%) improved, 44 patients (67.7%) were maintained, and 2 patients (3.1%) worsened. Approximately 44.6% and 29.2% of patients showed improved cartilage statuses on the MFC and MTP after open-wedge HTO without any cartilage regeneration procedures. Cartilage regenerations in both the MFC and MTP did not influence clinical outcomes.
Integrative Molecular Analysis of DNA Methylation Dynamics Unveils Molecules with Prognostic Potential in Breast Cancer
Authors: Mehmood Rashid , Alsaleh Alanoud , Want Muzamil Y. , Ahmad Ijaz , Siraj Sami , Ishtiaq Muhammad , Alshehri Faizah A. , Naseem Muhammad , Yasuhara Noriko
Published: June 2023

DNA methylation acts as a major epigenetic modification in mammals, characterized by the transfer of a methyl group to a cytosine. DNA methylation plays a pivotal role in regulating normal development, and misregulation in cells leads to an abnormal phenotype as is seen in several cancers. Any mutations or expression anomalies of genes encoding regulators of DNA methylation may lead to abnormal expression of critical molecules. A comprehensive genomic study encompassing all the genes related to DNA methylation regulation in relation to breast cancer is lacking. We used genomic and transcriptomic datasets from the Cancer Genome Atlas (TGCA) Pan-Cancer Atlas, Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes related to DNA methylation with respect to writing, reading and erasing this epigenetic mark. Analysis of mutations was conducted using cBioportal, while Xena and KMPlot were utilized for expression changes and patient survival, respectively. Our study identified multiple mutations in the genes encoding regulators of DNA methylation. The expression profiling of these showed significant differences between normal and disease tissues. Moreover, deregulated expression of some of the genes, namely DNMT3B, MBD1, MBD6, BAZ2B, ZBTB38, KLF4, TET2 and TDG, was correlated with patient prognosis. The current study, to our best knowledge, is the first to provide a comprehensive molecular and genetic profile of DNA methylation machinery genes in breast cancer and identifies DNA methylation machinery as an important determinant of the disease progression. The findings of this study will advance our understanding of the etiology of the disease and may serve to identify alternative targets for novel therapeutic strategies in cancer.
Cultural Differences in Inhibitory Control: An ALE Meta-Analysis
Authors: Gavazzi Gioele , Noferini Chiara , Benedetti Viola , Cotugno Maria , Giovannelli Fabio , Caldara Roberto , Mascalchi Mario , Viggiano Maria Pia
Published: June 2023

Culture greatly influences our attitudes, beliefs, and behaviors, affecting how we communicate and make decisions. There is an ongoing debate regarding the belief that people from Eastern cultures possess greater self-control abilities when compared to people from Western cultures. In this study, we conducted a meta-analysis using the Activation Likelihood Estimation (ALE) algorithm to compare 30 studies (719 subjects, 373 foci) that used fMRI to investigate the performance in Go–Nogo and Stop Signal Tasks of participants from Western and/or Eastern countries. Our meta-analysis found differences between the networks activated in Eastern and Western culture participants. The right prefrontal cortex showed distinct patterns, with the Inferior Frontal gyrus more active in the Eastern group and the middle and superior frontal gyri more active in the Western group. Our findings suggest that Eastern culture subjects have a higher tendency to activate brain regions involved in proactive inhibitory control, while Western culture subjects rely more on reactive inhibitory brain regions during cognitive control tasks. This implies that proactive inhibition may play a crucial role in promoting the collective and interdependent behavior typical of Eastern cultures, while reactive inhibition may be more important for efficient cognitive control in subjects of Western cultures that prioritize individualism and independence.
Cue Weighting in Perception of the Retroflex and Non-Retroflex Laterals in the Zibo Dialect of Chinese
Authors: Dong Bing , Liang Jie , Liu Chang
Published: June 2023

This study investigated cue weighting in the perception of the retroflex and non-retroflex lateral contrast in the monosyllabic words /ɭə/ and /lə/ in the Zibo dialect of Chinese. A binary forced-choice identification task was carried out among 32 natives, using computer-modified natural speech situated in a two-dimensional acoustic space. The results showed that both acoustic cues had a significant main effect on lateral identification, with F1 of the following schwa being the primary cue and the consonant-tos-vowel (C/V) duration ratio as a secondary cue. No interaction effect was found between these two acoustic cues. Moreover, the results indicated that acoustic cues were not equally weighted in production and perception of the syllables /ɭə/ and /lə/ in the Zibo dialect. Future studies are suggested involving other acoustic cues (e.g., the F1 of laterals) or adding noise in the identification task to better understand listeners’ listening strategies in their perception of the two laterals in the Zibo dialect.
Augmented Reality for Building Authorities: A Use Case Study in Austria
Authors: Gerger Alexander , Urban Harald , Schranz Christian
Published: June 2023

The widespread usage of BIM and technological advances in augmented reality (AR) paves the way for Construction 4.0. This digital transformation has reached the construction industry and requires consideration of all life cycle phases. The approval phase has been little researched to date. In Vienna, the analogous process takes up to 18 months. This long duration inhibits progress in the building industry. One reason for this is objections from parties who are nonexperts and have difficulty understanding the project solely from its 2D plans. Therefore, the City of Vienna wants to redesign the building authority processes through the use of BIM and AR in the BRISE-Vienna research project. This article examines possible applications for public authorities. AR can be utilised at the interface between authorities and stakeholders and is intended to accelerate processes through better communication. For the City of Vienna, 12 AR use cases were developed from process analyses and expert interviews. In addition to the conception of the AR use cases for public authorities, a study was carried out regarding their benefits and feasibility. The use cases have the potential to increase the understanding of the project for experts and nonexperts. The best-rated AR use cases (plan checking and hearing during the permission process) will be further developed in the research project. The AR use cases should help to significantly accelerate processes in Vienna and, thus, serve as a basis for other cities and countries.
Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping
Authors: Díaz-González Álvaro , Mora Elvira , Avetisyan Gayane , Furió Santiago , De la Puerta Rosalía , Gil José Vicente , Liquori Alessandro , Villamón Eva , García-Hernández Carmen , Santiago Marta , García-Ruiz Cristian , Llop Marta , Ferrer-Lores Blanca , Barragán Eva , García-Palomares Silvia , Mayordomo Empar , Luna Irene , Vicente Ana , Cordón Lourdes , Senent Leonor , Álvarez-Larrán Alberto , Cervera José , De la Rubia Javier , Hernández-Boluda Juan Carlos , Such Esperanza
Published: June 2023

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.
The Role of Adhesion Molecules and Extracellular Vesicles in an In Vitro Model of the Blood–Brain Barrier for Metastatic Disease
Authors: Vasco Chiara , Rizzo Ambra , Cordiglieri Chiara , Corsini Elena , Maderna Emanuela , Ciusani Emilio , Salmaggi Andrea
Published: June 2023

Metastatic brain disease (MBD) has seen major advances in clinical management, focal radiation therapy approaches and knowledge of biological factors leading to improved prognosis. Extracellular vesicles (EVs) have been found to play a role in tumor cross-talk with the target organ, contributing to the formation of a premetastatic niche. Human lung and breast cancer cell lines were characterized for adhesion molecule expression and used to evaluate their migration ability in an in vitro model. Conditioned culture media and isolated EVs, characterized by super resolution and electron microscopy, were tested to evaluate their pro-apoptotic properties on human umbilical vein endothelial cells (HUVECs) and human cerebral microvascular endothelial cells (HCMEC/D3) by annexin V binding assay. Our data showed a direct correlation between expression of ICAM1, ICAM2, β3-integrin and α2-integrin and the ability to firmly adhere to the blood–brain barrier (BBB) model, whereas the same molecules were down-regulated at a later step. Extracellular vesicles released by tumor cell lines were shown to be able to induce apoptosis in HUVEC while brain endothelial cells showed to be more resistant.
The BETTY Score to Predict Perioperative Outcomes in Surgical Patients
Authors: Baboudjian Michael , Abou-Zahr Rawad , Buhas Bogdan , Touzani Alae , Beauval Jean-Baptiste , Ploussard Guillaume
Published: June 2023

The aim of this study is to evaluate a new user-friendly scoring system, namely the BETTY score, that aims to predict 30-day patient outcomes after surgery. In this first description, we rely on a population of prostate cancer patients undergoing robot-assisted radical prostatectomy. The BETTY score includes the patient’s American Society of Anesthesiologists score, the body mass index, and intraoperative data, including operative time, estimated blood loss, any major intraoperative complications, hemodynamic, and/or respiratory instability. There is an inverse relationship between the score and severity. Three clusters assessing the risk of postoperative events were defined: low, intermediate, and high risk of postoperative events. A total of 297 patients was included. The median length of hospital stay was 1 day (IQR1-2). Unplanned visits, readmissions, any complications, and serious complications occurred in 17.2%, 11.8%, 28.3%, and 5% of cases, respectively. We found a statistically significant correlation between the BETTY score and all endpoints analyzed (all p ≤ 0.01). A total of 275, 20, and 2 patients were classified as low-, intermediate-, and high-risk according to the BETTY scoring system, respectively. Compared with low-risk patients, patients at intermediate-risk were associated with worse outcomes for all endpoints analyzed (all p ≤ 0.04). Future studies, in various surgical subspecialties, are ongoing to confirm the usefulness of this easy-to-use score in routine.
Utility of Patient-Reported Symptom and Functional Outcomes to Indicate Recovery after First 90 Days of Radical Cystectomy: A Longitudinal Study
Authors: Wang Xin Shelley , Bree Kelly K. , Navai Neema , Kamal Mona , Shen Shu-En , Letona Elizabeth , Cleeland Charles S. , Shi Qiuling , Gottumukkala Vijaya
Published: June 2023

This is a longitudinal prospective study that tracked multiple symptom burden and functioning status for bladder cancer (BLC) patients for 3 months post-radical cystectomy at The University of Texas MD Anderson Cancer Center, using a validated disease-specific patient-reported outcome measure (PROM) tool, the MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). The feasibility of collecting an objective measure for physical functioning, using “Timed Up & Go test” (TUGT) and PRO scores at baseline, discharge and end of study, was tested. Patients (n = 52) received care under an ERAS pathway. The more severe scores of fatigue, sleep disturbance, distress, drowsiness, frequent urination and urinary urgency at baseline predicted poor functional recovery postoperatively (OR = 1.661, 1.039–2.655, p = 0.034); other more severe symptoms at discharge (pain, fatigue, sleep disturbance, lack of appetite, drowsiness, bloating/abdominal tightness) predicted poor functional recovery (OR = 1.697, 1.114–2.584, p = 0.014) postoperatively. Compliance rates at preoperative, discharge and end of study were 100%, 79% and 77%, while TUGT completion rates were 88%, 54% and 13%, respectively. This prospective study found that more severe symptom burden at baseline and discharge is associated with poor functional recovery post-radical cystectomy for BLC. The collection of PROs is more feasible than using performance measures (TUGT) of function following radical cystectomy.
Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy
Authors: Golčić Marin , Simetić Luka , Herceg Davorin , Blažičević Krešimir , Kenđel Jovanović Gordana , Dražić Ivan , Belančić Andrej , Skočibušić Nataša , Palčevski Dora , Rubinić Igor , Vlahović-Palčevski Vera , Majnarić Tea , Dobrila-Dintinjana Renata , Pleština Stjepko
Published: June 2023

Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.
The Emerging, Multifaceted Role of WTAP in Cancer and Cancer Therapeutics
Authors: Ju Guomin , Lei Jiangchu , Cai Shuqi , Liu Siyuan , Yin Xinjia , Peng Chuanhui
Published: June 2023

Cancer is a grave and persistent illness, with the rates of both its occurrence and death toll increasing at an alarming pace. N6-methyladenosine (m6A), the most prevalent mRNA modification in eukaryotic organisms, is catalyzed by methyltransferases and has a significant impact on various aspects of cancer progression. WT1-associated protein (WTAP) is a crucial component of the m6A methyltransferase complex, catalyzing m6A methylation on RNA. It has been demonstrated to participate in numerous cellular pathophysiological processes, including X chromosome inactivation, cell proliferation, cell cycle regulation, and alternative splicing. A better understanding of the role of WTAP in cancer may render it a reliable factor for early diagnosis and prognosis, as well as a key therapeutic target for cancer treatment. It has been found that WTAP is closely related to tumor cell cycle regulation, metabolic regulation, autophagy, tumor immunity, ferroptosis, epithelial mesenchymal transformation (EMT), and drug resistance. In this review, we will focus on the latest advances in the biological functions of WTAP in cancer, and explore the prospects of its application in clinical diagnosis and therapy.
A Panorama of Immune Fighters Armored with CARs in Acute Myeloid Leukemia
Authors: Christodoulou Ilias , Solomou Elena E.
Published: June 2023

Acute myeloid leukemia (AML) is a devastating disease. Intensive chemotherapy is the mainstay of treatment but results in debilitating toxicities. Moreover, many treated patients will eventually require hematopoietic stem cell transplantation (HSCT) for disease control, which is the only potentially curative but challenging option. Ultimately, a subset of patients will relapse or have refractory disease, posing a huge challenge to further therapeutic decisions. Targeted immunotherapies hold promise for relapsed/refractory (r/r) malignancies by directing the immune system against cancer. Chimeric antigen receptors (CARs) are important components of targeted immunotherapy. Indeed, CAR-T cells have achieved unprecedented success against r/r CD19+ malignancies. However, CAR-T cells have only achieved modest outcomes in clinical studies on r/r AML. Natural killer (NK) cells have innate anti-AML functionality and can be engineered with CARs to improve their antitumor response. CAR-NKs are associated with lower toxicities than CAR-T cells; however, their clinical efficacy against AML has not been extensively investigated. In this review, we cite the results from clinical studies of CAR-T cells in AML and describe their limitations and safety concerns. Moreover, we depict the clinical and preclinical landscape of CAR used in alternative immune cell platforms with a specific focus on CAR-NKs, providing insight into the future optimization of AML.
Regulators of the Asexual Life Cycle of Aspergillus nidulans
Authors: Son Ye-Eun , Yu Jae-Hyuk , Park Hee-Soo
Published: June 2023

The genus Aspergillus, one of the most abundant airborne fungi, is classified into hundreds of species that affect humans, animals, and plants. Among these, Aspergillus nidulans, as a key model organism, has been extensively studied to understand the mechanisms governing growth and development, physiology, and gene regulation in fungi. A. nidulans primarily reproduces by forming millions of asexual spores known as conidia. The asexual life cycle of A. nidulans can be simply divided into growth and asexual development (conidiation). After a certain period of vegetative growth, some vegetative cells (hyphae) develop into specialized asexual structures called conidiophores. Each A. nidulans conidiophore is composed of a foot cell, stalk, vesicle, metulae, phialides, and 12,000 conidia. This vegetative-to-developmental transition requires the activity of various regulators including FLB proteins, BrlA, and AbaA. Asymmetric repetitive mitotic cell division of phialides results in the formation of immature conidia. Subsequent conidial maturation requires multiple regulators such as WetA, VosA, and VelB. Matured conidia maintain cellular integrity and long-term viability against various stresses and desiccation. Under appropriate conditions, the resting conidia germinate and form new colonies, and this process is governed by a myriad of regulators, such as CreA and SocA. To date, a plethora of regulators for each asexual developmental stage have been identified and investigated. This review summarizes our current understanding of the regulators of conidial formation, maturation, dormancy, and germination in A. nidulans.
A Sensor for Electrochemical pH Monitoring Based on Laser-Induced Graphene Modified with Polyfolate
Authors: Žutautas Vytautas , Trusovas Romualdas , Sartanavičius Aivaras , Ratautas Karolis , Selskis Algirdas , Pauliukaite Rasa
Published: June 2023

A laser-induced graphene (LIG) modified with chitosan (Chit) and conducting polymer polyfolate (PFA) was used as a base to develop a flat and flexible pH sensor. LIGs were formed using two different irradiation wavelengths of 355 nm and 532 nm. Depending on the wavelengths, the obtained electrodes were named LIG355 and LIG532. Microscopic imaging revealed that the bare LIG electrode surface had rough structures after laser treatment giving hydrophilic properties, and that PFA forms fibre-like structures on Chit coated LIG. Electrochemical investigation with the redox probe demonstrated that diffusion is a limiting process at the bare and modified LIG electrodes. A capacitive behaviour was observed from electrochemical impedance spectra at bare electrodes, showing a rather rough interface at LIG355 but a microporous one at LIG532. The developed flat and flexible electrode was sensitive to pH in the region from 6.0 to 9.0. In the studied pH range, the sensitivity was 27.86 ± 0.81 for PFA/Chit/LIG355 and 30.32 ± 0.50 mV/pH for PFA/Chit/LIG532 with moderate stability for a period of more than two months.
A ‘Turn-On’ Carbamazepine Sensing Using a Luminescent SiO2/-(CH2)3NH2/-C6H5 + Rh6G System
Authors: Yankovych Halyna , Dutková Erika , Kyshkarova Viktoriia , Vaclavikova Miroslava , Melnyk Inna
Published: June 2023

Carbamazepine is a crucial medication used to treat nervous system disorders, and its low level of absorption in the human body suggests that a significant amount of it may be present in sewage water. Consequently, this pioneering research deals with the synthesis and application of a luminescent sensor based on rhodamine 6 G-modified bifunctional silica particles for the determination of carbamazepine. The sensing material was fabricated in one step by the sol–gel technique and the dye was adsorbed onto the surface from an alcohol solution. The composition, morphology and size of functionalized silica particles were determined by physico-chemical methods. The material’s features provide the possibility of its application as a sensing material for carbamazepine determination at a variety of concentrations. The sensor possesses a linear response towards carbamazepine in the concentration range of 0.8–200.0 μM with a limit of detection (LOD) of 17.9 μM and a limit of quantification (LOQ) of 59.7 μM and has demonstrated reliable quantification over a wide range of concentrations, from therapeutic to high fatal concentrations. Additionally, the sensing mechanism has been proposed, which involves the formation of hydrogen bonding between carbamazepine and Rhodamine 6G immobilized bifunctional silica particles.
Recent Progress in Fluorescent Probes for the Detection and Research of Hydrogen Sulfide in Cells
Authors: Liang Weier , Zhang Yong , Xiong Shaoqing , Su Dongdong
Published: June 2023

Hydrogen sulfide (H2S) is a gaseous signaling molecule that plays an important role in regulating various physiological activities in biological systems. As the fundamental structural and functional unit of organisms, cells are closely related to the homeostasis of their internal environment. The levels of H2S in different organelles maintain a certain balance, and any disruption of this balance will lead to various functional abnormalities that affect the health of organisms. Fluorescent imaging technology provides unique merits, such as simplicity, non-invasiveness, and real-time monitoring, and has become a powerful approach for the detection of molecules in biological systems. Based on the special physicochemical properties of H2S, numerous H2S-specific fluorogenic probes have been designed with different recognition mechanisms that enable rapid and accurate detection of H2S in cells. Therefore, this review briefly illustrates the design strategies, response principles, and biological applications of H2S-specific fluorescent probes and aims to provide relevant researchers with insight for future research.
N-Doped Graphene and Its Derivatives as Resistive Gas Sensors: An Overview
Authors: Mirzaei Ali , Bharath Somalapura Prakasha , Kim Jin-Young , Pawar Krishna K. , Kim Hyoun Woo , Kim Sang Sub
Published: June 2023

Today, resistance gas sensors which are mainly realized from metal oxides are among the most used sensing devices. However, generally, their sensing temperature is high and other materials with a lower operating temperature can be an alternative to them. Graphene and its derivatives with a 2D structure are among the most encouraging materials for gas-sensing purposes, because a 2D lattice with high surface area can maximize the interaction between the surface and gas, and a small variation in the carrier concentration of graphene can cause a notable modulation of electrical conductivity in graphene. However, they show weak sensing performance in pristine form. Hence, doping, and in particular N doping, can be one of the most promising strategies to enhance the gas-sensing features of graphene-based sensors. Herein, we discuss the gas-sensing properties of N-doped graphene and its derivatives. N doping can induce a band gap inside of graphene, generate defects, and enhance the conductivity of graphene, all factors which are beneficial for sensing studies. Additionally, not only is experimental research reviewed in this review paper, but theoretical works about N-doped graphene are also discussed.
Hybrid Palliation for Hypoplastic Left Heart Syndrome: Role of Echocardiography
Authors: Oreto Lilia , Guccione Paolo , Gitto Placido , Bruno Letteria , Zanai Rosanna , Grasso Nadia , Iannace Enrico , Zito Concetta , Carerj Scipione , Agati Salvatore
Published: June 2023

Hypoplastic left heart syndrome is a spectrum of complex congenital cardiac defects. Although in borderline cases, biventricular repair is a viable option, in the majority of cases, univentricular palliation is the treatment of choice. Hybrid palliation can be a valid alternative to classic Norwood operation in the neonatal period, especially in selected cases such as high-risk patients or borderline left ventricles. Echocardiography is the main diagnostic modality in this pediatric population, from the fetal diagnosis to the subsequent surgical steps of palliative treatment. Hybrid palliation is performed after birth and is characterized by surgical banding of the pulmonary arteries along with transcatheter stenting of the ductus arteriosus. There are some peculiar aspects of cardiac imaging that characterize this type of palliation, and that should be considered in the different phases before and after the procedure. We aimed to review the current literature about the role of echocardiography in the management of patients with hypoplastic left heart undergoing hybrid palliation.