bluuebunny/crossref_metadata_2025 huggingface dataset:
CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression
Authors: Luksik Andrew S. , Yazigi Eli , Shah Pavan , Jackson Christopher M.
Published: February 2023

Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.
Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options
Authors: Winter Jochen , Kunze Rudolf , Veit Nadine , Kuerpig Stefan , Meisenheimer Michael , Kraus Dominik , Glassmann Alexander , Probstmeier Rainer
Published: February 2023

(1) Background: the potency of drugs that interfere with glucose metabolism, i.e., glucose transporters (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT) was analyzed in neuroendocrine tumor (NET, BON-1, and QPG-1 cells) and small cell lung cancer (SCLC, GLC-2, and GLC-36 cells) tumor cell lines. (2) Methods: the proliferation and survival rate of tumor cells was significantly affected by the GLUT-inhibitors fasentin and WZB1127, as well as by the NAMPT inhibitors GMX1778 and STF-31. (3) Results: none of the NET cell lines that were treated with NAMPT inhibitors could be rescued with nicotinic acid (usage of the Preiss–Handler salvage pathway), although NAPRT expression could be detected in two NET cell lines. We finally analyzed the specificity of GMX1778 and STF-31 in NET cells in glucose uptake experiments. As previously shown for STF-31 in a panel NET-excluding tumor cell lines, both drugs specifically inhibited glucose uptake at higher (50 μM), but not at lower (5 μM) concentrations. (4) Conclusions: our data suggest that GLUT and especially NAMPT inhibitors are potential candidates for the treatment of NET tumors.
Degradation of Antibiotic Vancomycin by UV Photolysis and Pulsed Corona Discharge Combined with Extrinsic Oxidants
Authors: Nikitin Dmitri , Kaur Balpreet , Preis Sergei , Dulova Niina
Published: February 2023

Antibiotics are the most frequently detected pharmaceuticals in the environment creating conditions for the development of resistant genes in bacteria. Degradation and mineralization of glycopeptide antibiotic vancomycin (VMN) were examined by UV photolysis, pulsed corona discharge (PCD), and their combinations with extrinsic oxidants, hydrogen peroxide (HP), peroxydisulfate (PDS), and peroxymonosulfate (PMS). Both combinations were effective in VMN degradation and faster at pH 11 than in acidic or neutral media. Combined with the UV photolysis, HP showed a higher oxidation rate than other oxidants, whereas PMS and PDS proved to be more efficient in combinations with PCD. In contrast to low-to-moderate mineralization of VMN in the UV/oxidant combinations, PCD and PCD/oxidant combinations appeared to be more effective, reaching up to 90% of TOC removal in acidic/neutral solutions. Application of extrinsic oxidants resulted in an energy efficiency of VMN 90% oxidation improved from 36 to 61 g kW−1 h−1 in HP-assisted photolysis, and from 195 to 250 g kW−1 h−1 in PCD with additions of HP and PDS, thus showing the promising character of the combined treatment.
An Efficient Strategy for Chemoenzymatic Conversion of Corn Stover to Furfuryl Alcohol in Deep Eutectic Solvent ChCl:PEG10000−Water Medium
Authors: Xu Daozhu , Tang Wei , Tang Zhengyu , He Yucai
Published: February 2023

As a versatile and valuable intermediate, furfuryl alcohol (FOL) is widely utilized in manufacturing vitamin C, perfume, fruit acid, lubricant, lysine, plasticizer, dispersing agent, resin, fuel additive, and biofuel. This study aimed at the establishment of a cascade catalysis of biomass to FOL via a hybrid approach in a deep eutectic solvent medium. The catalysis of corn stover (75 g/L) with solid acid AT-Sn-WLS (1.2 wt%) produced 110.5 mM FAL in a ChCl:PEG10000–water (20:80, wt/wt) system at 170 °C for 30 min, and then the formed FAL was biologically transformed into FOL with recombinant E. coli SF harboring aldehyde reductase at pH 7.0 and 35 °C. This established hybrid strategy could efficiently valorize corn stover into FOL, with the productivity of 0.41 g FOL per g xylan in corn stover. Consequently, one combination of chemocatalytic and biocatalytic reactions leading to a one-pot catalytic process was shown as an attractive approach in the valorization of lignocellulose into valuable biobased chemicals.
Comparative and Temporal Characterization of LPS and Blue-Light-Induced TLR4 Signal Transduction and Gene Expression in Optogenetically Manipulated Endothelial Cells
Authors: Stierschneider Anna , Neuditschko Benjamin , Colleselli Katrin , Hundsberger Harald , Herzog Franz , Wiesner Christoph
Published: February 2023

In endothelial cells (ECs), stimulation of Toll-like receptor 4 (TLR4) by the endotoxin lipopolysaccharide (LPS) induces the release of diverse pro-inflammatory mediators, beneficial in controlling bacterial infections. However, their systemic secretion is a main driver of sepsis and chronic inflammatory diseases. Since distinct and rapid induction of TLR4 signaling is difficult to achieve with LPS due to the specific and non-specific affinity to other surface molecules and receptors, we engineered new light-oxygen-voltage-sensing (LOV)-domain-based optogenetic endothelial cell lines (opto-TLR4-LOV LECs and opto-TLR4-LOV HUVECs) that allow fast, precise temporal, and reversible activation of TLR4 signaling pathways. Using quantitative mass-spectrometry, RT-qPCR, and Western blot analysis, we show that pro-inflammatory proteins were not only expressed differently, but also had a different time course when the cells were stimulated with light or LPS. Additional functional assays demonstrated that light induction promoted chemotaxis of THP-1 cells, disruption of the EC monolayer and transmigration. In contrast, ECs incorporating a truncated version of the TLR4 extracellular domain (opto-TLR4 ΔECD2-LOV LECs) revealed high basal activity with fast depletion of the cell signaling system upon illumination. We conclude that the established optogenetic cell lines are well suited to induce rapid and precise photoactivation of TLR4, allowing receptor-specific studies.
The Protein Network in Subcutaneous Fat Biopsies from Patients with AL Amyloidosis: More Than Diagnosis?
Authors: Di Silvestre Dario , Brambilla Francesca , Lavatelli Francesca , Chirivì Maila , Canetti Diana , Bearzi Claudia , Rizzi Roberto , Bijzet Johan , Hazenberg Bouke P. C. , Bellotti Vittorio , Gillmore Julian D. , Mauri Pierluigi
Published: February 2023

AL amyloidosis is caused by the misfolding of immunoglobulin light chains leading to an impaired function of tissues and organs in which they accumulate. Due to the paucity of -omics profiles from undissected samples, few studies have addressed amyloid-related damage system wide. To fill this gap, we evaluated proteome changes in the abdominal subcutaneous adipose tissue of patients affected by the AL isotypes κ and λ. Through our retrospective analysis based on graph theory, we have herein deduced new insights representing a step forward from the pioneering proteomic investigations previously published by our group. ECM/cytoskeleton, oxidative stress and proteostasis were confirmed as leading processes. In this scenario, some proteins, including glutathione peroxidase 1 (GPX1), tubulins and the TRiC complex, were classified as biologically and topologically relevant. These and other results overlap with those already reported for other amyloidoses, supporting the hypothesis that amyloidogenic proteins could induce similar mechanisms independently of the main fibril precursor and of the target tissues/organs. Of course, further studies based on larger patient cohorts and different tissues/organs will be essential, which would be a key point that would allow for a more robust selection of the main molecular players and a more accurate correlation with clinical aspects.
Clinical Relevance of Mortalin in Ovarian Cancer Patients
Authors: Rajtak Alicja , Czerwonka Arkadiusz , Pitter Michael , Kotarski Jan , Okła Karolina
Published: February 2023

Background: Ovarian cancer (OC) is the most lethal malignancy of the female reproductive tract. Consequently, a better understanding of the malignant features in OC is pertinent. Mortalin (mtHsp70/GRP75/PBP74/HSPA9/HSPA9B) promotes cancer development, progression, metastasis, and recurrence. Yet, there is no parallel evaluation and clinical relevance of mortalin in the peripheral and local tumor ecosystem in OC patients. Methods: A cohort of 92 pretreatment women was recruited, including 50 OC patients, 14 patients with benign ovarian tumors, and 28 healthy women. Blood plasma and ascites fluid-soluble mortalin concentrations were measured by ELISA. Mortalin protein levels in tissues and OC cells were analyzed using proteomic datasets. The gene expression profile of mortalin in ovarian tissues was evaluated through the analysis of RNAseq data. Kaplan–Meier analysis was used to demonstrate the prognostic relevance of mortalin. Results: First, we found upregulation of local mortalin in two different ecosystems, i.e., ascites and tumor tissues in human OC compared to control groups. Second, abundance expression of local tumor mortalin is associated with cancer-driven signaling pathways and worse clinical outcome. Third, high mortalin level in tumor tissues, but not in the blood plasma or ascites fluid, predicts worse patient prognosis. Conclusions: Our findings demonstrate a previously unknown mortalin profile in peripheral and local tumor ecosystem and its clinical relevance in OC. These novel findings may serve clinicians and investigators in the development of biomarker-based targeted therapeutics and immunotherapies.
Quanty-cFOS, a Novel ImageJ/Fiji Algorithm for Automated Counting of Immunoreactive Cells in Tissue Sections
Authors: Beretta Carlo Antonio , Liu Sheng , Stegemann Alina , Gan Zheng , Wang Lirong , Tan Linette Liqi , Kuner Rohini
Published: February 2023

Analysis of neural encoding and plasticity processes frequently relies on studying spatial patterns of activity-induced immediate early genes’ expression, such as c-fos. Quantitatively analyzing the numbers of cells expressing the Fos protein or c-fos mRNA is a major challenge owing to large human bias, subjectivity and variability in baseline and activity-induced expression. Here, we describe a novel open-source ImageJ/Fiji tool, called ‘Quanty-cFOS’, with an easy-to-use, streamlined pipeline for the automated or semi-automated counting of cells positive for the Fos protein and/or c-fos mRNA on images derived from tissue sections. The algorithms compute the intensity cutoff for positive cells on a user-specified number of images and apply this on all the images to process. This allows for the overcoming of variations in the data and the deriving of cell counts registered to specific brain areas in a highly time-efficient and reliable manner. We validated the tool using data from brain sections in response to somatosensory stimuli in a user-interactive manner. Here, we demonstrate the application of the tool in a step-by-step manner, with video tutorials, making it easy for novice users to implement. Quanty-cFOS facilitates a rapid, accurate and unbiased spatial mapping of neural activity and can also be easily extended to count other types of labelled cells.
Stem Cell Factor and Granulocyte Colony-Stimulating Factor Promote Remyelination in the Chronic Phase of Severe Traumatic Brain Injury
Authors: Qiu Xuecheng , Ping Suning , Kyle Michele , Chin Lawrence , Zhao Li-Ru
Published: February 2023

Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination, which is characterized by myelin sheath disruption and oligodendrocyte cell death, leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF + G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF + G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF + G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF + G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF + G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF + G-CSF-enhanced remyelination in chronic TBI.
Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation Analysis
Authors: Yamashita Hitomi , Nakayama Kentaro , Kanno Kosuke , Ishibashi Tomoka , Ishikawa Masako , Sato Seiya , Iida Koji , Razia Sultana , Kyo Satoru
Published: February 2023

Background: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. Methods: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. Results: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. Conclusions: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.
Review of Degradation Mechanism and Health Estimation Method of VRLA Battery Used for Standby Power Supply in Power System
Authors: Yu Ruxin , Liu Gang , Xu Linbo , Ma Yanqiang , Wang Haobin , Hu Chen
Published: February 2023

As the backup power supply of power plants and substations, valve-regulated lead-acid (VRLA) batteries are the last safety guarantee for the safe and reliable operation of power systems, and the batteries’ status of health (SOH) directly affects the stability and safety of power system equipment. In recent years, serious safety accidents have often occurred due to aging and failure of VRLA batteries, so it is urgent to accurately evaluate the health status of batteries. Accurate estimation of battery SOH is conducive to real-time monitoring of single-battery health information, providing a reliable guarantee for fault diagnosis and improving the overall life and economic performance of the battery pack. In this paper, first, the floating charging operation characteristics and aging failure mechanism of a VRLA battery are summarized. Then, the definition and estimation methods of battery SOH are reviewed, including an experimental method, model method, data-driven method and fusion method. The advantages and disadvantages of various methods and their application conditions are analyzed. Finally, for a future big data power system backup power application scenario, the existing problems and development prospects of battery health state estimation are summarized and prospected.
Electrochemical Dealloying Preparation and Morphology Evolution of Nanoporous Au with Enhanced SERS Activity
Authors: Li Fei , Luo Silang , Qu Fengsheng , Wang Dou , Li Chao , Liu Xue
Published: February 2023

Nanoporous Au (NPG) prepared by dealloying is one of the most used substrates for surface-enhanced Raman scattering (SERS). The morphology tailoring of the NPG to obtain both ultrafine pores and suitable Au/Ag ratio is of great importance for the acquiring of enhanced SERS performance. Compared with the chemical dealloying, the electrochemical dealloying can tailor the NPG to be more flexible by the additional adjustment of dealloying voltage and current. Thus, further understanding on the morphology evolution of NPG during the electrochemical dealloying to obtain enhanced SERS performance is of great importance. In the presented work, the morphology and composition evolution of the NPG film during the electrochemical dealloying was investigated. NPG films with a stable pore diameter of approximately 11 nm as well as diverse compositions were obtained by electrochemical dealloying an Au-Ag alloy film. The prepared NPG film exhibits an enhanced SERS activity with an enhancement factor (EF) of 7.3 × 106 and an excellent detection limit of 10−9 M. This work provides insights into the morphology and composition evolution of the NPG during the electrochemical dealloying process to obtain enhanced SERS performance.
Effect of a New Multi-Walled CNT (MWCNT) Type on the Strength and Elastic Properties of Cement-Based Mortar
Authors: Alexa-Stratulat Sergiu-Mihai , Stoian George , Ghemeş Iulian-Adrian , Toma Ana-Maria , Covatariu Daniel , Toma Ionut-Ovidiu
Published: February 2023

Creating new construction materials with improved strength, elasticity, and durability properties represent the focus of many research works. Significant research effort has been invested in investigating the use of carbon nanotubes (CNTs) in cementitious materials, especially multi-walled carbon nanotubes (MWCNTs) which consist of a series of concentric graphite tubes. The use of MWCNTs is closely related to the use of surfactants and ultra-sonication procedures which may alter their properties and the properties of cement-based materials. The paper presents the preliminary results of an experimental investigation on the suitability of using a new, modified, MWCNT type aimed at eliminating the need of using surfactants and ultrasonication. The modified MWCNTs have a much lower surface energy compared to “classical” ones which would result in a decreased tendency of self-aggregation. A comparison was carried out from the point of view of density, flexural and compressive strength as well as dynamic modulus of elasticity of the obtained mortars. The mortar mix incorporating the modified MWCNTs showed improved mechanical properties even for a low percentage of CNT addition (0.025% by mass of cement). The results are discussed based on the material structure determined from a series of scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses.
3D Claying: 3D Printing and Recycling Clay
Authors: Alonso Madrid Javier , Sotorrío Ortega Guillermo , Gorostiza Carabaño Javier , Olsson Nils O. E. , Tenorio Ríos José Antonio
Published: February 2023

Clay is of great interest as a 3D printing material thanks to its ease of use, recyclability and reusability. This paper analyses the technical aspects of the whole printing process. The behaviour of 3D printing clay is studied with respect to the environment and its specific application as a temporary or definitive formwork system for cement parts. The study addresses the performance of clay and the loss of its properties and characteristics according to the type of protection, whether it is in direct contact with air or cement, or protected with plastics, metal sheets, or combinations of both. A 3D printing system with various printers and 3D models has been considered, observing a direct relationship between the prototype shape, extrusion process and resulting material. The most important variables in 3D printing have been considered: layer height, line thickness, base definition, total model height, overhang angles, overlap between layers, etc. The main technical aspects have been analysed such as raw material properties, kneading, process control, post-treatments and material hardening. As a natural material, clay can be reused indefinitely under certain conditions to be part of a circular economy with low energy consumption and minimal resources. It is concluded that the option of using ceramics in 3D printing for very diverse uses in the architecture, engineering & construction (AEC) sector is very promising due to their ease of implementation, recycling capability and suitability to different environments.
DNA Barcoding of Moon Jellyfish (Cnidaria, Scyphozoa, Ulmaridae, Aurelia): Two Cryptic Species from the Azores (NE Atlantic, Macaronesia), and Evaluation of the Non-Indigenous Species (NIS)
Authors: Moura Carlos J. , Magalhães Bruno I. , Gonçalves João M.
Published: February 2023

Moon jellies are some of the most popular, widely distributed, and best-studied marine jellyfish. By the end of the past century only two or three Aurelia species were recognized, but with the rise of DNA barcoding studies, around thirty Aurelia species are presently accepted. Most of the species are morphologically indistinguishable and have restricted biogeography. We reveal, with COI, 16S, and ITS1-5.8S sequence data, two (pseudo-)cryptic species of Aurelia, potentially endemic to the Azores ecoregion, herein provisionally classified as A. “cf. pseudosolida” and A. “misteriosa”. These species are closely related to the Mediterranean lineages of A. pseudosolida and A. persea, respectively. In the Azores, the shape of the campanula and oral arms readily distinguishes the two species: the former with folded oral arms and globose campanula, and the latter with flattened campanula and thick and long oral arms. Previous reports of A. solida and A. aurita in the Azores should generally correspond to A. “misteriosa” and A. cf. pseudosolida, respectively. The phylogenetic (re-)examination of the available DNA barcodes of Aurelia only evidenced human-mediated dispersal for A. coerulea, A. relicta, and A. aurita. Aurelia solida cannot be yet considered NIS in the Mediterranean. More jellyfish DNA (meta)barcoding should reveal further cryptic diversity, biological invasions, and phylogeographic inferences.
Under-Ice Development of Silica-Scaled Chrysophytes with Different Trophic Mode in Two Ultraoligotrophic Lakes of Yakutia
Authors: Bessudova Anna , Firsova Alena , Bukin Yurij , Kopyrina Lubov , Zakharova Yulia , Likhoshway Yelena
Published: February 2023

Silica-scaled chrysophytes are a widespread group of microeukaryotes, an important component of aquatic habitats. They belong to different evolutionary lineages and they are characterized by the presence of siliceous scales, but differ in trophic mode. We studied the diversity of these organisms in different months of the ice cover period in two subarctic lakes of Yakutia, Labynkyr and Vorota. Silica-scaled chrysophytes, due to various trophic modes, have a competitive advantage in conditions of a long period of ice cover. Statistical analysis has shown the relationship between the relative abundance of mixotrophic and photoautotrophic representatives of silica-scaled chrysophytes with the thickness of the snow cover and the transparency of the ice. An increase in snow cover thickness and the process of melting ice with a decrease in its transparency reduce the relative abundance of photoautotrophic and mixotrophic species. Photoautotrophic representatives of silica-scaled chrysophytes begin to develop already in April, when a thick, solid, and transparent layer of ice and a small layer of snow were observed. During the research period, from April to June, the relative abundance of colorless heterotrophic silica-scaled chrysophytes genera Paraphysomonas and Lepidochromonas was more or less stable. A new species of Spiniferomonas heterospina sp. nov. has been discovered in Lake Labynkyr.
Telemetry and Accelerometer Tracking of Green Toads in an Urban Habitat: Methodological Notes and Preliminary Findings
Authors: Spieẞberger Magdalena , Burgstaller Stephan , Mesnil Marion , Painter Michael S. , Landler Lukas
Published: February 2023

Advancements in tracking technologies provide an increasingly important tool in animal monitoring and conservation that can describe animal spatial behavior in native habitats and uncover migratory routes that otherwise may be difficult or impossible to map. In addition, high-resolution accelerometer sensors provide powerful insights into animal activity patterns and can help to identify specific behaviors from accelerometer profiles alone. Previously, such accelerometers were restricted to larger animals due to size and mass constraints. However, recent advances make it possible to use such devices on smaller animals such as the European green toad (Bufotes viridis), the focus of our current study. We deploy custom made tracking devices, that consist of very-high-frequency transmitters and tri-axial accelerometers, to track toads in their native urban environment in Vienna (Austria). A total of nine toads were tracked, ranging from three to nine tracking days per individual during the post-breeding season period. We demonstrate that our devices could reliably monitor toad movement and activity during the observation period. Hence, we confirmed the predominantly nocturnal activity patterns and recorded low overall movement at this urban site. Accelerometer data revealed that toads exhibited brief but intense activity bursts between 10 pm and midnight, resting periods during the night and intermittent activity during the day. Positional tracking alone would have missed the major activity events as they rarely resulted in large positional displacements. This underscores the importance of and value in integrating multiple tracking sensors for studies of movement ecology. Our approach could be adapted for other amphibians or other animals with mass constraints and may become standard monitoring equipment in the near future.
Echocardiography as a Tool to Assess Cardiac Function in Critical Care—A Review
Authors: Keller Marius , Magunia Harry , Rosenberger Peter , Koeppen Michael
Published: February 2023

In critically ill patients, hemodynamic disturbances are common and often lead to a detrimental outcome. Frequently, invasive hemodynamic monitoring is required for patients who are hemodynamically unstable. Although the pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile, this technique carries a substantial inherent risk of complications. Other less invasive techniques do not offer a full range of results to guide detailed hemodynamic therapies. An alternative with a lower risk profile is transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). After training, intensivists can obtain similar parameters on the hemodynamic profile using echocardiography, such as stroke volume and ejection fraction of the right and left ventricles, an estimate of the pulmonary artery wedge pressure, and cardiac output. Here, we will review individual echocardiography techniques that will help the intensivist obtain a comprehensive assessment of the hemodynamic profile using echocardiography.
Systemic Immune-Inflammation Index and Mortality in Testicular Cancer: A Systematic Review and Meta-Analysis
Authors: Salazar-Valdivia Farley E. , Valdez-Cornejo Valeria A. , Ulloque-Badaracco Juan R. , Hernandez-Bustamante Enrique A. , Alarcón-Braga Esteban A. , Mosquera-Rojas Melany D. , Garrido-Matta Diana P. , Herrera-Añazco Percy , Benites-Zapata Vicente A. , Hernandez Adrian V.
Published: February 2023

The systemic immune-inflammation index (SIII) is a marker studied in multiple types of urologic cancer. This systematic review evaluates the association between SIII values with overall survival (OS) and progression-free survival (PFS) in testicular cancer. We searched observational studies in five databases. The quantitative synthesis was performed using a random-effects model. The risk of bias was assessed using the Newcastle–Ottawa Scale (NOS). The only measure of the effect was the hazard ratio (HR). A sensitivity analysis was performed according to the risk of bias in the studies. There were 833 participants in a total of 6 cohorts. We found that high SIII values were associated with worse OS (HR = 3.28; 95% CI 1.3–8.9; p < 0.001; I2 = 78) and PFS (HR = 3.9; 95% CI 2.53–6.02; p < 0.001; I2 = 0). No indication of small study effects was found in the association between SIII values and OS (p = 0.5301). High SIII values were associated with worse OS and PFS. However, further primary studies are suggested to enhance the effect of this marker in different outcomes of testicular cancer patients.
The Clinical Significance of Salusins in Systemic Sclerosis—A Cross-Sectional Study
Authors: Nowaczyk Joanna , Blicharz Leszek , Zawistowski Michał , Sikora Mariusz , Zaremba Michał , Czuwara Joanna , Rudnicka Lidia
Published: February 2023

Background: Systemic sclerosis (SSc) is a connective tissue disease manifesting with progressive fibrosis of the skin and internal organs. Its pathogenesis is strictly associated with vascular disfunction and damage. Salusin-α and salusin-β, endogenous peptides regulating secretion of pro-inflammatory cytokines and vascular smooth muscle proliferation, may potentially play a role in SSc pathogenesis. Objectives: The aim of this study was to assess the concentration of salusins in sera of patients with SSc and healthy controls and to evaluate correlations between the salusins levels and selected clinical parameters within the study group. Materials and methods: 48 patients with SSc (44 women; mean age, 56.4, standard deviation, 11.4) and 25 adult healthy volunteers (25 women; mean age, 55.2, standard deviation, 11.2) were enrolled. All patients with SSc were treated with vasodilators and twenty-seven of them (56%) also received immunosuppressive therapy. Results: Circulating salusin-α was significantly elevated in patients with SSc in comparison to healthy controls (U = 350.5, p = 0.004). Patients with SSc receiving immunosuppression had higher serum salusin-α concentrations compared with those without immunosuppressive therapy (U = 176.0, p = 0.026). No correlation was observed between salusins concentrations and skin or internal organ involvement parameters. Conclusions: Salusin-α, a bioactive peptide mitigating the endothelial disfunction, was elevated in patients with systemic sclerosis receiving vasodilators and immunosuppressants. Increased salusin-α concertation may be associated with the initiation of atheroprotective processes in patients with SSc managed pharmacologically, which requires verification in future studies.
Diagnostic Performance of Selected MRI-Derived Radiomics Able to Discriminate Progression-Free and Overall Survival in Patients with Midline Glioma and the H3F3AK27M Mutation
Authors: Chilaca-Rosas Maria-Fatima , Garcia-Lezama Melissa , Moreno-Jimenez Sergio , Roldan-Valadez Ernesto
Published: February 2023

Background: Radiomics refers to a recent area of knowledge that studies features extracted from different imaging techniques and subsequently transformed into high-dimensional data that can be associated with biological events. Diffuse midline gliomas (DMG) are one of the most devastating types of cancer, with a median survival of approximately 11 months after diagnosis and 4–5 months after radiological and clinical progression. Methods: A retrospective study. From a database of 91 patients with DMG, only 12 had the H3.3K27M mutation and brain MRI DICOM files available. Radiomic features were extracted from MRI T1 and T2 sequences using LIFEx software. Statistical analysis included normal distribution tests and the Mann–Whitney U test, ROC analysis, and calculation of cut-off values. Results: A total of 5760 radiomic values were included in the analyses. AUROC demonstrated 13 radiomics with statistical significance for progression-free survival (PFS) and overall survival (OS). Diagnostic performance tests showed nine radiomics with specificity for PFS above 90% and one with a sensitivity of 97.2%. For OS, 3 out of 4 radiomics demonstrated between 80 and 90% sensitivity. Conclusions: Several radiomic features demonstrated statistical significance and have the potential to further aid DMG diagnostic assessment non-invasively. The most significant radiomics were first- and second-order features with GLCM texture profile, GLZLM_GLNU, and NGLDM_Contrast.
Retinitis Pigmentosa Associated with EYS Gene Mutations: Disease Severity Staging and Central Retina Atrophy
Authors: Placidi Giorgio , Maltese Paolo , Savastano Maria , D’Agostino Elena , Cestrone Valentina , Bertelli Matteo , Chiurazzi Pietro , Maceroni Martina , Minnella Angelo , Ziccardi Lucia , Parisi Vincenzo , Rizzo Stanislao , Falsini Benedetto
Published: February 2023

Background. Eyes shut homolog (EYS) gene mutations are estimated to affect at least 5% of patients with autosomal recessive retinitis pigmentosa. Since there is no mammalian model of human EYS disease, it is important to investigate its age-related changes and the degree of central retinal impairment. Methods. A cohort of EYS patients was studied. They underwent full ophthalmic examination as well as assessment of retinal function and structure, by full-field and focal electroretinograms (ERGs) and spectral domain optical coherence tomography (OCT), respectively. The disease severity stage was determined by the RP stage scoring system (RP-SSS). Central retina atrophy (CRA) was estimated from the automatically calculated area of the sub-retinal pigment epithelium (RPE) illumination (SRI). Results. The RP-SSS was positively correlated with age, showing an advanced severity score (≥8) at an age of 45 and a disease duration of 15 years. The RP-SSS was positively correlated with the CRA area. LogMAR visual acuity and ellipsoid zone width, but not ERG, were correlated with CRA. Conclusions. In EYS-related disease, the RP-SSS showed advanced severity at a relative early age and was correlated with the central area of the RPE/photoreceptor atrophy. These correlations may be relevant in view of therapeutic interventions aimed at rescuing rods and cones in EYS-retinopathy.
Advanced Autoantibody Testing in Systemic Sclerosis
Authors: Almaabdi Kholoud , Ahmad Zareen , Johnson Sindhu R.
Published: February 2023

Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. Many clinicians now have improved access to an expanded profile of autoantibody testing. In this narrative review article, we review the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in people with systemic sclerosis.
Oral and Periodontal Risk Factors of Prosthetic Success for 3-Unit Natural Tooth-Supported Bridges versus Implant-Supported Fixed Dental Prostheses
Authors: Cristea Ioana , Agop-Forna Doriana , Martu Maria-Alexandra , Dascălu Cristina , Topoliceanu Claudiu , Török Roland , Török Bianca , Bardis Dimitrios , Bardi Panagiota Moulavasili , Forna Norina
Published: February 2023

The goals of this research are: (1) to compare the survival and prosthetic success of metal-ceramic 3-unit tooth- versus implant-supported fixed dental prostheses; (2) to evaluate the influence of several risk factors on the prosthetic success of tooth- and implant-supported fixed dental prostheses (FPDs). A total of 68 patients with posterior short edentulous spaces (mean age 61.00 ± 1.325 years), were divided into two groups: 3-unit tooth-supported FPDs (40 patients; 52 FPD; mean follow-up 10.27 ± 0.496 years) and 3-unit implant-supported FPDs (28 patients; 32 FPD; mean follow-up 8.656 ± 0.718 years). Pearson-chi tests were used to highlight the risk factors for the prosthetic success of tooth- and implant-supported FPDs and multivariate analysis was used to determine significant risk predictors for the prosthetic success of the tooth-supported FPDs. The survival rates of 3-unit tooth- versus implant-supported FPDs were 100% and 87.5%, respectively, while the prosthetic success was 69.25% and 68.75%, respectively. The prosthetic success of tooth-supported FPDs was significantly higher for patients older than 60 years (83.3%) vs. 40–60 years old (57.1%) (p = 0.041). Periodontal disease history decreased the prosthetic success of tooth- versus implant-supported FPDs when compared with the absence of periodontal history (45.5% vs. 86.7%, p = 0.001; 33.3% vs. 90%, p = 0.002). The prosthetic success of 3-unit tooth- vs. implant-supported FPDs was not significantly influenced by gender, location, smoking, or oral hygiene in our study. In conclusion, similar rates of prosthetic success were recorded for both types of FPDs. In our study, prosthetic success of tooth- versus implant-supported FPDs was not significantly influenced by gender, location, smoking, or oral hygiene; however, history of periodontal disease is a significant negative predictor of success in both groups when compared with patients without periodontal history.
A Review on Biological Effects of Ultrasounds: Key Messages for Clinicians
Authors: Quarato Carla Maria Irene , Lacedonia Donato , Salvemini Michela , Tuccari Giulia , Mastrodonato Grazia , Villani Rosanna , Fiore Lucia Angela , Scioscia Giulia , Mirijello Antonio , Saponara Annarita , Sperandeo Marco
Published: February 2023

Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the “safety” of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.
Entropy, Ecology and Evolution: Toward a Unified Philosophy of Biology
Authors: Cushman Samuel A.
Published: February 2023

Darwin proposed that the capacity of organisms to produce more offspring that can be supported by the environment would lead to a struggle for existence, and individuals that are most fit for survival and reproduction would be selected through natural selection. Ecology is the science that studies the interaction between organisms and their environment within the context of Darwinian evolution, and an ecosystem is defined as a community of living organisms in conjunction with the nonliving components of their environment, interacting as a system. One topic that has been very much understudied and largely ignored in evolutionary biology is the overarching context of thermodynamics in controlling all biological processes and the evolution of life. Most fundamentally, organisms are self-replicating dissipative structures. Evolution is the process whereby variation in the structure of organisms have differential fitness in terms of their effectiveness at building and maintaining their structure, efficiently consuming free energy, and effectively reproducing and passing on those heritable variations, leading to change in the frequency of genetic variation and associated change in the characteristics in the population. The central process is dissipation of free energy according to the second law of thermodynamics, and evolution therefore is better conceptualized as the emergence of self-replicating dissipative structures that through natural selection become increasingly more efficient at degrading free energy. Ecosystems are linked series of dissipative structures with heat engine dynamics driven by random dissipation of energy and increasing entropy. The structure and composition of ecosystems across scales are emergent dissipative structures driven by the flow of energy and the increase in entropy. Communities and ecosystems are emergent properties of a system that has evolved to most efficiently dissipate energy and increase entropy. By focusing on the fundamental entity (energy), and the fundamental process (dissipation and disordering of energy and increasing of entropy), we are able to have a much clearer and powerful understanding of what life is, from the level of biochemistry, to evolution, to the nature of the organism itself, and to the emergent structures of ecosystems, food webs and communities.
Adapting an Educational Software Internationally: Cultural and Linguistical Adaptation
Authors: Ozorio Dutra Samia Valeria , Chee Vanessa , Clochesy John M.
Published: February 2023

This study protocol proposes an adaptation of the participatory and iterative process framework for language adaptation (PIPFLA). The adapted model follows five dimensions for a cross-cultural equivalence model: semantic, content, technical, criterion, and conceptual. Iterative adaptations were conducted through the Delphi technique of expert consultation that comprised nursing professionals from academic, administrative, and practice fields, professional translators, and students’ online focus groups to arrive at consensus. The adapted process of PIPFLA proposed in this paper uses a standardized and transparent documentation, including expert judgment. Neither systematic reviews nor empirical research currently published describe the methodology used with enough details to allow for replication or improvement. This work illustrates innovation that takes concepts related to cultural adaptation of tools and applies these ideas to cultural adaptation of an online learning platform, based on the use of committees and codebook development strategies.
Fine-Grained Facial Expression Recognition in Multiple Smiles
Authors: Jin Zhijia , Zhang Xiaolu , Wang Jie , Xu Xiaolin , Xiao Jiangjian
Published: February 2023

Smiling has often been incorrectly interpreted as “happy” in the popular facial expression datasets (AffectNet, RAF-DB, FERPlus). Smiling is the most complex human expression, with positive, neutral, and negative smiles. We focused on fine-grained facial expression recognition (FER) and built a new smiling face dataset, named Facial Expression Emotions. This dataset categorizes smiles into six classes of smiles, containing a total of 11,000 images labeled with corresponding fine-grained facial expression classes. We propose Smile Transformer, a network architecture for FER based on the Swin Transformer, to enhance the local perception capability of the model and improve the accuracy of fine-grained face recognition. Moreover, a convolutional block attention module (CBAM) was designed, to focus on important features of the face image and suppress unnecessary regional responses. For better classification results, an image quality evaluation module was used to assign different labels to images with different qualities. Additionally, a dynamic weight loss function was designed, to assign different learning strategies according to the labels during training, focusing on hard yet recognizable samples and discarding unidentifiable samples, to achieve better recognition. Overall, we focused on (a) creating a novel dataset of smiling facial images from online annotated images, and (b) developing a method for improved FER in smiling images. Facial Expression Emotions achieved an accuracy of 88.56% and could serve as a new benchmark dataset for future research on fine-grained FER.
Hierarchical Motion Excitation Network for Few-Shot Video Recognition
Authors: Wang Bing , Wang Xiaohua , Ren Shiwei , Wang Weijiang , Shi Yueting
Published: February 2023

Most of the existing deep learning algorithms are supervised learning and rely on a tremendous number of manually labeled samples. However, in most domains, due to the scarcity of samples or the excessive cost of labeling, it would be impracticable to provide numerous labeled training samples to the network. In this paper, a few-shot video classification network termed Hierarchical Motion Excitation Network (HME-Net) is proposed from the perspective of accumulated feature-level motion information. An HME module composed of Motion Excitation (ME) and Interval Frame Motion Excitation (IFME) is designed to extract feature-level motion patterns from adjacent frames and interval frames. The HME module can discover and enhance the feature-level motion-sensitive information in the original features. The accumulative time window is expanded to four frames in a hierarchical manner, which achieves the purpose of increasing the receptive field. After extensive experimentation, HME-Net is demonstrated to be able to consistently outperform the existing few-shot video classification models. On the UCF101 and HMDB51 datasets, our method is established as a new state-of-the-art technique for the few-shot settings of five-way three-shot and five-way five-shot video recognition.