bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning and Physics-Based Hybridization Models for Evaluation of the Effects of Climate Change and Urban Expansion on Photosynthetically Active Radiation
Authors: Nwokolo Samuel Chukwujindu , Proutsos Nikolaos , Meyer Edson L. , Ahia Chinedu Christian
Published: April 2023

Given the interdependence of climate change (CLC) and urban expansion (URE) on ecosystem productivity in China and India, hybrid physics-based models were fitted in this study to evaluate the effects of these variables on photosynthetically active radiation (PAR). This was accomplished by interpolating the most recent five general circulation models (GCMs) from coupled model intercomparison project phase 6 (CMIP6) into the CMIP6 multi-ensemble model. The potential of PAR is projected to increase by 0.001 to 2.077% in China and by 0.002 to 6.737% in India, on a seasonal and annual basis, if the warming is kept at 1.5 °C from now until the end of this century. The effects of CLC and URE on the changes in PAR in China and India were investigated, and URE had a greater impact than CLC when compared to effective contributions, with 49.47% for China and 28.41% for India in the entire case scenario. In contrast, CLC and PAR residual factor (PRF) have a greater impact in India than in China, with effects of 13.79% and 57.79% compared to 0.89% and 49.64%, respectively. Preferences for exotic, high-productivity plant species, irrigation, CO2 fertilization, and nitrogen deposition are suggested as measures for replenishing PAR in both countries.
Impacts of Cyclones on Arctic Clouds during Autumn in the Early 21st Century
Authors: Liu Xue , Diao Yina , Sun Ruipeng , Gong Qinglong
Published: April 2023

Our study shows that, during 2001–2017, when the sea ice was melting rapidly, cyclone days accounted for more than 50% of the total autumn days at the sounding stations in the Arctic marginal seas north of the Eurasian continent and almost 50% of the total autumn days at the sounding station on the northern coast of Canada. It is necessary to investigate the influence of Arctic cyclones on the cloud fraction in autumn when the sea ice refreezes from its summer minimum and the infrared cloud radiative effect becomes increasingly important. Cyclones at the selected stations are characterized by a narrow maximum rising zone with vertically consistent high relative humidity (RH) and a broad region outside the high RH zone with low RH air from the middle troposphere covering the low troposphere’s high relative humidity air. Consequently, on approximately 40% of the cyclone days, the cloud formation condition was improved from the near surface to the upper troposphere due to the cooling of strong rising warm humid air. Therefore, cyclones lead to middle cloud increases and sometimes high cloud increases, since the climatological Arctic autumn clouds are mainly low clouds. On approximately 60% of the cyclone days, only low cloud formed, but the low cloud formation condition was suppressed due to the mixing ratio decrease induced by cold dry air sinking. As a result, cyclones generally lead to a decrease in low clouds. However, the correlation between the cyclones and low clouds is complex and varies with surface ice conditions.
Biomechanical Effects of a Novel Pedicle Screw W-Type Rod Fixation for Lumbar Spondylolysis: A Finite Element Analysis
Authors: Pan Jo-Hsi , Chen Chen-Sheng , Liu Chien-Lin , Chou Po-Hsin
Published: April 2023

Lumbar spondylolysis involves anatomical defects of the pars interarticularis, which causes instability during motion. The instability can be addressed through instrumentation with posterolateral fusion (PLF). We developed a novel pedicle screw W-type rod fixation system and evaluated its biomechanical effects in comparison with PLF and Dynesys stabilization for lumbar spondylolysis via finite element (FE) analysis. A validated lumbar spine model was built using ANSYS 14.5 software. Five FE models were established simulating the intact L1–L5 lumbar spine (INT), bilateral pars defect (Bipars), bilateral pars defect with PLF (Bipars_PLF), Dynesys stabilization (Bipars_Dyn), and W-type rod fixation (Bipars_Wtyp). The range of motion (ROM) of the affected segment, the disc stress (DS), and the facet contact force (FCF) of the cranial segment were compared. In the Bipars model, ROM increased in extension and rotation. Compared with the INT model, Bipars_PLF and Bipars_Dyn exhibited remarkably lower ROMs for the affected segment and imposed greater DS and FCF in the cranial segment. Bipars_Wtyp preserved more ROM and generated lower stress at the cranial segment than Bipars_PLF or Bipars_Dyn. The injury model indicates that this novel pedicle screw W-type rod for spondylolysis fixation could return ROM, DS, and FCF to levels similar to preinjury.
High Chromosomal Reorganization and Presence of Microchromosomes in Chactidae Scorpions from the Brazilian Amazon
Authors: Almeida Bruno , Malcher Stella , Costa Marlyson , Martins Jonas , Procópio Rudi , Noronha Renata , Nagamachi Cleusa , Pieczarka Julio
Published: April 2023

Scorpions are of particular interest in cytogenomic studies, as they can present a high incidence of chromosomal rearrangements heterozygous in natural populations. In this study, we cytogenetically analyzed four species of Chactidae. In Brotheas, 2n = 40 was observed in Brotheas silvestris, 2n = 48 in Brotheas paraensis, and 2n = 50 (cytotype A) or 2n = 52 (cytotype B) among populations of Brotheas amazonicus. Our results showed a bimodal karyotype in Neochactas parvulus, 2n = 54, with microchromosomes and a concentration of constitutive heterochromatin in macrochromosomes. The 45S rDNA is located in only one pair of the karyotype, with different heteromorphisms of clusters of this rDNA in the cytotype B of B. amazonicus, with NOR-bearing chromosomes involved in multi-chromosomal associations during meiosis I. The U2 snDNA was mapped in the interstitial region of distinct karyotype pairs of three Chactidae species. Our results indicate the possible formation of cryptic species in B. amazonicus; the different 45S rDNA configurations in the genome of this species may result from amplification and degeneration. We suggest that the bimodal karyotype in N. parvulus results from fusion/fission events and that the unequal distribution of repetitive DNAs between macro and microchromosomes contributes to the maintenance of its asymmetry.
Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial
Authors: Di Stadio Arianna , Cantone Elena , De Luca Pietro , Di Nola Claudio , Massimilla Eva A. , Motta Giovanni , La Mantia Ignazio , Motta Gaetano
Published: April 2023

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin’ Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.
State of the Art of microRNAs Signatures as Biomarkers and Therapeutic Targets in Parkinson’s and Alzheimer’s Diseases: A Systematic Review and Meta-Analysis
Authors: Zotarelli-Filho Idiberto José , Mogharbel Bassam Felipe , Irioda Ana Carolina , Stricker Priscila Elias Ferreira , de Oliveira Nathalia Barth , Saçaki Claudia Sayuri , Perussolo Maiara Carolina , da Rosa Nádia Nascimento , Lührs Larissa , Dziedzic Dilcele Silva Moreira , Vaz Rogério Saad , de Carvalho Katherine Athayde Teixeira
Published: April 2023

Identifying target microRNAs (miRNAs) might serve as a basis for developing advanced therapies for Parkinson’s disease (PD) and Alzheimer’s disease. This review aims to identify the main therapeutic targets of miRNAs that can potentially act in Parkinson’s and Alzheimer’s diseases. The publication research was conducted from May 2021 to March 2022, selected from Scopus, PubMed, Embase, OVID, Science Direct, LILACS, and EBSCO. A total of 25 studies were selected from 1549 studies evaluated. The total number of miRNAs as therapeutic targets evidenced was 90 for AD and 54 for PD. An average detection accuracy of above 84% for the miRNAs was observed in the selected studies of AD and PD. The major signatures were miR-26b-5p, miR-615-3p, miR-4722-5p, miR23a-3p, and miR-27b-3p for AD and miR-374a-5p for PD. Six miRNAs of intersection were found between AD and PD. This article identified the main microRNAs as selective biomarkers for diagnosing PD and AD and therapeutic targets through a systematic review and meta-analysis. This article can act as a microRNA guideline for laboratory research and pharmaceutical industries for treating Alzheimer’s and Parkinson’s diseases and offers the opportunity to evaluate therapeutic interventions earlier in the disease process.
Early Diagnosis of Atrial Fibrillation and Stroke Incidence in Primary Care: Translating Measurements into Actions—A Retrospective Cohort Study
Authors: Clua-Espuny Josep-Lluis , Molto-Balado Pedro , Lucas-Noll Jorgina , Panisello-Tafalla Anna , Muria-Subirats Eulalia , Clua-Queralt Josep , Queralt-Tomas Lluïsa , Reverté-Villarroya Silvia ,   Investigators EBRICTUS Research
Published: April 2023

(1) Background: AF-related strokes will triple by 2060, are associated with an increased risk of cognitive decline, and alone or in combination, will be one of the main health and economic burdens on the European population. The main goal of this paper is to describe the incidence of new AF associated with stroke, cognitive decline and mortality among people at high risk for AF. (2) Methods: Multicenter, observational, retrospective, community-based studies were conducted from 1 January 2015 to 31 December 2021. The setting was primary care centers. A total of 40,297 people aged ≥65 years without previous AF or stroke were stratified by AFrisk at 5 years. The main measurements were the overall incidence density/1000 person-years (CI95%) of AF and stroke, prevalence of cognitive decline, and Kaplan–Meier curve. (3) Results: In total, 46.4% women, 77.65 ± 8.46 years old on average showed anAF incidence of 9.9/103/year (CI95% 9.5–10.3), associated with a four-fold higher risk of stroke (CI95% 3.4–4.7), cognitive impairment(OR 1.34 (CI95% 1.1–1.5)), and all-cause mortality (OR 1.14 (CI95% 1.0–1.2)), but there was no significant difference in ischemic heart disease, chronic kidney disease, or peripheral arteriopathy. Unknown AF was diagnosed in 9.4% and of these patients, 21.1% were diagnosed with new stroke. (4) Conclusions: The patients at high AF risk (Q4th) already had an increased cardiovascular risk before they were diagnosed with AF.
Status of Omics Research Capacity on Oral Cancer in Africa: A Systematic Scoping Review Protocol
Authors: Nnyanzi Lawrence Achilles , Adisa Akinyele Olumuyiwa , Kanmodi Kehinde Kazeem , Aladelusi Timothy Olukunle , Salami Afeez Abolarinwa , Amzat Jimoh , Angione Claudio , Nwafor Jacob Njideka , Uwambaye Peace , Okee Moses , Kuba Shweta Yogesh , Mujuni Brian , Ibingira Charles , Ogbureke Kalu Ugwa Emmanuel , Jayasinghe Ruwan Duminda
Published: April 2023

Over the past decade, omics technologies such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics have been used in the scientific understanding of diseases. While omics technologies have provided a useful tool for the diagnosis and treatment of diseases globally, there is a dearth of literature on the use of these technologies in Africa, particularly in the diagnosis and treatment of oral cancer. This systematic scoping review aims to present the status of the omics research capacity on oral cancer in Africa. The guidelines by the Joanna Brigg’s Institute for conducting systematic scoping reviews will be adopted for this review’s methodology and it will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The literature that will be reviewed will be scooped out from PubMed, SCOPUS, Dentistry and Oral Sciences Source, AMED, CINAHL, and PsycInfo databases. In conclusion, the findings that will be obtained from this review will aid the in-depth understanding of the status of oral cancer omics research in Africa, as this knowledge is paramount for the enhancement of strategies required for capacity development and the prioritization of resources in the fight against oral cancer in Africa.
Subtraction-Average-Based Optimizer: A New Swarm-Inspired Metaheuristic Algorithm for Solving Optimization Problems
Authors: Trojovský Pavel , Dehghani Mohammad
Published: April 2023

This paper presents a new evolutionary-based approach called a Subtraction-Average-Based Optimizer (SABO) for solving optimization problems. The fundamental inspiration of the proposed SABO is to use the subtraction average of searcher agents to update the position of population members in the search space. The different steps of the SABO’s implementation are described and then mathematically modeled for optimization tasks. The performance of the proposed SABO approach is tested for the optimization of fifty-two standard benchmark functions, consisting of unimodal, high-dimensional multimodal, and fixed-dimensional multimodal types, and the CEC 2017 test suite. The optimization results show that the proposed SABO approach effectively solves the optimization problems by balancing the exploration and exploitation in the search process of the problem-solving space. The results of the SABO are compared with the performance of twelve well-known metaheuristic algorithms. The analysis of the simulation results shows that the proposed SABO approach provides superior results for most of the benchmark functions. Furthermore, it provides a much more competitive and outstanding performance than its competitor algorithms. Additionally, the proposed approach is implemented for four engineering design problems to evaluate the SABO in handling optimization tasks for real-world applications. The optimization results show that the proposed SABO approach can solve for real-world applications and provides more optimal designs than its competitor algorithms.
Electrophysiological Evidence Reveals the Asymmetric Transfer from the Right to Left Hemisphere as Key to Reading Proficiency
Authors: Kim Sangyub , Kim Joonwoo , Nam Kichun
Published: April 2023

The present investigation aimed to explore the interhemispheric interactions that contribute to changes in reading proficiency by examining the processing of visual word recognition in relation to word familiarity. A lexical decision task was administered to 25 participants, and their electrophysiological activity was recorded. A behavioral analysis showed the faster and more accurate processing of highly familiar words compared to less familiar ones. An event-related potential analysis uncovered an asymmetric familiarity effect over the N100 and N400 components across the two hemispheres, indicating an asymmetrical word familiarity processing. Granger causality analyses demonstrated a stronger transfer of information from the right hemisphere (RH) to the left hemisphere (LH) during the N100 processing and a weaker transfer from the LH to the RH during the N400 processing for highly familiar word recognition. These findings suggest that the asymmetric coordination between the RH and LH occurs early in visual word recognition and highlight the importance of interhemispheric interactions in efficient visual word recognition and proficient reading.
Application of Quantitative Computed Tomographic Perfusion in the Prognostic Assessment of Patients with Aneurysmal Subarachnoid Hemorrhage Coexistent Intracranial Atherosclerotic Stenosis
Authors: Yang Jun , Han Heze , Chen Yu , Lin Fa , Li Runting , Lu JunLin , Li Ruinan , Li Zhipeng , Shi Guangzhi , Wang Shuo , Zhao Yuanli , Chen Xiaolin , Zhao Jizong
Published: April 2023

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11–13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS.
Is Balance Training Using Biofeedback Effective in the Prophylaxis of Falls in Women over the Age of 65?
Authors: Sadura-Sieklucka Teresa , Czerwosz Leszek Tomasz , Kądalska Ewa , Kożuchowski Marcin , Księżopolska-Orłowska Krystyna , Targowski Tomasz
Published: April 2023

The paper aims to investigate the usefulness of training in improving mobility and reducing the risk of falls of patients with osteoarthritis by using a force plate and virtual reality as rehabilitation tools. The study involved 72 women randomly divided into two equal groups: the force plate training group, which underwent virtual balance training with visual motor feedback, and the gym training group, which received conventional balance training only. The functional balance assessment was performed before and after the rehabilitation by computerized posturography in a relaxed upright position with open and closed eyes, with visual motor feedback. In the FPT group in the feedback measurement, the mean radius of sways was 30% smaller after rehabilitation (p < 0.00002); the feedback coordination coefficient was more than 10% bigger after rehabilitation (p < 0.001) and reached 92%, which is excellent for elderly people. Total stagnation and stumbling reported by patients decreased after rehabilitation compared to the first examination. Both tested forms of training can contribute to reducing the risk of falls. However, a more significant improvement was obtained in the force plate training group perhaps because the physical effort on a force plate trains the precise movements needed to reposition the centre of gravity without generating excessive inertia forces responsible for loss of balance and falls. Perhaps the most desirable method of intervention is to train a person’s ability to perform slow but definite body movements.
Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells
Authors: Payne Ashley , Taka Equar , Adinew Getinet M. , Soliman Karam F. A.
Published: April 2023

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related neurodegenerative diseases involving activated microglia cells. The objective of the current study was to examine the molecular targets underlying the anti-inflammatory effects of EGCG in activated microglia cells. BV-2 microglia cells were grown, stimulated, and treated with EGCG. Cytotoxicity and nitric oxide (NO) production were evaluated. Immunoassay, PCR array, and WES™ Technology were utilized to evaluate inflammatory, neuroprotective modulators as well as signaling pathways involved in the mechanistic action of neuroinflammation. Our findings showed that EGCG significantly inhibited proinflammatory mediator NO production in LPS-stimulated BV-2 microglia cells. In addition, ELISA analysis revealed that EGCG significantly decreases the release of proinflammatory cytokine IL-6 while it increases the release of TNF-α. PCR array analysis showed that EGCG downregulated MIF, CCL-2, and CSF2. It also upregulated IL-3, IL-11, and TNFS10. Furthermore, the analysis of inflammatory signaling pathways showed that EGCG significantly downregulated mRNA expression of mTOR, NF-κB2, STAT1, Akt3, CCL5, and SMAD3 while significantly upregulating the expression of mRNA of Ins2, Pld2, A20/TNFAIP3, and GAB1. Additionally, EGCG reduced the relative protein expression of NF-κB2, mTOR, and Akt3. These findings suggest that EGCG may be used for its anti-inflammatory effects to prevent neurodegenerative diseases.
A Comparative Case Study of Certified and Non-Certified Green Buildings and Their Response to Climate Change
Authors: Almeida Laura , Bamdad Keivan , Razavi Mohammad Reza
Published: April 2023

Green buildings (GBs) employ a wide range of passive and active energy-saving strategies to improve buildings’ energy performance. The suitability and performance of some of these strategies depend on outdoor climate conditions and may change over time due to global warming. Therefore, a GB may not retain its performance in the future. To address this issue and explore how much GB performance may be affected by climate change, this research aims to (1) evaluate the energy performance and thermal comfort of a GB and non-GB under present climate conditions; (2) predict the impact of climate change on these buildings, and (3) evaluate the climate resilience of a GB as opposed to a non-GB. To this end, a university GB and non-GB are simulated using DesignBuilder and calibrated with measured data. Future weather files based on Representative Concentration Pathways (RCPs) are used to predict climate conditions in the 2050s and 2090s. A comparison between the GB and non-GB revealed that the GB would save 15.1% and up to 21.9% of site energy under present and future climate conditions, respectively. It was also found that the thermal comfort level in the GB will remain significantly higher than in the non-GB in the future. The overheating issue in non-GBs will deteriorate in the future, with an increase of nearly 70% by the 2090s. The GB produces approximately 15% and up to 22% fewer GHG emissions than the non-GB under present and future climate conditions (RCP 8.5), respectively.
A General Contractor’s Perspective on Construction Digital Twin: Implementation, Impacts and Challenges
Authors: Esmaeili Iraj , Simeone Davide
Published: April 2023

The Digital Twin (DT), as a real-time and data-connected virtual replica of a physical asset, introduces a new paradigm in the construction industry. To date, the use of DT in the construction phase has not been addressed sufficiently. Hence, this research studies the implementation of DT during the construction phase of projects to support general contractors’ decisions and operations. Starting from existing literature, a Construction Digital Twin (CDT) framework has been developed from a general contractor’s perspective and a case study was implemented as an application of the proposed CDT to validate the framework and demonstrate its benefits. In the selected project, the simulation of the construction operations in evaluating various “what-if” scenarios for optimum resource allocation and operation management proved the benefits of using a CDT in the construction phase of projects for general contractors. By implementing the proposed CDT framework, several impacts such as reduced costs, improved collaboration and information exchange and data-driven construction management can be anticipated.
Raman Spectroscopic Imaging of Human Bladder Resectates towards Intraoperative Cancer Assessment
Authors: Krafft Christoph , Popp Jürgen , Bronsert Peter , Miernik Arkadiusz
Published: April 2023

Raman spectroscopy offers label-free assessment of bladder tissue for in vivo and ex vivo intraoperative applications. In a retrospective study, control and cancer specimens were prepared from ten human bladder resectates. Raman microspectroscopic images were collected from whole tissue samples in a closed chamber at 785 nm laser excitation using a 20× objective lens and 250 µm step size. Without further preprocessing, Raman images were decomposed by the hyperspectral unmixing algorithm vertex component analysis into endmember spectra and their abundancies. Hierarchical cluster analysis distinguished endmember Raman spectra that were assigned to normal bladder, bladder cancer, necrosis, epithelium and lipid inclusions. Interestingly, Raman spectra of microplastic particles, pigments or carotenoids were detected in 13 out of 20 specimens inside tissue and near tissue margins and their identity was confirmed by spectral library surveys. Hypotheses about the origin of these foreign materials are discussed. In conclusion, our Raman workflow and data processing protocol with minimal user interference offers advantages for future clinical translation such as intraoperative tumor detection and label-free material identification in complex matrices.
Exploring Spatial Heterogeneity of Immune Cells in Nasopharyngeal Cancer
Authors: Sobti Aastha , Sakellariou Christina , Nilsson Johan S. , Askmyr David , Greiff Lennart , Lindstedt Malin
Published: April 2023

Nasopharyngeal cancer (NPC) is a malignant tumor. In a recent publication, we described the presence and distribution of CD8+ T cells in NPC and used the information to identify ‘inflamed’, ‘immune-excluded’, and ‘desert’ immune phenotypes, where ‘inflamed’ and ‘immune-excluded’ NPCs were correlated with CD8 T cell infiltration and survival. Arguably, more detailed and, in particular, spatially resolved data are required for patient stratification and for the identification of new treatment targets. In this study, we investigate the phenotype of CD45+ leukocytes in the previously analyzed NPC samples by applying multiplexed tissue analysis to assess the spatial distribution of cell types and to quantify selected biomarkers. A total of 47 specified regions-of-interest (ROIs) were generated based on CD45, CD8, and PanCK morphological staining. Using the GeoMx® Digital Spatial Profiler (DSP), 49 target proteins were digitally quantified from the selected ROIs of a tissue microarray consisting of 30 unique NPC biopsies. Protein targets associated with B cells (CD20), NK cells (CD56), macrophages (CD68), and regulatory T cells (PD-1, FOXP3) were most differentially expressed in CD45+ segments within ‘immune-rich cancer cell islet’ regions of the tumor (cf. ‘surrounding stromal leukocyte’ regions). In contrast, markers associated with suppressive populations of myeloid cells (CD163, B7-H3, VISTA) and T cells (CD4, LAG3, Tim-3) were expressed at a higher level in CD45+ segments in the ‘surrounding stromal leukocyte’ regions (cf. ‘immune-rich cancer cell islet’ regions). When comparing the three phenotypes, the ‘inflamed’ profile (cf. ‘immune-excluded’ and ‘desert’) exhibited higher expression of markers associated with B cells, NK cells, macrophages, and myeloid cells. Myeloid markers were highly expressed in the ‘immune-excluded’ phenotype. Granulocyte markers and immune-regulatory markers were higher in the ‘desert‘ profile (cf. ‘inflamed’ and ‘immune-excluded’). In conclusion, this study describes the spatial heterogeneity of the immune microenvironment in NPC and highlights immune-related biomarkers in immune phenotypes, which may aid in the stratification of patients for therapeutic purposes.
Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy Response in High-Grade Serous Ovarian Cancer
Authors: Arentz Georgia , Mittal Parul , Klingler-Hoffmann Manuela , Condina Mark R. , Ricciardelli Carmela , Lokman Noor A. , Kaur Gurjeet , Oehler Martin K. , Hoffmann Peter
Published: April 2023

Eighty percent of ovarian cancer patients initially respond to chemotherapy, but the majority eventually experience a relapse and die from the disease with acquired chemoresistance. In addition, 20% of patients do not respond to treatment at all, as their disease is intrinsically chemotherapy resistant. Data-independent acquisition nano-flow liquid chromatography–mass spectrometry (DIA LC-MS) identified the three protein markers: gelsolin (GSN), calmodulin (CALM1), and thioredoxin (TXN), to be elevated in high-grade serous ovarian cancer (HGSOC) tissues from patients that responded to chemotherapy compared to those who did not; the differential expression of the three protein markers was confirmed by immunohistochemistry. Analysis of the online GENT2 database showed that mRNA levels of GSN, CALM1, and TXN were decreased in HGSOC compared to fallopian tube epithelium. Elevated levels of GSN and TXN mRNA expression correlated with increased overall and progression-free survival, respectively, in a Kaplan–Meier analysis of a large online repository of HGSOC patient data. Importantly, differential expression of the three protein markers was further confirmed when comparing parental OVCAR-5 cells to carboplatin-resistant OVCAR-5 cells using DIA LC-MS analysis. Our findings suggest that GSN, CALM1, and TXN may be useful biomarkers for predicting chemotherapy response and understanding the mechanisms of chemotherapy resistance. Proteomic data are available via ProteomeXchange with identifier PXD033785.
R-Loops at Chromosome Ends: From Formation, Regulation, and Cellular Consequence
Authors: Gong Yi , Liu Yie
Published: April 2023

Telomeric repeat containing RNA (TERRA) is transcribed from subtelomeric regions to telomeres. TERRA RNA can invade telomeric dsDNA and form telomeric R-loop structures. A growing body of evidence suggests that TERRA-mediated R-loops are critical players in telomere length homeostasis. Here, we will review current knowledge on the regulation of R-loop levels at telomeres. In particular, we will discuss how the central player TERRA and its binding proteins modulate R-loop levels through various mechanisms. We will further provide an overview of the consequences of TERRA-mediated persistent or unscheduled R-loops at telomeres in human ALT cancers and other organisms, with a focus on telomere length regulation after replication interference-induced damage and DNA homologous recombination-mediated repair.
Characteristics of Cancer-Related Fatigue and an Efficient Model to Identify Patients with Gynecological Cancer Seeking Fatigue-Related Management
Authors: Wang Ying-Wen , Ou Yu-Che , Lin Hao , Huang Kun-Siang , Fu Hung-Chun , Wu Chen-Hsuan , Chen Ying-Yi , Huang Szu-Wei , Tu Hung-Pin , Tsai Ching-Chou
Published: April 2023

Cancer-related fatigue (CRF) is the most common somatic discomfort in patients with gynecological cancers. CRF is often overlooked; however, it can impair the patients’ quality of life considerably. This cross-sectional study aimed to identify the clinical characteristics of CRF in gynecological cancer patients. Questionnaires and the International Classification of Diseases 10th Revision (ICD-10) criteria were used to identify CRF. The enrolled patients were further categorized according to the amount of fatigue-related management received. Of the enrolled 190 patients, 40.0% had endometrial cancer, 28.9% had cervical cancer, and 31.1% had ovarian cancer. On the basis of the ICD-10 diagnostic criteria, 42.6% had non-cancer-related fatigue, 10% had CRF, and 51% had BFI-T questionnaire-based fatigue. Moreover, 77.9% of the study cohort had ever received fatigue-related management. Further analysis showed that patients with endometrial/cervical cancer, International Federation of Gynecology and Obstetrics stage >1, Eastern Cooperative Oncology Group performance status score ≥1, inadequate cancer treatment response, and receiving cancer treatment in the past week had a higher probability of receiving more fatigue-related management. The five-item predictive model developed from these factors may help physicians recognize patients seeking more fatigue-related management more efficiently. This is important as they may suffer from a more profound CRF.
The Role of Molecular Imaging in Patients with Brain Metastases: A Literature Review
Authors: Urso Luca , Bonatto Elena , Nieri Alberto , Castello Angelo , Maffione Anna Margherita , Marzola Maria Cristina , Cittanti Corrado , Bartolomei Mirco , Panareo Stefano , Mansi Luigi , Lopci Egesta , Florimonte Luigia , Castellani Massimo
Published: April 2023

Over the last several years, molecular imaging has gained a primary role in the evaluation of patients with brain metastases (BM). Therefore, the “Response Assessment in Neuro-Oncology” (RANO) group recommends amino acid radiotracers for the assessment of BM. Our review summarizes the current use of positron emission tomography (PET) radiotracers in patients with BM, ranging from present to future perspectives with new PET radiotracers, including the role of radiomics and potential theranostics approaches. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2022 were reviewed. Current evidence confirms the important role of amino acid PET radiotracers for the delineation of BM extension, for the assessment of response to therapy, and particularly for the differentiation between tumor progression and radionecrosis. The newer radiotracers explore non-invasively different biological tumor processes, although more consistent findings in larger clinical trials are necessary to confirm preliminary results. Our review illustrates the role of molecular imaging in patients with BM. Along with magnetic resonance imaging (MRI), the gold standard for diagnosis of BM, PET is a useful complementary technique for processes that otherwise cannot be obtained from anatomical MRI alone.
Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases
Authors: Bailly Christian , Thuru Xavier
Published: April 2023

Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.
Correction: Verdoliva et al. Zeolites as Acid/Basic Solid Catalysts: Recent Synthetic Developments. Catalysts 2019, 9, 248
Authors: Verdoliva Valentina , Saviano Michele , De Luca Stefania
Published: April 2023

The authors wish to make the following correction to this paper [...]
Integrated Placental Modelling of Histology with Gene Expression to Identify Functional Impact on Fetal Growth
Authors: Yong Hannah Ee Juen , Maksym Katarzyna , Yusoff Muhammad Ashraf Bin , Salazar-Petres Esteban , Nazarenko Tatiana , Zaikin Alexey , David Anna L. , Hillman Sara L. , Sferruzzi-Perri Amanda N.
Published: April 2023

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Altered placental formation and functional capacity are major contributors to FGR pathogenesis. Relating placental structure to function across the placenta in healthy and FGR pregnancies remains largely unexplored but could improve understanding of placental diseases. We investigated integration of these parameters spatially in the term human placenta using predictive modelling. Systematic sampling was able to overcome heterogeneity in placental morphological and molecular features. Defects in villous development, elevated fibrosis, and reduced expression of growth and functional marker genes (IGF2, VEGA, SLC38A1, and SLC2A3) were seen in age-matched term FGR versus healthy control placentas. Characteristic histopathological changes with specific accompanying molecular signatures could be integrated through computational modelling to predict if the placenta came from a healthy or FGR pregnancy. Our findings yield new insights into the spatial relationship between placental structure and function and the etiology of FGR.
The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells
Authors: Cardinali Giorgia , Kovacs Daniela , Mosca Sarah , Bellei Barbara , Flori Enrica , Morrone Aldo , Mileo Anna Maria , Maresca Vittoria
Published: April 2023

Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture. Given that cytoskeleton integrity requires energy, we next evaluated ATP levels and we observed a drop in ATP after exposure to αMSH plus LY294002. To evaluate if the αMSH-activated PI3K pathway could modulate energy metabolism, we focused on glucose uptake by analyzing the expression of the Glut-1 glucose translocator. Compared with cells treated with αMSH alone, those exposed to combined treatment showed a reduction of Glut-1 on the plasma membrane. This metabolic alteration was associated with changes in mitochondrial mass. A significant decrease of the cell migratory potential was also observed. We demonstrated that the αMSH-dependent PI3K pathway acts as a regulator of energy metabolism via glucose uptake, influencing the actin cytoskeleton, which is involved in melanosome release and cell motility. Hence, these results could constitute the basis for innovative therapeutical strategies.
Novel SAW Temperature Sensor with Pt/Ti/AlN/Mo/AlN/Si Structure for High Temperature Application
Authors: Ruan Yong , Chen Yang , Wu Yu , Shi Meng , Du Yan , Song Zhiqiang , Chen Yiyang , Dong Helei , Zhang Congchun , Teng Jiao
Published: April 2023

In this paper, a surface acoustic wave (SAW) temperature sensor with a Pt/Ti/AlN/Mo/AlN/Si structure was prepared, and the high temperature characteristics of the sensors at 20–600 °C under different electrode metallization rates (ղ) were measured. It was found that frequent device mutation occurred in the first high-temperature test, and that the mutation point decreased with the increase in the electrode metallization rate (ղ). In the subsequent test, the data became stable, the sensor’s center frequency increased, the return loss (S11) decreased and the factor of merit (Q) increased. After annealing the same sensors at 600 °C for 30 min, they could achieve performance improvement in the first test, meaning that proper annealing can improve sensor performance. In addition, the annealed SAW sensor was tested in the temperature range of 20–1000 °C, which met the requirement of a temperature range of 20–900 °C, its f–T curve was linear, the factor of merit (Q) was 34.5 and the sensitivity was 46.6 KHz/K.
Efficient Monitoring of Microbial Communities and Chemical Characteristics in Incineration Leachate with Electronic Nose and Data Mining Techniques
Authors: Zhang Zhongyuan , Zhou Qiaomei , Qiu Shanshan , Zhou Jie , Huang Jingang
Published: April 2023

Incineration leachate is a hazardous liquid waste that requires careful management due to its high levels of organic and inorganic pollutants, and it can have serious environmental and health implications if not properly treated and monitored. This study applied a novel electronic nose to monitor the microbial communities and chemical characteristics of incineration leachate. The e-nose data were aggregated using principal component analysis (PCA) and T-distributed stochastic neighbor embedding (TSNE). Random forest (RF) and gradient-boosted decision tree (GBDT) algorithms were employed to establish relationships between the e-nose signals and the chemical characteristics (such as pH, chemical oxygen demand, and ammonia nitrogen) and microbial communities (including Proteobacteria, Firmicutes, and Bacteroidetes) of the incineration leachate. The PCA-GBDT models performed well in recognizing leachate samples, achieving 100% accuracy for the training set and 98.92% accuracy for the testing data without overfitting. The GBDT models based on the original data performed exceptionally well in predicting changes in chemical parameters, with R2 values exceeding 0.99 for the training set and 0.86 for the testing set. The PCA-GBDT models also demonstrated superior performance in predicting microbial community composition, achieving R2 values above 0.99 and MSE values below 0.0003 for the training set and R2 values exceeding 0.86 and MSE values below 0.015 for the testing set. This research provides an efficient monitoring method for the effective enforcement and implementation of monitoring programs by utilizing e-noses combined with data mining to provide more valuable insights compared with traditional instrumental measurements.
Automatic Analysis of Isothermal Amplification via Impedance Time-Constant-Domain Spectroscopy: A SARS-CoV-2 Case Study
Authors: Ramírez-Chavarría Roberto G. , Castillo-Villanueva Elizabeth , Alvarez-Serna Bryan E. , Carrillo-Reyes Julián , Torres Lizeth , Ramírez-Zamora Rosa María , Buitrón Germán , Alvarez-Icaza Luis
Published: April 2023

The development of sensitive and affordable testing devices for infectious diseases is essential to preserve public health, especially in pandemic scenarios. In this work, we have developed an attractive analytical method to monitor products of genetic amplification, particularly the loop-mediated isothermal amplification reaction (RT-LAMP). The method is based on electrochemical impedance measurements and the distribution of relaxation times model, to provide the so-called time-constant-domain spectroscopy (TCDS). The proposed method is tested for the SARS-CoV-2 genome, since it has been of worldwide interest due to the COVID-19 pandemic. Particularly, once the method is calibrated, its performance is demonstrated using real wastewater samples. Moreover, we propose a simple classification algorithm based on TCDS data to discriminate among positive and negative samples. Results show how a TCDS-based method provides an alternative mechanism for label-free and automated assays, exhibiting robustness and specificity for genetic detection.
Inhibitory Effect of Phosphorothioate Oligonucleotide Complementary to G6PD mRNA on Murine Melanoma
Authors: Yurchenko Kseniya A. , Laikova Kateryna V. , Golovkin Ilya O. , Novikov Ilya A. , Yurchenko Alyona A. , Makalish Tatyana P. , Oberemok Volodymyr V.
Published: April 2023

In terms of the incidence among all tumors, skin cancer is on top, with the most deadly among them being melanoma. The search for new therapeutic agents to combat melanoma is very relevant. In our opinion, antisense oligonucleotides (ASO) aimed at suppressing the genes responsible for their viability in cancer cells give hope for treatment, which makes it possible to eliminate cancer cells near the tumor site both before and after surgery. In this article, we describe how Skeen-11 phosphorothioate oligonucleotide significantly decreased the proliferative activity of murine melanoma cells. Injections of Skeen-11 also inhibited tumor growth in mice with inoculated melanoma. A toxicity study showed no side effects with dose adjustments. The results show that the use of ASO Skeen-11 in vivo reduced the tumor size within 7 days, reduced the number of mitoses in the tumor cells, and increased the amount of necrosis compared with the control group.
Knockdown of KDM5B Leads to DNA Damage and Cell Cycle Arrest in Granulosa Cells via MTF1
Authors: Yang Yingnan , Cai Yu , Guo Jinjing , Dai Keke , Liu Liang , Chen Zili , Wang Feng , Deng Mingtian
Published: April 2023

KDM5B is essential for early embryo development, which is under the control of maternal factors in oocytes. Granulosa cells (GCs) play a critical role during oocyte mature. However, the role of KDM5B in GCs remains to be elucidated. In the current study, we found that KDM5B expressed highly in the ovaries and located in goat GCs. Using an RNA sequence, we identified 1353 differentially expressed genes in the KDM5B knockdown GCs, which were mainly enriched in cell cycle, cell division, DNA replication and the cellular oxidative phosphorylation regulation pathway. Moreover, we reported a decrease in the percentage of proliferated cells but an increase in the percentage of apoptotic cells in the KDM5B knockdown GCs. In addition, in the KDM5B knockdown GCs, the percentage of GCs blocked at the S phase was increased compared to the NC group, suggesting a critical role of KDM5B in the cell cycle. Moreover, in the KDM5B knockdown GCs, the reactive oxygen species level, the mitochondrial depolarization ratio, and the expression of intracellular phosphorylated histone H2AX (γH2AX) increased, suggesting that knockdown of KDM5B leads to DNA damage, primarily in the form of DNA double-strand breaks (DSBs). Interestingly, we found a down-regulation of MTF1 in the KDM5B knockdown GCs, and the level of cell proliferation, as well as the cell cycle block in the S phase, was improved. In contrast, in the group with both KDM5B knockdown and MTF1 overexpression, the level of ROS, the expression of γH2AX and the number of DNA DSB sites decreased. Taken together, our results suggest that KDM5B inhibits DNA damage and promotes the cell cycle in GCs, which might occur through the up-regulation of MTF1.