bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemopreventive Effects of Concomitant or Individual Use of Statins, Aspirin, Metformin, and Angiotensin Drugs: A Study Using Claims Data of 23 Million Individuals
Authors: Wang Ching-Huan , Huang Chih-Wei , Nguyen Phung Anh , Lin Ming-Chin , Yeh Chih-Yang , Islam Md. Mohaimenul , Rahmanti Annisa Ristya , Yang Hsuan-Chia
Published: February 2022

Despite previous studies on statins, aspirin, metformin, and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), little has been studied about all their possible combinations for chemoprevention against cancers. This study aimed to comprehensively analyze the composite chemopreventive effects of all the combinations. In this case-control study, health records were retrieved from claims databases of Taiwan’s Health and Welfare Data Science Center. Eligible cases were matched at a 1:4 ratio with controls for age and sex. Both cases and controls were categorized into 16 exposure groups based on medication use. A total of 601,733 cancer cases were identified. Cancer risks (denoted by adjusted odds ratio; 99% confidence interval) were found to be significantly decreased: overall risk of all cancers in statin-alone (0.864; 0.843, 0.886), aspirin-alone (0.949; 0.939, 0.958), and ACEIs/ARBs (0.982; 0.978, 0.985) users; prostate (0.924; 0.889, 0.962) and female breast (0.967; 0.936, 1.000) cancers in metformin-alone users; gastrointestinal, lung, and liver cancers in aspirin and/or ACEIs/ARBs users; and liver cancer (0.433; 0.398, 0.471) in statin users. In conclusion, the results found no synergistic effect of multiple use of these agents on cancer prevention. Use of two (statins and aspirin, statins and metformin, statins and ACEIs/ARBs, and aspirin and ACEIS/ARBs) showed chemopreventive effects in some combinations, while the use of four, in general, did not.
Diagnosis of Fabry Disease in a Patient with a Surgically Repaired Congenital Heart Defect: When Clinical History and Genetics Make the Difference
Authors: Rubino Marta , Monda Emanuele , Caiazza Martina , Palmiero Giuseppe , Lioncino Michele , Cirillo Annapaola , Fusco Adelaide , Verrillo Federica , Perna Alessia , Diana Gaetano , Amodio Federica , Cesaro Arturo , Duro Giovanni , Sarubbi Berardo , Russo Maria , Calabrò Paolo , Limongelli Giuseppe
Published: February 2022

Fabry disease (FD) is a multiorgan disease, which can potentially affect any organ or tissue, with the heart, kidneys, and central nervous system representing the major disease targets. FD can be suspected based on the presence of specific red flags, and the subsequent evaluation of the α-Gal A activity and GLA sequencing, are required to confirm the diagnosis, to evaluate the presence of amenable GLA mutation, and to perform a cascade program screening in family members. An early diagnosis is required to start an etiological treatment and to prevent irreversible organ damage. Here, we describe a case of a 37-years-old patient, with a surgically repaired congenital heart defect in his childhood, who had a late diagnosis of FD based on the clinical history and targeted genetic evaluation. This case highlights the importance to perform a correct phenotyping and definite diagnosis of FD, to start an early and appropriate treatment in the index patient, and a cascade clinical and genetic screening to identify other family members at risk, which may benefit from specific treatment and/or a close follow-up.
Hydrogen-Rich Gas Production from Two-Stage Catalytic Pyrolysis of Pine Sawdust with Nano-NiO/Al2O3 Catalyst
Authors: Xu Tao , Zheng Xiuren , Xu Jue , Wu Yongping
Published: February 2022

Hydrogen production from biomass pyrolysis is economically and technologically attractive from the perspectives of energy and the environment. The two-stage catalytic pyrolysis of pine sawdust for hydrogen-rich gas production is investigated using nano-NiO/Al2O3 as the catalyst at high temperatures. The influences of residence time (0–30 s) and catalytic temperature (500–800 °C) on pyrolysis performance are examined in the distribution of pyrolysis products, gas composition, and gas properties. The results show that increasing the residence time decreased the solid and liquid products but increased gas products. Longer residence times could promote tar cracking and gas-phase conversion reactions and improve the syngas yield, H2/CO ratio, and carbon conversion. The nano-NiO/A12O3 exhibits excellent catalytic activity for tar removal, with a tar conversion rate of 93% at 800 °C. The high catalytic temperature could significantly improve H2 and CO yields by enhancing the decomposition of tar and gas-phase reactions between CO2 and CH4. The increasing catalytic temperature increases the dry gas yield and carbon conversion but decreases the H2/CO ratio and low heating value.
Green Synthesis of Flowerball-like MoS2/VC Nanocomposite and Its Efficient Catalytic Performance for Oxygen Reduction Either in Alkaline or Acid Media
Authors: Zhang Xiaofeng , Ke Yayun , Wang Ting , Cai Jiannan , Huang Qiufeng , Lin Shen
Published: February 2022

Opening up electrocatalysts for oxygen reduction reaction (ORR) is essential for practical application in fuel cells and metal-air batteries; however, how to make the catalysts with both good performance and low cost is difficult. Recently, research on the ORR of molybdenum disulfide-based catalysts in alkaline electrolytes has been on the rise. However, the development of MoS2 catalyst for acidic ORR is still in its infancy. Herein, without using reductant and morphology control reagent, we firstly obtained flowerball-like MoS2/Vulcan XC-72R (VC) nanocomposites via hydrothermal method. The designed composite exhibits a nearly 4e− ORR process with 0.78 and 0.92 V onset potentials in 0.1 M KOH and HClO4, respectively. Furthermore, the flowerball-like composite shows utmost electrochemical stability judging by 87 and 80% current retention for about 5.5 h either in alkaline or acid media, long term durability for continuous 10,000 cycles, and stronger resistance to methanol than the commercial Pt/C catalyst. The abundant Mo edges as catalytic active centers of flowerball-like structure, high electron conductivity, and enhanced mass transport in either alkaline or acidic electrolyte are favorable for catalytic performance. The prepared catalyst provides great potential for the substitution of noble metal based catalysts in fuel cells and metal-air batteries.
Thermodynamic Stability and Intrinsic Activity of La1−xSrxMnO3 (LSM) as an Efficient Bifunctional OER/ORR Electrocatalysts: A Theoretical Study
Authors: Hale William , Choudhury Pabitra
Published: February 2022

Perovskite oxides, being transition metal oxides, show promise as bifunctional catalysts being able to catalyze both oxygen evolution reactions (OER) and oxygen reduction reactions (ORR). These two reactions play a crucial role in energy storage and energy conversion devices. An important feature of perovskite catalyst is their ability to be tuned, as tuning can positively affect both reactivity and stability. In this study, Density Functional Theory (DFT) has been utilized to calculate both the equilibrium phase stability and the overpotentials (reactivity performance indicator of the catalysts) of La1−xSrxMnO3 (LSM) structures with different stoichiometry by introducing Mn and O vacancies for both the OER/ORR reactions. The electronic structures reveal that combined Mn and O vacancies can lead to higher catalytic activity for both OER and ORR due to the optimum filling of antibonding orbital electrons. Moreover, both O p-band centers and equilibrium phase stability plots show that LSM structures can be stable at normal OER/ORR operating conditions in an alkali medium.
The Effect of pH, Metal Ions, and Insoluble Solids on the Production of Fumarate and Malate by Rhizopus delemar in the Presence of CaCO3
Authors: Ronoh Dominic Kibet , Swart Reuben Marc , Nicol Willie , Brink Hendrik
Published: February 2022

Calcium carbonate has been extensively used as a neutralising agent in acid-forming microbial processes. The effect of increasing calcium carbonate concentrations on Rhizopus delemar has not been previously investigated. In this study, an evaluation of fumaric acid (FA) and malic acid (MA) production was conducted at three CaCO3 concentrations in shake flask cultivations. Increased CaCO3 concentrations resulted in the co-production of FA and MA in the first 55 h of the fermentation (regime 1), and the subsequent depletion of FA thereafter (regime 2). Three factors were highlighted as likely causes of this response: insoluble solids, metal ion concentrations, and pH. Further shake flask cultivations as well as a continuous fermentation with immobilised R. delemar were used to explore the effect of the three factors on regime 1 and 2. Insoluble solids were found to have no effect on the response in either regime 1 or 2. Increasing the aqueous calcium ion concentrations to 10 g L−1 resulted in a three-fold increase in MA titres (regime 1). Moreover, an increase in pH above 7 was associated with a drop in FA concentrations in regime 2. Further tests established that this was due to the hydration of FA to MA, influenced by high pH conditions (7 or higher), nitrogen starvation, and glucose depletion. Anaerobic conditions were also found to significantly improve the hydration process. This study presents the first investigation in which the production of FA followed by in situ hydration of FA to MA with R. delemar has been achieved.
The Role of Mitochondria in Human Fertility and Early Embryo Development: What Can We Learn for Clinical Application of Assessing and Improving Mitochondrial DNA?
Authors: Podolak Amira , Woclawek-Potocka Izabela , Lukaszuk Krzysztof
Published: February 2022

Mitochondria are well known as ‘the powerhouses of the cell’. Indeed, their major role is cellular energy production driven by both mitochondrial and nuclear DNA. Such a feature makes these organelles essential for successful fertilisation and proper embryo implantation and development. Generally, mitochondrial DNA is exclusively maternally inherited; oocyte’s mitochondrial DNA level is crucial to provide sufficient ATP content for the developing embryo until the blastocyst stage of development. Additionally, human fertility and early embryogenesis may be affected by either point mutations or deletions in mitochondrial DNA. It was suggested that their accumulation may be associated with ovarian ageing. If so, is mitochondrial dysfunction the cause or consequence of ovarian ageing? Moreover, such an obvious relationship of mitochondria and mitochondrial genome with human fertility and early embryo development gives the field of mitochondrial research a great potential to be of use in clinical application. However, even now, the area of assessing and improving DNA quantity and function in reproductive medicine drives many questions and uncertainties. This review summarises the role of mitochondria and mitochondrial DNA in human reproduction and gives an insight into the utility of their clinical use.
Improving Cell Recovery: Freezing and Thawing Optimization of Induced Pluripotent Stem Cells
Authors: Uhrig Markus , Ezquer Fernando , Ezquer Marcelo
Published: February 2022

Achieving good cell recovery after cryopreservation is an essential process when working with induced pluripotent stem cells (iPSC). Optimized freezing and thawing methods are required for good cell attachment and survival. In this review, we concentrate on these two aspects, freezing and thawing, but also discuss further factors influencing cell recovery such as cell storage and transport. Whenever a problem occurs during the thawing process of iPSC, it is initially not clear what it is caused by, because there are many factors involved that can contribute to insufficient cell recovery. Thawing problems can usually be solved more quickly when a certain order of steps to be taken is followed. Under optimized conditions, iPSC should be ready for further experiments approximately 4–7 days after thawing and seeding. However, if the freezing and thawing protocols are not optimized, this time can increase up to 2–3 weeks, complicating any further experiments. Here, we suggest optimization steps and troubleshooting options for the freezing, thawing, and seeding of iPSC on feeder-free, Matrigel™-coated, cell culture plates whenever iPSC cannot be recovered in sufficient quality. This review applies to two-dimensional (2D) monolayer cell culture and to iPSC, passaged, frozen, and thawed as cell aggregates (clumps). Furthermore, we discuss usually less well-described factors such as the cell growth phase before freezing and the prevention of osmotic shock during thawing.
IFN-γ Induces PD-L1 Expression in Primed Human Basophils
Authors: Bonam Srinivasa Reddy , Chauvin Camille , Mathew Mano J. , Bayry Jagadeesh
Published: February 2022

Programmed death-ligand 1 (PD-L1) plays a key role in maintaining immune tolerance and also in immune evasion of cancers and pathogens. Though the identity of stimuli that induce PD-L1 in various human innate cells and their function are relatively well studied, data on the basophils remain scarce. In this study, we have identified one of the factors, such as IFN-γ, that induces PD-L1 expression in human basophils. Interestingly, we found that basophil priming by IL-3 is indispensable for IFN-γ-induced PD-L1 expression in human basophils. However, priming by other cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF) and thymic stromal lymphopoietin (TSLP) was dispensable. Analyses of a published microarray data set on IL-3-treated basophils indicated that IL-3 enhances IFNGR2, one of the chains of the IFNGR heterodimer complex, and CD274, thus providing a mechanistic insight into the role of IL-3 priming in IFN-γ-induced PD-L1 expression in human basophils.
Virus–Host Cell Interactions
Authors: Hoenen Thomas , Groseth Allison
Published: February 2022

As obligate intracellular parasites, viruses are intimately interconnected with their host cells [...]
Metastatic Tumor Cell-Specific FABP7 Promotes NSCLC Metastasis via Inhibiting β-Catenin Degradation
Authors: Bai Qiaorui , Yang Xia , Li Quanfeng , Chen Weizhong , Tian Han , Lian Rong , Liu Ximeng , Wang Shuang , Yang Yi
Published: February 2022

Metastasis accounts for 90% of cancer-related deaths and represents a prominent malignant feature in non-small cell lung cancer (NSCLC), while tumor cell-specific mechanisms and molecules pivotal for the metastatic capacity remain unclear. By analyzing single-cell RNA sequencing data, we found that fatty acid binding protein 7 (FABP7) was specifically up-regulated in tumor cells of metastatic NSCLC patients and might be a prognostic indicator for poor survival. Experimental studies based on NSCLC cell lines showed that FABP7 promoted the metastatic competencies of NSCLC cells in vitro and in vivo. Mechanistically, we demonstrated that FABP7 was important to canonical Wnt signaling activation and competitively inhibited the interaction between β-catenin and components of its cytoplasmic degradation complex, thereby repressing the phosphorylation-dependent ubiquitination and degradation of β-catenin. Our present study identifies FABP7 as a metastatic tumor cell-specific pro-metastatic gene and uncovers a previously unknown regulatory mechanism underlying Wnt hyperactivation via FABP7-impaired cytoplasmic β-catenin degradation, implicating a novel molecule in regulating NSCLC metastasis.
Deciphering the Retinal Epigenome during Development, Disease and Reprogramming: Advancements, Challenges and Perspectives
Authors: Zibetti Cristina
Published: February 2022

Retinal neurogenesis is driven by concerted actions of transcription factors, some of which are expressed in a continuum and across several cell subtypes throughout development. While seemingly redundant, many factors diversify their regulatory outcome on gene expression, by coordinating variations in chromatin landscapes to drive divergent retinal specification programs. Recent studies have furthered the understanding of the epigenetic contribution to the progression of age-related macular degeneration, a leading cause of blindness in the elderly. The knowledge of the epigenomic mechanisms that control the acquisition and stabilization of retinal cell fates and are evoked upon damage, holds the potential for the treatment of retinal degeneration. Herein, this review presents the state-of-the-art approaches to investigate the retinal epigenome during development, disease, and reprogramming. A pipeline is then reviewed to functionally interrogate the epigenetic and transcriptional networks underlying cell fate specification, relying on a truly unbiased screening of open chromatin states. The related work proposes an inferential model to identify gene regulatory networks, features the first footprinting analysis and the first tentative, systematic query of candidate pioneer factors in the retina ever conducted in any model organism, leading to the identification of previously uncharacterized master regulators of retinal cell identity, such as the nuclear factor I, NFI. This pipeline is virtually applicable to the study of genetic programs and candidate pioneer factors in any developmental context. Finally, challenges and limitations intrinsic to the current next-generation sequencing techniques are discussed, as well as recent advances in super-resolution imaging, enabling spatio-temporal resolution of the genome.
Nonlinear Multivariate Regression Algorithms for Improving Precision of Multisensor Potentiometry in Analysis of Spent Nuclear Fuel Reprocessing Solutions
Authors: Kravić Nadan , Savosina Julia , Agafonova-Moroz Marina , Babain Vasily , Legin Andrey , Kirsanov Dmitry
Published: February 2022

Potentiometric multisensor systems were shown to be very promising tools for the quantification of numerous analytes in complex radioactive samples deriving from spent nuclear fuel reprocessing. Traditional multivariate calibration for these multisensor systems is performed with partial least squares regression—an intrinsically linear regression method that can provide suboptimal results when handling potentiometric signals from very complex multi-component samples. In this work, a thorough investigation was performed on the performance of a multisensor system in combination with non-linear multivariate regression models for the quantification of analytes in the PUREX (Plutonium–URanium EXtraction) process. The multisensor system was composed of 17 cross-sensitive potentiometric sensors with plasticized polymeric membranes containing different lipophilic ligands capable of heavy metals, lanthanides, and actinides binding. Regression algorithms such as support vector machines (SVM), random forest (RF), and kernel-regularized least squares (KRLS) were tested and compared to the traditional partial least squares (PLS) method in the simultaneous quantification of the following elements in aqueous phase samples of the PUREX process: U, La, Ce, Sm, Zr, Mo, Zn, Ru, Fe, Ca, Am, and Cm. It was shown that non-linear methods outperformed PLS for most of the analytes.
Treatment of Pediatric Inflammatory Myofibroblastic Tumor: The Experience from China Children’s Medical Center
Authors: Dong Youhong , Zahid Kashif Rafiq , Han Yidi , Hu Pengchao , Zhang Dongdong
Published: February 2022

Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor with intermediate malignancy that tends to affect children primarily. To date, no standardized therapies exist for the treatment of IMT. This study aimed to share experience from China Children’s Medical Center for the explorative treatment of IMT. Methods: Patients with newly diagnosed IMT between January 2013 and December 2018 were included. Patients were grouped according to surgical margins and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging. The clinical characteristic, therapeutic schedules, treatment response and clinical outcome were described. Results: Six patients were enrolled in this study, including two boys and four girls, with a median age of 57 months (range 10–148 months). Among them, five patients were anaplastic lymphoma kinase positive. Four patients achieved complete remission and two patients attained partial remission after treatment with this protocol. All patients were alive after a median follow-up of 4 years (range 3–7 years). The most common treatment-related adverse reaction was myelosuppression. Conclusion: In this study, we demonstrated that IMT has a good prognosis and the treatment selected according to risk stratification was effective and feasible.
Greening Roadway Infrastructure with Vetiver Grass to Support Transportation Resilience
Authors: Kim Karl , Riley Sequoia , Fischer Elizabeth , Khan Sadik
Published: February 2022

With flooding and other weather events intensifying, more cost-effective erosion and flood control systems are needed. Vetiver (Chrysopogon zizanioides (L.) Roberty), is part of an arsenal of sustainable, low cost, and green infrastructure tools to reduce the risks of erosion, landslides, and flooding. This study investigates vetiver and its broader application to transportation planning. Based on a literature review and interviews with experts, vetiver as a green infrastructure tool is summarized. An evaluation framework was devised in which the plant’s effectiveness to stabilize hillsides and manage stormwater is investigated. This framework is applied to a recent highway flooding case where vetiver could have been used. While site-specific conditions and roadway requirements are critical to its effectiveness as a mitigation tool, additional pathways to understanding, acceptance, and use of vetiver to support transportation resilience requires convergence in engineering, design, and planning disciplines. Understanding barriers to the adoption of vetiver will also support efforts to increase other green infrastructure tools in transportation planning. Improvements in policies, standards, guidance and training and education on vetiver and green infrastructure will support the mitigation of transportation disruptions and community resilience.
Effects of Modified Atmosphere Packaging, Storage Temperature, and Absorbent Pads on the Quality of Fresh Cape Hake Fish Fillets
Authors: Opara Umezuruike Linus , Fadiji Tobi , Caleb Oluwafemi James , Oluwole Adebanji Olasupo
Published: February 2022

This study investigated the effects of modified atmosphere packaging (MAP), storage temperature, and the use of absorbent pads (PAD) on the quality attributes of Cape hake (Merluccius capensis) fish fillets. Fresh Cape hake fillets were packaged under active-MA (40% CO2 + 30% O2 + 30% N2) or passive-MA (0.039% CO2 + 20.95% O2 + 78% N2), with and without PAD, and stored at 0 °C, 4 °C, and 8 °C (to mimic abuse temperature). The control fresh fillets were stored under passive-MAP without PAD at 0 °C, 4 °C, and 8 °C. Headspace O2 gas composition continuously decreased below critical limits under passive-MAP, with an increase in storage temperature. Similarly, O2 levels decreased under active-MAP but did not reach critical levels, with the lowest being 9.5% at 0 °C. The interaction of storage temperature and modified atmosphere had a significant effect on quality attributes of Cape hake fillets. Drip loss was higher in active-MAP packaged fillets without PAD (0.64%) than passive-MAP packaged fillets without PAD (0.27%). Drip loss was significantly reduced when using absorbent pads (p < 0.05). Firmness, color, and pH were better maintained under active-MAP at the lowest temperature of 0 °C. Firmness (work of shear) of active-MA packaged fillets on day 12 at 0 °C and 4 °C was 527 N/s and 506 N/s, respectively. Fillets packaged under active-MAP at 0 °C had longer shelf-life than control passive-MAP fillets.
Trends in Cosmetics: Product Packaging at the Point of Sale
Authors: Borja Guerrero Belén , López Pecharromán Aránzazu , Sánchez León Rosario C.
Published: February 2022

Recently, there has been a proliferation of establishments where cosmetics products are packaged at the purchaser’s request, promoting the circular economy with the aim of reusing, recycling and reducing packaging. At the Spanish Agency of Medicines and Medical Devices (AEMPS, for its Spanish acronym), we asked ourselves whether this was a legal and safe practice. In order to verify this, a bibliographic analysis of the applicable legislation and regulations was carried out, and the conclusion reached was that it is legal practice, but a series of guidelines are necessary for it to be carried out with guarantees. Consequently, an instruction was developed which provides recommendations to ensure that the packaging of cosmetic products at the point of sale is carried out under optimum conditions. This instruction is aimed at both responsible persons and the personnel who carry out product packaging at the point of sale.
The Effect of an External Electric Field on the Electronic Properties of Defective CBN Nanotubes: A Density Functional Theory Approach
Authors: Salman Saed , Rekik Najeh , Abuzir Alaaedeen , Alshoaibi Adil , Suleiman Jamal
Published: February 2022

We investigated the effects of applying an external electric field on the electronic properties of Stone-Wales (SW) defective carbon-boron-nitride nanotubes (CBN) using first principles calculations. The defective CBN nanotubes were modeled by introducing Stone–Wales defects in the boron-nitride segment (BN-SW), the carbon segment (C-SW), and the carbon-boron-nitride interface segment (CBN-SW). Initially, we studied the formation energies and the structural stability for all models. As a result of adding the SW defects, the calculated bandgap values of the C-SW and CBN-SW models showed significant changes compared to the pristine CBN nanotube. Meanwhile, the BN-SW model showed a slight bandgap change because of the strong covalent bonding between the boron and nitrogen atoms. Applying a transverse electric field induced a fast bandgap closing response in all models, indicating a rapid semiconductor-to-metal phase transition. The defective C-SW and CBN-SW models demonstrated unique bandgap closing patterns in response to applied transverse and longitudinal electric fields, while pristine and BN-SW models had similar bandgap responses.
Comparison of Natural and Dyed Fire Opal
Authors: Wu Jinlin , Ma Hong , Ma Ying , Ning Peiying , Tang Na , Li Huihuang
Published: February 2022

Fire opal is much sought after for its flame-like red-orange-yellow body-color. With consumers’ enthusiasm for fire opals, dyed fire opal has gradually entered the jewelry market, which has made an impact on consumer perception and trade. In this work, we present a combined spectroscopic (FTIR, Raman, UV-Vis) investigation and chemical analysis of four natural fire opals from Mexico and Ethiopia and four dyed samples. Ultra-depth microphotographs revealed uniform color distribution in the natural fire opal, while patches of color were observed in the dyed fire opal. The main infrared peak around 1099 cm−1 indicated the hydrophane origin of all the dyed materials. The color of natural fire opals is related to the presence of Fe oxides and hydroxides (hematite, goethite) as confirmed by the Raman spectra, the first derivative of the UV-Vis spectral curves, and the relatively high Fe content by chemical analysis. By contrast, dyeing opals created several Raman peaks produced by external materials, and an extremely low Fe content was detected. The first derivative of the UV-Vis spectral curves can aid in detecting the use of a dyeing treatment in red and yellow opal.
Polarization of Macrophages in Granulomatous Cutaneous T Cell Lymphoma Granulomatous Mycosis Fungoides Microenvironment
Authors: Johanny Lopez Dominguez , Sokumbi Olayemi , Hobbs Misty M. , Jiang Liuyan
Published: February 2022

Polarization of tumor associated macrophages (TAMs) has been shown to have prognostic significance in different cancer types. This study evaluates the macrophage subtypes that predominates in GMF. Cases of GCTCL from 2007–2020 were identified (n = 6), clinical data was extracted from the electronic medical record, and all pathology slides were reviewed to confirm the diagnosis. Immunohistochemistry (IHC) studies were performed to characterize M1 and M2 macrophage polarization. CD68 (PGM1), pSTAT1, and CD163 were used as pan macrophage, M1, and M2 markers, respectively. The macrophages with positive staining at hot spot per high power field were counted and recorded for data analysis. The average age of patients was 60.5 years [range, 21–78], five patients (83%) were women and 1 (17%) was a man. Five patients were Caucasian (83%), and 1 was Black/African American (17%). Two patients had late stage GMF with M2 (CD163) predominance and the other three had early stage GMF with M1 (pSTAT1) predominance. Our study suggests that macrophage polarization present in GMF tends to be M1 in early stages and M2 in advanced stages. Additional studies are needed to further elucidate the microenvironment of macrophages present in GMF. Such findings may lead to prognostic and therapeutic advances in GMF.
Evaluation of Computer-Aided Detection (CAD) in Screening Automated Breast Ultrasound Based on Characteristics of CAD Marks and False-Positive Marks
Authors: Lee Jeongmin , Kang Bong Joo , Kim Sung Hun , Park Ga Eun
Published: February 2022

The present study evaluated the effectiveness of computer-aided detection (CAD) system in screening automated breast ultrasound (ABUS) and analyzed the characteristics of CAD marks and the causes of false-positive marks. A total of 846 women who underwent ABUS for screening from January 2017 to December 2017 were included. Commercial CAD was used in all ABUS examinations, and its diagnostic performance and efficacy in shortening the reading time (RT) were evaluated. In addition, we analyzed the characteristics of CAD marks and the causes of false-positive marks. A total of 1032 CAD marks were displayed based on the patient and 534 CAD marks on the lesion. Five cases of breast cancer were diagnosed. The sensitivity, specificity, PPV, and NPV of CAD were 60.0%, 59.0%, 0.9%, and 99.6% for 846 patients. In the case of a negative study, it was less time-consuming and easier to make a decision. Among 530 false-positive marks, 459 were identified clearly for pseudo-lesions; the most common cause was marginal shadowing, followed by Cooper’s ligament shadowing, peri-areolar shadowing, rib, and skin lesions. Even though CAD does not improve the performance of ABUS and a large number of false-positive marks were detected, the addition of CAD reduces RT, especially in the case of negative screening ultrasound.
Semi-Automatic MRI Feature Assessment in Small- and Medium-Volume Benign Prostatic Hyperplasia after Prostatic Artery Embolization
Authors: Schmidt Vanessa F. , Schirren Mirjam , Heimer Maurice M. , Kazmierczak Philipp M. , Cyran Clemens C. , Wildgruber Moritz , Seidensticker Max , Ricke Jens , Solyanik Olga
Published: February 2022

(1) Background: To assess the treatment response of benign prostatic syndrome (BPS) following prostatic artery embolization (PAE) using a semi-automatic software analysis of magnetic resonance imaging (MRI) features and clinical indexes. (2) Methods: Prospective, monocenter study of MRI and clinical data of n = 27 patients with symptomatic BPS before and (1, 6, 12 months) after PAE. MRI analysis was performed using a dedicated semi-automatic software for segmentation of the central and the total gland (CG, TG), respectively; signal intensities (SIs) of T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted images (DWI), as well as intravesical prostatic protrusion (IPP) and prostatic volumes (CGV, TGV), were evaluated at each time point. The semi-automatic assessed TGV was compared to conventional TGV by an ellipse formula. International prostate symptom score (IPSS) and international consultation on incontinence questionnaire–urinary incontinence short form (ICIQ-UI SF) questionnaires were used as clinical indexes. Statistical testing in the form of ANOVA, pairwise comparisons using Bonferroni correction, and multiple linear correlations, were conducted using SPSS. (3) Results: TGV was significantly reduced one, six, and 12 months after PAE as assessed by the semi-automatic approach and conventional ellipse formula (p = 0.005; p = 0.025). CGV significantly decreased after one month (p = 0.038), but showed no significant differences six and 12 months after PAE (p = 0.191; p = 0.283). IPP at baseline was demonstrated by 25/27 patients (92.6%) with a significant decrease one, six, and 12 months after treatment (p = 0.028; p = 0.010; p = 0.008). Significant improvement in IPSS and ICIQ-UI SF (p = 0.002; p = 0.016) after one month correlated moderately with TGV reduction (p = 0.031; p = 0.05, correlation coefficients 0.52; 0.69). Apparent diffusion coefficient (ADC) values of CG significantly decreased one month after embolization (p < 0.001), while there were no significant differences in T1w and T2w SIs before and after treatment at each time point. (4) Conclusions: The semi-automatic approach is appropriate for the assessment of volumetric and morphological changes in prostate MRI following PAE, able to identify significantly different ADC values post-treatment without the need for manual identification of infarct areas. Semi-automatic measured TGV reduction is significant and comparable to the TGV calculated by the conventional ellipse formula, confirming the clinical response after PAE.
The Impact of the Early COVID-19 Pandemic on ST-Segment Elevation Myocardial Infarction Presentation and Outcomes—A Systematic Review and Meta-Analysis
Authors: Furnica Cristina , Chistol Raluca Ozana , Chiran Dragos Andrei , Stan Cristinel Ionel , Sargu Gabriela Dumachita , Girlescu Nona , Tinica Grigore
Published: February 2022

Background: The influence of the early COVID-19 pandemic on non-COVID-19 emergencies is uncertain. We conducted a systematic review and a meta-analysis to evaluate the impact of the first months of the COVID-19 pandemic on the presentation, management, and prognosis of patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: We searched the PubMed, Scopus, and Embase databases from January to August 2020. A meta-analysis of studies comparing the profile, STEMI severity at presentation, reperfusion delay, and in-hospital mortality for patients presenting before and during the early COVID-19 pandemic was conducted. Fifteen cross-sectional observational studies including 20,528 STEMI patients from the pre-COVID period and 2190 patients diagnosed and treated during the first months of the COVID-19 pandemic met the inclusion criteria. Results: Patients presenting with STEMI during the pandemic were younger and had a higher comorbidity burden. The time interval between symptoms and first medical contact increased from 93.22 ± 137.37 min to 142 ± 281.60 min (p < 0.001). Door-to-balloon time did not differ significantly between the two periods (p = 0.293). The pooled odds ratio (OR) for low left ventricular ejection fraction at presentation during the pandemic was 2.24 (95% confidence interval (CI) 1.54–3.26) and for a presentation delay >24 h was 2.9 (95% CI 1.54–5.45) relative to before the pandemic. In-hospital mortality did not increase significantly during the outbreak (p = 0.97). Conclusion: During the first months of the COVID-19 pandemic, patients presenting with STEMI were addressed later in the course of the disease with more severe left ventricular impairment. In-hospital emergency circuits and care functioned properly with no increase in door-to-balloon time and early mortality.
Accuracy and Efficiency of Right-Lobe Graft Weight Estimation Using Deep-Learning-Assisted CT Volumetry for Living-Donor Liver Transplantation
Authors: Park Rohee , Lee Seungsoo , Sung Yusub , Yoon Jeeseok , Suk Heung-Il , Kim Hyoungjung , Choi Sanghyun
Published: February 2022

CT volumetry (CTV) has been widely used for pre-operative graft weight (GW) estimation in living-donor liver transplantation (LDLT), and the use of a deep-learning algorithm (DLA) may further improve its efficiency. However, its accuracy has not been well determined. To evaluate the efficiency and accuracy of DLA-assisted CTV in GW estimation, we performed a retrospective study including 581 consecutive LDLT donors who donated a right-lobe graft. Right-lobe graft volume (GV) was measured on CT using the software implemented with the DLA for automated liver segmentation. In the development group (n = 207), a volume-to-weight conversion formula was constructed by linear regression analysis between the CTV-measured GV and the intraoperative GW. In the validation group (n = 374), the agreement between the estimated and measured GWs was assessed using the Bland–Altman 95% limit-of-agreement (LOA). The mean process time for GV measurement was 1.8 ± 0.6 min (range, 1.3–8.0 min). In the validation group, the GW was estimated using the volume-to-weight conversion formula (estimated GW [g] = 206.3 + 0.653 × CTV-measured GV [mL]), and the Bland–Altman 95% LOA between the estimated and measured GWs was −1.7% ± 17.1%. The DLA-assisted CT volumetry allows for time-efficient and accurate estimation of GW in LDLT.
KCTD15 Is Overexpressed in her2+ Positive Breast Cancer Patients and Its Silencing Attenuates Proliferation in SKBR3 CELL LINE
Authors: Coppola Luigi , Baselice Simona , Messina Francesco , Giannatiempo Rosa , Farina Amalia , Vitagliano Luigi , Smaldone Giovanni , Salvatore Marco
Published: February 2022

Studies carried out in the last decade have demonstrated that the members of the KCTD protein family play active roles in carcinogenesis. Very recently, it has been reported that KCTD15, a protein typically associated with other physio-pathological processes, is involved in medulloblastoma and leukemia. Starting with some preliminary indications that emerged from the analysis of online databases that suggested a possible overexpression of KCTD15 in breast cancer, in this study, we evaluated the expression levels of the protein in breast cancer cell lines and in patients and the effects of its silencing in the HER2+ cell model. The analysis of the KCTD15 levels indicates a significant overexpression of the protein in Luminal A and Luminal B breast cancer patients as well as in the related cell lines. The greatest level of over-expression of the protein was found in HER2+ patients and in the related SKBR3 cell line model system. The effects of KCTD15 silencing in terms of cell proliferation, cell cycle, and sensitivity to doxorubicin were evaluated in the SKBR3 cell line. Notably, the KCTD15 silencing in SKBR3 cells by CRISPR/CAS9 technology significantly attenuates their proliferation and cell cycle progression. Finally, we demonstrated that KCT15 silencing also sensitized SKBR3 cells to the cytotoxic agent doxorubicin, suggesting a possible role of the protein in anti HER2+ therapeutic strategies. Our results highlight a new possible player in HER2 breast cancer carcinogenesis, paving the way for its use in breast cancer diagnosis and therapy.
Systematic Review of Prognostic Role of Blood Cell Ratios in Patients with Gastric Cancer Undergoing Surgery
Authors: Schiefer Sabine , Wirsik Naita Maren , Kalkum Eva , Seide Svenja Elisabeth , Nienhüser Henrik , Müller Beat , Billeter Adrian , Büchler Markus W. , Schmidt Thomas , Probst Pascal
Published: February 2022

Various blood cell ratios exist which seem to have an impact on prognosis for resected gastric cancer patients. The aim of this systematic review was to investigate the prognostic role of blood cell ratios in patients with gastric cancer undergoing surgery in a curative attempt. A systematic literature search in MEDLINE (via PubMed), CENTRAL, and Web of Science was performed. Information on survival and cut-off values from all studies investigating any blood cell ratio in resected gastric cancer patients were extracted. Prognostic significance and optimal cut-off values were calculated by meta-analyses and a summary of the receiver operating characteristic. From 2831 articles, 65 studies investigated six different blood cell ratios (prognostic nutritional index (PNI), lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index (SII), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)). There was a significant association for the PNI and NLR with overall survival and disease-free survival and for LMR and NLR with 5-year survival. The used cut-off values had high heterogeneity. The available literature is flawed by the use of different cut-off values hampering evidence-based patient treatment and counselling. This article provides optimal cut-off values recommendations for future research.
The Use of 18F-FDG PET/CT Metabolic Parameters in Predicting Overall Survival in Patients Undergoing Restaging for Malignant Melanoma
Authors: Hlongwa Khanyisile N. , Mokoala Kgomotso M. G. , Matsena-Zingoni Zvifadzo , Vorster Mariza , Sathekge Mike M.
Published: February 2022

Malignant melanoma is one of the more aggressive cancers in the skin, with an increasing incidence every year. Melanoma has a better prognosis if diagnosed early and survival tends to decrease once the disease has metastasized. Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) has been used extensively over the past two decades in staging and assessing responses to therapy in patients with melanoma. Metabolic PET parameters have been demonstrated to be independent prognostic factors for progression-free survival (PFS) and overall survival (OS) in different malignancies, melanoma included. In our study, we evaluated the metabolic parameters of 18F-FDG PET/CT (flourodeoxyglucose positron emission tomography/computed tomography) in predicting the overall survival in patients with malignant melanoma who presented for restaging. Metabolic PET parameters (maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) of the primary tumor, as well as whole-body MTV and TLG of the metastatic disease, were measured. Survival curves for OS were constructed and mortality rates were determined using the different PET variables. Forty-nine patients who presented for a PET/CT restaging in melanoma were included in this study. We found that non-survivors had significantly higher median MTV (11.86 cm3 vs. 5.68 cm3; p-value = 0.022), TLG (3125 vs. 14; p-value = 0.0357), whole-body MTV (53.9 cm3 vs. 14.4 cm3; p-value = 0.0076) and whole-body TLG (963.4 vs. 114.6; p-value = 0.0056). This demonstrated that high MTV and TLG values of the primary tumor and whole-body TLG as quantified by 18F-FDG PET/CT were prognostic factors for overall survival. The findings may potentially guide clinicians in decision making and identifying patients with a poorer prognosis.
Use of Internet Technology among Older Adults in Residential Aged Care Facilities: Protocol for a Systematic Review and Meta-Analysis
Authors: Pantha Sandesh , Shrestha Sumina , Collier Janette
Published: February 2022

Internet usage may help promote the physical and mental health of older adults living in Residential Aged Care Facilities (RACF). There is little evidence of how these older citizens use internet services. This systematic review aims to explore the trends and factors contributing to internet use among aged care residents. A systematic search will be conducted on nine online databases—MEDLINE, EMBASE, PsycInfo, CINAHL, AgeLine, ProQuest, Web of Science, Scopus, and the Cochrane Library. Two reviewers will independently conduct title and abstract screening, full-text reading, critical appraisal, and data extraction. Any discrepancies will be resolved by consensus. Methodological risk of bias will be assessed using the Effective Public Health Practice Project measure and Joanna Briggs Institute checklist. We will report a narrative synthesis of the evidence. Information on factors contributing to internet use and their strength of association will be reported. If feasible, we will undertake a meta-analysis and meta-synthesis. Our review will provide information on the factors predicting internet use among older adults in residential aged care facilities. The evidence from this review will help to formulate further research objectives and, potentially, to design an intervention to trial internet access for these groups. (Protocol Registration: PROSPERO-CRD 42020161227).
Clear Cell Odontogenic Carcinoma: A Series of Three Cases
Authors: Ullah Asad , Cullen Christian , Mattox Samantha N. , Kozman Diana , Patel Nikhil , Sharma Suash , Abdelsayed Rafik
Published: February 2022

Background: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic epithelial neoplasm of the jaws. It is composed of irregular nests of clear to faintly eosinophilic cells resembling clear cell rests of primitive dental lamina and an intermixed hyalinized fibrous stroma. Most cases occur in the 5th and 6th decades of life, with a female predominance. The mandible is affected more than the maxilla. Clinical features vary from asymptomatic to non-specific pain, ill-defined radiolucency, root resorption, and sometimes soft tissue extension. Histology varies from bland to high grade. CCOC demonstrated a significant tendency to recur. Metastasis typically involves regional lymph nodes, which haves been reported in 20–25% of cases. Pulmonary metastasis rarely occurs. Differential diagnoses are broad and include odontogenic, salivary, melanocytic, and metastatic neoplasia. CCOCs are positive for cytokeratins, mainly AE1/AE3 and CK19. Most cases show EWSR1 rearrangement and rarely, the BRAFV600E mutation. Design: Patient charts were reviewed at our institution. A total of three cases were found in electronic medical records, which were diagnosed as clear cell odontogenic carcinoma over a period of six years (2014–2019). Patient charts were reviewed for medical history and radiology data. The pathology slides were reviewed by one or more faculty members. Results: We present three cases of CCOC, ranging in age from 40 to 69 years (two women and one man). Two cases involved the maxilla and one involved the mandible. Two presented with painful swelling and one with mass recurrence. Radiography results show that two had poorly defined radiolucent lesions, and one was heterogeneous with a small nodule projecting into the maxillary sinus. Histological examination revealed an epithelial neoplasm composed of irregular sheets, cords, and nests of polygonal cells with central hyperchromatic, mildly pleomorphic nuclei surrounded by clear to pale eosinophilic cytoplasm, with occasional mitotic figures. The tumor had infiltrated the bone and soft tissues. Two cases were immunopositive for CK5/6 and one case was positive for p63 and CK19. Interestingly, the eosinophilic dentinoid matrix interspersed among tumor cells in one case was consistent with its odontogenic origin. Histochemical staining showed PAS-positive and diastase-labile intracytoplasmic material consistent with glycogen. Conclusion: Our study highlights the potential diagnostic significance of dentinoid (although reportedly seen in only 7% of cases), along with CK5/6 immunopositivity, in supporting the histologic diagnosis of CCOC among a variety of neoplasia in its differential diagnosis.