bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant Arachnoid Granulations: Diagnostic Workup and Characterization in Three Symptomatic Adults
Authors: Mehta Rupal I. , Mangla Rajiv , Mehta Rashi I.
Published: July 2023

Giant arachnoid granulations (GAGs) are poorly investigated. Here, we document clinical findings associated with five new GAGs and illustrate the anatomical composition of these structures as well as diagnostic considerations in three symptomatic adults. The GAGs ranged from 1.1 to 3.6 cm (mean, 2.2 cm) in maximum dimension and manifested in middle-aged individuals who presented with long-standing brain mass and/or chronic headache. On imaging examinations, the tissues appeared as irregular parasagittal and/or perisinus structures that demonstrated heterogeneous internal elements. The GAGs abutted dura, extended through calvarial marrow spaces, and impinged on dural venous sinuses, causing their stenosis. The histologic workup of two GAG specimens resected from separate individuals revealed central collagen with pronounced internal vascular proliferation. One specimen additionally exhibited reactive changes within the lesion, including venous thrombosis, hemorrhage, and conspicuous inflammation. The salient immune component consisted of a foam cell-rich infiltrate that obstructed subcapsular and internal sinusoidal GAG spaces. Within this specimen, meningothelial hyperplasia was also appreciated. Notably, proliferated lymphatic vascular elements were additionally observed within the structure, extending into deep central collagen regions and engulfing many extravasated erythrocytes in the subcapsular space. In both surgically treated patients, symptoms resolved completely following resection. This report is the first to definitively depict reactive vascular and immunological changes within GAGs that were clinically associated with headache. The frequency of reactive changes within these meningeal structures is unclear in the literature, as GAGs are rarely sampled and investigated. Further systematic analyses are warranted to elucidate the causes and consequences of GAG genesis and their roles in physiology and disease states.
Assessment of Therapeutic Potential of a Dual AAV Approach for Duchenne Muscular Dystrophy
Authors: Albini Sonia , Palmieri Laura , Dubois Auriane , Bourg Nathalie , Lostal William , Richard Isabelle
Published: July 2023

Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic D2.B10-Dmdmdx/J (DBA2mdx) mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible Inverted Terminal Repeats (ITR)-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches.
Systematic Review, Meta-Analysis and Radiomics Quality Score Assessment of CT Radiomics-Based Models Predicting Tumor EGFR Mutation Status in Patients with Non-Small-Cell Lung Cancer
Authors: Felfli Mehdi , Liu Yan , Zerka Fadila , Voyton Charles , Thinnes Alexandre , Jacques Sebastien , Iannessi Antoine , Bodard Sylvain
Published: July 2023

Assessment of the quality and current performance of computed tomography (CT) radiomics-based models in predicting epidermal growth factor receptor (EGFR) mutation status in patients with non-small-cell lung carcinoma (NSCLC). Two medical literature databases were systematically searched, and articles presenting original studies on CT radiomics-based models for predicting EGFR mutation status were retrieved. Forest plots and related statistical tests were performed to summarize the model performance and inter-study heterogeneity. The methodological quality of the selected studies was assessed via the Radiomics Quality Score (RQS). The performance of the models was evaluated using the area under the curve (ROC AUC). The range of the Risk RQS across the selected articles varied from 11 to 24, indicating a notable heterogeneity in the quality and methodology of the included studies. The average score was 15.25, which accounted for 42.34% of the maximum possible score. The pooled Area Under the Curve (AUC) value was 0.801, indicating the accuracy of CT radiomics-based models in predicting the EGFR mutation status. CT radiomics-based models show promising results as non-invasive alternatives for predicting EGFR mutation status in NSCLC patients. However, the quality of the studies using CT radiomics-based models varies widely, and further harmonization and prospective validation are needed before the generalization of these models.
Novel Tools for Comprehensive Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants
Authors: Jasiecki Jacek , Targońska Monika , Janaszak-Jasiecka Anna , Chmara Magdalena , Żuk Monika , Kalinowski Leszek , Waleron Krzysztof , Wasąg Bartosz
Published: July 2023

Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused mainly by substitutions in the low-density lipoprotein receptor (LDLR) gene, leading to an increased risk of premature cardiovascular diseases. Tremendous advances in sequencing techniques have resulted in the discovery of more than 3000 variants of the LDLR gene, but not all of them are clinically relevant. Therefore, functional studies of selected variants are needed for their proper classification. Here, a single-cell, kinetic, fluorescent LDL uptake assay was applied for the functional analysis of LDLR variants in a model of an LDLR-deficient human cell line. An LDLR-defective HEK293T cell line was established via a CRISPR/Cas9-mediated luciferase–puromycin knock-in. The expressing vector with the LDLR gene under the control of the regulated promoter and with a reporter gene has been designed to overproduce LDLR variants in the host cell. Moreover, an LDLR promoter–luciferase knock-in reporter system has been created in the human cell line to study transcriptional regulation of the LDLR gene, which can serve as a simple tool for screening and testing new HMG CoA reductase-inhibiting drugs for atherosclerosis therapy. The data presented here demonstrate that the obtained LDLR-deficient human cell line HEK293T-ldlrG1 and the dedicated pTetRedLDLRwt expression vector are valuable tools for studying LDL internalization and functional analysis of LDLR and its genetic variants. Using appropriate equipment, LDL uptake to a single cell can be measured in real time. Moreover, the luciferase gene knock-in downstream of the LDLR promotor allows the study of promoter regulation in response to diverse conditions or drugs. An analysis of four known LDLR variants previously classified as pathogenic and benign was performed to validate the LDLR-expressing system described herein with the dedicated LDLR-deficient human cell line, HEK293T-ldlrG1.
A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
Authors: Varlamova Elena G. , Uspalenko Nina I. , Khmil Natalia V. , Shigaeva Maria I. , Stepanov Mikhail R. , Ananyan Mikhail A. , Timchenko Maria A. , Molchanov Maxim V. , Mironova Galina D. , Turovsky Egor A.
Published: July 2023

Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology and pharmacology. The cytoprotective action of taxifolin (TAX) in ischemia is well known, but its limitations are also known due to its poor solubility and low capacity to pass through the hematoencephalic barrier. Molecular mechanisms underlying the protective effect of TAX in complex systems such as the brain remain poorly understood. It is known that the main cell types of the brain are neurons, astrocytes, and microglia, which regulate the activity of each other through neuroglial interactions. In this work, a comparative study of cytoprotective mechanisms of the effect of TAX and its new water-soluble form aqua taxifolin (aqTAX) was performed on cultured brain cells under ischemia-like conditions (oxygen–glucose deprivation (OGD)) followed by the reoxygenation of the culture medium. The concentration dependences of the protective effects of both taxifolin forms were determined using fluorescence microscopy, PCR analysis, and vitality tests. It was found that TAX began to effectively inhibit necrosis and the late stages of apoptosis in the concentration range of 30–100 µg/mL, with aqTAX in the range of 10–30 µg/mL. At the level of gene expression, aqTAX affected a larger number of genes than TAX; enhanced the basic and OGD/R-induced expression of genes encoding ROS-scavenging proteins with a higher efficiency, as well as anti-inflammatory and antiapoptotic proteins; and lowered the level of excitatory glutamate receptors. As a result, aqTAX significantly inhibited the OGD-induced increase in the Ca2+ levels in the cytosol ([Ca2+]i) in neurons and astrocytes under ischemic conditions. After a 40 min preincubation of cells with aqTAX under hypoxic conditions, these Ca2+ signals were completely inhibited, resulting in an almost complete suppression of necrotic death of cerebral cortical cells, which was not observed with the use of classical TAX.
Genomic Instability Evolutionary Footprints on Human Health: Driving Forces or Side Effects?
Authors: Veschetti Laura , Treccani Mirko , De Tomi Elisa , Malerba Giovanni
Published: July 2023

In this work, we propose a comprehensive perspective on genomic instability comprising not only the accumulation of mutations but also telomeric shortening, epigenetic alterations and other mechanisms that could contribute to genomic information conservation or corruption. First, we present mechanisms playing a role in genomic instability across the kingdoms of life. Then, we explore the impact of genomic instability on the human being across its evolutionary history and on present-day human health, with a particular focus on aging and complex disorders. Finally, we discuss the role of non-coding RNAs, highlighting future approaches for a better living and an expanded healthy lifespan.
Equine Hoof Progenitor Cells Display Increased Mitochondrial Metabolism and Adaptive Potential to a Highly Pro-Inflammatory Microenvironment
Authors: Pielok Ariadna , Kępska Martyna , Steczkiewicz Zofia , Grobosz Sylwia , Bourebaba Lynda , Marycz Krzysztof
Published: July 2023

Medicinal signaling cells (MSC) exhibit distinct molecular signatures and biological abilities, depending on the type of tissue they originate from. Recently, we isolated and described a new population of stem cells residing in the coronary corium, equine hoof progenitor cells (HPCs), which could be a new promising cell pool for the treatment of laminitis. Therefore, this study aimed to compare native populations of HPCs to well-established adipose-derived stem cells (ASCs) in standard culture conditions and in a pro-inflammatory milieu to mimic a laminitis condition. ASCs and HPCs were either cultured in standard conditions or subjected to priming with a cytokines cocktail mixture. The cells were harvested and analyzed for expression of key markers for phenotype, mitochondrial metabolism, oxidative stress, apoptosis, and immunomodulation using RT-qPCR. The morphology and migration were assessed based on fluorescent staining. Microcapillary cytometry analyses were performed to assess the distribution in the cell cycle, mitochondrial membrane potential, and oxidative stress. Native HPCs exhibited a similar morphology to ASCs, but a different phenotype. The HPCs possessed lower migration capacity and distinct distribution across cell cycle phases. Native HPCs were characterized by different mitochondrial dynamics and oxidative stress levels. Under standard culture conditions, HPCs displayed different expression patterns of apoptotic and immunomodulatory markers than ASCs, as well as distinct miRNA expression. Interestingly, after priming with the cytokines cocktail mixture, HPCs exhibited different mitochondrial dynamics than ASCs; however, the apoptosis and immunomodulatory marker expression was similar in both populations. Native ASCs and HPCs exhibited different baseline expressions of markers involved in mitochondrial dynamics, the oxidative stress response, apoptosis and inflammation. When exposed to a pro-inflammatory microenvironment, ASCs and HPCs differed in the expression of mitochondrial condition markers and chosen miRNAs.
A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome
Authors: Iazzi Melissa , Sadeghi Sara , Gupta Gagan D.
Published: July 2023

The aim of this review article is to collate recent contributions of proteomic studies to cystic fibrosis transmembrane conductance regulator (CFTR) biology. We summarize advances from these studies and create an accessible resource for future CFTR proteomic efforts. We focus our attention on the CFTR interaction network at the cell surface, thus generating a CFTR ‘surfaceome’. We review the main findings about CFTR interactions and highlight several functional categories amongst these that could lead to the discovery of potential biomarkers and drug targets for CF.
miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients
Authors: Sanchez-Cabrero Darío , Garcia-Guede Álvaro , Burdiel Miranda , Pernía Olga , Colmenarejo-Fernandez Julián , Gutierrez Laura , Higuera Oliver , Rodriguez Isabel Esteban , Rosas-Alonso Rocío , Rodriguez-Antolín Carlos , Losantos-García Itsaso , Vera Olga , De Castro-Carpeño Javier , Ibanez de Caceres Inmaculada
Published: July 2023

Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.
A Microfluidic Approach for Synthesis of Silver Nanoparticles as a Potential Antimicrobial Agent in Alginate–Hyaluronic Acid-Based Wound Dressings
Authors: Bîrcă Alexandra Cătălina , Gherasim Oana , Niculescu Adelina-Gabriela , Grumezescu Alexandru Mihai , Neacșu Ionela Andreea , Chircov Cristina , Vasile Bogdan Ștefan , Oprea Ovidiu Cristian , Andronescu Ecaterina , Stan Miruna Silvia , Curuțiu Carmen , Dițu Lia Mara , Holban Alina Maria
Published: July 2023

The recognized antimicrobial activity of silver nanoparticles is a well-studied property, especially when designing and developing biomaterials with medical applications. As biological activity is closely related to the physicochemical characteristics of a material, aspects such as particle morphology and dimension should be considered. Microfluidic systems in continuous flow represent a promising method to control the size, shape, and size distribution of synthesized nanoparticles. Moreover, using microfluidics widens the synthesis options by creating and controlling parameters that are otherwise difficult to maintain in conventional batch procedures. This study used a microfluidic platform with a cross-shape design as an innovative method for synthesizing silver nanoparticles and varied the precursor concentration and the purging speed as experimental parameters. The compositional and microstructural characterization of the obtained samples was carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Four formulations of alginate-based hydrogels with the addition of hyaluronic acid and silver nanoparticles were obtained to highlight the antimicrobial activity of silver nanoparticles and the efficiency of such a composite in wound treatment. The porous structure, swelling capacity, and biological properties were evaluated through physicochemical analysis (FT-IR and SEM) and through contact with prokaryotic and eukaryotic cells. The results of the physicochemical and biological investigations revealed desirable characteristics for performant wound dressings (i.e., biocompatibility, appropriate porous structure, swelling rate, and degradation rate, ability to inhibit biofilm formation, and cell growth stimulation capacity), and the obtained materials are thus recommended for treating chronic and infected wounds.
Synthesis, In Vitro, and In Vivo Investigations of Pterostilbene-Tethered Analogues as Anti-Breast Cancer Candidates
Authors: Li Guoxun , Li Jian , Wang Wenqian , Feng Xiaoqing , Yu Xingkang , Yuan Shuo , Zhang Wei , Chen Jialing , Hu Caijuan
Published: July 2023

Pterostilbene has been found to be an active scaffold with anti-breast cancer (BC) action. In this study, fourteen pterostilbene-tethered analogues (2A–2N) were prepared and screened in vitro against MDA-MB-231 and MCF-7 cells. Meanwhile, their structures were characterized using 1H-NMR, 13C-NMR, and HRMS (ESI) spectroscopy techniques. Among them, analogue 2L displayed the most potent anti-proliferation effect on MDA-MB-231 (IC50 = 10.39 μM) and MCF-7 cells (IC50 = 11.73 μM). Furthermore, the meaningful structure–activity relationships suggested that the introduction of a saturated six-membered nitrogen heterocyclic ring into the side chain favored anti-BC capacity. Biological observations indicated that 2L could cause the typical morphological changes in apoptosis, namely an increase in reactive oxygen species level and a loss of mitochondrial membrane potential in BC cells. Importantly, 2L could induce mitochondrial-mediated apoptosis by regulating the expression of caspase-related proteins. Consistent with the results of our in vitro study, 2L apparently inhibited tumor growth in MDA-MB-231 xenograft mice without obvious toxicity. These findings revealed that 2L is expected to be a promising anti-BC lead compound that merits further investigations.
Addiction and Spending in Gacha Games
Authors: Lakić Nikola , Bernik Andrija , Čep Andrej
Published: July 2023

Gacha games are the most dominant games on the mobile market. These are free-to-play games with a lottery-like system, where the user pays with in-game currency to enter a draw in order to obtain the character or item they want. If a player does not obtain what he hoped for, there is the option of paying with his own money for more draws, and this is the main way to monetize the Gacha game. The purpose of this study is to show the playing and spending habits of Gacha players: the reasons they like such games, the reasons for spending, how much they spend, what they spend on, how long they have been spending, and whether they are aware of their spending. The paper includes studies by other researchers on various aspects of Gacha games as well. The aim of the paper is to conduct a study with the hypothesis that players who play the same game for a while and have a habit of playing it are willing to give more of their money to enter a draw. Therefore, two research questions and two hypotheses were analyzed. A total of 713 participants took part in the study.
A CNN-Based Method for Enhancing Boring Vibration with Time-Domain Convolution-Augmented Transformer
Authors: Zhang Huarong , Li Juhu , Cai Gaoyuan , Chen Zhibo , Zhang Haiyan
Published: July 2023

Recording vibration signals induced by larvae activity in the trunk has proven to be an efficient method for detecting trunk-boring insects. However, the accuracy of the detection is often limited because the signals collected in real-world environments are heavily disrupted by environmental noises. To deal with this problem, we propose a deep-learning-based model that enhances trunk-boring vibration signals, incorporating an attention mechanism to optimize its performance. The training data utilized in this research consist of the boring vibrations of Agrilus planipennis larvae recorded within trunk sections, as well as various environmental noises that are typical of the natural habitats of trees. We mixed them at different signal-to-noise ratios (SNRs) to simulate the realistically collected sounds. The SNR of the enhanced boring vibrations can reach up to 17.84 dB after being enhanced by our model, and this model can restore the details of the vibration signals remarkably. Consequently, our model’s enhancement procedure led to a significant increase in accuracy for VGG16, a commonly used classification model. All results demonstrate the effectiveness of our approach for enhancing the detection of larvae using boring vibration signals.
The Transformation of the Healthcare Business through the COVID-19 Pandemic (2020–2021)
Authors: Patel Rishi
Published: July 2023

The COVID-19 pandemic has had a marked impact on healthcare businesses since 2020. Healthcare organizations suffered greatly from financial stress coupled with disruptions in national and global supply chains. Healthcare workers and patients alike experienced significant downturns in their physical and mental health. Large government and legislative reforms were enacted to combat the progression of the pandemic. This paper explores these areas in detail in order to provide a clearer understanding of the successes and inadequacies that exist within the United States healthcare system as illuminated by the COVID-19 pandemic.
Correlation of Magnetomechanical Coupling and Damping in Fe80Si9B11 Metallic Glass Ribbons
Authors: Zhang Xu , Sun Yu , Yan Bin , Zhuang Xin
Published: July 2023

Understanding the correlation between magnetomechanical coupling factors (k) and damping factors (Q−1) is a key pathway toward enhancing the magnetomechanical power conversion efficiency in laminated magnetoelectric (ME) composites by manipulating the magnetic and mechanical properties of Fe-based amorphous metals through engineering. The k and Q−1 factors of FeSiB amorphous ribbons annealed in air at different temperatures are investigated. It is found that k and Q−1 factors are affected by both magnetic and elastic properties. The magnetic and elastic properties are characterized in terms of the magnetomechanical power efficiency for low-temperature annealing. The k and Q−1 of FeSiB-based epoxied laminates with different stacking numbers show that a −3 dB bandwidth and Young’s modulus are expressed in terms of the magnetomechanical power efficiency for high lamination stacking.
Effect of a 3.5% NaCl−10% HCl Corrosive Environment on the Fatigue Behavior of Hot Rolled Aluminum 5083-H111
Authors: Elhasslouk Masoud M. M. , Esen İsmail , Ahlatcı Hayrettin , Akın Bengu
Published: July 2023

This study deals with the microstructure of rolled Al5083-H111 materials, their hardness, corrosion in different solutions, and rotary bending fatigue properties of non-corroded and corroded samples in different solutions. This study is the first to report the fatigue behavior of corroded samples in different aggressive corrosion environments of Al5083. The microstructure of the Al5083-H111 material is in the form of grains oriented towards the rolling direction and it consists of binary Al-Mg, Al-Mn, and Mg-Si; ternary Al-Mg-Si; and quaternary Al-Mn-Fe-Si and Al-Cr-Mn precipitated randomly at the grain boundary. The Brinell hardness of the Al5083-H111 material is 68.67 HB. According to the results of the immersion corrosion, while the sample was more resistant to corrosion in a 3.5% NaCl environment, it showed a less resistant behavior in a 3.5% NaCl + 10% HCl environment. As a result of the fatigue test, it was observed that the sample that did not undergo corrosion showed a higher fatigue life than the samples that were exposed to corrosion. The fatigue rate of the 3.5% NaCl corrosion sample was 3.5 times lower than the fatigue rate of the 3.5% NaCl + 10% HCl corrosion sample.
Updates and Expert Opinions on Liver Transplantation for Gastrointestinal Malignancies
Authors: Shannon Alexander H. , Ruff Samantha M. , Schenk Austin D. , Washburn Kenneth , Pawlik Timothy M.
Published: July 2023

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) of the liver. Although there are established criteria for LT in HCC, evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.
Matrix Metalloproteinases and Heart Transplantation—A Pathophysiological and Clinical View
Authors: Patrichi Gabriela , Patrichi Andrei , Satala Catalin-Bogdan , Sin Anca Ileana
Published: July 2023

Heart transplantation is undergoing a continuous development, with rates of success increasing substantially due to advances in immunosuppressive therapy and surgical techniques. The most worrying complication occurring after cardiac transplantation is graft rejection, a phenomenon that is much affected by matrix metalloproteinases (MMPs), with the role of these proteases in the cardiac remodeling process being well established in the literature. A detailed investigation of the association between MMPs and cardiac rejection is necessary for the future development of more targeted therapies in transplanted patients, and to discover prognostic serum and immunohistochemical markers that will lead to more organized therapeutic management in these patients. The aim of this review is therefore to highlight the main MMPs relevant to cardiovascular pathology, with particular emphasis on those involved in complications related to heart transplantation, including cardiac graft rejection.
Essential Thrombocythemia and Ischemic Stroke: A Case Series of Five JAK2-Positive Patients
Authors: Kim Byong-Kyu , Eah Kyung Yoon , Park Jin-Mo
Published: July 2023

Background and Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Materials and Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.
Made in the Womb: Maternal Programming of Offspring Cardiovascular Function by an Obesogenic Womb
Authors: Diniz Mariana S. , Grilo Luís F. , Tocantins Carolina , Falcão-Pires Inês , Pereira Susana P.
Published: July 2023

Obesity incidence has been increasing at an alarming rate, especially in women of reproductive age. It is estimated that 50% of pregnancies occur in overweight or obese women. It has been described that maternal obesity (MO) predisposes the offspring to an increased risk of developing many chronic diseases in an early stage of life, including obesity, type 2 diabetes, and cardiovascular disease (CVD). CVD is the main cause of death worldwide among men and women, and it is manifested in a sex-divergent way. Maternal nutrition and MO during gestation could prompt CVD development in the offspring through adaptations of the offspring’s cardiovascular system in the womb, including cardiac epigenetic and persistent metabolic programming of signaling pathways and modulation of mitochondrial metabolic function. Currently, despite diet supplementation, effective therapeutical solutions to prevent the deleterious cardiac offspring function programming by an obesogenic womb are lacking. In this review, we discuss the mechanisms by which an obesogenic intrauterine environment could program the offspring’s cardiovascular metabolism in a sex-divergent way, with a special focus on cardiac mitochondrial function, and debate possible strategies to implement during MO pregnancy that could ameliorate, revert, or even prevent deleterious effects of MO on the offspring’s cardiovascular system. The impact of maternal physical exercise during an obesogenic pregnancy, nutritional interventions, and supplementation on offspring’s cardiac metabolism are discussed, highlighting changes that may be favorable to MO offspring’s cardiovascular health, which might result in the attenuation or even prevention of the development of CVD in MO offspring. The objectives of this manuscript are to comprehensively examine the various aspects of MO during pregnancy and explore the underlying mechanisms that contribute to an increased CVD risk in the offspring. We review the current literature on MO and its impact on the offspring’s cardiometabolic health. Furthermore, we discuss the potential long-term consequences for the offspring. Understanding the multifaceted effects of MO on the offspring’s health is crucial for healthcare providers, researchers, and policymakers to develop effective strategies for prevention and intervention to improve care.
Organized Computational Measurement to Design a High-Performance Muffler
Authors: Saadabadi Mehran , Samimi Mahdieh , Hosseinlaghab Hassan
Published: July 2023

Engine noise, as a source of sound pollution for humans and the environment, can be reduced by designing a high-performance muffler. This study presents a novel, organized design process of that muffler for the KTM390 engine as a case study. The acoustic simulation analysis is performed in COMSOL software and aerodynamic analysis is performed in ANSYS Fluent. The features of the muffler considered in this designing process are the overall length of the muffler, the presence of baffles and related parameters (baffle distance, baffle hole diameter, and baffle hole offset), and the effects of extended tubes. In order to evaluate the acoustic performance of the muffler, an objective function has been defined and measured on two frequency ranges, 75–300 Hz and 300–1500 Hz. For evaluating the aerodynamic performance of that, the amount of backpressure is analyzed to achieve a maximum of 3.3 kilopascals for this muffler. The selection of the appropriate parameters includes comparing the resulting transmission loss curves and quantitative evaluation of objective functions (for transmission loss) and backpressure. This organized design process (i.e., tree diagram) leads to an increase in the efficiency of designing mufflers (for example, 41.2% improvement on backpressure).
A Free-Standing Chitosan Membrane Prepared by the Vibration-Assisted Solvent Casting Method
Authors: Cigane Urte , Palevicius Arvydas , Janusas Giedrius
Published: July 2023

Much attention has been paid to the surface modification of artificial skin barriers for the treatment of skin tissue damage. Chitosan is one of the natural materials that could be characterized by its biocompatibility. A number of methods for the preparation of chitosan membranes have been described in scientific articles, including solvent casting methods. This study investigates an improved technology to produce chitosan membranes. Thus, chitosan membranes were prepared using a vibration-assisted solvent casting method. First, aqueous acetic acid was used to pretreat chitosan. Then, free-standing chitosan membranes were prepared by solvent casting on nanoporous anodized aluminum oxide (AAO) membrane templates, allowing for the solvent to evaporate. Using finite element methods, a study was obtained showing the influence of chitosan solutions of different concentrations on the fluid flow into nanopores using high-frequency excitation. The height of the nanopillars and the surface area of the chitosan membrane were also evaluated. In this study, the surface area of the chitosan membrane was found to increase by 15, 10 and 6 times compared to the original flat surface area. The newly produced nanopillared chitosan membranes will be applicable in the fabrication of skin barriers due to the longer nanopillars on their surface and the larger surface area.
Oxyfluorides of Rare-Earth Elements in the Rocks of the Shatak Formation (Southern Urals)
Authors: Kovalev Sergey G. , Kovalev Sergey S. , Sharipova Aysylu A.
Published: July 2023

The Shatak Formation, comprising a part of the Mashak Suite (RF2), is located on the western slope of the Southern Urals. It consists of various rock types, including sedimentary rocks, such as conglomerates, polymictic sandstones, aleurolites, and carbonaceous clayey shales, as well as igneous rocks, including picrites, basalts, dacites, rhyodacites, and rhyolites, and volcanogenic–sedimentary rocks, such as tuffs and tuff breccias. In this article, oxyfluoride (La, Ce) (OnFm)3 mineralization, occurring in the contact zone between the metabasalts and quartz sandstones, is described for the first time in the literature. This is represented by compounds of variable compositions forming an isomorphic series: trifluoride, (La, Ce)F3–oxyfluoride, (La, Ce)OF–oxide, and (La, Ce)2O3. By analyzing several binary phase diagrams, significant coordination between oxygen, fluorine, and cerium in the chemical composition of oxyfluorides has been highlighted. However, the behavior of lanthanum has been shown to exhibit some irregularity. The genesis of oxyfluoride mineralization is attributed to the regional metamorphism of rocks within the Shatak Formation. During the hydrothermal process, the decomposition of fluorapatite, which is unstable during both hydrothermal metamorphism and supergene processes, resulted in the release of fluorine, as well as potentially lanthanum and cerium. Variations in the chemical composition of oxyfluorides, which are formed in the presence of an excess of oxygen resulting from water dissociation, are determined by local differences in the content of the main components within the forming microfractures.
Paleoproterozoic U Mineralization in Huayangchuan Deposit, Xiaoqinling Area: Evidence from the U–Rich Granitic Pegmatite
Authors: Li Putao , Li Yongjun , Gu Pingyang , He Shiping , Zhuang Yujun , Chen Ruiming
Published: July 2023

The Huayangchuan uranium deposit, located in the west of the Xiaoqinling belt on the southern margin of the North China Craton, is a large U–Nb–Pb deposit accompanied with rare–earth elements. The Huayangchuan uranium deposit, discovered in the 1950s, has long been known as a carbonatite–type uranium deposit. Recently, new geological work has found uranium mineralization in many granitic pegmatite veins in the Huayangchuan deposit and adjacent areas. Here, we report a systematic investigation of the petrography, whole–rock geochemistry, zircon U–Pb ages, and in situ Lu–Hf isotopic characteristics of newly discovered U–rich granitic pegmatite veins in the west of Huayangchuan deposit. The petrological results showed that the lithology of the samples is granite pegmatite. The U–Pb ages of zircon were 1826.3 ± 7.9 and 1829 ± 11 Ma. Microscopically, the paragenetic characteristics of zircon, betafite, and uraninite exist in the intergranular fissures of K–feldspar and quartz, reflecting metallogenic phenomena in the rock formation process. Almost all whole–rock samples were rich in SiO2 (64.37−70.69 wt.%), total alkalis (K2O + Na2O = 8.50–10.30 wt.%), and Al2O3 (12.20–14.41 wt.%) but poor in TiO2 (0.23–0.73 wt.%), MgO (0.38–0.90 wt.%), CaO (1.23–2.22 wt.%), P2O5 (0.14–0.83 wt.%), and MnO (0.04–0.57 wt.%). Additionally, they showed enrichment of LILEs (such as Rb, Ba, Th, U, and K), depletion of HFSEs (such as Ta, P, Ti, and Hf), and no alkaline dark minerals, and the characteristics are intraplate A1–type granite. The A1–type granite displayed low zircon εHf(t) values (−19.42–−15.02) with zircon two–stage Hf model aged 3.10–2.76 Ga, indicating that the U–rich granitic pegmatite was derived predominantly from partial melting of the ancient continental crust (such as the early Taihua group formed in Archean–Neoarchean). Combined with the above results and regional geological data, the U–rich granitic pegmatite discovered in the Huayangchuan deposit was formed in a post–collisional regime after the Luliang movement in the late Paleoproterozoic. This study suggests that future uranium prospecting work in this area should focus on late Paleoproterozoic U–rich granitic pegmatites.
Estimation of Carbon Content in High-Ash Coal Using Mid-Infrared Fourier-Transform Infrared Spectroscopy
Authors: Mishra Sameeksha , Prasad Anup Krishna , Shukla Anubhav , Vinod Arya , Preety Kumari , Varma Atul Kumar
Published: July 2023

The carbon content of different types of coal determines its utility in industries and thermal power generation. The most popular and widely used is the conventional method (ultimate analysis) to determine coal’s carbon content (C, wt.%), along with H, N, and S. In the present study, the authors attempted to analyze the carbon content (C in %) in coals via data from Fourier-transform infrared (FTIR) spectroscopy, which can be a promising alternative. As a reference, the carbon content in the coal samples, referred to as CCHNS (in wt.%), was determined from the ultimate analysis. The mid-infrared FTIR spectroscopic data were used to investigate the response of functional groups associated with carbon or its compounds, which were used to model and estimate the carbon content in coal samples (referred to as CFTIR, in wt.%). FTIR spectral signatures were utilized in specific zones (between wavenumbers 4000 and 400 cm−1) from a total of 18 coal samples from the Johilla coalfield, Umaria district, Madhya Pradesh, India. These 18 coal samples were used to produce 126 Coal+KBr pellets (at seven known dilution factors for each coal sample), and the spectral response (absorbance) from each pellet was recorded. For model development and validation, the training set and test set were formed using a 17:1 split (K-fold cross validation). The carbon content in the coal samples was modeled using the training set data by applying the piecewise linear regression method employing quasi-Newton (QN) with a breakpoint and least squares loss function. The model was validated using an independent test set. A pairwise comparison of estimates of carbon in the laboratory from the CHNS analyzer (CCHNS) and modeled carbon from FTIR data (CFTIR) exhibited a good correlation, relatively low error, and bias (coefficient of determination (R2) up to 0.93, RMSE of 23.71%, and MBE of −0.52%). Further, the significance tests for the mean and variance using the two-tailed t-test and F-test showed that no significant difference occurred between the pair of observed CCHNS and the model’s estimated CFTIR. For high-ash coals from the Johilla coalfield, the model presented here using mid-infrared FTIR spectroscopy data performs well. Thus, FTIR can potentially serve as an important method for quickly determining the carbon content of high-ash coals from various basins and can potentially be extended to soil and shale samples.
Computational Modeling of Human Serum Albumin Binding of Per- and Polyfluoroalkyl Substances Employing QSAR, Read-Across, and Docking
Authors: Gallagher Andrea , Kar Supratik , Sepúlveda Maria S.
Published: July 2023

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals in widespread use that have been shown to be toxic to wildlife and humans. Human serum albumin (HSA) is a known transport protein that binds PFAS at various sites, leading to bioaccumulation and long-term toxicity. In silico tools like quantitative structure-activity relationship (QSAR), read-across, and quantitative read-across structure-property relationship (q-RASPR) are proven techniques for modeling chemical toxicity based on experimental data which can be used to predict the toxicity of untested and new chemicals, while at the same time, help to identify the major features responsible for toxicity. Classification-based and regression-based QSAR models are employed in the present study to predict the binding affinities of 24 PFAS to HSA. Regression-based QSAR models revealed that the packing density index (PDI) and quantitative estimation of drug-likeness (QED) descriptors were both positively correlated with higher binding affinity, while the classification-based QSAR model showed the average connectivity index of order 4 (X4A) descriptor was inversely correlated with binding affinity. Whereas molecular docking studies suggested that PFAS with the highest binding affinity to HSA create hydrogen bonds with Arg348 and salt bridges with Arg348 and Arg485, PFAS with lower binding affinity either showed no interactions with either amino acid or only interactions with Arg348. Among the studied PFAS, perfluoroalkyl acids (PFAA) with large carbon chain length (>C10) have one of the lowest binding affinities, compared to PFAA with carbon chain length ranging from 7 to 9, which showed the highest affinity to HSA. Generalized Read-Across (GenRA) was used to predict toxicity outcomes for the top five highest binding affinity PFAS based on 10 structural analogs for each and found that all are predicted as being chronic to sub-chronically toxic to HSA. The developed in silico models presented in this work can provide a framework for designing PFAS alternatives, screening compounds currently in use, and for the study of PFAS mixture toxicity, which is an area of intense research.
New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies
Authors: Ahmad Saghir , Abdul Qadir Muhammad , Ahmed Mahmood , Imran Muhammad , Yousaf Numan , Wani Tanveer A. , Zargar Seema , Ali Ijaz , Muddassar Muhammad
Published: July 2023

The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide–sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.
1,8-Dihydroxy Naphthalene—A New Building Block for the Self-Assembly with Boronic Acids and 4,4′-Bipyridine to Stable Host–Guest Complexes with Aromatic Hydrocarbons
Authors: Manankandayalage Chamila P. , Unruh Daniel K. , Perry Ryan , Krempner Clemens
Published: July 2023

The new Lewis acid–base adducts of general formula X(nad)B←NC5H4-C5H4N→B(nad)X [nad = 1,8-O2C10H6, X = C6H5 (2c), 3,4,5-F3-C6H2 (2d)] were synthesized in high yields via reactions of 1,8-dihydroxy naphthalene [nadH2] and 4,4′-bipyridine with the aryl boronic acids C6H5B(OH)2 and 3,4,5-F3-C6H2B(OH)2, respectively, and structurally characterized by multi-nuclear NMR spectroscopy and SCXRD. Self-assembled H-shaped Lewis acid–base adduct 2d proved to be effective in forming thermally stable host–guest complexes, 2d × solvent, with aromatic hydrocarbon solvents such as benzene, toluene, mesitylene, aniline, and m-, p-, and o-xylene. Crystallographic analysis of these solvent adducts revealed host–guest interactions to primarily occur via π···π contacts between the 4,4′-bipyridyl linker and the aromatic solvents, resulting in the formation of 1:1 and 1:2 host–guest complexes. Thermogravimetric analysis of the isolated complexes 2d × solvent revealed their high thermal stability with peak temperatures associated with the loss of solvent ranging from 122 to 147 °C. 2d, when self-assembled in an equimolar mixture of m-, p-, and o-xylene (1:1:1), preferentially binds to o-xylene. Collectively, these results demonstrate the ability of 1,8-dihydroxy naphthalene to serve as an effective building block in the selective self-assembly to supramolecular aggregates through dative covalent N→B bonds.