bluuebunny/crossref_metadata_2025 huggingface dataset:
Germline and somatic drivers in inherited hematologic malignancies
Authors: Zoller Julian , Trajanova Despina , Feurstein Simone
Published: October 2023

Inherited hematologic malignancies are linked to a heterogenous group of genes, knowledge of which is rapidly expanding using panel-based next-generation sequencing (NGS) or whole-exome/whole-genome sequencing. Importantly, the penetrance for these syndromes is incomplete, and disease development, progression or transformation has critical clinical implications. With the earlier detection of healthy carriers and sequential monitoring of these patients, clonal hematopoiesis and somatic driver variants become significant factors in determining disease transformation/progression and timing of (preemptive) hematopoietic stem cell transplant in these patients. In this review, we shed light on the detection of probable germline predisposition alleles based on diagnostic/prognostic ‘somatic’ NGS panels. A multi-tier approach including variant allele frequency, bi-allelic inactivation, persistence of a variant upon clinical remission and mutational burden can indicate variants with high pre-test probability. We also discuss the shared underlying biology and frequency of germline and somatic variants affecting the same gene, specifically focusing on variants in DDX41, ETV6, GATA2 and RUNX1. Germline variants in these genes are associated with a (specific) pattern or over-/underrepresentation of somatic molecular or cytogenetic alterations that may help identify the underlying germline syndrome and predict the course of disease in these individuals. This review is based on the current knowledge about somatic drivers in these four syndromes by integrating data from all published patients, thereby providing clinicians with valuable and concise information.
Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study ‘NoVis’
Authors: Aulenkamp Jana Luisa , Icenhour Adriane , Elsenbruch Sigrid
Published: October 2023

The role of psychological factors in the pathophysiology and treatment of chronic visceral pain in disorders of gut-brain interactions (DGBI) is increasingly appreciated. Placebo research has underscored that expectations arising from the psychosocial treatment context and from prior experiences shape treatment responses. However, effects of negative expectations, i.e., nocebo effects, as they are likely crucial elements of DGBI patients’ clinical reality, have thus far only rarely been investigated in the context of visceral pain, with untapped potential for improved prevention and treatment. The experimental randomized-controlled pain study “NoVis,” carried out within the Collaborative Research Center (CRC) 289 (“Treatment Expectation”), aims to close gaps regarding the generation and persistence of nocebo effects in healthy volunteers. It is designed to elucidate effects of negative expectations in a multiple-threat paradigm with intensity-matched rectal distensions and cutaneous thermal stimuli, allowing to test nocebo effects in the visceral and somatic pain modalities. Negative expectations are experimentally induced by elements of doctor-patient communication (i.e., instruction) and/or by surreptitious amplification of symptom intensity (i.e., experience/learning) within a treatment context. Accordingly, the repeated measures between-subject design contains the between-group factors “treatment instruction” (negative vs. control) and “treatment experience” (negative vs. control), with volunteers randomized into four experimental groups undergoing several pain stimulation phases (repeated factor). This allows to compare the efficacy of instruction vs. experience, and more importantly, their combined effects on the magnitude of negative expectations and their impact on pain responses, which we expect will be greatest for the visceral modality. After a Baseline, short-term effects are assessed during a test phase accomplished on study day 1 (Test-1 Phase). To explore the persistence of effects, a second test phase is accomplished 1 week later (Test-2 Phase). Effects of negative expectations within and across pain modalities are assessed at the subjective and objective levels, with a focus on psychophysiological and neuroendocrine measures related to stress, fear, and anxiety. Since nocebo effects can play a considerable role in the generation, maintenance, or worsening of chronic visceral pain, and may even constitute risk factors for treatment failure, knowledge from experimental nocebo research has potential to improve treatment outcomes in DGBI and other clinical conditions associated with chronic visceral pain.
Substrate and fertigation management modulate microgreens production, quality and resource efficiency
Authors: Paglialunga Gabriele , El Nakhel Christophe , Proietti Simona , Moscatello Stefano , Battistelli Alberto , Formisano Luigi , Ciriello Michele , Del Bianco Marta , De Pascale Stefania , Rouphael Youssef
Published: October 2023

Long-term space missions will require a self-sustaining food production system to meet the crew’s nutritional and health needs. For this purpose, plant-based food production systems with elevated resource efficiency are required, based on advanced agricultural technologies that produce phytonutrient-rich crops. In addition to the resource requirements for crop production on Earth, volume and time efficiency become essential factors to consider for food production in space. Microgreens represent a promising candidate for space farming as they have a high harvest index, short cultivation cycle, and high nutritional potential. However, the development of specific technical protocols for growing microgreens in space is essential since different agronomic inputs, such as substrates and fertigation, can modulate productivity, quality and resource efficiency of microgreens cultivation. The current work examines the effects of different substrates (coconut fiber and cellulose sponge) and nutrient solution (NS) management strategies (quarter strength Hoagland and half strength Hoagland/osmotic water) on the production of two species of microgreens [Raphanus sativus cv. Saxa 2 (Radish); Brassica oleracea var. capitata f. sabauda cv. Vertus (Savoy cabbage)]. The appraisal focused on (i) biomass production and quality, and (ii) sizing of space facilities devoted to the production of phytonutrients required for the astronauts’ wellbeing. In our study, the interaction among species, substrate and NS significantly affected the accumulation of fructose, sucrose, total soluble non-structural carbohydrates and nitrate as well as the daily production of total ascorbic acid and, in turn, the required microgreens serving to supply its adequate daily intake. Species-substrate interaction effects on fresh yield, dry yield, dry matter, anthocyanins, TPC, β-carotene and sulfate content as well as the cultivation surface required to produce the adequate daily intake of ascorbic acid (AscA) were assessed. Substrate-NS interaction modulated the anthocyanins, violaxanthin and sulfate contents independently of species. On the other hand, single factor effects were identified with respect to the accumulation of lutein, chlorophylls, glucose, and starch. Therefore, the management of microgreens cultivation in terms of NS and substrate is an effective tool to meet the phytochemical requirements of the crew.
The Role of the Duffy Blood Group Antigens in Renal Transplantation and Rejection. A Mini Review
Authors: Hariri Dana , Bordas Jozsef , Elkins Matthew , Gallay Brian , Spektor Zhanna , Hod-Dvorai Reut
Published: October 2023

Finding a compatible donor for kidney transplant candidates requires overcoming immunological barriers such as human leukocyte antigens (HLA) compatibility and ABO compatibility. Emerging data suggest a role for red blood cell antigens (RCA) in renal transplant outcomes. The incidence of RCA alloimmunization is high in chronically transfused individuals, such as end stage renal disease patients, but whether antibodies to RCA can mediate renal graft rejection remains debatable. The Duffy blood group antigens (Fy) has been shown to be expressed in the kidney, among other tissues. There are some data to suggest that donor-recipient Fy mismatches may increase the risk for chronic allograft damage and that anti-Fy antibodies may be involved in renal graft rejection, however, while it is routine to screen renal transplant candidates for ABO antigens, detailed RCA phenotyping of the donor kidney is not routinely tested. In this paper, we review the current data on the role of Fy in renal transplantation and discuss the potential mechanisms of its biological function.
Non-Invasive Mapping of the Neuronal Networks of Language
Authors: Papanicolaou Andrew C.
Published: October 2023

This review consists of three main sections. In the first, the Introduction, the main theories of the neuronal mediation of linguistic operations, derived mostly from studies of the effects of focal lesions on linguistic performance, are summarized. These models furnish the conceptual framework on which the design of subsequent functional neuroimaging investigations is based. In the second section, the methods of functional neuroimaging, especially those of functional Magnetic Resonance Imaging (fMRI) and of Magnetoencephalography (MEG), are detailed along with the specific activation tasks employed in presurgical functional mapping. The reliability of these non-invasive methods and their validity, judged against the results of the invasive methods, namely, the “Wada” procedure and Cortical Stimulation Mapping (CSM), is assessed and their use in presurgical mapping is justified. In the third and final section, the applications of fMRI and MEG in basic research are surveyed in the following six sub-sections, each dealing with the assessment of the neuronal networks for (1) the acoustic and phonological, (2) for semantic, (3) for syntactic, (4) for prosodic operations, (5) for sign language and (6) for the operations of reading and the mechanisms of dyslexia.
DNA Double-Strand Break Response and Repair Gene Polymorphisms May Influence Therapy Results and Prognosis in Head and Neck Cancer Patients
Authors: Butkiewicz Dorota , Krześniak Małgorzata , Gdowicz-Kłosok Agnieszka , Składowski Krzysztof , Rutkowski Tomasz
Published: October 2023

Radiotherapy and cisplatin-based chemotherapy belong to the main treatment modalities for head and neck squamous cell carcinoma (HNSCC) and induce cancer cell death by generating DNA damage, including the most severe double-strand breaks (DSBs). Alterations in DSB response and repair genes may affect individual DNA repair capacity and treatment sensitivity, contributing to the therapy resistance and poor prognosis often observed in HNSCC. In this study, we investigated the association of a panel of single-nucleotide polymorphisms (SNPs) in 20 DSB signaling and repair genes with therapy results and prognosis in 505 HNSCC patients treated non-surgically with DNA damage-inducing therapies. In the multivariate analysis, there were a total of 14 variants associated with overall, locoregional recurrence-free or metastasis-free survival. Moreover, we identified 10 of these SNPs as independent predictors of therapy failure and unfavorable prognosis in the whole group or in two treatment subgroups. These were MRE11 rs2155209, XRCC5 rs828907, RAD51 rs1801321, rs12593359, LIG4 rs1805388, CHEK1 rs558351, TP53 rs1042522, ATM rs1801516, XRCC6 rs2267437 and NBN rs2735383. Only CHEK1 rs558351 remained statistically significant after correcting for multiple testing. These results suggest that specific germline variants related to DSB response and repair may be potential genetic modifiers of therapy effects and disease progression in HNSCC treated with radiotherapy and cisplatin-based chemoradiation.
Influence of MRI Follow-Up on Treatment Decisions during Standard Concomitant and Adjuvant Chemotherapy in Patients with Glioblastoma: Is Less More?
Authors: van Dijken Bart R. J. , Doff Annerieke R. , Enting Roelien H. , van Laar Peter Jan , Jeltema Hanne-Rinck , Dierckx Rudi A. J. O. , van der Hoorn Anouk
Published: October 2023

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2–3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty (p = 0.021) but did not influence treatment consequences (p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.
Heterogeneity in the Metastatic Microenvironment: JunB-Expressing Microglia Cells as Potential Drivers of Melanoma Brain Metastasis Progression
Authors: Adir Orit , Sagi-Assif Orit , Meshel Tsipi , Ben-Menachem Shlomit , Pasmanik-Chor Metsada , Hoon Dave S. B. , Witz Isaac P. , Izraely Sivan
Published: October 2023

Reciprocal signaling between melanoma brain metastatic (MBM) cells and microglia reprograms the phenotype of both interaction partners, including upregulation of the transcription factor JunB in microglia. Here, we aimed to elucidate the impact of microglial JunB upregulation on MBM progression. For molecular profiling, we employed RNA-seq and reverse-phase protein array (RPPA). To test microglial JunB functions, we generated microglia variants stably overexpressing JunB (JunBhi) or with downregulated levels of JunB (JunBlo). Melanoma-derived factors, namely leukemia inhibitory factor (LIF), controlled JunB upregulation through Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling. The expression levels of JunB in melanoma-associated microglia were heterogeneous. Flow cytometry analysis revealed the existence of basal-level JunB-expressing microglia alongside microglia highly expressing JunB. Proteomic profiling revealed a differential protein expression in JunBhi and JunBlo cells, namely the expression of microglia activation markers Iba-1 and CD150, and the immunosuppressive molecules SOCS3 and PD-L1. Functionally, JunBhi microglia displayed decreased migratory capacity and phagocytic activity. JunBlo microglia reduced melanoma proliferation and migration, while JunBhi microglia preserved the ability of melanoma cells to proliferate in three-dimensional co-cultures, that was abrogated by targeting leukemia inhibitory factor receptor (LIFR) in control microglia–melanoma spheroids. Altogether, these data highlight a melanoma-mediated heterogenous effect on microglial JunB expression, dictating the nature of their functional involvement in MBM progression. Targeting microglia highly expressing JunB may potentially be utilized for MBM theranostics.
Poor Cervical Cancer Knowledge and Awareness among Women and Men in the Eastern Cape Province Rural Community
Authors: Mbulawa Zizipho Z. A. , Mahlangu Lindelo L. , Makhabane Esihle , Mavivane Sisanda , Nongcula Sindisiwe , Phafa Anathi , Sihlobo Ayabonga , Zide Mbalentle , Mkiva Athenkosi , Ngobe Thembeka N. , Njenge Luxolo , Kwake Phumla , Businge Charles B.
Published: October 2023

Cervical cancer knowledge and awareness is low among South Africans despite high cervical cancer prevalence. This study aimed to investigate knowledge about the symptoms, signs, risk factors, and methods of prevention of cervical cancer among women and men in the rural Eastern Cape province, South Africa. This cross-sectional analytical study was conducted in the rural community of the OR Tambo municipality in the Eastern Cape province. 252 women and men aged ≥ 25 years were randomly recruited. Data were collected using semi-structured questionnaires. A knowledge score was categorized as “good” if it was ≥65%. The majority of participants (69.8%) were women. Only a proportion of 25.6% (51/199) of the participants had good overall knowledge about cervical cancer, and the majority of these (84.3%) were women. Women previously screened for cervical cancer had a significantly higher median cervical knowledge score than those who had never been screened (p = 0.002). Only among women, good knowledge about cervical cancer was associated with a tertiary education level (OR: 3.17, 95% CI: 1.08–9.57, p = 0.044) and high household income (OR: 3.40, 95% CI: 1.24–9.75, p = 0.027). Both women and men in rural Eastern Cape had limited knowledge about the risk factors and prevention methods of cervical cancer. Public health strategies to improve knowledge and awareness of cervical cancer among both men and women are necessary.
In Situ Observation of Bubbles and the Effect of Ultrasonic Vibration on Bubble Behavior in EDM
Authors: Wang Chenxue , Sasaki Tomohiro , Hirao Atsutoshi
Published: October 2023

Accumulation and concentration of debris in deep hole electrical discharge machining (EDM) significantly hinder its machining efficiency and accuracy. It is believed that the movement of bubbles associated with the discharge gap flow field play a pivotal role in debris removal and influence the discharge conditions. Ultrasonic vibration (USV) of the electrode is thought to be an effective method for improving EDM-generated bubbles and debris exclusion. In this study, we first elucidated the behavior of bubbles during EDM of holes with varying aspect ratios. Subsequently, USV was introduced to EDM. The behavior of dielectric fluid flow under the influence of ultrasonic vibration was analyzed using computational fluid dynamics (CFD), which revealed time-varying changes in discharge gap flow pressure and velocity. The velocity of the dielectric flow field near the electrode’s side face was found to reach a maximum of approximately 15.2 m/s, greatly facilitating debris removal. High-speed camera observations revealed that bubbles were dispersed within the side gap, with most of them adhering to the electrode’s wall. Furthermore, the bubbles exhibited a tendency to continuously break up and coalesce near the hole’s outlet before escaping in the USV-assisted EDM. These observed characteristics of bubble behavior under the influence of USV are expected to significantly enhance debris removal and promote efficient dielectric exchange.
Characterization of the Metal Fused Filament Fabrication Process for Manufacturing of Pure Copper Inductors
Authors: Schüßler Philipp , Franke Jonas , Czink Steffen , Antusch Steffen , Mayer Daniel , Laube Stephan , Hanemann Thomas , Schulze Volker , Dietrich Stefan
Published: October 2023

This work presents a comprehensive investigation into the optimization of critical process parameters associated with metal fused filament fabrication (Metal-FFF) for the production of copper-based components. The study focused on three different commercial and one self-manufactured filament, each with unique chemical compositions. These filaments were systematically optimized and the density was characterized for all processing steps, as well as the electrical conductivity on the specimen scale. Remarkably, two of the studied filaments exhibited exceptional properties after sintering with forming gas (up to 94% density and 55.75 MS/m electrical conductivity), approaching the properties measured for established manufacturing methods like metal injection molding. Finally, the research was extended to component-scale applications, demonstrating the successful fabrication of inductors with integrated cooling channels. These components exhibited water tightness and were used in induction hardening experiments, validating the practical utility of the optimized Metal-FFF process. In summary, the results show great promise in advancing the utilization of Metal-FFF in industrial contexts, particularly in the production of high-performance copper components.
Metal Complexes in the Synthesis of Biodegradable Polymers: Achievements and Prospects
Authors: Mankaev Badma N. , Karlov Sergey S.
Published: October 2023

This review describes recent advances in the synthesis of homopolymers of lactide and related cyclic esters via ring-opening polymerization (ROP) in the presence of metal complexes based on group 1, 2, 4, 12, 13 and 14 metals. Particular attention is paid to the influence of the initiator structure on the properties of the obtaining homo- and copolymers. Also, a separate chapter is devoted to the study of metal complexes in the synthesis of copolymers of lactide and lactones. This review highlights the efforts made over the last ten years or so, and shows how main-group metals have received increasing attention in the field of the polymerization of lactide and related cyclic esters.
Lower Intakes of Key Nutrients Are Associated with More School and Workplace Absenteeism in US Children and Adults: A Cross-Sectional Study of NHANES 2003–2008
Authors: Ye Qian , Devarshi Prasad P. , Grant Ryan W. , Higgins Kelly A. , Mitmesser Susan H.
Published: October 2023

The influence of individual macro- and micronutrients on absenteeism in the United States is largely unknown. The objective of this study was to determine whether nutritional status or nutrient intake were associated with absenteeism from school and work due to illness or injury. Data from NHANES 2003–2008 were used to assess nutrient intake from food and food plus supplements, nutritional biomarker levels, and school and work absenteeism per year in children and adults. Negative binomial regression models were used to predict mean days of missed work per year and to estimate incidence rate ratios (IRRs) of absenteeism by nutrient biomarker status. Of 7429 children, 77% reported missing school days (mean 4.0 days). Of 8252 adults, 51% reported missing work days (mean 4.9 days). Children and adults who reported more absent days had a significantly lower intake of protein and several essential micronutrients from the diet. When nutrients from supplements were included, this negative association was retained for protein, selenium, choline, and DHA in children and for protein, selenium, vitamin K, choline, potassium, fiber, octadecatrienoic acid, and lycopene in adults. Future studies are needed to ascertain whether dietary interventions, such as access to healthier food options and/or dietary supplements, can reduce absenteeism.
Regulation of Tumor Apoptosis of Poriae cutis-Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways In Vitro
Authors: Yue Shuai , Feng Xi , Cai Yousheng , Ibrahim Salam A. , Liu Ying , Huang Wen
Published: October 2023

Poria cocos is traditionally used as both food and medicine. Triterpenoids in Poria cocos have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased (p < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.
Taming Postoperative Delirium with Dexmedetomidine: A Review of the Therapeutic Agent’s Neuroprotective Effects following Surgery
Authors: Bargnes Vincent , Oliver Brian , Wang Emily , Greenspan Seth , Jin Zhaosheng , Yeung Isaac , Bergese Sergio
Published: October 2023

Postoperative delirium (POD) represents a perioperative neurocognitive disorder that has dreaded ramifications on a patient’s recovery from surgery. Dexmedetomidine displays multiple mechanisms of neuroprotection to assist in preventing POD as a part of a comprehensive anesthetic care plan. This review will cover dexmedetomidine’s pharmacological overlap with the current etiological theories behind POD along with pre-clinical and clinical studies on POD prevention with dexmedetomidine. While the body of evidence surrounding the use of dexmedetomidine for POD prevention still requires further development, promising evidence exists for the use of dexmedetomidine in select dosing and circumstances to enhance recovery from surgery.
Is a 4 J/cm2 PpIX-Weighted Simulated Daylight (SDL-PDT) Dose Still Efficient for Photodynamic Therapy of Actinic Keratosis?
Authors: Fronville Mathilde , Creusot Muriel , Mordon Serge R.
Published: October 2023

Background: Several solutions are now proposed to provide indoor illumination with so-called artificial white light or simulated daylight (SDL-PDT), resulting in an effective treatment for actinic keratosis (AK). However, the optimal PpIX-weighted light dose is still debated. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose and is a key parameter for the efficacy of the treatment. Objectives: The paper aims to report the clinical outcomes of SDL-PDT when using the PpIX-weighted light dose of 4 J/cm2, in patients treated for AK lesions of the scalp or the face at our medical dermatology center (ClinicalTrials.gov NCT052036). Methods: A total of 30 patients (16 males, 14 females), with a mean age of 71.0 ± 10.2, with phototype 1 (16 patients) and phototype 2 (14 patients) with grade I–II AK were treated with a drug light interval (DLI) of 10 min and a light exposure of 35 min (Dermaris, Surgiris, Croix, France), corresponding to a PpIX-weighted light dose of 4 J/cm2. The primary endpoint was the cure rate of patients at six months post-treatment. Secondary endpoints included scores of pain, erythema, crusts, and discomfort during or/and post the treatment. Results: In total, 762 AK were treated. Six months following treatment, the cure rate of the patients was 77%. The median pain score was less than 1 out of 10 for most of the patients. Erythema was observed in all patients and lasted 3 days (±1.5 day). Crusts were seen in 28 patients. Discomfort was reported as mild or less in more than 97% of patients. Conclusions: The shortening of the PpIX-weighted light dose to 4 J/cm2, corresponding to an illumination duration of 35 min with the Dermaris, does not modify the efficacy of the SDL-PDT. This observation is in agreement with recent published data demonstrating that the light dose can be reduced. Furthermore, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.
Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents
Authors: Yakkala Prasanna Anjaneyulu , Penumallu Naveen Reddy , Shafi Syed , Kamal Ahmed
Published: October 2023

Topoisomerases are very important enzymes that regulate DNA topology and are vital for biological actions like DNA replication, transcription, and repair. The emergence and spread of cancer has been intimately associated with topoisomerase dysregulation. Topoisomerase inhibitors have consequently become potential anti-cancer medications because of their ability to obstruct the normal function of these enzymes, which leads to DNA damage and subsequently causes cell death. This review emphasizes the importance of topoisomerase inhibitors as marketed, clinical and preclinical anti-cancer medications. In the present review, various types of topoisomerase inhibitors and their mechanisms of action have been discussed. Topoisomerase I inhibitors, which include irinotecan and topotecan, are agents that interact with the DNA-topoisomerase I complex and avert resealing of the DNA. The accretion of DNA breaks leads to the inhibition of DNA replication and cell death. On the other hand, topoisomerase II inhibitors like etoposide and teniposide, function by cleaving the DNA-topoisomerase II complex thereby effectively impeding the release of double-strand DNA breaks. Moreover, the recent advances in exploring the therapeutic efficacy, toxicity, and MDR (multidrug resistance) issues of new topoisomerase inhibitors have been reviewed in the present review.
Drug–Drug Interactions between Tamsulosin and Mirabegron in Healthy Individuals Do Not Affect Pharmacokinetics and Hemodynamic Parameters Significantly
Authors: Shin Wonsuk , Yang A-Young , Yoo Hyounggyoon , Kim Anhye
Published: October 2023

Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, substantially affecting quality of life. Tamsulosin and mirabegron combination therapy has been studied as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, three-period, drug–drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), or a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron was reduced by approximately 17% when administered with tamsulosin. No clinically significant changes in the safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug–drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination could be a promising treatment option for patients with OAB.
Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo
Authors: Timpani Cara A. , Rasmussen Lorna , Rybalka Emma
Published: October 2023

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year clinical trial data on Duchenne muscular dystrophy patients suggests it is a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and its acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50 > 5000 mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.
Enhancing Water Depth Estimation from Satellite Images Using Online Machine Learning: A Case Study Using Baidu Easy-DL with Acoustic Bathymetry and Sentinel-2 Data
Authors: Wu Zhongqiang , Wu Shulei , Yang Haixia , Mao Zhihua , Shen Wei
Published: October 2023

Water depth estimation is paramount in various domains, including navigation, environmental monitoring, and resource management. Traditional depth measurement methods, such as bathymetry, can often be expensive and time-consuming, especially in remote or inaccessible areas. This study delves into the application of machine learning techniques, specifically focusing on the Baidu Easy DL model for water depth estimation leveraging satellite imagery. Utilizing Sentinel-2 satellite data over Rushikonda Beach in India and processing it into remote sensing reflectance using ACOLITE software, this research compares the performance of several machine learning algorithms, including the Stumpf model, Log-Linear model, and the Baidu Easy DL model, for accurate depth estimation. The results indicate that the Easy-DL model outperforms traditional methods, particularly excelling in the 0–11 m depth range. This study showcases the substantial potential of machine learning in remote sensing, offering robust water depth estimates, even in complex coastal environments. Furthermore, it underscores the critical role of comprehensive training datasets and ensemble learning techniques in enhancing accuracy. This research opens avenues for the further exploration of machine learning applications in remote sensing and highlights the promising prospects of online model APIs when streamlining remote sensing data processing.
Interpretation of the Power Consumption Characterization of an Urban University Campus toward Power System Planning
Authors: Ghanavati Afsaneh , Rawlins Marisha , Dow Douglas , Sweeny Christopher , Smith Jackson
Published: October 2023

The power consumption analysis of a university campus can provide a unique opportunity to gain insight into the patterns and trends of multipurpose commercial buildings. The result of such an analysis may lead to the exploration of methods to integrate local and cleaner power generation. In this paper, we discuss the consumption patterns of the campus buildings of the Wentworth Institute of Technology for one calendar year. We analyzed the campus’s power consumption, comparing weekdays vs. weekends, academic vs. residential. The aggregate consumption of all buildings and examples of individual building consumption data were also included. This study was conducted on a campus that has unique characteristics such as being in an urban area, having a New England climate, and being composed of a mixture of old and new buildings. The findings could provide insightful information to other universities and commercial campuses in moving toward energy consumption improvement and efficiency.
Typical Power Grid Operation Mode Generation Based on Reinforcement Learning and Deep Belief Network
Authors: Wang Zirui , Zhou Bowen , Lv Chen , Yang Hongming , Ma Quan , Yang Zhao , Cui Yong
Published: October 2023

With the continuous expansion of power grids and the gradual increase in operational uncertainty, it is progressively challenging to meet the capacity requirements for power grid development based on manual experience. In order to further improve the efficiency of the operation mode calculation, reduce the consumption of manpower and material resources, and consider the sustainability of energy development, this paper proposes a typical power grid operation mode generation method based on Q-learning and the deep belief network (DBN) for the first time. Firstly, the operation modes of different generator combinations located in different regions are obtained through Q-learning intelligent generation. Subsequently, the generated operation modes are clustered as different operation mode sets according to the data characteristics. Furthermore, comprehensive evaluation indexes are proposed from the perspectives of the steady state, transient state, and the economy. These multi-dimensional indexes are integrated via the analytical hierarchy process–entropy weight method (AHP-EWM) to enhance the comprehensibility of the evaluation system. Finally, DBN is introduced to construct a rapid operation mode evaluation model to realize the evaluation of operation mode sets, and typical operation mode sets are obtained accordingly. In this way, the system calculator only needs to compare the composite values to obtain the typical operation modes. The proposed method is validated by the Northeast Power Grid in China. The experimental results show that the proposed method can quickly generate typical power grid operation modes according to actual demand and greatly improve the efficiency of operation mode calculation.
Should I Go Back to the Roots to Obtain My Food? Understanding Key Factors Driving U.S. Consumers’ Preferences for Food Foraging over Buying and Growing Food
Authors: Rombach Meike , Botero Julio , Dean David L.
Published: October 2023

Alternative forms of food procurement have increased in consumer popularity since the occurrence of food price inflation and the ongoing recession in the U.S. The present study explores predictors such as food engagement, food-related COVID-19 concerns, and the importance of sustainable foraging practices as determinants for U.S. consumers’ preferences for food foraging. Two scenarios are investigated, the preference for food foraging over growing food and food foraging over regular food buying. The study is based on an online consumer survey (n = 401) and used partial least square structural equation modeling (PLS-SEM) for the data analysis. Results indicate that food engagement is the strongest predictor for both foraging over buying and foraging over growing scenarios. However, food-related COVID-19 concern appears to only be relevant for the foraging over buying scenario and the importance of sustainable growing practices is only relevant for the foraging over growing scenario. These findings are important because they indicate the attitudinal triggers of food foraging and are therefore of relevance to foraging communities and managers in municipalities, food retail, and horticultural businesses who are associated with traditional and alternative forms of food procurement.
Beyond the Ecological Boundary: A Quasi-Natural Experiment on the Impact of National Marine Parks on Eco-Efficiency in Coastal Cities
Authors: Zhang Xiao , Wang Di
Published: October 2023

National marine parks (NMPs) are a crucial form of marine protected areas that serve an essential function in safeguarding marine ecosystems and the related inland urban ecosystems. Though 30 coastal cities in China have established NMPs, little is known about the ecological benefits national marine parks contribute to surrounding areas. This study takes China’s coastal cities as an example and employs a multi-period DID model to investigate how eco-efficiency responds to the establishment of national marine parks, based on panel data from 2003 to 2020. The results show that the establishment of NMPs contributed to a 3.87% enhancement in the eco-efficiency of coastal cities. This finding remains robust after a series of robustness tests such as PSM-DID. In addition, significant heterogeneities are captured, with NMPs exhibiting a more substantial enhancement effect for cities along the East China Sea and South China Sea. NMPs with a large area increased the eco-efficiency of coastal cities by 5.18%, but small-area NMPs failed the significance test. A mechanism analysis further reveals that NMPs could improve the eco-efficiency of coastal cities by optimizing the industrial structure, enlivening the local economy, and inhibiting sewage pollution behaviors. This study provides evidence of the impact of NMPs on local eco-efficiency in developing countries.
Unlocking the Potential of Microfinance Solutions on Urban Woman Entrepreneurship Development in East Africa: A Bibliometric Analysis Perspective
Authors: Kato Ahmed Idi
Published: October 2023

Empowering women is essential for poverty alleviation and open involvement of woman entrepreneurs in line for entrepreneurship development. Nonetheless, several woman-led enterprises and woman entrepreneurs have scarce opportunities to revitalize beyond the dearth of financial services to realize financial freedom. This article’s approach hinges on a bibliometric analysis to survey recent developments and trends in microfinancing woman-owned enterprises and how this field is expected to transform to recent financial technological progress over successive years. We review existing evidence from 402 published articles indexed in the Scopus database from January 2003 to March 2023 to explain the current research development and interrelated prospects for enhancing studies on microfinance for woman entrepreneurship. The results vividly indicate that access to a stream of microfinancing credit is fundamental to the prosperity of urban woman-led enterprises across all countries. Despite this, woman entrepreneurs still encounter several obstacles when starting new businesses or expanding existing ones. With a growing demand for substantial sums of external financing to transition to sustainable business practices, their contribution to sustainable development is most often unreachable. Thus, any financing strategies focused on allowing access to microfinance credit by woman entrepreneurs are necessary to enable this sector to receive the benefits of economic freedom. This study offers good insights for current and potential entrepreneurs to bridge the financing gaps in emerging economies as a strategy for strengthening the capability of woman entrepreneurs to pursue economic opportunities that can inspire sustainable business enterprises and contribute to sustainable development. Finally, the study provides a foundation for future research in the domain of entrepreneurial financing for MSMEs.
Assessment of Eutrophication Characteristics and Evaluation of the First-Generation Eutrophication Model in the Nearshore Waters of Shantou City
Authors: Wang Hongbing , Wan Xiaoming , Wang Si , Xia Lu , Song Yanwei
Published: October 2023

Based on the water quality monitoring results from 2002 to 2018 in the coastal waters of Shantou City, this study used eight methods, including the single-factor index method, eutrophication index method, nutrient status quality method, comprehensive index method, organic pollution index method, nitrogen–phosphorus ratio method, potential eutrophication evaluation, and dissolved oxygen saturation parameter method, to evaluate the eutrophication and organic pollution status of the area. The applicability of the first-generation eutrophication model was assessed from the perspective of red tide occurrence, and a comparison was made among the various evaluation methods. The results indicate that the coastal waters of the study area were mostly in a phosphorus-limited state, with a few periods of nutrient deficiency and a very small portion of time in a moderately nutritious state with both nitrogen and phosphorus limitations. The overall N/P ratio showed an increasing trend primarily due to the gradual increase in inorganic nitrogen content. In terms of evaluating eutrophication based on red tide symptoms, the comprehensive index method showed better performance in reflecting eutrophication conditions, while the eutrophication index method and dissolved oxygen saturation parameter method highlighted problematic areas but often exaggerated their extent. The nutrient status quality method and organic pollution index method did not provide distinctive indications and could not verify red tide symptoms. The nitrogen–phosphorus ratio method and potential eutrophication evaluation could reflect certain nutrient structures and eutrophication characteristics but also failed to verify red tide symptoms. Furthermore, this study found a certain correlation between the occurrence of red tide and the ratio of nitrate nitrogen to ammonia nitrogen, which consistently ranged from 1.15 to 1.94 during red tide events. Therefore, whether this ratio can serve as a characteristic value for red tide occurrence and be used for early warning and monitoring still requires further validation.
The Role of Heterocysts in Cyanotoxin Production during Nitrogen Limitation
Authors: Gomaa Mohamed N. , Carmichael Wayne W.
Published: October 2023

Cyanobacteria harmful algal blooms (cyanoHABs) can have impacts on human health, aquatic ecosystems, and the economy. Nutrient management is an important mitigation and even remediation strategy. In this work, the paralytic shellfish toxin (PST)-producing Aphanizomenon (Aphan.) flos-aquae (Linnaeus) Ralfs ex Bornet & Flahault (now identified as Aphan. sp.) single filament isolate NH-5 was grown in P-depleted media, N-depleted media, and complete BG-11 media. Growth and heterocyst and vegetative cells were monitored using dry weight and cell counts. Ultrasonication was used to separate heterocysts from vegetative cells. HPLC-FLD with post-column derivatization was used to determine the saxitoxin (STX) and neosaxitoxin (NEOSTX) concentration per cell. Aphan. sp. NH-5 biomass was lower in the P-depleted media than in the N-depleted media and the control, though higher heterocyst counts were detected in the N-depleted media. The heterocyst toxin concentration was significantly higher compared to the vegetative cells for the N-depleted media, control, and P-depleted media. However, no significant differences were found among all preparations with regard to the STX-to-NEOSTX ratio. We conclude that N limitation induced higher heterocyst numbers and that N fixation activity is a factor behind the increase in the STX and NEOSTX production of Aphan. sp. NH-5.
Efficient Removal of Cadmium (II) and Arsenic (V) from Water by the Composite of Iron Manganese Oxides Loaded Muscovite
Authors: Wu Yan , Zhao Yue , Xu Zhuben , Wang Rui , Zhang Han , Feng Shuaitao , Guo Jianhua
Published: October 2023

It is a great challenge for a material with high adsorption capacity for cadmium (Cd) and arsenic (As) simultaneously. To address the simultaneous removal of Cd and As from water and the utilization of waste muscovite, the muscovite-supported iron manganese oxides (FMM) were prepared. The FMM was easy to adsorb Cd(II) and As(V), and the adsorption capacity of Cd(II) and As(V) was 32.47 mg/g and 28.57 mg/g, respectively. Iron manganese oxides significantly improved the Cd(II) and As(V) adsorption capacity, specific surface area, and pore volume of the material. Moreover, the adsorption process of FMM for Cd(II) and As(V) fitted well with the pseudo-first-order model and pseudo-second-order model. The mechanism including chemical adsorption, electrostatic adsorption and covalent bond adsorption was proposed for As(V) removal, while Cd(II) removal was based on the combination of electrostatic adsorption and surface precipitation. In conclusion, FMM is a promising material for the treatment of As and Cd-contaminated wastewater, which provides insight into the resource utilization of waste muscovite.
Walter J. Ong. Sözlü ve Yazılı Kültür: Sözün Teknolojileşmesi
Authors: TÜLÜCE Hüseyin Adem
Published: October 2023

Sözlü ve yazılı kültür konusunda antropolog, felsefeci, edebiyatçı, sosyolog ve psikologlar tarafından meseleyi farklı boyutlarıyla inceleyen birçok çalışma yapılmıştır. Bilhassa günümüz dünyasında sinema, bilgisayar ve internet teknolojisinin gelişmesiyle birlikte sözlü ve yazılı kültür konusu görsellik ve işitsellik bağlamında tekrar gündeme gelmiştir. Sözlü ve yazılı kültür arasındaki ayrım özellikle edebiyat araştırmalarıyla ortaya çıkmıştır.