bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture Decreases Risk of Hypertension in Patients with Chronic Spontaneous Urticaria in Taiwan: A Nationwide Study
Authors: Chang Heng-Wei , Lin Wei-De , Shih Pai-Jun , Peng Shin-Lei , Hsu Chung-Y. , Lin Cheng-Li , Liao Wen-Ling , Sun Mao-Feng
Published: May 2023

Patients with chronic spontaneous urticaria (CSU) have a higher risk of developing hypertension. This study aimed to determine whether acupuncture could decrease the risk of hypertension in patients with CSU. We enrolled patients newly diagnosed with CSU between 1 January 2008, and 31 December 2018, from the Taiwanese National Health Insurance Research Database. The claims data were assessed from the index date to 31 December 2019. A Cox regression model was used to compare the hazard ratios (HRs) of the two cohorts. The cumulative incidence of hypertension was estimated using the Kaplan–Meier method. After propensity score matching with a 1:1 ratio, 43,547 patients with CSU who received acupuncture were matched with 43,547 patients with CSU who did not receive acupuncture in this study. After considering potential confounding factors, patients who received acupuncture had a significantly lower risk of hypertension than those in the control group (adjusted hazard ratio = 0.56, 95% confidence interval = 0.54–0.58). Patients who received medications combined with acupuncture tended to have the lowest risk of hypertension. This study revealed that acupuncture decreases the risk of hypertension in patients with CSU in Taiwan. The detailed mechanisms can be further clarified through prospective studies.
How Were Return-of-Service Schemes Developed and Implemented in Botswana, Eswatini and Lesotho?
Authors: Mabunda Sikhumbuzo A. , Durbach Andrea , Chitha Wezile W. , Moaletsane Oduetse , Angell Blake , Joshi Rohina
Published: May 2023

Botswana, Eswatini and Lesotho are three Southern African countries that make use of return-of-service (RoS) schemes to increase human resources for health in their countries. These initiatives bind beneficiaries to a pre-defined period of service upon the completion of their studies based on the length of funding support received. We aimed to review the history of these policies to understand the conceptualisation, intent and implementation of these schemes. We used a multi-methods research design which consisted of a literature review, a policy review and semi-structured interviews with policymakers and implementors. All three governments have a combination of grant-loan schemes and full bursaries or scholarships. The policies have all been operating for over 20 years, with Eswatini’s pre-service policy being the oldest since it was introduced in 1977, followed by Lesotho’s 1978 policy and Botswana’s 1995 pre-service policy. These policies have never been reviewed or updated. RoS schemes in these countries were introduced to address critical skills shortages, to improve employability prospects for citizens, to have competent public sector employees by global standards and to aid the career progress of government employees. Ministries of Health are passive role players. However, these schemes can only be efficient if there is clear cooperation and coordination between all stakeholders.
Pelvic Organ Prolapse Syndrome and Lower Urinary Tract Symptom Update: What’s New?
Authors: Munno Gaetano Maria , La Verde Marco , Lettieri Davide , Nicoletti Roberta , Nunziata Maria , Fasulo Diego Domenico , Vastarella Maria Giovanna , Pennacchio Marika , Scalzone Gaetano , Pieretti Gorizio , Fortunato Nicola , De Simone Fulvio , Riemma Gaetano , Torella Marco
Published: May 2023

(1) Background: This narrative review aimed to analyze the epidemiological, clinical, surgical, prognostic, and instrumental aspects of the link between pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), collecting the most recent evidence from the scientific literature. (2) Methods: We matched the terms “pelvic organ prolapse” (POP) and “lower urinary tract symptoms” (LUTS) on the following databases: Pubmed, Embase, Scopus, Google scholar, and Cochrane. We excluded case reports, systematic reviews, articles published in a language other than English, and studies focusing only on a surgical technique. (3) Results: There is a link between POP and LUTS. Bladder outlet obstruction (BOO) would increase variation in bladder structure and function, which could lead to an overactive bladder (OAB). There is no connection between the POP stage and LUTS. Prolapse surgery could modify the symptoms of OAB with improvement or healing. Post-surgical predictive factors of non-improvement of OAB or de novo onset include high BMI, neurological pathologies, age > 65 years, and the severity of symptoms; predictors of emptying disorders are neurological pathologies, BOO, perineal dysfunctions, severity of pre-surgery symptoms, and severe anterior prolapse. Urodynamics should be performed on a specific subset of patients (i.e., stress urinary incontinence, correct surgery planning), (4) Conclusions: Correction of prolapse is the primary treatment for detrusor underactivity and for patients with both POP and OAB.
An Evaluation Study of a New Designed Oscillating Hydraulic Trainer of Neck
Authors: Yang Hongchun , Lv Yawei , Chen Sisi , Xing Baixi , Wu Jianfeng
Published: May 2023

In view of the importance of neck strength training and the lack of adequate training equipment, this study designed a new oscillating hydraulic trainer (OHT) of neck based on oscillating hydraulic damper. We used surface electromyography (sEMG) and subjective ratings to evaluate the neck OHT and compared the results with a simple hat trainer (HATT) and traditional weight trainer (TWT) to verify the feasibility and validity of the OHT. Under similar exercise conditions, 12 subjects performed a set of neck flexion and extension exercise with these 3 trainers. The sEMG signals of targeted muscles were collected in real time, and subjects were asked to complete subjective evaluations of product usability after exercise. The results showed that the root mean square (RMS%) of sEMG indicated that the OHT could provide two-way resistance and train the flexors and extensors simultaneously. The overall degree of muscle activation with OHT was higher than that with the other two trainers in one movement cycle. In terms of resistance characteristics exhibited by the sEMG waveform, duration (D) with OHT was significantly longer than HATT and TWT when exercising at a high speed, while Peak Timing (PT) was later. The ratings of product usability and performing usability of OHT were remarkably higher than that of HATT and TWT. Based on the above results, the OHT was proved to be more suitable for strength training, such as neck muscles, which were getting more attention gradually, but lacked mature and special training equipment.
Indications of Induction and Caesarean Sections Performed Using the Robson Classification in a University Hospital in Spain from 2010 to 2021
Authors: Vila-Candel Rafael , Piquer-Martín Nadia , Perdomo-Ugarte Nerea , Quesada José Antonio , Escuriet Ramón , Martin-Arribas Anna
Published: May 2023

Background: The Robson Ten Group Classification System (RTGCS) enables the assessment, monitoring, and comparison of caesarean section rates both within healthcare facilities and between them, and the indications of caesarean sections (CS) performed in a maternity ward. The aims of the present study were to conduct an analysis to assess the levels and distribution of birth from a descriptive approach by CS in La Ribera University Hospital (Spain) between 2010–2021 using the Robson classification; to describe the indications for the induction of labour and the causes of caesarean sections performed; and to examine the association between the induction of labour and CS birth. Methods: A retrospective study between 1 January 2010 and 31 December 2021. All eligible women were classified according to the RTGCS to determine the absolute and relative contribution by each group to the overall CS rate. The odds ratio (OR) of the variables of interest was estimated by logistic regression. In an analysis of the subgroups, the level of significance was adjusted using the Bonferroni method. Results: 20,578 women gave birth during the study period, 19% of them by CS. In 33% of births, induction was performed, and the most common cause was the premature rupture of membranes. Group 2 (nulliparous with induced labour/elective CS before labour) accounted for the largest contribution to the overall rate of CS (31.5%) and showed an upward trend from 23.2% to 39.7% in the time series, increasing the CS rate by 6.7%. The leading cause of CS was suspected fetal distress, followed by induction failure. Conclusions: In our study, Robson Group 2 was identified as the main contributor to the hospital’s overall CS rate. Determining the causes of induction and CS in a population sample classified using the RTGCS enables the identification of the groups with the greatest deviation from the optimal rate of CS and the establishment of improvement plans to reduce the overall rate of caesarean sections in the maternity unit.
Using Twitter Data Analysis to Understand the Perceptions, Beliefs, and Attitudes about Pharmacotherapy Used in Rheumatology: An Observational Study
Authors: Abbasi-Perez Adrian , Alvarez-Mon Miguel Angel , Donat-Vargas Carolina , Ortega Miguel A. , Monserrat Jorge , Perez-Gomez Ana , Alvarez-Mon Melchor
Published: May 2023

Twitter has become an important platform for disseminating information about rheumatology drugs by patients, health professionals, institutions, and other users. The aim of this study was to analyze tweets related to 16 drugs used in rheumatology, including their volume, content, and type of user (patients, patients’ relatives, health professionals, health institutions, pharmaceutical industry, general press, scientific journals and patients’ associations), and to detect inappropriate medical content. A total of 8829 original tweets were obtained, with a random sample of 25% of the total number of tweets for each drug (at least 100 tweets) analyzed. Methotrexate (MTX) accounted for a quarter of all tweets, and there were significant differences in the proportion of tweets issued according to the type of user. Patients and their relatives mainly tweeted about MTX, while professionals, institutions, and patient associations posted more about TNF inhibitors. In contrast, the pharmaceutical industry focused on IL-17 inhibitors. Medical content prevailed in all drugs except anti-CD20 and IL-1 inhibitors and the most discussed medical topic was efficacy, followed by posology and adverse effects. Inappropriate or fake content was found to be very low. In conclusion, the majority of the tweets were about MTX, which is a first-line treatment for several diseases. The distribution of medical content varied according to the type of user. In contrast to other studies, the amount of medically inappropriate content was very low.
Higher-Institution-Based Film Festivals as a Vehicle to Improve Student Production Quality and Form University–Industry Connections
Authors: Liu Yong , Ling Mayyer , Nechita Florin
Published: May 2023

This paper will be focusing on discussions on how to use small-scale, higher-institution-based film festivals (including film competitions) as a vehicle to motivate students who are majoring in media and screen production to improve their production quality for both module assignments and competition-targeted special projects. Moreover, this paper will argue that, by inviting industry representatives to be involved in judging and commenting on student works, such small-scale film festivals organised by higher education institutions over time may grow into a platform that not only recognises and supports budding directors, screenwriters, actors, and actresses in Brunei but also acts as a playing field in which novice filmmakers can connect with experts, exchange ideas, acquire valuable skills, and enable further collaboration in the future. Based on first-hand data collection, an analysis, and semi-structured interviews of the multiple parties involved, our discussions cover how to launch the production process for screen-practice-based education, how to organise module assignments to fit the themes of specific film festivals/competitions, and how to overcome the challenges facing students working in a multicultural production team, etc. Two higher-institution-based film festivals, i.e., PRISM UBD Short Film Festival organised by Universiti Brunei Darussalam and the Dracula Digital competition, a mobile-phone filmmaking competition run by Transilvania University of Brasov, Romania, are used as analytical case studies.
Psychological Impact and Coping Strategies of Hispanic Parents of Children with Cancer: A Qualitative Study
Authors: Ochoa-Dominguez Carol Y. , Miller Kimberly A. , Banegas Matthew P. , Sabater-Minarim Daniel , Chan Randall Y.
Published: May 2023

Throughout the cancer trajectory, parents of childhood cancer survivors (CCSs) may experience mental and social challenges requiring continual adaptation to cancer-induced stress. Using Lazarus and Folkman’s Transactional Model of Stress and Coping framework, this qualitative study aimed to describe Hispanic parents’ psychological health and explore their coping strategies. Purposive sampling was used to recruit 15 Hispanic caregivers from a safety-net hospital in Los Angeles County. To be eligible, participants had to be: the primary caregiver of a CCS who had completed active treatment, the primary caregiver or child self-identified as Hispanic, and proficient in English or Spanish. The interviews lasted approximately 60 min, were audio-recorded (in English and Spanish), and professionally transcribed. Data were analyzed following a thematic content analysis with deductive and inductive approaches on Dedoose. Participants described high levels of stress and fear when their child was diagnosed with cancer. They also shared experiencing symptoms of social anxiety, post-traumatic stress disorder, and depression. Participants’ coping strategies were encompassed by three major themes: problem-focused, emotion-focused, and avoidant coping strategies. Problem-focused coping strategies included self-efficacy, behavioral change, and social support. Emotion-focused coping strategies included religious practices and positive reframing. Avoidant coping strategies included denial and self-distraction. Despite the evident disparities in psychological health for Hispanic parents of CCSs, gaps remain in designing a culturally tailored program to help alleviate the caregiver burden. This study provides insights regarding coping strategies that Hispanic caregivers use to deal with the psychological impact of their child’s cancer diagnosis. Our findings also delve into the contextual and cultural factors that impact psychological adjustment.
Construction and Analysis of Space–Time Paths for Moving Polygon Objects Based on Time Geography: A Case Study of Crime Events in the City of London
Authors: Yin Zhangcai , Chen Yuan , Ying Shen
Published: May 2023

Time geography considers that the motion of moving objects can be expressed using space–time paths. The existing time geography methods construct space-time paths using discrete trajectory points of a moving point object to characterize its motion patterns. However, these methods are not suitable for moving polygon objects distributed by point sets. In this study, we took a type of crime event as the moving object and extracted its representative point at each moment, using the median center to downscale the polygon objects distributed by the point sets into point objects with timestamps. On this basis, space–time paths were generated by connecting the representative points at adjacent moments to extend the application scope of space–time paths, representing the motion feature from point objects to polygon objects. For the case of the City of London, we constructed a space–time path containing 13 nodes for each crime type (n = 14). Then, each edge of the space–time paths was considered as a monthly vector, which was analyzed statistically from two dimensions of direction and norm, respectively. The results showed that crime events mainly shifted to the east and west, and crime displacement was the greatest in April. Therefore, space–time paths as proposed in this study can characterize spatiotemporal trends of polygon objects (e.g., crime events) distributed by point sets, and police can achieve improved success by implementing targeted crime prevention measures according to the spatiotemporal characteristics of different crime types.
Targeted Radionuclide Therapy of Cancer and Infections
Authors: van der Wal Bart C. H. , Dadachova Ekaterina
Published: May 2023

Targeted radionuclide therapy (TRT) has been burgeoning worldwide, with several radiopharmaceuticals for the treatment of metastatic cancers being approved for clinical use [...]
The Management of Diabetes Mellitus Using Medicinal Plants and Vitamins
Authors: Yedjou Clement G. , Grigsby Jameka , Mbemi Ariane , Nelson Daryllynn , Mildort Bryan , Latinwo Lekan , Tchounwou Paul B.
Published: May 2023

Diabetes mellitus (DM) is a serious chronic metabolic disease that is associated with hyperglycemia and several complications including cardiovascular disease and chronic kidney disease. DM is caused by high levels of blood sugar in the body associated with the disruption of insulin metabolism and homeostasis. Over time, DM can induce life-threatening health problems such as blindness, heart disease, kidney damage, and stroke. Although the cure of DM has improved over the past decades, its morbidity and mortality rates remain high. Hence, new therapeutic strategies are needed to overcome the burden of this disease. One such prevention and treatment strategy that is easily accessible to diabetic patients at low cost is the use of medicinal plants, vitamins, and essential elements. The research objective of this review article is to study DM and explore its treatment modalities based on medicinal plants and vitamins. To achieve our objective, we searched scientific databases of ongoing trials in PubMed Central, Medline databases, and Google Scholar websites. We also searched databases on World Health Organization International Clinical Trials Registry Platform to collect relevant papers. Results of numerous scientific investigations revealed that phytochemicals present in medicinal plants (Allium sativum, Momordica charantia, Hibiscus sabdariffa L., and Zingiber officinale) possess anti-hypoglycemic activities and show promise for the prevention and/or control of DM. Results also revealed that intake of vitamins C, D, E, or their combination improves the health of diabetes patients by reducing blood glucose, inflammation, lipid peroxidation, and blood pressure levels. However, very limited studies have addressed the health benefits of medicinal plants and vitamins as chemo-therapeutic/preventive agents for the management of DM. This review paper aims at addressing this knowledge gap by studying DM and highlighting the biomedical significance of the most potent medicinal plants and vitamins with hypoglycemic properties that show a great potential to prevent and/or treat DM.
A Promising Needle-Free Pyro-Drive Jet Injector for Augmentation of Immunity by Intradermal Injection as a Physical Adjuvant
Authors: Sonoda Jukito , Mizoguchi Izuru , Inoue Shinya , Watanabe Aruma , Sekine Ami , Yamagishi Miu , Miyakawa Satomi , Yamaguchi Natsuki , Horio Eri , Katahira Yasuhiro , Hasegawa Hideaki , Hasegawa Takashi , Yamashita Kunihiko , Yoshimoto Takayuki
Published: May 2023

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action.
Transcriptomic Analysis of the Effect of Torin-2 on the Central Nervous System of Drosophila melanogaster
Authors: Vershinina Yulia S. , Krasnov George S. , Garbuz David G. , Shaposhnikov Mikhail V. , Fedorova Maria S. , Pudova Elena A. , Katunina Irina V. , Kornev Alexey B. , Zemskaya Nadezhda V. , Kudryavtsev Alexander A. , Bulavkina Elizaveta V. , Matveeva Anna A. , Ulyasheva Natalia S. , Guvatova Zulfiya G. , Anurov Artemiy A. , Moskalev Alexey A. , Kudryavtseva Anna V.
Published: May 2023

Torin-2, a synthetic compound, is a highly selective inhibitor of both TORC1 and TORC2 (target of rapamycin) complexes as an alternative to the well-known immunosuppressor, geroprotector, and potential anti-cancer natural compound rapamycin. Torin-2 is effective at hundreds of times lower concentrations and prevents some negative side effects of rapamycin. Moreover, it inhibits the rapamycin-resistant TORC2 complex. In this work, we evaluated transcriptomic changes in D. melanogaster heads induced with lifetime diets containing Torin-2 and suggested possible neuroprotective mechanisms of Torin-2. The analysis included D. melanogaster of three ages (2, 4, and 6 weeks old), separately for males and females. Torin-2, taken at the lowest concentration being tested (0.5 μM per 1 L of nutrient paste), had a slight positive effect on the lifespan of D. melanogaster males (+4% on the average) and no positive effect on females. At the same time, RNA-Seq analysis revealed interesting and previously undiscussed effects of Torin-2, which differed between sexes as well as in flies of different ages. Among the cellular pathways mostly altered by Torin-2 at the gene expression level, we identified immune response, protein folding (heat shock proteins), histone modification, actin cytoskeleton organization, phototransduction and sexual behavior. Additionally, we revealed that Torin-2 predominantly reduced the expression of Srr gene responsible for the conversion of L-serine to D-serine and thus regulating activity of NMDA receptor. Via western blot analysis, we showed than in old males Torin-2 tends to increase the ratio of the active phosphorylated form of ERK, the lowest node of the MAPK cascade, which may play a significant role in neuroprotection. Thus, the complex effect of Torin-2 may be due to the interplay of the immune system, hormonal background, and metabolism. Our work is of interest for further research in the field of NMDA-mediated neurodegeneration.
“ThermoTRP” Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist)
Authors: Szallasi Arpad
Published: May 2023

Temperature-sensitive transient receptor potential (TRP) channels (so-called “thermoTRPs”) are multifunctional signaling molecules with important roles in cell growth and differentiation. Several “thermoTRP” channels show altered expression in cancers, though it is unclear if this is a cause or consequence of the disease. Regardless of the underlying pathology, this altered expression may potentially be used for cancer diagnosis and prognostication. “ThermoTRP” expression may distinguish between benign and malignant lesions. For example, TRPV1 is expressed in benign gastric mucosa, but is absent in gastric adenocarcinoma. TRPV1 is also expressed both in normal urothelia and non-invasive papillary urothelial carcinoma, but no TRPV1 expression has been seen in invasive urothelial carcinoma. “ThermoTRP” expression can also be used to predict clinical outcomes. For instance, in prostate cancer, TRPM8 expression predicts aggressive behavior with early metastatic disease. Furthermore, TRPV1 expression can dissect a subset of pulmonary adenocarcinoma patients with bad prognosis and resistance to a number of commonly used chemotherapeutic agents. This review will explore the current state of this rapidly evolving field with special emphasis on immunostains that can already be added to the armoire of diagnostic pathologists.
Introducing and Implementing Genetic Assessment in Cardio-Obstetrics Clinical Practice: Clinical and Genetic Workup of Patients with Cardiomyopathy
Authors: Mansoori Ghadeera Al , Mahmeed Wael Al , Wani Saleema , Salih Bashir Taha , Ansari Tarek El , Farook Fathima , Farooq Zenab , Khair Howaida , Zaręba Kornelia , Dhahouri Nahid Al , Raj Anjana , Foo Roger S. , Ali Bassam R. , Jasmi Fatma Al , Akawi Nadia
Published: May 2023

Cardiovascular disease (CVD) during pregnancy varies significantly worldwide, influenced by factors such as access to healthcare, delayed diagnosis, causes, and risk factors. Our study sought to explore the spectrum of CVD present in pregnant women in the United Arab Emirates to better understand this population’s unique needs and challenges. Central to our study is an emphasis on the importance of implementing a multidisciplinary approach that involves the collaboration of obstetricians, cardiologists, geneticists, and other healthcare professionals to ensure that patients receive comprehensive and coordinated care. This approach can also help identify high-risk patients and implement preventive measures to reduce the occurrence of adverse maternal outcomes. Furthermore, increasing awareness among women about the risk of CVD during pregnancy and obtaining detailed family histories can help in the early identification and management of these conditions. Genetic testing and family screening can also aid in identifying inherited CVD that can be passed down through families. To illustrate the significance of such an approach, we provide a comprehensive analysis of five women’s cases from our retrospective study of 800 women. The findings from our study emphasize the importance of addressing maternal cardiac health in pregnancy and the need for targeted interventions and improvements in the existing healthcare system to reduce adverse maternal outcomes.
The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers
Authors: Felípez Nayra , Montori Sheyla , Mendizuri Naroa , Llach Joan , Delgado Pedro G. , Moreira Leticia , Santamaría Enrique , Fernández-Irigoyen Joaquín , Albéniz Eduardo
Published: May 2023

Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, including microRNA, DNA methylation markers, and protein-based biomarkers. Although most studies have focused on identifying biomarkers in biofluids, the low specificity of these markers has limited their use in clinical practice. This is because many cancers share similar alterations and biomarkers, so obtaining them from the site of disease origin could yield more specific results. As a result, recent research efforts have shifted towards exploring gastric juice (GJ) as an alternative source for biomarker identification. Since GJ is a waste product during a gastroscopic examination, it could provide a “liquid biopsy” enriched with disease-specific biomarkers generated directly at the damaged site. Furthermore, as it contains secretions from the stomach lining, it could reflect changes associated with the developmental stage of GC. This narrative review describes some potential biomarkers for gastric cancer screening identified in gastric juice.
Glioblastoma Metabolism: Insights and Therapeutic Strategies
Authors: Bernhard Chloé , Reita Damien , Martin Sophie , Entz-Werle Natacha , Dontenwill Monique
Published: May 2023

Tumor metabolism is emerging as a potential target for cancer therapies. This new approach holds particular promise for the treatment of glioblastoma, a highly lethal brain tumor that is resistant to conventional treatments, for which improving therapeutic strategies is a major challenge. The presence of glioma stem cells is a critical factor in therapy resistance, thus making it essential to eliminate these cells for the long-term survival of cancer patients. Recent advancements in our understanding of cancer metabolism have shown that glioblastoma metabolism is highly heterogeneous, and that cancer stem cells exhibit specific metabolic traits that support their unique functionality. The objective of this review is to examine the metabolic changes in glioblastoma and investigate the role of specific metabolic processes in tumorigenesis, as well as associated therapeutic approaches, with a particular focus on glioma stem cell populations.
Effectiveness of Nonfunctionalized Graphene Oxide Nanolayers as Nanomedicine against Colon, Cervical, and Breast Cancer Cells
Authors: Hatshan Mohammad , Saquib Quaiser , Siddiqui Maqsood , Faisal Mohammad , Ahmad Javed , Al-Khedhairy Abdulaziz , Shaik Mohammed , Khan Mujeeb , Wahab Rizwan , De Matteis Valeria , Adil Syed
Published: May 2023

Recent studies in nanomedicine have intensively explored the prospective applications of surface-tailored graphene oxide (GO) as anticancer entity. However, the efficacy of nonfunctionalized graphene oxide nanolayers (GRO-NLs) as an anticancer agent is less explored. In this study, we report the synthesis of GRO-NLs and their in vitro anticancer potential in breast (MCF-7), colon (HT-29), and cervical (HeLa) cancer cells. GRO-NLs-treated HT-29, HeLa, and MCF-7 cells showed cytotoxicity in the MTT and NRU assays via defects in mitochondrial functions and lysosomal activity. HT-29, HeLa, and MCF-7 cells treated with GRO-NLs exhibited substantial elevations in ROS, disturbances of the mitochondrial membrane potential, an influx of Ca2+, and apoptosis. The qPCR quantification showed the upregulation of caspase 3, caspase 9, bax, and SOD1 genes in GRO-NLs-treated cells. Western blotting showed the depletion of P21, P53, and CDC25C proteins in the above cancer cell lines after GRO-NLs treatment, indicating its function as a mutagen to induce mutation in the P53 gene, thereby affecting P53 protein and downstream effectors P21 and CDC25C. In addition, there may be a mechanism other than P53 mutation that controls P53 dysfunction. We conclude that nonfunctionalized GRO-NLs exhibit prospective biomedical application as a putative anticancer entity against colon, cervical, and breast cancers.
Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability
Authors: Rajan Robin G. , Krutilina Raisa I. , Ignatova Tatyana N. , Pavicevich Zoran S. , Dulatova Galina M. , Lane Maria A. , Chatterjee Arindam R. , Rooney Robert J. , Antony Mymoon , Hagerty Vivian R. , Kukekov Nickolay V. , Hanafy Khalid A. , Vrionis Frank D.
Published: May 2023

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the Oct3/4 network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including Gata6, FoxA2, Sall4, Zic2, H2afJ, Stc1 and Bmi1 were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of Sall4, c-Myc, Mmp1, Mmp9 and Dkk1 genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus, Oct3/4 transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.
Pre-Existing Intrarenal Parvovirus B19 Infection May Relate to Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients
Authors: Bertazza Partigiani Nicola , Negrisolo Susanna , Carraro Andrea , Marzenta Diana , Manaresi Elisabetta , Gallinella Giorgio , Barzon Luisa , Benetti Elisa
Published: May 2023

Viral infections can lead to transplant dysfunction, and their possible role in rejection is described. In total, 218 protocol biopsies performed in 106 children at 6, 12 and 24 months after transplantation were analyzed according to Banff ’15. RT-PCR for cytomegalovirus, Epstein-Barr virus, BK virus and Parvovirus B19 was performed on blood and bioptic samples at the time of transplant and each protocol biopsy. The prevalence of intrarenal viral infection increases between 6 and 12 months after transplantation (24% vs. 44%, p = 0.007). Intrarenal Parvovirus B19 infection is also associated with antibody-mediated rejection (ABMR) (50% ABMR vs. 19% T-cell-mediated rejection, p = 0.04). Moreover, Parvovirus infection is higher at 12 months of follow-up and it decreases at 48 months (40.4% vs. 14%, p = 0.02), while in 24% of grafts, Parvovirus is already detectable at the moment of transplantation. Intrarenal Parvovirus B19 infection seems to be related to ABMR in pediatric kidney recipients. The graft itself may be the way of transmission for Parvovirus, so performance of a PCR test for Parvovirus B19 should be considered to identify high-risk patients. Intrarenal Parvovirus infection presents mainly during the first-year post-transplantation; thus, we recommend an active surveillance of donor-specific antibodies (DSA) in patients with intrarenal Parvovirus B19 infection during this period. Indeed, it should be considered a treatment with intravenous immunoglobulins in patients with intrarenal Parvovirus B19 infection and DSA positivity, even in the absence of ABMR criteria for kidney biopsy.
Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells
Authors: Mehus Aaron A. , Jones Madison , Trahan Mason , Kinnunen Kaija , Berwald Kaitlyn , Lindner Becker , Al-Marsoummi Sarmad , Zhou Xu Dong , Garrett Scott H. , Sens Donald A. , Sens Mary Ann , Somji Seema
Published: May 2023

Urothelial cancer (UC) is a common malignancy and its development is associated with arsenic exposure. Around 25% of diagnosed UC cases are muscle invasive (MIUC) and are frequently associated with squamous differentiation. These patients commonly develop cisplatin (CIS) resistance and have poor prognosis. SOX2 expression is correlated to reduced overall and disease-free survival in UC. SOX2 drives malignant stemness and proliferation in UC cells and is associated with development of CIS resistance. Using quantitative proteomics, we identified that SOX2 was overexpressed in three arsenite (As3+)-transformed UROtsa cell lines. We hypothesized that inhibition of SOX2 would reduce stemness and increase sensitivity to CIS in the As3+-transformed cells. Pevonedistat (PVD) is a neddylation inhibitor and is a potent inhibitor of SOX2. We treated non-transformed parent and As3+-transformed cells with PVD, CIS, or in combination and monitored cell growth, sphere forming abilities, apoptosis, and gene/protein expression. PVD treatment alone caused morphological changes, reduced cell growth, attenuated sphere formation, induced apoptosis, and elevated the expression of terminal differentiation markers. However, the combined treatment of PVD with CIS significantly elevated the expression of terminal differentiation markers and eventually led to more cell death than either solo treatment. Aside from a reduced proliferation rate, these effects were not seen in the parent. Further research is needed to explore the potential use of PVD with CIS as a differentiation therapy or alternative treatment for MIUC tumors that may have become resistant to CIS.
FUNDC1: An Emerging Mitochondrial and MAMs Protein for Mitochondrial Quality Control in Heart Diseases
Authors: Bai Xizhe , Zhang Zhe , Li Xi , Yang Yangjun , Ding Shuzhe
Published: May 2023

Heart diseases (HDs) are the leading cause of mortality worldwide, with mitochondrial dysfunction being a significant factor in their development. The recently discovered mitophagy receptor, FUNDC1, plays a critical role in regulating the homeostasis of the Mitochondrial Quality Control (MQC) system and contributing to HDs. The phosphorylation of specific regions of FUNDC1 and varying levels of its expression have been shown to have diverse effects on cardiac injury. This review presents a comprehensive consolidation and summary of the latest evidence regarding the role of FUNDC1 in the MQC system. The review elucidates the association of FUNDC1 with prevalent HDs, such as metabolic cardiomyopathy (MCM), cardiac remodeling/heart failure, and myocardial ischemia-reperfusion (IR) injury. The results indicate that the expression of FUNDC1 is elevated in MCM but reduced in instances of cardiac remodeling, heart failure, and myocardial IR injury, with divergent impacts on mitochondrial function among distinct HDs. Exercise has been identified as a powerful preventive and therapeutic approach for managing HDs. Additionally, it has been suggested that exercise-induced enhancement of cardiac function may be attributed to the AMPK/FUNDC1 pathway.
Significance of Astragaloside IV from the Roots of Astragalus mongholicus as an Acetylcholinesterase Inhibitor—From the Computational and Biomimetic Analyses to the In Vitro and In Vivo Studies of Safety
Authors: Stępnik Katarzyna , Kukula-Koch Wirginia , Plazinski Wojciech , Gawel Kinga , Gaweł-Bęben Katarzyna , Khurelbat Daariimaa , Boguszewska-Czubara Anna
Published: May 2023

The main aim of the study was to assess the acetylcholinesterase-inhibitory potential of triterpenoid saponins (astragalosides) found in the roots of Astragalus mongholicus. For this purpose, the TLC bioautography method was applied and then the IC50 values were calculated for astragalosides II, III and IV (5.9 μM; 4.2 μM, and 4.0 μM, respectively). Moreover, molecular dynamics simulations were carried outto assess the affinity of the tested compounds for POPC and POPG-containing lipid bilayers, which in this case are the models of the blood-brain barrier (BBB). All determined free energy profiles confirmed that astragalosides exhibit great affinity for the lipid bilayer. A good correlation was obtained when comparing the logarithm of n-octanol/water partition coefficient (logPow) lipophilicity descriptor values with the smallest values of free energy of the determined 1D profiles. The affinity for the lipid bilayers changes in the same order as the corresponding logPow values, i.e.,: I > II > III~IV. All compounds exhibit a high and also relatively similar magnitude of binding energies, varying from ca. −55 to −51 kJ/mol. Apositive correlation between the experimentally-determined IC50 values and the theoretically-predicted binding energies expressed by the correlation coefficient value equal 0.956 was observed.
Recent Advances in 64Cu/67Cu-Based Radiopharmaceuticals
Authors: Krasnovskaya Olga O. , Abramchuck Daniil , Erofeev Alexander , Gorelkin Peter , Kuznetsov Alexander , Shemukhin Andrey , Beloglazkina Elena K.
Published: May 2023

Copper-64 (T1/2 = 12.7 h) is a positron and beta-emitting isotope, with decay characteristics suitable for both positron emission tomography (PET) imaging and radiotherapy of cancer. Copper-67 (T1/2 = 61.8 h) is a beta and gamma emitter, appropriate for radiotherapy β-energy and with a half-life suitable for single-photon emission computed tomography (SPECT) imaging. The chemical identities of 64Cu and 67Cu isotopes allow for convenient use of the same chelating molecules for sequential PET imaging and radiotherapy. A recent breakthrough in 67Cu production opened previously unavailable opportunities for a reliable source of 67Cu with high specific activity and purity. These new opportunities have reignited interest in the use of copper-containing radiopharmaceuticals for the therapy, diagnosis, and theranostics of various diseases. Herein, we summarize recent (2018–2023) advances in the use of copper-based radiopharmaceuticals for PET, SPECT imaging, radiotherapy, and radioimmunotherapy.
Geopolymers: The Green Alternative to Traditional Materials for Engineering Applications
Authors: Jwaida Zahraa , Dulaimi Anmar , Mashaan Nuha , Othuman Mydin Md Azree
Published: May 2023

Researchers have been driven to investigate sustainable alternatives to cement production, such as geopolymers, due to the impact of global warming and climate change resulting from greenhouse gas emissions. Currently, they are exploring different methods and waste materials to enhance the mechanical and physical properties of geopolymer and expand its application range. This review paper offers a thorough analysis of the utilization of various waste materials in geopolymer manufacturing and shows the creative contribution of this research to the development of environmentally friendly cement substitutes. The article covers the properties, durability, and practical applications of geopolymer composites made from various waste binders. It includes a microstructure and chemical analysis. The research findings indicate that geopolymers are an effective cementitious binder substitute for cement in various applications. Additionally, the ecological and carbon footprint analysis highlights the sustainability of geopolymers compared to cement.
Investigations on Using Intelligent Learning Techniques for Anomaly Detection and Diagnosis in Sensors Signals in Li-Ion Battery—Case Study
Authors: Tudoroiu Nicolae , Zaheeruddin Mohammed , Tudoroiu Roxana-Elena , Radu Mihai Sorin , Chammas Hana
Published: May 2023

This research paper aims to design and implement an intelligent least short time memory (LSTM) deep learning classification technique to detect possible anomalies in measurements dataset within a particular Li-ion battery type. For the state of charge (SOC) and battery faults estimation, a Joint State and Parameter Extended Kalman Filter (JEKF) estimator is developed. The SOC accuracy performance is excellent, with less than 0.5% error during steady-state, compared to the 2% error reported in the literature. For the design and implementation of JEKF SOC and parameter estimation is chosen a preset Li-ion battery Simulink Simscape generic model. It is also helpful to generate the healthy and faulty measurement dataset to design and implement the proposed intelligent LSTM classifier deep learning technique. The generic Li-ion battery model is wisely selected for the “proof concept” purpose, model validation, and algorithms’ robustness, accuracy, and effectiveness. Compared to the traditional EKF fault diagnosis and isolation (FDI), a model-based estimation strategy, the proposed classification LSTM technique is an intelligent data-driven-based deep learning algorithm of high accuracy (around 80%) and loss performance close to zero. Therefore, this feature makes data collection of dataset measurements directly from Li-ion battery sensors possible, which is beneficial for generating online fault scenarios. Additionally, the LSTM deep learning technique can remarkably classify all detected anomalies with high accuracy, independent of battery model accuracy, uncertainties, and unmodeled dynamics. Also, high-performance accuracy root mean square error (RMSE) of 0.0588 (voltage fault), approximately 5.5×10−7 (healthy) and 8.87 × 10−6 (current fault) for deep learning shallow neural network (DLSNN) reveals an obvious superiority of both compared to the traditional FDI estimation strategies.
Solving the Riddle of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: The Added Role of Cardiac Magnetic Resonance
Authors: Stankowski Kamil , Figliozzi Stefano , Lisi Costanza , Catapano Federica , Panico Cristina , Cannata Francesco , Mantovani Riccardo , Frontera Antonio , Bragato Renato Maria , Stefanini Giulio , Monti Lorenzo , Condorelli Gianluigi , Francone Marco
Published: May 2023

Cardiac magnetic resonance (CMR) has been recently implemented in clinical practice to refine the daunting task of establishing the risk of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We present an exemplificative case highlighting the practical clinical utility of this imaging modality in a 24-year-old man newly diagnosed with an apical HCM. CMR was essential in unmasking a high risk of SCD, which appeared low-intermediate after traditional risk assessment. A discussion examines the essential role of CMR in guiding the patient’s therapy and underlines the added value of CMR, including novel and potential CMR parameters, compared to traditional imaging assessment for SCD risk stratification.