bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders
Authors: Theleritis Christos , Siarkos Kostas , Politis Anastasios , Smyrnis Nikolaos , Papageorgiou Charalabos , Politis Antonios M.
Published: July 2023

Objective: Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed. Design: A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised. Results: In patients with Alzheimer’s Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson’s Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects. Conclusions: Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.
Could Vulnerability to Motion Sickness and Chronic Pain Coexist within a Sensorimotor Phenotype? Insights from over 500 Pre-Pain Motion Sickness Reports
Authors: Harvie Daniel Simon
Published: July 2023

Background: The sensorimotor incongruence theory proposes that certain instances of pain result from conflicts in the brain’s sensorimotor networks. Indeed, injuries may cause abnormalities in afferent and cortical signaling resulting in such conflicts. Motion sickness also occurs in instances of incongruent sensorimotor data. It is possible that a sensory processing phenotype exists that predisposes people to both conditions. Aim: The aim of this study was to investigate whether participants with chronic pain recall greater susceptibility to motion sickness before chronic pain onset. Method: Data were collected via an online LimeSurvey. A self-report tendency toward motion sickness was measured using the Motion Sickness Susceptibility Questionnaire. Group differences were analysed using analysis of covariance methods. Results: 530 patients (low back pain, n = 198; neck pain, n = 59; whiplash-associated disorder, n = 72; fibromyalgia syndrome, n = 114; Migraine, n = 41) and 165 pain-free controls were surveyed. ANCOVA analysis, using sex and anxiety as covariates, suggested that childhood motion sickness susceptibility scores differed by group (F = 2.55 (6, 615), p = 0.019, (ηp2) = 0.024). Planned comparisons, with corrected p-values, suggested that childhood motion sickness was not statistically greater for low back pain, rheumatoid arthritis, migraine, neck pain or whiplash-associated disorder (ps > 0.05), although scores were on average 27%, 42%, 47%, 48% and 58% higher, respectively. Childhood susceptibility was statistically higher in people with FMS (p = 0.018), with scores on average 83% higher than controls. ANCOVA analysis, using sex and anxiety as covariates, suggested that adult motion sickness susceptibility scores did not differ by group (F = 1.86 (6, 613), p = 0.086), although average scores were, on average, at least 33% higher in persistent pain groups. Conclusions: According to retrospective reporting, greater susceptibility to motion sickness appears to pre-date persistent pain in some conditions. This supports the possibility that motion sickness and chronic pain may, in some cases, have overlapping mechanisms related to the handling of incongruent sensorimotor data.
Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
Authors: Tseng Hsiang-Chien , Wang Mao-Hsien , Fang Chih-Hsiang , Lin Yi-Wen , Soung Hung-Sheng
Published: July 2023

With its pathophysiological characteristics strongly similar to patients with tardive dyskinesia (TD), haloperidol (HP)-induced neurotoxicity and orofacial dyskinesia (OD) in animal models have long been used to study human TD. This study aimed to explore the potential protective effects of betaine (BT), a vital biochemical compound present in plants, microorganisms, animals, and various dietary sources. The study focused on investigating the impact of BT on haloperidol (HP)-induced orofacial dyskinesia (OD) in rats, as well as the underlying neuroprotective mechanisms. To induce the development of OD, which is characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), rats were administered HP (1 mg/kg i.p.) for 21 consecutive days. BT was administered intraperitoneally (i.p.) at doses of 30 and 100 mg/kg, 60 min later, for 21 successive days. On the 21st day, after evaluating OD behavior, the rats were sacrificed, and various measurements were taken to assess the nitrosative and oxidative status, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptotic markers in the striatum. The results demonstrated that (1) HP induced OD development, and (2) BT was found to prevent most of the HP-induced OD; decrease oxidative stress levels; increase anti-oxidation power; prevent mitochondrial dysfunction; and reduce the levels of neuroinflammatory and apoptotic markers in the striatum. Our results demonstrate that the neuroprotective effects of BT against HP-induced OD are credited to its antioxidant prevention of mitochondrial dysfunction, anti-neuroinflammatory effects, and anti-apoptotic effects, suggesting that BT may be a novel therapeutic candidate in delaying or treating human TD in clinical settings. However, further studies will be warranted to extrapolate preclinical findings into clinical studies for a better understanding of the role of BT.
Robot-Enabled Construction Assembly with Automated Sequence Planning Based on ChatGPT: RoboGPT
Authors: You Hengxu , Ye Yang , Zhou Tianyu , Zhu Qi , Du Jing
Published: July 2023

Robot-based assembly in construction has emerged as a promising solution to address numerous challenges such as increasing costs, labor shortages, and the demand for safe and efficient construction processes. One of the main obstacles in realizing the full potential of these robotic systems is the need for effective and efficient sequence planning for construction tasks. Current approaches, including mathematical and heuristic techniques or machine learning methods, face limitations in their adaptability and scalability to dynamic construction environments. To expand the current robot system’s sequential understanding ability, this paper introduces RoboGPT, a novel system that leverages the advanced reasoning capabilities of ChatGPT, a large language model, for automated sequence planning in robot-based assembly applied to construction tasks. The proposed system adapts ChatGPT for construction sequence planning and demonstrates its feasibility and effectiveness through experimental evaluation including two case studies and 80 trials involving real construction tasks. The results show that RoboGPT-driven robots can handle complex construction operations and adapt to changes on the fly. This paper contributes to the ongoing efforts to enhance the capabilities and performance of robot-based assembly systems in the construction industry, and it paves the way for further integration of large language model technologies in the field of construction robotics.
Flexural Behavior of Slabs with Different Anchorage Locations of Longitudinal Reinforcing Bars in a Composite Basement Wall Junction
Authors: Kim Sanghee , Mun Ju-Hyun , Hong Jong-Kook , Yang Keun-Hyeok , Kim Soo-Min , Sim Jae-Il
Published: July 2023

Although the anchorage location of longitudinal reinforcing bars is a significant design element for flexural behavior, the conventional anchorage method of using longitudinal reinforcing bars has limited applications in new types of structures, such as composite structures. Therefore, this study examined the effect of the anchorage location of longitudinal reinforcing bars on the flexural behavior of slabs at the junctions of developed composite basement walls (SCBW) under monotonic loads at the top free end of the slab. The test results showed that the slab with longitudinal reinforcing bars anchored to the cast-in-place pile (CIP) in the composite basement wall exhibited ductile behavior accompanied by the yielding of the longitudinal reinforcing bars, a relatively wide area of vertical cracks propagating along the slab length, and a plastic plateau flow in the load–deflection relationships. In particular, the slab with longitudinal reinforcing bars anchored to the basement wall experienced severe crack concentration localized at the junction of the composite basement walls and concrete spalling in the basement walls, which resulted in no yielding of the longitudinal reinforcing bars and no cracks in the slab. Consequently, in a slab, it is recommended that longitudinal reinforcing bars be anchored into the CIP by penetrating the steel plate.
Experimental Research Studies on Seismic Behaviour of Confined Masonry Structures: Current Status and Future Needs
Authors: Pérez Gavilán Escalante Juan , Brzev Svetlana , Espinosa Cazarin Eric , Ganzerli Sara , Quiun Daniel , Reiter Matthew T.
Published: July 2023

Confined masonry (CM) is a construction system that consists of loadbearing masonry wall panels enclosed by vertical and horizontal reinforced concrete confining elements. The presence of these confining elements distinguishes CM from unreinforced masonry systems, and makes this technology suitable for building construction in regions subject to intense seismic or wind activity. CM construction has been used in many countries and regions, and has performed well in past earthquakes. The purpose of this paper is to review experimental research studies related to the seismic in-plane and out-of-plane behaviour of CM structures. The authors identify the key design and construction parameters considered in previous research studies and perform statistical analyses to establish their influence on the seismic performance of CM walls. For the purposes of this study, the authors compiled databases of previous experimental studies on CM wall specimens, which were used for statistical analyses. Finally, the paper discusses research gaps and the need for future research studies that would contribute to the understanding of seismic behaviour and failure mechanisms of CM walls.
Architectural Design Criteria Considering the Circular Economy and Buildability for Smart Disaster Relief Shelter Prototyping
Authors: Karimi Reyhaneh , Shirowzhan Sara , Sepasgozar Samad M. E.
Published: July 2023

The frequency of natural disasters is exacerbated by the escalating impacts of climate change with the need for effective relief shelters for victims and displaced individuals. Providing accessible and easy-to-assemble relief shelters is essential in addressing these needs. Due to climate-related challenges and the need for sustainable solutions, the integration of circularity principles in shelter design has become imperative. Circular economy principles promote the efficient use of resources, minimising waste generation and the cost of shelters. Moreover, a considerable number of people usually suffer from homelessness, and an increasing number of families live in slums in every part of the globe. All such people are entitled to be housed in affordable, safe, and appropriate shelters for at least several months after a disaster until they can either rebuild their former houses or find somewhere decent to settle after recovering from the hardship. With the aim of investigating the immediate housing needs of people after a disaster, this paper identifies the essential factors that must be taken into account during shelter design. The paper also presents the prototype developed on the basis of theoretical criteria and the identified factors. The paper’s main objectives were to design an easy-to-assemble emergency shelter on circular economy principles, identify critical factors for the circularity and buildability of the shelter, and present a proposed smart shelter acceptance model. The methodology behind the research involves conducting an intensive literature review and creating a novel prototype of a smart disaster relief shelter on the basis of long-run laboratory work and various prototype iterations. The paper presents the details of the novel prototype and shows materials that enhance the circularity of the shelter, according to a unique architectural design strategy of ‘reusing’ materials to enhance circularity practice in the design and construction sectors. The prototype was developed in a workshop after 6 months of reiterations using plastic water bottles, basic pipes, and other reusable materials. Then, by incorporating the essential factors, a set of criteria was designed that can be used as a guide for the architectural design of shelters. The criteria offered in this paper are useful to evaluate each factor’s importance in shelter design. In total, 51 effective factors in designing and constructing such accommodation are presented, clustered into five design strategy groups: social–cultural, physical–technical, environmental, economic, and organisational.
Selection of tRNA Genes in Human Breast Tumours Varies Substantially between Individuals
Authors: Butterfield Sienna P. , Sizer Rebecca E. , Rand Emma , White Robert J.
Published: July 2023

Abnormally elevated expression of tRNA is a common feature of breast tumours. Rather than a uniform increase in all tRNAs, some are deregulated more strongly than others. Elevation of particular tRNAs has been associated with poor prognosis for patients, and experimental models have demonstrated the ability of some tRNAs to promote proliferation or metastasis. Each tRNA isoacceptor is encoded redundantly by multiple genes, which are commonly dispersed across several chromosomes. An unanswered question is whether the consistently high expression of a tRNA in a cancer type reflects the consistent activation of the same members of a gene family, or whether different family members are activated from one patient to the next. To address this question, we interrogated ChIP-seq data to determine which tRNA genes were active in individual breast tumours. This revealed that distinct sets of tRNA genes become activated in individual cancers, whereas there is much less variation in the expression patterns of families. Several pathways have been described that are likely to contribute to increases in tRNA gene transcription in breast tumours, but none of these can adequately explain the observed variation in the choice of genes between tumours. Current models may therefore lack at least one level of regulation.
Soft Tissue Sarcoma Mimicking Melanoma: A Systematic Review
Authors: Cassalia Fortunato , Cavallin Francesco , Danese Andrea , Del Fiore Paolo , Di Prata Claudia , Rastrelli Marco , Belloni Fortina Anna , Mocellin Simone
Published: July 2023

Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search of the MEDLINE/Pubmed, EMBASE, and SCOPUS databases was conducted through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%), and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%), and MiTF (3%). The main reasons for a second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found to be positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In cases of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.
Exploring Natural Products as Radioprotective Agents for Cancer Therapy: Mechanisms, Challenges, and Opportunities
Authors: Zhang Yi , Huang Ying , Li Zheng , Wu Hanyou , Zou Bingwen , Xu Yong
Published: July 2023

Radiotherapy is an important cancer treatment. However, in addition to killing tumor cells, radiotherapy causes damage to the surrounding cells and is toxic to normal tissues. Therefore, an effective radioprotective agent that prevents the deleterious effects of ionizing radiation is required. Numerous synthetic substances have been shown to have clear radioprotective effects. However, most of these have not been translated for use in clinical applications due to their high toxicity and side effects. Many medicinal plants have been shown to exhibit various biological activities, including antioxidant, anti-inflammatory, and anticancer activities. In recent years, new agents obtained from natural products have been investigated by radioprotection researchers, due to their abundance of sources, high efficiency, and low toxicity. In this review, we summarize the mechanisms underlying the radioprotective effects of natural products, including ROS scavenging, promotion of DNA damage repair, anti-inflammatory effects, and the inhibition of cell death signaling pathways. In addition, we systematically review natural products with radioprotective properties, including polyphenols, polysaccharides, alkaloids, and saponins. Specifically, we discuss the polyphenols apigenin, genistein, epigallocatechin gallate, quercetin, resveratrol, and curcumin; the polysaccharides astragalus, schisandra, and Hohenbuehelia serotina; the saponins ginsenosides and acanthopanax senticosus; and the alkaloids matrine, ligustrazine, and β-carboline. However, further optimization through structural modification, improved extraction and purification methods, and clinical trials are needed before clinical translation. With a deeper understanding of the radioprotective mechanisms involved and the development of high-throughput screening methods, natural products could become promising novel radioprotective agents.
Pre-Referral Primary Care Blood Tests and Symptom Presentation before Cancer Diagnosis: National Cancer Diagnosis Audit Data
Authors: Cranfield Ben M. , Abel Gary A. , Swann Ruth , Moore Sarah F. , McPhail Sean , Rubin Greg P. , Lyratzopoulos Georgios
Published: July 2023

Background: Blood tests can support the diagnostic process in primary care. Understanding how symptomatic presentations are associated with blood test use in patients subsequently diagnosed with cancer can help to benchmark current practices and guide interventions. Methods: English National Cancer Diagnosis Audit data on 39,751 patients with incident cancer in 2018 were analysed. The frequency of four generic (full blood count, urea and electrolytes, liver function tests, and inflammatory markers) and five organ-specific (cancer biomarkers (PSA or CA125), serum protein electrophoresis, ferritin, bone profile, and amylase) blood tests was described for a total of 83 presenting symptoms. The adjusted analysis explored variation in blood test use by the symptom-positive predictive value (PPV) group. Results: There was a large variation in generic blood test use by presenting symptoms, being higher in patients subsequently diagnosed with cancer who presented with nonspecific symptoms (e.g., fatigue 81% or loss of appetite 79%), and lower in those who presented with alarm symptoms (e.g., breast lump 3% or skin lesion 1%). Serum protein electrophoresis (reflecting suspicion of multiple myeloma) was most frequently used in cancer patients who presented with back pain (18%), and amylase measurement (reflecting suspicion of pancreatic cancer) was used in those who presented with upper abdominal pain (14%). Prostate-specific antigen (PSA) use was greatest in men with cancer who presented with lower urinary tract symptoms (88%), and CA125 in women with cancer who presented with abdominal distention (53%). Symptoms with PPV values between 2.00–2.99% were associated with greater test use (64%) compared with 52% and 51% in symptoms with PPVs in the 0.01–0.99 or 1.00–1.99% range and compared with 42% and 31% in symptoms with PPVs in either the 3.00–4.99 or ≥5% range (p < 0.001). Conclusions: Generic blood test use reflects the PPV of presenting symptoms, and the use of organ-specific tests is greater in patients with symptomatic presentations with known associations with certain cancer sites. There are opportunities for greater blood test use in patients presenting with symptoms that do not meet referral thresholds (i.e., <3% PPV for cancer) where information gain to support referral decisions is likely greatest. The findings benchmark blood test use in cancer patients, highlighting opportunities for increasing use.
Mirtazapine versus Megestrol in the Treatment of Anorexia–Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial
Authors: Almeida Olga Laura Sena , Ferriolli Eduardo , Taveira Roberta Cristina Cintra , Rosenburg Meire Gallo , Campanari Daniela Dalpubel , da Cruz Alves Natália Maira , Pfrimer Karina , Rapatoni Liane , Peria Fernanda Maris , Lima Nereida K. C.
Published: July 2023

This study compared mirtazapine with megestrol in the management of cancer-related anorexia–cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia–cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.
State of the Art of Pharmacological Activators of p53 in Ocular Malignancies
Authors: Casciano Fabio , Zauli Enrico , Busin Massimo , Caruso Lorenzo , AlMesfer Saleh , Al-Swailem Samar , Zauli Giorgio , Yu Angeli Christy
Published: July 2023

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival and corneal tumors, retinoblastoma, uveal melanoma, and intraocular melanoma. As non-selective cancer chemotherapies as well as ionizing radiation can be associated with either poor efficacy or dose-limiting toxicities in the eye, reconstitution of the p53 signaling pathway currently represents an attractive target for cancer therapy. The present review discusses the role of p53 in the pathogenesis of these ocular tumors and outlines the various pharmacological activators of p53 that are currently under investigation for the treatment of ocular malignancies.
Chemoradiotherapy Combined with Brachytherapy for the Definitive Treatment of Esophageal Carcinoma
Authors: Mangesius Julian , Hörmandinger Katharina , Jäger Robert , Skvortsov Sergej , Plankensteiner Marlen , Maffei Martin , Seppi Thomas , Dejaco Daniel , Santer Matthias , Sarcletti Manuel , Ganswindt Ute
Published: July 2023

This study aims to investigate the effect of dose escalation with brachytherapy (BT) as an addition to definitive chemoradiotherapy (CRT) on local control and survival in esophageal cancer. From 2001 to 2020, 183 patients with locally limited or locally advanced esophageal cancer received definitive CRT with or without brachytherapy in a two-center study. External-beam radiotherapy was delivered at 50.4 Gy in 1.8 Gy daily fractions, followed by a sequential boost to the primary tumor of 9 Gy in 1.8 Gy daily fractions if indicated. Intraluminal high dose rate (HDR) Ir-192 brachytherapy was performed on 71 patients at 10 Gy in two fractions, with one fraction per week. The combined systemic therapy schedules used included 5-fluorouracil/cisplatin or 5-fluorouracil alone. Cisplatin was not administered in patients receiving brachytherapy. The median local progression-free survival was significantly extended in the BT group (18.7 vs. 6.0 months; p < 0.0001), and the median local control was also significantly prolonged (30.5 vs. 11.3 months, p = 0.008). Overall survival (OS) significantly increased in the BT group (median OS 22.7 vs. 9.1 months, p < 0.0001). No significant difference in the overall rate of acute toxicities was observed; however, the rate of acute esophagitis was significantly higher in the BT group (94.4% vs. 81.2%). Likewise, the overall rate of late toxicities (43.7% vs. 18.8%) was significantly higher in the BT group, including the rate of esophageal stenosis (22.5% vs. 9.8%). There was no difference in the occurrence of life-threatening or lethal late toxicities (grades 4 and 5). Brachytherapy, after chemoradiation with single-agent 5-FU, represents a safe and effective alternative for dose escalation in the definitive treatment of esophageal cancer.
Clinical Implication of Bilateral and Unilateral Multifocality in Papillary Thyroid Carcinoma: A Propensity Score-Matched Study
Authors: Kim Youngmin , An Solji , Park Joonseon , Bae Ja Seong , Kim Jeong Soo , Kim Kwangsoon
Published: July 2023

Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary’s Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance.
A Role of PI3K/Akt Signaling in Oocyte Maturation and Early Embryo Development
Authors: Kalous Jaroslav , Aleshkina Daria , Anger Martin
Published: July 2023

A serine/threonine-specific protein kinase B (PKB), also known as Akt, is a key factor in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway that regulates cell survival, metabolism and proliferation. Akt phosphorylates many downstream specific substrates, which subsequently control the nuclear envelope breakdown (NEBD), centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. In vertebrates, Akt is also an important player during oogenesis and preimplantation development. In the signaling pathways regulating mRNA translation, Akt is involved in the control of mammalian target of rapamycin complex 1 (mTORC1) and thereby regulates the activity of a translational repressor, the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). In this review, we summarize the functions of Akt in mitosis, meiosis and early embryonic development. Additionally, the role of Akt in the regulation of mRNA translation is addressed with respect to the significance of this process during early development.
Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent
Authors: Drummond Sarah E. , Burns David P. , El Maghrani Sarah , Ziegler Oscar , Healy Vincent , O’Halloran Ken D.
Published: July 2023

Chronic intermittent hypoxia (CIH)-induced redox alterations underlie diaphragm muscle dysfunction. We sought to establish if NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) underpin CIH-induced changes in diaphragm muscle, which manifest as impaired muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); chronic intermittent hypoxia-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) administered in the drinking water throughout exposure to CIH. In separate studies, we examined sham and CIH-exposed NOX2-null mice (B6.129S-CybbTM1Din/J). Apocynin co-treatment or NOX2 deletion proved efficacious in entirely preventing diaphragm muscle dysfunction following exposure to CIH. Exposure to CIH had no effect on NOX2 expression. However, NOX4 mRNA expression was increased following exposure to CIH in wild-type and NOX2 null mice. There was no evidence of overt CIH-induced oxidative stress. A NOX2-dependent increase in genes related to muscle regeneration, antioxidant capacity, and autophagy and atrophy was evident following exposure to CIH. We suggest that NOX-dependent CIH-induced diaphragm muscle weakness has the potential to affect ventilatory and non-ventilatory performance of the respiratory system. Therapeutic strategies employing NOX2 blockade may function as an adjunct therapy to improve diaphragm muscle performance and reduce disease burden in diseases characterised by exposure to CIH, such as obstructive sleep apnoea.
Modulation of Lysosomal Cl− Mediates Migration and Apoptosis through the TRPML1 as a Lysosomal Cl− Sensor
Authors: Lee Dongun , Hong Jeong Hee
Published: July 2023

Lysosomes are responsible for protein degradation and clearance in cellular recycling centers. It has been known that the lysosomal chloride level is enriched and involved in the intrinsic lysosomal function. However, the mechanism by which chloride levels can be sensed and that of the chloride-mediated lysosomal function is unknown. In this study, we verified that reduced chloride levels acutely induced lysosomal calcium release through TRPML1 and lysosomal repositioning toward the juxtanuclear region. Functionally, low chloride-induced lysosomal calcium release attenuated cellular migration. In addition, spontaneous exposure to low chloride levels dysregulated lysosomal biogenesis and subsequently induced delayed migration and promoted apoptosis. Two chloride-sensing GXXXP motifs in the TRPML1 were identified. Mutations in the GXXXP motif of TRPML1 did not affect chloride levels, and there were no changes in migratory ability. In this study, we demonstrated that the depletion of chloride induces reformation of the lysosomal calcium pool and subsequently dysregulated cancer progression, which will assist in improving therapeutic strategies for lysosomal accumulation-associated diseases or cancer cell apoptosis.
Developing Oncolytic Viruses for the Treatment of Cervical Cancer
Authors: Kalafati Eleni , Drakopoulou Ekati , Anagnou Nicholas P. , Pappa Kalliopi I.
Published: July 2023

Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies.
Formation and Photophysical Properties of Silver Clusters in Bulk of Photo-Thermo-Refractive Glass
Authors: Mironov Leonid Yu. , Marasanov Dmitriy V. , Sannikova Mariia D. , Zyryanova Ksenia S. , Slobozhaninov Artem A. , Kolesnikov Ilya E.
Published: July 2023

The bright luminescence of silver clusters in glass have potential applications in solid-state lighting, optical memory, and spectral converters. In this work, luminescent silver clusters were formed in the bulk of photo-thermo-refractive glass (15Na2O-5ZnO-2.9Al2O3-70.3SiO2-6.5F, mol.%) doped with different Ag2O concentrations from 0.01 to 0.05 mol.%. The spontaneous formation of plasmonic nanoparticles during glass synthesis was observed at 0.05 mol.% of Ag2O in the glass composition, limiting the silver concentration range for cluster formation. The luminescence of silver clusters was characterized by steady-state and time-resolved spectroscopy techniques. The rate constants of fluorescence, phosphorescence, intersystem crossing, and nonradiative deactivation were estimated on the basis of an experimental study. A comparison of the results obtained for the photophysical properties of luminescent silver clusters formed in the ion-exchanged layers of photo-thermo-refractive glass is provided.
Numerical Study of CO2 Removal from Inhalational Anesthesia System by Using Gas-Ionic Liquid Membrane
Authors: Davidy Alon
Published: July 2023

Inhalational anesthesia is supplied through an assisted ventilation system. It is mostly composed of xenon or nitrous oxide, halogenated hydrocarbons (HHCs), and oxygen. In order to reduce costs of the anesthesia compounds, the remaining anesthetics present in exhalation are recycled and reused, in order to minimize the amount of fresh anesthesia. An alkali hydroxide mixture (called soda lime) is employed in order to remove CO2 from the exhalation. However toxic compounds may be formed during the reaction of soda lime with halogenated hydrocarbons. Ionic liquids (ILs) have several advantages such as non-volatility, functionality, high carbon solubility, and low energy requirements for regeneration. In the framework of this research, carbon dioxide removal with ionic liquids has been numerically studied. COMSOL multi-physics finite element software has been applied. It solves the continuity, fluid flow, and diffusion equations. A new algorithm has been developed for calculating the infrared (IR) radiation absorption of CO2. Its absorption coefficient has wavelength-dependent properties. The gaseous absorption coefficient has been calculated by using HITRAN spectral database. It has been found that the CO2 is absorbed almost completely by the 1-ethyl-3-methylimidazolium dicyanamide ([emim][DCA]) ionic liquid after a period of 1000 s. It has been shown that the absorption coefficient of CO2 can be neglected in the interval below 1.565 μm, and then at 1.6 μm, it increases to the same order as that for CO. Thus, it is possible to detect CO2 by applying a laser diode which is capable to transmit IR radiation at a wavelength of 1.6 μm. This time period is a function of the diffusion coefficient of the CO2 in the membrane and in the ionic liquid.
Basophils Predict Mite Sensitization in Patients with Kawasaki Disease
Authors: Chang Ling-Sai , Huang Ying-Hsien , Chang Hsin-Yu , Lee Zon-Min , Feng Wei-Ling , Kuo Ho-Chang
Published: July 2023

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE on allergy biomarkers after KD is diagnosed. Objective: This study aimed to investigate the pattern of specific IgE levels against food and inhalant allergens. Methods: This retrospective study was conducted in Taiwan to identify patients admitted with KD. A subset of 453 admitted KD children younger than or equal to five years of age with intravenous immunoglobulin (IVIG) was followed up at our clinic with available specific IgE data. Results: The most common allergens were Dermatophagoides farina or pteronyssinus, house-dust, and cockroach mix. Positive specific IgE for Dermatophagoides farina or pteronyssinus was less common in children diagnosed with KD who were two years old or younger (p = 0.028). KD patients with higher basophils before IVIG (p = 0.010 and 0.018 for two different mites) and higher C-reactive protein (CRP, p = 0.030 and 0.028) after IVIG were at higher risk of mite sensitization. Integrated mite sensitization demonstrated higher basophils before IVIG, age at KD diagnosis, and the male sex to be clinically meaningful after logistic regression models. Conclusions: This study is the first to suggest that specific IgE in KD patients may be correlated with age at KD diagnosis, as well as basophils. Further longitudinal prospective studies are warranted to clarify the unique profile of specific IgE in KD patients.
A DFT Study and Hirshfeld Surface Analysis of the Molecular Structures, Radical Scavenging Abilities and ADMET Properties of 2-Methylthio(methylsulfonyl)-[1,2,4]triazolo [1,5-a]quinazolines: Guidance for Antioxidant Drug Design
Authors: Bakheit Ahmed H. , Abuelizz Hatem A. , Al-Salahi Rashad
Published: July 2023

Optimisation at B3LYP/6-311G(d,p) was used in a DFT study of the characteristics of 2-methylthio(methylsulfonyl)-triazoloquinazolines (1, 2). The design-critical role of intramolecular hydrogen bonding in stabilising both structures is emphasised. The stability of a crystal is a consequence of interactions between its molecules. According to the global index, 2-methylthio-triazoloquinazoline (1) is more electrophilic and reactive, while 2-methylsulfonyl-triazoloquinazoline (2) is more electrophilic and less reactive. Electrophilic, nucleophilic, and radicalophilic sites, polarizable atoms, and charge distributions are all identified by local descriptors. Consistent with crystal structures, negative potentials imply 1 and 2 hydrogen bond acceptors, whereas positive potentials indicate donor capabilities. Antioxidant activity may be enabled via radical stabilisation, as suggested by radicalophilic features such as hydrogen atom donors, resonance, and antioxidants. H7, H8, and H9 atoms in triazoloquinazolines 1 and 2 have been hypothesised to contribute to the compounds’ antioxidant activity through HAT, SPLET, and SET-PT mechanisms. Calculations provide insights into stability, reactivity, electrostatic profiles, radical stabilization ability, toxicity risks. Radical stabilizing ability, reactive site hierarchies suggest possible antioxidant mechanisms. ADMET profiles identify challenges impacting candidate suitability.
Synthesis, X-ray Crystal Structure, and Computational Characterization of Tetraphenylborate, 3-(5H-Dibenzo[a,d] cyclohepten-5-ylidene)-N, N-Dimethyl-1-propanamine
Authors: Bakheit Ahmed H. , Al-Salahi Rashad , Ghabbour Hazem A. , Ali Essam A. , AlRuqi Obaid S. , Mostafa Gamal A. E.
Published: July 2023

A cyclobenzaprine-tetraphenylborate (CBP-TPB) complex was synthesized, achieving a 78% yield through an anion exchange reaction. The white crystals of the complex were formed in acetonitrile and characterized using a variety of spectroscopic and analytical techniques, including ultraviolet, infrared, mass, elemental, and nuclear magnetic resonance (NMR) spectroscopy, as well as X-ray crystallography. The study employed a comprehensive approach to investigate the structural properties, stability, and behavior of the CBP-TPB complex. The use of crystallographic analysis, Hirshfeld surface analysis, quantum theory of atoms in molecules, noncovalent interaction reduced density gradient, global reactivity descriptors, frontier molecular orbitals, molecular electrostatic potential, and ultraviolet-visible spectroscopy provided valuable insights into the complex’s molecular geometries, supramolecular features, and intermolecular interactions. These findings contribute to a better understanding of the CBP-TPB complex’s potential applications in fields such as pharmaceuticals and materials science and emphasize the importance of combining theoretical predictions and experimental measurements in understanding molecular properties. The study also demonstrated the potential of density functional theory-based computational methods for predicting NMR spectroscopic parameters.
Performance Comparison of SONOS-Type UV TD Sensor Using Indium Tin Oxide-Aluminum Oxide-Zirconia Aluminum Oxide-Silicon Oxide-Silicon and Indium Tin Oxide-Aluminum Oxide-Hafnium Aluminum Oxide-Silicon Oxide-Silicon
Authors: Jong Fun-Cheng , Hsieh Wen-Ching
Published: July 2023

This study compares the performance of two types of capacitive devices, indium tin oxide-aluminum oxide-zirconia aluminum oxide-silicon oxide-silicon (IAZAOS) and indium tin oxide-aluminum oxide-hafnium aluminum oxide-silicon oxide-silicon (IAHAOS), as silicon-oxide-nitride-oxide-silicon (SONOS) non-volatile memory (NVM) total dose of ultraviolet radiation (UV TD) sensors. Results show that IAZAOS with zirconia aluminum oxide as the charge-trapping layer outperforms IAHAOS with hafnium aluminum oxide for a UV TD sensor. After exposure to UV TD irradiation of 100 mW·s/cm2, the threshold voltage (VT) change of IAZAOS is almost 1.25 times that of IAHAOS. The study also found that annealing can significantly improve the response performance of IAZAOS UV TD sensors. Furthermore, IAZAOS devices with partially smaller nanocrystals in the charge-trapping layer greatly enhance the response of SONOS-type UV TD sensors. The study also compared the constant voltage stress-induced leakage current (CVSILC) and found that the CVSILC for annealed IAZAOS devices is 1000 times smaller than that of IAHAOS devices. Moreover, the IAZAOS-I2Z2 exhibits a superior performance regarding irradiation/refresh cycle endurance as compared to the IAHAOS-I2H1 device. These findings suggest that IAZAOS capacitive devices have superior performance and potential for use in SONOS-type UV TD sensors.
A New Basal Neornithischian Dinosaur from the Phu Kradung Formation (Upper Jurassic) of Northeastern Thailand
Authors: Manitkoon Sita , Deesri Uthumporn , Khalloufi Bouziane , Nonsrirach Thanit , Suteethorn Varavudh , Chanthasit Phornphen , Boonla Wansiri , Buffetaut Eric
Published: July 2023

An exceptional articulated skeleton of a new basal neornithischian dinosaur, Minimocursor phunoiensis gen. et sp. nov., was discovered in the Late Jurassic Phu Kradung Formation at the Phu Noi locality, Kalasin Province, Thailand, a highly productive non-marine fossil vertebrate locality of the Khorat Plateau. It is one of the best-preserved dinosaurs ever found in Southeast Asia. Minimocursor phunoiensis gen. et sp. nov. shows a combination of both plesiomorphic and apomorphic characters resembling those of Late Jurassic to Early Cretaceous small-bodied ornithischians from China: a low subtriangular boss is projected laterally on the surface of the jugal, the brevis shelf of the ilium is visible in lateral view along its entire length, a distinct supraacetabular flange is present on the pubic peduncle of the ilium, the prepubis tip extends beyond the distal end of the preacetabular process of the ilium, and the manus digit formula is ?-3-4-3-2. The phylogenetic analysis shows that this dinosaur is among the most basal neornithischians. This study provides a better understanding of the early evolution and taxonomic diversity of ornithischians in Southeast Asia.
Perforating Gout: Expanding the Differential for Transepidermal Elimination
Authors: Bohdanowicz Michal , Bradshaw Scott H.
Published: July 2023

Perforating dermatoses are dermatologic disorders with transepidermal elimination (TE) of dermal substances. While TE is typically associated with collagen and elastin, it can also occur as a secondary event in other processes, and it is important to keep a broad differential. We present a case of perforating tophaceous gout, which underscores the need for a thoughtful approach to perforating disorders. An updated review of recent literature is also presented.
Focal Liver Lesions in Budd-Chiari Syndrome: Spectrum of Imaging Findings
Authors: Rizzetto Francesco , Rutanni Davide , Carbonaro Luca Alessandro , Vanzulli Angelo
Published: July 2023

Budd–Chiari syndrome (BCS) is a rare clinical entity characterized by hepatic venous outflow obstruction, resulting in liver congestion and subsequent chronic parenchymal damage. This condition often leads to the development of focal liver lesions, including benign focal nodular hyperplasia-like regenerative nodules, hepatocellular carcinoma, and perfusion-related pseudo-lesions. Computed tomography, ultrasound, and magnetic resonance are the commonly employed imaging modalities for the follow-up of BCS patients and for the detection and characterization of new-onset lesions. The accurate differentiation between benign and malignant nodules is crucial for optimal patient management and treatment planning. However, it can be challenging due to the variable and overlapping characteristics observed. This review aims to provide a comprehensive overview of the imaging features and differential diagnosis of focal liver lesions in BCS, emphasizing the key findings and discussing the challenges associated with their interpretation, with the purpose of facilitating the subsequent clinical decision-making.