bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog
Authors: Gu Xin , Majumder Joydeb , Taratula Olena , Kuzmov Andriy , Garbuzenko Olga , Pogrebnyak Natalia , Minko Tamara
Published: May 2024

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.
Safflower CtFLS1-Induced Drought Tolerance by Stimulating the Accumulation of Flavonols and Anthocyanins in Arabidopsis thaliana
Authors: Ma Xintong , Hou Yuying , Umar Abdul Wakeel , Wang Yuhan , Yu Lili , Ahmad Naveed , Yao Na , Zhang Min , Liu Xiuming
Published: May 2024

Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower.
Large-Sample Genome-Wide Association Study of Resistance to Retained Placenta in U.S. Holstein Cows
Authors: Prakapenka Dzianis , Liang Zuoxiang , Zaabza Hafedh B. , VanRaden Paul M. , Van Tassell Curtis P. , Da Yang
Published: May 2024

A genome-wide association study of resistance to retained placenta (RETP) using 632,212 Holstein cows and 74,747 SNPs identified 200 additive effects with p-values < 10−8 on thirteen chromosomes but no dominance effect was statistically significant. The regions of 87.61–88.74 Mb of Chr09 about 1.13 Mb in size had the most significant effect in LOC112448080 and other highly significant effects in CCDC170 and ESR1, and in or near RMND1 and AKAP12. Four non-ESR1 genes in this region were reported to be involved in ESR1 fusions in humans. Chr23 had the largest number of significant effects that peaked in SLC17A1, which was involved in urate metabolism and transport that could contribute to kidney disease. The PKHD1 gene contained seven significant effects and was downstream of another six significant effects. The ACOT13 gene also had a highly significant effect. Both PKHD1 and ACOT13 were associated with kidney disease. Another highly significant effect was upstream of BOLA-DQA2. The KITLG gene of Chr05 that acts in utero in germ cell and neural cell development, and hematopoiesis was upstream of a highly significant effect, contained a significant effect, and was between another two significant effects. The results of this study provided a new understanding of genetic factors underlying RETP in U.S. Holstein cows.
Enhanced Efficacy against Drug-Resistant Tumors Enabled by Redox-Responsive Mesoporous-Silica-Nanoparticle-Supported Lipid Bilayers as Targeted Delivery Vehicles
Authors: Yang Shuoye , Zhang Beibei , Zhao Xiangguo , Zhang Mengwei , Zhang Mengna , Cui Lan , Zhang Lu
Published: May 2024

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.
Annona squamosa Fruit Extract Ameliorates Lead Acetate-Induced Testicular Injury by Modulating JAK-1/STAT-3/SOCS-1 Signaling in Male Rats
Authors: Mobasher Maysa A. , Alsirhani Alaa Muqbil , Alwaili Maha Abdullah , Baakdah Fadi , Eid Thamir M , Alshanbari Fahad A. , Alzahri Reem Yahya , Alkhodair Sahar Abdulrahman , El-Said Karim Samy
Published: May 2024

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.
Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke—A Systematic Review
Authors: Boxhammer Elke , Dienhart Christiane , Rezar Richard , Hoppe Uta C. , Lichtenauer Michael
Published: May 2024

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.
NDNOTA: NDN One-Time Authentication
Authors: Aldaoud Manar , Al-Abri Dawood , Kausar Firdous , Awadalla Medhat
Published: May 2024

Named Data Networking (NDN) stands out as a prominent architectural framework for the future Internet, aiming to address deficiencies present in IP networks, specifically in the domain of security. Although NDN packets containing requested content are signed with the publisher’s signature which establishes data provenance for content, the NDN domain still requires more holistic frameworks that address consumers’ identity verification while accessing protected contents or services using producer/publisher-preapproved authentication servers. In response, this paper introduces the NDN One-Time Authentication (NDNOTA) framework, designed to authenticate NDN online services, applications, and data in real time. NDNOTA comprises three fundamental elements: the consumer, producer, and authentication server. Employing a variety of security measures such as single sign-on (SSO), token credentials, certified asymmetric keys, and signed NDN packets, NDNOTA aims to reinforce the security of NDN-based interactions. To assess the effectiveness of the proposed framework, we validate and evaluate its impact on the three core elements in terms of time performance. For example, when accessing authenticated content through the entire NDNOTA process, consumers experience an additional time overhead of 70 milliseconds, making the total process take 83 milliseconds. In contrast, accessing normal content that does not require authentication does not incur this delay. The additional NDNOTA delay is mitigated once the authentication token is generated and stored, resulting in a comparable time frame to unauthenticated content requests. Additionally, obtaining private content through the authentication process requires 10 messages, whereas acquiring public data only requires two messages.
Behavioral and Transcriptomic Analyses in the Indoxacarb Response of a Non-Target Damselfly Species
Authors: Jiang Bin , Wang Wei , Yao Yu , Zhang Haobo , Zhang Yongmei , Sun Yang
Published: May 2024

Ischnura senegalensis, which widely spreads in paddy fields, has the potential to be used as a natural predator of insect pests. However, the application of insecticides in the field could pose a threat to the survival of I. senegalensis. Among these pesticides, indoxacarb, an oxadiazine insecticide, is renowned for its broad-spectrum efficacy against numerous insect pests. In this study, we examined the toxicity of indoxacarb towards the larvae of I. senegalensis. Behavioral experiments and transcriptome analyses were conducted under indoxacarb treatments. Results revealed that indoxacarb induced abnormal body gestures and significant locomotory impairments, which could ultimately reduce the survival rate of the larvae in their natural habitat. Moreover, transcriptome analyses indicated that genes related to muscle function were significantly affected. Interestingly, at lower concentrations of indoxacarb (0.004 mg/L), the larvae seem to detoxify the indoxacarb with the aid of the cytochrome P450 gene. However, under higher concentrations (0.4 mg/L), the sensory abilities of the larvae were significantly diminished, and they were unable to degrade the toxicity of indoxacarb. Our study underscores the importance of carefully evaluating the impact of insecticides on non-target predatory insects before their widespread application.
Biosynthesis of Pteridines in Insects: A Review
Authors: Ferré Juan
Published: May 2024

Pteridines are important cofactors for many biological functions of all living organisms, and they were first discovered as pigments of insects, mainly in butterfly wings and the eye and body colors of insects. Most of the information on their structures and biosynthesis has been obtained from studies with the model insects Drosophila melanogaster and the silkworm Bombyx mori. This review discusses, and integrates into one metabolic pathway, the different branches which lead to the synthesis of the red pigments “drosopterins”, the yellow pigments sepiapterin and sepialumazine, the orange pigment erythropterin and its related yellow metabolites (xanthopterin and 7-methyl-xanthopterin), the colorless compounds with violet fluorescence (isoxanthopterin and isoxantholumazine), and the branch leading to tetrahydrobiopterin, the essential cofactor for the synthesis of aromatic amino acids and biogenic amines.
Oxidative Stress Response of Honey Bee Colonies (Apis mellifera L.) during Long-Term Exposure at a Frequency of 900 MHz under Field Conditions
Authors: Vilić Marinko , Žura Žaja Ivona , Tkalec Mirta , Tucak Perica , Malarić Krešimir , Popara Nato , Žura Nikolino , Pašić Selim , Gajger Ivana Tlak
Published: May 2024

In this study, oxidative stress and lipid peroxidation in honey bee larvae, pupae and the midguts of adult bees were investigated during a one-year exposure to radiofrequency electromagnetic fields (RF-EMFs) at a frequency of 900 MHz under field conditions. The experiment was carried out on honey bee colonies at three locations with electric field levels of 30 mV m−1, 70 mV m−1 and 1000 mV m−1. Antioxidant enzymes, glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation were measured spectrophotometrically. The GST activity within the same developmental stage showed no significant differences regardless of electric field level or sampling time. The highest GST activity was found in the pupae, followed by activity in the larvae and midguts. Both CAT activity and TBARS concentration were the highest in the midguts, regardless of field level and sampling time. The larvae showed a significantly higher TBARS concentration at the location with an electric field level of 1000 mV m−1 compared to the locations with lower levels. Our results show that RF-EMFs at a frequency of 900 MHz can cause oxidative stress in honey bees, with the larval stage being more sensitive than the pupal stage, but there was no linear relationship between electric field level and effect in any of the developmental stages.
Balloon Valvuloplasty in Congenital Critical Aortic Valve Stenosis in Neonates and Infants: A Rescue Procedure for the Left Ventricle
Authors: Pfeifer Jochen , Rentzsch Axel , Poryo Martin , Abdul-Khaliq Hashim
Published: May 2024

Congenital critical aortic valve stenosis (CAVS) is a life-threatening disease requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS and (2) describe the techniques for improved feasibility of intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs were performed in 7 patients, and 3 BAVs were performed in 2 patients. The peak trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions. In the first BAV, Δp decreased from 73.7 ± 34.5 mmHg to 39.8 ± 11.9 mmHg (p = 0.003), and the LVSF improved from 22.3 ± 13.5% to 31.6 ± 10.2% (p = 0.001). In the second BAV, Δp decreased from 73.2 ± 33.3 mmHg to 35.0 ± 20.2 mmHg (p < 0.001), and the LVSF increased from 26.7 ± 9.6% to 33.3 ± 7.4% (p = 0.004). Cardiac surgery during the neonatal period was avoided for all children. The median time to valve surgery was 5.75 years. Few complications occurred, namely mild-to-moderate aortic regurgitation, one remediable air embolism, and one intimal injury to the ascending aorta. We conclude that BAV is a successful emergency treatment for CAVS, resulting in left ventricular relief, clinical stabilization, and a time gain until cardiac surgery.
Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer
Authors: Ha Jee Soo , Kim Do Kyung , Lee Hye Sun , Jeon Soyoung , Jeon Jinhyung , Kim Daeho , Kim June Seok , Kim Byeongseon , Kim Min , Cho Kang Su
Published: May 2024

Background/Objectives: to evaluate the association between androgen deprivation therapy (ADT) and newly developed neovascular age-related macular degeneration (AMD) in patients with prostate cancer. Methods: We identified 228,803 men from the nationwide claims database in the Republic of Korea diagnosed with prostate cancer between 1 August 2009 and 31 December 2018 and followed until April 2021. Cases were defined as those newly diagnosed with neovascular AMD during follow-up. Cases were matched with controls based on age, index date, and follow-up duration, at a case-to-control ratio of 1:4. Adjusted odds ratios (aORs) of incident neovascular AMD associated with ADT were estimated using conditional logistic regression. Results: The main analysis included 1700 cases and 6800 controls, with a median follow-up of 3.42 years. ADT was associated with a reduced risk of incident neovascular AMD in patients with prostate cancer (aOR = 0.840; 95% confidence interval [CI], 0.743–0.951; p = 0.0058) in the multivariable analysis. A cumulative ADT duration less than 1 year was associated with a reduced risk of neovascular AMD (aOR = 0.727; 95% CI, 0.610–0.866; p = 0.0004); however, no association was observed when the duration of ADT was between 1 and 2 years (aOR = 0.862; 95% CI, 0.693–1.074; p = 0.1854) or more than 2 years (aOR = 1.009; 95% CI, 0.830–1.226; p = 0.9304). Conclusions: In patients with prostate cancer, medical castration for less than a year is associated with a reduced risk of incident neovascular AMD. These results suggest that androgens are involved in the pathogenesis of neovascular AMD.
How Will Artificial Intelligence Shape the Future of Decision-Making in Congenital Heart Disease?
Authors: Pozza Alice , Zanella Luca , Castaldi Biagio , Di Salvo Giovanni
Published: May 2024

Improvements in medical technology have significantly changed the management of congenital heart disease (CHD), offering novel tools to predict outcomes and personalize follow-up care. By using sophisticated imaging modalities, computational models and machine learning algorithms, clinicians can experiment with unprecedented insights into the complex anatomy and physiology of CHD. These tools enable early identification of high-risk patients, thus allowing timely, tailored interventions and improved outcomes. Additionally, the integration of genetic testing offers valuable prognostic information, helping in risk stratification and treatment optimisation. The birth of telemedicine platforms and remote monitoring devices facilitates customised follow-up care, enhancing patient engagement and reducing healthcare disparities. Taking into consideration challenges and ethical issues, clinicians can make the most of the full potential of artificial intelligence (AI) to further refine prognostic models, personalize care and improve long-term outcomes for patients with CHD. This narrative review aims to provide a comprehensive illustration of how AI has been implemented as a new technological method for enhancing the management of CHD.
Factors Associated with All-Cause 30-Day Mortality in Indonesian Inpatient COVID-19 Patients at Cipto Mangunkusumo National General Hospital
Authors: Rinaldi Ikhwan , Yulianti Mira , Yunihastuti Evy , Rajabto Wulyo , Irawan Cosphiadi , Sukrisman Lugyanti , Rachman Andhika , Mulansari Nadia Ayu , Lubis Anna Mira , Prasetyawaty Findy , Cahyanur Rahmat , Priantono Dimas , Ahani Ardhi Rahman , Muthalib Abdul , Sudoyo Aru , Atmakusuma Tubagus Djumhana , Reksodiputro Arry Harryanto , Djoerban Zubairi , Tambunan Karmel , Winston Kevin , Shufiyani Yuli Maulidiya , Wiyono Lowilius , Pratama Samuel , Edina Brenda Cristie
Published: May 2024

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan–Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971–12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048–2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208–9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187–2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279–3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523–86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049–2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092–3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780–6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240–2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.
Digital Subtraction Angiography of Cerebral Arteries: Influence of Cranial Dimensions on X-ray Tube Performance
Authors: Modlińska Sandra , Czogalik Łukasz , Rojek Marcin , Dudek Piotr , Janik Michał , Mielcarska Sylwia , Kufel Jakub
Published: May 2024

(1) Background. Digital subtraction angiography (DSA) is indispensable for diagnosing cerebral aneurysms due to its superior imaging precision. However, optimizing X-ray parameters is crucial for accurate diagnosis, with X-ray tube settings significantly influencing image quality. Understanding the relationship between skull dimensions and X-ray parameters is pivotal for tailoring imaging protocols to individual patients. (2) Methods. A retrospective analysis of DSA data from a single center was conducted, involving 251 patients. Cephalometric measurements and statistical analyses were performed to assess correlations between skull dimensions and X-ray tube parameters (voltage and current). (3) Results. The study revealed significant correlations between skull dimensions and X-ray tube parameters, highlighting the importance of considering individual anatomical variations. Gender-based differences in X-ray parameters were observed, emphasizing the need for personalized imaging protocols. (4) Conclusions. Personalized approaches to DSA imaging, integrating individual anatomical variations and gender-specific differences, are essential for optimizing diagnostic outcomes. While this study provides valuable insights, further research across multiple centers and diverse imaging equipment is warranted to validate these findings.
Acute Respiratory Failure in Autoimmune Rheumatic Diseases: A Review
Authors: Poli Sofia , Sciorio Francesca , Piacentini Giorgio , Pietrobelli Angelo , Pecoraro Luca , Pieropan Sara
Published: May 2024

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes.
Synergistic Therapy for Graves’ Ophthalmopathy-Associated Eyelid Retraction: Steroid, 5-FU, and Botulinum Neurotoxin a Combination
Authors: Kim Yuri , Lew Helen
Published: May 2024

Background: Graves’ ophthalmopathy (GO) is characterized by upper eyelid retraction (UER), the most prevalent clinical sign. We aimed to assess the clinical efficacy of a multimodal combination of steroids, 5-fluorouracil (5-FU), and botulinum neurotoxin A (BoNT-A) injections in managing UER with GO and analyze the clinical factors in relation to the injection response. Methods: A total of 37 eyes from 23 patients were enrolled for UER with GO. At the endocrinology clinic, the patients were referred to the ophthalmology clinic after taking antithyroid medication for an average of 5.76 months (13 patients), while 10 patients were initially diagnosed with GO and referred to the endocrinology clinic for management of the thyroid hormone function. They performed an orbital computed tomography (CT) scan and measured the cross-sectional area of the orbit, orbital fat, and each extra ocular muscle (EOM) except for the inferior oblique muscle 4 mm behind the eyeball. Each of the EOMs and orbital fat were calculated as a ratio to the total orbit area. A total of 0.1 cc of triamcinolone (40 mg/mL), dexamethasone (5 mg/mL), 5-FU, and BoNT-A (2.5 units) was injected transconjunctivally. Medical records were examined and photographs were utilized to assess MRD1, inferior palpebral fissure (IPF), and lid lag during down gaze before and after the injection. The patients were divided into two groups: responders (more than 1 mm decrease in MRD1 after injection) and non-responders. During the follow-up period (11.0 ± 11.6 months), any potential adverse effects were monitored. Results: CAS decreased from 3.0 ± 0.8 to 1.4 ± 0.5 after the injection, and MRD1 decreased from 5.0 ± 0.9 mm to 4.5 ± 1.3 mm. Sixty percent of the patients were responders. Before and after the injection, the difference between IPF and MRD1 in responders was 0.60 ± 1.10 mm and 0.90 ± 0.90 mm, respectively, whereas, in non-responders, it was −0.57 ± 0.88 mm and −0.15 ± 0.75 mm, respectively. In the responders, pre-injection IPF and FT4 were significantly higher (p < 0.05). Responders had a larger EOM cross-sectional area (153.5 ± 18.0 mm2), including a larger lateral rectus muscle cross-sectional area (37.6 ± 9.7 mm2) than non-responders (132.0 ± 27.9 mm2; 29.1 ± 8.1 mm2). In responders, the treatment effect on IPF and MRD1 remained consistent at 1.2 ± 3.4 mm and 1.2 ± 1.6 mm, respectively, during the latest follow-up assessment. Conclusions: The combination injection of corticosteroids, 5-FU, and BoNT-A would be effective, especially, in patients with hyperthyroidism and an elongated IPF. Additionally, an increase in EOM cross-sectional area on CT, up to 150 mm2, may serve as an additional positive indicator for the use of multimodal injections in UER with GO.
Deregulated Long Non-Coding RNAs (lncRNA) as Promising Biomarkers in Hidradenitis Suppurativa
Authors: Radhakrishna Uppala , Ratnamala Uppala , Jhala Devendrasinh D. , Uppala Lavanya V. , Vedangi Aaren , Saiyed Nazia , Patel Maulikkumar , Shah Sushma R. , Rawal Rakesh M. , Jemec Gregor B. E. , Mazza Tommaso , Mazzoccoli Gianluigi , Damiani Giovanni
Published: May 2024

Background/Objectives: In recent times, epigenetics alterations in Hidradenitis suppurativa (HS) have been explored and exploited translationally to guide investigation of new therapeutic approaches. On the other hand, long noncoding RNAs (LncRNAs), main regulators of the epigenetic status of the human genome, have been scarcely investigated, notwithstanding their potential relevance in broad pathogenesis comprehension. Here, we aim to explore the methylation pattern of lncRNAs in HS. Methods: In this case-control study, 24 HS patients and age-, sex- and BMI-matched controls were analyzed to characterize the methylome of lncRNA genes in peripheral blood cells. Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network, and MCODE analysis were performed. Results: A set of fifteen lncRNA genes exhibited significantly differential methylation patterns, with ten of them showing hypomethylation and five displaying hypermethylation at specific CpG sites. The hypomethylated lncRNA genes were DLEU2, MESTIT1, CASC2, TUG1, KCNQ1DN, PSORS1C3, PCA3, DSCR8, RFPL1S, and PVT1, while the hypermethylated ones were HAR1A, FAM66B, SNHG9, HCG9, and HCP5. These lncRNA genes have been linked to various important biological processes, including cell proliferation, apoptosis, inflammation, chronic inflammatory skin diseases, and wound healing. Their altered methylation status suggests potential roles in regulating these processes, and may contribute to HS pathogenesis and healing mechanisms. Conclusions: This study revealed an interesting dysregulation pattern of definite lncRNAs in the methylome which is linked to both the development of HS and its comorbidities. Epigenetically altered lncRNAs genes could represent useful biomarkers, and could help in guiding innovative treatment strategies.
Mechanical Analysis and Simulation of Wood Textile Composites
Authors: von Boyneburgk Claudia L. , Oikonomou Dimitri , Seim Werner , Heim Hans-Peter
Published: May 2024

Wood Textile Composites (WTCs) represent a new and innovative class of materials in the field of natural fiber composites. Consisting of fabrics made from willow wood strips (Salix americana) and polypropylene (PP), this material appears to be particularly suitable for structural applications in lightweight construction. Since the threads of the fabric are significantly oversized compared to classic carbon or glass rovings, fundamental knowledge of the mechanical properties of the material is required. The aim of this study was to investigate whether WTCs exhibit classic behavior in terms of fiber composite theory and to classify them in relation to comparable composite materials. It was shown that WTCs meet all the necessary conditions for fiber-reinforced composites in tensile, bending, and compression tests and can be classified as natural-fiber-reinforced polypropylene composites. In addition, it was investigated whether delamination between the fiber and matrix can be simulated by using experimentally determined mechanical data as input. Using finite element analysis (FEA), it was shown that the shear stress components of a stress tensor in the area of the interface between the fiber and matrix are responsible for delamination in the composite material. It was also shown that the resistance to shear stress depends on the geometric conditions of the reinforcing fabric.
Fast Linde–Buzo–Gray (FLBG) Algorithm for Image Compression through Rescaling Using Bilinear Interpolation
Authors: Bilal Muhammmad , Ullah Zahid , Mujahid Omer , Fouzder Tama
Published: May 2024

Vector quantization (VQ) is a block coding method that is famous for its high compression ratio and simple encoder and decoder implementation. Linde–Buzo–Gray (LBG) is a renowned technique for VQ that uses a clustering-based approach for finding the optimum codebook. Numerous algorithms, such as Particle Swarm Optimization (PSO), the Cuckoo search algorithm (CS), bat algorithm, and firefly algorithm (FA), are used for codebook design. These algorithms are primarily focused on improving the image quality in terms of the PSNR and SSIM but use exhaustive searching to find the optimum codebook, which causes the computational time to be very high. In our study, our algorithm enhances LBG by minimizing the computational complexity by reducing the total number of comparisons among the codebook and training vectors using a match function. The input image is taken as a training vector at the encoder side, which is initialized with the random selection of the vectors from the input image. Rescaling using bilinear interpolation through the nearest neighborhood method is performed to reduce the comparison of the codebook with the training vector. The compressed image is first downsized by the encoder, which is then upscaled at the decoder side during decompression. Based on the results, it is demonstrated that the proposed method reduces the computational complexity by 50.2% compared to LBG and above 97% compared to the other LBG-based algorithms. Moreover, a 20% reduction in the memory size is also obtained, with no significant loss in the image quality compared to the LBG algorithm.
Transcriptome Analysis Reveals Potential Regulators of DMI Fungicide Resistance in the Citrus Postharvest Pathogen Penicillium digitatum
Authors: Xi Yue , Zhang Jing , Fan Botao , Sun Miaomiao , Cao Wenqian , Liu Xiaotian , Gai Yunpeng , Shen Chenjia , Wang Huizhong , Wang Mingshuang
Published: May 2024

Green mold, caused by Penicillium digitatum, is the major cause of citrus postharvest decay. Currently, the application of sterol demethylation inhibitor (DMI) fungicide is one of the main control measures to prevent green mold. However, the fungicide-resistance problem in the pathogen P. digitatum is growing. The regulatory mechanism of DMI fungicide resistance in P. digitatum is poorly understood. Here, we first performed transcriptomic analysis of the P. digitatum strain Pdw03 treated with imazalil (IMZ) for 2 and 12 h. A total of 1338 genes were up-regulated and 1635 were down-regulated under IMZ treatment for 2 h compared to control while 1700 were up-regulated and 1661 down-regulated under IMZ treatment for 12 h. The expression of about half of the genes in the ergosterol biosynthesis pathway was affected during IMZ stress. Further analysis identified that 84 of 320 transcription factors (TFs) were differentially expressed at both conditions, making them potential regulators in DMI resistance. To confirm their roles, three differentially expressed TFs were selected to generate disruption mutants using the CRISPR/Cas9 technology. The results showed that two of them had no response to IMZ stress while ∆PdflbC was more sensitive compared with the wild type. However, disruption of PdflbC did not affect the ergosterol content. The defect in IMZ sensitivity of ∆PdflbC was restored by genetic complementation of the mutant with a functional copy of PdflbC. Taken together, our results offer a rich source of information to identify novel regulators in DMI resistance.
Development of a Combat-Relevant Murine Model of Wound Mucormycosis: A Platform for the Pre-Clinical Investigation of Novel Therapeutics for Wound-Invasive Fungal Diseases
Authors: Samdavid Thanapaul Rex J. R. Samdavid , Alamneh Yonas A. , Finnegan Daniel K. , Antonic Vlado , Abu-Taleb Rania , Czintos Christine , Boone Dylan , Su Wanwen , Sajja Venkatasivasai S. , Getnet Derese , Roberds Ashleigh , Walsh Thomas J. , Bobrov Alexander G.
Published: May 2024

Wound-invasive fungal diseases (WIFDs), especially mucormycosis, have emerged as life-threatening infections during recent military combat operations. Many combat-relevant fungal pathogens are refractory to current antifungal therapy. Therefore, animal models of WIFDs are urgently needed to investigate new therapeutic solutions. Our study establishes combat-relevant murine models of wound mucormycosis using Rhizopus arrhizus and Lichtheimia corymbifera, two Mucorales species that cause wound mucormycosis worldwide. These models recapitulate the characteristics of combat-related wounds from explosions, including blast overpressure exposure, full-thickness skin injury, fascial damage, and muscle crush. The independent inoculation of both pathogens caused sustained infections and enlarged wounds. Histopathological analysis confirmed the presence of necrosis and fungal hyphae in the wound bed and adjacent muscle tissue. Semi-quantification of fungal burden by colony-forming units corroborated the infection. Treatment with liposomal amphotericin B, 30 mg/kg, effectively controlled R. arrhizus growth and significantly reduced residual fungal burden in infected wounds (p < 0.001). This study establishes the first combat-relevant murine model of wound mucormycosis, paving the way for developing and evaluating novel antifungal therapies against combat-associated WIFDs.
The Discovery of Acremochlorins O-R from an Acremonium sp. through Integrated Genomic and Molecular Networking
Authors: Cui Ge , Zhou Luning , Liu Hanwei , Qian Xuan , Yang Pengfei , Cui Leisha , Wang Pianpian , Li Dehai , Winter Jaclyn M. , Wu Guangwei
Published: May 2024

The fermentation of a soil-derived fungus Acremonium sp. led to the isolation of thirteen ascochlorin congeners through integrated genomic and Global Natural Product Social (GNPS) molecular networking. Among the isolated compounds, we identified two unusual bicyclic types, acremochlorins O (1) and P (2), as well as two linear types, acremochlorin Q (3) and R (4). Compounds 1 and 2 contain an unusual benzopyran moiety and are diastereoisomers of each other, the first reported for the ascochlorins. Additionally, we elucidated the structure of 5, a 4-chloro-5-methylbenzene-1,3-diol with a linear farnesyl side chain, and confirmed the presence of eight known ascochlorin analogs (6–13). The structures were determined by the detailed interpretation of 1D and 2D NMR spectroscopy, MS, and ECD calculations. Compounds 3 and 9 showed potent antibacterial activity against Staphylococcus aureus and Bacillus cereus, with MIC values ranging from 2 to 16 μg/mL.
Valuation of Goodwill for an Engineering Firm
Authors: Lohar Bhushan , Wade John , Walker Sean
Published: May 2024

The concept of valuing personal and enterprise goodwill is a study in the art of quantifying subjective values. Sellers strive to maximize goodwill, while buyers strive to minimize goodwill. No persons are denying the existence of goodwill; rather, the debate is centered around the value of that goodwill. This paper seeks to define a holistic approach to fairly quantifying the value of goodwill for an engineering firm. The Graph Model for Conflict Resolution (GMCR), a decision tool grounded in game theory, is used to illustrate the inherent conflict around setting an accurate goodwill value and the inherent negotiation between buyers and sellers.
Working Capital Management and Bank Mergers
Authors: Na Baoqi , Shimizu Katsutoshi
Published: May 2024

This study investigates the consequences of bank mergers on non-financial borrowers’ working capital management. We find evidence that bank mergers increase corporate cash holdings and decrease receivables and investments in inventories by reducing bank credit availability. Bank mergers also decrease trade credit used through the reduction in bank credit availability. These findings are new contributions to the literature, suggesting that borrowing firms find it more difficult to manage working capital after bank mergers occur and that bank-dependent firms find it more difficult to manage working capital than their non-dependent counterparts after mergers.
South African Real Estate Investment Trusts Prefer Tuesdays
Authors: Ajayi Oluwaseun Damilola , Gavu Emmanuel Kofi
Published: May 2024

This study examines the day-of-the-week effect on the returns of different classifications of South African REITs. Ordinary least squares regression (OLS), generalized autoregressive conditional heteroskedasticity (GARCH) (1,1) (2,1), and Kruskal–Wallis (KW) tests were performed on data obtained from the IRESS Expert database from 2013 to 2021. We found statistical differences in the day-of-the-week effects for SAREITs; the best day to invest in office REITs is Friday, for diversified REITs Thursday, and for industrial REITs Friday. Generally, Wednesday was found to be the least profitable day to invest in all REIT classifications because it had the least average daily return. Tuesdays were the most profitable days for all REIT classifications, with the highest average daily return. REITs traded the most on Fridays, while REITs traded the least on Mondays. Returns were the most volatile on Monday, while volume was the least volatile on Thursday. The KW test revealed a statistically significant difference between the median returns across days of the week. Based on the above, profitability is expressed on Tuesdays in South African REITs. By recognizing the day-of-the-week effect, investors can buy and sell South African REITs more effectively. This study, apart from being the first in the context of South African REITs, provides updated evidence of the contested calendar anomaly issues.
Can Urban Sprawl Promote Enterprise Innovation? Evidence from A-Share Listed Companies in China
Authors: Jiang Zeru , Zhang Bo , Yuan Chunlai , Han Zhaojie , Liu Jiangtao
Published: May 2024

Urban sprawl does not invariably impede factor agglomeration; rather, it can foster polycentric urban configurations, thereby enhancing productivity and encouraging enterprise innovation. This study investigates the effect of urban sprawl on enterprise innovation using data for A-share listed Chinese companies from 2010 to 2020. The results reveal a significant inverted U-shaped relationship between urban sprawl and enterprise innovation, particularly among large enterprises, well-established entities, non-state-owned enterprises, and those operating in non-manufacturing sectors. Additionally, the effects of urban sprawl on the inverted U-shaped relationship are more pronounced in the north-eastern regions and small cities. Regional integration significantly moderates the inverted U-shaped relationship between urban sprawl and enterprise innovation. This research contributes new insights to the field of enterprise innovation, offering theoretical and empirical support for analyzing the economic implications of urban sprawl.
Arabic Compound Numerals: New Insights on Case, Agreement, and Quantification
Authors: Al-Bataineh Hussein
Published: May 2024

This paper examines the syntax of additive compound numerals in Modern Standard Arabic (MSA), uncovering their unique properties related to number morphology, definiteness, and Case assignment within numeral–noun constructions. These properties necessitate a constituency analysis which reveals that compound numerals have the structure of copulative compounds in MSA, and they are phrases, not functional heads. Drawing on the distinction between inherent, lexical, and structural Cases, this paper posits that the accusative Case on the numerals is an inherent Case, inaccessible to syntactic transformations. Furthermore, the analysis of numeral–noun constructions as numerically quantified phrases (NQPs) explains the assignment of a structural accusative Case or the inherent genitive Case on the quantified noun, based on the overtness of NQ0. Finally, the paper addresses the intriguing question of how NQPs in MSA, despite lacking a nominative Case, can assume the subject position and govern agreement in both verbal and verbless sentences.
Cardiovascular Outcome in Patients with Major Depression: Role of Obstructive Sleep Apnea Syndrome, Insomnia Disorder, and COMISA
Authors: Hein Matthieu , Wacquier Benjamin , Conenna Matteo , Lanquart Jean-Pol , Point Camille
Published: May 2024

In this study, the 10-year cardiovascular risk associated with comorbid sleep disorders (insomnia disorder, obstructive sleep apnea syndrome, and COMISA [comorbid insomnia and sleep apnea]) was investigated for patients with major depression. To enable our analysis, 607 patients with major depression were selected from the data register of the Sleep Unit. High 10-year cardiovascular risk was considered present when the Framingham Risk Score was ≥10%. The 10-year cardiovascular risk associated with comorbid sleep disorders has been assessed using logistic regression analyzes. High 10-year cardiovascular risk is significant (40.4%) in patients with major depression. After successive introduction of the different confounders, multivariate logistic regressions showed that for patients with major depression high 10-year cardiovascular risk was significantly associated with COMISA but was not significantly associated with insomnia disorder or obstructive sleep apnea syndrome alone. Thus, these results highlight the existence of a negative synergistic action between insomnia disorder and obstructive sleep apnea syndrome on the 10-year cardiovascular risk in patients with major depression, which demonstrates the importance of researching and treating COMISA to improve the prognosis of this specific population subgroup characterized by higher cardiovascular morbidity and mortality.