bluuebunny/crossref_metadata_2025 huggingface dataset:
Different miRNAs Related to FBXW7 Mutations or High Mitotic Indices Contribute to Rectal Neuroendocrine Tumors: A Pilot Study
Authors: Kang Ho Suk , Park Ha Young , Lim Hyun , Son Il Tae , Kim Min-Jeong , Kim Nan Young , Kim Min Jeong , Nam Eun Sook , Cho Seong Jin , Kwon Mi Jung
Published: March 2023

Recent studies suggest that miRNA may be involved in the development of rectal neuroendocrine tumors (NETs). We explored the frequency of clinicopathologically relevant mutations and miRNA expression in rectal NETs to examine molecular profiles related to prognosis and behavior. Twenty-four eligible specimens with endoscopically excised rectal NETs were selected. Next-generation sequencing and an miRNA expression assay were used to evaluate the expression profile relevant to common genetic mutations in rectal NETs. Kyoto Encyclopedia of Genes and Genomes analysis predicted that the possible target signaling pathways were correlated with dysregulated miRNAs. Nineteen rectal NETs harbored more than one mutation in the 24 cancer-related genes. Seven miRNAs (hsa-miR-769-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-181c-5p, hsa-miR-1246, hsa-miR-324-5p, and hsa-miR-361-3p) were significantly down-regulated in tumors harboring the FBWX7 mutation. Unsupervised hierarchical clustering analysis showed that up-regulation of these seven miRNAs may result in high mitotic indices, indicating the role of miRNAs in tumor progression. Among the down-regulated miRNAs, hsa-miR-769-5p was strongly correlated with extracellular matrix–receptor interaction and lysine degradation. Among the clinicopathological factors, up-regulated hsa-miR-3934-5p was linked to an increased mitotic count. No change in miRNA expression was associated with a tumor size >1 cm, lymphovascular invasion, or Ki-67 index. In summary, we identified different miRNA signatures involved in FBXW7 mutations or high mitotic indices in rectal NETs, which may play a critical role in tumor behavior.
The Role of LFA-1 for the Differentiation and Function of Regulatory T Cells—Lessons Learned from Different Transgenic Mouse Models
Authors: Klaus Tanja , Wilson Alicia , Fichter Michael , Bros Matthias , Bopp Tobias , Grabbe Stephan
Published: March 2023

Regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Treg dysfunction results in diverse inflammatory and autoimmune diseases with life-threatening consequences. β2-integrins (CD11a-d/CD18) play important roles in the migration of leukocytes into inflamed tissues and cell signaling. Of all β2-integrins, T cells, including Treg, only express CD11a/CD18, termed lymphocyte function-associated antigen 1 (LFA-1), on their surface. In humans, loss-of-function mutations in the common subunit CD18 result in leukocyte adhesion deficiency type-1 (LAD-1). Clinical symptoms vary depending on the extent of residual β2-integrin function, and patients may experience leukocytosis and recurrent infections. Some patients can develop autoimmune diseases, but the immune processes underlying the paradoxical situation of immune deficiency and autoimmunity have been scarcely investigated. To understand this complex phenotype, different transgenic mouse strains with a constitutive knockout of β2-integrins have been established. However, since a constitutive knockout affects all leukocytes and may limit the validity of studies focusing on their cell type-specific role, we established a Treg-specific CD18-floxed mouse strain. This mini-review aims to delineate the role of LFA-1 for the induction, maintenance, and regulatory function of Treg in vitro and in vivo as deduced from observations using the various β2-integrin-deficient mouse models.
Genetic Evidence for Endolysosomal Dysfunction in Parkinson’s Disease: A Critical Overview
Authors: Yahya Vidal , Di Fonzo Alessio , Monfrini Edoardo
Published: March 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the aging population, and no disease-modifying therapy has been approved to date. The pathogenesis of PD has been related to many dysfunctional cellular mechanisms, however, most of its monogenic forms are caused by pathogenic variants in genes involved in endolysosomal function (LRRK2, VPS35, VPS13C, and ATP13A2) and synaptic vesicle trafficking (SNCA, RAB39B, SYNJ1, and DNAJC6). Moreover, an extensive search for PD risk variants revealed strong risk variants in several lysosomal genes (e.g., GBA1, SMPD1, TMEM175, and SCARB2) highlighting the key role of lysosomal dysfunction in PD pathogenesis. Furthermore, large genetic studies revealed that PD status is associated with the overall “lysosomal genetic burden”, namely the cumulative effect of strong and weak risk variants affecting lysosomal genes. In this context, understanding the complex mechanisms of impaired vesicular trafficking and dysfunctional endolysosomes in dopaminergic neurons of PD patients is a fundamental step to identifying precise therapeutic targets and developing effective drugs to modify the neurodegenerative process in PD.
Mesoporous Silica Nanoparticles as a Potential Nanoplatform: Therapeutic Applications and Considerations
Authors: Djayanti Krismala , Maharjan Pooja , Cho Kwan Hyung , Jeong Sehoon , Kim Man Su , Shin Meong Cheol , Min Kyoung Ah
Published: March 2023

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields.
Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability
Authors: Gokulan Kuppan , Mathur Aakriti , Kumar Amit , Vanlandingham Michelle M. , Khare Sangeeta
Published: March 2023

First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism.
The Role of Alternative Mitophagy in Heart Disease
Authors: Nah Jihoon
Published: March 2023

Autophagy is essential for maintaining cellular homeostasis through bulk degradation of subcellular constituents, including misfolded proteins and dysfunctional organelles. It is generally governed by the proteins Atg5 and Atg7, which are critical regulators of the conventional autophagy pathway. However, recent studies have identified an alternative Atg5/Atg7-independent pathway, i.e., Ulk1- and Rab9-mediated alternative autophagy. More intensive studies have identified its essential role in stress-induced mitochondrial autophagy, also known as mitophagy. Alternative mitophagy plays pathophysiological roles in heart diseases such as myocardial ischemia and pressure overload. Here, this review discusses the established and emerging mechanisms of alternative autophagy/mitophagy that can be applied in therapeutic interventions for heart disorders.
A Comparison of Etiology, Pathogenesis, Vaccinal and Antiviral Drug Development between Influenza and COVID-19
Authors: Luo Junhao , Zhang Zhuohan , Zhao Song , Gao Rongbao
Published: March 2023

Influenza virus and coronavirus, two kinds of pathogens that exist widely in nature, are common emerging pathogens that cause respiratory tract infections in humans. In December 2019, a novel coronavirus SARS-CoV-2 emerged, causing a severe respiratory infection named COVID-19 in humans, and raising a global pandemic which has persisted in the world for almost three years. Influenza virus, a seasonally circulating respiratory pathogen, has caused four global pandemics in humans since 1918 by the emergence of novel variants. Studies have shown that there are certain similarities in transmission mode and pathogenesis between influenza and COVID-19, and vaccination and antiviral drugs are considered to have positive roles as well as several limitations in the prevention and control of both diseases. Comparative understandings would be helpful to the prevention and control of these diseases. Here, we review the study progress in the etiology, pathogenesis, vaccine and antiviral drug development for the two diseases.
Sharing Augmented Reality between a Patient and a Clinician for Assessment and Rehabilitation in Daily Living Activities
Authors: De Cecco Mariolino , Luchetti Alessandro , Butaslac Isidro , Pilla Francesco , Guandalini Giovanni Maria Achille , Bonavita Jacopo , Mazzucato Monica , Hirokazu Kato
Published: March 2023

In rehabilitation settings that exploit Mixed Reality, a clinician risks losing empathy with the patient by being immersed in different worlds, either real and/or virtual. While the patient perceives the rehabilitation stimuli in a mixed real–virtual world, the physician is only immersed in the real part. While in rehabilitation, this may cause the impossibility for the clinician to intervene, in skill assessment, this may cause difficulty in evaluation. To overcome the above limitation, we propose an innovative Augmented Reality (AR) framework for rehabilitation and skill assessment in clinical settings. Data acquired by a distributed sensor network are used to feed a “shared AR” environment so that both therapists and end-users can effectively operate/perceive it, taking into account the specific interface requirements for each user category: (1) for patients, simplicity, immersiveness, engagement and focus on the task; (2) for clinicians/therapists, contextualization and natural interaction with the whole set of data that is linked with the users’ performances in real-time. This framework has a strong potential in Occupational Therapy (OT) but also in physical, psychological, and neurological rehabilitation. Hybrid real and virtual environments may be quickly developed and personalized to match end users’ abilities and emotional and physiological states and evaluate nearly all relevant performances, thus augmenting the clinical eye of the therapist and the clinician-patient empathy. In this paper, we describe a practical exploitation of the proposed framework in OT: setting-up the table for eating. Both a therapist and a user wear Microsoft HoloLens 2. First, the therapist sets up the table with virtual furniture. Next, the user places the corresponding real objects (also in shape) to match them as closely as possible to the corresponding virtual ones. The therapist’s view is augmented during the test with motion, balance, and physiological estimated cues. Once the training is completed, he automatically perceives deviations in the position and attitude of each object and the elapsed time. We used a camera-based localization algorithm achieving a level of accuracy of 5 mm with a confidence level of 95% for position and 1° for rotation. The framework was designed and tested in collaboration with clinical experts of Villa Rosa rehabilitation hospital in Pergine (Italy), involving both a set of patients and healthy users to demonstrate the effectiveness of the designed architecture and the significance of the analyzed parameters between healthy users and patients.
IoT-Enabled Precision Agriculture: Developing an Ecosystem for Optimized Crop Management
Authors: Atalla Shadi , Tarapiah Saed , Gawanmeh Amjad , Daradkeh Mohammad , Mukhtar Husameldin , Himeur Yassine , Mansoor Wathiq , Hashim Kamarul Faizal Bin , Daadoo Motaz
Published: March 2023

The Internet of Things (IoT) has the potential to revolutionize agriculture by providing real-time data on crop and livestock conditions. This study aims to evaluate the performance scalability of wireless sensor networks (WSNs) in agriculture, specifically in two scenarios: monitoring olive tree farms and stables for horse training. The study proposes a new classification approach of IoT in agriculture based on several factors and introduces performance assessment metrics for stationary and mobile scenarios in 6LowPAN networks. The study utilizes COOJA, a realistic WSN simulator, to model and simulate the performance of the 6LowPAN and Routing protocol for low-power and lossy networks (RPL) in the two farming scenarios. The simulation settings for both fixed and mobile nodes are shared, with the main difference being node mobility. The study characterizes different aspects of the performance requirements in the two farming scenarios by comparing the average power consumption, radio duty cycle, and sensor network graph connectivity degrees. A new approach is proposed to model and simulate moving animals within the COOJA simulator, adopting the random waypoint model (RWP) to represent horse movements. The results show the advantages of using the RPL protocol for routing in mobile and fixed sensor networks, which supports dynamic topologies and improves the overall network performance. The proposed framework is experimentally validated and tested through simulation, demonstrating the suitability of the proposed framework for both fixed and mobile scenarios, providing efficient communication performance and low latency. The results have several practical implications for precision agriculture by providing an efficient monitoring and management solution for agricultural and livestock farms. Overall, this study provides a comprehensive evaluation of the performance scalability of WSNs in the agriculture sector, offering a new classification approach and performance assessment metrics for stationary and mobile scenarios in 6LowPAN networks. The results demonstrate the suitability of the proposed framework for precision agriculture, providing efficient communication performance and low latency.
Paternity Analyses for the Planning of SIT Projects against the Red Palm Weevil
Authors: Belvedere Silvia , Arnone Silvia , Cristofaro Massimo , La Marca Alessandra , De Biase Alessio
Published: March 2023

The red palm weevil Rhynchophorus ferrugineus is an invasive pest from southeastern Asia and Melanesia that has spread widely across the Middle East and the Mediterranean Basin over the last 30 years. Its endophagous larvae cause huge amounts of damage to several palm tree species from the Arecaceae family. Many of these palms are economically important for agricultural and ornamental purposes. Therefore, a lot of attention has recently been focused on studying this species with the aim of identifying sustainable and effective eradication strategies. Sterile insect techniques are biological control strategies that are currently being investigated for their potential to eradicate this pest in selected invasion areas. Mating system features (e.g., polyandry and related features) can affect the success and suitability of these approaches. The main goal of this research was to assess the performance of a previously developed microsatellite panel in terms of the paternity assignment of progeny from laboratory mating experiments. Using a simulation approach, we evaluated the reliability of the microsatellite markers in the paternity tests both in complex laboratory experiment scenarios and on the progeny of wild-caught gravid females to help future studies on the RPW mating system. As a case study of the simulation results, we performed two double-mating experiments, genotyped the progeny and estimated the P2 values to compare to the expected progeny genotypes according to the crossing scheme of each experiment. The results of our simulations on laboratory experiments showed that it was possible to carry out paternity assignments for all progeny with reliable statistical confidence using our 13 microsatellites set. On the contrary the low genetic variability measured in red palm weevil populations in invaded areas made the resolution power of our loci too low to carry out paternity analyses on natural populations. Results of laboratory crossing were completely congruent with the expectations from the Mendelian laws.
Clinical Usefulness of Right Ventricle–Pulmonary Artery Coupling in Cardiovascular Disease
Authors: He Qing , Lin Yixia , Zhu Ye , Gao Lang , Ji Mengmeng , Zhang Li , Xie Mingxing , Li Yuman
Published: March 2023

Right ventricular–pulmonary artery coupling (RV-PA coupling) refers to the relationship between RV contractility and RV afterload. Normal RV-PA coupling is maintained only when RV function and pulmonary vascular resistance are appropriately matched. RV-PA uncoupling occurs when RV contractility cannot increase to match RV afterload, resulting in RV dysfunction and right heart failure. RV-PA coupling plays an important role in the pathophysiology and progression of cardiovascular diseases. Therefore, early and accurate evaluation of RV-PA coupling is of great significance for a patient’s condition assessment, clinical decision making, risk stratification, and prognosis judgment. RV-PA coupling can be assessed by using invasive or noninvasive approaches. The aim of this review was to summarize the pathological mechanism and evaluation methods of RV-PA coupling, the advantages and disadvantages of each method, and the application value of RV-PA coupling in various cardiovascular diseases.
Emotion Regulation Is Associated with Anxiety, Depression and Stress in Adults with Cerebral Palsy
Authors: Honan Ingrid , Waight Emma , Bratel Joan , Given Fiona , Badawi Nadia , McIntyre Sarah , Smithers-Sheedy Hayley
Published: March 2023

Emotion regulation difficulties are associated with many neurological conditions and negatively impact daily function. Yet little is known about emotion regulation in adults with cerebral palsy (CP). Our aim was to investigate emotion regulation in adults with CP and its relationship with condition-related and/or socio-demographic factors. In a cross-sectional study of adults with CP, participants completed a survey containing the Difficulties in Emotion Regulation Scale (DERS), Depression Anxiety and Stress Scale-21 (DASS-21), and socio-demographic and condition-related questions. Descriptive statistics, chi-squared and Mann–Whitney tests were performed. Of the 42 adults with CP (x31.5 years, SD13.5) that were tested, 38 had within normal limits DERS total scores; however, a significantly higher proportion of participants experienced elevated scores (i.e., more difficulties with emotion regulation) than would be expected in the general population across five of the six DERs subdomains. Moderate–extremely severe depression and anxiety symptoms were reported by 33% and 60% of participants, respectively. The DERS total scores for participants with elevated depression, anxiety, and stress scores were significantly higher than the DERS totals score for those without elevated depression, anxiety, and stress scores. DERS and DASS-21 scores did not differ significantly by condition-related nor socio-demographic characteristics. In conclusion, emotion regulation difficulties were associated with elevated symptoms of depression and anxiety, which were overrepresented in the adults with CP participating in this study.
Performance of a Smart Device over 12-Months for Home Monitoring of Patients with Intermediate Age-Related Macular Degeneration
Authors: Prea Selwyn , Guymer Robyn , Kong George , Vingrys Algis
Published: March 2023

Background: To determine the 12-month compliance with and retention of home monitoring (HM) with Melbourne Rapid Fields (MRFh) for patients with intermediate age-related macular degeneration (iAMD) and compare visual acuity (VA) and retinal sensitivity (RS) results to clinical measures. Methods: Participants were recruited to a 12-month HM study with weekly testing of vision with MRFh. Inclusion criteria were a diagnosis of iAMD, understand English instructions, VA ≥ 20/40, and access to an iPad. Supervised in-clinic testing of high contrast VA (HVA, ETDRS), low-luminance VA (LLVA, ETDRS with ND2 filter), and RS (Macular Integrity Assessment, MAIA, and MRF in-clinic, MRFc) was conducted every 6-months. Results: A total of 54 participants (67 ± 6.8 years) were enrolled. Compliance to weekly HM was 61% and study retention at 12-months was 50% of those with uptake (n = 46). No difference was observed between MRFc and MRFh across all RS and VA outcomes (p > 0.05). MRFh RS was higher than MAIA (29.1 vs. 27.1 dB, p < 0.001). MRFh HVA was not different from ETDRS (p = 0.08), but LLVA was 9 letters better (81.5 vs. 72.4 letters, p < 0.001). Conclusions: Over 12-months, MRFh yields a moderate level of compliance with (61%) and retention (50%) of weekly testing. Further studies are required to assess the ability of MRFh to detect early progression to nAMD.
Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?
Authors: Guo Xiaotong , Lin Lede , Zhu Jiang
Published: March 2023

(1) Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor arising from the pleural surface. For relapsed MPM, there is no accepted standard of- are for subsequent treatment. Thus, we aimed to compare the efficacy of chemotherapy, targeting drugs, and immune-checkpoint inhibitors (ICIs) as subsequent therapy for relapsed MPM. (2) Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched several acknowledged databases. Primary outcomes were defined as overall median progressive survival (mPFS) and median overall survival (mOS) in different treatment groups. Secondary outcomes were defined as objective response rate (ORR), the proportion of stable disease (SD), and progressive disease (PD). (3) Results: Ultimately, 43 articles were selected for the meta-analysis. According to the results of a pooled analysis of single-arm studies, ICIs showed a slight advantage in mOS, while chemotherapy showed a slight advantage in mPFS (mOS: 11.2 m vs. 10.39 m and mPFS: 4.42 m vs. 5.08 m for ICIs group and chemotherapy group, respectively). We identified only a few studies that directly compared the efficacy of ICIs with that of chemotherapy, and ICIs did not show significant benefits over chemotherapy based on mOS. (4) Conclusions: Based on current evidence, we considered that immunotherapy might not be superior to chemotherapy as a subsequent therapy for relapsed MPM. Although several studies investigated the efficacy of ICIs, targeting drugs, and chemotherapy in relapsed MPM, there was still no standard of care. Further randomized control trials with consistent criteria and outcomes are recommended to guide subsequent therapy in relapsed MPM and identify patients with certain characteristics that might benefit from such subsequent therapy.
Endothelial Function Is Preserved in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy
Authors: Hashimoto Yu , Yamaji Takayuki , Kitagawa Toshiro , Nakano Yukiko , Kajikawa Masato , Yoshimura Kenichi , Chayama Kazuaki , Goto Chikara , Tanigawa Syunsuke , Mizobuchi Aya , Harada Takahiro , Yusoff Farina Mohamad , Kishimoto Shinji , Maruhashi Tatsuya , Fujita Asuka , Uchiki Toshio , Nakashima Ayumu , Higashi Yukihito
Published: March 2023

Heart failure (HF) is associated with endothelial dysfunction. Vascular function per se plays an important role in cardiac function, whether it is a cause or consequence. However, there is no information on vascular function in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). The purpose of this study was to evaluate vascular function in patients with ATTRwt-CM. We measured flow-mediated vasodilation (FMD) as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function and brachial artery intima-media thickness (bIMT) and brachial-ankle pulse wave velocity (baPWV) as indices of arterial stiffness in 22 patients with ATTRwt-CM and in 22 one-by-one matched control patients using vascular function confounding factors. FMD was significantly greater in patients with ATTRwt-CM than in the controls (5.4 ± 3.4% versus 3.5 ± 2.4%, p = 0.038) and the N-terminal pro-brain natriuretic peptide (NT-proBNP) level was significantly greater in patients with ATTRwt-CM than in the controls (2202 ± 1478 versus 470 ± 677 pg/mL, p < 0.001). There were no significant differences in NID, bIMT or baPWV between the two groups. There was a significant relationship between NT-proBNP and FMD in patients with ATTRwt-CM (r = 0.485, p = 0.022). NT-proBNP showed no significant relationships with NID, bIMT or baPWV. Conclusions: Endothelial function was preserved in patients with ATTRwt-CM. Patients with ATTRwt-CM may have compensatory effects with respect to endothelial function through elevation of BNP.
Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge
Authors: Orecchioni Stefania , Falvo Paolo , Talarico Giovanna , Mitola Giulia , Bravetti Giulia , Mancuso Patrizia , Nicoli Paola , Bertolini Francesco
Published: March 2023

We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4+ and CD8+ TIM3+PD-1+ T cells in the spleens of treated mice.
Physiotherapy as an Effective Method to Support the Treatment of Male Urinary Incontinence: A Systematic Review
Authors: Mazur-Bialy Agnieszka , Tim Sabina , Kołomańska-Bogucka Daria , Burzyński Bartłomiej , Jurys Tomasz , Pławiak Natalia
Published: March 2023

Urinary incontinence (UI) is a serious health issue that affects both women and men. The risk of UI increases in men with age and after treatment for prostate cancer and affects up to 32% of men. Furthermore, UI may affect up to 69% of men after prostatectomy. Considering such a high incidence, it is critical to search for effective methods to mitigate this issue. Hence, the present review aims to provide an overview of physiotherapeutic methods and evaluate their effectiveness in treating UI in men. This systematic review was performed using articles included in PubMed, Embase, WoS, and PEDro databases. A total of 6965 relevant articles were found. However, after a risk of bias assessment, 39 studies met the inclusion criteria and were included in the review. The research showed that the available physiotherapeutic methods for treating men with UI, including those after prostatectomy, involve pelvic floor muscle training (PFMT) alone or in combination with biofeedback (BF) and/or electrostimulation (ES), vibrations, and traditional activity. In conclusion, PFMT is the gold standard of UI therapy, but it may be complemented by other techniques to provide a personalized treatment plan for patients. The effectiveness of the physiotherapeutic methods varies from study to study, and large methodological differences make it difficult to accurately compare individual results and draw unequivocal conclusions.
Comparison between Fasting and Non-Fasting Cut-Off Values of Triglyceride in Diagnosing High Triglyceride in Chinese Hypertensive Outpatients
Authors: Xie Yingying , Qu Peiliu , Guo Liling , Xu Jin , Zhu Liyuan , Tan Yangrong , Wen Tie , Liu Ling
Published: March 2023

Background: Hypertension (HBP) often occurs together with hypertriglyceridemia which indicates elevated triglyceride (TG) and remnant cholesterol (RC) levels. Non-fasting (i.e., postprandial) blood lipid test after a daily meal has been recommended by the European Atherosclerosis Society (EAS). However, little is known about the difference between fasting and non-fasting cut-off values in assessing high TG (HTG) and high RC (HRC) in HBP outpatients. Methods: 225 Chinese outpatients with HBP, including 119 fasting patients (i.e., fasting group) and 106 non-fasting patients (i.e., non-fasting group) were enrolled in this study. Non-fasting levels of blood lipids at 2 h after a daily breakfast were also tested in 33 patients among the fasting group. Venous blood samples were collected. Results: The non-fasting group had significantly higher levels of TG and RC while lower levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol than the fasting group (p < 0.05). According to the TG and RC cut-off values of the EAS, the percentages of HTG and HRC in the non-fasting group were 72.6% and 70.8%, respectively, whereas those in the fasting group were 57.1% and 52.9%, respectively. According to the cut-off value of marked HTG commonly used in the Chinese population in clinical practice, the percentage of marked HTG in the non-fasting group was 57.5%, whereas that in the fasting group was 34.5%. However, the percentages of HTG (57.6% vs. 51.5%) and HRC (51.5% vs. 51.5%) marked HTG (30.3% vs. 33.3%) in the fasting state and at 2 h after a daily breakfast in 33 outpatients did not reach statistical significance. Conclusion: Non-fasting blood lipid tests could find more individuals with HTG as well as those with marked HTG among Chinese outpatients with HBP. It indicates that non-fasting blood lipid tests are worth being recommended in patients with HBP.
Development and Validation of the Life for Low Vision Questionnaire (LIFE4LVQ) Using Rasch Analysis: A Questionnaire Evaluating Ability and Independence
Authors: Almpanidou Stavroula , Almaliotis Diamantis , Karamitopoulos Leonidas , Topouzis Fotios , Konstas Anastasios-Georgios , Labiris Georgios , Dardavesis Theodoros , Fountoulakis Konstantinos N. , Chatzisavvas Konstantinos Ch. , Karampatakis Vasileios
Published: March 2023

Low vision (LV) has a substantial impact on an individual’s daily functionality and patient-reported outcome measures (PROMs) are increasingly incorporated into the evaluation of this problem. The objective of this study was to describe the design of the new “Life for Low Vision Questionnaire (LIFE4LVQ)”, as a measure of daily functionality in LV and to explore its psychometric properties. A total of 294 participants completed the LIFE4LVQ and the data were subjected to Rasch analysis to determine the psychometric properties of the questionnaire, including response category ordering, item fit statistics, principal component analysis, precision, differential item functioning, and targeting. Test–retest reliability was evaluated with an interval of three weeks and intraclass correlation coefficients (ICC) were used. The correlation between the questionnaire score and Best Corrected Visual Acuity (BCVA) was examined using Spearman’s correlation coefficient. Rasch analysis revealed that for most items the infit and outfit mean square fit values were close to 1, both for the whole scale and its subscales (ability and independence). The separation index for person measures was 5.18 with a reliability of 0.96, indicating good discriminant ability and adequate model fit. Five response categories were found for all items. The ICC was 0.96 (p < 0.001; 95% CI, 0.93–0.98), suggesting excellent repeatability of the measure. Poorer BCVA was significantly associated with worse scores (rho = 0.559, p < 0.001), indicating excellent convergent validity. The functional, 40-item LIFE4LVQ proved to be a reliable and valid tool that effectively measures the impact of LV on ability and independence.
Velvet Family Members Regulate Pigment Synthesis of the Fruiting Bodies of Auricularia cornea
Authors: Ma Xiaoxu , Lu Lixin , Zhang Youmin , Fang Ming , Shao Kaisheng , Sun Xu , Yao Fangjie , Wang Peng
Published: March 2023

Color is a crucial feature to consider when breeding and improving strains of Auricularia cornea. To uncover the mechanism of white strain formation in A. cornea, this study selected parental strains that were homozygous for the color trait and analyzed the genetic laws of A. cornea color through genetic population construction, such as test-cross, back-cross, and self-cross populations, and the statistical analysis of color trait segregation. Moreover, the study developed SSR molecular markers to construct a genetic linkage map, perform the fine mapping the color-controlling genetic locus, and verify candidate genes using yeast two-hybrid, transcriptome analysis, and different light treatments. The results of the study indicated that the color trait of A. cornea is controlled by two pairs of alleles. When both pairs of loci are dominant, the fruiting body is purple, while when both pairs of loci are recessive or one pair of loci is recessive, the fruiting body is white. Based on the linkage map, the study finely mapped the color locus within Contig9_29,619bp-53,463bp in the A. cornea genome and successfully predicted the color-controlling locus gene A18078 (AcveA), which belongs to the Velvet factor family protein and has a conserved structure domain of the VeA protein. It can form a dimer with the VelB protein to inhibit pigment synthesis in filamentous fungi. Lastly, the study validated the interaction between AcVeA and VelB (AcVelB) in A. cornea at the gene, protein, and phenotype levels, revealing the mechanism of inhibition of pigment synthesis in A. cornea. Under dark conditions, dimerization occurs, allowing it to enter the nucleus and inhibit pigment synthesis, leading to a lighter fruiting body color. However, under light conditions, the dimer content is low and cannot enter the nucleus to inhibit pigment synthesis. In summary, this study clarified the mechanism of white strain formation in A. cornea, which could aid in improving white strains of A. cornea and studying the genetic basis of color in other fungi.
Lecanora s.lat. (Ascomycota, Lecanoraceae) in Brazil: DNA Barcoding Coupled with Phenotype Characters Reveals Numerous Novel Species
Authors: Santos Lidiane Alves dos , Aptroot André , Lücking Robert , Cáceres Marcela Eugenia da Silva
Published: March 2023

We sequenced over 200 recent specimens of Lecanora s.lat. from Brazil, delimiting 28 species in our material. Many seem to represent undescribed species, some of which being morphologically and chemically similar to each other or to already described species. Here, we present a phylogenetic analysis based on ITS, including our specimens and GenBank data. We describe nine new species. The purpose of the paper is to illustrate the diversity of the genus in Brazil, not to focus on segregate genera. However, we found that all Vainionora species cluster together and these will be treated separately. Other Lecanora species with dark hypothecium clustered in several different clades. Species with the morphology of Lecanora caesiorubella, in which currently several subspecies with different chemistry and distribution are recognized, fall apart in different, distantly related clades, so they cannot be regarded as subspecies but should be recognized at species level. A key is given for the Lecanora species from Brazil.
Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe
Authors: Afolabi Boluwatife Lawrence , Mazhindu Tinashe , Zedias Chikwambi , Borok Margaret , Ndlovu Ntokozo , Masimirembwa Collen ,   on behalf of Consortium for Genomics and Therapeutics in Africa (CGTA)
Published: March 2023

Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry. This study aimed to evaluate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood and used for DPYD genotyping. Adverse events were monitored for six months using the Common Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). However, severe AEs were high (36%) compared to those reported in the literature from other populations. There was a statistically significant association between BSA (p = 0.0074) and BMI (p = 0.0001) with severe global AEs. This study has shown the absence of the currently known actionable DPYD variants in the Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might not be feasible for all populations hence the call for modification of the current DPYD guidelines to include minority populations for the benefit of all diverse patients.
Effects of Dezocine on the Reduction of Emergence Delirium after Laparoscopic Surgery: A Retrospective Propensity Score-Matched Cohort Study
Authors: Wang Lu , Yi Qiong , Ye Chunyan , Luo Ning , Wang E
Published: March 2023

In China, dezocine is commonly employed as a partial agonist of mu/kappa opioid receptors during anesthesia induction for surgical patients, yet evidence supporting its causal association with emergence delirium is limited. The objective of this investigation was to evaluate the impact of intravenous dezocine administered during anesthesia induction on emergence delirium. The retrospective studied existing data containing medical records of patients undergoing an elective laparoscopy procedure and the study was conducted with ethics-board approval. The primary outcome was the incidence of emergence delirium. Secondary outcomes included the VAS in the PACU and 24 h after surgery, the RASS score in the PACU, postoperative MMSE, hospital stay, and ICU stay. A total of 681 patients were analyzed, after being propensity score-matched, the dezocine and non-dezocine group each had 245 patients. Emergence delirium occurred in 26/245 (10.6%) of patients who received dezocine and 41/245 (16.7%) of patients did not receive dezocine. Patients on whom dezocine was used were associated with a significantly lower incidence of emergence delirium (absolute risk difference, −6.1%, 95% CI, −12% to −0.2%; relative risk [RR], 0.63; 95% CI, 0.18–0.74). All secondary outcome measures and adverse outcomes were not significantly different. The use of dezocine during anesthesia induction was associated with a decreased incidence of emergence delirium after elective laparoscopic surgeries.
The Impact of FASB Staff Position APB 14-1 on Corporate Financing: A Debt Contracting Perspective
Authors: Jin Justin Y. , Kanagaretnam Kiridaran , Li Na
Published: March 2023

Using a set of hand-collected data, we study the economic consequences of FASB Staff Position APB 14-1, which was adopted in 2008 and intended to increase reported interest expense and decrease reported leverage. First, we document that issuers are more likely to respond to APB 14-1 by reducing the outstanding amount of cash-settled convertible debt when they are more able to bear the cost of repurchase. Second, we explore the debt contracting explanations for issuers’ repurchase decisions. In particular, we focus on the contracting practice for GAAP changes and the inclusion of financial covenants related to interest coverage ratios. We find that issuers are less likely to repurchase the outstanding cash-settled convertibles when their bank loan contracts allow them to request a freeze on GAAP provisions to exclude mandatory GAAP changes in calculating accounting-based covenants. Further, when firms’ bank loan contracts contain financial covenants related to interest coverage ratios, issuers are more likely to repurchase outstanding cash-settled convertibles to avoid technical default due to the higher reported interest expense resulting from requirements under APB 14-1. These empirical results are consistent with the notion that firms do respond to mandatory GAAP changes when they are more able to afford the cost of such responses. Furthermore, debt contracting practices can help explain firms’ decisions to respond to mandatory GAAP changes.
Embolization of Ruptured Infratentorial Pial AVM in Pregnancy
Authors: Zeleňák Kamil , Šalát Dušan , Kolarovszki Branislav , Kurča Egon , Zeleňáková Jana , Koçer Naci
Published: March 2023

A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, AVM embolization was performed. Complete occlusion of the AVM was achieved by embolization with PHIL (precipitating hydrophobic injectable liquid). The calculated dose in the uterus was less than 1 µSv, which represents a negligible risk of harmful effects on the fetus. She delivered a baby at 37 weeks of gestation by cesarean section without complications. No congenital disorders were diagnosed by standard screening methods until the age of the newborn was two years. The angiography protocol must be optimized to minimize the radiation dose. Adequate shielding protection of the uterus is important. Premature termination of pregnancy is not necessary. Multidisciplinary care of neurologists, neurosurgeons, interventional radiologists, anesthesiologists, neonatologists, and obstetricians is necessary.
The Effect of GFRP Powder on the High and Low-Temperature Properties of Asphalt Mastic
Authors: Zhen Tao , Zhao Pinxue , Zhang Xing , Si Wei , Ling Tianqing
Published: March 2023

Glass fiber reinforced polymer (GFRP) is the main composite material used in wind turbine blades. In recent years, zero-carbon energy sources such as wind power have been widely used to reduce carbon emissions, resulting in a large amount of waste GFRP, and causing serious environmental problems. To explore efficient ways to recycle waste GFRP, this study explores the impact of adding GFRP powder (nominal maximum particle size ≤ 0.075 mm) on the high and low temperature properties of asphalt mastic. Samples of GFRP asphalt mastics were prepared with filler-asphalt mass ratios of 0.01:1, 0.1:1, 0.8:1, and 1:1, as well as two control samples of limestone filler asphalt mastics with filler-asphalt mass ratios of 0.8:1 and 1:1. The study analyzed the effect of GFRP on the asphalt mastic’s performance using temperature sweep, MSCR, and BBR tests. Results showed that the presence of GFRP improved the high-temperature resistance and recovery of asphalt mastic but led to decreased low-temperature crack resistance. The results suggest that GFRP has the potential to be used as a filler in asphalt mastic, with a recommended filler-asphalt mass ratio range of less than 0.8:1 for optimal low-temperature performance. However, further research is necessary to determine the optimal content of GFRP in asphalt mastic and to study its impact on other road performance metrics.
Towards an Optimized Artificial Neural Network for Predicting Flow Stress of In718 Alloys at High Temperatures
Authors: Zhang Chunbo , Shi Qingyu , Wang Yihe , Qiao Junnan , Tang Tianxiang , Zhou Jun , Liang Wu , Chen Gaoqiang
Published: March 2023

Artificial neural networks (ANNs) have been an important approach for predicting the value of flow stress, which is dependent on temperature, strain, and strain rate. However, there is still a lack of sufficient knowledge regarding what structure of ANN should be used for predicting metal flow stress. In this paper, we train an ANN for predicting flow stress of In718 alloys at high temperatures using our experimental data, and the structure of the ANN is optimized by comparing the performance of four ANNs in predicting the flow stress of In718 alloy. It is found that, as the size of the ANN increases, the ability of the ANN to retrieve the flow stress results from a training dataset is significantly enhanced; however, the ability to predict the flow stress results absent from the training does not monotonically increase with the size of the ANN. It is concluded that the ANN with one hidden layer and four nodes possesses optimized performance for predicting the flow stress of In718 alloys in this study. The reason why there exists an optimized ANN size is discussed. When the ANN size is less than the optimized size, the prediction, especially the strain dependency, falls into underfitting and fails to predict the curve. When the ANN size is less than the optimized size, the predicted flow stress curves with the temperature, strain, and strain rate will contain non-physical fluctuations, thus reducing their prediction accuracy of extrapolation. For metals similar to the In718 alloy, ANNs with very few nodes in the hidden layer are preferred rather than the large ANNs with tens or hundreds of nodes in the hidden layers.