bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Renewal of Macrophages: Tumor-Released Factors and Signaling Pathways
Authors: Filiberti Serena , Russo Mariapia , Lonardi Silvia , Bugatti Mattia , Vermi William , Tournier Cathy , Giurisato Emanuele
Published: October 2022

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating TAMs self-renewal capacity may help to identify promising targets for the development of novel anticancer agents. In this review, we focus on the environmental factors that promote the capacity of macrophages to self-renew and the molecular mechanisms that govern TAMs proliferation. We also highlight the impact of tumor-derived factors on macrophages metabolism and how distinct metabolic pathways affect macrophage self-renewal.
Artificial Intelligence Driven Biomedical Image Classification for Robust Rheumatoid Arthritis Classification
Authors: Obayya Marwa , Alamgeer Mohammad , S. Alzahrani Jaber , Alabdan Rana , N. Al-Wesabi Fahd , Mohamed Abdullah , Alsaid Hassan Mohamed Ibrahim
Published: October 2022

Recently, artificial intelligence (AI) including machine learning (ML) and deep learning (DL) models has been commonly employed for the automated disease diagnosis process. AI in biological and biomedical imaging is an emerging area and will be a future trend in the field. At the same time, biomedical images can be used for the classification of Rheumatoid arthritis (RA) diseases. RA is an autoimmune illness that affects the musculoskeletal system causing systemic, inflammatory and chronic effects. The disease frequently becomes progressive and decreases physical function, causing articular damage, suffering, and fatigue. After a time, RA causes harm to the cartilage of the joints and bones, weakens the tendons and joints, and finally causes joint destruction. Sensors (thermal infrared camera sensor, accelerometers and wearable sensors) are more commonly employed to collect data for RA. This study develops an Automated Rheumatoid Arthritis Classification using an Arithmetic Optimization Algorithm with Deep Learning (ARAC-AOADL) model. The goal of the presented ARAC-AOADL technique lies in the classification of health disorders depending upon RA and orthopaedics. Primarily, the presented ARAC-AOADL technique pre-processes the input images by median filtering (MF) technique. Then, the ARAC-AOADL technique uses AOA with an enhanced capsule network (ECN) model to produce feature vectors. For RA classification, the ARAC-AOADL technique uses a multi-kernel extreme learning machine (MKELM) model. The experimental result analysis of the ARAC-AOADL technique on a benchmark dataset reported a maximum accuracy of 98.57%. Therefore, the ARAC-AOADL technique can be employed for accurate and timely RA classification.
Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway
Authors: Zhou Yan , Zhang Yunna , Cheng Haipeng , Li Xiaohong , Feng Dandan , Yue Shaojie , Xu Jianping , Xie Hui , Luo Ziqiang
Published: October 2022

Idiopathic pulmonary fibrosis (IPF) is a fatal age-related chronic lung disease, characterized by progressive scarring of the lungs by activated fibroblasts. The effect of omentin-1 against pulmonary fibrosis and fibroblast activation has not been investigated. The purpose of this experiment is to investigate the role of omentin-1 in bleomycin (BLM)-induced lung fibrosis and its mechanism. Our results showed that the loss of omentin-1 exaggerated lung fibrosis induced by BLM. On the contrary, adenoviral-overexpression of omentin-1 significantly alleviated BLM-induced lung fibrosis both in preventive and therapeutic regimens. Moreover, omentin-1 prevented fibroblast activation determined by a decreased number of S100A4+ (fibroblasts marker) α-SMA+ cells in vivo, and a decreased level of α-SMA expression both in mice primary fibroblasts and human primary fibroblasts induced by TGF-β in vitro. Furthermore, the phosphorylation of AMP-activated protein kinase (p-AMPK) was significantly lower in the fibrotic foci induced by BLM, and the adenoviral-overexpression of omentin-1 significantly increased the p-AMPK level in vivo. Importantly, Compound C, the inhibitor of AMPK, significantly attenuated the protective effect of omentin-1 on BLM-induced lung fibrosis and reversed the effect of omentin-1 on fibroblast activation by TGF-β. Omentin-1 can be a promising therapeutic agent for the prevention and treatment of lung fibrosis.
Vinpocetine Ameliorates Metabolic-Syndrome-Associated Bladder Overactivity in Fructose-Fed Rats by Restoring Succinate-Modulated cAMP Levels and Exerting Anti-Inflammatory Effects in the Bladder Detrusor Muscle
Authors: Lee Wei-Chia , Yu Hong-Ren , Tain You-Lin , Wu Kay L.H. , Chuang Yao-Chi , Chan Julie Y.H.
Published: October 2022

Succinate and its receptor, the G protein-coupled receptor 91 (GPR91), have pathological implications in metabolic syndrome (MetS) and its associated bladder dysfunction, particularly in decreasing bladder cAMP levels and promoting proinflammation. Using fructose-fed rats (FFRs), a rat model of MetS, we investigate the effects of vinpocetine (a phosphodiesterase-1 inhibitor) and celecoxib (a selective cyclooxygenase-2 inhibitor) on MetS-associated bladder overactivity. Phenotypes of the overactive bladder, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with elevated succinate levels in the liver and serum and the downregulation of GPR91 in the liver and urinary bladder. Treatments with vinpocetine and celecoxib improved tissue fibrosis and ameliorated the overexpression of the inflammatory cytokines, such as IL-1β, in the liver and bladder. In bladder organ bath studies, vinpocetine, but not celecoxib, treatment restored the contraction and relaxation responses of the detrusor muscle strip in response to KCl, carbachol, and forskolin stimulation. At a molecular level, vinpocetine and celecoxib treatments modulated the downstream messengers of GPR91 (i.e., ERK1/2 and JNK), suppressed NF-κB and IL-1β expressions in the bladder, and prevented the fibrogenesis observed in FFRs. The exogenous application of succinate to a bladder organ bath significantly reduced the forskolin-induced cAMP production by the detrusor muscle, which was notably restored in the presence of vinpocetine. Together, these results suggest that vinpocetine may alleviate the MetS-associated bladder overactivity by restoring the succinate-modulated detrusor cAMP production and exerting the anti-inflammatory effects in the bladder detrusor muscle.
Derivative-Free Observability Analysis for Sensor Placement Optimization of Bioinspired Flexible Flapping Wing System
Authors: Jin Bingyu , Xu Hao , Peng Jicheng , Lu Kelin , Lu Yuping
Published: October 2022

Observability analysis of a bioinspired flexible flapping wing system provides a measure of how well the states of flexible flapping wing micro-aerial vehicles can be estimated from real-time measurements during high-speed flight. However, the traditional observability analysis approaches have trouble in terms of lack of quantitative analysis index, high computational complexity, low accuracy, and unavailability in stochastic systems with memory, including bioinspired flexible flapping wing systems. Therefore, a novel derivative-free observability analysis method is proposed here based on the generalized polynomial chaos expansion. By formulating a surrogate model to represent the relationship between the cumulative measurement and the random initial state, the observability coefficient matrix is calculated and the observability rank condition is stated. Consequently, several observability indices are proposed to quantity the observability of the system. Altogether, the proposed method avoids the disadvantages of the traditional approaches, especially in assessing the observability degree of each state and the effect of stochastic noise on observability. The validation of the proposed method is first provided by demonstrating the equivalence between the traditional and proposed methods and subsequently by comparing the observability of the Lorenz system calculated via three different approaches. Finally, the proposed method is applied on a bioinspired flexible wing system to optimize the placement of sensors, which is consistent with the natural configuration of campaniform sensilla on the wing of the hawkmoth.
Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free
Authors: Serwer Philip , Wright Elena T.
Published: October 2022

Chemotherapy-inhibiting tumor cell evolution to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence.
Leveraging Accelerometry as a Prognostic Indicator for Increase in Opioid Withdrawal Symptoms
Authors: Lambert Tamara P. , Gazi Asim H. , Harrison Anna B. , Gharehbaghi Sevda , Chan Michael , Obideen Malik , Alavi Parvaneh , Murrah Nancy , Shallenberger Lucy , Driggers Emily G. , Alvarado Ortega Rebeca , Washington Brianna , Walton Kevin M. , Tang Yi-Lang , Gupta Rahul , Nye Jonathon A. , Welsh Justine W. , Vaccarino Viola , Shah Amit J. , Bremner J. Douglas , Inan Omer T.
Published: October 2022

Treating opioid use disorder (OUD) is a significant healthcare challenge in the United States. Remaining abstinent from opioids is challenging for individuals with OUD due to withdrawal symptoms that include restlessness. However, to our knowledge, studies of acute withdrawal have not quantified restlessness using involuntary movements. We hypothesized that wearable accelerometry placed mid-sternum could be used to detect withdrawal-related restlessness in patients with OUD. To study this, 23 patients with OUD undergoing active withdrawal participated in a protocol involving wearable accelerometry, opioid cues to elicit craving, and non-invasive Vagal Nerve Stimulation (nVNS) to dampen withdrawal symptoms. Using accelerometry signals, we analyzed how movements correlated with changes in acute withdrawal severity, measured by the Clinical Opioid Withdrawal Scale (COWS). Our results revealed that patients demonstrating sinusoidal–i.e., predominantly single-frequency oscillation patterns in their motion almost exclusively demonstrated an increase in the COWS, and a strong relationship between the maximum power spectral density and increased withdrawal over time, measured by the COWS (R = 0.92, p = 0.029). Accelerometry may be used in an ambulatory setting to indicate the increased intensity of a patient’s withdrawal symptoms, providing an objective, readily-measurable marker that may be captured ubiquitously.
A Molecular Lateral Flow Assay for SARS-CoV-2 Quantitative Detection
Authors: Maglaras Panagiotis , Lilis Ioannis , Paliogianni Fotini , Bravou Vasiliki , Kalogianni Despina P.
Published: October 2022

Since the onset of the SARS-CoV-2 pandemic, several COVID-19 detection methods, both commercially available and in the lab, have been developed using different biomolecules as analytes and different detection and sampling methods with high analytical performance. Developing novel COVID-19 detection assays is an exciting research field, as rapid accurate diagnosis is a valuable tool to control the current pandemic, and also because the acquired knowledge can be deployed for facing future infectious outbreaks. We here developed a novel gold-nanoparticle-based nucleic acid lateral flow assay for the rapid, visual, and quantitative detection of SARS-CoV-2. Our method was based on the use of a DNA internal standard (competitor) for quantification and involved RT-PCR, the hybridization of biotinylated PCR products to specific oligonucleotide probes, and detection with a dual lateral flow assay using gold nanoparticles conjugated to an anti-biotin antibody as reporters. The developed test allowed for rapid detection by the naked eye and the simultaneous quantification of SARS-CoV-2 in nasopharyngeal swabs with high specificity, detectability, and repeatability. This novel molecular strip test for COVID-19 detection represents a simple, cost-effective, and accurate rapid test that is very promising to be used as a future diagnostic tool.
Correction: Zhang et al. Admission Serum Iron as an Independent Risk Factor for Postoperative Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Matched Analysis. Brain Sci. 2022, 12, 1183
Authors: Zhang Yi-Bin , Zheng Feng , Stavrinou Lampis , Wang Hao-Jie , Fan Wen-Jian , Yao Pei-Sen , Lin Yuan-Xiang , Goldbrunner Roland , Zheng Shu-Fa , Stavrinou Pantelis , Kang De-Zhi
Published: October 2022

We would like to submit the following corrections to our recently published paper [...]
Metalloproteinases and Tissue Inhibitors in Generalized Myasthenia Gravis. A Preliminary Study
Authors: Di Stefano Vincenzo , Tubiolo Chiara , Gagliardo Andrea , Presti Rosalia , Montana Maria , Todisco Massimiliano , Lupica Antonino , Caimi Gregorio , Tassorelli Cristina , Fierro Brigida , Brighina Filippo , Cosentino Giuseppe
Published: October 2022

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have recently been proposed as promising biomarkers in different immune-mediated disorders. We evaluated the plasma levels of MMP-9 and MMP-2 and their tissue inhibitors TIMP-1 and TIMP-2 in a patients’ cohort with generalized myasthenia gravis (MG). Methods: Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were evaluated in 14 patients with generalized MG and 13 age- and sex-matched healthy controls. The severity of disease was assessed by the modified Osserman classification. Results: Compared to the healthy subjects, MG patients had increased plasma concentrations of MMP-9, but reduced plasma levels of MMP-2 and TIMP-1. MG patients also showed a positive correlation between MMP-2 concentrations and disease severity. An increase in MMP-9 levels and MMP-9/TIMP-1 ratio and a decrease in MMP-2 levels and MMP-2/TIMP-2 ratio were detected in patients with generalized MG. Higher levels of MMP-2 correlated with greater disease severity. Discussion: Our preliminary findings suggest that MMPs and TIMPs could play a role in the pathogenesis of MG and might be associated with the risk of clinical deterioration.
Nutrition, Sleep, and Exercise as Healthy Behaviors in Schizotypy: A Scoping Review
Authors: Wong Keri Ka-Yee , Raine Adrian
Published: October 2022

This scoping review identifies the role of nutrition, sleep, and exercise as healthy behaviors in non-clinical individuals with schizotypy throughout the lifespan. Methods: We systematically reviewed the existing literature on these topics through databases including: PsycINFO, Scopus, APA PsycNet, ScienceDirect, Wiley Online Library, and SpringerLink. Results: Of the 59 studies found, a total of 29 studies met the inclusion criteria on the review topic. Included studies reflect varying study designs (cross-sectional, multiple time-point, intervention, randomized-placebo controlled trials), assessment of schizotypy and associated healthy behaviors, focus on various samples and lifespan (e.g., undergraduates, adolescents, at-risk individuals), and stem from different countries. Conclusion: While a moderate number of studies address the role of nutrition, sleep, and physical exercise in relation to schizotypy, studies intersecting these topics are limited. Of the limited studies that do exist, the majority are correlational with the beginnings of causal support from intervention studies. As such, more research is needed on the topics of nutrition, sleep, and exercise in relation to schizotypy. Specifically, future research should focus on providing a more holistic understanding of schizotypal traits and its subtypes, and which specific or combination of behaviors may reduce levels of schizotypy.
Full-Scale Test and Bearing Capacity Evaluation of Large Diameter Prestressed Concrete Cylinder Pipe under Internal Water Pressure
Authors: Qu Fulai , Zhang Di , Shang Pengran , Wang Hao , Zheng Wenkui , Zhao Shunbo
Published: October 2022

In practical applications, the safe operation of large-diameter prestressed concrete cylinder pipes (PCCPs) depends on the loading performance under internal water pressure. However, there is lack of damage tests for the full-scale large-diameter PCCPs due to economic cost and experimental difficulty. In this paper, a full-scale PCCP with diameter of 3.2 m was tested to verify the bearing capacity for applying to an actual water transfer project. The PCCP was designed by the limit state method and manufactured in a prefabrication plant. During the test, the strains of concrete, prestressed steel wire, and mortar were detected to evaluate the limit state of bearing capacity under internal water pressure. Based on the test results and the strain analysis at the limit state, it was found that when the water pressure reached 1.9 MPa, the concrete outside the steel cylinder was at the serviceability limit state, and the prestressed steel wire was in elastic, while some protective mortar exceeded the serviceability limit state due to the appearance of visible cracks. A good accuracy of the theoretical calculation with the predicted results lower about 9.4% and 8% than tested pressures at decompression and cracking states. Moreover, the cracking pressure of concrete and bursting pressure of pipe were 2.5 and 6 times of the working pressure according to the calculation results. This indicated that the PCCP used in this study had sufficient safety in actual operation. However, it should be noted that the tensile control strain of mortar may be overestimated by the current code.
Clinical Outcomes of Acute Myeloid Leukemia Patients Harboring the RUNX1 Mutation: Is It Still an Unfavorable Prognosis? A Cohort Study and Meta-Analysis
Authors: Rungjirajittranon Tarinee , Siriwannangkul Theerapat , Kungwankiattichai Smith , Leelakanok Nattawut , Rotchanapanya Wannaphorn , Vittayawacharin Pongthep , Mekrakseree Benjamaporn , Kulchutisin Kamolchanok , Owattanapanich Weerapat
Published: October 2022

Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1mut) is considered to have an unfavorable prognosis. However, recent studies have reported comparable survival outcomes with wild-type RUNX1 (RUNX1wt). To assess the clinical outcomes of AML with and without RUNX1mut, we performed a prospective cohort study and systematic review and meta-analysis. The study enrolled 135 patients (27 with RUNX1mut; 108 with RUNX1wt). There were no significant differences in the median OS and RFS of the RUNX1mut and RUNX1wt groups (9.1 vs. 12.2 months; p = 0.268 and 7.8 vs. 14.6 months; p = 0.481, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics showed similar outcomes. Our meta-analysis pooled data from 23 studies and our study. The complete remission rate was significantly lower in the RUNX1mut group (pooled odds ratio: 0.42). The OS, RFS, and event-free survival rates also favored the RUNX1wt group (pooled risk ratios: 1.36, 1.37, and 1.37, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics demonstrated nearly identical OS and RFS outcomes. This study confirms that patients with AML and RUNX1mut had poor prognoses. Nonetheless, in de novo AML with intermediate-risk cytogenetics, the survival outcomes of both groups were comparable.
Monoclonal Gammopathies of Clinical Significance: A Critical Appraisal
Authors: Ríos-Tamayo Rafael , Paiva Bruno , Lahuerta Juan José , López Joaquín Martínez , Duarte Rafael F.
Published: October 2022

Monoclonal gammopathies of clinical significance (MGCSs) represent a group of diseases featuring the association of a nonmalignant B cells or plasma cells clone, the production of an M-protein, and singularly, the existence of organ damage. They present a current framework that is difficult to approach from a practical clinical perspective. Several points should be addressed in order to move further toward a better understanding. Overall, these entities are only partially included in the international classifications of diseases. Its definition and classification remain ambiguous. Remarkably, its real incidence is unknown, provided that a diagnostic biopsy is mandatory in most cases. In fact, amyloidosis AL is the final diagnosis in a large percentage of patients with renal significance. On the other hand, many of these young entities are syndromes that are based on a dynamic set of diagnostic criteria, challenging a timely diagnosis. Moreover, a specific risk score for progression is lacking. Despite the key role of the clinical laboratory in the diagnosis and prognosis of these patients, information about laboratory biomarkers is limited. Besides, the evidence accumulated for many of these entities is scarce. Hence, national and international registries are stimulated. In particular, IgM MGCS deserves special attention. Until now, therapy is far from being standardized, and it should be planned on a risk and patient-adapted basis. Finally, a comprehensive and coordinated multidisciplinary approach is needed, and specific clinical trials are encouraged.
Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review
Authors: Chauhan Aman , Del Rivero Jaydira , Ramirez Robert A. , Soares Heloisa P. , Li Daneng
Published: October 2022

Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.
Perioperative and Oncological Outcomes of Robotic-Assisted, Video-Assisted Thoracoscopic and Open Lobectomy for Patients with N1-Metastatic Non-Small Cell Lung Cancer: A Propensity Score-Matched Study
Authors: Pan Hanbo , Tian Yu , Wang Hui , Jiang Long , Gu Zenan , Zhu Hongda , Ning Junwei , Huang Jia , Luo Qingquan
Published: October 2022

(1) Background: Despite the fact that robotic-assisted thoracoscopic lobectomy (RATL) has been prevalently applied for early stage non-small cell lung cancer (NSCLC), its superiorities are still to be fully revealed for patients with metastatic N1 lymph nodes (LNs). We aim to evaluate the advantages of RATL for N1 NSCLC. (2) Methods: This retrospective study identified consecutive pathological N1 NSCLC patients undergoing RATL, video-assisted thoracoscopic lobectomy (VATL), or open lobectomy (OL) in Shanghai Chest Hospital between 2014 and 2020. Further, perioperative and oncological outcomes were investigated. (3) Results: A total of 855 cases (70 RATL, 435 VATL, and 350 OL) were included. Propensity score matching resulted in 70, 140, and 140 cases in the RATL, VATL, and OL groups, respectively. RATL led to (1) the shortest surgical time (p = 0.005) and lowest intraoperative blood loss (p < 0.001); (2) the shortest ICU (p < 0.001) and postsurgical hospital (p < 0.001) stays as well as chest tube duration (p < 0.001); and (3) the lowest morbidities of postsurgical complications (p = 0.016). Moreover, RATL dissected more N1 (p = 0.027), more N1 + N2 (p = 0.027) LNs, and led to a higher upstaging incidence rate (p < 0.050) than VATL. Finally, RATL achieved a comparable 5-year disease-free and overall survival in relation to VATL and OL. (4) Conclusions: RATL led to the most optimal perioperative outcomes among the three surgical approaches and showed superiority in assessing N1 and total LNs over VATL, though it did achieve comparable oncological outcomes in relation to VATL and OL for N1 NSCLC patients.
The Association of Tumor Immune Microenvironment of the Primary Lesion with Time to Metastasis in Patients with Renal Cell Carcinoma: A Retrospective Analysis
Authors: Fujita Kazutoshi , Kimura Go , Tsuzuki Toyonori , Kato Taigo , Banno Eri , Kazama Akira , Yamashita Ryo , Matsushita Yuto , Ishii Daisuke , Fukawa Tomoya , Nakagawa Yuki , Fukuyama Tamaki , Sano Fumikazu , Kondo Yukihiro , Uemura Hirotsugu
Published: October 2022

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.
Development and Implementation of an Advanced Program for Robotic Treatment of Prostate Cancer—Is Surgical Quality Transferable?
Authors: Sigle August , Jilg Cordula A. , Weishaar Moritz , Schlenker Boris , Stief Christian , Gratzke Christian , Grabbert Markus
Published: October 2022

Introduction: Robot-assisted radical prostatectomy (RARP) is a surgical treatment option for prostate cancer (PC). Quality in RARP depends on the surgeon´s operative volume and expertise. When implementing RARP, it is standard practice to hire a pre-trained surgeon. The aim of our study was to investigate the transferability of quality in RARP. Patients and Methods: We analyzed two consecutive retrospective cohorts of 100 and 108 men, respectively, who underwent RARP at two different centers and on whom surgery was performed by the same surgeon. Results: There were more men with high-grade PC in Cohort 1: 25/100 (25.0%) vs. 9/108 (8.3%), p < 0.01, and infiltration of the seminal vesicles was more frequent (23/100 (23.0%) vs. 10/108 (9.2%), p < 0.01). In Cohort 2, the duration of surgery was shorter and blood loss was lower: 149 (134–174) vs. 172 min (150–196), p < 0.01 and 300 (200–400) vs. 131 (99–188) mL, p < 0.01. No difference was found in the proportion of positive surgical margins in the T2 cohort (8.8% vs. 8.2%, p = 1.00). Conclusion: The procedural and oncological outcome parameters of Cohort 2 do not appear to be inferior to the results obtained for the first cohort. The quality of RARP is transferable if a pre-trained surgeon is hired.
Inflammation as a Therapeutic Target in Cancer Cachexia
Authors: Clamon Gerald , Byrne Margaret M. , Talbert Erin E.
Published: October 2022

Cachexia is a common complication of cancer and is associated with poor quality of life and a decrease in survival. Many patients with cancer cachexia suffer from inflammation associated with elevated cytokines, such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Single-agent trials to treat cancer cachexia have not led to substantial benefit as the type of cytokine which is elevated has rarely been specified and targeted. Cachexia may also be multifactorial, involving inflammation, anorexia, catabolism, depression, and pain, and targeting the multiple causes will likely be necessary to achieve improvement in weight and appetite. A PUBMED search revealed over 3000 articles on cancer cachexia in the past ten years. We attempted to review any studies related to inflammation and cancer cachexia identified by Google Scholar and PUBMED and further search for articles listed in their references. The National Comprehensive Cancer Network (NCCN) guidelines do not provide any suggestion for managing cancer cachexia except a dietary consult. A more targeted approach to developing therapies for cancer cachexia might lead to more personalized and effective therapy.
Overall Survival for Esophageal Squamous Cell Carcinoma with Multiple Primary Cancers after Curative Esophagectomy—A Retrospective Single-Institution Study
Authors: Tsai Ping-Chung , Ting Ying-Che , Hsu Po-Kuei , Hung Jung-Jyh , Huang Chien-Sheng , Hsu Wen-Hu , Hsu Han-Shui
Published: October 2022

Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous cell carcinoma (SCC) associated with MPCs. Methods: Data from 544 patients with esophageal SCC who underwent surgery between 2005 and 2017 were reviewed to identify the presence of simultaneous or metachronous primary cancers. The prognostic factors for overall survival (OS) were analyzed. Results: Three hundred and ninety-seven patients after curative esophagectomy were included, with a median observation time of 44.2 months (range 2.6–178.6 months). Out of 52 patients (13.1%) with antecedent/synchronous cancers and 296 patients without MPCs (control group), 49 patients (12.3%) developed subsequent cancers after surgery. The most common site of other primary cancers was the head and neck (69/101; 68.3%), which showed no inferiority in OS. Sex and advanced clinical stage (III/IV) were independent risk factors (p = 0.031 and p < 0.001, respectively). Conclusion: Once curative esophagectomy can be achieved, surgery should be selected as a potential therapeutic approach if indicated, even with antecedent/synchronous MPCs. Subsequent primary cancers were often observed in esophageal SCC, and optimal surveillance planning was recommended.
Photoreactive Carbon Dots Modified g-C3N4 for Effective Photooxidation of Bisphenol-A under Visible Light Irradiation
Authors: Iqbal Anwar , Shittu Fatimah Bukola , Ibrahim Mohamad Nasir Mohamad , Bakar N. H. H. Abu , Yahaya Noorfatimah , Rajappan Kalaivizhi , Hussin M. Hazwan , Danial Wan Hazman , Wilson Lee D.
Published: October 2022

A series of carbon dots (CDs) modified g-C3N4 (xCDs/g-C3N4; x = 0.5, 1.0, and 1.5 mL CDs solution) was synthesized via the microwave-assisted hydrothermal synthesis method for the photooxidation of bisphenol-A (BPA) under visible light irradiation. The X-ray diffraction (XRD) analysis indicates that the CDs may have a turbostratic structure and the resulting photocatalysts have distorted crystal structure, as compared with pure g-C3N4. The high-resolution transmission electron microscope (HR-TEM) analysis revealed amorphous, mono-disperse, spherical CDs with an average particle size of 3.75 nm. The distribution of CDs within the matrix of g-C3N4 appear as small dark dot-like domains. The N2 adsorption-desorption analysis indicates that the nanocomposites are mesoporous with a density functional theory (DFT) estimate of the pore size distribution between 2–13 nm. The CDs quantum yield (QY) was determined to be 12% using the UV-vis spectral analysis, where the CDs/g-C3N4 has improved absorption in the visible region than g-C3N4. The higher BET surface area of CDs/g-C3N4 provided more adsorption sites and the ability to yield photogenerated e−/h+ pairs, which caused the 1.5 CDs/g-C3N4 to have better photocatalytic efficiency compared to the rest of the systems. The highest removal, 90%, was achieved at the following optimum conditions: BPA initial concentration = 20 mg L−1, catalyst dosage = 30 mg L−1, and pH = 10. The photooxidation process is mainly driven by photogenerated holes (h+) followed by •OH and O2•−. The synthesis of the 1.5 CDs/g-C3N4 system is simple and cost-effective, where this photocatalyst is highly stable and reusable versus other systems reported in the literature.
Nanotubes Formation in P. aeruginosa
Authors: Ahmed Faraz , Mirani Zulfiqar Ali , Ahmed Ayaz , Urooj Shaista , Khan Fouzia Zeeshan , Siddiqi Anila , Khan Muhammad Naseem , Imdad Muhammad Janees , Ullah Asad , Khan Abdul Basit , Zhao Yong
Published: October 2022

The present study discusses a biofilm-positive P. aeruginosa isolate that survives at pH levels ranging from 4.0 to 9.0. The biofilm consortia were colonized with different phenotypes i.e., planktonic, slow-growing and metabolically inactive small colony variants (SCVs). The lower base of the consortia was occupied by SCVs. These cells were strongly attached to solid surfaces and interconnected through a network of nanotubes. Nanotubes were observed at the stationary phase of biofilm indwellers and were more prominent after applying weight to the consortia. The scanning electron micrographs indicated that the nanotubes are polar appendages with intraspecies connectivity. The micrographs indicated variations in physical dimensions (length, width, and height) and a considerable reduction in volume due to weight pressure. A total of 35 cells were randomly selected. The mean volume of cells before the application of weight was 0.288 µm3, which was reduced to 0.144 µm3 after the application of weight. It was observed that a single cell may produce as many as six nanotubes, connected simultaneously to six neighbouring cells in different directions. The in-depth analysis confirmed that these structures were the intra-species connecting tools as no free nanotubes were found. Furthermore, after the application of weight, cells incapable of producing nanotubes were wiped out and the surface was covered by nanotube producers. This suggests that the nanotubes give a selective advantage to the cells to resist harsh environmental conditions and weight pressure. After the removal of weight and proper supply of nutrients, these phenotypes reverted to normal planktonic lifestyles. It is concluded that the nanotubes are not merely the phenomenon of dying cells; rather they are a connectivity tool which helps connected cells to tolerate and resist environmental stress.
Insights into White Matter Defect in Huntington’s Disease
Authors: Sun Yize , Tong Huichun , Yang Tianqi , Liu Li , Li Xiao-Jiang , Li Shihua
Published: October 2022

Huntington’s disease (HD) is an autosomal-dominant inherited progressive neurodegenerative disorder. It is caused by a CAG repeat expansion in the Huntingtin gene that is translated to an expanded polyglutamine (PolyQ) repeat in huntingtin protein. HD is characterized by mood swings, involuntary movement, and cognitive decline in the late disease stage. HD patients often die 15–20 years after disease onset. Currently, there is no cure for HD. Due to the striking neuronal loss in HD, most studies focused on the investigation of the predominantly neuronal degeneration in specific brain regions. However, the pathology of the white matter area in the brains of HD patients was also reported by clinical imaging studies, which showed white matter abnormalities even before the clinical onset of HD. Since oligodendrocytes form myelin sheaths around the axons in the brain, white matter lesions are likely attributed to alterations in myelin and oligodendrocyte-associated changes in HD. In this review, we summarized the evidence for white matter, myelin, and oligodendrocytes alterations that were previously observed in HD patients and animal models. We also discussed potential mechanisms for white matter changes and possible treatment to prevent glial dysfunction in HD.
Multiplexed Digital Spatial Protein Profiling Reveals Distinct Phenotypes of Mononuclear Phagocytes in Livers with Advanced Fibrosis
Authors: Lee Jaejun , Kim Chang Min , Cha Jung Hoon , Park Jin Young , Yu Yun Suk , Wang Hee Jung , Sung Pil Soo , Jung Eun Sun , Bae Si Hyun
Published: October 2022

Background and Aims: Intrahepatic mononuclear phagocytes (MPs) are critical for the initiation and progression of liver fibrosis. In this study, using multiplexed digital spatial protein profiling, we aimed to derive a unique protein signature predicting advanced liver fibrosis. Methods: Snap-frozen liver tissues from various chronic liver diseases were subjected to spatially defined protein-based multiplexed profiling (Nanostring GeoMXTM). A single-cell RNA sequencing analysis was performed using Gene Expression Omnibus (GEO) datasets from normal and cirrhotic livers. Results: Sixty-four portal regions of interest (ROIs) were selected for the spatial profiling. Using the results from the CD68+ area, a highly sensitive and specific immune-related protein signature (CD68, HLA-DR, OX40L, phospho-c-RAF, STING, and TIM3) was developed to predict advanced (F3 and F4) fibrosis. A combined analysis of single-cell RNA sequencing data from GEO datasets (GSE136103) and spatially-defined, protein-based multiplexed profiling revealed that most proteins upregulated in F0–F2 livers in portal CD68+ cells were specifically marked in tissue monocytes, whereas proteins upregulated in F3 and F4 livers were marked in scar-associated macrophages (SAMacs) and tissue monocytes. Internal validation using mRNA expression data with the same cohort tissues demonstrated that mRNA levels for TREM2, CD9, and CD68 are significantly higher in livers with advanced fibrosis. Conclusions: In patients with advanced liver fibrosis, portal MPs comprise of heterogeneous populations composed of SAMacs, Kupffer cells, and tissue monocytes. This is the first study that used spatially defined protein-based multiplexed profiling, and we have demonstrated the critical difference in the phenotypes of portal MPs between livers with early- or late-stage fibrosis.
The Role of Clay Mineral-Derived Photocatalysts in Insights of Remediation
Authors: Freitas Walber , Trigueiro Pollyana , Marinho Thiago , Honorio Luzia M. , Silva-Filho Edson C. , Furtini Marcelo B. , Cecília Juan A. , Fonseca Maria G. , Osajima Josy
Published: October 2022

Clay minerals have advantages to be used as supports for obtaining new catalysts, in which colloidal and surface characteristics play a significant role. In addition to their favorable physicochemical properties, clay minerals allow different modifications to form structures with broad photochemical capabilities. This review collects pertinent works of semiconductor nanoparticles loaded onto clay minerals and their potential application in hazardous contaminant photodegradation. Web of Science, Scopus, and Science Direct were used for bibliographic research databases. The sol–gel method is the most frequent technique used to obtain semiconductors immobilized onto clay minerals, but other methods have also proven helpful in forming these structures. Thence, the types of synthesis and different parameters that influence their photocatalytic efficiency will be discussed. Pillared clay minerals have been applied to photo-oxidation reactions involving photodecomposition of environmental contaminants. The homogeneous dispersion of nanoparticles on the surface of clay minerals, reduction of fine particles, its non-toxicity, and the generation of a suitable suspension for photocatalytic reactions may be the main characteristics of these inorganic supports to obtain successful photoactive materials.
Enhanced Electromagnetic Coupling in the Walnut-Shaped Nanostructure Array
Authors: Mao Deyuan , Zhao Xiaoyu , Wen Jiahong , Wang Aofang , Gao Renxian , Wang Yaxin
Published: October 2022

It is a challenging yet valuable work to prepare a surface-enhanced Raman scattering (SERS) substrate with low cost and high performance by simple methods. In this study, the Ag nanoparticles were sputtered on PS spheres by the magnetron sputtering, which was used as the mask to create the nanostructures by etching the spheres. Because of the heating effect in the etching process, the Ag nanoparticles gathered on the surfaces of PS spheres when the etching time was 60 s. Strong electromagnetic coupling was observed between the gathered Ag nanoparticles as confirmed by FDTD simulation and SERS signals from the probe molecule 4-mercaptobenzoic acid. This structure showed the detection limit for thiram down to 10−8 M.
Development and Application of AR-Based Assessment System for Infant Airway Obstruction First Aid Training
Authors: Chen Pao-Ju , Liou Wei-Kai
Published: October 2022

Airway obstruction refers to suffocation caused by blockage of the airway due to a foreign body and is a common cause of accidental death in infants below one year of age. However, the current infant CPR manikins used for training in first aid for foreign body airway obstruction can only be applied to one single scenario. Furthermore, trainees’ first aid skills cannot be recorded and quantified with a digital system and, consequently, assessment of their skills is difficult to conduct. This study aims to overcome the technical limitations by developing an AR-based assessment system for training in first aid for infant airway obstruction. With this assessment system, trainees can learn first aid more efficiently and correctly and conduct a quantitative assessment of their skills digitally. For instructors, the time required for assessment, potential human error, and the cost of training can also be reduced. The system can be a practical learning tool that helps trainees assess emergencies and integrate their knowledge and skills.
Obstetric and Neonatal Outcomes in Mild Idiopathic Polyhydramnios
Authors: Pasquini Lucia , Ponziani Ilaria , Pallottini Marta , Masini Giulia , Seravalli Viola , Dani Carlo , Di Tommaso Mariarosaria
Published: October 2022

Background: Idiopathic polyhydramnios is a controversial clinical condition, as data on perinatal outcomes are conflicting and vary depending on the severity of the condition. The aim of the present study was to compare obstetric and neonatal outcomes between pregnant women with mild idiopathic polyhydramnios and a control population. Methods: A retrospective cohort study was performed at a single university hospital comparing the obstetrics and neonatal outcomes of pregnancies with mild idiopathic polyhydramnios (n = 109) and control pregnancies (n = 2550). Results: Cesarean section (CS) was significantly increased in the group with polyhydramnios compared to controls (46% vs. 32%, respectively, p = 0.047) due to a higher rate of emergency CS in the polyhydramnios group (p = 0.041) because of abnormal cardiotocography (7.3% vs. 2.9%; p = 0.018) or labor dystocia (8.2% vs. 2.9%; p = 0.006). No statistically significant difference was found in the Apgar score, in the rate of neonatal hypoxia, or in the incidence of macrosomia between groups. In four cases, additional diagnoses of anomalies were made after birth, with a rate of 3.2%, which is comparable to the general population. Conclusion: Besides an increased risk of CS, patients with mild idiopathic polyhydramnios should be reassured regarding maternal and feto-neonatal outcomes. The management of pregnancies with stable mild idiopathic polyhydramnios should not differ from uncomplicated pregnancies, except for the need for increased labor surveillance.
Atrioventricular Block in Celiac Disease: An Unusual Clinical Presentation in a Child. A Case-Based Review
Authors: Mannarino Savina , Santacesaria Sara , Raso Irene , Fini Giulia , Pozzi Elena , Cocuccio Cristina , Calcaterra Valeria , Zuccotti Gianvincenzo
Published: October 2022

Congenital or acquired atrioventricular block (AVB) is a rare disorder in the pediatric population, while celiac disease (CeD) is a common multisystemic autoimmune disorder that is characterized by intestinal manifestations as they are the typical clinical presentation. Sometimes CeD presents more complex multisystemic involvement which includes the heart. Cardiac involvement, such as dilated cardiomyopathy, myocarditis or conduction disease, have been mainly described in untreated adult patients with or without gastro-intestinal symptoms; rare cases of AVB and CeD have been also reported, particularly in association with extra-cardiac manifestations. We describe a case of a progressive acquired AVB block in a 4-year-old child, in which CeD was later diagnosed. A rapid and significantly improvement of the AVB grade has been obtained after the child started a strict gluten-free diet, and so we suggest including diagnostic exams for CeD in all of the children with acquired AVB.