bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoid Receptor Signaling in Diabetes
Authors: Kokkinopoulou Ioanna , Diakoumi Andriana , Moutsatsou Paraskevi
Published: October 2021

Stress and depression increase the risk of Type 2 Diabetes (T2D) development. Evidence demonstrates that the Glucocorticoid (GC) negative feedback is impaired (GC resistance) in T2D patients resulting in Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity and hypercortisolism. High GCs, in turn, activate multiple aspects of glucose homeostasis in peripheral tissues leading to hyperglycemia. Elucidation of the underlying molecular mechanisms revealed that Glucocorticoid Receptor (GR) mediates the GC-induced dysregulation of glucose production, uptake and insulin signaling in GC-sensitive peripheral tissues, such as liver, skeletal muscle, adipose tissue, and pancreas. In contrast to increased GR peripheral sensitivity, an impaired GR signaling in Peripheral Blood Mononuclear Cells (PBMCs) of T2D patients, associated with hyperglycemia, hyperlipidemia, and increased inflammation, has been shown. Given that GR changes in immune cells parallel those in brain, the above data implicate that a reduced brain GR function may be the biological link among stress, HPA hyperactivity, hypercortisolism and hyperglycemia. GR polymorphisms have also been associated with metabolic disturbances in T2D while dysregulation of micro-RNAs—known to target GR mRNA—has been described. Collectively, GR has a crucial role in T2D, acting in a cell-type and context-specific manner, leading to either GC sensitivity or GC resistance. Selective modulation of GR signaling in T2D therapy warrants further investigation.
S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury
Authors: Chen Tzu-Jou , Yeh Yen-Ting , Peng Fu-Shiang , Li Ai-Hsien , Wu Shinn-Chih
Published: October 2021

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.
PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation
Authors: Spirina Liudmila , Avgustinovich Alexandra , Afanas’ev Sergei , Volkov Maxim , Dobrodeev Alexey , Cheremisina Olga , Kostromitsky Dmitry
Published: October 2021

Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients with GC. The combined treatment consisted of neoadjuvant FOLFOX6, or FLOT, chemotherapy and surgery. PD-L1 + tumor status was recorded in 12 patients (CPS > 5), with a negative status recorded in 26 patients. RT-PCR determined the expression of molecular markers. The level of LC3B protein was detected by Western Blotting analysis. Results: An overexpression of PD-1, PD-L2 in the tumor is associated with AKT/mTOR mRNA profile change and autophagy initiation in IHC PD-L1 positive GCs. NACT influences these biological features, modifying the expression of AKT/mTOR components and autophagic flux. In PD-L1 positive cancers, the effect of NACT and molecular markers rearrangements are essential compared to the PD-L1 negative cancers. Conclusion: The IHC PD-L1 status in gastric cancers is the significant marker of cancer progression, recovering the multiple inner mechanisms of cancer spreading and leading to ineffective therapy. Autophagy induction and angiogenesis are found in PD-L1 positive gastric cancers.
Atypical Renal Clearance of Nanoparticles Larger Than the Kidney Filtration Threshold
Authors: Adhipandito Christophorus F. , Cheung Siu-Hung , Lin Yu-Han , Wu Si-Han
Published: October 2021

In recent years, several publications reported that nanoparticles larger than the kidney filtration threshold were found intact in the urine after being injected into laboratory mice. This theoretically should not be possible, as it is widely known that the kidneys prevent molecules larger than 6–8 nm from escaping into the urine. This is interesting because it implies that some nanoparticles can overcome the size limit for renal clearance. What kinds of nanoparticles can “bypass” the glomerular filtration barrier and cross into the urine? What physical and chemical characteristics are essential for nanoparticles to have this ability? And what are the biomolecular and cellular mechanisms that are involved? This review attempts to answer those questions and summarize known reports of renal-clearable large nanoparticles.
Discovery and Chromosomal Location a Highly Effective Oat Crown Rust Resistance Gene Pc50-5
Authors: Toporowska Joanna , Sowa Sylwia , Kilian Andrzej , Koroluk Aneta , Paczos-Grzęda Edyta
Published: October 2021

Crown rust, caused by Puccinia coronata f. sp. avenae, is one of the most destructive fungal diseases of oat worldwide. Growing disease-resistant oat cultivars is the preferred method of preventing the spread of rust and potential epidemics. The object of the study was Pc50-5, a race-specific seedling crown rust resistant gene, highly effective at all growth stages, selected from the differential line Pc50 (Avena sterilis L. CW 486-1 × Pendek). A comparison of crown rust reaction as well as an allelism test showed the distinctiveness of Pc50-5, whereas the proportions of phenotypes in segregating populations derived from a cross with two crown rust-susceptible Polish oat cultivars, Kasztan × Pc50-5 and Bingo × Pc50-5, confirmed monogenic inheritance of the gene, indicating its usefulness in oat breeding programs. Effective gene introgression depends on reliable gene identification in the early stages of plant development; thus, the aim of the study was to develop molecular markers that are tightly linked to Pc50-5. Segregating populations of Kasztan × Pc50-5 were genotyped using DArTseq technology based on next-generation Illumina short-read sequencing. Markers associated with Pc50-5 were located on chromosome 6A of the current version of the oat reference genome (Avena sativa OT3098 v2, PepsiCo) in the region between 434,234,214 and 440,149,046 bp and subsequently converted to PCR-based SCAR (sequence-characterized amplified region) markers. Furthermore, 5426978_SCAR and 24031809_SCAR co-segregated with the Pc50-5 resistance allele and were mapped to the partial linkage group at 0.6 and 4.0 cM, respectively. The co-dominant 58163643_SCAR marker was the best diagnostic and it was located closest to Pc50-5 at 0.1 cM. The newly discovered, very strong monogenic crown rust resistance may be useful for oat improvement. DArTseq sequences converted into specific PCR markers will be a valuable tool for marker-assisted selection in breeding programs.
Production of Trans-Cinnamic Acid by Immobilization of the Bambusa oldhamii BoPAL1 and BoPAL2 Phenylalanine Ammonia-Lyases on Electrospun Nanofibers
Authors: Hong Pei-Yu , Huang Yi-Hao , Lim GiGi Chin Wen , Chen Yen-Po , Hsiao Che-Jen , Chen Li-Hsien , Ciou Jhih-Ying , Hsieh Lu-Sheng
Published: October 2021

Phenylalanine ammonia-lyase (PAL) catalyzes the nonoxidative deamination of phenylalanine to yield trans-cinnamic acid and ammonia. Recombinant Bambusa oldhamii BoPAL1/2 proteins were immobilized onto electrospun nanofibers by dextran polyaldehyde as a cross-linking agent. A central composite design (CCD)-response surface methodology (RSM) was utilized to optimize the electrospinning parameters. Escherichia coli expressed eBoPAL2 exhibited the highest catalytic efficiency among four enzymes. The optimum conditions for fabricating nanofibers were determined as follows: flow rate of 0.10 mL/h, voltage of 13.8 kV, and distance of 13 cm. The response surface models were used to obtain the smaller the fiber diameters as well as the highest PAL activity in the enzyme immobilization. Compared with free BoPALs, immobilized BoPALs can be reused for at least 6 consecutive cycles. The remained activity of the immobilized BoPAL proteins after storage at 4 °C for 30 days were between 75 and 83%. In addition, the tolerance against denaturants of the immobilized BoPAL proteins were significantly enhanced. As a result, the dextran polyaldehyde natural cross-linking agent can effectively replace traditional chemical cross-linking agents for the immobilization of the BoPAL enzymes. The PAL/nylon 6/polyvinyl alcohol (PVA)/chitosan (CS) nanofibers made are extremely stable and are practical for industrial applications in the future.
Biphasic Roles of Clock Genes and Bone Morphogenetic Proteins in Gonadotropin Expression by Mouse Gonadotrope Cells
Authors: Soejima Yoshiaki , Iwata Nahoko , Nakano Yasuhiro , Yamamoto Koichiro , Suyama Atsuhito , Nada Takahiro , Otsuka Fumio
Published: October 2021

Roles of Clock genes and the bone morphogenetic protein (BMP) system in the regulation of gonadotropin secretion by gonadotropin-releasing hormone (GnRH) were investigated using mouse gonadotropin LβT2 cells. It was found that luteinizing hormone (LH)β mRNA expression level in LβT2 cells changed gradually over time, with LHβ expression being suppressed in the early phase up to 12 h and then elevated in the late phase 24 h after GnRH stimulation. In addition, the mRNA expression levels of Clock genes, including Bmal1, Clock, Per2, and Cry1, also showed temporal changes mimicking the pattern of LHβ expression in the presence and absence of GnRH. Notably, the expression levels of Bmal1 and Clock showed strong positive correlations with LHβ mRNA expression levels. Moreover, a functional link of the ERK signaling of mitogen-activated protein kinases (MAPKs) in the suppression of LHβ mRNA expression, as well as Bmal1 and Clock mRNA expression by GnRH at the early phase, was revealed. Inhibition of Bmal1 and Clock expression using siRNA was involved in the reduction in LHβ mRNA levels in the late phase 24 h after GnRH stimulation. Furthermore, in the presence of BMP-6 and -7, late-phase Bmal1 and LHβ mRNA expression after GnRH stimulation was significantly attenuated. Collectively, the results indicated that LH expression in gonadotrope cells exhibits Bmal1/Clock-dependent fluctuations under the influence of GnRH and that the fluctuations are regulated by ERK and BMPs in the early and late stages, respectively, in a phase-dependent manner after GnRH stimulation.
Application of Mesenchymal Stem Cells in Targeted Delivery to the Brain: Potential and Challenges of the Extracellular Vesicle-Based Approach for Brain Tumor Treatment
Authors: Do Anh Duy , Kurniawati Ida , Hsieh Chia-Ling , Wong Tai-Tong , Lin Yu-Ling , Sung Shian-Ying
Published: October 2021

Treating brain tumors presents enormous challenges, and there are still poor prognoses in both adults and children. Application of novel targets and potential drugs is hindered by the function of the blood-brain barrier, which significantly restricts therapeutic access to the tumor. Mesenchymal stem cells (MSCs) can cross biological barriers, migrate to sites of injuries to exert many healing effects, and be engineered to incorporate different types of cargo, making them an ideal vehicle to transport anti-tumor agents to the central nervous system. Extracellular vesicles (EVs) produced by MSCs (MSC-EVs) have valuable innate properties from parent cells, and are being exploited as cell-free treatments for many neurological diseases. Compared to using MSCs, targeted delivery via MSC-EVs has a better pharmacokinetic profile, yet avoids many critical issues of cell-based systems. As the field of MSC therapeutic applications is quickly expanding, this article aims to give an overall picture for one direction of EV-based targeting of brain tumors, with updates on available techniques, outcomes of experimental models, and critical challenges of this concept.
A Tendon-Specific Double Reporter Transgenic Mouse Enables Tracking Cell Lineage and Functions Alteration In Vitro and In Vivo
Authors: Chen Rui , Zhou Xunlei , Skutella Thomas
Published: October 2021

We generated and characterized a transgenic mouse line with the tendon-specific expression of a double fluorescent reporter system, which will fulfill an unmet need for animal models to support real-time monitoring cell behaviors during tendon development, growth, and repair in vitro and in vivo. The mScarlet red fluorescent protein is driven by the Scleraxis (Scx) promoter to report the cell lineage alteration. The blue fluorescent protein reporter is expressed under the control of the 3.6kb Collagen Type I Alpha 1 Chain (Col1a1) proximal promoter. In this promoter, the existence of two promoter regions named tendon-specific cis-acting elements (TSE1, TSE2) ensure the specific expression of blue fluorescent protein (BFP) in tendon tissue. Collagen I is a crucial marker for tendon regeneration that is a major component of healthy tendons. Thus, the alteration of function during tendon repair can be estimated by BFP expression. After mechanical stimulation, the expression of mScarlet and BFP increased in adipose-derived mesenchymal stem cells (ADMSCs) from our transgenic mouse line, and there was a rising trend on tendon key markers. These results suggest that our tendon-specific double reporter system is a novel model used to study cell re-differentiation and extracellular matrix alteration in vitro and in vivo.
Head-to-Head Comparison of Fibroblast Activation Protein Inhibitors (FAPI) Radiotracers versus [18F]F-FDG in Oncology: A Systematic Review
Authors: Treglia Giorgio , Muoio Barbara , Roustaei Hessamoddin , Kiamanesh Zahra , Aryana Kamran , Sadeghi Ramin
Published: October 2021

Several recent studies comparing radiolabeled fibroblast activation protein inhibitors (FAPI) and fluorine-18 fluorodeoxyglucose ([18F]F-FDG) as positron emission tomography (PET) radiotracers in oncology have been published. The aim of this systematic review is to perform an updated evidence-based summary about the comparison of these PET radiotracers in oncology to better address further research in this setting. Studies or subsets of studies comparing radiolabeled FAPI and [18F]F-FDG as PET radiotracers in oncology were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until August 2021. Literature data about the comparison of [18F]F-FDG and radiolabeled FAPI are rapidly increasing. Overall, taking into account radiotracer uptake and tumor-to-background uptake ratio, compared to [18F]F-FDG PET, an equal or higher detection of primary tumors and/or metastatic lesions was usually demonstrated by using radiolabeled FAPI PET. In particular, the cancer entities with better detection rate of tumor lesions by using radiolabeled FAPI PET, compared to [18F]F-FDG PET, were gastrointestinal tumors, liver tumors, breast cancer and nasopharyngeal carcinoma. Further comparison studies are needed to better evaluate the best field of application of radiolabeled FAPI PET.
LncRNAs in the Regulation of Genes and Signaling Pathways through miRNA-Mediated and Other Mechanisms in Clear Cell Renal Cell Carcinoma
Authors: Braga Eleonora A. , Fridman Marina V. , Filippova Elena A. , Loginov Vitaly I. , Pronina Irina V. , Burdennyy Alexey M. , Karpukhin Alexander V. , Dmitriev Alexey A. , Morozov Sergey G.
Published: October 2021

The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer—clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis. For the most studied oncogenic lncRNAs, such as HOTAIR, MALAT1, and TUG1, several regulatory axes were identified in ccRCC, demonstrating a number of sites for various miRNAs. Interestingly, the LINC00973/miR-7109/Siglec-15 axis represents a novel agent that can suppress the immune response in patients with ccRCC, serving as a valuable target in addition to the PD1/PD-L1 pathway. Other mechanisms of action of lncRNAs in ccRCC, involving direct binding with proteins, mRNAs, and genes/DNA, are also considered. Our review briefly highlights methods by which various mechanisms of action of lncRNAs were verified. We pay special attention to protein targets and signaling pathways with which lncRNAs are associated in ccRCC. Thus, these new data on the different mechanisms of lncRNA functioning provide a novel basis for understanding the pathogenesis of ccRCC and the identification of new prognostic markers and targets for therapy.
Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease
Authors: Kourtidou Christodoula , Stangou Maria , Marinaki Smaragdi , Tziomalos Konstantinos
Published: October 2021

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.
Missing Data Imputation in Internet of Things Gateways
Authors: França Cinthya M. , Couto Rodrigo S. , Velloso Pedro B.
Published: October 2021

In an Internet of Things (IoT) environment, sensors collect and send data to application servers through IoT gateways. However, these data may be missing values due to networking problems or sensor malfunction, which reduces applications’ reliability. This work proposes a mechanism to predict and impute missing data in IoT gateways to achieve greater autonomy at the network edge. These gateways typically have limited computing resources. Therefore, the missing data imputation methods must be simple and provide good results. Thus, this work presents two regression models based on neural networks to impute missing data in IoT gateways. In addition to the prediction quality, we analyzed both the execution time and the amount of memory used. We validated our models using six years of weather data from Rio de Janeiro, varying the missing data percentages. The results show that the neural network regression models perform better than the other imputation methods analyzed, based on the averages and repetition of previous values, for all missing data percentages. In addition, the neural network models present a short execution time and need less than 140 KiB of memory, which allows them to run on IoT gateways.
Hemp Pest Spectrum and Potential Relationship between Helicoverpa zea Infestation and Hemp Production in the United States in the Face of Climate Change
Authors: Ajayi Olufemi S. , Samuel-Foo Michelle
Published: October 2021

There has been a resurgence in the cultivation of industrial hemp, Cannabis sativa L., in the United States since its recent legalization. This may facilitate increased populations of arthropods associated with the plant. Hemp pests target highly marketable parts of the plant, such as flowers, stalks, and leaves, which ultimately results in a decline in the quality. Industrial hemp can be used for several purposes including production of fiber, grain, and cannabidiol. Thus, proper management of pests is essential to achieve a substantial yield of hemp in the face of climate change. In this review, we provide updates on various arthropods associated with industrial hemp in the United States and examine the potential impact of climate change on corn earworm (CEW) Helicoverpa zea Boddie, a major hemp pest. For example, temperature and photoperiod affect the development and diapause process in CEW. Additionally, drought can lead to a reduction in hemp growth. Host plant diversity of CEW may prevent populations of the pest from reaching outbreak levels. It is suggested that hemp varieties resistant to drought, high soil salinity, cold, heat, humidity, and common pests and diseases should be selected. Ongoing research on effective management of CEW in hemp is critical.
Immature Insect Assemblages from the Early Cretaceous (Purbeck/Wealden) of Southern England
Authors: Coram Robert A. , Jarzembowski Edmund A.
Published: October 2021

The record of immature insects from the non-marine Purbeck and Wealden groups (Lower Cretaceous) of southern England is reviewed and expanded. Fossils of adult terrestrial insects are locally common, but terrestrial immature remains are restricted to transported hemipterans, most of which are sessile nymphs or puparia resembling those of extant whiteflies (Aleyrodidae). Remains of immature aquatic insects are more diverse and comprise the extant orders Plecoptera, Ephemeroptera, Odonata, Trichoptera, Hemiptera and Diptera. The Trichoptera are represented by larval cases constructed from a variety of materials corresponding to several ichnogenera. The Wealden immature insects were preserved in predominantly freshwater fluvial settings, whereas the Purbeck ones occur in lagoonal palaeoenvironments, ranging in salinity from brackish to hypersaline. The composition of aquatic immature insect faunas in the latter offers potential for palaeosalinity analysis, although there are complicating factors relating to habitat stability. Uncommon trace fossils such as beetle borings in wood provide evidence of immature insects not represented by body fossils.
Combined Use of Electrocardiography and Ultrasound to Detect Cardiac and Pulmonary Involvement after Recovery from COVID-19 Pneumonia: A Case Series
Authors: Marazzato Jacopo , De Ponti Roberto , Verdecchia Paolo , Masnaghetti Sergio , Visca Dina , Spanevello Antonio , Trapasso Monica , Zappa Martina , Mancinelli Antonella , Angeli Fabio
Published: October 2021

Background: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. Methods: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). Results: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. Conclusions: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.
Diosmetin Induces Modulation of Igf-1 and Il-6 Levels to Alter Rictor-Akt-PKCα Cascade in Inhibition of Prostate Cancer
Authors: Pakradooni Rebecca , Shukla Nishka , Gupta Kalpana , Kumar Jatinder , Isali Ilaha , Khalifa Ahmed O. , Shukla Sanjeev
Published: October 2021

Growth signals, which typically originate from the surrounding microenvironment, are important for cells. However, when stimulation by growth factors becomes excessive and exceeds their threshold limit, deleterious effects may ensue. In patients with cancer, maintenance of tumors depends, at least in part, on growth factor stimulation, which can also facilitate cancer progression into advanced stages. This is particularly important when the tumor grows beyond its tissue boundaries or when it invades and colonizes other tissues. These aforementioned malignant events are known to be partly supported by elevated cytokine levels. Among the currently known growth signals, insulin-like growth factor (IGF)-1 and IL-6 have been previously studied for their roles in prostate cancer. Both IGF-1 and IL-6 have been reported to activate the RAPTOR independent companion of MTOR complex 2 (Rictor)/AKT/protein kinase C α (PKCα) signaling pathway as one of their downstream mechanisms. At present, research efforts are mainly focused on the exploration of agents that alter growth factor (such as IGF-1) and cytokine (such as IL-6) signaling for their potential application as therapeutic agents, as both of these have been reported to modulate disease outcome. In the present study, IGF-1 and IL-6 served distinct roles in the androgen responsive LNCaP cell line and in the androgen refractory PC-3 cell line in a dose- and time-dependent manner. Increased phosphorylation of Rictor at the Thr-1135 residue, AKT at the Ser-473 residue and PKCα at the Ser-657 residue were observed after treatment with IGF-1 and IL-6. Subsequently, it was found that diosmetin, a natural plant aglycone, had the potential to modulate the downstream signaling cascade of Rictor/AKT/PKCα to inhibit the progression of prostate cancer. Treatment of LNCaP and PC-3 cells with diosmetin inhibited the phosphorylation of Rictor (Thr-1135), AKT (Ser-473) and PKCα (Ser-657) in a dose-dependent manner. Furthermore, the Bax/Bcl-2 expression ratio was increased in response to diosmetin treatment, which would result in increased apoptosis. Based on these observations, diosmetin may represent a novel therapeutic target for prostate cancer.
Colchicine Improves Clinical Outcomes and Quality of Life in Hidradenitis Suppurativa Patients: A Retrospective Study
Authors: Liakou Aikaterini I. , Kontochristopoulos Georgios , Agiasofitou Efthymia , Tsantes Andreas G. , Papadakis Marios , Marnelakis Ioannis , Tsante Konstantina A. , Kapsiocha Anastasia , Katoulis Alexandros , Gregoriou Stamatios , Rigopoulos Dimitris
Published: October 2021

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the follicular epithelium. The aim of the study was to investigate the effectiveness of colchicine on the clinical outcomes of HS patients, and to evaluate wither colchicine as monotherapy or in combination with doxycycline would provide better outcomes. Methods: A retrospective study was conducted including 44 patients with established HS, divided into three groups. The first group (n = 15 patients) received colchicine as monotherapy, the second group (n = 14 patients) received colchicine and doxycycline 100 mg/d, while the third group (n = 15 patients) received colchicine and doxycycline 40 mg/d. Disease severity during treatment was assessed at baseline and follow-up, using the Hurley Scoring System and the International Hidradenitis Suppurativa Severity Score System (IHS4). All patients were also asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. These scores were compared among the study groups. Results: The DLQI and IHS4 scores significantly improved after treatment with colchicine (p < 0.001) in all groups. All colchicine regimes, including the single colchicine regime, colchicine plus doxycycline 100 mg regime, and colchicine plus doxycycline 40 mg regime, resulted in significant improvements in the DLQI and IHS4 scores (p < 0.001). Clinical improvement based on DLQI and IHS4 scores was similar in all groups. None of the patients had to discontinue the treatment due to adverse events. Discussion: In conclusion, our findings suggest that colchicine may improve clinical severity and quality of life in HS patients, either as monotherapy or in combination with doxycycline, both at antimicrobial (100 mg) and sub-antimicrobial (40 mg) doses.
Coexisting and Second Primary Cancers in Patients with Uveal Melanoma: A 10-Year Nationwide Database Analysis
Authors: Kim Yong Joon , Lee Myeongjee , Kim Eun Hwa , Jung Inkyung , Lee Christopher Seungkyu
Published: October 2021

Uveal melanoma is the most common intraocular tumor in adults. Metastatic disease occurs in about 30% of patients, for which there is currently no effective treatment. More than half of patients are long-term survivors, and it is well established that cancer survivors are prone to developing second primary cancers. In this study, we analyzed 10 years’ worth of data from the nationwide database to determine the rates of coexisting malignancies and second primary cancers associated with uveal melanoma. The mean annual incidence of uveal melanoma was 1.1 per million. Approximately 43% of patients had coexisting cancers. The most common coexisting cancer was lung cancer (10%) followed by liver cancer (6%) and non-Hodgkin lymphoma (6%). In patients whose first cancer in their lifetime was uveal melanoma, the 10-year cumulative incidence of second primary cancers was 22% (95% confidence interval, 9–31%). The age- and sex-adjusted standard incidence rates was 3.61 (95% confidence interval, 2.61–4.86). The most common second primary cancers were lung cancer and hepatocellular carcinoma, followed by prostate, thyroid, pancreatic, and ovarian cancers. Age was the only factor associated with second primary cancer development. Our findings will be helpful in providing counseling for cancer screening in uveal melanoma patients.
Machine Learning Prediction Model for Inflammatory Bowel Disease Based on Laboratory Markers. Working Model in a Discovery Cohort Study
Authors: Kraszewski Sebastian , Szczurek Witold , Szymczak Julia , Reguła Monika , Neubauer Katarzyna
Published: October 2021

Inflammatory bowel disease (IBD) is a chronic, incurable disease involving the gastrointestinal tract. It is characterized by complex, unclear pathogenesis, increased prevalence worldwide, and a wide spectrum of extraintestinal manifestations and comorbidities. Recognition of IBD remains challenging and delays in disease diagnosis still poses a significant clinical problem as it negatively impacts disease outcome. The main diagnostic tool in IBD continues to be invasive endoscopy. We aimed to create an IBD machine learning prediction model based on routinely performed blood, urine, and fecal tests. Based on historical patients’ data (702 medical records: 319 records from 180 patients with ulcerative colitis (UC) and 383 records from 192 patients with Crohn’s disease (CD)), and using a few simple machine learning classificators, we optimized necessary hyperparameters in order to get reliable few-features prediction models separately for CD and UC. Most robust classificators belonging to the random forest family obtained 97% and 91% mean average precision for CD and UC, respectively. For comparison, the commonly used one-parameter approach based on the C-reactive protein (CRP) level demonstrated only 81% and 61% average precision for CD and UC, respectively. Results of our study suggest that machine learning prediction models based on basic blood, urine, and fecal markers may with high accuracy support the diagnosis of IBD. However, the test requires validation in a prospective cohort.
Effects of COVID-19 Lockdown on Weight, Body Composition, and Behavior of Children, Adolescents, and Young Adults with Prader–Willi Syndrome
Authors: Mohr Andrea Karoline , Laemmer Constanze , Schulte Sandra , Gohlke Bettina
Published: October 2021

To reduce transmission of the coronavirus disease 2019 (COVID-19), many countries implemented lockdowns, causing the closure of childcare services. This study was designed to evaluate the impact of the COVID-19 lockdown in March–April 2020 on children, adolescents, and young adults with Prader–Willi syndrome (PWS) living in Germany. We recruited 180 participants with a genetically confirmed PWS. All families completed a questionnaire, and participants underwent a post-lockdown assessment; the last examination before the lockdown was determined as the pre-lockdown assessment. We used bivariate analyses to compare pre- and post-lockdown outcomes. Weight standard deviation scores (SDSPWS) and body mass index (BMI)-SDSPWS remained stable or even decreased in some age groups. A statistically significant gain in lean body mass (LBM) was found in all groups <18 years of age. We observed an increase in IGF-I and IGFBP-3 concentrations without a significant change in growth hormone (GH) dosage. Most families (95.4%) reported set mealtimes and implementation of structured activities (72.2%) during the lockdown period. We therefore suggest that the favorable development of weight/BMI and LBM was caused by an interplay of a suspected enhanced GH administration and continuous parental commitment. However, more intense behavioral problems were observed in 45.7%, which persisted post-lockdown in 33.7%.
The Role of Uric Acid in Acute and Chronic Coronary Syndromes
Authors: Maloberti Alessandro , Biolcati Marco , Ruzzenenti Giacomo , Giani Valentina , Leidi Filippo , Monticelli Massimiliano , Algeri Michela , Scarpellini Sara , Nava Stefano , Soriano Francesco , Oreglia Jacopo , Sacco Alice , Morici Nuccia , Oliva Fabrizio , Piani Federica , Borghi Claudio , Giannattasio Cristina
Published: October 2021

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.
Flexible Magnifying Endoscopy with Narrow Band Imaging for Diagnosing Uterine Cervical Neoplasms: A Multicenter Prospective Study
Authors: Kobara Hideki , Uchita Kunihisa , Uedo Noriya , Kunikata Jun , Yorita Kenji , Tada Naoya , Nishiyama Noriko , Shigehisa Yuriko , Kuroiwa Chihiro , Matsuura Noriko , Takahashi Yohei , Kai Yuka , Hanaoka Uiko , Kiyohara Yumiko , Kamiura Shoji , Kanenishi Kenji , Masaki Tsutomu , Hirano Koki
Published: October 2021

We aimed to investigate the diagnostic ability of magnifying endoscopy with narrow band imaging (ME-NBI) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). This was a multicenter prospective study. Eligible patients had positive Pap smear results or follow-up high-grade cytology or CIN3 diagnosed in referring hospitals. Patients underwent ME-NBI by a gastrointestinal endoscopist, followed by colposcopy by a gynecologist. One lesion with the worst finding was considered the main lesion. Punch biopsies were collected from all indicated areas and one normal area. The reference standard was the highest histological grade among all biopsy specimens. The primary endpoint was the detection rate of patients with CIN2+ in the main lesion. The secondary endpoints were diagnostic ability for CIN2+ lesions and patients’ acceptability. We enrolled 88 patients. The detection rate of ME-NBI for patients with CIN2+ was 79% (95% CI: 66–88%; p = 1.000), which was comparable to that of colposcopy (79%; p = 1.000). For diagnosing CIN2+ lesions, ME-NBI showed a better sensitivity than colposcopy (87% vs. 74%, respectively; p = 0.302) but a lower specificity (50% vs. 68%, respectively; p = 0.210). Patients graded ME-NBI as having significantly less discomfort and involving less embarrassment than colposcopy. ME-NBI did not show a higher detection ability than colposcopy for patients with CIN2+, whereas it did show a better patient acceptability.
Comparison of Cortisol, Androstenedione and Metanephrines to Assess Selectivity and Lateralization of Adrenal Vein Sampling in Primary Aldosteronism
Authors: Ceolotto Giulio , Antonelli Giorgia , Caroccia Brasilina , Battistel Michele , Barbiero Giulio , Plebani Mario , Rossi Gian Paolo
Published: October 2021

Success of adrenal vein sampling (AVS) is verified by the selectivity index (SI), i.e., by a step-up of cortisol levels between the adrenal vein and the infrarenal inferior vena cava samples, beyond a given cut-off. We tested the hypothesis that androstenedione, metanephrine, and normetanephrine, which have higher gradients than cortisol, could increase the rate of AVS studies judged to be bilaterally successful and usable for the clinical decision making. We prospectively compared within-patient, head-to-head, the selectivity index of androstenedione (SIA), metanephrine (SIM), and normetanephrine (SINM), and cortisol (SIC) in consecutive hypertensive patients with primary aldosteronism submitted to AVS. Main outcome measures were rate of bilateral success, SI values, and identification of unilateral PA. We recruited 136 patients (55 + 10 years, 35% women). Compared to the SIC, the SIA values were 3.5-fold higher bilaterally, and the SIM values were 7-fold and 4.4-fold higher on the right and the left side, respectively. With the SIA and the SIM the rate of bilaterally successful AVS increased by 14% and 15%, respectively without impairing the identification of unilateral PA. We concluded that androstenedione and metanephrine outperformed cortisol for ascertaining AVS success, thus increasing the AVS studies useable for the clinical decision making.
Different Inspiratory Flow Waveform during Volume-Controlled Ventilation in ARDS Patients
Authors: Chiumello Davide , Meli Andrea , Pozzi Tommaso , Lucenteforte Manuela , Simili Paolo , Sterchele Elda , Coppola Silvia
Published: October 2021

The most used types of mechanical ventilation are volume- and pressure-controlled ventilation, respectively characterized by a square and a decelerating flow waveform. Nowadays, the clinical utility of different inspiratory flow waveforms remains unclear. The aim of this study was to assess the effects of four different inspiratory flow waveforms in ARDS patients. Twenty-eight ARDS patients (PaO2/FiO2 182 ± 40 and PEEP 11.3 ± 2.5 cmH2O) were ventilated in volume-controlled ventilation with four inspiratory flow waveforms: square (SQ), decelerating (DE), sinusoidal (SIN), and trunk descending (TDE). After 30 min in each condition, partitioned respiratory mechanics and gas exchange were collected. The inspiratory peak flow was higher in the DE waveform compared to the other three waveforms, and in SIN compared to the SQ and TDE waveforms, respectively. The mean inspiratory flow was higher in the DE and SIN waveforms compared with TDE and SQ. The inspiratory peak pressure was higher in the SIN and SQ compared to the TDE waveform. Partitioned elastance was similar in the four groups; mechanical power was lower in the TDE waveform, while PaCO2 in DE. No major effect on oxygenation was found. The explored flow waveforms did not provide relevant changes in oxygenation and respiratory mechanics.
Laparoscopic Heated Intraperitoneal Chemotherapy in the Treatment of Carcinomatosis of Gastric Adenocarcinoma Origin
Authors: White Michael G. , Badgwell Brian D.
Published: October 2021

The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible.
Using Graphene Nanoplatelets Nanofluid in a Closed-Loop Evacuated Tube Solar Collector—Energy and Exergy Analysis
Authors: Iranmanesh Soudeh , Silakhori Mahyar , Naghavi Mohammad S. , Ang Bee C. , Ong Hwai C. , Esmaeilzadeh Alireza
Published: October 2021

Recently, nanofluid application as a heat transfer fluid for a closed-loop solar heat collector is receiving great attention among the scientific community due to better performance. The performance of solar systems can be assessed effectively with the exergy method. The present study deals with the thermodynamic performance of the second law analysis using graphene nanoplatelets nanofluids. Second law analysis is the main tool for explaining the exergy output of thermodynamic and energy systems. The performance of the closed-loop system in terms of energy and exergy was determined by analyzing the outcome of field tests in tropical weather conditions. Moreover, three parameters of entropy generation, pumping power and Bejan number were also determined. The flowrates of 0.5, 1 and 1.5 L/min and GNP mass percentage of 0.025, 0.5, 0.075 and 0.1 wt% were used for these tests. The results showed that in a flow rate of 1.5 L/min and a concentration of 0.1 wt%, exergy and thermal efficiencies were increased to about 85.5 and 90.7%, respectively. It also found that entropy generation reduced when increasing the nanofluid concentration. The Bejan number surges up when increasing the concentration, while this number decreases with the enhancement of the volumetric flow rate. The pumping power of the nanofluid-operated system for a 0.1 wt% particle concentration at 0.5 L/min indicated 5.8% more than when pure water was used as the heat transfer fluid. Finally, this investigation reveals the perfect conditions that operate closest to the reversible limit and helps the system make the best improvement.
Influence of Heat Treatment on the Corrosion Behaviour of Aluminium Silver Nano Particle/Calcium Carbonate Composite
Authors: Ikumapayi Omolayo Michael , Akinlabi Esther T. , Abegunde Olayinka Oluwatosin , Ken-Ezihuo Precious , Benjamin Henry A. , Afolalu Sunday Adeniran , Akinlabi Stephen A.
Published: October 2021

Corrosion is one of the leading sources of material failure and deterioration in society. Scholars have proposed different techniques to mitigate corrosion. This research study explores and validates one of these techniques. An Aluminium metal matrix (AMC) was produced using the stir casting method with various weight percentages of AgNp and CaCO3 reinforcements. Heat treatment was performed on the samples to enhance the metallurgical and corrosion properties of the materials. The corrosion rate of the AMC samples was tested in different corrosive media (neutral and acidic) with different concentrations using the weight loss analysis technique for several days. It was observed that the corrosion rate of the AMC relies on the nature of the electrolyte and the percentage concentration of this electrolyte. The heat treatment improves the corrosion resistance of the AMC samples. In addition, an increase in the % weight composition of the reinforcement (AgNp + CaCO3) results in a reduction in the corrosion rate of the AMC in both corrosive media. The optimal %weight composition was found to be 4% for the hybrid reinforcement of AgNp + CaCO3 and 6% for the CaCO3 reinforcement in both the untreated and heat-treated samples.
Mitral Valve Segmentation Using Robust Nonnegative Matrix Factorization
Authors: Dröge Hannah , Yuan Baichuan , Llerena Rafael , Yen Jesse T. , Moeller Michael , Bertozzi Andrea L.
Published: October 2021

Analyzing and understanding the movement of the mitral valve is of vital importance in cardiology, as the treatment and prevention of several serious heart diseases depend on it. Unfortunately, large amounts of noise as well as a highly varying image quality make the automatic tracking and segmentation of the mitral valve in two-dimensional echocardiographic videos challenging. In this paper, we present a fully automatic and unsupervised method for segmentation of the mitral valve in two-dimensional echocardiographic videos, independently of the echocardiographic view. We propose a bias-free variant of the robust non-negative matrix factorization (RNMF) along with a window-based localization approach, that is able to identify the mitral valve in several challenging situations. We improve the average f1-score on our dataset of 10 echocardiographic videos by 0.18 to a f1-score of 0.56.