bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Effects of Resveratrol and Its Derivatives on the Radiation Response of MCF-7 Breast Cancer Cells
Authors: Komorowska Dominika , Gajewska Agnieszka , Hikisz Paweł , Bartosz Grzegorz , Rodacka Aleksandra
Published: September 2021

Radiotherapy is among the most important methods for breast cancer treatment. However, this method’s effectiveness is limited by radioresistance. The aim of this study was to investigate whether the stilbene derivatives piceid, resveratrol, and piceatannol have a radiosensitising effect on breast cancer cells (MCF-7). The conducted research enabled us to determine which of the tested compounds has the greatest potential in sensitising cells to ionising radiation (IR). Among the stilbene derivatives, resveratrol significantly increased the effect of IR. Resveratrol and IR used in combination had a higher cytotoxic effect on MCF-7 cells than using piceatannol, piceid, or radiation alone. This was due to a significant decrease in the activity of antioxidant enzymes, which resulted in the accumulation of formed reactive oxygen species (ROS). The effect of resveratrol and IR enhanced the expression of apoptotic genes, such as Bax, p53, and caspase 8, leading to apoptosis.
Antimicrobial Face Shield: Next Generation of Facial Protective Equipment against SARS-CoV-2 and Multidrug-Resistant Bacteria
Authors: Tuñón-Molina Alberto , Martí Miguel , Muramoto Yukiko , Noda Takeshi , Takayama Kazuo , Serrano-Aroca Ángel
Published: September 2021

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can become infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.
Does the Rainbow Trout Ovarian Fluid Promote the Spermatozoon on Its Way to the Egg?
Authors: Kholodnyy Vitaliy , Dzyuba Borys , Rodina Marek , Bloomfield-Gadêlha Hermes , Yoshida Manabu , Cosson Jacky , Boryshpolets Sergii
Published: September 2021

The fertilization of freshwater fish occurs in an environment that may negatively affect the gametes; therefore, the specific mechanisms triggering the encounters of gametes would be highly expedient. The egg and ovarian fluid are likely the major sources of these triggers, which we confirmed here for rainbow trout (Oncorhynchus mykiss). The ovarian fluid affected significantly spermatozoa performance: it supported high velocity for a longer period and changed the motility pattern from tumbling in water to straightforward moving in the ovarian fluid. Rainbow trout ovarian fluid induced a trapping chemotaxis-like effect on activated male gametes, and this effect depended on the properties of the activating medium. The interaction of the spermatozoa with the attracting agents was accompanied by the “turn-and-run” behavior involving asymmetric flagellar beating and Ca2+ concentration bursts in the bent flagellum segment, which are characteristic of the chemotactic response. Ovarian fluid created the optimal environment for rainbow trout spermatozoa performance, and the individual peculiarities of the egg (ovarian fluid)–sperm interaction reflect the specific features of the spawning process in this species.
Interleukin-21 in Viral Infections
Authors: Asao Hironobu
Published: September 2021

Interleukin (IL)-21 is a cytokine that affects the differentiation and function of lymphoid and myeloid cells and regulates both innate and adaptive immune responses. In addition to regulating the immune response to tumor and viral infections, IL-21 also has a profound effect on the development of autoimmune and inflammatory diseases. IL-21 is produced mainly from CD4+ T cells—in particular, follicular helper T (Tfh) cells—which have a great influence on the regulation of antibody production. It is also an important cytokine for the activation of CD8+ T cells, and its role in recovering the function of CD8+ T cells exhausted by chronic microbial infections and cancer has been clarified. Thus, IL-21 plays an extremely important role in viral infections, especially chronic viral infections. In this review, I will introduce the findings to date on how IL-21 is involved in some typical viral infections and the potential of treating viral diseases with IL-21.
αV Integrin Expression and Localization in Male Germ Cells
Authors: Palenikova Veronika , Frolikova Michaela , Valaskova Eliska , Postlerova Pavla , Komrskova Katerina
Published: September 2021

Integrins are transmembrane receptors that facilitate cell adhesion and cell–extracellular matrix communication. They are involved in the sperm maturation including capacitation and gamete interaction, resulting in successful fertilization. αV integrin belongs to the integrin glycoprotein superfamily, and it is indispensable for physiological spermiogenesis and testosterone production. We targeted the gene and protein expression of the αV integrin subunit and described its membrane localization in sperm. Firstly, in mouse, we traced αV integrin gene expression during spermatogenesis in testicular fraction separated by elutriation, and we detected gene activity in spermatogonia, spermatocytes, and round spermatids. Secondly, we specified αV integrin membrane localization in acrosome-intact and acrosome-reacted sperm and compared its pattern between mouse, pig, and human. Using immunodetection and structured illumination microscopy (SIM), the αV integrin localization was confined to the plasma membrane covering the acrosomal cap area and also to the inner acrosomal membrane of acrosome-intact sperm of all selected species. During the acrosome reaction, which was induced on capacitated sperm, the αV integrin relocated and was detected over the whole sperm head. Knowledge of the integrin pattern in mature sperm prepares the ground for further investigation into the pathologies and related fertility issues in human medicine and veterinary science.
Fibroblast Growth Factor Inhibitors for Treating Locally Advanced/Metastatic Bladder Urothelial Carcinomas via Dual Targeting of Tumor-Specific Oncogenic Signaling and the Tumor Immune Microenvironment
Authors: Lee Hye Won , Seo Ho Kyung
Published: September 2021

Locally advanced or metastatic urothelial bladder cancer (a/m UBC) is currently treated using platinum-based combination chemotherapy. Immune checkpoint inhibitors (ICIs) are the preferred second-line treatment options for cisplatin-eligible a/m UBC patients and as first-line options in cisplatin-ineligible settings. However, the response rates for ICI monotherapy are modest (~20%), which necessitates the exploration of alternative strategies. Dysregulated activation of fibroblast growth factor receptor (FGFR) signaling enhances tumor proliferation, survival, invasion, angiogenesis, and immune evasion. The recent U.S. Food and Drug Administration approval of erdafitinib and the emergence of other potent and selective FGFR inhibitors (FGFRis) have shifted the treatment paradigm for patients with a/m UBC harboring actionable FGFR2 or FGFR3 genomic alterations, who often have a minimal-to-modest response to ICIs. FGFRi–ICI combinations are therefore worth exploring, and their preliminary response rates and safety profiles are promising. In the present review, we summarize the impact of altered FGFR signaling on a/m UBC tumor evolution, the clinical development of FGFRis, the rationale for FGFRi–ICI combinations, current trials, and prospective research directions.
Nitrate Regulates Maize Root Transcriptome through Nitric Oxide Dependent and Independent Mechanisms
Authors: Ravazzolo Laura , Trevisan Sara , Iori Silvia , Forestan Cristian , Malagoli Mario , Quaggiotti Silvia
Published: September 2021

Maize root responds to nitrate by modulating its development through the coordinated action of many interacting players. Nitric oxide is produced in primary root early after the nitrate provision, thus inducing root elongation. In this study, RNA sequencing was applied to discover the main molecular signatures distinguishing the response of maize root to nitrate according to their dependency on, or independency of, nitric oxide, thus discriminating the signaling pathways regulated by nitrate through nitric oxide from those regulated by nitrate itself of by further downstream factors. A set of subsequent detailed functional annotation tools (Gene Ontology enrichment, MapMan, KEGG reconstruction pathway, transcription factors detection) were used to gain further information and the lateral root density was measured both in the presence of nitrate and in the presence of nitrate plus cPTIO, a specific NO scavenger, and compared to that observed for N-depleted roots. Our results led us to identify six clusters of transcripts according to their responsiveness to nitric oxide and to their regulation by nitrate provision. In general, shared and specific features for the six clusters were identified, allowing us to determine the overall root response to nitrate according to its dependency on nitric oxide.
Title Current Status of the Search for Biomarkers for Optimal Therapeutic Drug Selection for Patients with Rheumatoid Arthritis
Authors: Tsuchiya Haruka , Fujio Keishi
Published: September 2021

Rheumatoid arthritis (RA) is an autoimmune disease characterized by destructive synovitis. It is significantly associated with disability, impaired quality of life, and premature mortality. Recently, the development of biological agents (including tumor necrosis factor-α and interleukin-6 receptor inhibitors) and Janus kinase inhibitors have advanced the treatment of RA; however, it is still difficult to predict which drug will be effective for each patient. To break away from the current therapeutic approaches that could be described as a “lottery,” there is an urgent need to establish biomarkers that stratify patients in terms of expected therapeutic responsiveness. This review deals with recent progress from multi-faceted analyses of the synovial tissue in RA, which is now bringing new insights into diverse features at both the cellular and molecular levels and their potential links with particular clinical phenotypes.
A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs
Authors: Xie Yuhuai , Wei Yuanyuan
Published: September 2021

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.
Does Coenzyme Q10 Supplementation Improve Human Oocyte Quality?
Authors: Rodríguez-Varela Cristina , Labarta Elena
Published: September 2021

Acquiring oocyte competence requires optimal mitochondrial function and adequate ATP levels. In this context, CoQ10 supplementation may improve human oocyte quality and subsequent reproductive performance given its role in ATP synthesis and mitochondrial protection from ROS oxidative damage. In infertility treatments, CoQ10 therapy can be orally supplied to promote a more favorable environment for oocyte development in vivo or by its addition to culture media in an attempt to improve its quality in vitro. Human clinical studies evaluating the impact of CoQ10 on reproductive performance are summarized in this review, although the available data do not clearly prove its ability to improve human oocyte quality. The main objective is to provide readers with a complete overview of this topic’s current status as well as the keys for potential future research lines that may help to take this therapy to clinical practice. Indeed, further clinical trials are needed to confirm these results along with molecular studies to evaluate the impact of CoQ10 supplementation on oxidative stress status and mitochondrial function in human gametes.
Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers
Authors: Kučuk Nika , Primožič Mateja , Knez Željko , Leitgeb Maja
Published: September 2021

Exosomes are becoming increasingly important therapeutic biomaterials for use in a variety of therapeutic applications due to their unique characteristics, especially due to the ineffectiveness and cytotoxicity of some existing therapies and synthetic therapeutic nanocarriers. They are highly promising as carriers of drugs, genes, and other therapeutic agents that can be incorporated into their interior or onto their surface through various modification techniques to improve their targeting abilities. In addition, they are biocompatible, safe, and stable. The review focuses on different types of exosomes and methods of their preparation, including the incorporation of different kinds of cargo, especially for drug delivery purposes. In particular, their importance and effectiveness as delivery vehicles of various therapeutic agents for a variety of therapeutic applications, including different diseases and disorders such as cancer treatment, cardiovascular and neurodegenerative diseases, are emphasized. Administration routes of exosomes into the body are also included. A novelty in the article is the emphasis on global companies that are already successfully developing and testing such therapeutic biomaterials, with a focus on the most influential ones. Moreover, a comparison of the advantages and disadvantages of the various methods of exosome production is summarized for the first time.
The Copper-microRNA Pathway Is Integrated with Developmental and Environmental Stress Responses in Arabidopsis thaliana
Authors: Perea-García Ana , Andrés-Bordería Amparo , Huijser Peter , Peñarrubia Lola
Published: September 2021

As an essential nutrient, copper (Cu) scarcity causes a decrease in agricultural production. Cu deficiency responses include the induction of several microRNAs, known as Cu-miRNAs, which are responsible for degrading mRNAs from abundant and dispensable cuproproteins to economize copper when scarce. Cu-miRNAs, such as miR398 and miR408 are conserved, as well as the signal transduction pathway to induce them under Cu deficiency. The Arabidopsis thaliana SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) family member SPL7 binds to the cis-regulatory motifs present in the promoter regions of genes expressed under Cu deficiency, including Cu-miRNAs. The expression of several other SPL transcription factor family members is regulated by miR156. This regulatory miR156-SPL module plays a crucial role in developmental phase transitions while integrating internal and external cues. Here, we show that Cu deficiency also affects miR156 expression and that SPL3 overexpressing plants, resistant to miR156 regulation, show a severe decrease in SPL7-mediated Cu deficiency responses. These include the expression of Cu-miRNAs and their targets and is probably due to competition between SPL7 and miR156-regulated SPL3 in binding to cis-regulatory elements in Cu-miRNA promoters. Thus, the conserved SPL7-mediated Cu-miRNA pathway could generally be affected by the miR156-SPL module, thereby underscoring the integration of the Cu-miRNA pathway with developmental and environmental stress responses in Arabidopsis thaliana.
The Influence of the pH and Salinity of Water in Breeding Sites on the Occurrence and Community Composition of Immature Mosquitoes in the Green Belt of the City of São Paulo, Brazil
Authors: Multini Laura Cristina , Oliveira-Christe Rafael , Medeiros-Sousa Antônio Ralph , Evangelista Eduardo , Barrio-Nuevo Karolina Morales , Mucci Luis Filipe , Ceretti-Junior Walter , Camargo Amanda Alves , Wilke André Barretto Bruno , Marrelli Mauro Toledo
Published: September 2021

The physicochemical parameters of water, such as pH, salinity, conductivity, and total dissolved solids, can influence mosquito larval development, survival, and abundance. Therefore, it is important to elucidate how these factors influence mosquito occurrence. We hypothesized that the occurrence and community composition of immature mosquito species are driven not only by the availability of suitable aquatic habitats, but also by the physicochemical factors of these habitats. The primary objective of this study was therefore to investigate the influence of the physicochemical parameters of water in different types of aquatic habitats on the occurrence of mosquito species in two remnants of Atlantic Forest in the city of São Paulo, Brazil. Collections of immature mosquitoes and assessment of the physicochemical characteristics of the water in the collection sites were carried out for twelve months. The variation in species composition and occurrence with the measured physicochemical parameters and the type of breeding site was assessed using constrained ordination methods. The results indicate that there was a statistically significant difference in species composition as a function of the different types of aquatic habitats, and that pH had an influence on species occurrence even when the variance explained by the type of aquatic habitat was removed from the analysis. There was a statistically significant association between mosquito species occurrence and pH and salinity, and the former had a significant influence on the mosquito species collected regardless of the type of aquatic habitat, showing that the pH of the breeding site water is an important factor in driving mosquito population dynamics and species distribution.
Targeting Mitochondria and Metabolism in Acute Kidney Injury
Authors: Li Ying , Hepokoski Mark , Gu Wanjun , Simonson Tatum , Singh Prabhleen
Published: September 2021

Acute kidney injury (AKI) significantly contributes to morbidity and mortality in critically ill patients. AKI is also an independent risk factor for the development and progression of chronic kidney disease. Effective therapeutic strategies for AKI are limited, but emerging evidence indicates a prominent role of mitochondrial dysfunction and altered tubular metabolism in the pathogenesis of AKI. Therefore, a comprehensive, mechanistic understanding of mitochondrial function and renal metabolism in AKI may lead to the development of novel therapies in AKI. In this review, we provide an overview of current state of research on the role of mitochondria and tubular metabolism in AKI from both pre-clinical and clinical studies. We also highlight current therapeutic strategies which target mitochondrial function and metabolic pathways for the treatment of AKI.
The Rapid Atrial Swirl Sign for Ultrasound-Guided Tip Positioning of Retrograde-Tunneled Hemodialysis Catheters: A Cross-Sectional Study from a Single Center
Authors: Korsten Peter , Kuczera Tim , Wallbach Manuel , Tampe Björn
Published: September 2021

Background: Chronic kidney disease (CKD) is a common medical problem in patients worldwide, with an increasing prevalence of patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT). In patients requiring RRT for more than two weeks or those who develop ESKD, tunneled hemodialysis catheter (HDC) insertion is preferred, based on a lower risk for infectious complications. While the efficacy of ultrasound (US)-guided tip positioning in antegrade-tunneled HDCs has previously been shown, its application for the insertion of retrograde-tunneled HDCs has not been described yet. This is especially important, since the retrograde-tunneled technique has several advantages over the antegrade-tunneled HDC insertion technique. Therefore, we here report our first experience of applying the rapid atrial swirl sign (RASS) for US-guided tip positioning of retrograde-tunneled HDCs. Methods: We performed a cross-sectional study to assess the feasibility of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs. We performed a total number of 24 retrograde-tunneled HDC insertions in 23 patients (requiring placement of a HDC for the temporary or permanent treatment of ESKD) admitted to our Department of Nephrology and Rheumatology at the University Medical Center Göttingen, Germany. Results: The overall success rate of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs was 24/24 (100%), with proper tip position in the right atrium in 18/23 (78.3%), or cavoatrial junction in 5/23 (21.7%) when RASS was positive and improper position when RASS was negative in 1/1 (100%), confirmed by portable anterior-posterior chest radiography, with only minor post-procedural bleeding in 2/24 (8.3%). In addition, this insertion technique allows optimal HDC flow, without any observed malfunction. Conclusion: This is the first study to investigate the efficacy of the RASS for US-guided tip positioning of retrograde-tunneled HDCs in patients with ESKD. Application of the RASS for US-guided tip positioning is an accurate and safe procedure for the proper placement of retrograde-tunneled HDCs.
Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial
Authors: Yu Hannah J. , Ehlers Justis P. , Sevgi Duriye Damla , O’Connell Margaret , Reese Jamie L. , Srivastava Sunil K. , Wykoff Charles C.
Published: September 2021

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.
Impact of Palonosetron on Cough Suppression in Females Undergoing Sevoflurane-Remifentanil Anesthesia for Laparoscopic Cholecystectomy: A Randomized Trial
Authors: Gil Ho-Young , Kim Ha-Yeon , Lee Hye-Sun , Kim Na-Young , Kim Ji-Eun
Published: September 2021

Remifentanil has been used to suppress peri-extubation cough. Palonosetron, a 5-HT3 receptor antagonist, is an effective antiemetic, and 5-HT receptors mediate the cough reflex. We assessed the impact of palonosetron on effect-site concentration (Ce) of remifentanil for preventing emergence cough in females. Forty-five female patients undergoing laparoscopic cholecystectomy randomly received 0.075 mg of palonosetron (n = 21) or normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce for 50% (EC50) and for 95% (EC95) of patients were estimated via Dixon’s up-and-down method or isotonic regression. Using Dixon’s method, EC50 in the control group (1.33 ± 0.38 ng/mL) was comparable to that of the palonosetron group (1.42 ± 0.75 ng/mL) (p = 0.813). Using isotonic regression, EC50 (83% CIs) and EC95 (95% CIs) did not reveal significant differences between the control and the palonosetron groups (1.17 (0.86–1.43) and 1.90 (1.45–1.96) ng/mL and 0.88 (0.78–1.23) and 2.43 (1.94–2.47) ng/mL, respectively). No difference was found in the remifentanil Ce to suppress emergence cough in the palonosetron group compared with the control group. It may indicate no effect of palonosetron on antitussive activity of remifentanil.
An Unnatural Amino Acid-Regulated Growth Controller Based on Informational Disturbance
Authors: Kato Yusuke
Published: September 2021

We designed a novel growth controller regulated by feeding of an unnatural amino acid, Nε-benzyloxycarbonyl-l-lysine (ZK), using a specific incorporation system at a sense codon. This system is constructed by a pair of modified pyrrolisyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl). Although ZK is non-toxic for normal organisms, the growth of Escherichia coli carrying the ZK incorporation system was inhibited in a ZK concentration-dependent manner without causing rapid bacterial death, presumably due to generation of non-functional or toxic proteins. The extent of growth inhibition strongly depended on the anticodon sequence of the tRNApyl gene. Taking advantage of the low selectivity of PylRS for tRNApyl anticodons, we experimentally determined the most effective anticodon sequence among all 64 nucleotide sequences in the anticodon region of tRNApyl gene. The results suggest that the ZK-regulated growth controller is a simple, target-specific, environmental noise-resistant and titratable system. This technique may be applicable to a wide variety of organisms because the growth inhibitory effects are caused by “informational disturbance”, in which the highly conserved system for transmission of information from DNA to proteins is perturbed.
Psoas Muscle Area Predicts Mortality after Left Ventricular Assist Device Implantation
Authors: Wittmann Franziska , Schlöglhofer Thomas , Riebandt Julia , Schaefer Anne-Kristin , Wiedemann Dominik , Tschernko Edda , Beitzke Dietrich , Loewe Christian , Laufer Günther , Zimpfer Daniel
Published: September 2021

Several risk scores and classifications are available to predict peri- and post-operative mortality of patients with end stage heart failure receiving Left Ventricular Assist Device (LVAD) therapy. Sarcopenia has been suggested as a sensitive predictor for post-operative mortality. We evaluated whether the psoas muscle area can predict mortality in patients undergoing LVAD implantation. The indexed psoas mean area (PMAi) was obtained by measuring the psoas muscle area at the superior endplate of the third lumbar vertebra correlated to body surface area of 106 adult patients undergoing LVAD implantation (Medtronic HVAD n = 41, Abbott HeartMate II n = 4, Abbott HeartMate 3 n = 61; mean age 65, IQR 12, 90.6% male; INTERMACS Level 1 24.5%; ischemic CMP 64.2%). Patients were divided in two groups: high/moderate and low muscle mass. The primary endpoint was 30-day mortality, assessed using a multivariate Cox proportional hazards model. Baseline characteristics did not differ between patients with high or moderate and low PMAi. Estimated survival calculated a significant higher 30-day mortality in patients with low PMAi (p = 0.04). Multivariable Cox proportional hazards regression analysis indicated low PMAi, history of previous cardiac surgery and levels of bilirubin as independent predictors of mortality in the first 30 days. In conclusion, indexed psoas muscle area predicts mortality after LVAD implantation and can be used as an additional tool for risk stratification.
The Prognostic Significance of MACC1 Expression in Breast Cancer and Its Relationship to Immune Cells in the Tumor Microenvironment and Patient Survival
Authors: Ali Dina A. , El-Guindy Dina M. , Elrashidy Mohamed A. , Sabry Nesreen M. , Kabel Ahmed M. , Gaber Rasha A. , Ibrahim Rowida R. , Samy Sara M. , Shalaby Marwa M. , Salama Samir A. , Abdelhai Dina
Published: September 2021

Breast cancer (BC) is one of the most prevalent malignancies among females worldwide. Globally, distant metastases were reported to be responsible for a large proportion of breast cancer-related deaths. The metastasis-associated colon cancer-1 (MACC1) gene was reported as a reliable biomarker for early detection of metastasis and prediction of prognosis of breast cancer. This study investigated the prognostic significance of MACC1 in breast cancer in relation to the clinicopathologic characteristics and patients’ survival. Furthermore, the possible correlation between MACC1 expression and the different immune cells in the tumor microenvironment was explored. MACC1 mRNA was identified using quantitative reverse transcription polymerase chain reaction in 120 breast cancer specimens and adjacent non-cancerous tissues. MACC1 mRNA expression was significantly higher in the cancerous relative to the non-cancerous tissues (p < 0.001). High MACC1 expression was significantly associated with poor prognostic parameters, such as larger tumor size, grade III tumors, positive nodal metastasis, lymphovascular invasion, stage III tumors, and elevated Ki-67 expression. Higher MACC1 mRNA levels were positively correlated with CD163+ tumor-associated macrophages (r = 0.614, p < 0.001), and were negatively correlated with CD56+ natural killer cells (r = −0.398, p < 0.001) and CD8+ cytotoxic T lymphocytes (r = −0.323, p < 0.001). MACC1 expression was associated with poor patient overall survival (OS) and progression-free survival (PFS) (p < 0.001). Multivariate analysis suggested that MACC1 expression and the presence of lymphovascular invasion could be independent prognostic indicators for breast cancer (p = 0.015 and 0.042, respectively). In conclusion, MACC1 is highly expressed in cancerous tissues and is significantly related to poor prognostic factors, overall survival, and progression-free survival. MACC1 may influence infiltration of the immune cells in the tumor microenvironment, enhance immune escape of tumor cells, and may serve as a reliable independent prognostic factor for breast cancer.
Left Ventricular Systolic Function Has Strong Independent Genetic Background from Diastolic Function: A Classical Twin Study
Authors: Molnár Andrea Ágnes , Kolossváry Márton , Lakatos Bálint , Tokodi Márton , Tárnoki Ádám Domonkos , Tárnoki Dávid László , Kovács Attila , Szilveszter Bálint , Voros Szilard , Jermendy György , Maurovich-Horvat Pál , Merkely Béla
Published: September 2021

Background and Objectives: No data are available on whether the heritability of left ventricle (LV) systolic and diastolic parameters are independent of each other. Therefore, our aim was to assess the magnitude of common and independent genetic and environmental factors defining LV systolic and diastolic function. Materials and Methods: We analyzed 184 asymptomatic twins (65% female, mean age: 56 ± 9 years). Transthoracic echocardiography was performed to measure LV systolic (global longitudinal and circumferential strain; basal and apical rotation) and diastolic (early diastolic velocity of mitral inflow and lateral mitral annulus tissue; deceleration time and early diastolic strain rate) parameters using conventional and speckle-tracking echocardiography. Genetic structural equation models were evaluated to quantify the proportion of common and specific genetic (Ac, As) and environmental factors (Ec, Es) contributing to the phenotypes. Results: LV systolic parameters had no common genetic or environmental heritability (Ac range: 0–0%; Ec range: 0–0%; As range: 57–77%; Es range: 24–43%). Diastolic LV parameters were mainly determined by common genetic and environmental effects (Ac range: 9–40%; Ec range: 11–49%; As range: 0–29%; Es range: 0–51%). Systolic parameters had no common genetic or environmental factors (Ac = 0%; Ec = 0%) with diastolic metrics. Conclusions: Systolic LV parameters have a strong genetic predisposition to any impact. They share no common genetic or environmental factors with each other or with diastolic parameters, indicating that they may deteriorate specifically to given effects. However, diastolic functional parameters are mainly affected by common environmental influences, suggesting that pathological conditions may deteriorate them equally. Estimation of the genetic and environmental influence and interdependence on systolic and diastolic LV function may help the understanding of the pathomechanism of different heart failure classification types.
Association between Inflammation-Based Parameters and Prognosis in Patients with Acute Kidney Injury
Authors: Joo Hyelim , Min Sun Young , Park Min-Su
Published: September 2021

Background and Objectives: this study aimed to clarify the relationship between inflammation-based parameters and prognosis in patients with acute kidney injury (AKI). Materials and Methods: We analyzed the prospectively collected data of patients with AKI, who were admitted through the emergency department between March 2020 and April 2021. Their clinical characteristics, inflammation-based parameters, resolving/non-resolving AKI pattern, and major adverse kidney event (MAKE) rates were analyzed. Results: Among 177 patients, 129 (72.9%) had a resolving AKI pattern and 48 (27.1%) had a non-resolving AKI pattern. The outcome of MAKE occurred in 30 (16.9%) participants. Multivariate analyses showed that the neutrophil-to-monocyte ratio was an independent predictor of resolving AKI, and that the neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios were independent predictors of MAKE occurrence. Conclusions: we demonstrated that inflammation-based parameters are valuable predictors of early recovery and MAKE occurrence in patients with AKI.
Clinicopathological Significance and Prognostic Implications of REG4 Immunohistochemical Expression in Colorectal Cancer
Authors: Kang Guhyun , Oh Ilhwan , Pyo Jungsoo , Kang Dongwook , Son Byoungkwan
Published: September 2021

Background and objectives: The present study aimed to evaluate the clinicopathological significance and prognostic implications of REG4 immunohistochemical expression in colorectal cancer (CRC). Materials and Methods: We performed immunohistochemical analysis for REG4 cytoplasmic expression in 266 human CRC tissues. Correlations between REG4 expression, clinicopathological characteristics, and survival were investigated in CRC. Results: REG4 was expressed in 84 of 266 CRC tissues (31.6%). REG4 expression was significantly more frequent in the right colon than that in the left colon and rectum (p = 0.002). However, we observed no significant correlation between REG4 expression and other clinicopathological parameters. REG4 expression was significantly higher in CRCs with low stroma than in those with high stroma (p = 0.006). In addition, REG4 was more frequently expressed in CRCs with the mucinous component than in those without it (p < 0.001). There was no significant correlation between REG4 expression and overall recurrence-free survival (p = 0.132 and p = 0.480, respectively). Patients with REG4 expression showed worse overall and recurrence-free survival in the high-stroma subgroup (p = 0.001 and p = 0.017, respectively), but no such correlation was seen in the low stroma subgroup (p = 0.232 and p = 0.575, respectively). Conclusions: REG4 expression was significantly correlated with tumor location, amount of stroma, and mucinous component in CRCs. In patients with high stroma, REG4 expression was significantly correlated with poor overall and recurrence-free survival.
Design Strategies for Alkaline Exchange Membrane–Electrode Assemblies: Optimization for Fuel Cells and Electrolyzers
Authors: Ashdot Aviv , Kattan Mordechai , Kitayev Anna , Tal-Gutelmacher Ervin , Amel Alina , Page Miles
Published: September 2021

Production of hydrocarbon-based, alkaline exchange, membrane–electrode assemblies (MEA’s) for fuel cells and electrolyzers is examined via catalyst-coated membrane (CCM) and gas-diffusion electrode (GDE) fabrication routes. The inability effectively to hot-press hydrocarbon-based ion-exchange polymers (ionomers) risks performance limitations due to poor interfacial contact, especially between GDE and membrane. The addition of an ionomeric interlayer is shown greatly to improve the intimacy of contact between GDE and membrane, as determined by ex situ through-plane MEA impedance measurements, indicated by a strong decrease in the frequency of the high-frequency zero phase angle of the complex impedance, and confirmed in situ with device performance tests. The best interfacial contact is achieved with CCM’s, with the contact impedance decreasing, and device performance increasing, in the order GDE >> GDE+Interlayer > CCM. The GDE+interlayer fabrication approach is further examined with respect to hydrogen crossover and alkaline membrane electrolyzer cell performance. An interlayer strongly reduces the rate of hydrogen crossover without strongly decreasing electrolyzer performance, while crosslinking the ionomeric layer further reduces the crossover rate though also limiting device performance. The approach can be applied and built upon to improve the design and production of alkaline, and more generally, hydrocarbon-based MEA’s and exchange membrane devices.
Interfacial Microstructure and Formation of Direct Laser Welded CFRP/Ti-6Al-4V Joint
Authors: Zou Pengyuan , Zhang Hua , Lei Min , Cheng Donghai , Huang Shuo , Yang Fan
Published: September 2021

Joining fiber reinforced polyether ether ketone resin matrix composite (PEEK-CFRP) with Ti-6Al-4V titanium alloy to form a composite structure is a promising manufacturing process. Huge difference of material properties is the biggies challenge to join them. Continuous laser welding process is conducted in this experiment to join the two materials. In this study, joints under different welding speeds were obtained. Mechanical properties and microstructures were observed, and the interfacial structures were tested. The results showed that fixed joint could be obtained. As the welding speed decreased, the tensile shear first increased and then decreased. The shear force reached a maximum value of 36.8 N/mm at the speed of 10 mm/s. The quality of joint could be observably affected by welding speed. The formation of bubbles, cracks, and anchor effect at the interface were the main factors affecting the mechanical property of joint. Thus, adhesion failure was the main failure form for CFRP fracture. Ti, Al and some other elements had been diffused across the interface, resulting in the formation of intermediate transition layer. The result of EDS, X-ray and XPS test indicated that CTi0.42V1.58 phase could be formed, and Ti at the interface could react with the oxygen and carbon of CFRP to form TiO2, TiO and TiC, forming a stable joint structure.
Modeling Intraperitoneal Insulin Absorption in Patients with Type 1 Diabetes
Authors: Schiavon Michele , Cobelli Claudio , Dalla Man Chiara
Published: September 2021

Standard insulin therapy to treat type 1 diabetes (T1D) consists of exogenous insulin administration through the subcutaneous (SC) tissue. Despite recent advances in insulin formulations, the SC route still suffers from delays and large inter/intra-subject variability that limiting optimal glucose control. Intraperitoneal (IP) insulin administration, despite its higher invasiveness, was shown to represent a valid alternative to the SC one. To date, no mathematical model describing the absorption and distribution of insulin after IP administration is available. Here, we aim to fill this gap by using data from eight patients with T1D, treated by implanted IP pump, studied in a hospitalized setting, with frequent measurements of plasma insulin and glucose concentration. A battery of models describing insulin kinetics after IP administration were tested. Model comparison and selection were performed based on model ability to predict the data, precision of parameters and parsimony criteria. The selected model assumed that the insulin absorption from the IP space was described by a linear, two-compartment model, coupled with a two-compartment model of whole-body insulin kinetics with hepatic insulin extraction controlled by hepatic insulin. Future developments include model incorporation into the UVa/Padova T1D Simulator for testing open- and closed-loop therapies with IP insulin administration.
Geochemical, Geotechnical, and Microbiological Changes in Mg/Ca Bentonite after Thermal Loading at 150 °C
Authors: Kašpar Vlastislav , Šachlová Šárka , Hofmanová Eva , Komárková Bára , Havlová Václava , Aparicio Claudia , Černá Kateřina , Bartak Deepa , Hlaváčková Veronika
Published: September 2021

Bentonite buffers at temperatures beyond 100 °C could reduce the amount of high-level radioactive waste in a deep geological repository. However, it is necessary to demonstrate that the buffer surrounding the canisters withstands such elevated temperatures, while maintaining its safety functions (regarding long-term performance). For this reason, an experiment with thermal loading of bentonite powder at 150 °C was arranged. The paper presents changes that the Czech Mg/Ca bentonite underwent during heating for one year. These changes were examined by X-ray diffraction (XRD), thermal analysis with evolved gas analysis (TA-EGA), aqueous leachates, Cs sorption, cation exchange capacity (CEC), specific surface area (SSA), free swelling, saturated hydraulic conductivity, water retention curves (WRC), quantitative polymerase chain reaction (qPCR), and next-generation sequencing (NGS). It was concluded that montmorillonite was partially altered, in terms of the magnitude of the surface charge density of montmorillonite particles, based on the measurement interpretations of CEC, SSA, and Cs sorption. Montmorillonite alteration towards low- or non-swelling clay structures corresponded well to significantly lower swelling ability and water uptake ability, and higher saturated hydraulic conductivity of thermally loaded samples. Microbial survivability decreased with the thermal loading time, but it was not completely diminished, even in samples heated for one year.
Lab-In-Syringe with Bead Injection Coupled Online to High-Performance Liquid Chromatography as Versatile Tool for Determination of Nonsteroidal Anti-Inflammatory Drugs in Surface Waters
Authors: Gemuh Celestine Vubangsi , Horstkotte Burkhard , Solich Petr
Published: September 2021

We report on the hyphenation of the modern flow techniques Lab-In-Syringe and Lab-On-Valve for automated sample preparation coupled online with high-performance liquid chromatography. Adopting the bead injection concept on the Lab-On-Valve platform, the on-demand, renewable, solid-phase extraction of five nonsteroidal anti-inflammatory drugs, namely ketoprofen, naproxen, flurbiprofen, diclofenac, and ibuprofen, was carried out as a proof-of-concept. In-syringe mixing of the sample with buffer and standards allowed straightforward pre-load sample modification for the preconcentration of large sample volumes. Packing of ca. 4.4 mg microSPE columns from Oasis HLB® sorbent slurry was performed for each sample analysis using a simple microcolumn adapted to the Lab-On-Valve manifold to achieve low backpressure during loading. Eluted analytes were injected into online coupled HPLC with subsequent separation on a Symmetry C18 column in isocratic mode. The optimized method was highly reproducible, with RSD values of 3.2% to 7.6% on 20 µg L−1 level. Linearity was confirmed up to 200 µg L−1 and LOD values were between 0.06 and 1.98 µg L−1. Recovery factors between 91 and 109% were obtained in the analysis of spiked surface water samples.
Genome Mining and Molecular Networking-Based Metabolomics of the Marine Facultative Aspergillus sp. MEXU 27854
Authors: Martínez-Cárdenas Anahí , Cruz-Zamora Yuridia , Fajardo-Hernández Carlos A. , Villanueva-Silva Rodrigo , Cruz-García Felipe , Raja Huzefa A. , Figueroa Mario
Published: September 2021

The marine-facultative Aspergillus sp. MEXU 27854, isolated from the Caleta Bay in Acapulco, Guerrero, Mexico, has provided an interesting diversity of secondary metabolites, including a series of rare dioxomorpholines, peptides, and butyrolactones. Here, we report on the genomic data, which consists of 11 contigs (N50~3.95 Mb) with a ~30.75 Mb total length of assembly. Genome annotation resulted in the prediction of 10,822 putative genes. Functional annotation was accomplished by BLAST searching protein sequences with different public databases. Of the predicted genes, 75% were assigned gene ontology terms. From the 67 BGCs identified, ~60% belong to the NRPS and NRPS-like classes. Putative BGCs for the dioxomorpholines and other metabolites were predicted by extensive genome mining. In addition, metabolomic molecular networking analysis allowed the annotation of all isolated compounds and revealed the biosynthetic potential of this fungus. This work represents the first report of whole-genome sequencing and annotation from a marine-facultative fungal strain isolated from Mexico.