bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavior of Ultra-High-Performance Concrete with Hybrid Synthetic Fiber Waste Exposed to Elevated Temperatures
Authors: Tayeh Bassam , Hadzima-Nyarko Marijana , Riad Magdy Youssef Riad , Hafez Radwa Defalla Abdel
Published: January 2023

The reinforcement of ultra-high-performance concrete (UHPC) with fibers was investigated in this study. Concrete is the most widely used manmade construction material, and UHPC has remarkable mechanical properties. The mechanical properties of UHPC can be modified by a variety of curing procedures and the amount of cement used. This study aimed to examine the impact of fiber reinforcement, temperature, and exposure time on UHPC. Initially, the temperature for UHPC was changed from 300 °C to 500 °C and the exposure time set to 1 and 2 h. Various combinations of the ultrasonic pulse, thermal conductivity, compressive strength, flexural strength, splitting, modulus of elasticity, and drop hammer impact (impact resistance, impact energy, and ductility index) were investigated after 91 days of steam curing. For steam curing, the temperature was kept at 90 °C for three days. The mechanical characteristics of UHPC were the primary focus of this research. The test results showed that the accelerated curing regime achieved a maximum compressive strength of 102.6 MPa for UHPC specimens without fibers and 124.7 MPa for UHPC specimens with fibers, which represents a 22% increase in compressive strength. When compared to UHPC without fibers, all the qualities of UHPC with fibers were improved, especially when subjected to high temperatures. The incorporation of hybrid synthetic waste fibers was a key aspect in developing new ultra-high-strength concrete features.
A Simplified Framework for Historic Cities to Define Strategies Aimed at Implementing Resilience Skills: The Case of Lisbon Downtown
Authors: Barchetta Lucia , Petrucci Enrica , Xavier Válter , Bento Rita
Published: January 2023

The concepts of resistance to unforeseen disasters and rapid post-disaster recovery of historic cities are necessary due to the earthquakes that have profoundly influenced their evolution. The improvement of this property strongly depends on the effectiveness of the preventive tools. In this work, an operational framework for the resilience assessment of a historical city characterized by high cultural and historical elements is developed, which corresponds to the main contribution of this research. The research includes multicriteria analysis based on the in-depth knowledge of the city’s historical development, the study of the effects of past earthquakes, structural vulnerability analysis of pombalino buildings, architectural types and socio-economic aspects. The aim is to obtain the necessary elements to guide an aware plan for improving resilience and the reduction of vulnerability through a GIS tool aimed at preventing and defining urban intervention priorities. The framework proposed is applied to Lisbon downtown.
Smart or Intelligent Assets or Infrastructure: Technology with a Purpose
Authors: Serrano Will
Published: January 2023

Smart or intelligent built assets including infrastructure, buildings, real estate, and cities provide enhanced functionality to their different users such as occupiers, passengers, consumers, patients, managers or operators. This enhanced functionality enabled by the Internet of Things (IoT), Artificial Intelligence (AI), Big Data, Mobile Apps, Virtual Reality (VR) and 5G does not only translate into a superior user experience; technology also supports sustainability and energy consumption to meet regulation (ESG, NZC) while optimising asset management and operations for enhanced business economic performance. The main peculiarity is that technology is standardised, ubiquitous and independent from the physical built assets whereas asset users including humans, machines and devices are also common to different assets. This article analyses the atomic differences between built assets and proposes an asset omni-management model based on micro-management of services that will support the macro-functionality of the asset. The proposed key concept is based on the standardisation of different assets based on common and specific functionality and services delivered by the technology stack that is supporting already the transition to Industry 5.0 based on Web 3.0 and Tokenisation.
Application of Scheduling Techniques for Load-Shifting in Smart Homes with Renewable-Energy-Sources Integration
Authors: Dragomir Otilia Elena , Dragomir Florin
Published: January 2023

The general context of this proposal is represented by the energy-efficient smart home that integrates renewable energy sources such as photovoltaic panels. The objective of this article is to minimize the amount of energy consumed from the national energy grid by producer-consumers of energy from renewable sources, in their own smart homes. In order to fulfill this goal, it was necessary to estimate the amount of renewable energy produced on the day-ahead horizon and to schedule the operation of controllable consumers in a smart home. To predict the amount of energy produced, two approaches were used: the first was based on data, and used techniques specific to artificial intelligence, more specifically, multilayer perceptron and radial-basis-function neural networks, and the second was based on models. The accuracy of the short-term prediction horizon of the techniques used was evaluated with quantitative performance indicators so that the most appropriate one in relation to the goal of the article could be selected to be used in the test scenarios. The scheduling of consumer functioning was based on their classification in relation to their ability to be controlled, and on the selection from the peer-reviewed literature of an optimization algorithm which, by load shifting from a smart home, ensured the optimal fulfillment of the objective function. The selected load-shifting algorithm was then integrated into and tested on a real database. The data used were monitored for two representative days, in terms of the amount of energy from renewable energy sources produced and consumed. The load-shifting algorithm proved its effectiveness through the results obtained and which are reported in the article.
An Explainable AI-Enabled Framework for Interpreting Pulmonary Diseases from Chest Radiographs
Authors: Naz Zubaira , Khan Muhammad Usman Ghani , Saba Tanzila , Rehman Amjad , Nobanee Haitham , Bahaj Saeed Ali
Published: January 2023

Explainable Artificial Intelligence is a key component of artificially intelligent systems that aim to explain the classification results. The classification results explanation is essential for automatic disease diagnosis in healthcare. The human respiration system is badly affected by different chest pulmonary diseases. Automatic classification and explanation can be used to detect these lung diseases. In this paper, we introduced a CNN-based transfer learning-based approach for automatically explaining pulmonary diseases, i.e., edema, tuberculosis, nodules, and pneumonia from chest radiographs. Among these pulmonary diseases, pneumonia, which COVID-19 causes, is deadly; therefore, radiographs of COVID-19 are used for the explanation task. We used the ResNet50 neural network and trained the network on extensive training with the COVID-CT dataset and the COVIDNet dataset. The interpretable model LIME is used for the explanation of classification results. Lime highlights the input image’s important features for generating the classification result. We evaluated the explanation using radiologists’ highlighted images and identified that our model highlights and explains the same regions. We achieved improved classification results with our fine-tuned model with an accuracy of 93% and 97%, respectively. The analysis of our results indicates that this research not only improves the classification results but also provides an explanation of pulmonary diseases with advanced deep-learning methods. This research would assist radiologists with automatic disease detection and explanations, which are used to make clinical decisions and assist in diagnosing and treating pulmonary diseases in the early stage.
Predictors of Symptomatic Venous Thromboembolism in Patients with Soft Tissue Sarcoma in the Lower Extremity
Authors: Kamalapathy Pramod N. , Kline Adam , Hollow Hannah , Raskin Kevin , Schwab Joseph H. , Lozano-Calderón Santiago
Published: January 2023

Orthopedic surgery and soft-tissue sarcoma (STS) both independently increase the risk of developing symptomatic venous thromboembolic events (SVTE), but there are no established risk factors or guidelines for how to prophylactically treat patients with STS undergoing surgery. The objectives of this study were to (1) identify the prevalence of SVTE in patients undergoing STS surgery, (2) identify risk factors for SVTE, and (3) determine the risk of wound complications associated with VTE prophylaxis. This retrospective study was conducted in a tertiary level, academic hospital. A total of 642 patients were treated for soft-tissue sarcoma in the lower extremity with follow up for at least 90 days for the development of SVTE such as deep venous thrombosis and pulmonary embolism. Multivariate logistic regression was used to identify predictors for these events by controlling for patient characteristics, surgical characteristics, and treatment variables, with significance held at p < 0.05. Twenty eight patients (4.36%) were diagnosed with SVTE. Multivariate analysis found six significant predictors ordered based on standardized coefficients: pre-operative (PTT) partial thromboplastin time (p < 0.001), post-operative PTT (p = 0.010), post-op chemotherapy (p = 0.013), metastasis at diagnosis (p = 0.025), additional surgery for metastasis or local recurrence (p = 0.004), and tumor size larger than 10 cm (p < 0.001). The risk of wound complications (p = 0.04) and infection (p = 0.017) increased significantly in patients who received chemical prophylaxis. Our study identifies risk factors for patients at increased risk of developing VTE. Further prospective research is necessary to identify which protocols would be beneficial in preventing SVTE in high-risk patients with a low profile of wound complications.
Pancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate
Authors: Miebach Lea , Mohamed Hager , Wende Kristian , Miller Vandana , Bekeschus Sander
Published: January 2023

Survival rates among patients with pancreatic cancer, the most lethal gastrointestinal cancer, have not improved compared to other malignancies. Early tumor dissemination and a supportive, cancer-promoting tumor microenvironment (TME) limit therapeutic options and consequently impede tumor remission, outlining an acute need for effective treatments. Gas plasma-oxidized liquid treatment showed promising preclinical results in other gastrointestinal and gynecological tumors by targeting the tumor redox state. Here, carrier solutions are enriched with reactive oxygen (ROS) and nitrogen (RNS) species that can cause oxidative distress in tumor cells, leading to a broad range of anti-tumor effects. Unfortunately, clinical relevance is often limited, as many studies have forgone the use of medical-grade solutions. This study investigated the efficacy of gas plasma-oxidized Ringer’s lactate (oxRilac), a physiological solution often used in clinical practice, on two pancreatic cancer cell lines to induce tumor toxicity and provoke immunogenicity. Tumor toxicity of the oxRilac solutions was further confirmed in three-dimensional tumor spheroids monitored over 72 h and in ovo using stereomicroscope imaging of excised GFP-expressing tumors. We demonstrated that cell death signaling was induced in a dose-dependent fashion in both cell lines and was paralleled by the increased surface expression of key markers of immunogenic cell death (ICD). Nuclear magnetic resonance (NMR) spectroscopy analysis suggested putative reaction pathways that may cause the non-ROS related effects. In summary, our study suggests gas plasma-deposited ROS in clinically relevant liquids as an additive option for treating pancreatic cancers via immune-stimulating and cytotoxic effects.
Novel Adaption of the SARC-F Score to Classify Pediatric Hemato-Oncology Patients with Functional Sarcopenia
Authors: Verwaaijen Emma J. , van der Torre Patrick , Vormoor Josef , Pieters Rob , Fiocco Marta , Hartman Annelies , van den Heuvel-Eibrink Marry M.
Published: January 2023

Sarcopenia in pediatric hemato-oncology patients is undesirable because of the consequences it may have for treatment continuation and outcome, physical abilities and participation in daily life. An easy-to-use screening tool for sarcopenia will facilitate the identification of children at risk who need interventions to prevent serious physical deterioration. In the elderly, the use of the SARC-F score as a case-finding tool for sarcopenia is recommended. The aim of this cross-sectional study was to investigate the accuracy of the pediatric SARC-F (PED-SARC-F) for identifying sarcopenia in pediatric hemato-oncology patients, including the determination of a cut-off point for clinical use. Patients 3–20 years of age, under active treatment or within 12 months after treatment cessation were eligible. Patients had a physiotherapy assessment including a PED-SARC-F (0–10) and measurements of muscle strength (handheld dynamometry), physical performance (various tests) and/or muscle mass (bio-impedance analysis), as part of the standard of care. Spearman’s correlation coefficient (rs) between the PED-SARC-F and physiotherapy outcomes were calculated. Structural sarcopenia was defined as low appendicular skeletal muscle mass (ASMM) in combination with low muscle strength and/or low physical performance. Functional sarcopenia indicated low muscle strength combined with low physical performance. Multiple logistic regression models were estimated to study the associations between the PED-SARC-F and structural/functional sarcopenia. To evaluate which cut-off point provides the most accurate classification, the area under the receiver operating characteristic curve (AUCs), sensitivity and specificity per point were calculated. In total, 215 assessments were included, 62% were performed in boys and the median age was 12.9 years (interquartile range: 8.5–15.8). The PED-SARC-F scores correlated moderately with the measurements of muscle strength (rs = −0.37 to −0.47, p < 0.001) and physical performance (rs = −0.45 to −0.66, p < 0.001), and weakly with ASMM (rs = −0.27, p < 0.001). The PED-SARC-F had an AUC of 0.90 (95% confidence interval (CI) = 0.84–0.95) for functional sarcopenia and 0.79 (95% CI = 0.68–0.90) for structural sarcopenia. A cut-off point of ≥5 had the highest specificity of 96% and a sensitivity of 74%. In conclusion, we adapted the SARC-F to a pediatric version, confirmed its excellent diagnostic accuracy for identifying functional sarcopenia and defined a clinically useful cut-off point in pediatric hemato-oncology patients.
Validation of a Temperature-Feedback Controlled Automated Magnetic Hyperthermia Therapy Device
Authors: Sharma Anirudh , Jangam Avesh , Shen Julian Low Yung , Ahmad Aiman , Arepally Nageshwar , Rodriguez Benjamin , Borrello Joseph , Bouras Alexandros , Kleinberg Lawrence , Ding Kai , Hadjipanayis Constantinos , Kraitchman Dara L. , Ivkov Robert , Attaluri Anilchandra
Published: January 2023

We present in vivo validation of an automated magnetic hyperthermia therapy (MHT) device that uses real-time temperature input measured at the target to control tissue heating. MHT is a thermal therapy that uses heat generated by magnetic materials exposed to an alternating magnetic field. For temperature monitoring, we integrated a commercial fiber optic temperature probe containing four gallium arsenide (GaAs) temperature sensors. The controller device used temperature from the sensors as input to manage power to the magnetic field applicator. We developed a robust, multi-objective, proportional-integral-derivative (PID) algorithm to control the target thermal dose by modulating power delivered to the magnetic field applicator. The magnetic field applicator was a 20 cm diameter Maxwell-type induction coil powered by a 120 kW induction heating power supply operating at 160 kHz. Finite element (FE) simulations were performed to determine values of the PID gain factors prior to verification and validation trials. Ex vivo verification and validation were conducted in gel phantoms and sectioned bovine liver, respectively. In vivo validation of the controller was achieved in a canine research subject following infusion of magnetic nanoparticles (MNPs) into the brain. In all cases, performance matched controller design criteria, while also achieving a thermal dose measured as cumulative equivalent minutes at 43 °C (CEM43) 60 ± 5 min within 30 min.
Aquaporins as Prognostic Biomarker in Prostate Cancer
Authors: Kushwaha Prem Prakash , Verma Shiv , Gupta Sanjay
Published: January 2023

Prostate cancer is a complex heterogeneous disease that affects millions of males worldwide. Despite rapid advances in molecular biology and innovation in technology, few biomarkers have been forthcoming in prostate cancer. The currently available biomarkers for the prognosis of prostate cancer are inadequate and face challenges, thus having limited clinical utility. To date, there are a number of prognostic and predictive biomarkers identified for prostate cancer but lack specificity and sensitivity to guide clinical decision making. There is still tremendous scope for specific biomarkers to understand the natural history and complex biology of this heterogeneous disease, and to identify early treatment responses. Accumulative studies indicate that aquaporins (AQPs) a family of membrane water channels may serve as a prognostic biomarker for prostate cancer in monitoring disease advancement. In the present review, we discuss the existing prostate cancer biomarkers, their limitations, and aquaporins as a prospective biomarker of prognostic significance in prostate cancer.
Cell-of-Origin Targeted Drug Repurposing for Triple-Negative and Inflammatory Breast Carcinoma with HDAC and HSP90 Inhibitors Combined with Niclosamide
Authors: Bhattacharya Udayan , Kamran Mohammad , Manai Maroua , Cristofanilli Massimo , Ince Tan A.
Published: January 2023

We recently identified a cell-of-origin-specific mRNA signature associated with metastasis and poor outcome in triple-negative carcinoma (TNBC). This TNBC cell-of-origin signature is associated with the over-expression of histone deacetylases and zinc finger protein HDAC1, HDAC7, and ZNF92, respectively. Based on this signature, we discovered that the combination of three drugs (an HDAC inhibitor, an anti-helminthic Niclosamide, and an antibiotic Tanespimycin that inhibits HSP90) synergistically reduces the proliferation of the twelve tested TNBC cell lines. Additionally, we discovered that four out of five inflammatory breast carcinoma cell lines are sensitive to this combination. Significantly, the concentration of the drugs that are used in these experiments are within or below clinically achievable dose, and the synergistic activity only emerged when all three drugs were combined. Our results suggest that HDAC and HSP90 inhibitors combined with the tapeworm drug Niclosamide can achieve remarkably synergistic inhibition of TNBC and IBC. Since Niclosamide, HDAC, and HSP90 inhibitors were approved for clinical use for other cancer types, it may be possible to repurpose their combination for TNBC and IBC.
CsxCo/Na-MOR Coating on Ceramic Monoliths for Co-Adsorption of Hydrocarbons Mixture and Selective Catalytic Reduction of NOx
Authors: Serra Ramiro M. , Gómez Leticia E. , Tiscornia Inés S. , Deharbe María de los Milagros , Boix Alicia V.
Published: January 2023

In this work, ceramic monoliths were coated with powders based on exchanged Cs and/or Co cations in Na-mordenite (MOR) zeolite. SEM images showed that zeolite particles fill the macropores of cordierite walls and form a continuous layer of approximately 40 µm with good adherence. XPS analysis revealed that Co and Cs are present on the film surface solely as Co2+ and Cs+ at exchange positions in zeolite. The monolithic structures were evaluated for the butane-toluene co-adsorption and SCR of NOx with hydrocarbon mixture as the reducing agent. The presence of alkali metal cations in the zeolitic lattice favored the adsorption capacity of both hydrocarbons, while cobalt cations provoked a decrease in the adsorbed amounts due to its weak interaction with the HCs. Breakthrough curves of butane adsorption showed a roll-up phenomenon, associated with a competitive adsorption effect generated from toluene presence. In the desorption process, it was observed that adsorbed toluene hindered the butane diffusion through mordenite channels, which released at higher temperatures (above 250 °C). Cs2CoM and Cs7CoM monoliths were more active than the CoM monolith for NO-SCR. The presence of Cs cations close to Co cations increased the hydrocarbons concentration around active sites at high temperatures, according to TPD results, promoting the reduction activity of NO.
Heterofunctional Methacrylate Beads Bearing Octadecyl and Vinyl Sulfone Groups: Tricks to Obtain an Interfacially Activated Lipase from Thermomyces lanuginosus and Covalently Attached to the Support
Authors: Guimarães José R. , Carballares Diego , Rocha-Martin Javier , Alcántara Andrés R. , Tardioli Paulo W. , Fernandez-Lafuente Roberto
Published: January 2023

Lipase from Thermomyces lanuginosus (TLL) has been immobilized on a methacrylate macroporous resin coated with octadecyl groups (Purolite Lifetech®® ECR8806F). This immobilization protocol gave a biocatalyst with significantly higher stability than that obtained using octyl agarose. To further improve the biocatalyst features, we tried to covalently immobilize the enzyme using this support. For this purpose, the support was activated with divinyl sulfone. The results showed that at least 1/3 of the immobilized enzyme molecules were not covalently immobilized. To solve the problem, we produced an aminated support and then activated it with divinyl sulfone. This permitted the full covalent immobilization of the previously immobilized TLL. The use of different blocking agents as the reaction endpoint (using ethylenediamine, Asp, Gly, and Cys) greatly altered the biocatalyst functional features (activity, specificity, or stability). For example, the blocking with ethylenediamine increased the ratio of the activity versus R- and S-methyl mandelate by a three-fold factor. The blocking with Cys produced the most stable biocatalyst, maintaining close to 90% of the activity under conditions where the just adsorbed enzyme maintained less than 55%. That way, this strategy to modify the support has permitted obtaining an enzyme interfacially activated versus the octadecyl layer and, later, covalently immobilized by reaction with the vinyl sulfone groups.
Pervasive Platelet Secretion Defects in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Kalbhenn Johannes , Pooth Jan-Steffen , Trummer Georg , Kranzhöfer David , Schlagenhauf Axel , Zieger Barbara
Published: January 2023

Critically ill COVID-19 patients suffer from thromboembolic as well as bleeding events. Endothelial dysfunction, spiking of von Willebrand factor (vWF), and excessive cytokine signaling result in coagulopathy associated with substantial activation of plasmatic clotting factors. Thrombocytopenia secondary to extensive platelet activation is a frequent finding, but abnormal platelet dysfunction may also exist in patients with normal platelet counts. In this study, we performed analyses of platelet function and of von Willebrand factor in critically ill COVID-19 patients (n = 13). Platelet aggregometry was performed using ADP, collagen, epinephrin, and ristocetin. VWF and fibrinogen binding of platelets and CD62 and CD63 expression after thrombin stimulation were analyzed via flow cytometry. In addition, VWF antigen (VWF:Ag), collagen binding capacity (VWF:CB), and multimer analysis were performed next to routine coagulation parameters. All patients exhibited reduced platelet aggregation and decreased CD62 and CD63 expression. VWF binding of platelets was reduced in 12/13 patients. VWF:CB/VWF:Ag ratios were pathologically decreased in 2/13 patients and elevated in 2/13 patients. Critically ill COVID-19 patients exhibit platelet secretion defects independent of thrombocytopenia. Platelet exhaustion and VWF dysfunction may result in impaired primary hemostasis and should be considered when treating coagulopathy in these patients.
Synergism of Feeding and Digestion Regulated by the Neuropeptide F System in Ostrinia furnacalis Larvae
Authors: Zhao Jiajia , Song Yu , Jiang Xuemin , He Lei , Wei Liya , Zhao Zhangwu
Published: January 2023

Feeding is crucial for the growth and survival of animals, including humans, but relatively little is known about how it is regulated. Here, we show that larval feeding in Ostrinia furnacalis is regulated by neuropeptide F (NPF, the homologous peptide of mammalian NPY) via the insulin signalling pathway in the midgut. Furthermore, the genes pi3k and mtor in the insulin pathway positively regulate α-amylase and lipase of the midgut by recruiting the transcription factors c-Myc and PPARγ for binding to the promotors of these two enzymes. Importantly, we find that the feeding behaviour and the digestive system of midgut in O. furnacalis larvae are closely related and interactive in that knocking down α-amylase or lipase induces a reduction in larval feeding, while food-deprived larvae lead to fewer expressions of α-amylase and lipase. Importantly, it is the gut NPF that regulates the α-amylase and lipase, while variations of α-amylase and lipase may feed back to the brain NPF. This current study reveals a molecular feedback mechanism between feeding behaviour and the digestive system that is regulated by the conserved NPF via insulin signalling systems in the midgut of O. furnacalis larvae.
Investigating the Association between Diabetic Neuropathy and Vitamin D in Emirati Patients with Type 2 Diabetes Mellitus
Authors: Al Ali Tahra , Ashfaq Alizeh , Saheb Sharif-Askari Narjes , Abusnana Salah , Mussa Bashair M.
Published: January 2023

(1) Background: Vitamin D deficiency is a common public health problem in the United Arab Emirates (UAE) and globally, and interestingly, improvements in diabetic neuropathy after taking Vitamin D supplementation for a short time have been reported. Despite living in a country that is sunny all year round, hypovitaminosis D, indicated by an obvious low serum vitamin D level, has been recurrently noted in the UAE, as well as in the surrounding Arabian Gulf countries. This problem is receiving much attention and attracting clinical and academic interest. Therefore, the main objective of the present study is to identify the association, if any, between vitamin D deficiency and the development of diabetic neuropathy in the UAE population with T2DM. (2) Methods: a total of 600 Emirati patients (male and female) with T2DM, aged between 20 and 80, were recruited from University Hospital Sharjah (UHS). The medical records of the patients were reviewed and analyzed. (3) Results: The results of the present study showed that among the 600 patients, 50% were affected with diabetic neuropathy. Vitamin D level in patients with neuropathy were estimated to be around 20 ng/mL (IQR 14–25), and vitamin D levels were significantly higher (33 ng/mL (IQR 20–42)) among patients without neuropathy, with p < 0.001. Another important finding was that patients without neuropathy had a better vitamin D status, with only 19% being deficient and 18% having insufficient vitamin D levels, compared to patients with neuropathy, where 39% were deficient (vitamin D < 20 ng/mL) and 44% had insufficient vitamin D levels (20–30 ng/mL). (4) Conclusion: The findings of the present study show that the prevalence of vitamin D deficiency (low serum 25-hydroxy vitamin D 25-OHD level) is significantly high in diabetic neuropathy in Emirati patients with T2DM.
Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics
Authors: Wood Stephen J. , Kuzel Timothy M. , Shafikhani Sasha H.
Published: January 2023

Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections.
A Live Cell Protein Complementation Assay for ORFeome-Wide Probing of Human HOX Interactomes
Authors: Jia Yunlong , Reboulet Jonathan , Gillet Benjamin , Hughes Sandrine , Forcet Christelle , Tribollet Violaine , Hajj Sleiman Nawal , Kundlacz Cindy , Vanacker Jean-Marc , Bleicher Françoise , Merabet Samir
Published: January 2023

Biological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies the development of tools that allow one to capture transient and low-affinity protein–protein interactions (PPIs) in live conditions. Here we presented an experimental strategy: the Cell-PCA (cell-based protein complementation assay), which was based on bimolecular fluorescence complementation (BiFC) for ORFeome-wide screening of proteins that interact with different bait proteins in the same live cell context, by combining high-throughput sequencing method. The specificity and sensitivity of the Cell-PCA was established by using a wild-type and a single-amino-acid-mutated HOXA9 protein, and the approach was subsequently applied to seven additional human HOX proteins. These proof-of-concept experiments revealed novel molecular properties of HOX interactomes and led to the identification of a novel cofactor of HOXB13 that promoted its proliferative activity in a cancer cell context. Taken together, our work demonstrated that the Cell-PCA was pertinent for revealing and, importantly, comparing the interactomes of different or highly related bait proteins in the same cell context.
The E3 Ligase TRIM25 Impairs Apoptotic Cell Death in Colon Carcinoma Cells via Destabilization of Caspase-7 mRNA: A Possible Role of hnRNPH1
Authors: Nasrullah Usman , Stanke Kristina , Recknagel Victoria , Bozkurt Süleyman , Wurzel Patrick , Gauer Stefan , Imre Gergely , Münch Christian , Pfeilschifter Josef , Eberhardt Wolfgang
Published: January 2023

Therapy resistance is still a major reason for treatment failure in colorectal cancer (CRC). Previously, we identified the E3 ubiquitin ligase TRIM25 as a novel suppressor of caspase-2 translation which contributes to the apoptosis resistance of CRC cells towards chemotherapeutic drugs. Here, we report the executioner caspase-7 as being a further target of TRIM25. The results from the gain- and loss-of-function approaches and the actinomycin D experiments indicate that TRIM25 attenuates caspase-7 expression mainly through a decrease in mRNA stability. The data from the RNA pulldown assays with immunoprecipitated TRIM25 truncations indicate a direct TRIM25 binding to caspase-7 mRNA, which is mediated by the PRY/SPRY domain, which is also known to be highly relevant for protein–protein interactions. By employing TRIM25 immunoprecipitation, we identified the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) as a novel TRIM25 binding protein with a functional impact on caspase-7 mRNA stability. Notably, the interaction of both proteins was highly sensitive to RNase A treatment and again depended on the PRY/SPRY domain, thus indicating an indirect interaction of both proteins which is achieved through a common RNA binding. Ubiquitin affinity chromatography showed that both proteins are targets of ubiquitin modification. Functionally, the ectopic expression of caspase-7 in CRC cells caused an increase in poly ADP-ribose polymerase (PARP) cleavage concomitant with a significant increase in apoptosis. Collectively, the negative regulation of caspase-7 by TRIM25, which is possibly executed by hnRNPH1, implies a novel survival mechanism underlying the chemotherapeutic drug resistance of CRC cells. The targeting of TRIM25 could therefore offer a promising strategy for the reduction in therapy resistance in CRC patients.
Cell Pair Algorithm-Based Immune Infiltrating Cell Signature for Improving Outcomes and Treatment Responses in Patients with Hepatocellular Carcinoma
Authors: Zhang Xiao , Xie Jun , He Dan , Yan Xin , Chen Jian
Published: January 2023

Background: Immune interactions play important roles in the regulation of T cells’ cytotoxic function, further impacting the anti-tumor efficacy of immunotherapy. A comprehensive analysis of immune cell types in HCC and immune-cell-related signatures predicting prognosis and monitoring immunotherapy efficacy is still absent. Methods: More than 1,300 hepatocellular carcinomas (HCC) patients were collected from public databases and included in the present study. The ssGSEA algorithm was applied to calculate the infiltration level of 28 immunocyte subpopulations. A cell pair algorithm was applied to construct an immune-cell-related prognostic index (ICRPI). Survival analyses were performed to measure the survival difference across ICRPI risk groups. Spearman’s correlation analyses were used for the relevance assessment. A Wilcoxon test was used to measure the expression level’s differences. Results: In this study, 28 immune subpopulations were retrieved, and 374 immune cell pairs (ICPs) were established, 38 of which were picked out by the least absolute shrinkage and selection operator (LASSO) algorithm. By using the selected ICPs, the ICRPI was constructed and validated to play crucial roles in survival stratification and dynamic monitoring of immunotherapy effect. We also explored several candidate drugs targeting ICRPI. A composite ICRPI and clinical prognostic index (ICPI) was then constructed, which achieved a more accurate estimation of HCC’s survival and is a better choice for prognosis predictions in HCC. Conclusions: In conclusion, we constructed and validated ICRPI based on the cell pair algorithm in this study, which might provide some novel insights for increasing the survival estimation and clinical response to immune therapy for individual HCC patients and contribute to the personalized precision immunotherapy strategy of HCC.
NFκB-Mediated Expression of Phosphoinositide 3-Kinase δ Is Critical for Mesenchymal Transition in Retinal Pigment Epithelial Cells
Authors: Han Haote , Yang Yanhui , Han Zhuo , Wang Luping , Dong Lijun , Qi Hui , Liu Bing , Tian Jingkui , Vanhaesebroeck Bart , Kazlauskas Andrius , Zhang Guoming , Zhang Shaochong , Lei Hetian
Published: January 2023

Epithelial mesenchymal transition (EMT) plays a vital role in a variety of human diseases including proliferative vitreoretinopathy (PVR), in which retinal pigment epithelial (RPE) cells play a key part. Transcriptomic analysis showed that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was up-regulated in human RPE cells upon treatment with transforming growth factor (TGF)-β2, a multifunctional cytokine associated with clinical PVR. Stimulation of human RPE cells with TGF-β2 induced expression of p110δ (the catalytic subunit of PI3Kδ) and activation of NFκB/p65. CRISPR-Cas9-mediated depletion of p110δ or NFκB/p65 suppressed TGF-β2-induced fibronectin expression and activation of Akt as well as migration of these cells. Intriguingly, abrogating expression of NFκB/p65 also blocked TGF-β2-induced expression of p110δ, and luciferase reporter assay indicated that TGF-β2 induced NFκB/p65 binding to the promoter of the PIK3CD that encodes p110δ. These data reveal that NFκB/p65-mediated expression of PI3Kδ is essential in human RPE cells for TGF-β2-induced EMT, uncovering hindrance of TGF-β2-induced expression of p110δ as a novel approach to inhibit PVR.
Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration
Authors: Varga Attila , Nguyen Minh Tu , Pénzes Kinga , Bátai Bence , Gyulavári Pál , Gurbi Bianka , Murányi József , Csermely Péter , Csala Miklós , Vántus Tibor , Sőti Csaba
Published: January 2023

Prostate cancer metastasis is a significant cause of mortality in men. PKD3 facilitates tumor growth and metastasis, however, its regulation is largely unclear. The Hsp90 chaperone stabilizes an array of signaling client proteins, thus is an enabler of the malignant phenotype. Here, using different prostate cancer cell lines, we report that Hsp90 ensures PKD3 conformational stability and function to promote cancer cell migration. We found that pharmacological inhibition of either PKDs or Hsp90 dose-dependently abrogated the migration of DU145 and PC3 metastatic prostate cancer cells. Hsp90 inhibition by ganetespib caused a dose-dependent depletion of PKD2, PKD3, and Akt, which are all involved in metastasis formation. Proximity ligation assay and immunoprecipitation experiments demonstrated a physical interaction between Hsp90 and PKD3. Inhibition of the chaperone–client interaction induced misfolding and proteasomal degradation of PKD3. PKD3 siRNA combined with ganetespib treatment demonstrated a specific involvement of PKD3 in DU145 and PC3 cell migration, which was entirely dependent on Hsp90. Finally, ectopic expression of PKD3 enhanced migration of non-metastatic LNCaP cells in an Hsp90-dependent manner. Altogether, our findings identify PKD3 as an Hsp90 client and uncover a potential mechanism of Hsp90 in prostate cancer metastasis. The molecular interaction revealed here may regulate other biological and pathological functions.
Notch Blockade Specifically in Bone Marrow-Derived FSP-1-Positive Cells Ameliorates Renal Fibrosis
Authors: Wu Yongdong , Liang Ming , Huang Fengzhang , Cheng Owen H. , Xiao Xiaoguang , Lee Tae Hoon , Truong Luan , Cheng Jizhong
Published: January 2023

Background: The infiltration of inflammatory cells during a kidney injury stimulates myofibroblast activation leading to kidney fibrosis. Fibroblast-specific protein 1 (FSP-1) positive cells have been reported as either myofibroblasts or monocytes during tissue fibrosis. The functions of FSP-1+ cells that are associated with the development of renal fibrosis and the signaling pathways that regulate FSP-1+ cell activation have not been well defined. Methods: In mice with unilateral ureteral obstruction (UUO), we characterized FSP-1+ cells and determined the role of the Notch signaling pathway in the activation of bone marrow-derived FSP-1+ cells during kidney fibrosis. Results: In kidneys from mice with UUO, the FSP-1+ cells accumulated significantly in the tubulointerstitial area. By using immunostaining and FSP-1 reporter mice, we found that FSP-1 was co-stained with inflammatory cell markers, but not myofibroblast markers. Results from mice with bone marrow transplantations showed that FSP-1+ cells in obstructed kidneys represent a bone marrow-derived population of inflammatory cells. In cultured FSP-1+ cells, the inhibition of Notch signaling suppressed the activation and cytokine secretion of FSP-1+ cells that were induced by LPS but not by IL-4. The specific KO or blockade of Notch signaling in bone marrow-derived FSP-1+ cells suppressed UUO-induced ECM deposition, the infiltration of FSP-1+ inflammatory cells, and cytokine production. These responses ameliorated myofibroblast accumulation and renal fibrosis in obstructed kidneys. Conclusion: Our study reveals that most FSP-1+ cells in obstructed kidneys are activated macrophages that are derived from bone marrow and that Notch signaling activates the production of M1 cytokines in FSP-1+ monocytes/macrophages, which is important for renal inflammation and fibrosis.
Neurodevelopmental Disorders (NDDs): Beyond the Clinical Definition and Translational Approach
Authors: Pallanti Stefano , Salerno Luana
Published: January 2023

Neurodevelopmental disorders (NDDs) are complex and heterogeneous disorders that affect the growth and development of the brain and are often associated with impairments in cognitive and motor functions, communication, and adaptive behavior [...]
Aplastic Anemia in Triple X Syndrome
Authors: Aldarwish Mohammed , Alaithan Israa , Alawami Fatimah
Published: January 2023

Triple X syndrome is the most common sex chromosome aneuploidies (SCA) in females. Still, it is underdiagnosed because patients are usually without clear dysmorphism, and the syndrome is not associated with any significant congenital anomalies. We are reporting a case of a 5-year-old girl who presented with aplastic anemia, confirmed by a bone marrow aspiration and biopsy. Her complete workup showed that she has three copies of chromosome X, which, given the diagnosis of triple X syndrome, requires a supportive treatment but not a bone marrow transplant. Few cases of aplastic anemia with sex chromosome abnormalities have been reported. We are reviewing the triple X syndrome in different aspects of the presentation.
Illness Perception and Medication Adherence among Adult Patients with Type 2 Diabetes Mellitus: A Scoping Review
Authors: Alharbi Samaher , Alhofaian Aisha , Alaamri Marym M.
Published: January 2023

(1) Background: Type 2 diabetes mellitus (T2DM) is a global disease with a compelling impact on developed and developing economies across the globe. The World Health Organization (WHO) (2020) reported a global prevalence of 8.5% in 2014 among adults aged at least 18 years. Consequently, the condition led to a 5% increase in premature mortality from 2000 to 2016. Aim: The scoping review sought to examine illness perception and medication adherence among adult patients with T2DM. (2) Methods: The study was conducted in 2021 and covered articles published in English in the last five years. PubMed, MEDLINE, CINAHL, and ScienceDirect were the primary search engines used to generate the required scholarly records. A total of 20 studies met the inclusion criteria. (3) Results: The 20 studies selected for the scoping review covered different themes on the overall concept of illness perception and medication adherence in adults with Type 2 Diabetes Mellitus. Each study presented unique implications for research and influence on the policymaking relating to the treatment or the management of type 2 diabetes mellitus in adults of different aged groups. (4) Conclusions: The studies reveal both high and low adherence to medications in adults with type 2 diabetes mellitus. The management and treatment of the condition depend on the uptake of oral hypoglycemic agents or insulin as well as the recommended therapies to enhance the clinical outcomes of the patients.
A Facile Two-Step PVP-Assisted Deposition of Co-Activated Nanosized Nickel Hydroxide Directly on a Substrate for Large-Scale Production of Supercapacitor Electrodes
Authors: Kotok Valerii , Ondrejka Peter , Mikolášek Miroslav , Sojková Michaela , Novák Patrik , Gregor Maroš , Kovalenko Vadym , Sukhyy Kostyantyn
Published: January 2023

The self-decomposition reaction of the nickel ammonia complex was used for the nickel hydroxide formation on the nickel foam with further modification in several ways. The addition of polyvinyl pyrrolidone (PVP) and the electrochemical or chemical activation with cobalt hydroxide was used to modify the formation method. In all cases, structures with Ni(OH)2 nanoflakes were formed. It was found that the flower-like particles of Co(OH)2 were precipitated during chemical activation among the nanoflakes. It was shown that the presence of PVP during the nickel ammonia complex decomposition suppressed the highly branched particles. The absence of the highly branched particles increased the capacitive properties of the formed electrode at high current densities. The highest capacitance in 1408 F/g at 1 A/g was shown for the sample precipitated with the PVP presence and the further chemical activation by cobalt.
Mechanical Properties, Biocompatibility and Antibacterial Behaviors of TaO0.2N0.8 and TaO0.2N0.8-Ag Nanocomposite Thin Coatings
Authors: Hsieh Jang-Hsing , Li Chuan , Wu Weite , Lai Yi-Hwa , Liao Shu-Chuan , Hu Chih-Chien , Chang Yu-Han
Published: January 2023

TaOx = 0.2Ny = 0.8 was reported previously to have the highest modulus (E), hardness (H), and H to E ratio attributed to the embedment of substituting oxygen atoms in the TaN crystal structure, among some TaOxNy coatings studied. In the present study, TaO0.2N0.8-Ag nanocomposite coatings were fabricated by reactive multi-target sputtering with O/N ratio adjusted to the expected value. The various Ag contents were doped to induce antibacterial behaviors. After deposition and annealing with rapid thermal process (RTP) at 400 °C for 4 min, the coatings’ mechanical and structural properties were studied. After these examinations, the samples were then studied for their cell attachment, cell viability, and biocompatibility with 3-T-3 cells, as well as for their antibacterial behaviors against Escherichia coli. It appeared that hardness and crack resistance could be improved further with suitable amount of Ag doped to the coatings, followed by rapid thermal annealing treatment. The coating with 1.5 at. % Ag had the highest hardness and good H/E ratio. It was also found that the antibacterial efficiency of TaO0.2N0.8-Ag coatings could be much improved, comparing with that of TaO0.2N0.8 coatings. The antibacterial efficiency increased with the increased Ag contents. There was no negative effect of Ag on the biocompatibility of TaO0.2N0.8-Ag. Through the cell attachment and viability testing using MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, it can be summarized that surface roughness could be the dominating factor for cell viability and attachment, which means the improvement of biocompatibility. Accordingly, the samples with 1.5 at. % and 11.0 at. % Ag show the best biocompatibility. The variation of surface roughness was affected by the incorporation of Ag and oxygen atoms after rapid thermal annealing.
Influence of Wax and Silver Nanoparticles on Preservation Quality of Murcott Mandarin Fruit during Cold Storage and after Shelf-Life
Authors: Gemail Mohamed M. , Elesawi Ibrahim Eid , Jghef Muthana M. , Alharthi Badr , Alsanei Woroud A. , Chen Chunli , El-Hefnawi Sayed M. , Gad Mohamed M.
Published: January 2023

Citrus fruits are perishable and considered the most prominent and essential crops at the local and global levels. The world is focused on minimizing fruit postharvest losses, maintaining fruit quality, and prolonging its storability and marketability. Thus, this study was carried out throughout the two successive seasons of 2018 and 2019 on Murcott mandarin fruits, with the purpose of extending their storage period and shelf life by making a mixture of nanosilver and wax as a coating. The fruits were picked on the first of March, washed, and coated with the following treatments: 1000 ppm imazalil (IMZ as a control), wax, 50 ppm nanosilver, 100 ppm nanosilver, and finally, the combination of wax plus 100 ppm nanosilver, packaged in 0.005% perforated polyethylene (PPE), and stored at 5 ± 1 °C and 90%–95% relative humidity for four months. Samples of each treatment were randomly taken at monthly intervals to evaluate the tested treatments’ effects on fruit quality during cold storage and 6 days of shelf life. The data proved that the combination of wax plus 100 ppm nanosilver packaged in 0.005% perforated polyethylene (PPE) was the most effective treatment for reducing discarded fruits, fresh weight loss, and catalase enzyme activity, as well as maintaining pulp firmness and vitamin C content and keeping a better taste panel index. Therefore, these coatings could be promising alternative materials for extending mandarin fruits’ postharvest life and marketing period.