bluuebunny/crossref_metadata_2025 huggingface dataset:
Shell Disorder Models Detect That Omicron Has Harder Shells with Attenuation but Is Not a Descendant of the Wuhan-Hu-1 SARS-CoV-2
Authors: Goh Gerard Kian-Meng , Dunker A. Keith , Foster James A. , Uversky Vladimir N.
Published: April 2022

Before the SARS-CoV-2 Omicron variant emergence, shell disorder models (SDM) suggested that an attenuated precursor from pangolins may have entered humans in 2017 or earlier. This was based on a shell disorder analysis of SARS-CoV-1/2 and pangolin-Cov-2017. The SDM suggests that Omicron is attenuated with almost identical N (inner shell) disorder as pangolin-CoV-2017 (N-PID (percentage of intrinsic disorder): 44.8% vs. 44.9%—lower than other variants). The outer shell disorder (M-PID) of Omicron is lower than that of other variants and pangolin-CoV-2017 (5.4% vs. 5.9%). COVID-19-related CoVs have the lowest M-PIDs (hardest outer shell) among all CoVs. This is likely to be responsible for the higher contagiousness of SARS-CoV-2 and Omicron, since hard outer shell protects the virion from salivary/mucosal antimicrobial enzymes. Phylogenetic study using M reveals that Omicron branched off from an ancestor of the Wuhan-Hu-1 strain closely related to pangolin-CoVs. M, being evolutionarily conserved in COVID-19, is most ideal for COVID-19 phylogenetic study. Omicron may have been hiding among burrowing animals (e.g., pangolins) that provide optimal evolutionary environments for attenuation and increase shell hardness, which is essential for fecal–oral–respiratory transmission via buried feces. Incoming data support SDM e.g., the presence of fewer infectious particles in the lungs than in the bronchi upon infection.
A Novel High-Throughput Assay Reveals That the Temperature Induced Increases in Transphosphatidylation of Phospholipase D Are Dependent on the Alcohol Acceptor Concentration
Authors: Yang Hengzhang , Woscholski Rüdiger
Published: April 2022

Phospholipase D reacts with alcohols or water, transphosphatidylating or hydrolysing lipids such as phosphatidylcholine, generating phosphatidylalcohols or phosphatidic acid, respectively. The enzyme has been employed in many applications making use of the transphosphatidylation reaction and the enzyme’s tolerance for organic solvents in order to synthesize natural and artificial phospholipids. Yet, its catalytic properties with respect to the transphosphatidylation reaction are not well understood. Here, we introduce a novel high-throughput assay, making use of 96-well plates, that employs Fluorescamine for the detection of transphosphatidylated amino alcohols. This assay allowed to monitor the KM and VMax at different temperatures, revealing that the former will be elevated by the temperature, while the latter is increased by a combination of both temperature and alcohol acceptor concentration being elevated, suggesting that increase in temperature may open up a new binding site for the alcohol acceptor.
Administration of Hookworm Excretory/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes
Authors: Khudhair Zainab , Alhallaf Rafid , Eichenberger Ramon M. , Field Matt , Krause Lutz , Sotillo Javier , Loukas Alex
Published: April 2022

Diabetes is recognised as the world’s fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insulin resistance, we treated mice fed on normal or diabetes-promoting diets with excretory/secretory products (ES) from the gastrointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycaemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune response measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the community composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and suggest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.
Anti-Protease Activity Deficient Secretory Leukocyte Protease Inhibitor (SLPI) Exerts Cardioprotective Effect against Myocardial Ischaemia/Reperfusion
Authors: Mongkolpathumrat Podsawee , Kijtawornrat Anusak , Suwan Eukote , Unajak Sasimanas , Panya Aussara , Pusadee Tonapha , Kumphune Sarawut
Published: April 2022

Inhibition of proteases shows therapeutic potential. Our previous studies demonstrated the cardioprotection by the Secretory Leukocyte Protease Inhibitor (SLPI) against myocardial ischaemia/reperfusion (I/R) injury. However, it is unclear whether the cardioprotective effect of SLPI seen in our previous works is due to the inhibition of protease enzymes. Several studies demonstrate that the anti-protease independent activity of SLPI could provide therapeutic benefits. Here, we show for the first time that recombinant protein of anti-protease deficient mutant SLPI (L72K, M73G, L74G) (mt-SLPI) could significantly reduce cell death and intracellular reactive oxygen species (ROS) production against an in vitro simulated I/R injury. Furthermore, post-ischaemic treatment of mt-SLPI is found to significantly reduce infarct size and cardiac biomarkers lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity, improve cardiac functions, attenuate I/R induced-p38 MAPK phosphorylation, and reduce apoptotic regulatory protein levels, including Bax, cleaved-Caspase-3 and total Capase-8, in rats subjected to an in vivo I/R injury. Additionally, the beneficial effect of mt-SLPI was not significantly different from the wildtype (wt-SLPI). In summary, SLPI could provide cardioprotection without anti-protease activity, which could be more clinically beneficial in terms of providing cardioprotection without interfering with basal serine protease activity.
Intra-Articular Injection of Platelet-Rich Plasma Is More Effective than Hyaluronic Acid or Steroid Injection in the Treatment of Mild to Moderate Knee Osteoarthritis: A Prospective, Randomized, Triple-Parallel Clinical Trial
Authors: Szwedowski Dawid , Mobasheri Ali , Moniuszko Andrzej , Zabrzyński Jan , Jeka Sławomir
Published: April 2022

Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly assigned to one of three groups receiving a single injection of either leukocyte-poor platelet-rich plasma (25 knees), hyaluronic acid (25 knees), or glucocorticosteroid (25 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was collected at baseline and 6, 12, and 26 weeks after treatment. Results: After 6 weeks of PRP administration, a decrease in the mean WOMAC value was observed in all three study groups. Three months after administration, the greatest decrease in the mean WOMAC value was obtained in the PRP group. The results in the HA and CS groups were similar (p = 0.681). In the one-way analysis of variance and post hoc analysis using the HSD Tukey test, a significantly greater improvement was shown by comparing the PRP and CS groups (p = 0.001), and the PRP and HA groups (p = 0.010). After intra-articular injection of CS, the reduction in pain was greatest 6 weeks after administration, and the mean value was the lowest among all groups. During subsequent visits, the value of the pain subscale increased, and after 6 months, it was the highest among the studied groups. Using the Wilcoxon paired test, no PRP effect was found to reduce stiffness at the 6-month follow-up (p = 0.908). Functional improvement was achieved in all groups, i.e., a decrease in the value of this subscale 6 months after administration. The largest decrease was seen in the group that received PRP (p < 0.001) and then in the HA group. The smallest decrease among the investigated methods was shown in the CS group. Conclusions: Intra-articular injections of PRP can provide clinically significant functional improvement for at least 6 months in patients with mild to moderate KOA which is superior to HA or CS injections.
Repetitive Transcranial Magnetic Stimulation (rTMS) of Dorsolateral Prefrontal Cortex May Influence Semantic Fluency and Functional Connectivity in Fronto-Parietal Network in Mild Cognitive Impairment (MCI)
Authors: Esposito Sabrina , Trojsi Francesca , Cirillo Giovanni , de Stefano Manuela , Di Nardo Federica , Siciliano Mattia , Caiazzo Giuseppina , Ippolito Domenico , Ricciardi Dario , Buonanno Daniela , Atripaldi Danilo , Pepe Roberta , D’Alvano Giulia , Mangione Antonella , Bonavita Simona , Santangelo Gabriella , Iavarone Alessandro , Cirillo Mario , Esposito Fabrizio , Sorbi Sandro , Tedeschi Gioacchino
Published: April 2022

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer’s disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks (n = 11), and the other received sham stimulation (n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency (p = 0.026) and visuo-spatial (p = 0.014) performances and increased FC within the salience network (p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network (p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain.
Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)/Drug-Induced Hypersensitivity Syndrome (DiHS)—Readdressing the DReSS
Authors: Stirton Hannah , Shear Neil H. , Dodiuk-Gad Roni P.
Published: April 2022

Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe, systemic, T cell mediated drug reaction with combinations of cutaneous, hematologic, and internal organ involvement. Pathogenesis of DReSS is multi-factorial, involving drug-exposure, genetic predisposition through specific human leukocyte antigen (HLA) alleles and metabolism defects, viral reactivation, and immune dysregulation. Clinical features of this condition are delayed, stepwise, and heterogenous, making this syndrome challenging to recognize and diagnose. Two sets of validated diagnostic criteria exist that can be employed to diagnose DReSS/DiHS. Methods to improve early recognition of DReSS and predict disease severity has been a recent area of research focus. In vitro and in vivo tests can be employed to confirm the diagnosis and help identify culprit drugs. The mainstay treatment of DReSS is prompt withdrawal of the culprit drug, supportive treatment, and immunosuppression depending on the severity of disease. We present a comprehensive review on the most recent research and literature on DReSS, with emphasis on pathogenesis, clinical features, diagnosis, confirmatory testing modalities, and treatment. Additionally, this summary aims to highlight the differing viewpoints on this severe disease and broaden our perspective on the condition known as DReSS.
Parkinson’s Disease and SARS-CoV-2 Infection: Particularities of Molecular and Cellular Mechanisms Regarding Pathogenesis and Treatment
Authors: Anghelescu Aurelian , Onose Gelu , Popescu Cristina , Băilă Mihai , Stoica Simona , Postoiu Ruxandra , Brumă Elena , Petcu Irina , Ciobanu Vlad , Munteanu Constantin
Published: April 2022

Accumulating data suggest that chronic neuroinflammation-mediated neurodegeneration is a significant contributing factor for progressive neuronal and glial cell death in age-related neurodegenerative pathology. Furthermore, it could be encountered as long-term consequences in some viral infections, including post-COVID-19 Parkinsonism-related chronic sequelae. The current systematic review is focused on a recent question aroused during the pandemic’s successive waves: are there post-SARS-CoV-2 immune-mediated reactions responsible for promoting neurodegeneration? Does the host’s dysregulated immune counter-offensive contribute to the pathogenesis of neurodegenerative diseases, emerging as Parkinson’s disease, in a complex interrelation between genetic and epigenetic risk factors? A synthetic and systematic literature review was accomplished based on the ”Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses” (PRISMA) methodology, including registration on the specific online platform: International prospective register of systematic reviews—PROSPERO, no. 312183. Initially, 1894 articles were detected. After fulfilling the five steps of the selection methodology, 104 papers were selected for this synthetic review. Documentation was enhanced with a supplementary 47 bibliographic resources identified in the literature within a non-standardized search connected to the subject. As a final step of the PRISMA method, we have fulfilled a Population-Intervention-Comparison-Outcome-Time (PICOT)/Population-Intervention-Comparison-Outcome-Study type (PICOS)—based metanalysis of clinical trials identified as connected to our search, targeting the outcomes of rehabilitative kinesitherapeutic interventions compared to clinical approaches lacking such kind of treatment. Accordingly, we identified 10 clinical trials related to our article. The multi/interdisciplinary conventional therapy of Parkinson’s disease and non-conventional multitarget approach to an integrative treatment was briefly analyzed. This article synthesizes the current findings on the pathogenic interference between the dysregulated complex mechanisms involved in aging, neuroinflammation, and neurodegeneration, focusing on Parkinson’s disease and the acute and chronic repercussions of COVID-19. Time will tell whether COVID-19 neuroinflammatory events could trigger long-term neurodegenerative effects and contribute to the worsening and/or explosion of new cases of PD. The extent of the interrelated neuropathogenic phenomenon remains obscure, so further clinical observations and prospective longitudinal cohort studies are needed.
Looking for the Holy Grail—Drug Candidates for Glioblastoma Multiforme Chemotherapy
Authors: Pająk Beata
Published: April 2022

Glioblastoma multiforme (GBM) is the deadliest and the most heterogeneous brain cancer. The median survival time of GBM patients is approximately 8 to 15 months after initial diagnosis. GBM development is determined by numerous signaling pathways and is considered one of the most challenging and complicated-to-treat cancer types. Standard GBM therapy consist of surgery followed by radiotherapy or chemotherapy, and combined treatment. Current standard of care (SOC) does not offer a significant chance for GBM patients to combat cancer, and the selection of available drugs is limited. For almost 20 years, there has been only one drug, Temozolomide (TMZ), approved as a first-line GBM treatment. Due to the limited efficacy of TMZ and the high rate of resistant patients, the implementation of new chemotherapeutics is highly desired. However, due to the unique properties of GBM, many challenges still need to be overcome before reaching a ‘breakthrough’. This review article describes the most recent compounds introduced into clinical trials as drug candidates for GBM chemotherapy.
Exploring the Utility of NK Cells in COVID-19
Authors: Deng Xuewen , Terunuma Hiroshi , Nieda Mie
Published: April 2022

Coronavirus disease 2019 (COVID-19) can manifest as acute respiratory distress syndrome and is associated with substantial morbidity and mortality. Extensive data now indicate that immune responses to SARS-CoV-2 infection determine the COVID-19 disease course. A wide range of immunomodulatory agents have been tested for the treatment of COVID-19. Natural killer (NK) cells play an important role in antiviral innate immunity, and anti-SARS-CoV-2 activity and antifibrotic activity are particularly critical for COVID-19 control. Notably, SARS-CoV-2 clearance rate, antibody response, and disease progression in COVID-19 correlate with NK cell status, and NK cell dysfunction is linked with increased SARS-CoV-2 susceptibility. Thus, NK cells function as the key element in the switch from effective to harmful immune responses in COVID-19. However, dysregulation of NK cells has been observed in COVID-19 patients, exhibiting depletion and dysfunction, which correlate with COVID-19 severity; this dysregulation perhaps contributes to disease progression. Given these findings, NK-cell-based therapies with anti-SARS-CoV-2 activity, antifibrotic activity, and strong safety profiles for cancers may encourage the rapid application of functional NK cells as a potential therapeutic strategy to eliminate SARS-CoV-2-infected cells at an early stage, facilitate immune–immune cell interactions, and favor inflammatory processes that prevent and/or reverse over-inflammation and inhibit fibrosis progression, thereby helping in the fight against COVID-19. However, our understanding of the role of NK cells in COVID-19 remains incomplete, and further research on the involvement of NK cells in the pathogenesis of COVID-19 is needed. The rationale of NK-cell-based therapies for COVID-19 has to be based on the timing of therapeutic interventions and disease severity, which may be determined by the balance between beneficial antiviral and potential detrimental pathologic actions. NK cells would be more effective early in SARS-CoV-2 infection and prevent the progression of COVID-19. Immunomodulation by NK cells towards regulatory functions could be useful as an adjunct therapy to prevent the progression of COVID-19.
Effect of Composition Strategies on Mycelium-Based Composites Flexural Behaviour
Authors: Rigobello Adrien , Colmo Claudia , Ayres Phil
Published: April 2022

Mycelium-based composites (MBC) are a promising class of relatively novel materials that leverage mycelium colonisation of substrates. Being predicated on biological growth, rather than extraction based material sourcing from the geosphere, MBC are garnering attention as potential alternatives for certain fossil-based materials. In addition, their protocols of production point towards more sustainable and circular practices. MBC remains an emerging practice in both production and analysis of materials, particularly with regard to standardisation and repeatability of protocols. Here, we show a series of flexural tests following ASTM D1037, reporting flexural modulus and flexural modulus of rupture. To increase the mechanical proprieties, we contribute with an approach that follows the composition strategy of reinforcement by considering fibre topology and implementing structural components to the substrate. We explore four models that consist of a control group, the integration of inner hessian, hessian jacketing and rattan fibres. Apart from the inner hessian group, the introduction of rattan fibres and hessian jacketing led to significant increases in both strength and stiffness (α = 0.05). The mean of the flexural modulus for the most performative rattan series (1.34 GPa) is still close to three times lower than that of Medium-Density Fibreboard, and approximately 16 times lower in modulus of rupture. A future investigation could focus on developing a hybrid strategy of composition and densification so as to improve aggregate interlocking and resulting strength and stiffness.
Assessment of Contributing Factors and Treatment Practices for Therapeutic Efficacy and Drug-Related Problems in Suicidal Psychotic Patients
Authors: Shahzad Saimon , Ullah Sami , Nazar Zahid , Riaz Muhammad , Khuda Fazli , Khalil Atif Ali Khan , Almutairi Mikhlid H. , Sayed Amany A. , Büyüker Sultan Mehtap , Khan Nazimuddin
Published: April 2022

Suicide, a deliberate act of self-harm with the intention to die, is an emerging health concern but, unfortunately, the most under-researched subject in Pakistan, especially in Khyber Pukhtunkhwa (KPK). In this study, we aimed to identify risk factors that can be associated with suicidal behavior (SB) and to evaluate the prevailing treatment practices for therapeutic efficacy and drug-related problems (DRPs) in psychotic patients among the local population of KPK. A prospective, multicenter study was conducted for suicidal cases admitted to the study centers by randomized sampling. Socio-demographics and data on suicidal behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), socioeconomic condition by Kuppuswamy socioeconomic scale (KSES) and treatment adherence by Morisky Medication-Taking Adherence Scale (MMAS-4). Drug-related problems and the therapeutic efficacy of prevailing treatment practices were assessed at baseline and follow-up after 3 months of treatment provided. Regarding suicidality (N = 128), females reported more ideations (63.1%), while males witnessed more suicidal behavior (66.6%, p < 0.001). Suicide attempters were mostly married (55.6%, p < 0.002); highly educated (53.9%, p = 0.004); dissatisfied with their life and had a previous history (p < 0.5) of suicide attempt (SA) (20.6%), self-injurious behavior (SIB) (39.7%) and interrupted (IA) or aborted attempts (AA) (22.2%). A greater improvement was observed in patients receiving combination therapy (p = 0.001) than pharmacotherapy (p = 0.006) or psychotherapy (p = 0.183), alone. DRPs were also detected, including drug-selection problems (17.88%), dose-related problems (20.64%), potential drug–drug interactions (24.31%), adverse drug reactions (11.46%) and other problems like inadequate education and counseling (21.55%). Furthermore, it was also found that psychotic patients with suicidal ideations (SI) were significantly (p = 0.01) more adherent to the treatment as compared to those with suicidal attempts. We concluded that suicide attempters differed significantly from patients with suicidal ideations in psychotic patients and presented with peculiar characteristics regarding socio-demographic factors. A combination of therapies and adherence to the treatment provided better outcomes, and targeted interventions are warranted to address drug-related problems.
FLAIRectomy: Resecting beyond the Contrast Margin for Glioblastoma
Authors: Haddad Alexander F. , Young Jacob S. , Morshed Ramin A. , Berger Mitchel S.
Published: April 2022

The standard of care for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is maximal resection followed by chemotherapy and radiation. Studies investigating the resection of GBM have primarily focused on the contrast enhancing portion of the tumor on magnetic resonance imaging. Histopathological studies, however, have demonstrated tumor infiltration within peri-tumoral fluid-attenuated inversion recovery (FLAIR) abnormalities, which is often not resected. The histopathology of FLAIR and local recurrence patterns of GBM have prompted interest in the resection of peri-tumoral FLAIR, or FLAIRectomy. To this point, recent studies have suggested a significant survival benefit associated with safe peri-tumoral FLAIR resection. In this review, we discuss the evidence surrounding the composition of peri-tumoral FLAIR, outcomes associated with FLAIRectomy, future directions of the field, and potential implications for patients.
Application of Wasted and Recycled Materials for Production of Stabilized Layers of Road Structures
Authors: Marinković Milan , Zavadskas Edmundas Kazimieras , Matić Bojan , Jovanović Stanislav , Das Dillip Kumar , Sremac Siniša
Published: April 2022

The construction industry, as one of the most complex sectors, depends on using wasted and recycled materials, timely decision-making, and adequate execution of all activities in supply chains. This paper presents tests of mixtures for cold in-place recycling where existing material is used. In this research, we used cement and bitumen emulsion as well as fly ash, zeolite, slag, and Bakelite. A total of seven mixtures were tested in order to increase sustainability. It was tested the indirect tensile strength and dynamic modulus of elasticity after seven and 28 days for dry specimens, after 28 days for water-saturated specimens and for specimens exposed to frost. After completing the tests using the MEREC (MEthod based on the Removal Effects of Criteria) and CoCoSo (Combined Compromise Solution) multi-criteria model, mixtures were evaluated and ranked in terms of mechanical properties, price, and environmental protection. Considering the ranking of mixtures using the CoCoSo method, the highest quality mixtures, for most combinations of weight factors, are mixtures with slag, mixtures with fly ash, and mixtures with 2% of cement and 2% of bitumen emulsion. Sensitivity analysis was also performed with new simulated values of the criteria in order to determine the individual influence of the criteria on the ranking of mixtures. The conclusions are as follows: the use of bitumen emulsion, cement, waste materials, and other materials in cold recycling would reduce the cost of recycling pavement structures, increase environmental protection, while the mechanical properties of the pavement structures are within acceptable limits.
Quality Management Framework for Housing Construction in a Design-Build Project Delivery System: A BIM-UAV Approach
Authors: Faraji Amir , Rashidi Maria , Meydani Haji Agha Tahereh , Rahnamayiezekavat Payam , Samali Bijan
Published: April 2022

Quality management in project administration can affect the costs and schedule of a project considerably. The immediate notable result of unacceptable quality in a construction project is the “dissatisfied client.” which can be interpreted as “customer loss”. Additionally, defective work is a synonym for problems such as dispute, because items of non-compliance with early agreements can be considered the main factor in triggering claims by the client. The integrated use of two modern technologies, namely Building Information Modeling (BIM) and Unmanned Aerial Vehicles (UAV) is proposed in this study to support project quality management (PQM). This study aims to develop the theoretical underpinnings to provide a quality management framework, formed by BIM-UAV, for housing projects in design-build (D&B) contracts. For this purpose, in the first step the causes of client dissatisfaction rooted in quality concerns were identified in two phases of design and construction. The next step was dedicated to the mapping of BIM-UAV capacities to address the identified causes of dissatisfaction of the client. In the final step, expert opinion was obtained to integrate the BIM-UAV capacities to the quality management framework. The findings and main contribution of this study to the body of knowledge is a guide for design-builders to implement BIM-UAV as an innovative quality management solution to improve their services and to gain the maximum level of client satisfaction, focusing on house building.
Laser-Assisted Growth of Carbon-Based Materials by Chemical Vapor Deposition
Authors: Odusanya Abiodun , Rahaman Imteaz , Sarkar Pallab Kumar , Zkria Abdelrahman , Ghosh Kartik , Haque Ariful
Published: April 2022

Carbon-based materials (CBMs) such as graphene, carbon nanotubes (CNT), highly ordered pyrolytic graphite (HOPG), and pyrolytic carbon (PyC) have received a great deal of attention in recent years due to their unique electronic, optical, thermal, and mechanical properties. CBMs have been grown using a variety of processes, including mechanical exfoliation, pulsed laser deposition (PLD), and chemical vapor deposition (CVD). Mechanical exfoliation creates materials that are irregularly formed and tiny in size. On the other hand, the practicality of the PLD approach for large-area high-quality CMB deposition is quite difficult. Thus, CVD is considered as the most effective method for growing CBMs. In this paper, a novel pulsed laser-assisted chemical vapor deposition (LCVD) technique was explored to determine ways to reduce the energy requirements to produce high quality CBMs. Different growth parameters, such as gas flow rate, temperature, laser energy, and deposition time were considered and studied thoroughly to analyze the growth pattern. CBMs are grown on Si and Cu substrates, where we find better quality CBM films on Cu as it aids the surface solubility of carbon. Raman spectroscopy confirms the presence of high-quality PyC which is grown at a temperature of 750 °C, CH4 gas flow rate of 20 sccm, a laser frequency of 10 Hz, and an energy density of 0.116 J/cm2 per pulse. It is found that the local pulsed-laser bombardment helps in breaking the carbon-hydrogen bonds of CH4 at a much lower substrate temperature than its thermal decomposition temperature. There is no significant change in the 2D peak intensity in the Raman spectrum with the further increase in temperature which is the indicator of the number of the graphene layer. The intertwined graphene flakes of the PyC are observed due to the surface roughness, which is responsible for the quenching in the Raman 2D signal. These results will provide the platform to fabricate a large area single layer of graphene, including the other 2D materials, on different substrates using the LCVD technique.
Synthesis, Characterization, and Catalytic Activity of Nickel Sulfided Catalysts for the Dehydrogenation of Propane: Effect of Sulfiding Agent and Sulfidation Temperature
Authors: Tahier Tayyibah , Mohiuddin Ebrahim , Botes Alicia , Frazenburg Madelaine , Botha Subelia , Mdleleni Masikana M.
Published: April 2022

The effect of sulfiding agent and sulfidation temperature on nickel catalysts supported on MgAl2O4 were investigated for propane dehydrogenation. The catalysts were prepared by reduction of NiO/MgAl2O4, followed by sulfidation using (NH4)2SO4 (S1), (NH4)2S (S2), and DMSO (S3) as sulfiding agents. The catalysts were sulfided at 200 °C, 400 °C, and 550 °C to form Ni/MgAl2O4-Sx-y, where x and y represent the sulfiding agent and sulfidation temperature, respectively. Physiochemical properties of the catalysts were characterized by XRD, BET, SEM, TEM, and TGA to investigate the type of nickel-sulfur species, surface area, morphology, particle size, and stability of the catalysts. Structural and textural properties revealed that the anion present on the sulfiding agent as well as the sulfidation temperature affect both the type and the strength of the Ni-S species. For the S1 catalysts, the SO42− ion interacted with the support to form MgSO4, while the S2− ion on the S2 and S3 catalysts was responsible for the formation of the Ni3S2 phase. The sulfidation temperature contributed to the %S present on each catalyst. Although the catalysts sulfided by S3 contained the least %S, Ni/MgAl2O4-S3-550 displayed the best catalytic performance as a result of the higher particle dispersion and stronger Ni-S interaction compared to S1 and S2 catalysts.
Effect of the Heterovalent Doping of TiO2 with Sc3+ and Nb5+ on the Defect Distribution and Photocatalytic Activity
Authors: Murzin Petr D. , Rudakova Aida V. , Emeline Alexei V. , Bahnemann Detlef W.
Published: April 2022

Two series of Sc3+- and Nb5+-doped TiO2 (rutile) samples were synthesized and characterized by SEM, ICPE spectroscopy, XPS, and BET methods. Photocatalytic activity of the doped TiO2 samples was tested in photocatalytic degradation of phenol. Dependences of the photocatalytic activities of the doped TiO2 samples demonstrate a volcano-like behavior, indicating the existence of the optimal dopant concentrations to achieve the highest activity of photocatalysts. Remarkably, the optimal dopant concentrations correspond to the extrema observed in work function dependences on the dopant concentrations, that indicates a significant energy redistribution of the defect states within the bandgap of TiO2. Such a redistribution of the defect states is also proven by the alterations of the optical and EPR spectra of the intrinsic Ti3+ defect states in TiO2. Based on the analysis of the experimental results, we conclude that both Sc3+ and Nb5+ doping of TiO2 results in redistribution of the defect states and the optimal dopant concentrations correspond to the defect structures, which are ineffective in charge carrier recombination, that ultimately leads to the higher photocatalytic activity of doped TiO2.
Synthesis, Structure, and Photocatalytic Activity of TiO2-Montmorillonite Composites
Authors: Zhang Yonghui , Miao Baoji , Chen Qiuling , Bai Zhiming , Cao Yange , Davaa Basandorj
Published: April 2022

In the present study, TiO2-montmorillonite (MMT) composites were synthesized hydrothermally under variable conditions, including the TiO2/MMT mass ratio, reaction pH, reaction temperature, and dwelling time. These samples were determined by X-ray photoelectron spectrometry (XPS), ultraviolet–visible spectroscopy% (UV-Vis DRS), electrochemical impedance spectroscopy (EIS), transient photocurrent responses, photoluminescence (PL) spectra, electron paramagnetic resonance (EPR), and N2 adsorption–desorption isotherms. The photocatalytic activity was evaluated as the ability to promote the visible-light-driven degradation of 30 mg/L of aqueous methylene blue, which was maximized for the composite with a TiO2 mass ratio of 30 wt% prepared at a pH of 6, a reaction temperature of 160 °C, and a dwelling time of 24 h (denoted as 30%-TM), which achieved a methylene blue removal efficiency of 95.6%, which was 4.9 times higher than that of pure TiO2. The unit cell volume and crystallite size of 30%-TM were 92.43 Å3 and 9.28 nm, respectively, with a relatively uniform distribution of TiO2 particles on the MMT’s surface. In addition, 30%-TM had a large specific surface area, a strong light absorption capacity, and a high Ti3+ content among the studied catalysts. Thus, the present study provides a basis for the synthesis of composites with controlled structures.
Transcriptome Reveals Granulosa Cells Coping through Redox, Inflammatory and Metabolic Mechanisms under Acute Heat Stress
Authors: Sammad Abdul , Luo Hanpeng , Hu Lirong , Zhu Huabin , Wang Yachun
Published: April 2022

Heat stress affects granulosa cells (GCs) and the ovarian follicular microenvironment, causing poor oocyte developmental competence and fertility. This study aimed to investigate the physical responses and global transcriptomic changes in bovine GCs to acute heat stress (43 °C for 2 h) in vitro. Heat-stressed GCs exhibited transient proliferation senescence and resumed proliferation at 48 h post-stress, while post-stress immediate culture-media change had a relatively positive effect on proliferation resumption. Increased accumulation of reactive oxygen species and apoptosis was observed in the heat-stress group. In spite of the upregulation of inflammatory (CYCS, TLR2, TLR4, IL6, etc.), pro-apoptotic (BAD, BAX, TNFSF9, MAP3K7, TNFRSF6B, FADD, TRADD, RIPK3, etc.) and caspase executioner genes (CASP3, CASP8, CASP9), antioxidants and anti-apoptotic genes (HMOX1, NOS2, CAT, SOD, BCL2L1, GPX4, etc.) were also upregulated in heat-stressed GCs. Progesterone and estrogen hormones, along with steroidogenic gene expression, declined significantly, in spite of the upregulation of genes involved in cholesterol synthesis. Out of 12,385 differentially expressed genes (DEGs), 330 significant DEGs (75 upregulated, 225 downregulated) were subjected to KEGG functional pathway annotation, gene ontology enrichment, STRING network analyses and manual querying of DEGs for meaningful molecular mechanisms. High inflammatory response was found to be responsible for oxidative-stress-mediated apoptosis of GCs and nodes towards the involvement of the NF-κB pathway and repression of the Nrf2 pathway. Downregulation of MDM4, TP53, PIDD1, PARP3, MAPK14 and MYC, and upregulation of STK26, STK33, TGFB2, CDKN1A and CDKN2A, at the interface of the MAPK and p53 signaling pathway, can be attributed to transient cellular senescence and apoptosis in GCs. The background working of the AMPK pathway through upregulation of AKT1, AMPK, SIRT1, PYGM, SLC2A4 and SERBP1 genes, and downregulation of PPARGCIA, IGF2, PPARA, SLC27A3, SLC16A3, TSC1/2, KCNJ2, KCNJ16, etc., evidence the repression of cellular transcriptional activity and energetic homeostasis modifications in response to heat stress. This study presents detailed responses of acute-heat-stressed GCs at physical, transcriptional and pathway levels and presents interesting insights into future studies regarding GC adaptation and their interaction with oocytes and the reproductive system at the ovarian level.
Rhodnius prolixus Hemolymph Immuno-Physiology: Deciphering the Systemic Immune Response Triggered by Trypanosoma cruzi Establishment in the Vector Using Quantitative Proteomics
Authors: Ouali Radouane , Vieira Larissa Rezende , Salmon Didier , Bousbata Sabrina
Published: April 2022

Understanding the development of Trypanosoma cruzi within the triatomine vector at the molecular level should provide novel targets for interrupting parasitic life cycle and affect vectorial competence. The aim of the current study is to provide new insights into triatomines immunology through the characterization of the hemolymph proteome of Rhodnius prolixus, a major Chagas disease vector, in order to gain an overview of its immune physiology. Surprisingly, proteomics investigation of the immunomodulation of T. cruzi-infected blood reveals that the parasite triggers an early systemic response in the hemolymph. The analysis of the expression profiles of hemolymph proteins from 6 h to 24 h allowed the identification of a broad range of immune proteins expressed already in the early hours post-blood-feeding regardless of the presence of the parasite, ready to mount a rapid response exemplified by the significant phenol oxidase activation. Nevertheless, we have also observed a remarkable induction of the immune response triggered by an rpPGRP-LC and the overexpression of defensins 6 h post-T. cruzi infection. Moreover, we have identified novel proteins with immune properties such as the putative c1q-like protein and the immunoglobulin I-set domain-containing protein, which have never been described in triatomines and could play a role in T. cruzi recognition. Twelve proteins with unknown function are modulated by the presence of T. cruzi in the hemolymph. Determining the function of these parasite-induced proteins represents an exciting challenge for increasing our knowledge about the diversity of the immune response from the universal one studied in holometabolous insects. This will provide us with clear answers for misunderstood mechanisms in host–parasite interaction, leading to the development of new generation strategies to control vector populations and pathogen transmission.
In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A mRNA Expression and a Correlation Analysis in Kidney Cancer
Authors: Rudzinska-Radecka Magdalena , Frolova Anastasia S. , Balakireva Anastasia V. , Gorokhovets Neonila V. , Pokrovsky Vadim S. , Sokolova Darina V. , Korolev Dmitry O. , Potoldykova Natalia V. , Vinarov Andrey Z. , Parodi Alessandro , Zamyatnin Andrey A.
Published: April 2022

The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant CTSB and STFA increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.
The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth
Authors: Dultz Elisa , Wojtynek Matthias , Medalia Ohad , Onischenko Evgeny
Published: April 2022

Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle.
SARS-CoV-2 Attacks in the Brain: Focus on the Sialome
Authors: Wielgat Przemyslaw , Narejko Karolina , Car Halina
Published: April 2022

The epidemiological observations suggest that respiratory and gastrointestinal symptoms caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) are accompanied by short- and long-term neurological manifestations. There is increasing evidence that the neuroinvasive potential of SARS-CoV-2 is closely related to its capacity to interact with cell membrane sialome. Given the wide expression of sialylated compounds of cell membranes in the brain, the interplay between cell membrane sialoglycans and the virus is crucial for its attachment and cell entry, transport, neuronal damage and brain immunity. Here, we focus on the significance of the brain sialome in the progress of coronavirus disease 2019 (COVID-19) and SARS-CoV-2-induced neuropathology.
Overexpression of Renin-B Induces Warburg-like Effects That Are Associated with Increased AKT/mTOR Signaling
Authors: Golchert Janine , Staar Doreen , Bennewitz Jonathan , Hartmann Miriam , Hoffmann Nadin , Ameling Sabine , Völker Uwe , Peters Jörg , Wanka Heike
Published: April 2022

The classical secretory renin-a is known to be involved in angiotensin generation, thereby regulating not only blood pressure, but also promoting oxidative stress as well as apoptotic and necrotic cell death. In contrast, another cytosolic renin isoform named renin-b has been described, exerting protective effects under ischemia-related conditions in H9c2 cardiomyoblasts. Using microarray-based transcriptome analyses, we aimed to identify the signaling pathways involved in mediating cardioprotection in H9c2 cells overexpressing renin-b. By transcriptome profiling, we identified increased gene expression of several genes encoding glycolytic enzymes and glucose transporters, while the transcript levels of TCA-cycle enzymes were decreased. Complementing data from metabolic analyses revealed enhanced glucose consumption and lactate accumulation due to renin-b overexpression. Renin-b overexpression further stimulated AKT/mTOR signaling, where numerous genes involved in this pathway showed altered transcript levels. For AKT, we also detected enhanced phosphorylation levels by means of Western blotting, suggesting an activation of this kinase. Moreover, analysis of the ROS levels identified an increase in ROS accumulation in renin-b-overexpressing cells. Altogether, our data demonstrate that renin-b overexpression induces the metabolic remodeling of H9c2 cells similar to that seen under oxygen deprivation. This metabolic phenotype exerting so-called aerobic glycolysis is also known as the Warburg effect.
Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D3
Authors: Bernicke Birthe , Engelbogen Nils , Klein Katharina , Franzenburg Jeanette , Borzikowsky Christoph , Peters Christian , Janssen Ottmar , Junker Ralf , Serrano Ruben , Kabelitz Dieter
Published: April 2022

In addition to its role in bone metabolism, vitamin D3 exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D3 levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity. We studied the seasonal fluctuation of γδ T cells, the possible influence of vitamin D3, and the effect of the active metabolite 1α,25(OH)2D3 on the in vitro activation of human γδ T cells. In a retrospective analysis with 2625 samples of random blood donors, we observed higher proportions of γδ T cells in winter when compared with summer. In a prospective study over one year with a small cohort of healthy adults who did or did not take oral vitamin D3 supplementation, higher proportions of γδ T cells were present in donors without oral vitamin D3 uptake, particularly in spring. However, γδ T cell frequency in blood did not directly correlate with serum levels of 25(OH)D3. The active metabolite 1α,25(OH)2D3 inhibited the in vitro activation of γδ T cells at the level of proliferation, cytotoxicity, and interferon-γ production. Our study reveals novel insights into the seasonal fluctuation of γδ T cells and the immunomodulatory effects of vitamin D3.