bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteoblast Attachment on Titanium Coated with Hydroxyapatite by Atomic Layer Deposition
Authors: Kylmäoja Elina , Holopainen Jani , Abushahba Faleh , Ritala Mikko , Tuukkanen Juha
Published: April 2022

Background: The increasing demand for bone implants with improved osseointegration properties has prompted researchers to develop various coating types for metal implants. Atomic layer deposition (ALD) is a method for producing nanoscale coatings conformally on complex three-dimensional surfaces. We have prepared hydroxyapatite (HA) coating on titanium (Ti) substrate with the ALD method and analyzed the biocompatibility of this coating in terms of cell adhesion and viability. Methods: HA coatings were prepared on Ti substrates by depositing CaCO3 films by ALD and converting them to HA by wet treatment in dilute phosphate solution. MC3T3-E1 preosteoblasts were cultured on ALD-HA, glass slides and bovine bone slices. ALD-HA and glass slides were either coated or non-coated with fibronectin. After 48h culture, cells were imaged with scanning electron microscopy (SEM) and analyzed by vinculin antibody staining for focal adhesion localization. An 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test was performed to study cell viability. Results: Vinculin staining revealed similar focal adhesion-like structures on ALD-HA as on glass slides and bone, albeit on ALD-HA and bone the structures were thinner compared to glass slides. This might be due to thin and broad focal adhesions on complex three-dimensional surfaces of ALD-HA and bone. The MTT test showed comparable cell viability on ALD-HA, glass slides and bone. Conclusion: ALD-HA coating was shown to be biocompatible in regard to cell adhesion and viability. This leads to new opportunities in developing improved implant coatings for better osseointegration and implant survival.
Towards Understanding the Lymph Node Response to Skin Infection with Saprophytic Staphylococcus epidermidis
Authors: Cąkała-Jakimowicz Marta , Puzianowska-Kuznicka Monika
Published: April 2022

In individuals with lymphedema, diabetic foot, or other diseases, infections with saprophytes are common. The response of major cell subpopulations in the draining lymph nodes to skin infection with Staphylococcus epidermidis was assessed using the rat model. After massive subepidermal infection, a cytometric evaluation showed an increase in cytotoxic and helper T lymphocytes and major subpopulations of the innate immune response. Three weeks later, signs of inflammation reduction with an increase in the content of memory T helper lymphocytes and effector memory T cytotoxic lymphocytes were observed. After skin re-infection, a rapid response of cytotoxic, helper, and memory T lymphocytes, memory B lymphocytes and plasmablasts, and macrophages was detected. In addition, a reduction in the number of naïve B lymphocytes, activated MHC class II+ cells, and some cells of the innate immune system was observed. T regulatory lymphocyte response after the initial and secondary S. epidermidis skin infection was not detected. The morphometric evaluation showed significant changes in the main cell subpopulations in each functional zone of the node and then confirmed the efficient elimination of the administered antigen, as evidenced by the observations on day 28. Notably, after re-infection, the cellular response did not exceed the level after the initial infection and was reduced in many cell subpopulations. Understanding how the lymph nodes eliminate S. epidermidis can provide valuable insights into creating immunological therapies against infections with saprophytes.
Mortality in Severe Antibody Deficiencies Patients during the First Two Years of the COVID-19 Pandemic: Vaccination and Monoclonal Antibodies Efficacy
Authors: Milito Cinzia , Cinetto Francesco , Palladino Andrea , Garzi Giulia , Punziano Alessandra , Lagnese Gianluca , Scarpa Riccardo , Rattazzi Marcello , Pesce Anna Maria , Pulvirenti Federica , Di Napoli Giulia , Spadaro Giuseppe , Carsetti Rita , Quinti Isabella
Published: April 2022

Patients with severely impaired antibody responses represent a group at-risk in the SARS-CoV-2 pandemic due to the lack of Spike-specific neutralizing antibodies. The main objective of this paper was to assess, by a longitudinal prospective study, COVID-19 infection and mortality rates, and disease severity in the first two years of the pandemic in a cohort of 471 Primary Antibody Defects adult patients. As secondary endpoints, we compared SARS-CoV-2 annual mortality rate to that observed over a 10-year follow-up in the same cohort, and we assessed the impact of interventions done in the second year, vaccination and anti-SARS-CoV-2 monoclonal antibodies administration on the disease outcome. Forty-one and 84 patients were infected during the first and the second year, respectively. Despite a higher infection and reinfection rate, and a higher COVID-19-related mortality rate compared to the Italian population, the pandemic did not modify the annual mortality rate for any cause in our cohort compared to that registered over the last ten years in the same cohort. PADs patients who died from COVID-19 had an underlying end-stage lung disease. We showed a beneficial effect of MoAbs administration on the likelihood of hospitalization and development of severe disease. In conclusion, COVID-19 did not cause excess mortality in Severe Antibody Deficiencies.
Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts
Authors: Lee Ji Eun , Boo Yong Chool
Published: April 2022

The purpose of this study is to present a novel strategy to enhance collagen production in cells. To identify amino acid analogs with excellent collagen production-enhancing effects, human dermal fibroblasts (HDFs) were treated with 20 kinds of amidated amino acids and 20 kinds of free amino acids, individually at 1 mM. The results showed that glycinamide enhanced collagen production (secreted collagen level) most effectively. Glycine also enhanced collagen production to a lesser degree. However, other glycine derivatives, such as N-acetyl glycine, N-acetyl glycinamide, glycine methyl ester, glycine ethyl ester, and glycyl glycine, did not show such effects. Glycinamide increased type I and III collagen protein levels without affecting COL1A1 and COL3A1 mRNA levels, whereas transforming growth factor-β1 (TGF-β1, 10 ng mL−1) increased both mRNA and protein levels of collagens. Ascorbic acid (AA, 1 mM) increased COL1A1 and COL3A1 mRNA and collagen I protein levels. Unlike TGF-β1, AA and glycinamide did not increase the protein level of α-smooth muscle actin, a marker of differentiation of fibroblasts into myofibroblasts. The combination of AA and glycinamide synergistically enhanced collagen production and wound closure in HDFs to a level similar to that in cells treated with TGF-β1. AA derivatives, such as magnesium ascorbyl 3-phosphate (MAP), 3-O-ethyl ascorbic acid, ascorbyl 2-O-glucoside, and ascorbyl tetraisopalmitate, enhanced collagen production, and the mRNA and protein levels of collagens at 1 mM, and their effects were further enhanced when co-treated with glycinamide. Among AA derivatives, MAP had a similar effect to AA in enhancing wound closure, and its effect was further enhanced by glycinamide. Other AA derivatives had different effects on wound closure. This study provides a new strategy to enhance cell collagen production and wound healing using glycinamide in combination with AA.
Duplication of the Pituitary Gland: CT, MRI and DTI Findings and Updated Review of the Literature
Authors: Serrallach Bettina L. , Rauch Ronald , Lyons Sarah K. , Huisman Thierry A. G. M.
Published: April 2022

Duplication of the pituitary gland (DPG) is an extremely rare malformation. DPG is associated with a wide variety of midline and central nervous system malformations (DPG-plus syndrome). We present the computed tomography (CT), magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) findings of a rare case of DPG with associated tuberomammillary fusion resulting in a hypothalamic mass-like configuration, oropharyngeal teratoma, cleft palate, hypertelorism, duplicated/broad sella, duplication/low bifurcation of the basilar artery, and craniovertebral midline anomalies. Qualitative interpretation of DTI yielded normal white matter organization of the brain. The duplication of the prechordal plate and the rostral end of the notochordal plate/notochord is thought to be the main factor leading to a duplication of the pituitary primordium and resulting in the formation of two morphologically normal glands. The time of induction of the teratogenic influence, the extent of the prechordal plate and notochordal plate/notochord abnormalities, and the faulty interactions are believed to be the reason for the wide spectrum of associated midline abnormalities.
Wind Pressure Characteristics Based on the Rise–Span Ratio of Spherical Domes with Openings on the Roof
Authors: Park Min Jae , Yoon Sung Won , Kim Yong Chul , Cheon Dong Jin
Published: April 2022

Wind loads are a primary concern in dome roof structures with openings such as retractable dome roofs. This is because the openings can cause damage to the cladding owing to high internal pressure. In this study, the wind pressure characteristics of a dome with an opening that varied based on the opening, rise–span ratio, and height span were examined by comparing the results from wind tunnel tests with those from previous studies. The negative pressure dominated the internal pressure of the roof in all regions and was not significantly affected by changes in the rise–span and height–span ratios. The reattachment distance of the windward region increased as the rise–span ratio increased, increasing the negative net pressure and decreasing the positive net pressure owing to a relatively large vortex. The roof inclination angle of the leeward region decreased as the rise–span ratio decreased, resulting in a decrease in the negative net pressure and an increase in the positive net pressure owing to a relatively small vortex. Based on the experimental results, a peak net pressure coefficient for cladding design was proposed for an open dome roof with a rise–span ratio of 0.05.
Automated Selection and Localization of Mobile Cranes in Construction Planning
Authors: Guo Hongling , Zhou Ying , Pan Zaiyi , Zhang Zhitian , Yu Yantao , Li Yan
Published: April 2022

Accurate selection and location of mobile cranes is a critical issue on construction sites, being able to contribute to the improvement of the safety and efficiency of lifting operations. Considering the complexities and dynamics of construction sites, this study aimed to develop a useful approach for automated selection and localization of mobile cranes based on the simulation of crane operations. First, the information required for crane selection and localization is analyzed and extracted from BIM (building information modeling). Then, mainly considering the crane capacity, the initial crane type is selected with candidate location points. Based on the simulation of lifting operation at the candidate points, feasible location points and crane types are determined through three constraint checks (i.e., environment constraint, operation constraint, and safety constraint). Besides, two kinds of efficiency optimization, namely lifting time minimization and crane movement minimization, are presented to figure out the best location points from the feasible points. Finally, the proposed approach is validated using a case study. This research contributes to not only crane operation planning but also automatic construction simulation, thus supporting the implementation of intelligent construction in the future.
Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide
Authors: Conteduca Vincenza , Casadei Chiara , Scarpi Emanuela , Brighi Nicole , Schepisi Giuseppe , Lolli Cristian , Gurioli Giorgia , Toma Ilaria , Poti Giulia , Farolfi Alberto , De Giorgi Ugo
Published: April 2022

Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divided patients into high and low ctDNA level and in AR gain and AR normal. Results: 220 baseline samples were collected from mCRPC treated with abiraterone (n = 140) or enzalutamide (n = 80). A lower rate of PSA decline ≥ 50% was observed in patients with high ctDNA (p = 0.017) and AR gain (p = 0.0003). Combining ctDNA fraction and AR CN, we found a different median PSA progression-free survival (PFS) among four groups: (1) low ctDNA/AR normal, (2) high ctDNA/AR normal, (3) low ctDNA/AR gain, and (4) high ctDNA/AR gain (11.4 vs. 5.0 vs. 4.8 vs. 3.7 months, p < 0.0001). In a multivariable analysis, high ctDNA, AR gain, PSA DT, PSA DT velocity remained independent predictors of PSA PFS. Conclusions: Elevated ctDNA levels and AR gain are negatively and independently correlated with PSA kinetics in mCRPC men treated with abiraterone or enzalutamide.
Handheld PET Probe for Pediatric Cancer Surgery
Authors: Rinehardt Hannah N. , Longo Sadie , Gilbert Ryan , Shoaf Jennifer N. , Edwards Wilson B. , Kohanbash Gary , Malek Marcus M.
Published: April 2022

18F-fluorodeoxyglucose (FDG) is a glucose analog that acts as a marker for glucose uptake and metabolism. FDG PET scans are used in monitoring pediatric cancers. The handheld PET probe localization of FDG-avid lesions is an emerging modality for radio-guided surgery (RGS). We sought to assess the utility of PET probe in localizing occult FDG-avid tumors in pediatric patients. PET probe functionality was evaluated by using a PET/CT scan calibration phantom. The PET probe was able to detect FDG photon emission from simulated tumors with an expected decay of the radioisotope over time. Specificity for simulated tumor detection was lower in a model that included background FDG. In a clinical model, eight pediatric patients with FDG-avid primary, recurrent or metastatic cancer underwent a tumor excision, utilizing IV FDG and PET probe survey. Adequate tissue for diagnosis was present in 16 of 17 resected specimens, and pathology was positive for malignancy in 12 of the 17 FDG-avid lesions. PET probe gamma counts per second were higher in tumors compared with adjacent benign tissue in all operations. The median ex vivo tumor-to-background ratio (TBR) was 4.0 (range 0.9–12). The PET probe confirmed the excision of occult FDG-avid tumors in eight pediatric patients.
LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells
Authors: Cho Jung Hee , You Yeon-Mi , Koo Han , Lee Dong Chul , Yeom Young Il , Park Kyung Chan
Published: April 2022

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival. Additionally, LPIN1 increased the production of lipid droplets, which play an important role in TKI drug resistance. All results were recapitulated in a patient-derived EGFR-mutant NSCLC cell line. In in vivo tumorigenesis assay, we identified that both shRNA-mediated depletion and pharmaceutical inhibition of LPIN1 clearly reduced tumor growth and confirmed that gefitinib treatment induced LPIN1 expression and LPIN1-dependent NF-κB activation (an increase in p-IκBα level) in tumor tissues. These results suggest an effective strategy of co-treating TKIs and LPIN1 inhibitors to prevent TKI resistance in NSCLC patients.
Diagnostic Workup for Patients with Solid Renal Masses: A Cost-Effectiveness Analysis
Authors: Runtemund Jasmin , Rübenthaler Johannes , von Münchhausen Niklas , Ingenerf Maria , Grawe Freba , Biechele Gloria , Gassert Felix Gerhard , Tollens Fabian , Rink Johann , Cecatka Sasa , Schmid-Tannwald Christine , Froelich Matthias F. , Clevert Dirk-André , Schnitzer Moritz L.
Published: April 2022

Background: For patients with solid renal masses, a precise differentiation between malignant and benign tumors is crucial for forward treatment management. Even though MRI and CT are often deemed as the gold standard in the diagnosis of solid renal masses, CEUS may also offer very high sensitivity in detection. The aim of this study therefore was to evaluate the effectiveness of CEUS from an economical point of view. Methods: A decision-making model based on a Markov model assessed expenses and utilities (in QALYs) associated with CEUS, MRI and CT. The utilized parameters were acquired from published research. Further, a Monte Carlo simulation-based deterministic sensitivity analysis of utilized variables with 30,000 repetitions was executed. The willingness-to-pay (WTP) is at USD 100,000/QALY. Results: In the baseline, CT caused overall expenses of USD 10,285.58 and an efficacy of 11.95 QALYs, whereas MRI caused overall expenses of USD 7407.70 and an efficacy of 12.25. Further, CEUS caused overall expenses of USD 5539.78, with an efficacy of 12.44. Consequently, CT and MRI were dominated by CEUS, and CEUS remained cost-effective in the sensitivity analyses. Conclusions: CEUS should be considered as a cost-effective imaging strategy for the initial diagnostic workup and assessment of solid renal masses compared to CT and MRI.
Development of an Image Analysis-Based Prognosis Score Using Google’s Teachable Machine in Melanoma
Authors: Forchhammer Stephan , Abu-Ghazaleh Amar , Metzler Gisela , Garbe Claus , Eigentler Thomas
Published: April 2022

Background: The increasing number of melanoma patients makes it necessary to establish new strategies for prognosis assessment to ensure follow-up care. Deep-learning-based image analysis of primary melanoma could be a future component of risk stratification. Objectives: To develop a risk score for overall survival based on image analysis through artificial intelligence (AI) and validate it in a test cohort. Methods: Hematoxylin and eosin (H&E) stained sections of 831 melanomas, diagnosed from 2012–2015 were photographed and used to perform deep-learning-based group classification. For this purpose, the freely available software of Google’s teachable machine was used. Five hundred patient sections were used as the training cohort, and 331 sections served as the test cohort. Results: Using Google’s Teachable Machine, a prognosis score for overall survival could be developed that achieved a statistically significant prognosis estimate with an AUC of 0.694 in a ROC analysis based solely on image sections of approximately 250 × 250 µm. The prognosis group “low-risk” (n = 230) showed an overall survival rate of 93%, whereas the prognosis group “high-risk” (n = 101) showed an overall survival rate of 77.2%. Conclusions: The study supports the possibility of using deep learning-based classification systems for risk stratification in melanoma. The AI assessment used in this study provides a significant risk estimate in melanoma, but it does not considerably improve the existing risk classification based on the TNM classification.
The Fight Just Born—Neonatal Cancer: Rare Occurrence with a Favorable Outcome but Challenging Management
Authors: De Ioris Maria Antonietta , Fabozzi Francesco , Lodi Mariachiara , Vitali Giulia , De Pasquale Maria Debora , Del Baldo Giada , Abbas Rachid , Agolini Emanuele , Crocoli Alessandro , Iacusso Chiara , Milano Giuseppe Maria , Serra Annalisa , Mastronuzzi Angela
Published: April 2022

The occurrence of cancer in newborns within the first 28 days of life is uncommon, with different clinical presentation from other age groups. Prenatal diagnosis is reported in about half of patients, while a genetic predisposition condition is supposed. The management of a newborn with cancer can be challenging and needs to be tailored according to the histology and the primary tumor site; surgery represents the main strategy, while chemotherapy should be considered with caution because of the higher toxicity and mortality due to different pharmacokinetics in neonates compared to older children. We describe the first Italian series over a 15-year period of patients affected by both benign and malignant neoplastic diseases diagnosed within the first 28 days of life; 74 newborns were diagnosed with neonatal tumors, representing 1.5% of the cancer population in the same period, and a prevalence of germ cell tumors (55%) and neuroblastoma (16%) was observed. Surgery was performed on 80% of patients, while chemotherapy was necessary for about 20% of patients. The 5-year overall survival (OS) exceeded 90%; treatment-related deaths are a major concern, representing 80% of overall deaths. A genetic/syndromic condition was detected in 16% of the population; additionally, a cancer predisposition syndrome (CPS) was identified in about 10% of patients. According to our experience, all newborns affected by cancer should warrant genetic counselling and a screening test for CPS.
Novel Heterogeneous Catalysts for Advanced Oxidation Processes (AOPs)
Authors: Soares Olívia Salomé G. P. , Orge Carla A. , Rocha Raquel Pinto
Published: April 2022

With the increasing global usage of water and the continuous addition of contaminants to water sources, new challenges associated with the abatement of organic pollutants, particularly those that are refractory to conventional water and wastewater treatment technologies, have arisen [...]
Changes in Inflammatory Markers in Patients with Chronic Thromboembolic Pulmonary Hypertension Treated with Balloon Pulmonary Angioplasty
Authors: Magoń Wojciech , Stępniewski Jakub , Waligóra Marcin , Jonas Kamil , Przybylski Roman , Podolec Piotr , Kopeć Grzegorz
Published: April 2022

Background: Inflammatory response and endothelial dysfunction contribute to the progression of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess changes in biomarkers involved in those processes in inoperable CTEPH patients treated with balloon pulmonary angioplasty (BPA). Methods: We enrolled 20 patients with inoperable CTEPH qualified for BPA and a control group. Interleukin 6, 8, 10 (IL-6, IL-8, IL-10), monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (hsCRP) constituted the markers of systemic inflammation. Endothelin 1 (ET-1) served as a marker of endothelial dysfunction. Selected markers were assessed before the BPA treatment, 24 h after the first BPA, and six months after completion of the BPA treatment. Results: At baseline, the CTEPH patients had increased serum concentrations of IL-6, IL-8 and ET-1. Twenty-four hours after a BPA session, we observed an increase in concentrations of IL-6 (∆ = 3.67 (1.41; 7.16); p < 0.001), of IL-10 (∆ = 0.25 (0; 0.47); p = 0.003), of MCP-1 (∆ = 111 (60.1; 202.8); p = 0.002), and of hsCRP (∆ = 4.81 (3.46; 8.47); p < 0.001). Six months after completion of the BPA treatment, there was a decrease in concentrations of IL-6 (∆ = −1.61 (−3.11; −0.20); p = 0.03), of IL8 (∆ = −3.24 (−7.72; 0.82); p = 0.01), and of ET-1 (∆ = −0.47 (−0.96; 0.05); p = 0.005). Conclusions: Patients with inoperable CTEPH exhibit increased systemic inflammation and endothelial dysfunction, which improves after completion of the BPA treatment. A single BPA session evokes an acute inflammatory response.
The Lysosome in Malignant Melanoma: Biology, Function and Therapeutic Applications
Authors: Hsu Chia-Hsin , Lee Keng-Jung , Chiu Yi-Han , Huang Kuo-Ching , Wang Guo-Shou , Chen Lei-Po , Liao Kuang-Wen , Lin Chen-Si
Published: April 2022

Lysosomes are membrane-bound vesicles that play roles in the degradation and recycling of cellular waste and homeostasis maintenance within cells. False alterations of lysosomal functions can lead to broad detrimental effects and cause various diseases, including cancers. Cancer cells that are rapidly proliferative and invasive are highly dependent on effective lysosomal function. Malignant melanoma is the most lethal form of skin cancer, with high metastasis characteristics, drug resistance, and aggressiveness. It is critical to understand the role of lysosomes in melanoma pathogenesis in order to improve the outcomes of melanoma patients. In this mini-review, we compile our current knowledge of lysosomes’ role in tumorigenesis, progression, therapy resistance, and the current treatment strategies related to lysosomes in melanoma.
A Phase II Study on the Effect of Taurisolo® Administered via AEROsol in Hospitalized Patients with Mild to Moderate COVID-19 Pneumonia: The TAEROVID-19 Study
Authors: Sanduzzi Zamparelli Stefano , Capitelli Ludovica , Coppola Nicola , Venditto Claudia , Santoro Ciro , Annunziata Giuseppe , Bruzzese Dario , Cuomo Nunzia , Gentile Ivan , Bocchino Marialuisa , Sanduzzi Zamparelli Alessandro
Published: April 2022

Background: Polyphenols are the largest class of bioactive compounds in plants, which are synthesized as secondary metabolites. In the last few years, interesting studies have demonstrated the efficacy of polyphenols against coronavirus infections. Methods: we conducted a phase II multicentric clinical trial (TAEROVID-19) during the first wave of the COVID-19 pandemic in order to assess the safety and feasibility of Taurisolo® aerosol formulation in hospitalized patients suffering from SARS-CoV-2 pneumonia. Results: we observed a rapid decline of symptoms and a low rate of intensive care in patients treated with Taurisolo®, with a faster decline of symptoms. Conclusions: This is the first trial assessing the safety and feasibility of Taurisolo® aerosol formulation. We could argue that this treatment could act as an add-on therapy in the treatment of COVID-19 patients, owing to both its anti-inflammatory and antioxidant effects. Further controlled trials are needed, which may be of interest to evaluate the compound’s efficacy.
Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways
Authors: Bakshi Hamid A. , Quinn Gerry A. , Nasef Mohamed M. , Mishra Vijay , Aljabali Alaa A. A. , El-Tanani Mohamed , Serrano-Aroca Ángel , Webba Da Silva Mateus , McCarron Paul A. , Tambuwala Murtaza M.
Published: April 2022

Angiogenesis and metastasis play pivotal roles in the progression of cancer. We recently discovered that crocin, a dietary carotenoid derived from the Himalayan crocus, inhibited the growth of colon cancer cells. However, the exact role of crocin on the angiogenesis and metastasis in colorectal cancer remains unclear. In the present study, we demonstrated that crocin significantly reduces the viability of colon cancer cells (HT-29, Caco-2) and human umbilical vein endothelial cells (HUVEC), but was not toxic to human colon epithelial (HCEC) cells. Furthermore, pre-treatment of human carcinoma cells (HT-29 and Caco-2) with crocin inhibited cell migration, invasion, and angiogenesis in concentration -dependent manner. Further studies demonstrated that crocin inhibited TNF-α, NF-κB and VEGF pathways in colon carcinoma cell angiogenesis and metastasis. Crocin also inhibited cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVEC) in a concentration -dependent manner. We also observed that crocin significantly reduced the secretion of VEGF and TNF-α induced activation of NF-kB by human colon carcinoma cells. In the absence of TNF-α, a concentration-dependent reduction in NF-kB was observed. Many of these observations were confirmed by in vivo angiogenesis models, which showed that crocin significantly reduced the progression of tumour growth. Collectively, these finding suggest that crocin inhibits angiogenesis and colorectal cancer cell metastasis by targeting NF-kB and blocking TNF-α/NF-κB/VEGF pathways.
Evaluation of Intranasal Midazolam for Pediatric Sedation during the Suturing of Traumatic Lacerations: A Systematic Review
Authors: Gómez-Manzano Francisco , Laredo-Aguilera José , Cobo-Cuenca Ana , Rabanales-Sotos Joseba , Rodríguez-Cañamero Sergio , Martín-Espinosa Noelia , Carmona-Torres Juan
Published: April 2022

Objective: The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments. Methodology: A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library. Eligibility criteria: randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route. Conclusions: The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.
Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis
Authors: Tchetina Elena V. , Markova Galina A. , Satybaldyev Azamat M. , Lila Aleksandr M.
Published: April 2022

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Efficacy of personalized therapy in RA is associated with correct choice of therapeutic agent and a possibility to predict its effect prior to treatment. Our objective was to examine the association of baseline expression of metalloproteinase (MMP)-9 and cathepsin K, which are involved in cartilage and bone degradation, as well as proinflammatory cytokines tumour necrosis factor (TNF)α and interleukin (IL)-1β in the peripheral blood mononuclear cells (PBMCs) obtained from patients with RA cultured with tofacitinib (TFCN) and remission achievement. We examined 12 tofacitinib-naïve patients with RA, with a median age of 51 years and disease duration of 37.6 months. After three months of TFCN therapy, six of these patients reached clinical remission criteria while others preserved high and moderate disease activity. PBMCs were tested prior to therapy followed by their isolation in Ficoll density gradient and cultured with 100 nM TFCN for 48 h. Gene expression analysis for MMP-9, cathepsin K, IL-1β, and TNFα was performed with quantitative real-time RT-PCR using total RNA isolated from and cultured with TFCN PBMCs compared with untreated cells. Expression of all the examined genes was significantly upregulated in those cultured with TFCN PBMCs from patients who maintained high and moderate disease activity after TFCN therapy while TNFα gene expression was significantly downregulated in patients who gained remission compared with untreated counterparts. Downregulation of TNFα gene expression in PBMCs from TFCN-naïve patients with RA cultured with TFCN prior to therapy compared with untreated counterparts might serve a prognostic biomarker for remission attainment in response to tofacitinib therapy.
Determination of the Coefficient of Friction in a Pulley Groove by the Indirect Method
Authors: Hrabovský Leopold , Fries Jiří , Kudrna Lukáš , Gaszek Jakub
Published: April 2022

In lifting systems used for the vertical transport of bulk materials and individual items or persons, so-called frictional force transmission between a steel cable and pulley is used. Due to the sufficient contact pressure between the pulley groove and the surface of the steel cable, the steel cable moves as a result of fibre friction. In general, it is possible to define fibre (also called belt) friction as the resistance that is imposed on a flexible steel cable sliding over the rounded surface of a pulley. The frictional transmission of the tractive force is considered safe if there is no slippage of the cable in the pulley groove. In the event of insufficient cable pressure against the pulley groove or insufficient friction, the transport process fails, and the lifting device is unable to perform its function. The purpose of the article and of the created measuring devices is to obtain by experimental measurements the most accurate true value possible of the coefficient of friction acting on the contact surface of the cable with the pulley groove. The values of the friction coefficients obtained by indirect measurements on laboratory equipment when the tractive force is transferred by friction differ in many cases and do not coincide with the values calculated using theoretical relationships. The aim of the paper is to present a method of measurement and to identify the magnitude of the forces acting on both sides of a cable belted in the V-groove of a cable drum. From the results obtained from the experimental measurements, to express the value of the random variable is based on the knowledge of the known values obtained from the measurements for their use in a failure analysis. This paper presents results that can be applied in the field of online monitoring of this type of lifting equipment for failure analysis, prediction and evaluation of their operational indicators.
Two-Layer Rt-QFN: A New Coreless Substrate Based on Lead Frame Technology
Authors: Kim Hong-Chan , Ryu Ho-Jun , Kang Sung-Il , Bae In-Seob
Published: April 2022

Lead frames have been widely used in the semiconductor package assembly industry; a lot of demand is still maintained in fields requiring high reliability, such as automobiles, although many fields are being replaced by laminated substrates according to the recent electronic package product trend that requires high I/O pin count. The purpose of this paper is to introduce two-layer Rt-QFN, one of the lead frame-based coreless substrates. (Rt-QFN is a trademark of Haesung DS, which means premold type lead frame substrate.) two-layer Rt-QFN can secure more advanced design freedom compared with the lead frame and thus has I/O pin count coverage intermediate between the lead frame and laminated substrate. In addition, Rt-QFN can exhibit excellent heat dissipation performance by replacing via holes of the laminated substrate with Cu bumps formed by etching. CAE analysis showed that the thermal resistance of the two-layer Rt-QFN substrate was about 23% lower than that of the laminate substrate. The excellent heat dissipation property of two-layer Rt-QFN allows it to replace the existing expensive ceramic substrate and can achieve cost savings. In addition, the sputtering technique, including the LIS (Linear Ion Source) module, was introduced as a method to sufficiently secure the interfacial adhesion between the resin/Cu interface, which is a key factor in producing a two-layer substrate. As a method to enhance the interfacial adhesion between the resin/Cu interface, the collimated mode of LIS was used in the Ar atmosphere inside the vacuum chamber to activate the resin surface. After plasma pretreatment on the surface of the resin, a Cu seed layer was continuously formed by sputtering. As a result, it was possible to secure the high reliability of the two-layer Rt-QFN substrate, and it was confirmed through the evaluation of interfacial adhesion of more than 1.2 kgƒ/cm during the peel-off tape test at the resin/Cu interface and further moisture absorption evaluation.
Traffic Request Generation through a Variational Auto Encoder Approach
Authors: Chiesa Stefano , Taraglio Sergio
Published: April 2022

Traffic and transportation forecasting is a key issue in urban planning aimed to provide a greener and more sustainable environment to residents. Their privacy is a second key issue that requires synthetic travel data. A possible solution is offered by generative models. Here, a variational autoencoder architecture has been trained on a floating car dataset in order to grasp the statistical features of the traffic demand in the city of Rome. The architecture is based on multilayer dense neural networks for encoding and decoding parts. A brief analysis of parameter influence is conducted. The generated trajectories are compared with those in the dataset. The resulting reconstructed synthetic data are employed to compute the traffic fluxes and geographic distribution of parked cars. Further work directions are provided.
Identifying Complex DNA Contamination in Pig-Footed Bandicoots Helps to Clarify an Anomalous Ecological Transition
Authors: Phillips Matthew J. , Cascini Manuela , Celik Mélina
Published: April 2022

Our understanding of the biology of the extinct pig-footed bandicoots (Chaeropus) has been substantially revised over the past two decades by both molecular and morphological research. Resolving the systematic and temporal contexts of Chaeropus evolution has relied heavily on sequencing DNA from century-old specimens. We have used sliding window BLASTs and phylogeny reconstruction, as well as cumulative likelihood and apomorphy distributions, to identify contamination in sequences from both species of pig-footed bandicoot. The sources of non-target DNA that were identified range from other bandicoot species to a bird—emphasizing the importance of sequence authentication for historical museum specimens, as has become standard for ancient DNA studies. Upon excluding the putatively contaminated fragments, Chaeropus was resolved as the sister to all other bandicoots (Peramelidae), to the exclusion of bilbies (Macrotis). The estimated divergence time between the two Chaeropus species also decreases in better agreement with the fossil record. This study provides evolutionary context for testing hypotheses on the ecological transition of pig-footed bandicoots from semi-fossorial omnivores towards cursorial grazers, which in turn may represent the only breach of deeply conserved ecospace partitioning between modern Australo-Papuan marsupial orders.
Photodynamic Therapy-Adjunctive Therapy in the Treatment of Prostate Cancer
Authors: Osuchowski Michał , Aebisher David , Bartusik-Aebisher Dorota , Krupka-Olek Magdalena , Dynarowicz Klaudia , Przygoda Maria , Kawczyk-Krupka Aleksandra
Published: April 2022

The alarming increase in the number of advanced-stage prostate cancer cases with poor prognosis has led to a search for innovative methods of treatment. In response to the need for implementation of new and innovative methods of cancer tissue therapy, we studied photodynamic action in excised prostate tissue in vitro as a model for photodynamic therapy. To ascertain the effects of photodynamic action in prostate tissue, Rose Bengal (0.01 to 0.05 mM) was used as a photosensitizer in the presence of oxygen and light to generate singlet oxygen in tissues in vitro. Five preset concentrations of Rose Bengal were chosen and injected into prostate tissue samples (60 samples with 12 replications for each RB concentration) that were subsequently exposed to 532 nm light. The effects of irradiation of the Rose Bengal infused tissue samples were determined by histopathological analysis. Histopathological examination of prostate samples subjected to photodynamic action revealed numerous changes in the morphology of the neoplastic cells and the surrounding tissues. We conclude that the morphological changes observed in the prostate cancer tissues were a result of the photogeneration of cytotoxic singlet oxygen. The tissue damage observed post photodynamic action offers an incentive for continued in vitro investigations and future in vivo clinical trials.
The Clinical Manifestation of SARS-CoV-2 in Critically Ill Patients with Klebsiella pneumoniae NDM Hospitalized in the ICU of a Modular Hospital during the Third Wave of the Pandemic in Poland—An Observational Cohort Study
Authors: Guzek Aneta , Rybicki Zbigniew , Woźniak-Kosek Agnieszka , Tomaszewski Dariusz
Published: April 2022

There is limited information on the clinical characteristics of critically ill patients infected with SARS-CoV-2 and Klebsiella pneumoniae NDM. The objective of this study was to describe such a group of patients hospitalised in the intensive care unit of a large academic hospital during the third wave of the COVID-19 pandemic in Poland. Between 1 March and 30 June 2021, 103 patients were hospitalised, of whom 23 (22.3%) were positive for K. pneumoniae NDM; 14 (61%) of those patients died. Their hospitalisation time varied between 9 and 47 days. Five of the 23 patients (21.7%) were otherwise healthy. In contrast, the others suffered from cardiovascular problems (11, 47.8%), obesity (6, 26.1%), diabetes (5, 21.7%), neurological problems (4, 17.4%), or kidney disease (1, 4.3%); 4 (17.4%) were heavy smokers, and 1 (4.3%) had a history of alcohol abuse. K. pneumoniae NDM was isolated from urine samples of all patients. In 17 patients (73.9%), it was also isolated from other sources: from the respiratory tract in 10 (43.8%), from the blood in 2 (8.7%), and the central venous catheter was contaminated in 1 case (4.3%). Fourteen of the patients (60.9%) were colonised K. pneumoniae NDM. In four patients (17.4%), bacterial and fungal coinfection occurred. In one case (4.4%), two fungal species, Candida albicans and Candida glabrata, were isolated simultaneously. The most frequently administered antimicrobial agent was colistin (60.9%), followed by meropenem (47.8%), vancomycin (47.8%), ceftriaxone (34.8%), linezolid (30.4%), piperacillin/tazobactam (30.4%), and trimethoprim/sulfamethoxazole (30.4%). Other less-frequently administered agents included amikacin, amoxicillin/clavulanate, tigecycline, ciprofloxacin, fosfomycin, clindamycin, and cloxacillin. Fluconazole was administered in 14 patients (60.7%) and micafungin was administered in 2 (8.7%).
The Time of Day Is Key to Discriminate Cultivars of Sugarcane upon Imagery Data from Unmanned Aerial Vehicle
Authors: Barbosa Júnior Marcelo Rodrigues , Tedesco Danilo , Carreira Vinicius dos Santos , Pinto Antonio Alves , Moreira Bruno Rafael de Almeida , Shiratsuchi Luciano Shozo , Zerbato Cristiano , Silva Rouverson Pereira da
Published: April 2022

Remote sensing can provide useful imagery data to monitor sugarcane in the field, whether for precision management or high-throughput phenotyping (HTP). However, research and technological development into aerial remote sensing for distinguishing cultivars is still at an early stage of development, driving the need for further in-depth investigation. The primary objective of this study was therefore to analyze whether it could be possible to discriminate market-grade cultivars of sugarcane upon imagery data from an unmanned aerial vehicle (UAV). A secondary objective was to analyze whether the time of day could impact the expressiveness of spectral bands and vegetation indices (VIs) in the biophysical modeling. The remote sensing platform acquired high-resolution imagery data, making it possible for discriminating cultivars upon spectral bands and VIs without computational unfeasibility. 12:00 PM especially proved to be the most reliable time of day to perform the flight on the field and model the cultivars upon spectral bands. In contrast, the discrimination upon VIs was not specific to the time of flight. Therefore, this study can provide further information about the division of cultivars of sugarcane merely as a result of processing UAV imagery data. Insights will drive the knowledge necessary to effectively advance the field’s prominence in developing low-altitude, remotely sensing sugarcane.
Probabilistic Inference with Polymerizing Biochemical Circuits
Authors: Katz Yarden , Fontana Walter
Published: April 2022

Probabilistic inference—the process of estimating the values of unobserved variables in probabilistic models—has been used to describe various cognitive phenomena related to learning and memory. While the study of biological realizations of inference has focused on animal nervous systems, single-celled organisms also show complex and potentially “predictive” behaviors in changing environments. Yet, it is unclear how the biochemical machinery found in cells might perform inference. Here, we show how inference in a simple Markov model can be approximately realized, in real-time, using polymerizing biochemical circuits. Our approach relies on assembling linear polymers that record the history of environmental changes, where the polymerization process produces molecular complexes that reflect posterior probabilities. We discuss the implications of realizing inference using biochemistry, and the potential of polymerization as a form of biological information-processing.
Fabrication of Maize-Based Nanoparticles at Home: A Research-Based Learning Activity
Authors: Alvarez Mario Moisés , del Carmen Flores-Cruz Lilia , Pedroza-González Sara Cristina , Trujillo-de Santiago Grissel
Published: April 2022

Nanotechnology is an interdisciplinary field that promises to reshape many spheres of our lives. One core activity in nanotechnology is the synthesis of nanoparticles. Here, we introduce a research-based activity centered on the use of zein, the main constitutive protein in maize, as a raw material for the synthesis of nanoparticles. In the context of the contingency imposed by COVID-19, this experimental activity was designed to be independent of a central laboratory. Therefore, it was enabled by a portable heating do-it-yourself (DIY) device that the students assembled in their own home. We describe the implementation of this activity as part of a graduate-level seminar series, and share our observations. We assessed the students’ knowledge on seven topics related to nanotechnology, do-it-yourself devices, and protein synthesis. The students appeared to perceive that their degree of knowledge had advanced (on average) in all the learning topics; the students stated that their degree of knowledge in the topics of assembly of devices and protein structure had advanced the most. The results of this assessment suggest that this simple, hands-on, research-based activity effectively engaged students in a learning process that allowed them to integrate knowledge while exercising their experimental skills. In addition, we show that these types of activities are suitable for implementation even in circumstances of restricted access to laboratory facilities, such as the ones recently experienced during the pandemic.
Advances in Machine Learning
Authors: Yang Jihoon , Park Unsang
Published: April 2022

Since its inception as a branch of Artificial Intelligence, Machine Learning (ML) has flourished in recent years [...]