bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Epidermal Growth Factor Effect on Animal Intestinal Phosphate Absorption: A Review
Authors: Tang Xiaopeng , Liu Xuguang , Liu Hu
Published: June 2021

Phosphorus is one of the essential mineral elements of animals that plays an important role in animal growth and development, bone formation, energy metabolism, nucleic acid synthesis, cell signal transduction, and blood acid–base balance. It has been established that the Type IIb sodium-dependent phosphate cotransporters (NaPi-IIb) protein is the major sodium-dependent phosphate (Pi) transporter, which plays an important role in Pi uptake across the apical membrane of epithelial cells in the small intestine. Previous studies have demonstrated that epidermal growth factor (EGF) is involved in regulating intestinal Pi absorption. Here we summarize the effects of EGF on active Pi transport of NaPi-IIb under different conditions. Under normal conditions, EGF inhibits the active transport of Pi by inhibiting the expression of NaPi-IIb, while, under intestinal injury condition, EGF promotes the active absorption of Pi through upregulating the expression of NaPi-IIb. This review provides a reference for information about EGF-regulatory functions in Pi absorption in the animal intestine.
Molecular Survey on Kobuviruses in Domestic and Wild Ungulates From Northwestern Italian Alps
Authors: Di Martino Barbara , Di Profio Federica , Robetto Serena , Fruci Paola , Sarchese Vittorio , Palombieri Andrea , Melegari Irene , Orusa Riccardo , Martella Vito , Marsilio Fulvio
Published: June 2021

Since the first identification in 1989 in humans, kobuviruses (KoVs) have been identified from a wide range of animal species including carnivores, rodents, birds, ungulates, rabbits, and bats. Several studies have described the identification of genetically related KoVs in the fecal virome of domestic and wild animals suggesting a mutual exchange of viruses. By screening a total of 231 fecal samples from wild and domestic ungulates, KoVs RNA was detected in wild boars (3.2%; 2/63), chamois (4.6%; 2/43), and goats (2.6%; 2/77). On phylogenetic analysis of the partial RdRp sequence, the wild boar strains clustered within the species Aichivirus C whilst the strains identified in domestic and wild ruminants grouped into the species Aichivirus B. The complete VP1 gene was obtained for chamois and goat KoVs. Interestingly, upon phylogenetic analysis the strains grouped together with a KoV of ovine origin within a distinct genetic type (B3) of the species Aichivirus B.
Polymorphic Phase Transition and Piezoelectric Performance of BaTiO3-CaSnO3 Solid Solutions
Authors: Wang Qian , Yan Hong-Ze , Zhao Xian , Wang Chun-Ming
Published: June 2021

BaTiO3-based piezoelectric ceramics have attracted considerable attention in recent years due to their tunable phase structures and good piezoelectric properties. In this work, the (1 − x)BaTiO3−xCaSnO3 (0.00 ≤ x ≤ 0.16, abbreviated as BT−xCS) solid solutions, were prepared by traditional solid-state reaction methods. The phase transitions, microstructure, dielectric, piezoelectric, and ferroelectric properties of BT-xCS have been investigated in detail. The coexistence of rhombohedral, orthorhombic, and tetragonal phases near room temperature, i.e., polymorphic phase transition (PPT), has been confirmed by X-ray diffraction and temperature-dependent dielectric measurements in the compositions range of 0.06 ≤ x ≤ 0.10. The multiphase coexistence near room temperature provides more spontaneous polarization vectors and facilitates the process of polarization rotation and extension by an external electric field, which is conducive to the enhancement of piezoelectric response. Remarkably, the composition of BT-0.08CS exhibits optimized piezoelectric properties with a piezoelectric coefficient d33 of 620 pC/N, electromechanical coupling factors kp of 58%, kt of 40%, and a piezoelectric strain coefficient d33* of 950 pm/V.
A Novel Design of Water-Activated Variable Stiffness Endoscopic Manipulator with Safe Thermal Insulation
Authors: Gao Qian , Sun Zhenglong
Published: June 2021

In natural orifice transluminal endoscopic surgery (NOTES), an ideal endoscope platform should be flexible and dexterous enough to go through the natural orifices to access the lesion site inside the human body, and meanwhile provide sufficient rigidity to serve as a base for the end-effectors to operate during the surgical tasks. However, the conventional endoscope has limited ability for maintaining high rigidity over the length of the body. This paper presents a novel design of a variable stiffness endoscopic manipulator. By using a new bioplastic named FORMcard, whose stiffness can be thermally adjusted, water at different temperatures is employed to switch the manipulator between rigid mode and flexible mode. A biocompatible microencapsulated phase change material (MEPCM) with latent heat storage properties is adopted as the thermal insulation for better safety. Experiments are conducted to test the concept design, and the validated advantages of our proposed variable stiffness endoscopic manipulator include: shorter mode activation time (25 s), significantly improved stiffness in rigid mode (547.9–926.3 N·cm2) and larger stiffness-adjusting ratio (23.9–25.1 times).
Almond Fruit Drop Patterns under Mediterranean Conditions
Authors: Lordan Jaume , Zazurca Lourdes , Rovira Mercè , Torguet Laura , Batlle Ignasi , DeJong Theodore , Miarnau Xavier
Published: June 2021

Almond is an important tree nut crop worldwide, and planted areas have been increasing year after year. While self-fertility is one of the key factors when it comes to improved almond productivity of new cultivars, yield is also affected by the number of flowers produced, pollination, fruit set, fruit drop, and fruit weight. Almond fruit drop patterns of 20 Mediterranean almond cultivars were studied over three years. In addition, fruit drop patterns of two scion cultivars ‘Marinada’ and ‘Vairo’ budded onto eight to 10 different rootstocks managed with three different pruning strategies were studied for two years. Cumulative flower and fruit drop ranged from 50% to 90% among cultivars and treatments, and there were up to four fruit drop events during the growing season, the main one occurring from 20–60 days from full bloom (DFFB). Subsequent drops were at 100 DFFB, 120–140 DFFB, and the last one at 160–180 DFFB. The later drops were less apparent. In general, about half of the cumulative drop was comprised of buds and flowers, and the remaining percentage was fruit that dropped 20 or more days after full bloom. Furthermore, different fruit drop patterns were observed depending on the cultivar. For late- and extra-late flowering cultivars, cumulative fruit drop began to decrease earlier, with most of the drops occurred already at full bloom, whereas the opposite was observed for the early flowering cultivars. Rootstocks also had an important effect on the fruit drop pattern, with different effects depending on the scion cultivar. Tree management, such as type of pruning, also had an important effect on the rate of fruit drop and cumulative drop. Therefore, each combination of cultivar × rootstock × pruning type will require different strategies in order to reduce the fruit drop and optimize crop loads.
Nitrogen Dynamics in Tropical Soils Treated with Liquid and Granular Urea Fertilizers
Authors: Motasim Ahmmed Md , Samsuri Abd Wahid , Abdul Sukor Arina Shairah , Adibah Amin Mohd
Published: June 2021

The mineralization of urea fertilizer mostly regulates the nitrogen dynamics in the soil. A laboratory-scale study was conducted to compare the nitrogen dynamics in two tropical soil series incubated with either liquid urea (LU) or granular urea (GU) at 0, 300, 400 or 500 mg/kg of soil. The soils samples used in the experiment were the Bungor and Selangor soil series which have a sandy clay loam and clay texture, respectively. The NH4+-N, NO3−-N concentration in the soils were measured for four weeks to determine the urea-N mineralization while ten pore volumes of water were used for the NH4+-N and NO3−-N leaching loss. At the same application rate, higher NH4+-N and NO3−-N concentrations were recorded in the LU applied soils throughout the incubation period in case of N mineralization. Urea-N recovery was higher in GU than LU treated soils in the first two weeks while no urea-N was present in both GU and LU treated soils after the third week of incubation. The leaching of N (NH4+-N and NO3−-N) was higher in GU treated soils than that of LU and leaching was increased with increased application rate in both LU and GU in both soils. The NH4+-N and NO3−-N concentrations were higher in the Selangor soil whereas the total N leaching loss was higher in Bungor soil. The results suggest that the LU was a better N fertilizer source than GU for rapid mineralization, quicker N availability and lower N leaching loss.
Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo
Authors: Sleha Radek , Radochova Vera , Malis Jiri , Mikyska Alexander , Houska Milan , Krofta Karel , Bogdanova Katerina , Janovska Sylva , Pejchal Jaroslav , Kolar Milan , Cermak Pavel , Bostik Pavel
Published: June 2021

Staphylococcus (S.) aureus is an important causative agent of wound infections with increasing incidence in the past decades. Specifically, the emergence of methicillin-resistant S. aureus (MRSA) causes serious problems, especially in nosocomial infections. Therefore, there is an urgent need to develop of alternative or supportive antimicrobial therapeutic modalities to meet these challenges. Purified compounds from hops have previously shown promising antimicrobial effects against MRSA isolates in vitro. In this study, purified beta-acids from hops were tested for their potential antimicrobial and healing properties using a porcine model of wounds infected by MRSA. The results show highly significant antimicrobial effects of the active substance in both the powder and Ambiderman-based application forms compared to both no-treatment control and treatment with Framycoin. Moreover, the macroscopic evaluation of the wounds during the treatment using the standardized Wound Healing Continuum indicated positive effects of the beta-acids on the overall wound healing. This is further supported by the microscopic data, which showed a clear improvement of the inflammatory parameters in the wounds treated by beta-acids. Thus, using the porcine model, we demonstrate significant therapeutic effects of hops compounds in the management of wounds infected by MRSA. Beta-acids from hops, therefore, represent a suitable candidate for the treatment of non-responsive nosocomial tissue infections by MRSA.
Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand
Authors: Wongkuna Supapit , Janvilisri Tavan , Phanchana Matthew , Harnvoravongchai Phurt , Aroonnual Amornrat , Aimjongjun Sathid , Malaisri Natamon , Chankhamhaengdecha Surang
Published: June 2021

Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A−B+CDT− (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT− (8%), five A−B+CDT+ (19%), seven A−B+CDT− (27%), and six A−B−CDT− (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand.
A MLP-Hedge-Algebras Admittance Controller for Physical Human–Robot Interaction
Authors: Toan Nguyen-Van , Khoi Phan-Bui , Yi Soo-Yeong
Published: June 2021

Recently, the identification of inertia and damping matrices (IIDM) and safety issues, as well as natural cooperation, are interestingly considered to enhance the quality of the physical human–robot interaction (pHRI). To cover all of these issues, advanced admittance controllers, such as those based on fuzzy logic or hedge algebras, have been formulated and successfully applied in several industrial problems. However, the inference mechanism of those kinds of controllers causes the discreteness of the super surface describing the input–output relationship in the Cartesian coordinates. As a consequence, the quality of the safe-natural cooperation between humans and robots is negatively affected. This paper presents an alternative admittance controller for pHRI by using a combination of hedge algebras and multilayer perceptron neural network (MLP), whose purpose is to create a more accurate inference mechanism for the admittance controller. To our best knowledge, this is the first time that such a neural network is considered for the inference mechanism of hedge algebras and also the first time that such an admittance controller is used for pHRI. The proposed admittance controller is verified on a teaching task using a 6-DOF manipulator. Experimental results have shown that the proposed method provides better cooperation compared with previous methods.
A Novel Patient-to-Image Surface Registration Technique for ENT- and Neuro-Navigation Systems: Proper Point Set in Patient Space
Authors: Choi Ahnryul , Chae Seungheon , Kim Tae-Hyong , Jung Hyunwoo , Lee Sang-Sik , Lee Ki-Young , Mun Joung-Hwan
Published: June 2021

Patient-to-medical image registration is a crucial factor that affects the accuracy of image-guided ENT- and neurosurgery systems. In this study, a novel registration protocol that extracts the point cloud in the patient space using the contact approach was proposed. To extract the optimal point cloud in patient space, we propose a multi-step registration protocol consisting of augmentation of the point cloud and creation of an optimal point cloud in patient space that satisfies the minimum distance from the point cloud in the medical image space. A hemisphere mathematical model and plastic facial phantom were used to validate the proposed registration protocol. An optical and electromagnetic tracking system, of the type that is commonly used in clinical practice, was used to acquire the point cloud in the patient space and evaluate the accuracy of the proposed registration protocol. The SRE and TRE of the proposed protocol were improved by about 30% and 50%, respectively, compared to those of a conventional registration protocol. In addition, TRE was reduced to about 28% and 21% in the optical and electromagnetic methods, respectively, thus showing improved accuracy. The new algorithm proposed in this study is expected to be applied to surgical navigation systems in the near future, which could increase the success rate of otolaryngological and neurological surgery.
Laminar-Turbulent Transition Localization in Thermographic Flow Visualization by Means of Principal Component Analysis
Authors: Gleichauf Daniel , Oehme Felix , Sorg Michael , Fischer Andreas
Published: June 2021

Thermographic flow visualization is a contactless, non-invasive technique to visualize the boundary layer flow on wind turbine rotor blades, to assess the aerodynamic condition and consequently the efficiency of the entire wind turbine. In applications on wind turbines in operation, the distinguishability between the laminar and turbulent flow regime cannot be easily increased artificially and solely depends on the energy input from the sun. State-of-the-art image processing methods are able to increase the contrast slightly but are not able to reduce systematic gradients in the image or need excessive a priori knowledge. In order to cope with a low-contrast measurement condition and to increase the distinguishability between the flow regimes, an enhanced image processing by means of the feature extraction method, principal component analysis, is introduced. The image processing is applied to an image series of thermographic flow visualizations of a steady flow situation in a wind tunnel experiment on a cylinder and DU96W180 airfoil measurement object without artificially increasing the thermal contrast between the flow regimes. The resulting feature images, based on the temporal temperature fluctuations in the images, are evaluated with regard to the global distinguishability between the laminar and turbulent flow regime as well as the achievable measurement error of an automatic localization of the local flow transition between the flow regimes. By applying the principal component analysis, systematic temperature gradients within the flow regimes as well as image artefacts such as reflections are reduced, leading to an increased contrast-to-noise ratio by a factor of 7.5. Additionally, the gradient between the laminar and turbulent flow regime is increased, leading to a minimal measurement error of the laminar-turbulent transition localization. The systematic error was reduced by 4% and the random error by 5.3% of the chord length. As a result, the principal component analysis is proven to be a valuable complementary tool to the classical image processing method in flow visualizations. After noise-reducing methods such as the temporal averaging and subsequent assessment of the spatial expansion of the boundary layer flow surface, the PCA is able to increase the laminar-turbulent flow regime distinguishability and reduce the systematic and random error of the flow transition localization in applications where no artificial increase in the contrast is possible. The enhancement of contrast increases the independence from the amount of solar energy input required for a flow evaluation, and the reduced errors of the flow transition localization enables a more precise assessment of the aerodynamic condition of the rotor blade.
Objective Evaluation of Therapeutic Effects of ADHD Medication by Analyzing Movements Using a Smart Chair with Piezoelectric Material
Authors: Yang Rei-Cheng , Wu Rong-Ching , Chiang Ching-Tai , Chiu Yi-Hung , Ouyang Chen-Sen , Lin Ying-Tong , Lin Lung-Chang
Published: June 2021

Attention-deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in schoolchildren. Several methods are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In this study, a piezoelectric material was applied to a medical chair to objectively evaluate the therapeutic effect of ADHD medication before and after treatment. A total of 22 patients (18 boys and 4 girls) with ADHD were enrolled. During the appointment, the patients’ movements were recorded by the piezoelectric material before being analyzed. The variance, zero-crossing rate, and high energy rate of movements were used to analyze the signal in this study. The results showed the variance, zero-crossing rate, and high energy rate in patients with ADHD all decreased significantly after 1 month of methylphenidate use. Although the hyperactivity subscales of SNAP obtained from parents and teachers demonstrated significant decreases after 1 month of medication, the reduction rate of the three aforementioned measurements decreased more than hyperactivity subscales. This suggests that the use of a smart chair equipped with a piezoelectric material is an objective and useful method for evaluating the therapeutic effects of ADHD medication.
Evaluation of Maturity and Odor Emissions in the Process of Combined Composting of Kitchen Waste and Garden Waste
Authors: Zhang Bangxi , Fan Feifei , Guo Chao , Yu Mingji , Zhao Mingcan , Song Yuan , Li Yun
Published: June 2021

With the development of urbanization, kitchen waste and garden waste have become an important part of municipal solid waste (MSW), which is in urgent need of resource treatment. This study investigated the impacts of garden waste as auxiliary materials on maturity and odor emissions (NH3 and H2S) during kitchen waste composting. The result showed that the combined composting product of kitchen waste and garden waste achieved the maturity effect, and the co-composting effect was better than that of separate composting of kitchen waste. Meanwhile, compared with the separate composting treatment of kitchen waste, the co-composting treatment of kitchen waste and garden waste can effectively reduce the cumulative emissions of H2S by more than 85%, and effectively reduce the cumulative emissions of NH3 by more than 75%. This study provides a technical reference for the green fertilizer utilization of kitchen waste and garden waste.
Recent Advances in Experimental Burn Models
Authors: Hao Dandan , Nourbakhsh Mahtab
Published: June 2021

Experimental burn models are essential tools for simulating human burn injuries and exploring the consequences of burns or new treatment strategies. Unlike clinical studies, experimental models allow a direct comparison of different aspects of burns under controlled conditions and thereby provide relevant information on the molecular mechanisms of tissue damage and wound healing, as well as potential therapeutic targets. While most comparative burn studies are performed in animal models, a few human or humanized models have been successfully employed to study local events at the injury site. However, the consensus between animal and human studies regarding the cellular and molecular nature of systemic inflammatory response syndrome (SIRS), scarring, and neovascularization is limited. The many interspecies differences prohibit the outcomes of animal model studies from being fully translated into the human system. Thus, the development of more targeted, individualized treatments for burn injuries remains a major challenge in this field. This review focuses on the latest progress in experimental burn models achieved since 2016, and summarizes the outcomes regarding potential methodological improvements, assessments of molecular responses to injury, and therapeutic advances.
DNA Damage Repair Gene Set as a Potential Biomarker for Stratifying Patients with High Tumor Mutational Burden
Authors: Chiu To-Yuan , Lin Ryan Weihsiang , Huang Chien-Jung , Yeh Da-Wei , Wang Yu-Chao
Published: June 2021

Tumor mutational burden (TMB) is a promising predictive biomarker for cancer immunotherapy. Patients with a high TMB have better responses to immune checkpoint inhibitors. Currently, the gold standard for determining TMB is whole-exome sequencing (WES). However, high cost, long turnaround time, infrastructure requirements, and bioinformatics demands have prevented WES from being implemented in routine clinical practice. Panel-sequencing-based estimates of TMB have gradually replaced WES TMB; however, panel design biases could lead to overestimation of TMB. To stratify TMB-high patients better without sequencing all genes and avoid overestimating TMB, we focused on DNA damage repair (DDR) genes, in which dysfunction may increase somatic mutation rates. We extensively explored the association between the mutation status of DDR genes and TMB in different cancer types. By analyzing the mutation data from The Cancer Genome Atlas, which includes information for 33 different cancer types, we observed no single DDR gene/pathway in which mutation status was significantly associated with high TMB across all 33 cancer types. Therefore, a computational algorithm was proposed to identify a cancer-specific gene set as a surrogate for stratifying patients with high TMB in each cancer. We applied our algorithm to skin cutaneous melanoma and lung adenocarcinoma, demonstrating that the mutation status of the identified cancer-specific DDR gene sets, which included only 9 and 14 genes, respectively, was significantly associated with TMB. The cancer-specific DDR gene set can be used as a cost-effective approach to stratify patients with high TMB in clinical practice.
Regulation of Viral Infection in Diabetes
Authors: Nagafuchi Seiho
Published: June 2021

Though there is no ‘Diabetes Virus’, multiple agents such as mumps virus, rubella virus, influenza virus, type A hepatitis virus, enterovirus, rotavirus, cytomegalovirus, varicella-zoster virus, human herpesvirus 6, Epstein-Barr virus, and also SARS-CoV-2 have been reported to be associated to diabetes [...]
SARS-CoV-2 Variants in Lebanon: Evolution and Current Situation
Authors: Fayad Nancy , Abi Habib Walid , Kandeil Ahmed , El-Shesheny Rabeh , Kamel Mina Nabil , Mourad Youmna , Mokhbat Jacques , Kayali Ghazi , Goldstein Jimi , Abdallah Jad
Published: June 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen a worldwide spread since its emergence in 2019, including to Lebanon, where 534,968 confirmed cases (8% of the population) and 7569 deaths have been reported as of 14 May 2021. With the genome sequencing of strains from various countries, several classification systems were established via genome comparison. For instance, the GISAID clades classification highlights key mutations in the encoded proteins that could potentially affect the virus’ infectivity and transmission rates. In this study, 58 genomes of Lebanese SARS-CoV-2 strains were analyzed, 28 of which were sequenced for this study, and 30 retrieved from the GISAID and GenBank databases. We aimed to classify these strains, establish their phylogenetic relationships, and extract the mutations causing amino acid substitutions within, particularly, the structural proteins. The sequenced Lebanese SARS-COV-2 strains were classified into four GISAID clades and 11 Pango lineages. Moreover, 21 uncommon mutations in the structural proteins were found in the newly sequenced strains, underlining interesting combinations of mutations in the spike proteins. Hence, this study constitutes an observation and description of the current SARS-CoV-2 genetic and clade situation in Lebanon according to the available sequenced strains.
Assessment of MicroRNA (miR)-365 Effects on Oral Squamous Carcinoma Cell Line Phenotypes
Authors: Coon Jeffrey , Kingsley Karl
Published: June 2021

miR-365 is a microRNA that regulates transcription and has been demonstrated to promote oncogenesis and metastasis in some cancers while suppressing these effects in others. Virtually no information is known about the presence or function of miR-365 in oral cancers. Based upon this information, the primary goal of this project was to evaluate the expression of miR-365 in existing oral cancer cell lines. Five commercially available oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, and CAL27) were obtained and cultured. RNA was then screened by PCR using primers specific for miR-365, as well as matrix metalloproteinase (MMP-2) and a downstream cancer stem cell regulator (NKX2.1), and structural and metabolic standards (beta actin, GAPDH). miR-365 was detected among these oral cancers, and some cells also expressed NKX2.1 and MMP-2, which correlated with miR-365 levels. The relative expression of miR-365, NKX2.1, and MMP-2 RNA was higher than expected. Transfection of miR-365 resulted in a significant increase in proliferation, which was not observed in the negative controls. These data appear to confirm miR-365 expression in oral cancers, which may also be correlated with MMP-2 and NKX2.1 expression. Moreover, the fastest growing oral cancers with the highest viability produced the most miR-365. In addition, miR-365 transfected into cells significantly increased growth, even in normal cells. More research is needed to elucidate the pathways responsible for these observations.
Association of Serum Alkaline Phosphatase with the TG/HDL Ratio and TyG Index in Korean Adults
Authors: Son Da-Hye , Ha Hyun-Su , Lee Yong-Jae
Published: June 2021

Alkaline phosphatase (ALP) has long been considered a marker of hepatobiliary and bone disorders, but recent studies have shown that increased ALP activity is correlated with various cardio-metabolic diseases. Thus, we investigated the association of serum ALP level with surrogate markers of insulin resistance such as triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C ratio) and triglyceride and glucose (TyG) index in the general population. The study included 12,868 men and women aged 19 years and older. Participants were categorized into four groups based on serum ALP level (U/L) as follows: Q1: 55–190 U/L, Q2: 191–224 U/L, Q3: 225–265 U/L, and Q4: 266–923 U/L for men, Q1: 48–161 U/L, Q2: 162–198 U/L, Q3: 199–245 U/L, Q4: 246–790 U/L for women. The insulin resistance cut-off levels were defined corresponding to the 75th percentile of the TyG index and TG/HDL-C ratio in the current samples. Odds ratios (ORs) with 95% confidence intervals (CIs) of insulin resistance according to quartile of serum ALP level were calculated using weighted multivariate logistic regression analysis. Compared with Q1, the adjusted OR (95% CI) for insulin resistance of the Q4 serum ALP group was 1.517 (1.234–1.866) in men and 1.881 (1.399–2.528) in women using the TG/HDL-C ratio and 1.374 (1.093–1.728) in men and 2.047 (1.468–2.855) in women using the TyG index after adjusting for confounding variables. Serum ALP levels are independently and positively associated with surrogate markers of insulin resistance in Korean adults.
Context-Specific Osteogenic Potential of Mesenchymal Stem Cells
Authors: Kostina Aleksandra , Lobov Arseniy , Semenova Daria , Kiselev Artem , Klausen Polina , Malashicheva Anna
Published: June 2021

Despite the great progress in the field of bone tissue regeneration, the early initiating mechanisms of osteogenic differentiation are not well understood. Cells capable of osteogenic transformation vary from mesenchymal stem cells of various origins to mural cells of vessels. The mechanisms of pathological calcification are thought to be similar to those of bone formation. Notch signaling has been shown to play an important role in osteogenic differentiation, as well as in pathological calcification. Nevertheless, despite its known tissue- and context-specificity, the information about its role in the osteogenic differentiation of different cells is still limited. We compared mesenchymal stem cells from adipogenic tissue (MSCs) and interstitial cells from the aortic valve (VICs) by their ability to undergo Notch-dependent osteogenic differentiation. We showed differences between the two types of cells in their ability to activate the expression of proosteogenic genes RUNX2, BMP2, BMP4, DLX2, BGLAP, SPRY, IBSP, and SPP1 in response to Notch activation. Untargeted metabolomic profiling also confirms differences between MSCs and VICs in their osteogenic state. Analysis of the activity of RUNX2 and SPP1 promoters shows fine-tuned dose-dependency in response to Notch induction and suggests a direct link between the level of Notch activation, and the proostogenic gene expression and corresponding osteogenic induction. Our data suggest that osteogenic differentiation is a context-dependent process and the outcome of it could be cell-type dependent.
Mucus, Microbiomes and Pulmonary Disease
Authors: Meldrum Oliver W. , Chotirmall Sanjay H.
Published: June 2021

The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.
Zeb1 and SK3 Channel Are Up-Regulated in Castration-Resistant Prostate Cancer and Promote Neuroendocrine Differentiation
Authors: Bery Fanny , Cancel Mathilde , Guéguinou Maxime , Potier-Cartereau Marie , Vandier Christophe , Chantôme Aurélie , Guibon Roseline , Bruyère Franck , Fromont Gaëlle , Mahéo Karine
Published: June 2021

Therapeutic strategies for metastatic castration-resistant prostate cancer aim to target androgen receptor signaling. Despite initial survival benefits, treatment resistance invariably occurs, leading to lethal disease. Therapies targeting the androgen receptor can induce the emergence of a neuroendocrine phenotype and reactivate embryonic programs associated with epithelial to mesenchymal transition. We recently reported that dysregulation of the calcium signal can induce the transcription factor Zeb1, a key determinant of cell plasticity during tumor progression. The aim of this study was to determine whether the androgen receptor-targeted treatment Enzalutamide could induce dysregulation of the calcium signal involved in the progression toward epithelial to mesenchymal transition and neuroendocrine differentiation, contributing to therapeutic escape. Our results show that Zeb1 and the SK3 potassium channel are overexpressed in vivo in neuroendocrine castration-resistant prostate cancer and in vitro in LNCaP cells neurodifferentiated after Enzalutamide treatment. Moreover, the neuroendocrine phenotype is associated with a deregulation of the expression of Orai calcium channels. We showed that Zeb1 and SK3 are critical drivers of neuroendocrine differentiation. Interestingly, Ohmline, an SK3 inhibitor, can prevent the expression of Zeb1 and neuroendocrine markers induced by Enzalutamide. This study offers new perspectives to increase hormone therapy efficacy and improve clinical outcomes.
Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors
Authors: Ma Jin , Ren Jiang , Thorikay Midory , van Dinther Maarten , Sanchez-Duffhues Gonzalo , Caradec Josselin , Benderitter Pascal , Hoflack Jan , ten Dijke Peter
Published: June 2021

Angiogenesis, i.e., the formation of new blood vessels from pre-existing endothelial cell (EC)-lined vessels, is critical for tissue development and also contributes to neovascularization-related diseases, such as cancer. Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs) are among many secreted cytokines that regulate EC function. While several pharmacological anti-angiogenic agents have reached the clinic, further improvement is needed to increase clinical efficacy and to overcome acquired therapy resistance. More insights into the functional consequences of targeting specific pathways that modulate blood vessel formation may lead to new therapeutic approaches. Here, we synthesized and identified two macrocyclic small molecular compounds termed OD16 and OD29 that inhibit BMP type I receptor (BMPRI)-induced SMAD1/5 phosphorylation and downstream gene expression in ECs. Of note, OD16 and OD29 demonstrated higher specificity against BMPRI activin receptor-like kinase 1/2 (ALK1/2) than the commonly used small molecule BMPRI kinase inhibitor LDN-193189. OD29, but not OD16, also potently inhibited VEGF-induced extracellular regulated kinase MAP kinase phosphorylation in ECs. In vitro, OD16 and OD29 exerted strong inhibition of BMP9 and VEGF-induced ECs migration, invasion and cord formation. Using Tg (fli:EGFP) zebrafish embryos, we found that OD16 and OD29 potently antagonized dorsal longitudinal anastomotic vessel (DLAV), intra segmental vessel (ISV), and subintestinal vessel (SIV) formation during embryonic development. Moreover, the MDA-MB-231 breast cancer cell-induced tumor angiogenesis in zebrafish embryos was significantly decreased by OD16 and OD29. Both macrocyclic compounds might provide a steppingstone for the development of novel anti-angiogenesis therapeutic agents.
WWOX Loses the Ability to Regulate Oncogenic AP-2γ and Synergizes with Tumor Suppressor AP-2α in High-Grade Bladder Cancer
Authors: Kołat Damian , Kałuzińska Żaneta , Bednarek Andrzej K. , Płuciennik Elżbieta
Published: June 2021

The cytogenic locus of the WWOX gene overlaps with the second most active fragile site, FRA16D, which is present at a higher frequency in bladder cancer (BLCA) patients with smoking habit, a known risk factor of this tumor. Recently, we demonstrated the relevance of the role of WWOX in grade 2 BLCA in collaboration with two AP-2 transcription factors whose molecular actions supported or opposed pro-cancerous events, suggesting a distinct character. As further research is needed on higher grades, the aim of the present study was to examine WWOX-AP-2 functionality in grade 3 and 4 BLCA using equivalent in vitro methodology with additional transcriptome profiling of cellular variants. WWOX and AP-2α demonstrated similar anti-cancer functionality in most biological processes with subtle differences in MMP-2/9 regulation; this contradicted that of AP-2γ, whose actions potentiated cancer progression. Simultaneous overexpression of WWOX and AP-2α/AP-2γ revealed that single discrepancies appear in WWOX-AP-2α collaboration but only at the highest BLCA grade; WWOX-AP-2α collaboration was considered anti-cancer. However, WWOX only appeared to have residual activity against oncogenic AP-2γ in grade 3 and 4: variants with either AP-2γ overexpression alone or combined WWOX and AP-2γ overexpression demonstrated similar pro-tumoral behavior. Transcriptome profiling with further gene ontology certified biological processes investigated in vitro and indicated groups of genes consisting of AP-2 targets and molecules worth investigation as biomarkers. In conclusion, tumor suppressor synergism between WWOX and AP-2α is unimpaired in high-grade BLCA compared to intermediate grade, yet the ability of WWOX to guide oncogenic AP-2γ is almost completely lost.
The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI
Authors: Kamada Yasuyuki , Hida Koya , Yonemura Yutaka , Sugarbaker Paul H. , Ghabra Shadin , Ishihara Soichiro , Nagata Hiroshi , Murono Koji , Goi Takanori , Katayama Kanji , Morikawa Mitsuhiro , Rau Beate , Piso Pompiliu , Acs Miklos , Coccolini Federico , Canbay Emel , Hsieh Mao-Chih , Bhatt Aditi , Bonnot Pierre-Emmanuel , Glehen Olivier
Published: June 2021

Background: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). Methods: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. Results: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2–7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0–2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2–2.6) years. Conclusions: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.
Long-Term Follow-Up of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: Aims and Methodological Approach for Fondazione Italiana Linfomi Systematic Reviews
Authors: Gerardi Chiara , Allocati Eleonora , Minoia Carla , Guarini Attilio , Banzi Rita
Published: June 2021

Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). FIL set up multidisciplinary teams, representing all different skills relevant for cancer survivors. They conducted a series of systematic reviews focused on three main aspects: incidence of long-term toxicity; comparison of old or standard therapies and more recent ones; and evidence on specific follow-up approaches. The teams applied this framework to cardiological, endocrine-metabolic, neurological/cognitive, and psychological disorders, secondary cancers, fertility preservation, and lifestyles. Each team conducted comprehensive literature searches on PubMed, Embase and Cochrane Library databases up to 2020. Screening followed the PRISMA statement for reporting systematic reviews. The reviews report the results of this wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-up. From a clinical point of view, the series confirmed that the evidence on follow-up tended to focus on solid tumors with scant evidence on hematological malignancies.
Lengthening the Lower Extremities of Children with Ollier’s and Maffucci’s Enchondromatosis Using Implantable Lengthening Nails
Authors: Huser Aaron J. , Hoellwarth Jason Shih , Coppa Valentino , Feldman David S. , Paley Dror
Published: June 2021

There are multiple forms of enchondromatosis with Ollier’s and Maffucci’s being the most prevalent types. Limb length discrepancy is a common problem in patients with Ollier’s and Maffucci’s enchondromatosis. There are multiple reports about lengthening bones in patients with enchondromatosis using external fixators. However, there are no case series regarding the use of implantable lengthening technology. The purpose of this paper is to describe our experience with implantable nail lengthening in patients with enchondromatosis. A retrospective chart and radiographic review of patients with enchondromatosis who underwent implantable nail limb lengthening was performed. Seven patients with 14 bony segments were reviewed. A total of 11/14 lengthenings were completed without difficulty. There were no issues in terms of fixation location in patients with Ollier’s disease. One patient with Maffucci’s syndrome experienced migration of the nail during two lengthenings due to a combination of intralesional fixation and preconsolidation. One patient with Ollier’s disease developed a knee extension contracture requiring manipulation under anesthesia. No other complications were recorded. The use of implantable nail lengthening to resolve limb length discrepancies in patients with Ollier’s disease appears to be safe and effective.
STEM Faculty Instructional Data-Use Practices: Informing Teaching Practice and Students’ Reflection on Students’ Learning
Authors: Lenhart Cindy , Bouwma-Gearhart Jana
Published: June 2021

This paper explores the affordances and constraints of STEM faculty members’ instructional data-use practices and how they engage students (or not) in reflection around their own learning data. We found faculty used a wide variety of instructional data-use practices. We also found several constraints that influenced their instructional data-use practices, including perceived lack of time, standardized curriculum and assessments predetermined in scope and sequence, and a perceived lack of confidence and competence in their instructional data-use practices. Novel findings include faculty descriptions of instructional technology that afforded them access to immediate and nuanced instructional data. However, faculty described limited use of instructional data that engaged students in reflecting on their own learning data. We consider implications for faculty’s instructional data-use practices on departmental and institutional policies and procedures, professional development experts, and for faculty themselves.
Identification of Prognostic Factors and Predicting the Therapeutic Effect of Laser Photocoagulation for DME Treatment
Authors: Ilyasova Nataly , Shirokanev Aleksandr , Kirsh Dmitriy , Demin Nikita , Zamytskiy Evgeniy , Paringer Rustam , Antonov Alexey
Published: June 2021

Diabetic retinopathy is among the most severe complications of diabetes, most often leading to rapid and irreversible vision loss. The laser coagulation procedure, which consists of applying microburns to the fundus, has proven to be an effective method for treating diabetic retinopathy. Unfortunately, modern research does not pay enough attention to the study of the arrangement of microburns in the edema area—One of the key factors affecting the quality of therapy. The aim of this study was to propose a computational decision-making support system for retina laser photocoagulation based on the analysis of photocoagulation plans. Firstly, we investigated a set of prognostic factors based on 29 features describing the geometric arrangement of coagulates. Secondly, we designed a technology for the intelligent analysis of the photocoagulation plan that allows the effectiveness of the treatment to be predicted. The studies were carried out using a large database of fundus images from 108 patients collected in clinical trials. The results demonstrated a high classification accuracy at a level of over 85% using the proposed prognostic factors. Moreover, the designed technology proved the superiority of the proposed algorithms for the automatic arrangement of coagulates, predicting a 99% chance of a positive therapeutic effect.