bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Interactions of Non-structural Protein-W61 with Nucleoprotein: And as a Potential Therapeutic Target in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Replication
Authors: Park Ji-Young , Chandran Sivasankar , Perumalraja Kirthika , Dhamodharan Prabhu , Lee John Hwa
Published: August 2023

The non-structural protein (NS) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NS and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at NSs1-32, NSs56-82, and NSs207-237. Rationally, three mutant NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NS. Over-expression of wild-type NS in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NS-NP interaction and viral replication. Thus, the present study identified a critical NS site, which could be targeted for development of therapeutic regimens against SFTSV.
AWS-S3-Integrity-Check: An Open-Source Bash Tool to Verify the Integrity of a Dataset Stored on Amazon S3
Authors: García-Ruiz Sonia , H Reynolds Regina , Grant-Peters Melissa , K Gustavsson Emil , Fairbrother-Browne Aine , Chen Zhongbo , W Brenton Jonathan , Ryten Mina
Published: August 2023

Amazon Simple Storage Service (Amazon S3) has become a widely used and reliable platform for storing large biomedical datasets. However, unintended changes to the original data can occur during the data writing and transmission, ultimately altering the original contents of the object transferred and producing unexpected results when later accessed. Despite the interest in verifying end-to-end data integrity, there are no existing open-source and easy-to-use tools to accomplish this mission. To bridge this gap, here we present aws-s3-integrity-check, a user-friendly, lightweight and reliable bash tool to verify the integrity of a dataset stored within an Amazon S3 bucket. By using this tool, we completed the integrity verification of 1,045 records ranging between 5 Bytes and 10 Gigabytes (GB) in size and occupying a total of ~935 GigaBytes (GB) of Amazon S3 cloud storage space in ~114 minutes. The aws-s3-integrity-check tool also provides file-by-file on-screen and log-file-based information about the status of each individual integrity check. To the best of our knowledge, the aws-s3-integrity-check bash tool is the only open-source tool that allows verifying the integrity of a dataset uploaded to the Amazon S3 Storage system in a quick, reliable and efficient manner. The aws-s3-integrity-check tool is freely available for download and use at https://github.com/SoniaRuiz/aws-s3-integrity-check and https://hub.docker.com/r/soniaruiz/aws-s3-integrity-check.
The Effect of High-Intensity Interval Exercise on Short-Term Glycaemic Control, Serum Level of Key Mediator in Hypoxia and Pro-Inflammatory Cytokines in Patients with Type 1 Diabetes
Authors: Hall Barbara , Żebrowska Aleksandra , Sikora Marcin , Siatkowski Szymon , Robins Anna
Published: August 2023

Type 1 diabetes (T1D) is associated with hyperglycaemia-induced hypoxia and inflammation. The study assessed the effects of a single high-intensity interval exercise (HIIE) on glycaemia (BG) and serum level of pro-inflammatory cytokines and an essential mediator of adaptive response to hypoxia in T1D patients. The macronutrients intake was also evaluated. Nine patients suffering from T1D for about 12 years and nine healthy individuals (CG) were enrolled and completed one session of HIIE at the intensity of 120% lactate threshold and duration of 4 x 5 min intermittent with 5 min rest after each bout of exercise. Capillary and venous blood was withdrawn at rest, immediately after and at the 24 h post-HIIE for analysis of BG, hypoxia-inducible factor alpha (HIF-1α), tumour necrosis factor alpha (TNF-α) and vascular-endothelial growth factor (VEGF). Pre-exercise BG was significantly higher in the T1D compared to the CG (p = 0.043). HIIE led to a significant decline in T1D patients’ BG (p = 0.027) and to a tendency for a lower BG at 24-h post-HIIE vs pre-HIIE. HIF-1α was significantly elevated in the T1D compared to CG and there was a trend for HIF-1α to decline, and VEGF, TNF-α to increase in response to HIIE in the T1D group. Both groups consumed higher and lower than recommended amounts of protein and fat, respectively. In T1D group, a tendency for a higher digestible carbohydrate intake and more frequent hyperglycaemic episodes on the day after HIIE were observed. HIIE was effective in reducing T1D patients’ glycaemia and improving the short-term glycaemic control. HIIE has the potential to improve adaptive response to hypoxia by elevating the serum level of VEGF. Patients’ diet and level of physical activity should be screened on a regular basis, and they should be educated on the glycaemic effects of digestible carbohydrates.
Differences in Land Tax Planning on New Risk Reduced Products in Europe: Assessment and Implications for Public Policies
Authors: Hernandez Fernando Pinto , Delgado-Rodríguez María Jesús
Published: August 2023

Taxes on the consumption of certain products have played a key role in public revenue analysis in European countries. This work aims to assess the differences in tax planning on new non-combustion products across some European territories. Through theoretical analysis, the paper has three distinct aspects. Firstly, we show the taxpayer profile in different countries. Secondly, the study analyzes the risks for the health system and the individual. Thirdly, the design of the land tax is based on previous experience and planning in Europe. This paper concludes with a case study for different countries: 1) Spain “vapers” and “smokers”, where the analysis is based on micro-data from the European Health Interview Survey 2020. 2) Sweden with the analysis of snus, shows it as a practice to reach economic savings while decreasing economic costs thanks to the nudging of consumers towards better products. The results show taxation and, specially, land taxation, should consider differences in planning in the case of new products, such as the non-combustion products, given the user per capita income and the potential lower health risks involved.
Actinide ion (Americium-241 and Uranium-232) Interaction with Hybrid Silica-Hyperbranched Poly(ethylene imine) Nanoparticles and Xerogels
Authors: Ioannidis Ioannis , Pashalidis Ioannis , Arkas Michael
Published: August 2023

The binding of actinide ions (Am(III) and U(VI)) in aqueous solutions by hybrid silica-hyperbranched poly(ethylene imine) nanoparticles (NP) and xerogels (XG) has been studied by means of batch experiments at different pH values (4, 7 and 9) under ambient atmospheric conditions. Both materials present relatively high removal efficiency at pH 4 and pH 7 (> 70%) for Am(III) and U(VI). The lower removal efficiency for the nanoparticles is basically associated with the compact structure of the nanoparticles and the lower permeability and access to active amine groups compared to xerogels, and the negative charge of the radionuclide species formed under alkaline conditions (e.g. UO2(CO3)34- and Am(CO3)2-). Generally, the adsorption process is relatively slow due to the very low radionuclide concentrations used in the study and is basically governed by the actinide diffusion from the aqueous phase to the solid surface. On the other hand, the adsorption is favored with increasing temperature assuming that the reaction is endothermic and entropy-driven, which is associated with increasing randomness at the solid-liquid interphase upon actinide adsorption. To the best of our knowledge, this is the first study on hybrid silica-hyperbranched poly(ethylene imine) nanoparticle and xerogel materials used as adsorbents for americium and uranium at ultra-trace levels. Compared to other adsorbent materials used for binding americium and uranium ions, both materials show far higher binding efficiency. Xerogels could remove both actinides even from seawater by almost 90%, whereas nanoparticles could remove uranium by 80% and americium by 70%. The above, along with their simple derivatization to increase the selectivity towards a specific radionuclide and their easy processing to be included in separation technologies, could make these materials attractive candidates for the treatment of radionuclide/actinide contaminated water.
Valorization of Cheese Whey through Bioethanol Production and Probiotic Drink Development: A Sustainable Approach for Organic Waste Management
Authors: Maidali Devraj , Thapa Magar Sabina , Ghimire Sita , Pun Manju , Pandey Shreejana , Chataut Guheswari , Maharjan Suja , Aryal Pramod
Published: August 2023

Cheese whey, a significant byproduct of the dairy industry, poses a substantial environmental challenge due to its organic pollutant load and large size demands for effective and affordable valorization methods. The abundance of lactose and other organic compounds in whey contributes to its elevated Biological Oxygen Demand (BOD) and Chemical Oxygen Demand (COD), further straining natural ecosystems. This study aimed to investigate the nutritional potential of whey and its conversion into value-added products: bioethanol and probiotic drinks. To achieve this, Bacillus megaterium and Bacillus subtilis strains, isolated from soil samples in Nepal, were co-cultured with Lactobacillus and Saccharomyces cerevisiae in the whey broth for fermentation. Ethanol distillation was carried out using a Rota-evaporator to maintain the viability of the fermenting organisms within the broth. Moreover, the probiotic criteria of the fermenting strains were extensively examined. Experimental observations revealed a remarkable concentration of 9.2 g/L of ethanol, resulting in an ethanol yield of 0.23 g/L. Extrapolating this rate, it is theoretically possible to produce an annual global bioethanol output of 5 million tons using whey as a sustainable and abundant resource. Furthermore, the study explores novel advancements in the distillation process, demonstrating the successful extraction of ethanol at room temperature. Additionally, the fermentation organisms employed in this research exhibit robust viability, surviving various in-vitro stress-tolerant tests, including exposure to bile salt, pH fluctuations, and gastric juice. These resilient strains also demonstrated long-term stability in fermented whey broth, making them promising candidates for the development of probiotic beverages. This dual approach not only enables the sustainable management of organic waste but also presents an opportunity to create value-added products with positive implications for both the environment and human health.
Microgranular Fertilizers as an Option to Reduce Nutrient Sur-Pluses When Growing Maize (Zea mays) in Regions with High Livestock Farming Intensity
Authors: Eulenstein Frank , Ahlborn Julian , Thielicke Matthias
Published: August 2023

The present contribution provides the first agro-economic and ecological account of the in-furrow application of a mineral and an organomineral microgranular fertilizer in comparison to a wide spread mineral band fertilizer in temperate climate regions. The reduction of phosphorus inputs while maintaining the yield of maize plants (Zea mays) is the focus of the study. In a three-year field trial, the dry matter yields gained with the two phosphorus-reduced microgranular fertilizers and standard diammonium phosphate (DAP) fertilization were examined. The application of the organomineral microgranular fertilizer resulted in dry matter yields that were 15% higher (2.8 tons per hectare) than the DAP variant, while higher yields using the mineral microgranular fertilizer occurred only in a single year. The higher yield of the organomineral microgranular fertilizer and the lower phosphorus amounts applied with that product resulted in a moderate phosphorus excess of 2.7 kg P ha-1, while DAP fertilization resulted in a surplus of 25.5 kg per hectare. A similar pattern of phosphorus balance was observed on the plots fertilized with the mineral microgranular fertilizer. We conclude that both tested microgranular fertilizers provide an adequate alternative to the wide-spread DAP fertilization in maize cultivation on fertile soils.
Tissue Metalloproteinases as Crohn Disease Recurrence Markers
Authors: Pasternak Grzegorz , Chrzanowski Grzegorz , Aebisher David , Mysliwiec Angelika , Dynarowicz Klaudia , Bartusik-Aebisher Dorota , Filip Rafał
Published: August 2023

Crohn's disease is a non-specific inflammatory bowel disease, which is a chronic condition that affects the ileum and/or large intestine. At the same time, it can also involve any other part of the human body, that is, from the mouth to the anus. The symptoms are very bothersome and cause a significant reduction in quality of life and sometimes even crippling permanent damage to the gastrointestinal tract, which requires enteral or parenteral nutrition for life. The purpose of this study was to investigate tissue metalloproteinases as markers of recurrent Crohn's disease. The experimental groups included 31 patients and 10 patients with normal Crohn's disease, ranging in age from 23-70 years, with a mean age of 40.4. Collected tissues were frozen and then fragmented tissues were homogenized with Ripa Lysis buffer on ice. The supernatant was collared and four metalloproteinases - MMP 3, MMP 7, MMP 8 and MMP 9 - were an-alized by Enzyme-linked Immunosorbent Assay using SEA101HU, SEA102Hu, SEA103Hu and SEA553Hu kits (Cloud-Clone Corp., Kata, TX, USA). All chemical analyses were performed in triplicate. Metalloproteinase content was expressed as mean ± standard deviation. Metalloproteinase 3 and metalloproteinase 8) significantly influenced the possibility of Crohn recurrence
Optimizing Nitrogen Application for Jojoba under Intensive Cultivation
Authors: Dag Arnon , Badichi Shamir , Ben-Gal Alon , Perry Aviad , Tel-Zur Noemi , Ron Yonatan , Tietel Zipora , Yermiyahu Uri
Published: August 2023

Although jojoba (Simmondsia chinensis) has been cultivated for years, information on its N re-quirements is limited. A 6-year study of mature jojoba plants grown under field conditions with an intensive management regime evaluated the effect of N-application rate on plant nutrient status, growth and productivity, and nitrate accumulation in the soil. Five levels of N application were tested: 50, 150, 250, 370 and 500 kg N ha-1. The fertilizers were provided all along the growing season via subsurface drip irrigation system. Leaf N concentration, in both spring and summer, reflected the level of N applied. Diagnostic leaf (youngest leaf that has reached full size) concentration of 1.3% N was identified as the threshold for N deficiency. Increasing rates of N application resulted in higher P levels in young leaves. Plant K status, as reflected by leaf analysis, was not affected by N treatment but was strongly affected by fruit load. Vegetative growth was inhibited when only 50 kg N ha-1 was applied. Soil analysis at the end of the fertilization season showed substantial accumulation of nitrate for the two highest application rates. Considering productivity, N costs, and environmental risk, 150 kg N ha-1 is the recommended dosage for in-tensively grown jojoba. N deficiencies can be identified using leaf analysis and excess N can be detected by soil sampling toward the end of the growing season. These results and tools will fa-cilitate precise N fertilization in intensive jojoba plantations.
Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells
Authors: Lee Seung-On , Lee Mee-Hyun , Kwak Ah-Won , Lee Jin-Young , Yoon Goo , Joo Sang Hoon , Choi Yung Hyun , Park Jin Woo , Shim Jung-Hyun
Published: August 2023

Licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata. CRC treatment has always been challenged by the development of resistance. We investigated the antiproliferative activity of LCH in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including phospho (p)-EGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation, as verified by N-acetyl-L-cysteine (NAC) treatment, and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP and increased. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of subG1 cells and arrested the cell cycle at the G1 phase. LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.
Can BPA Analogs Affect Cellular and Biochemical Responses in the Microalga Phaeodactylum tricornutum Bohlin?
Authors: Fabrello Jacopo , Ciscato Maria , Moschin Emanuela , Vecchia Francesca Dalla , Moro Isabella , Matozzo Valerio
Published: August 2023

Bisphenol A analogs (BPA analogs) are emerging contaminants with a rising production caused by the replacement of BPA with these compounds. The increased production of BPA analogs is leading to an increased release into various ecosystems, including sea. The aim of this study was to evaluate the biological effects of BPA analogs on a primary producer, the diatom Phaeodactylum tricornutum Bohlin. Three different BPA analogs (BPAF, BPF, and BPS) and their mixture were tested at the environmental relevant concentration of 300 ng/L. Growth curve, cell size and several biomarkers of oxidative stress and oxidative damage were measured. Our results indicated that the tested compounds caused alteration of the growth and induced oxidative stress altering many antioxidant enzymes. However, no oxidative damages were observed.
Drosophila melanogaster as a Translational Model System to Explore the Impact of Phytochemicals on Human Health
Authors: Lopez-Ortiz Carlos , Gracia-Rodriguez Celeste , Belcher Samantha , Flores-Iga Gerardo , Das Amartya , Nimmakayala Padma , Balagurusamy Nagamani , Reddy Umesh K
Published: August 2023

Fruits, vegetables, and spices are natural sources of bioactive phytochemicals such as polyphenols, carotenoids, flavonoids, curcuminoids, terpenoids, and capsaicinoids, possessing multiple health benefits and relatively low toxicity. These compounds found in the diet play a central role in organism development and fitness. Given the complexity of the whole-body response to dietary changes, invertebrate model organisms can serve as valuable tools to examine the interplay between genes, signaling pathways, and metabolism. Drosophila melanogaster, an invertebrate model with its extensively studied genome, has more than 70% gene homology to humans and has been used as a model system in biological studies for a long time. The notable advantages of Drosophila as a model system, such as their low maintenance cost, high reproductive rate, short generation time and lifespan, and the high similarity of metabolic pathways between Drosophila and mammals, have encouraged the use of Drosophila in the context of screening and evaluating the impact of phytochemicals present in the diet. In this chapter, we summarize and review the benefits of Drosophila as a model system for use in the study of phytochemical ingestion and describe the previously reported effects of phytochemical consumption in Drosophila.
Exploring the Potential of Heteroatom-Doped Graphene Nanoribbons as a Catalyst for Oxygen Reduction
Authors: Cardoso Eduardo S , Fortunato Guilherme V , Rodrigues Clauber D , Lanza Marcos R , MAIA GILBERTO
Published: August 2023

In this study, we created a series of N, S, and P-doped and co-doped carbon catalysts using a single graphene nanoribbon (GNR) matrix and thoroughly evaluated the impact of doping on ORR activity and selectivity in acidic, neutral, and alkaline conditions. The results obtained showed no significant changes in the GNR structure after the doping process, though changes were observed in the surface chemistry in view of the heteroatom insertion and oxygen depletion. Of all the dopants investigated, nitrogen (mainly in the form of pyrrolic-N and graphitic-N) was the most easily inserted and detected in the carbon matrix. The electrochemical analyses conducted showed that doping impacted the performance of the catalyst in ORR through changes in the chemical composition of the catalyst, as well as in the double-layer capacitance and electrochemically accessible surface area. In terms of selectivity, GNR doped with phosphorus and sulfur favored the 2e- ORR pathway, while nitrogen favored the 4e- ORR pathway. These findings can provide useful insights into the design of more efficient and versatile catalytic materials for ORR in different electrolyte solutions, based on functionalized carbon.
UV-C Light: A Promising Preservation Technology for Vegetable-based Nonsolid Food Products
Authors: Tchonkouang Rose Daphnee , Lima Alexandre Ribeiro , Quintino Andreia Costa , Cristofoli Nathana Lazarotto , Vieira Maria Margarida Cortês
Published: August 2023

A variety of bioactive substances present in fruits and vegetables processed products have health-promoting properties. Consumption of nutrient-rich plant-based products is essential to address undernutrition and micronutrient deficiencies. Preservation is paramount in manufacturing plant-based non-solid foods such as juices, purees, and sauces. Thermal processing has been widely used to preserve fruit and vegetable-based products by reducing enzymatic and microbial activities, thereby ensuring safety and prolonged shelf life. However, the nutritional value of products is compromised due to the deleterious effects of thermal treatments on essential nutrients and bioactive compounds. To prevent the loss of nutrients associated with thermal treatment, alternative technologies are being researched extensively. In studies conducted on non-solid food, UV-C treatment has been proven to preserve quality and minimize nutrient degradation. This review compiles information on the use of UV-C technology in preserving the nutritional attributes of non-solid foods derived from fruit and vegetables. Legislation, market potential, consumer acceptance, and limitations of UV-C are reviewed.
A Study on the Effects of Digital Finance on Green and Low Carbon Cyclic Development Based on Machine Learning Models
Authors: Zhang Xuewei , Ai Xiaoqing , Wang Xiaoxiang , Zong Gang , Zhang Jinghao
Published: August 2023

With technological transformations such as big data, blockchain, artificial intelligence, and cloud computing, digital techniques are penetrating the field of finance. Digital finance is a resource-saving and environmentally friendly innovative financial service. It shows great green attributes and can drive the flow of financial resources towards environmentally friendly enterprises, thereby promoting green and low-carbon development. This paper investigates the effects of digital finance on green and low-carbon cyclic development and the mechanism. First, the level of green and low carbon cyclic development in China is estimated from multiple aspects based on the panel data of 31 provinces by using the spatio-temporal range entropy weight method. Then, the working mechanism of digital finance on green and low carbon cyclic development is revealed by performing empirical tests based on panel regression models, mediating effect models, and threshold models. Finally, the effects of digital finance and conventional variables on green and low-carbon cyclic development are investigated by using a random forest model and a CatBoost model in based on the machine learning. The results show that digital finance has significant positive effects on green and low-carbon cyclic development, and technological innovation plays a key role in the effects of digital finance on green and low-carbon cyclic development; meanwhile, the driving effect of digital finance on green and low carbon cyclic development shows nonlinear features with increasing “marginal effect”; besides, both digital finance and conventional factors have significant impacts on green and low carbon cyclic development. This study provides an empirical basis and path reference for digital finance to achieve “carbon peak, carbon neutralization” in China.
Comparison of Cefazolin/Metronidazole versus Ampicillin-Sulbactam as Preoperative Antibiotics in Colorectal Surgery: Retrospective, Single-Center Cohort Study
Authors: Im Jae Hyoung , Lee Dong Yeop , Baek Ji Hyeon , Lee Se-joo , Jung Sungtaek , Kim Eunjung , Kang Dong Yoon , Lee Jin-Soo
Published: August 2023

Aim
The use of prophylactic antibiotics prior to colorectal surgery reduces surgical site infections. Cefazolin and metronidazole is a standard regimen. Ampicillin-sulbactam may be an alternative, but the data are limited. We compared the efficacy of ampicillin-sulbactam with cefazolin and metronidazole as prophylactic antibiotics.
Methods
Patients who underwent colorectal surgery at Inha University Hospital between 2010 and 2020 were treated prophylactically with cefazolin and metronidazole or ampicillin-sulbactam, and observed for 30 days following surgery. The primary outcome was surgical site infections. Secondary outcomes were deep/organ infections and the need for drainage.
Results
SSIs occurred in 2.6% (17/646) of the ampicillin-sulbactam group and was not inferior to the occurrence in the cefazolin and metronidazole group (3.8%, 21/556). There was no significant difference between the two groups in the secondary outcomes.
Conclusion
Compared with the cefazolin and metronidazole combination, the ampicillin-sulbactam group is non-inferior as a preoperative prophylactic antibiotic regimen for colorectal surgery.
Emerging Novel Therapies to Treat Urothelial Carcinoma
Authors: Rani Berkha , Ignatz-Hoover James J. , Rana Priyanka S. , Driscoll James Joseph
Published: August 2023

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.
The Huntington’s Disease Gene in an Italian Cohort of Patients With Bipolar Disorder
Authors: Ferrari Camilla , Capacci Elena , Bagnoli Silvia , Ingannato Assunta , Sorbi Sandro , Nacmias Benedetta
Published: August 2023

Background and objectives: Huntington disease (HD) is characterized by motor, cognitive and psychiatric manifestations and is caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and to evaluate any differences between bipolar patients carrying normal HTT allele and patients with expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients affected by bipolar disorder type 1 and type 2. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls.
Calibration Technique for MBE Growth of Long Wavelength InAlAs/InGaAs Quantum Cascade Lasers
Authors: Gutowski Piotr , Sankowska Iwona , Bugajski Maciej , Sobczak Grzegorz , Kuźmicz Aleksandr , Pierściński Kamil
Published: August 2023

In this paper we present methodology for precise calibration of Molecular Beam Epitaxy (MBE) growth process and achieving run to run stability of growth parameters. We present the analysis of the influence of fluxes stability during the growth of long wavelength quantum cascade laser structures designed for the range λ ~ 12–16 µm on wavelength accuracy with respect to desired emission wavelength. The active region of the lasers has a complex structure of nanometer thickness InxGa1-xAs/InyAl1-yAs superlattice. As a consequence, the compositional and thickness control of the structure via bulk growth parameters is rather difficult. To deal with this problem we employ methodology based on double-superlattice test structures, that precede the growth of the actual structures. The test structures are analyzed by high-resolution X-ray diffraction which allows to calibrate the growth of the complex active region of quantum cascade laser structures. We also study theoretically the effect of individual flux changes on emission wavelength and gain parameters of the laser. The results of simulations allow for determination of flux stability tolerance, preserving acceptable parameters of the laser and provide means of emission wavelength control. The proposed methodology was verified by the growth of laser structures for emission at around 13.5 μm.
Exploring Host-Specificity: Untangling the relationship between Leishmania (Viannia) species and its endosymbiont Leishmania RNA Virus 1
Authors: Santana Mayara Cristhine de Oliveira , Chourabi Khaled , Cantanhêde Lilian Motta , Cupolillo And Elisa
Published: August 2023

A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) is the Leishmania parasites carrying a viral endosymbiont Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in cultured strains of five L. (Viannia) species, and host specificity was suggested when studying LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and in 2 out of 4 L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent.
Dr Jekyll and Mr Hyde: From Two Branches of Immune Response to Three Types of Interferon Response
Authors: Brown Brent
Published: August 2023

Interferons were the original prototype cytokine system discovered during research of the 20th century. As the name suggests these were originally considered to be synthesised and secreted between cells. However, technological advancements since dictate processes involved in secreting these proteins can be extensively explained through both genetic and biochemical pathways comparatively clearer. Interferon (IFN) discovery occurred when genetic research was in its infancy. Simultaneous discovery by Franklin and Wilkins of deoxyribonucleic acid (DNA) structure and function occurred with Crick and Watson concurrently; however, two scientists Isaac and Lindemann described the first IFN in 1957. Technological advancement allows comparison, since many pathogens and genetic mutations can be factors in IFN regulation. Cancer cell regulation in research has long been central to host IFN synthesis and/or affected with differential IFN protein subunits defined further acting through 6 protein domains. Type II IFN remains central to immune cell function as it is released by a myriad of immune cells, mainly Natural Killer and T cells and is commonly used as a quantitative measurement of adaptive cellular immunity. Single–stranded and/or double–stranded RNA and DNA viruses as well as bacterial infections (e.g., Escherichia) and fungal infections (e.g., Mycobacteria) can affect IFN systems. These utilise intra/extracellular proteins like Toll–like Receptors (TLRs) affected by mutations within the overall IFN transduction pathways. Questions remain over immunological mechanisms contributing to innate and adaptive host immune regulation since type III IFN discovery in 2003 with immune cell phenotypes characterised further. Changes to synthesis of host type I/II/III IFNs may alter homeostatic cellular pathways differentially and beneficially in pathological disorders. We therefore aim to present the rationale of this regulatory protein mechanism of action in context with research developments recently with the functional effects
Untousling the Role of Tousled like Kinase 1 in DNA Damage Repair
Authors: Ghosh Ishita , De benedetti Arrigo
Published: August 2023

DNA damage repair lies at the core of all cells’ survival strategy, including cancerous. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on Tousled like Kinases have brought significant clarity on the effectors of these kinases which stands to regulate DSB repair. In addition to their well-established role in the DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation as well as defined steps during NHEJ ends processing were earlier hints of its important involvement broadly in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.
Mitochondrial Dynamics and Insulin Secretion
Authors: Kabra Uma D. , Jastroch Martin
Published: August 2023

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.
Comparative Analysis of Machine Learning Models for Image Detection of Colonic Polyps versus Resected Polyps
Authors: Abraham Adriel , Jose Rejath , Ahmad Jawad , Joshi Jai , Jacob Thomas , Khalid Aziz-ur-rahman , Ali Hassam , Patel Pratik , Singh Jaspreet , Toma Milan
Published: August 2023

(1) Background: Colon polyps are common protrusions in the colon’s lumen with potential risks of developing colorectal cancer. Early detection and intervention of these polyps are vital for reducing colorectal cancer incidence and mortality rates. This research aims to evaluate and compare the performance of three machine-learning image classification models’ performance in detecting and classifying colon polyps. (2) Methods: The performance of three machine learning image classification models, Google Teachable Machine (GTM), Roboflow3 (RF3), and You Only Look Once version 8 (YOLOV8), in the detection and classification of colon polyps were evaluated. The study used a dataset of colonoscopy images of normal colon, polyps, and resected polyps. The study assessed the models’ ability to correctly classify the images into their respective classes using precision, recall, and F1 score generated from confusion matrix analysis and performance graphs. (3) Results: All three models successfully distinguished between normal colon, polyps, and resected polyps in colonoscopy images. GTM achieved the highest accuracies: 0.99, with consistent precision, recall, and F1 scores of 1.00 for the `normal’ class, 0.97 - 1.00 for `polyps,’ and 0.97 - 1.00 for `resected polyps.’ While GTM exclusively classified images into these three categories, both YOLOV8 and RF3 extended their capabilities to detect normal colonic tissue, polyps, and resected polyps, with YOLOV8 and RF3 achieving overall accuracies of 0.84 and 0.87, respectively. (4) Conclusions: Machine learning, particularly models like GTM, shows promising results in ensuring comprehensive detection of polyps during colonoscopies.
Unveiling Inertia Constants by Exploring Mass Distribution in Wind Turbine Blades and Review of the Drive Train Parameters
Authors: Gonzalez-Rodriguez Angel Gaspar , Roldan-Fernandez Juan Manuel , Nieto-Nieto Luis Miguel
Published: August 2023

In studies of dynamic stability and power quality, it is necessary to know the mechanical parameters that determine the transient response of a wind turbine. The exact value of these parameters is not as decisive as the power curve can be, but an estimate that is far from reality can distort or even invalidate the simulation results. Despite its importance, this information, especially the inertia, but also the stiffness and damping constant of the drive-train, is hardly available for the turbine model under investigation.

In this work, the different bibliographical sources that provide values of blade inertia in kg·m2 will be reviewed, and above all, those that provide a distribution of masses along the span of the blade.

With this, different reliable relations will be obtained that allow calculating the inertia of the turbine rotor, based on the mass and length of the blade. When the center of gravity is also available, a very correlated expression is provided to obtain the inertia.

The even rarer references to the stiffness and damping constant of the drive-train will also be reviewed.
The Practice of Teaching and Scientific Research on Cadaveric Material Remains Crucial for Medical Education: Finally, in Italy Too, a Comprehensive Legislation Has Been Introduced
Authors: Bolino Giorgio , Fineschi Vittorio , Cecannecchia Camilla , D’Antonio Gianpiero , Frati And Paola
Published: August 2023

The practice of teaching and scientific research on cadaveric material remains crucial for medical education, especially in surgical disciplines. However, in Italy, this practice has been neglected due to legislative insufficiency and financial constraints. Although innovative methods and tools like simulators and e-learning have been adopted, direct hands-on experience with human cadavers remains irreplaceable for medical and surgical education. The absence of clear legislation governing cadaveric dissection has limited availability for teaching and research, resulting in economic burdens for universities and individuals seeking proper surgical training. To address this issue, the Law No. 10/2020 and the recent implementing decree were introduced in Italy, providing detailed legislation on the donation of bodies for educational and research purposes. The law emphasizes the importance of respecting the donor's specific choices and aligns with constitutional principles promoting culture, research, and health protection. However, some critical issues related to consent procedures, duration of body availability, and preservation of anatomical parts remain. Additionally, the law's dissemination among the population needs improvement. Future optimization could include allowing donors to choose the timing of body donation and considering different timeframes for body availability. Furthermore, the implementation of consent procedures could be simplified to increase donations. The law should also address the need for appropriate reception centers and allocate resources for effective dissemination. Despite these challenges, Law No. 10/2020 represents a significant step forward in enhancing medical-surgical training, scientific research, and the overall quality of patient care in Italy.
The Mazenod-Sue-Dianne IOCG District of the Great Bear Magmatic Zone, Northwest Territories, Canada
Authors: Mumin Hamid , Hamilton Mark
Published: August 2023

The Mazenod Lake region of the southern Great Bear Magmatic Zone (GBMZ) of the Northwest Territories, Canada comprises the north-central portion of the Faber volcano-plutonic belt. Mazenod geology is dominated by rhyodacite to basaltic-andesite ignimbrite sheets with interlayered volcaniclastic sedimentary rocks dominated by fine-grained laminated tuff sequences. Much of the intermediate to mafic nature of volcanic rocks is disguised by low-intensity but pervasive metasomatism. The region is affected by a series of coalescing magmatic-hydrothermal systems that host the Sue-Dianne magnetite-hematite IOCG deposit and several related showings including magnetite, skarn, and IOA styles of alteration ± mineralization. Exposed at surface are dominantly mid to upper levels of these systems, with underlying batholith, pluton and stocks exposed along the periphery, as well as locally within volcanic rocks associated with more intense alteration and mineralization. Widespread alteration includes potassic and sodic metasomatism, and silicification with structurally controlled giant quartz complexes. Localized tourmaline, skarn, magnetite-actinolite, and iron-oxides occur within structural breccias, and where most intense formed the Sue-Dianne Cu-Ag-Au diatreme-like breccia deposit. Magmatism, volcanism, hydrothermal alteration and mineralization formed during a negative tectonic inversion within the Wopmay Orogen. This generated a series of oblique offset rifted basins with continental style arc magmatism and extensional structures unique to GBMZ rifting. All significant hydrothermal centres in the Mazenod region occur along and at the intersections of crustal faults either unique to or put under tension during the GBMZ inversion.
POSTURE OF HEALTHY SUBJECTS MODULATED BY TRANSCUTANEOUS SPINAL CORD STIMULATION
Authors: Shamantseva Natalia , Timofeeva Olga , Gvozdeva Alisa , Andreeva Irina , Moshonkina Tatiana
Published: August 2023

Transcutaneous electrical stimulation of the spinal cord is used to restore locomotion and body weight support in patients with severe motor disorders. We studied effects of this non-invasive stimulation on postural control in healthy subjects. Stimulation at the L1-L2 vertebrae was performed to activate the extensor muscles of the lower limbs. Because postural regulation depends on the cognitive style, the effects of the stimulation were analyzed separately in field-dependent (FD) and field-independent (FI) participants. During the study young adults (N=16, half FD and half FI participants, all right dominant leg) stood on a force platform in a soundproof chamber with their eyes closed. Stimulation was applied in the midline between the L1-L2 vertebrae or over the left or right dorsal roots of the spinal cord; under control condition there was no stimulation. Stimulation destabilized posture in healthy subjects, whereas patients with movement disorders usually showed an improvement in postural control. In FD participants, left dorsal root and midline stimulation increased several postural parameters by up to 30%. Dorsal root stimulation on the side of the supporting leg reduced postural control, while stimulation on the side of the dominant leg did not. No significant changes were observed in the FI participants.
Delta Cord as A Radiological Localization Sign of Postoperative Adhesive Arachnoiditis: A Case Report and Literature Review
Authors: Lin Jiann-Her , Tu Yi-Ting , Chiang Yung-Hsiao
Published: August 2023

Postoperative adhesive arachnoiditis is an inflammatory response of the spinal leptomeninges that occurs after surgery, resulting in scar formation in the avascular nature of the arachnoid layer. Clinical manifestations of this condition include pain, sensory deficits, motor dysfunction, reflex abnormalities, and bladder/bowel impairments. In MRI scans, the signs of postoperative adhesive arachnoiditis can vary, but some specific indicators can assist surgeons in locating the lesion and planning surgical interventions more accurately. In this report, we reported a 37-year-old man with postoperative adhesive arachnoiditis after two surgeries for Chiari I malformation, demonstrating that the gradually-forming the delta cord sign with sequential syringomyelia. During the intraoperative examination, we identified the presence of the delta cord sign, which was formed by an arachnoid scar that was tethering the dorsal spinal cord to the dura. This discovery allowed us to precisely pinpoint the location of the arachnoid scar, thereby providing valuable guidance to avoid any unnecessary exploration of innocent structures during the procedure. Other localization signs were also reviewed.