MDPI-artikkelit: Recent submissions

Now showing items 1-20 of 1600
  • Forsberg, Elin M. V.; Riise, Rebecca; Saellström, Sara; Karlsson, Joakim; Alsén, Samuel; Bucher, Valentina; Hemminki, Akseli E.; Olofsson Bagge, Roger; Ny, Lars; Nilsson, Lisa M.; Rönnberg, Henrik; Nilsson, Jonas A. (Multidisciplinary Digital Publishing Institute, 2023)
    Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
  • Es-Haghi, Masoumeh; Neustroeva, Olga; Chowdhury, Iftekhar; Laitinen, Pia; Väänänen, Mari-Anna; Korvenlaita, Nea; Malm, Tarja; Turunen, Mikko P.; Turunen, Tiia A. (Multidisciplinary Digital Publishing Institute, 2023)
    Extracellular vesicles (EVs) naturally carry cargo from producer cells, such as RNA and protein, and can transfer these messengers to other cells and tissue. This ability provides an interesting opportunity for using EVs as delivery vehicles for therapeutic agents, such as for gene therapy. However, endogenous loading of cargo, such as microRNAs (miRNAs), is not very efficient as the copy number of miRNAs per EV is quite low. Therefore, new methods and tools to enhance the loading of small RNAs is required. In the current study, we developed fusion protein of EV membrane protein CD9 and RNA-binding protein AGO2 (hCD9.hAGO2). We show that the EVs engineered with hCD9.hAGO2 contain significantly higher levels of miRNA or shRNA (miR-466c or shRNA-451, respectively) compared to EVs that are isolated from cells that only overexpress the desired miRNA or shRNA. These hCD9.hAGO2 engineered EVs also transfer their RNA cargo to recipient cells more efficiently. We were not able to detect changes in gene expression levels in recipient cells after the EV treatments, but we show that the cell viability of HUVECs was increased after hCD9.hAGO2 EV treatments. This technical study characterizes the hCD9.hAGO2 fusion protein for the future development of enhanced RNA loading to EVs.
  • Nomden, Mark; Alizai, Naved K.; Betalli, Pietro; Bruggink, Janneke L. M.; Cananzi, Mara; Christensen, Vibeke Brix; D’Antiga, Lorenzo; Davenport, Mark; Fischler, Björn; Hindemith, Luise; Hukkinen, Maria; Johansen, Lars S.; de Kleine, Ruben H.; Madadi-Sanjani, Omid; Ong, Evelyn G. P.; Pakarinen, Mikko P.; Petersen, Claus; Ruiz, Mathias; Schunn, Matthias; Sturm, Ekkehard; Verkade, Henkjan J.; Wildhaber, Barbara E.; Hulscher, Jan B. F.; on behalf of members of the Biliary Atresia and Related Disorders (BARD) Community & the ERN RA-RE-LIVER, (Multidisciplinary Digital Publishing Institute, 2023)
    Background: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries. This study aimed to investigate if there was an association between strictness of lockdown and change in isolated BA (IBA) incidence in Europe. Methods: We approached European centres involved in the European Reference Network RARE-LIVER. We included IBA patients born between 2015 and June 2020. We calculated the number of IBA patients born per centre per month. The Stringency Index (SI) was used as lockdown strictness indicator. The association between percentage change of mean number of IBA patients born per month and the SI was assessed. Results: We included 412 IBA patients from thirteen different centres. The median number of patients per month did not change: 6 (1–15) pre-lockdown and 7 (6–9) during lockdown (p = 0.34). There was an inverse association between SI and percentage change in IBA (B = -0.73, p = 0.03). Median age at Kasai portoenterostomy (days) did not differ between time periods (51 (9–179) vs. 53 (19–126), p = 0.73). Conclusion: In this European study, a stricter COVID-lockdown was seemingly accompanied by a simultaneous larger decrease in the number of IBA patients born per month in the lockdown. Results should be interpreted with caution due to the assumptions and limitations of the analysis.
  • Poorazimy, Maryam; Shataee, Shaban; Aghababaei, Hossein; Tomppo, Erkki; Praks, Jaan (Multidisciplinary Digital Publishing Institute, 2023)
    Structural diversity is recognized as a complementary aspect of biological diversity and plays a fundamental role in forest management, conservation, and restoration. Hence, the assessment of structural diversity has become a major effort in the primary international processes, dealing with biodiversity and sustainable forest management. Because of prohibitive costs associated with the ground measurements of forest structure, despite their high accuracy, space-borne polarization coherence tomography (PCT) can introduce an alternative approach given its ability to provide a vertical reflectivity profile and spatiotemporal resolutions related to detecting forest structural changes. In this study, for the first time ever, the potential of space-borne PCT was evaluated in a broad-leaved Hyrcanian forest of Iran over 308 circular sample plots with an area of 0.1 ha. Two aspects of horizontal structure diversity, including standard deviation of diameter at breast height (σdbh) and the number of trees (N), were predicted as important characteristics in wood production and biomass estimation. In addition, the performance of prediction algorithms, including multiple linear regression (MLR), k-nearest neighbors (k-NN), random forest (RF), and support vector regression (SVR) were compared. We addressed the issue of temporal decorrelation in space-borne PCT utilizing the single-pass TanDEM-X interferometer. The data were acquired in standard DEM mode with single polarization of HH. Consequently, airborne laser scanning (ALS) was used to estimate initial values of height hv and ground phase φ0. The Fourier–Legendre series was used to approximate the relative reflectivity profile of each pixel. To link the relative reflectivity profile averaged within each plot with corresponding ground measurements of σdbh and N, thirteen geometrical and physical parameters were defined (P1−P13). Leave-one-out cross validation (LOOCV) showed a better performance of k-NN than the other algorithms in predicting σdbh and N. It resulted in a relative root mean square error (rRMSE) of 32.80%, mean absolute error (MAE) of 4.69 cm, and R2* of 0.25 for σdbh, whereas only 22% of the variation in N was explained using the PCT algorithm with an rRMSE of 41.56%. This study revealed promising results utilizing TanDEM-X data even though the accuracy is still limited. Hence, an entire assessment of the used framework in characterizing the reflectivity profile and the possible effect of the scale is necessary for future studies.
  • Meng, Jiali; Mäkelä, Miia R.; de Vries, Ronald P. (Multidisciplinary Digital Publishing Institute, 2023)
    l-arabitol is an intermediate of the pentose catabolic pathway in fungi but can also be used as a carbon source by many fungi, suggesting the presence of transporters for this polyol. In this study, an l-arabitol transporter, LatA, was identified in Aspergillus niger. Growth and expression profiles as well as sugar consumption analysis indicated that LatA only imports l-arabitol and is regulated by the arabinanolytic transcriptional activator AraR. Moreover, l-arabitol production from wheat bran was increased in a metabolically engineered A. niger mutant by the deletion of latA, indicating its potential for improving l-arabitol-producing cell factories. Phylogenetic analysis showed that homologs of LatA are widely conserved in fungi.
  • Moullé, Valentine S.; Frapin, Morgane; Amarger, Valérie; Parnet, Patricia (Multidisciplinary Digital Publishing Institute, 2023)
    Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of “metabolic programming”. The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood.
  • Azzaz, Fodil; Chahinian, Henri; Yahi, Nouara; Fantini, Jacques; Di Scala, Coralie (Multidisciplinary Digital Publishing Institute, 2023)
    A broad range of data identify Ca2+-permeable amyloid pores as the most neurotoxic species of Alzheimer’s β-amyloid peptide (Aβ1–42). Following the failures of clinical trials targeting amyloid plaques by immunotherapy, a consensus is gradually emerging to change the paradigm, the strategy, and the target to cure Alzheimer’s disease. In this context, the therapeutic peptide AmyP53 was designed to prevent amyloid pore formation driven by lipid raft microdomains of the plasma membrane. Here, we show that AmyP53 outcompetes Aβ1–42 binding to lipid rafts through a unique mode of interaction with gangliosides. Using a combination of cellular, physicochemical, and in silico approaches, we unraveled the mechanism of action of AmyP53 at the atomic, molecular, and cellular levels. Molecular dynamics simulations (MDS) indicated that AmyP53 rapidly adapts its conformation to gangliosides for an optimal interaction at the periphery of a lipid raft, where amyloid pore formation occurs. Hence, we define it as an adaptive peptide. Our results describe for the first time the kinetics of AmyP53 interaction with lipid raft gangliosides at the atomic level. Physicochemical studies and in silico simulations indicated that Aβ1–42 cannot interact with lipid rafts in presence of AmyP53. These data demonstrated that AmyP53 prevents amyloid pore formation and cellular Ca2+ entry by competitive inhibition of Aβ1–42 binding to lipid raft gangliosides. The molecular details of AmyP53 action revealed an unprecedent mechanism of interaction with lipid rafts, offering innovative therapeutic opportunities for lipid raft and ganglioside-associated diseases, including Alzheimer’s, Parkinson’s, and related proteinopathies.
  • Silva, Maria Elena; Hernández-Andrade, Matías; Abasolo, Nerea; Espinoza-Cruells, Cristóbal; Mansilla, Josselyne B.; Reyes, Carolina R.; Aranda, Selena; Esteban, Yaiza; Rodriguez-Calvo, Ricardo; Martorell, Lourdes; Muntané, Gerard; Rivera, Francisco J.; Vilella, Elisabet (Multidisciplinary Digital Publishing Institute, 2023)
    Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor expressed in epithelial cells from different tissues in which collagen binding activates pleiotropic functions. In the brain, DDR1 is mainly expressed in oligodendrocytes (OLs), the function of which is unclear. Whether collagen can activate DDR1 in OLs has not been studied. Here, we assessed the expression of DDR1 during in vitro OL differentiation, including collagen IV incubation, and the capability of collagen IV to induce DDR1 phosphorylation. Experiments were performed using two in vitro models of OL differentiation: OLs derived from adult rat neural stem cells (NSCs) and the HOG16 human oligodendroglial cell line. Immunocytofluorescence, western blotting, and ELISA were performed to analyze these questions. The differentiation of OLs from NSCs was addressed using oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP). In HOG16 OLs, collagen IV induced DDR1 phosphorylation through slow and sustained kinetics. In NSC-derived OLs, DDR1 was found in a high proportion of differentiating cells (MBP+/Olig2+), but its protein expression was decreased in later stages. The addition of collagen IV did not change the number of DDR1+/MBP+ cells but did accelerate OL branching. Here, we provide the first demonstration that collagen IV mediates the phosphorylation of DDR1 in HOG16 cells and that the in vitro co-expression of DDR1 and MBP is associated with accelerated branching during the differentiation of primary OLs.
  • Chayka, Ivan F.; Baykov, Nikolay I.; Kamenetsky, Vadim S.; Kutyrev, Anton V.; Pushkarev, Evgenii V.; Abersteiner, Adam; Shcherbakov, Vasily D. (Multidisciplinary Digital Publishing Institute, 2023)
    Zoned plutons, composed of dunites, pyroxenites, and gabbroic rocks, have been referred to as the Ural-Alaskan type complexes (UA-complexes) and occur in numerous paleo-arc settings worldwide. Many of these complexes are source rocks for economic placers of platinum-group metals. Thus, it is important to understand how UA-complexes form and the origin and behavior of platinum-group elements (PGEs). It is widely assumed that the UA-complexes result from differentiation of supra-subduction high-Ca high-Mg sub-alkaline magmas. However, there is a lack of direct evidence for the existence and differentiation of such magmas, mainly because cases of UA-complexes being spatially and temporally linked to co-genetic volcanics are unknown. We studied an UA-complex from the Tumrok range (Eastern Kamchatka) where a dunite-clinopyroxenite-gabbro assemblage is spatially and temporary related to high-Ca volcanics (i.e., picrites and basalts). Based on the mineral and chemical composition of the rocks, mineral chemistry, and composition of melt inclusions hosted within rock-forming minerals, we conclude that the intrusive assemblage and the volcanics are co-genetic and share the same parental magma of ankaramitic composition. Furthermore, the compositions of the plutonic rocks are typical of UA-complexes worldwide. Finally, the rocks studied exhibit a full differentiation sequence from olivine-only liquidus in picrites and dunites to eutectic crystallization of diopside or hornblende, plagioclase, and K-Na feldspar in plagio-wehrlites and gabbroic rocks. All these results make the considered volcano–plutonic complex a promising case for petrological studies and modelling of UA-complex formation.
  • Zare, Mina; Pemmada, Rakesh; Madhavan, Maya; Shailaja, Aswathy; Ramakrishna, Seeram; Kandiyil, Sumodan Padikkala; Donahue, James M.; Thomas, Vinoy (Multidisciplinary Digital Publishing Institute, 2023)
    In the original publication [...]
  • Grabala, Pawel; Danowska-Idziok, Kinga; Helenius, Ilkka J. (Multidisciplinary Digital Publishing Institute, 2023)
    Background: Horner’s syndrome (HS) classically consists of the symptom triad of miosis, ptosis, and anhidrosis. It is caused by impairment of a certain pathway in the sympathetic nervous system. It may also appear as part of the clinical signs of other diseases and syndromes, including Pancoast tumors, intradural and/or epidural tumors, thoracic outlet syndrome, syringomyelia, brachial plexus injury, and aortic dissection. Here, we report a very rare complication of vertebral column resection in children, and we present the clinical findings of a case of Horner’s syndrome with a current literature review. Case presentation: A five-year-old child with severe congenital kyphoscoliosis qualified for surgical treatment of the spinal deformity via a posterior approach, with three-column osteotomy and fusion. Results: After successful surgery, the patient presented with HS due to distraction of the sympathetic nerve trunk and, thus, innervation to the left eye. At the 4-year follow-up, the child had fully recovered. Conclusions: Pediatric HS after posterior instrumented scoliosis correction surgery with posterior vertebral column resection of the thoracic spine is very rare. This is the first reported case of HS after posterior vertebral column resection and spinal fusion for congenital kyphoscoliosis without the use of epidural analgesia. Symptom resolution may be variable and, in some cases, delayed.
  • Mursu, Jaakko; Ristimäki, Maija; Malinen, Inga; Petäjä, Pirita; Isola, Ville; Ahtiainen, Juha P.; Hulmi, Juha J. (Multidisciplinary Digital Publishing Institute, 2023)
    As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 in DXA) in female and male PA was ~41.3 and ~37.2, and in GE ~39.4 and ~35.3, respectively. Low EA (LEA) was found in 10% and 26% of female PA and GE, respectively, and in 11% of male GE. In PA, daily protein intake (g/kg body mass) was ~2.9–3.0, whereas carbohydrate and fat intakes were ~3.6–4.3 and ~0.8–1.0, respectively. PA had higher protein and carbohydrate and lower fat intakes than GE (p < 0.05). Estradiol, testosterone, IGF-1, insulin, leptin, TSH, T4, T3, cortisol, or BMD did not differ between PA and GE. Serum IGF-1 and leptin were explained 6% and 7%, respectively, by EA. In non-users of hormonal contraceptives, amenorrhea was found only in PA (27%) and was associated with lower fat percentage, but not EA, BMD, or hormones. In conclusion, off-season dietary intakes, hormone levels, and BMD meet the recommendations in most of the PA and GE. Maintaining too-low body fat during the off-season may predispose to menstrual disturbances.
  • Das, C.R.; Huitu, Katri; Kärkkäinen, Timo J. (Multidisciplinary Digital Publishing Institute, 2023)
    In the extended scalar sector of the SMASH (Standard Model - Axion-Seesaw-Higgs portal inflation) framework, we conduct a phenomenological investigation of the observable effects. In a suitable region of the SMASH scalar parameter spaces, we solve the vacuum metastability problem and discuss the one-loop correction to the triple Higgs coupling, λHHH. The λHHH and SM Higgs quartic coupling λH corrections are found to be proportional to the threshold correction. A large λHHH correction (≳5%) implies vacuum instability in the model and thus limits the general class of theories that use threshold correction. We performed a full two-loop renormalization group analysis of the SMASH model. The SMASH framework has also been used to estimate the evolution of lepton asymmetry in the universe.
  • Kemppainen, Laura; Kemppainen, Teemu; Fokkema, Tineke; Wrede, Sirpa; Kouvonen, Anne (Multidisciplinary Digital Publishing Institute, 2023)
    So far, little attention has been paid to contextual factors shaping loneliness and their interaction with individual characteristics. Moreover, the few existing studies have not included older migrants, identified as a group who are vulnerable to loneliness. This study examined the association between neighbourhood ethnic density (the proportion of own-group residents and the proportion of other ethnic residents in an area) and loneliness among older migrants. Furthermore, we investigated whether local language skills moderated this association. A population-based representative survey (The CHARM study, n = 1082, 57% men, mean age 63.2 years) and postal code area statistics were used to study Russian-speaking migrants aged 50 or older in Finland. The study design and data are hierarchical, with individuals nested in postcode areas. We accounted for this by estimating corresponding mixed models. We used a linear outcome specification and conducted logistic and ordinal robustness checks. After controlling for covariates, we found that ethnic density variables (measured as the proportion of Russian speakers and the proportion of other foreign speakers) were not associated with loneliness. Our interaction results showed that increased own-group ethnic density was associated with a higher level of loneliness among those with good local language skills but not among those with weaker skills. Good local language skills may indicate a stronger orientation towards the mainstream destination society and living in a neighbourhood with a higher concentration of own-language speakers may feel alienating for those who wish to be more included in mainstream society.
  • Heinaro, Einari; Tanhuanpää, Topi; Vastaranta, Mikko; Yrttimaa, Tuomas; Kukko, Antero; Hakala, Teemu; Mattsson, Teppo; Holopainen, Markus (Multidisciplinary Digital Publishing Institute, 2023)
    Fallen tree mapping provides valuable information regarding the ecological value of boreal forests. Airborne laser scanning (ALS) enables mapping fallen trees on a large scale. We compared the performance of line-detection-based individual fallen tree detection when using moderate point density ALS data (15 points/m2) and high-point-density unmanned aerial vehicle-based laser scanning (ULS) data (285 points/m2). Furthermore, we inspected the dataset and detection methodology-related factors impacting performance in each case. The results of this study showed that increasing the point density of the laser scanning dataset enables the detection of a larger proportion of fallen trees. However, based on our experiment, a line-detection-based fallen tree detection approach is sensitive to noise, thus generating a large number of false detections, especially with high-point-density data. Different types of filters, such as a simple height-based filter and machine-learning-based filters, can be used for reducing noise. However, using such filters is always a compromise, as in addition to reducing noise and thus false detections, they also reduce the number of true detections. Hence, a less noise-sensitive fallen tree detection method utilizing the finer details visible in high-density point clouds could be more suitable for high-point-density laser scanning data.
  • Jõgi, Indrek; Paris, Peeter; Bernard, Elodie; Diez, Mathilde; Tsitrone, Emmanuelle; Hakola, Antti; Likonen, Jari; Vuoriheimo, Tomi; Grigore, Eduard; the WEST Team,; EUROfusion WP PFC/PWIE Contributors, (Multidisciplinary Digital Publishing Institute, 2023)
    Fuel retention monitoring in tokamak walls requires the development of remote composition analysis methods such as laser-induced breakdown spectroscopy (LIBS). The present study investigates the feasibility of the LIBS method to analyse the composition and fuel retention in three samples from WEST divertor erosion marker tiles after the experimental campaign C3. The investigated samples originated from tile regions outside of strong erosion and deposition regions, where the variation of thin deposit layers is relatively small and facilitates cross-comparison between different analysis methods. The depth profiles of main constituents W, Mo and C were consistent with depth profiles determined by other composition analysis methods, such as glow-discharge optical emission spectroscopy (GDOES) and secondary ion mass spectrometry (SIMS). The average LIBS depth resolution determined from depth profiles was 100 nm/shot. The averaging of the spectra collected from multiple spots of a same sample allowed us to improve the signal-to-noise ratio, investigate the presence of fuel D and trace impurities such as O and B. In the investigated tile regions with negligible erosion and deposition, these impurities were clearly detectable during the first laser shot, while the signal decreased to noise level after a few subsequent laser shots at the same spot. LIBS investigation of samples originating from the deposition regions of tiles may further clarify LIBS’ ability to investigate trace impurities.
  • Balewski, Łukasz; Kokoszka, Jakub; Fedorowicz, Joanna; Ilina, Polina; Tammela, Päivi; Gdaniec, Maria; Kornicka, Anita (Multidisciplinary Digital Publishing Institute, 2022)
    As a continuation of our previous investigations aimed at the synthesis of novel nitrogen-containing heterocycles and their metal complexes, we have now prepared two series of compounds incorporating a phthalazine ring at the position C2 of 4,5-dihydro-1H-imidazole. The starting phthalazine (I) in the reaction with 2-chloroimidazoline (II) gives rise to the formation of pseudobase III. Then, compound III upon treatment with HOSA yields betaine which under basic conditions gives 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV). In turn, the reactions of compound IV with a variety of acyl and sulfonyl chlorides lead to the formation of benzamides (V) and benzenesulfonamides (VI). Moreover, compounds V and VI can be transformed into corresponding 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one derivatives VII and VIII. Such ligands are susceptible to the reaction with CuCl2 giving rise to the formation of corresponding copper(II) complexes: dichloro[2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine]copper(II) (1), dichloro[2-(1-benzoyl-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]copper(II) (2) and dichloro{bis-[2-(1-(phenylsulfonyl)-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]}copper(II) (3). The most promising results of biological studies were obtained for complex 1 towards the HeLa cell line (IC50 = 2.13 μM) without a toxic effect against fibroblasts BALB/3T3 (IC50 = 135.30 μM), which pointed towards its selectivity as a potential antitumor agent. It should be pointed out, that corresponding free ligand 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV) was less active than its metal complex (IC50 = 87.74 μM).
  • Marano, Pierpaolo; Li, Shu (Multidisciplinary Digital Publishing Institute, 2023)
    Insurance distributors are increasingly using robo-advisors for a variety of tasks, ranging from facilitating communication with customers to providing substantive advice. Like many other AI-empowered applications, robo-advisors have the potential to pose substantial risks that should be regulated and corrected by legal instruments. In this article, we attempt to discuss the regulation of robo-advisors from the perspective of the Insurance Distribution Directive and the draft AI Act. We ask two questions for each. (1) From a positive legal perspective, what obligations are imposed on insurance distributors by the legislation when they deploy robo-advisors in their business? (2) From a normative perspective, are the incumbent provisions within that legislation effective at ensuring the ethical and responsible use of robo-advisors? Our results show that neither the Insurance Distribution Directive nor the AI Act adequately address the emerging risks associated with robo-advisors. The rules implicated by them regarding the use of robo-advisors for insurance distribution are inconsistent, disproportionate, and implicit. Legislators shall further address these issues, and authorities such as EIOPA and national competent authorities must also participate by providing concrete guidelines.
  • Penna, Suprasanna; Jain, Shri Mohan (Multidisciplinary Digital Publishing Institute, 2023)
    Fruit species contribute to nutritional and health security by providing micronutrients, antioxidants, and bioactive phytoconstituents, and hence fruit-based products are becoming functional foods presently and for the future. Although conventional breeding methods have yielded improved varieties having fruit quality, aroma, antioxidants, yield, and nutritional traits, the threat of climate change and need for improvement in several other traits such as biotic and abiotic stress tolerance and higher nutritional quality has demanded complementary novel strategies. Biotechnological research in fruit crops has offered immense scope for large-scale multiplication of elite clones, in vitro, mutagenesis, and genetic transformation. Advanced molecular methods, such as genome-wide association studies (GWAS), QTLomics, genomic selection for the development of novel germplasm having functional traits for agronomic and nutritional quality, and enrichment of bioactive constituents through metabolic pathway engineering and development of novel products, are now paving the way for trait-based improvement for developing genetically superior varieties in fruit plant species for enhanced nutritional quality and agronomic performance. In this article, we highlight the applications of in vitro and molecular breeding approaches for use in fruit breeding.
  • Suominen, Eetu N.; Saarinen, Antti J. (Multidisciplinary Digital Publishing Institute, 2023)
    Traumatic hip dislocation is a rare injury in pediatric populations. Dislocation may be associated with low-energy trauma, such as a minor fall. Traumatic hip dislocation is associated with severe complications, such as avascular necrosis of the femoral head. Timely diagnosis and reposition decrease the rate of complications. In this study we retrospectively assessed traumatic hip dislocations in pediatric patients during a 10-year timespan in a university hospital. There were eight cases of traumatic hip dislocations. All patients had a minimum follow-up of two years and were followed with MRI scans. One patient developed avascular necrosis during the follow-up which resolved conservatively. There were no other significant complications. In conclusion, traumatic hip dislocation is a rare injury which is associated with severe complications. Patients in our case series underwent a timely reposition. The complication rate was similar to previous reports.