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Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.Food markets are becoming popular as new spaces for recreation, and this research aims to discover the motivations driving the tourists that visit these markets. Factorial analysis, cluster analysis and Student's t-test were applied on 456 surveys from two food markets in Córdoba (Spain). Three motivational factors were obtained Gastronomic experience and novelty; hedonism and leisure; and the relationship of the experience with work. Segmenting and analyzing the profile of the tourist may help economic agents develop new strategies for the tourism management of a destination and more accurate marketing and branding strategies that target specific customers with a niche message. The study could help develop products that align with tourists' motives to increase satisfaction and loyalty.In the present study, the essential oils obtained by hydrodistillation of the organs of Eryngium maritimum and E. alpinum were analyzed by GC-FID-MS. The dominant constituents assessed in the essential oil of E. maritimum were germacrene D (45.2%) in the fruits; hexadecanoic acid (18.5%), menthol (16.8%), and menthone (10.9%) in the roots; 2,3,4-trimethylbenzaldehyde (11.3%) and germacrene D (10.5%) in the leaves; 2,3,4-trimethylbenzaldehyde (11.3%) in the shoot culture. In the case of E. alpinum, the main components of the leaf oil were β-elemenone (10.3%), germacrone (5.8%), two selinadienes (7.1% and 6.7%), and 1,8-cineole (5.3%), which were not found in the oil from shoot culture, whereas the shoot culture oil was dominated by hexadecanoic acid (15.5%), spathulenol (7.5%), (E)-β-farnesene (4.9%), germacra-4(15),5,10(14)-trien-1α-ol (4.7%), and falcarinol (4.3%). The essential oils obtained from E. maritimum fruits and leaves of the intact plants, measured by the broth microdilution method, were the most active against T. mentagophytes and S. aureus. AT2 Agonist C21 Moreover, the essential oil of leaves had the moderate activity against C. albicans and E. coli. The results showed that the chemical compositions of the essential oils differed decidedly between the two studied species and between the organs. Furthermore, the essential oil of E. maritimum may play an important role as antimicrobial agent.We develop a deep learning refined kinematic model for accurately assessing upper limb joint angles using a single Kinect v2 sensor. We train a long short-term memory recurrent neural network using a supervised machine learning architecture to compensate for the systematic error of the Kinect kinematic model, taking a marker-based three-dimensional motion capture system (3DMC) as the golden standard. A series of upper limb functional task experiments were conducted, namely hand to the contralateral shoulder, hand to mouth or drinking, combing hair, and hand to back pocket. Our deep learning-based model significantly improves the performance of a single Kinect v2 sensor for all investigated upper limb joint angles across all functional tasks. Using a single Kinect v2 sensor, our deep learning-based model could measure shoulder and elbow flexion/extension waveforms with mean CMCs >0.93 for all tasks, shoulder adduction/abduction, and internal/external rotation waveforms with mean CMCs >0.8 for most of the tasks. The mean deviations of angles at the point of target achieved and range of motion are under 5° for all investigated joint angles during all functional tasks. Compared with the 3DMC, our presented system is easier to operate and needs less laboratory space.Our knowledge of voiding is derived from studies comprised of cisgender males and females, with relatively little known about the impact of sexual and gender minority status on voiding perceptions, symptoms, and function [...].Contactless ultrasonic power transmission (UPT) through a metal barrier has become an exciting field of research, as metal barriers prevent the use of electromagnetic wireless power transfer due to Faraday shielding effects. In this paper, we demonstrate power transfer through a metal wall with the use of ultrasonic waves generated from a piezoelectric transducer. Accurate characterization and modeling of the transducer and investigation of the influence of the acoustic properties of the transmitting medium are instrumental for the performance prediction and optimal design of an ultrasonic power link. In this work, we applied the KLM model for the emitting and receiving transducers, with respect to the transmitting medium and model for both the emission and reception function. A practical UPT system was built by mechanically coupling and co-axially aligning two composite transducers on opposite sides of a transmitting medium wall. The optimal transmission performance of the ultrasonic power link through thickness-stretch vibrations of the wall together with two piezoelectric transducers working in TE mode was determined. Eventually, the operating frequency and ohmic loading condition for maximum power transmission were obtained for two different media, aluminium and polyoxymethylene (POM), with contrasting specific acoustic impedances. The results showed that the measured optimal electric loads and operating frequency for maximum power transfer agreed well with the theoretical predictions.

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