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Checkpoint inhibitors treat a variety of tumor types with significant benefits. Unfortunately, these therapies come with diverse adverse events. Skin rash is observed early into treatment and might serve as an indicator of downstream responses to therapy. We studied the cellular composition of cutaneous eruptions and whether their contribution varies with the treatment applied. Skin samples from 18 patients with cancer and 11 controls were evaluated by mono- and multiplex imaging, quantification, and statistical analysis. T cells were the prime contributors to skin rash, with T cells and macrophages interacting and proliferating on site. Among T cell subsets examined, type 1 and 17 T cells were relatively increased among inflammatory skin infiltrates. A combination of increased cytotoxic T cell content and decreased macrophage abundance was associated with dual checkpoint inhibition over PD1 inhibition alone. Importantly, responders significantly separated from nonresponders by greater CD68+ macrophage and either CD11c+ antigen-presenting cell or CD4+ T cell abundance in skin rash. The microenvironment promoted epidermal proliferation and thickening as well. The combination of checkpoint inhibitors used affects the development and composition of skin infiltrates, whereas the combined abundance of two cell types in cutaneous eruptions aligns with responses to checkpoint inhibitor therapy.

Besides visual assessment of the intra-vascular appearance, intravascular optical coherence tomography (IVOCT) enables precise diameter measurements within the coronary arteries. The current study presents an upgraded test setup allowing the investigation of the elastic properties of porcine coronary arteries ex vivounder pulsatile flow conditions. IV-OCT imaging was performed within the left circumflex artery of a porcine heart applying a normotensive and a hypertensive pressure regime at different pulse rates. Radial compliance was derived from the luminal diameter as well as intra-arterial pressure measurements. Test results show a significant reduction of radial compliance under pulsatile conditions, when compared to reference measurements under steady flow. The mean radial compliance decreased with increasing pulse rate, which can be attributed to the viscoelastic properties of the arterial wall.

Współczesna, zachodnioeuropejska myśl społeczna stroni od prób opisania przestrzeni społecznej za pomocą kategorii „narodu”. Tymczasem, jak przekonują liczni polscy myśliciele podejmujący zagadnienie społecznego wymiaru istnienia człowieka, właściwie rozumiane pojęcie narodu pozwala wyjaśnić i uporządkować wiele fenomenów życia wspólnotowego. Niniejszy artykuł jest próbą syntetycznego ukazania tego, jak ujmowana jest rzeczywistość narodu w pracach najwybitniejszych przedstawicieli szeroko rozumianej polskiej myśli personalistycznej.

The paper studies the problem of the transcendence of the person suggested by Karol Wojtyła/John Paul II. It originates in the philosophical thought of this Polish personalist and is complemented in his theological works. According to Wojtyła transcendence can be described as “another name for the person” as it is closely related to the fulfilment of man as a personal being. The paper contains analyses of three dimensions of transcendence, and these are: 1) transcendence in action; 2) transcendence towards another “I”; and 3) transcendence towards personal God.

The following article is one of the voices in the debate about the universality of priestly celibacy. It attempts to track the development of the theological and personalist arguments for celibacy contained in the most significant documents of the Magisterium of the Church. A special emphasis has been put on contemporary texts, issued after the Second Vatican Council. This choice has been caused by two major reasons. First, post-conciliar documents introduce a new quality to the argument of the universality of celibacy. Second, they have a far bigger impact on the discipline of the Church than previous texts.

Niniejszy tekst jest jednym z głosów we współczesnej debacie na temat celibatu. Jego specyfiką jest próba prześledzenia rozwoju argumentacji teologicznej i personalistycznej zawartej w najważniejszych dokumentach Urzędu Nauczycielskiego Kościoła. Szczególny nacisk został położony na teksty współczesne, wydane już po Soborze Watykańskim II. To uwrażliwienie podyktowane jest dwoma zasadniczymi powodami. Po pierwsze, dokumenty posoborowe wprowadzają zupełnie nową jakość do argumentacji na temat powszechności celibatu. Po drugie, mają one o wiele większy wpływ na dzisiejszą dyscyplinę Kościoła niż teksty wcześniejsze.

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-Wolbachia azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: Brugia malayi--CB.17 SCID mice, B. malayi--Mongolian gerbils, B. pahangi--Mongolian gerbils, and Litomosoides sigmodontis-- Mongolian gerbils. Combination treatments synergised to elicit threshold (>90%) Wolbachia depletion from female worms in 5 days of treatment, using 2-fold lower dose-exposures of AWZ1066S than monotherapy. Short-course lowered dose AWZ1066S-albendazole combination treatments also delivered partial adulticidal activities and/or long-lasting inhibition of embryogenesis, resulting in complete transmission blockade in B. pahangi and L. sigmodontis gerbil models. We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases ofmedical and veterinary importance. [ABSTRACT FROM AUTHOR]

The article constitutes an attempt to present the synthetic understanding of the person as a social and relational being based on the Lublin conception of personalism of late twentieth and early twenty-first century. The analyses of the social horizon of the person cannot be limited to one, however brilliant, perspective. Person needs to be illuminated using cognitive lights of various kinds to approach a broad range of information relevant to it. The personalism of the Lublin School, which is characterised by a multiplicity of methods and forms of the description of a person, while preserving a certain common axiomatic and axiological foundation, is perfectly suited for this. Moreover, in line with the hermeneutic method of a “medium ground,” to describe the personal being personalists from Lublin such as Wincenty Granat, Karol Wojtyła/John Paul II or Czesław Stanisław Bartnik have utilized both philosophical and theological data. Deriving methodological inspiration from the masters mentioned above, the whole inquiry featured in this article is divided into two parts. They include the analyses of philosophical and theological horizons of understanding the social and interpersonal dimension of the person.

The paper studies the problem of the transcendence of the person suggested by Karol Wojtyła/John Paul II. It originates in the philosophical thought of this Polish personalist and is complemented in his theological works. According to Wojtyła transcendence can be described as “another name for the person” as it is closely related to the fulfilment of man as a personal being. The paper contains analyses of three dimensions of transcendence, and these are: 1) transcendence in action; 2) transcendence towards another “I”; and 3) transcendence towards personal God.

The aim of this article is to advance the field of metamaterials by proposing formulas for the design of high-contrast metamaterials with prescribed subwavelength defect mode eigenfrequencies. This is achieved in two settings: (i) design of non-Hermitian static materials and (ii) design of instantly changing non-Hermitian time-dependent materials. The design of static materials is achieved via characterizing equations for the defect mode eigenfrequencies in the setting of a defected dimer material. These characterizing equations are the basis for obtaining formulas for the material parameters of the defect which admit given defect mode eigenfrequencies. Explicit formulas are provided in the setting of one and two given defect mode eigenfrequencies in the setting of a defected chain of dimers. In the time-dependent case, we first analyze the influence of time boundaries on the subwavelength solutions. We find that subwavelength solutions are preserved if and only if the material parameters satisfy a temporal Snell's law across the time boundary. The same result also identifies the change of the time frequencies uniquely. Combining this result with those on the design of static materials, we obtain an explicit formula for the material design of instantly changing defected dimer materials which admit subwavelength modes with prescribed time-dependent defect mode eigenfrequency. Finally, we use this formula to create materials which admit spatio-temporally localized defect modes. [ABSTRACT FROM AUTHOR]

Physical inactivity has caused serious effects on the health of the population, having an impact on the quality of life and the cost of healthcare for many countries. This has motivated government and private institutions to promote regular physical activity, which, paradoxically, can involve health risks when it is carried out in areas with poor air quality. This review collects information from studies conducted on healthy humans related to the pulmonary effects caused by the practice of physical activity when there is poor air quality. In addition, several challenges related to the technological and educational areas, as well as to applied and basic research, have been identified to facilitate the rational practice of exercise in poor air quality conditions.

BACKGROUND Perianal malignancies are rare tumors with unique presentations and treatment options. OBJECTIVE To review published literature about primary malignancies that present on perianal skin and published guidelines and treatment options. MATERIALS AND METHODS A PubMed search was conducted for original articles about perianal malignancies. RESULTS Squamous cell carcinoma, basal cell carcinoma, melanoma, and extramammary Paget disease are the most common tumors to present on perianal skin. Anal squamous cell carcinoma incidence is increasing and certain populations may benefit from screening. Surgical management is often recommended for localized perianal tumors. CONCLUSION Dermatologic surgeons should be familiar with the presentation and treatment options available for perianal malignancies. [ABSTRACT FROM AUTHOR]

Współczesna, zachodnioeuropejska myśl społeczna stroni od prób opisania przestrzeni społecznej za pomocą kategorii „narodu”. Tymczasem, jak przekonują liczni polscy myśliciele podejmujący zagadnienie społecznego wymiaru istnienia człowieka, właściwie rozumiane pojęcie narodu pozwala wyjaśnić i uporządkować wiele fenomenów życia wspólnotowego. Niniejszy artykuł jest próbą syntetycznego ukazania tego, jak ujmowana jest rzeczywistość narodu w pracach najwybitniejszych przedstawicieli szeroko rozumianej polskiej myśli personalistycznej.

Reliable markers for both renal cell carcinoma (RCC) and transitional cell carcinoma of the bladder (TCC) are lacking.During tumor progression and invasion components of extracellular matrix (ECM) are degraded and parts of these different components are detectable in plasma. Cellular fibronectin (cFN) represents a well characterized ECM protein. In contrast to fibronectin in plasma produced by hepatocytes (FN) cFN has a total extra domain sequence and occurs in much smaller amounts in the circulation. The aim of our study was to evaluate cFN as a marker and to determine its possible role in clinical staging of TCC and RCC.Blood samples were collected from 30 patients before they underwent transurethral resection of the bladder because of newly diagnosed TCC. Additionally samples were collected from 69 patients with RCC before therapy. Sixty patients with non-malignant urological disorders were recruited as control group. Determination of cFN in plasma was performed by using a highly sensitive time-resolved fluorescence immunoassay (TRFIA).The control group had median cFN plasma levels of 437 ng/ml. Patients suffering from TCC or RCC showed significantly higher cFN levels. In patients with muscle invasive TCC significant higher cFN levels (p < 0.05) could be demonstrated compared to non-muscle invasive TCC. Similar results were found in RCC with significant elevated cFN levels in metastatic RCC (p < 0.005) compared to localized stage of disease. No differences were found concerning tumor grading in both malignancies.In the face of significant elevated cFN levels in TCC and RCC our data underline the important role of cFN. For future investigations the elevated cFN levels in locally progressed and metastastic disease, indicating a clinically useful tool for preoperative staging and postoperative monitoring, are of high interest.

An absent factor of a string w is a string u which does not occur as a contiguous substring (a.k.a. factor) inside w. We extend this well-studied notion and define absent subsequences: a string u is an absent subsequence of a string w if u does not occur as subsequence (a.k.a. scattered factor) inside w. Of particular interest to us are minimal absent subsequences, i.e., absent subsequences whose every subsequence is not absent, and shortest absent subsequences, i.e., absent subsequences of minimal length. We show a series of combinatorial and algorithmic results regarding these two notions. For instance: we give combinatorial characterisations of the sets of minimal and, respectively, shortest absent subsequences in a word, as well as compact representations of these sets; we show how we can test efficiently if a string is a shortest or minimal absent subsequence in a word, and we give efficient algorithms computing the lexicographically smallest absent subsequence of each kind; also, we show how a data structure for answering shortest absent subsequence-queries for the factors of a given string can be efficiently computed. [ABSTRACT FROM AUTHOR]

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