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Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists. Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Metastasis is the primary cause of cancer-related death in oncology patients. A comprehensive understanding of the molecular mechanisms that cancer cells usurp to promote metastatic dissemination is critical for the development and implementation of novel diagnostic and treatment strategies. Here we show that the membrane protein RECK (Reversion-inducing cysteine-rich protein with kazal motifs) controls breast cancer metastasis by modulating a novel, non-canonical and convergent signal transducer and activator of transcription factor 3 (STAT3)-dependent angiogenic program. Neoangiogenesis and STAT3 hyperactivation are known to be fundamentally important for metastasis, but the root molecular initiators of these phenotypes are poorly understood. Our study identifies loss of RECK as a critical and previously unknown trigger for these hallmarks of metastasis. Using multiple xenograft mouse models, we comprehensively show that RECK inhibits metastasis, concomitant with a suppression of neoangiogenesis at secondary sites, while leaving primary tumor growth unaffected. Further, with functional genomics and biochemical dissection we demonstrate that RECK controls this angiogenic rheostat through a novel complex with cell surface receptors to regulate STAT3 activation, cytokine signaling, and the induction of both vascular endothelial growth factor and urokinase plasminogen activator. In accordance with these findings, inhibition of STAT3 can rescue this phenotype both in vitro and in vivo . Taken together, our study uncovers, for the first time, that RECK is a novel regulator of multiple well-established and robust mediators of metastasis; thus, RECK is a keystone protein that may be exploited in a clinical setting to target metastatic disease from multiple angles.

The emergence of epigenetic mechanisms as key regulators of gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, epigenetic aberrations have emerged as critical processes that disrupt cellular machinery and homeostasis. Recent discoveries have already translated into successful clinical trials and improved patient care, with several agents approved for hematologic disease and others undergoing study. As the field matures, substantial challenges persist that will require resolution. These include the need to decipher more fully the interplay between the epigenetic and genetic machinery, patient selection and improving treatment efficacy in solid tumors, and optimizing combination therapies to counteract chemoresistance and minimize adverse effects. Here, we review recent progress in epigenetic treatments and consider their implications for future cancer therapy.

This article offers a theo-phenomenological investigation of the body, exploring the dialogue between contemporary phenomenology—especially its theological turn—and Eastern Orthodox spirituality as found in the Philokalia. Building on the phenomenological distinction between body and flesh and drawing on Orthodox theology’s understanding of the body–soul unity, the article analyzes the intramundanity and finitude of the human body, as well as its transfiguration through ascetic practices and divine grace. The Incarnation of Christ is examined as a central paradigm for rethinking embodiment, revealing the eschatological promise of glorified flesh. Concepts such as ipseity, self-affection, intentionality, and counter-intentionality are employed to articulate a phenomenological vision open to theological transcendence. Ultimately, this interdisciplinary approach affirms the possibility of a body transformed by grace and destined for resurrection.

This study proposes a theo-phenomenological reading of asceticism in Eastern Orthodox spirituality, with particular attention to the Philokalic tradition, analyzing the relationship between the body, emotions, and spiritual freedom. Drawing on the phenomenological distinction between the physical body (Körper) and the lived body (Leib), the article describes asceticism as a limit-experience that de-limits: an exercise of bodily and affective finitude oriented toward the transfiguration of life within the horizon of divine grace. Methodologically, the research combines textual analysis of representative Philokalic authors with insights from modern Orthodox thinkers and phenomenological concepts such as intentionality, affectivity, reduction, and apatheia, in order to describe from within the lived body, the synergy between ascetic will and the working of grace as it manifests itself in lived ascetic experience. Asceticism is presented as a dynamic process unfolding in stages: inauguration through the discovery of finitude; confrontation, in which the limits of the body and emotions are tested; and liberation as apatheia, in which the body becomes co-praying and co-serving with the soul. Emotions are interpreted as an intermediate space between body and soul—as affects of awareness, struggle, and ultimately transfiguration—through which human existence before God is manifested. The contribution of the article lies in articulating a theo-phenomenological model of Philokalic asceticism in which freedom is not the absence of emotions nor the negation of the body, but an affective and bodily reconfiguration through grace, making possible the communion of love with God and with others.

This article explores the phenomenology of time and eschatology in the thought of Jean-Yves Lacoste, including his recent book on the philosophy of history. Lacoste’s idea of “the hidden present” is examined within the context of his broader theological and philosophical framework, with a particular focus on the way it addresses the intersection of temporality and eternity. Human temporality is characterized by finitude and death, which are interpreted both philosophically—under the influence of Heidegger’s philosophy—and theologically. Using Husserlian and Heideggerian concepts, Lacoste proposes a theologically inspired conceptual network: phenomenological reduction versus theological reduction, world versus creation, death versus resurrection, care (Sorge) versus eschatological restlessness, and time versus eschaton. All of these describe the liturgical experience of man before God and the possibility of an eternity which, from the point of view of the world and of our experience in the world, can only take on the ever-provisional figure of anticipation. The present article argues for the existence of a theological paradox of eschatology in the writings of the French phenomenologist: even if eschatology is only anticipated, the liturgical man, situated before God (coram Deo), experiences it in an incomplete and apophatic manner.

This article is a theo-phenomenological study on discernment in Eastern Orthodox spirituality, particularly as it is described in the Philokalia and the Apophthegmata Patrum . The article focuses on two fundamental dimensions: firstly, discernment as both theoretical and practical wisdom, characterized by the importance of preliminary discernment criteria; secondly, discernment as a spiritual gift of the Holy Spirit, which can be interpreted phenomenologically through the figure of the saturated phenomenon. In its concluding sections, the article proposes a new approach to religious thought, termed “diacritical thought”. This innovative approach evolves from objective thought, grounded in value criteria and contextual understanding, towards relational thought. It emphasizes affectivity and the importance of engaging with others, ultimately leading to prayer and mystical experiences. Throughout these stages, discernment undergoes a transformation: it evolves from a poor phenomenon into a saturated phenomenon, going on a journey from ordinary experience to testing the boundaries of human experience.

The present article analyzes the relationship between phenomenology and theology, starting from some examples of the phenomenology of prayer. First, the article presents the phenomenology of prayer in the writings of phenomenologists such as Jean-Luc Marion, Jean-Yves Lacoste, Christina Gschwandtner and Natalie Depraz, indicating that the type of phenomenology and its relationship with theology influence the way in which they approach the theme of prayer. Second, the paper proposes a systematization of prayer, starting from the personal pronouns uttered when praying: I, you (thou) and he. “I” sees oneself as being called by God to a transfiguration which is impossible through one’s own powers and visible in the experience of the plenitude and joy of prayer; “You” provides the predicative dimension of the discourse and reveals communion either with God or, in the case of liturgy, with others; “He”, used less frequently in prayer, can constitute a source for a later theoretical discourse, being recognized as a “mysterious presence”. Following these analyses, the article concludes that there are two major relationships between phenomenology and theology: that of partial overlap, called theo-phenomenology, and that of rigorous delimitation. Regardless of the preferred model, the use of phenomenology for theology proves to be fruitful.

The Orthodox liturgy is a religious phenomenon that can be analyzed phenomenologically and theologically alike, given the emphasis that both phenomenology and Orthodox theology place on experience. By proposing the Kingdom of God instead of the natural world without being able to annihilate the latter in the name of the former, the liturgy seeks divine-human communion. Through the dialogue of prayer, through symbolic and iconic openings, as well as through apophatic theology, the liturgy emphasizes the horizon of mystery as a horizon essential to the way man positions himself before God. The present text attempts to demonstrate that apophaticism, understood as an experience of the mysterious presence of God, is one of the crucial dimensions of the Orthodox liturgy; and that this apophatic presence of God reveals a way of thinking which does not become onto-theology, not even when using concepts borrowed from metaphysics. The overcoming of onto-theology is achieved here not by abandoning concepts such as “being” and “cause” but by placing the language game in the field of prayer and apophatic theology.

Drawing a clear line between phenomenology and theology remains a challenging endeavor. This article has two parts: The first one argues that, from a methodological point of view, there is a need for a theo-phenomenology, a phenomenology which acknowledges religious faith as a given. The second part of the article tries to present the essence of religious call in Eastern Orthodox spirituality. Using ideas such as appeal and communion, divine grace, love, prayer, fidelity, apophatic intentionality, and a hyper-intelligible gaze before the Revelation, I will describe the phenomenon of religious call—God calling man and man calling God. The conclusion shows that religious call and answer are existential and theandric experiences, where one can work on askesis, the fidelity of thought, and mystical experience. Life in the Holy Spirit no longer distinguishes between call and answer for one who became a son of God by grace, faith, and good works.