Search Results (19)

Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10⁻⁵). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article

The drastic and historic fall in natural rubber prices has prompted many smallholders around the world to abandon rubber plantations in favor of other survival alternatives. In the Lomela and Lodja territories of Sankuru Province (Democratic Republic of Congo), where a historical absence of a rubber market prevails, local communities have conserved rubber plantations inherited from the colonial era (dating back to 1955). Data collected from 401 households enabled us to identify the perceptions and determinants of rubber plantation conservation. The results show that households are highly dependent on forest ecosystem services. Agriculture is the main activity for 81.3% of respondents, in the context of extreme poverty where daily incomes amount to 0.33 USD/person. The patriarchal system favored men, who inherited 97% of the plantations. Men perceived the conservation of the plantations as beneficial, while women perceived it as serving external project interests. Perceptions were significantly influenced by gender, age, social and legal organization, geographical origin, mode of acquisition, main activity, diversification of income sources, membership in a tribal mutuality, access to the informal mutual aid networks, membership in an association and contact with extension services. Conservation was positively and significantly correlated with geographical origin, membership in an association, contact with extension service, consideration of plantations as natural heritage and the ecosystem services provided. These results underline that rubber plantations cannot be understood only in terms of rubber production, but also in terms of their socio-ecological and heritage dimensions. Full article

Introduction: Early-onset colorectal cancer (EOCRC) is rising rapidly, particularly among the Hispanic/Latino (H/L) populations, who face disproportionately poor outcomes. The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in colorectal cancer (CRC) progression by mediating epithelial-to-mesenchymal transition (EMT), immune evasion, and metastasis. However, integrative analyses linking TGF-β alterations to clinical features remain limited—particularly for diverse populations—hindering translational research and the development of precision therapies. To address this gap, we developed AI-HOPE-TGFbeta (Artificial Intelligence agent for High-Optimization and Precision Medicine focused on TGF-β), the first conversational artificial intelligence (AI) agent designed to explore TGF-β dysregulation in CRC by integrating harmonized clinical and genomic data via natural language queries. Methods: AI-HOPE-TGFbeta utilizes a large language model (LLM), Large Language Model Meta AI 3 (LLaMA 3), a natural language-to-code interpreter, and a bioinformatics backend to automate statistical workflows. Tailored for TGF-β pathway analysis, the platform enables real-time cohort stratification and hypothesis testing using harmonized datasets from the cBio Cancer Genomics Portal (cBioPortal). It supports mutation frequency comparisons, odds ratio testing, Kaplan–Meier survival analysis, and subgroup evaluations across race/ethnicity, microsatellite instability (MSI) status, tumor stage, treatment exposure, and age. The platform was validated by replicating findings on the SMAD4, TGFBR2, and BMPR1A mutations in EOCRC. Exploratory queries were conducted to examine novel associations with clinical outcomes in H/L populations. Results: AI-HOPE-TGFbeta successfully recapitulated established associations, including worse survival in SMAD4-mutant EOCRC patients treated with FOLFOX (fluorouracil, leucovorin and oxaliplatin) (p = 0.0001) and better outcomes in early-stage TGFBR2-mutated CRC patients (p = 0.00001). It revealed potential population-specific enrichment of BMPR1A mutations in H/L patients (OR = 2.63; p = 0.052) and uncovered MSI-specific survival benefits among SMAD4-mutated patients (p = 0.00001). Exploratory analysis showed better outcomes in SMAD2-mutant primary tumors vs. metastatic cases (p = 0.0010) and confirmed the feasibility of disaggregated ethnicity-based queries for TGFBR1 mutations, despite small sample sizes. These findings underscore the platform’s capacity to detect both known and emerging clinical–genomic patterns in CRC. Conclusions: AI-HOPE-TGFbeta introduces a new paradigm in cancer bioinformatics by enabling natural language-driven, real-time integration of genomic and clinical data specific to TGF-β pathway alterations in CRC. The platform democratizes complex analyses, supports disparity-focused investigation, and reveals clinically actionable insights in underserved populations, such as H/L EOCRC patients. As a first-of-its-kind system studying TGF-β, AI-HOPE-TGFbeta holds strong promise for advancing equitable precision oncology and accelerating translational discovery in the CRC TGF-β pathway. Full article

The open society is under threat from populism and fake news. But what do we mean by the ‘open society’? The notion was made popular by Bergson and Popper. Under the impact of totalitarianism, Popper distinguished open from closed societies. They differ by their degree of institutionalized critical scrutiny of political and societal practices. Modern sociological theory uses the notions of differentiation (or complexity) and reflexivity to distinguish these types of society (Habermas, Giddens). Reflexivity goes beyond critical scrutiny; it describes the constant examination and revision of social practices in the light of incoming information. An evaluation of these criteria shows that a necessary and sufficient condition for the distinction between open and closed societies is the degree of institutionalized critical scrutiny (contestability) and, even more, reflexivity. Openness is not a function of the complexity of societal development. It is a function of appropriate political structures. Therein lies its deeper connection with democracy: drawing upon several historical and contemporary examples thisarticle suggests that open societies can be characterized by critical scrutiny and even more reflexivity. In the final section, this article analyses the malaise of modern democracies with respect to the risks posed by populism and disinformation through social media. But rather than focusing on immigration or the economy, it considers the risks in terms of the erosion of institutional trust. Institutional trust is one of the civic virtues which the Enlightenment regarded as an essential feature of a democratic society. I conclude that populism and the deliberate spread of false information undermine civic virtues; a return to civic virtues is an important feature of the survival of democracy as an open society. Full article

Out-of-hospital cardiac arrest (OHCA) mortality remains alarmingly high in most countries. The majority of pharmacological attempts to improve outcomes have failed. Randomized trials have shown limited survival benefits with vasopressin, fibrinolysis, amiodarone, or lidocaine. Even the benefits of adrenaline remain a matter of debate. In this context, relying on technology may seem appealing. However, technological strategies have also yielded disappointing results. This is exemplified by automated external chest compression devices. When first introduced, theoretical models, animal studies, and early clinical trials suggested they could improve survival. Yet, randomized trials failed to confirm this benefit. Similarly, to date, extracorporeal membrane oxygenation (ECMO), therapeutic hypothermia, and primary angioplasty have demonstrated inconsistent survival advantage. Other technological innovations continue to be explored, such as artificial intelligence to improve the diagnosis of cardiac arrest during emergency calls, mobile applications to dispatch citizen responders to patients in cardiac arrest, geolocation of defibrillators, and even the delivery of defibrillators via drones. Nevertheless, it is clear that the focus and investment should prioritize the initial links in the chain of survival: early alerting, chest compressions, and defibrillation. Significant improvements in these critical steps can be achieved through the education of children. Modern technological tools must be leveraged to enhance this training by incorporating gamification and democratizing access to education. These strategies hold the potential to fundamentally improve the management of cardiac arrest. Full article

Background/Objectives: This study investigated vaso-occlusive crises (VOCs) in sickle cell disease in Lubumbashi, Democratic Republic of Congo, aiming to understand the disease complexities amidst limited resources. With sickle cell hemoglobinopathies on the rise in sub-Saharan Africa, this nine-year study explored factors associated with VOCs and hematological components. Methods: This study comprised 838 patients, analyzing VOCs and hematological changes over time. Demographic characteristics and blood composition changes were carefully categorized. A total of 2910 crises were observed and managed, with analyses conducted on severity, localization, and age groups using statistical methods. Results: The majority of crises were mild or moderate, primarily affecting osteoarticular regions. Statistical analysis revealed significant disparities in crisis intensity based on location and age. The association between blood samples and the number of comorbidities was investigated. Significant positive associations were found for all parameters, except monocytes, indicating a potential link between blood variables and complication burden. Survival analysis using Cox regression was performed to predict the probability of experiencing a second crisis. No significant effects of medication or localization were observed. However, intensity (p < 0.001), age (p < 0.001), and gender (p < 0.001) showed significant effects. Adjusted Hazard Ratios indicated increased risk with age and male gender and reduced risk with mild or severe crisis intensity compared to light. Conclusions: This research sheds light on the complexities of VOCs in resource-limited settings where sickle cell disease is prevalent. The intricate interplay between clinical, laboratory, and treatment factors is highlighted, offering insights for improved patient care. It aims to raise awareness of patient challenges and provide valuable information for targeted interventions to alleviate their burden. Full article

Anthropogenic activities put biodiversity under pressure, adversely affecting the forest ecosystem and wildlife habitats. Habitat disturbance and modification are among the main threats to animal populations in tropical forests. In the Democratic Republic of Congo (DRC), Grauer’s gorillas (Gorilla beringei graueri) are continuously threatened through forest encroachment for agricultural expansion, human settlements, new refugee camps, illegal logging, and mining across the country. Moreover, poaching and bushmeat trafficking continuously threaten gorillas’ existence. These drivers increase the proximity of humans and the risk of disease transmission. The emerging and existing zoonotic diseases, including Ebola, are continuously impacting gorillas’ lives. All of these pressures combined are disrupting natural behavior patterns and are leading to the decline in the Grauer’s gorillas’ population. Therefore, this review scrutinizes findings on the anthropogenic pressures on the habitats and survival of Grauer’s gorillas. Also, it is important to engage with people for the shared conservation role and ecotourism to support the conservation of forest biodiversity and Grauer’s gorillas’ habitats, particularly for the Maiko National Park in the DRC. Full article

The underlying risk factors associated with the duration and termination of biological, sociological, economic, or political processes often exhibit spatial clustering. However, existing nonspatial survival models, including those that account for “immune” and “at-risk” subpopulations, assume that these baseline risks are spatially independent, leading to inaccurate inferences in split-population survival settings. In this paper, we develop a Bayesian spatial split-population survival model that addresses these methodological challenges by accounting for spatial autocorrelation among units in terms of their probability of becoming immune and their survival rates. Monte Carlo experiments demonstrate that, unlike nonspatial models, this spatial model provides accurate parameter estimates in the presence of spatial autocorrelation. Applying our spatial model to data from published studies on authoritarian reversals and civil war recurrence reveals that accounting for spatial autocorrelation in split-population models leads to new empirical insights, reflecting the need to theoretically and statistically account for space and non-failure inflation in applied research. Full article

The feminist agenda in Russia experienced a phase of intense aesthetic search in the field of contemporary art and contemporary theater. The split in society, war, increased censorship and state propaganda, and mass emigration stopped this process. Feminist ethics and aesthetics are oriented toward democratic values and the absolute value of human life; it is difficult for them to survive in totalitarian states. Using material from the history of feminism and aesthetic practices in the post-perestroika decades of Russia, this article examines two historical forms of such survival: the Stockholm syndrome and, in more detail, “anti-propaganda”, the popularization of the feminist agenda through aesthetic practices with mandatory feedback and the utmost attention to individual fate and personal trauma. Full article

In a previous article we proposed that spiritual traditions and practices emerged to counterbalance humans inherent “dualism”, or perceived separation from the world around us, by cultivating experiences of “subject-object nonduality” more commonly referred to as “unification with the divine” or “enlightenment”. This implies that religions (social and political institutions ostensibly based in spiritual practices) similarly aim towards overcoming the separation of self and other. However, many religions include dualistic elements. In particular, many religions incorporate “ethical dualism” in which certain individuals and groups are seen as essentially “good” or “bad”, a feature not seen in nondual traditions. Here, we explore this seeming paradox, highlighting an intriguing correspondence between the degree to which religions include dualistic or nondualistic elements and, respectively, the prevalence of conflict or cooperation as the organizing principle in their associated social context. We find major “dualistic” religions to be generally traceable to pastoral societies largely organized around intergroup conflict, whereas major “nondual religions” are generally traceable to societies in which large-scale cooperation and rule-based behavior was necessary for collective survival. Finally, we apply this pattern to the modern world, speculating that large-scale cooperation and rule-based behavior in modern society may be currently encouraging the renewal of nondual practices in modern social and political institutions that is indicated by the growing popularity of “spiritual but not religious” groups, and that this renewal of nondual practices may in turn set the frame for and reinforce behavior that will be necessary to address the historic challenges of our day like climate change and democratic backsliding. Full article

This study aims to determine the factors influencing HIV-related mortality in settings experiencing continuous armed conflict atrocities. In such settings, people living with HIV (PLHIV), and the partners of those affected may encounter specific difficulties regarding adherence to antiretroviral therapy (ART), and retention in HIV prevention, treatment, and care programs. Between July 2019 and July 2021, we conducted an observational prospective cohort study of 468 PLHIV patients treated with Dolutegravir at all the ART facilities in Bunia. The probability of death being the primary outcome, as a function of time of inclusion in the cohort, was determined using Kaplan–Meier plots. We used the log-rank test to compare survival curves and Cox proportional hazard modeling to determine mortality predictors from the baseline to 31 July 2021 (endpoint). The total number of person-months (p-m) was 3435, with a death rate of 6.70 per 1000 p-m. Compared with the 35-year-old reference group, older patients had a higher mortality risk. ART-naïve participants at the time of enrollment had a higher mortality risk than those already using ART. Patients with a high baseline viral load (≥1000 copies/mL) had a higher mortality risk compared with the reference group (adjusted hazard ratio = 6.04; 95% CI: 1.78–20.43). One-fourth of deaths in the cohort were direct victims of armed conflict, with an estimated excess death of 35.6%. Improving baseline viral load monitoring, starting ART early in individuals with high baseline viral loads, the proper tailoring of ART regimens and optimizing long-term ART, and care to manage non-AIDS-related chronic complications are recommended actions to reduce mortality. Not least, fostering women’s inclusion, justice, peace, and security in conflict zones is critical in preventing premature deaths in the general population as well as among PLHIV. Full article

During the COVID-19 pandemic, the protection of public health became a political priority worldwide. Slovakia’s COVID-19 response was initially praised as a global success. However, major rights restrictions were introduced in spring 2020, with some of these endorsed by the parliament. This article uses Rossiter’s and Schmitt’s concepts of the exception and Agamben’s distinction between life and survival to highlight the risks pertaining to the framing of the protection of public health as contradictory to human rights guarantees. It investigates how human rights were discussed by Slovak parliamentarians in relation to key legislation, that introduced a COVID-19 contact tracing app and allowed repeated prolongation of health emergencies by the executive with parliamentary approval. The findings indicate that democratic parliamentarians prioritized public health considerations framed in terms of security and effectiveness rather than rights, dissociating biological survival from political life. In contrast, extreme political actors became outspoken critics of emergencies, referring to human rights. As such, the deliberations represent a missed opportunity by democratic legislators to justify public health protection via a human rights lens and risk undermining democracy in Slovakia. Full article

In this paper, we want to address how the educative growth of children’s spirituality within religious education can be better understood through Dewey’s theory of valuation. We would like to draw attention to the link between an education for authentic spirituality and the pursuit of a genuine democratic life, because education, even religious education, is always political. In doing so, we point to the urgency and importance of fostering spiritual education for children in the face of the current rise of authoritarianism throughout the world and the demise of authentic democratic life. In order for genuine democracies to survive and thrive, their citizens must be educated. Unlike indoctrination and propaganda, which control populations through manufacturing public opinion by which individuals are compelled to comply to an officially approved consensus, education is emancipatory by offering opportunity for dissensus. Emancipatory education enables individual citizens to initiate and participate in activities at the grass-roots level that pursue public and global goods, without waiting to be led by various authorities. Such an educated way of being, which is essential for democratic life, requires young people to be educated spiritually so that they are able to transcend the pressures to conform to public consensus and the will of authoritarianism, and instead to actively live their spirituality by undertaking activities that pursue the good, even when such activities are deemed to dissent from public opinion. Full article

Surface water contamination by pathogen bacteria remains a threat to public health in the rural areas of developing countries. Fecal indicator bacteria (FIB) like Escherichia coli (E. coli) are widely used to assess water contamination, but their behavior in tropical ecosystems is poorly documented. Our study focused on headwater wetlands which are likely to play a key role in stream water purification of fecal pollutants. Our main objectives were to: (i) evaluate decay rates (k) of the total, particle-attached and free-living E. coli; (ii) quantify the relative importance of solar radiation exposition and suspended particles deposition on k; and (iii) investigate E. coli survival in the deposited sediment. We installed and monitored 12 mesocosms, 4500 mL each, across the main headwater wetland of the Houay Pano catchment, northern Lao People’s Democratic Republic (Lao PDR), for 8 days. The four treatments with triplicates were: sediment deposition-light (DL); sediment deposition-dark (DD); sediment resuspension-light (RL); and sediment resuspension-dark (RD). Particle-attached bacteria predominated in all mesocosms (97 ± 6%). Decay rates ranged from 1.43 ± 0.15 to 1.17 ± 0.13 day⁻¹ for DL and DD treatments, and from 0.50 ± 0.15 to −0.14 ± 0.37 day⁻¹ for RL and RD treatments. Deposition processes accounted for an average of 92% of E. coli stock reduction, while solar radiation accounted for around 2% over the experiment duration. The sampling of E. coli by temporary resuspension of the deposited sediment showed k values close to zero, suggesting potential survival or even growth of bacteria in the sediment. The present findings may help parameterizing hydrological and water quality models in a tropical context. Full article

Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy. Full article