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This study explores the role of eminent buildings and shrines of cultural and religious significance for collective and individual identities, in the context of present culture with its disruptions of tradition, in cultural and religious regard. It draws on the renewed awareness of this connection, that developed in public debate in France, after the arson of eminent cathedrals, and in Germany, in debate about the reconstruction of historic buildings after reunification. The controversies are presented and viewed with regard to the changing contexts of secularisation, migration and religious plurality. The recent debates are understood as indication of a gradual recognition of the role of ‘symbolic landscapes’ and of the value of relating to them, for the sake of strengthening the bond with historical identity and heritage, as intrinsically connected. The growing or reluctant realisation that this includes the religious dimension, is noted – with both Christianity and Paganism. Theory about the symbolic function of eminent religious buildings is included. This is considered, in particular, with regard to religious and cultural pluralism as condition of reception, for a strengthening of a common and shared symbolic landscape, relevant to identity. It includes a view to ‘pilgrimage’ as mode of connecting to such sites. The essay also takes restored and rediscovered sacred sites in Africa into view. Here the disruptions and devaluation of historical identity due to colonialism is kept in view as background. Eminent examples of reconstructed shrines as centres of a spiritual and cultural geography, reinforcing collective and individual identity, are presented, as. An example of active appropriation of ancient sacred sites of previous populations is also mentioned, from South Africa, as means of cultural and spiritual ‘territorialisation’.

BackgroundGestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells.ObjectiveThis systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood.MethodsLiterature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: τ2, χ2, and I2. Study quality was assessed using a modified version of the Newcastle-Ottawa scale.ResultsThe search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, −0.76; 95% CI, −1.37, −0.15; I2 = 90%). This was reflected in the analysis by specific Treg markers (SMD −0.55; 95% CI, −1.04, −0.07; I2 = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4+FoxP3+, CD4+CD127−, and CD4+CD127−FoxP3) of both analyses.ConclusionGDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022309796.

This study introduces the Failure Decision Function, a novel approach for evaluating the structural capacity of rectangular reinforced concrete columns under axial forces and moments, both uniaxial and biaxial. The method simplifies existing practices, enhancing accuracy and integration into design software. The methodology hinges on deriving exact biaxial bending failure surfaces, utilizing integral expressions based on material properties and cross-sectional geometry. This direct integration process uncovers failure surface characteristics previously undocumented. Results confirm the utility of the Failure Decision Function through comparative analysis with established literature, showcasing its potential for simplifying and improving structural capacity assessments. The analytic procedure developed enables efficient computation of failure surfaces, streamlining the inclusion of these functions in structural engineering software in two key ways: (1) compiling a library of pre-calculated functions for quick capacity checks and (2) creating a dynamic application that generates these functions based on specific design parameters, allowing users to explore various load and moment scenarios. In conclusion, the Failure Decision Function represents a significant advancement in structural engineering design, offering an accurate and user-friendly method for assessing column performance under critical loading conditions.

Cardiovascular disease (CVD) diagnosis and treatment are challenging since symptoms appear late in the disease’s progression. Despite clinical risk scores, cardiac event prediction is inadequate, and many at-risk patients are not adequately categorised by conventional risk factors alone. Integrating genomic-based biomarkers (GBBM), specifically those found in plasma and/or serum samples, along with novel non-invasive radiomic-based biomarkers (RBBM) such as plaque area and plaque burden can improve the overall specificity of CVD risk. This review proposes two hypotheses: (i) RBBM and GBBM biomarkers have a strong correlation and can be used to detect the severity of CVD and stroke precisely, and (ii) introduces a proposed artificial intelligence (AI)—based preventive, precision, and personalized (aiP3) CVD/Stroke risk model. The PRISMA search selected 246 studies for the CVD/Stroke risk. It showed that using the RBBM and GBBM biomarkers, deep learning (DL) modelscould be used for CVD/Stroke risk stratification in the aiP3 framework. Furthermore, we present a concise overview of platelet function, complete blood count (CBC), and diagnostic methods. As part of the AI paradigm, we discuss explainability, pruning, bias, and benchmarking against previous studies and their potential impacts. The review proposes the integration of RBBM and GBBM, an innovative solution streamlined in the DL paradigm for predicting CVD/Stroke risk in the aiP3 framework. The combination of RBBM and GBBM introduces a powerful CVD/Stroke risk assessment paradigm. aiP3 model signifies a promising advancement in CVD/Stroke risk assessment.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Background: BRAFV600E mutation is present in a subset of pediatric brain tumors. Vemurafenib is an oral, selective ATP-competitive inhibitor of BRAFV600E kinase. The goal of this multi-center study conducted through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) was to determine the recommended phase 2 dose (RP2D) and dose limiting toxicities (DLTs) in children < 18 years with recurrent or progressive BRAFV600E mutant brain tumors. Results: Nineteen eligible patients were enrolled. Eleven patients had received three or more prior therapies. Data reported are from the start of treatment for the first patient (April 30 2014) through August 31 2019. The RP2D was defined as 550 mg/m2 twice daily after DLT criteria adjustment for rash. Related grade ≥ 3 adverse events included secondary keratoacanthoma (n = 1); rash (n =16); and fever (n = 5). Subjects received a median of 23 cycles (range 3-63). Four patients remain on treatment. Centrally reviewed best radiographic responses included 1 complete response, 5 partial responses, and 13 stable disease. The steady-state area under the curve (AUC0-∞median) was 604 mg*h/L (range 329-1052). Methods: Vemurafenib was given starting at 550 mg/m2, twice daily which corresponds to the adult RP2D. Adverse events were graded using the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Central imaging review was performed. Pharmacokinetic sampling was performed. Conclusions: Vemurafenib has promising anti-tumor activity in recurrent BRAF V600E-positive brain tumors with manageable toxicity. A phase 2 study is ongoing (NCT01748149).

In recent times, it has been recognized that atherosclerotic cardiovascular disease (ASCVD) risk stratification using algorithms such as Framingham risk score, prospective cardiovascular Munster, QRISK2 or SCORE2/SCORE2-OP which are based on conventional risk factors could be improved by ultrasound arterial scanning. In the past, much emphasis was placed on intima-media thickness (IMT), but two recent meta-analyses have demonstrated that IMT provides only a marginal improvement on risk factors. In contrast to IMT, the presence, thickness, area or volume of plaques at the carotid and/or common femoral bifurcations are the stronger independent predictors of future ASCVD events than conventional risk factors alone. A recent study has shown that the number of bifurcations with plaque, total plaque thickness (sum of thickness of larger plaque in each bifurcation), and total plaque area (sum of areas of all plaques present in four bifurcations) have a similar net reclassification improvement of 16.1%–16.7%. In addition to this, previous studies demonstrated that common femoral bifurcation plaques are the stronger predictors of risk than carotid plaques. Thus, as far as screening is concerned, it appears that the number of bifurcations with plaque would be sufficient. However, for clinical monitoring of the effect of therapy on plaque progression or regression, measurements of plaque area or volume are the most appropriate. The commercial availability of three-dimensional-probes for superficial vessels will now make measurements of plaque volume relatively easy and the ability to monitor plaque volume changes in a clinical setting possible.

Abstract Background Twin anemia polycythemia sequence is a rare complication in monochorionic twin pregnancy. Case presentation We describe a case of dichorionic twin pregnancy presenting with suspected twin anemia polycythemia sequence. A 31-year-old White female, on her third pregnancy, had a routine ultrasound scan at 12 weeks gestation, which demonstrated a dichorionic twin pregnancy with one placenta located in the anterior wall and the other in the posterior wall of the uterus. At 21 weeks, a scan demonstrated a 24% growth discordance between the two fetuses with normal Doppler studies and amniotic fluid. At 27 weeks, one twin showed signs of anemia and the other polycythemia; the fetal middle cerebral artery peak systolic velocity was high in the anemic fetus and low in the polycythemic twin (1.8 and 0.5 multiples of the median). An intrauterine blood transfusion was carried out and this increased the fetal hemoglobin concentration in the anemic twin from 3.5 to 12.5 g/dL. At 29 weeks, delivery by cesarean section was carried out because of evidence from middle cerebral artery peak systolic velocity of recurrence of anemia in one twin and worsening polycythemia in the co-twin; at birth the hemoglobin concentrations were 5.6 and 24.9 g/dL, respectively. Histopathological examination confirmed dichorionicity with no communicating vessels between the two placentas. Conclusions This is the first case of twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy where intrauterine blood transfusion was used to prolong the pregnancy by almost 2 weeks in a “twin anemia polycythemia sequence-like” setting.

The purpose of this study was to assess the validity and reliability of the Transformative Learning Outcomes and Processes Survey (TROPOS) in the workplace context. The results of a confirmatory factor analysis of the data gathered from 132 employees of a steel manufacturing company in the United States have shown that the TROPOS is an appropriate instrument for measuring transformative learning in the workplace context. Implications for transformative learning research and practice will be discussed.

Abstract Diffuse intrinsic pontine glioma (DIPG) is an aggressive incurable brainstem tumor that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. This study aimed to identify potential therapeutic agents using a computational pipeline to perform an in silico screen for novel drugs. We then tested the identified drugs against a panel of patient-derived DIPG cell lines. Using a systematic computational approach with publicly available databases of gene signature in DIPG patients and cancer cell lines treated with a library of clinically available drugs, we identified drug hits with the ability to reverse a DIPG gene signature to one that matches normal tissue background. The biological and molecular effects of drug treatment was analyzed by cell viability assay and RNA sequence. In vivo DIPG mouse model survival studies were also conducted. As a result, two of three identified drugs showed potency against the DIPG cell lines Triptolide and mycophenolate mofetil (MMF) demonstrated significant inhibition of cell viability in DIPG cell lines. Guanosine rescued reduced cell viability induced by MMF. In vivo, MMF treatment significantly inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, we identified clinically available drugs with the ability to reverse DIPG gene signatures and anti-DIPG activity in vitro and in vivo. This novel approach can repurpose drugs and significantly decrease the cost and time normally required in drug discovery.

The purpose of this work is to assist partners in identifying, naming, and facilitating dynamic relational forces and learning processes that shape the effectiveness of community engagement practice and partnerships. We offer a hypothetical case to assist in framing and discussing concepts of reciprocity and power in partnerships and how these dynamics can be mediated through practices and processes of civic engagement and transformative learning. We advocate that mapping intersects of power and reciprocity, and attending to capacities for deliberative civic engagement and transformative learning, are crucial practices in effective community-engaged partnerships. These three vital practices contribute to the creation of conditions that nurture the emergence of individual, institutional, organizational, and social transformation generated through community-engaged scholarship.

Karl Jaspers (1883–1969) was an important philosopher and thinker chiefly in the areas of epistemology, existentialism, the philosophy of religion, and also political theory amongst others. However, his ideas have to a very large degree become obscured over the years. This notwithstanding, among his important contributions, Jaspers articulated the notion that individuals do not cognize objects but explain and objectify their being as often unique thinkers and consequently they become themselves. It is a question of delineating and analysing the structure of Being, as such, which leads to ultimate illumination. Humanity may understand the mechanical operations of our corporeal world through science, but it is only philosophy that is proficient in giving insights into the human condition and the individual being who, in turn, has a capacity to exercise freedom. This article considers Jaspers’ ideas on transcendence and how they differ from mainline Eastern Orthodoxy. It argues that only a person whose entire being has been transformed by faith has some access to truth. It is further advanced that, faith is a priori philosophical and not religious issue because it is ultimately a personal and thus subjective matter and has no support in authority. Faith is thus not to be viewed as an objective and communicable subjugator of reason. It is through suffering and a range of experiences and ultimately the reconning with death, that one encounters ultimate situations wherein the Transcendent God is encountered. God is not an object and can be known and described only through myths and symbols or ciphers. The Transcendent Being (God) is symbolically expressed in religion. Jaspers view of Being in its various facets is in opposition to Eastern Orthodox Christian views which is what this work interrogates to a limited extent. The Orthodox doctrine of God perceives God as a Transcendent Being in each of the material and immaterial domains of His Creation.

Glass is considered a sustainable material with achievable recovery rates within the EU. However, there are limited data available for construction glass waste management. Furthermore, glass is a heavy material, and considering the geographical limitations of Cyprus, the transportation trading cost within the EU is extremely high. Therefore, another method for utilizing this by-product should be developed. The aim of this research is to investigate the production of a low-cost, lightweight and fireproof material able to retain its structural integrity, using the geopolymerization method with the incorporation of randomly collected construction glass waste. The glass waste was initially processed in a Los Angeles abrasion machine and then through a Micro-Deval apparatus in order to be converted to a fine powder. Mechanical (compressive and flexural strength), physical (setting time and water absorption) and thermal properties (thermal conductivity) were investigated. The fire-resistant materials presented densities averaging 450 kg/m3 with a range of compressive strengths of 0.5 to 3 MPa. Additionally, a techno-economic analysis was conducted to evaluate the viability of the adopted material. Based on the results, the final geopolymer product has the potential to be utilized as a fire resistance material, preventing yielding or spalling.