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2025
The International Agency for Research on Cancer (IARC) Monographs Programme plays an important role in cancer prevention by identifying potential carcinogenic hazards. However, the terminology used in IARC’s classifications and Monographs can confuse the public, health professionals, and policymakers. Terms like “carcinogenic to humans” imply causation, although classifications only indicate increased risk under certain conditions. For example, the lifetime incidence of mesothelioma among firefighters is approximately 14 in 10,000, compared to 7 in 10,000 in the general population. Despite doubling the risk, occupational exposure as a firefighter does not cause this type of cancer in 9,986 out of 10,000 firefighters. However, the IARC concludes that “occupational exposure as a firefighter causes mesothelioma” (IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Occupational Exposure as a Firefighter. Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addition, the lack of essential information about dosage and context in the IARC carcinogen lists can lead to agents with health benefits under certain conditions (e.g., solar radiation, red meat consumption, approved drugs) being perceived as universally harmful, discouraging beneficial exposures, behaviors, or treatments. Here, I propose renaming the groups of agents classified by the IARC and adding basic labels to specific agents to improve the accuracy and interpretability of the IARC classification lists. These adjustments do not interfere with the IARC’s objective of identifying potential hazards, are easy to implement, and enhance accuracy and clarity, providing stronger support to guide cancer prevention strategies.- Book : ()
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2025
AbstractMast cells (MCs) have a well-established detrimental role in allergic conditions, but they can also impact on diverse malignant conditions, including melanoma. To study the latter, previous studies have mainly evaluated how MCs can influence melanomas/melanoma cells. However, the inverse scenario, i.e., whether melanoma/melanoma cells might impact on MCs has received less attention. Here we investigated this issue and show that melanoma cell-conditioned medium had a strong growth-inhibitory impact on MCs, which was attributed to inhibition of MC proliferation combined with induction of apoptosis. Further, our data indicate that such effects were attributable to melanin present in the melanoma cell-conditioned medium, as similar anti-proliferative effects were seen in response to both free melanin and to melanocores enriched from melanoma-conditioned medium. Melanin did not reduce the expression of MC markers, but was shown to impair MC activation. We also demonstrate that melanin is taken up by MCs, both in cultured MCs andin vivoin melanoma tumors, and it was observed that melanin, after uptake, can be found in the MC nucleus. Further, we show that melanin had marked effects on the nuclear morphology in MCs accompanied by clipping of core histone 3, and it is demonstrated that these events were dependent on translocation of tryptase, a granule-localized protease, into the MC nucleus. Tryptase was also shown to affect the mechanism of melanin-induced cell death. Altogether, the present study outlines a novel mechanism by which melanoma cells can suppress MC function, potentially representing an immunosuppressive mechanism that may influence tumor growth.- Book : ()
- Pub. Date : 2025
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2025
ABSTRACTBackgroundDuring the last decades, gamma spectrometry data have increasingly been used in soil science, for example, for mapping. However, the full data potential could not be exploited due to certain constraints, among which the insufficient representation of attenuating materials (in particular, water) in correction algorithms is the most important one. Due to this problem, most often only the potassium/thorium intensity ratio is used in soil science.AimHowever, the ultimate goal must be to derive from field gamma spectrometry the real content of the chemical elements that can be sensed (i.e., normally , , , and ). The first enabling step is to deterministically model the gamma radiation at the soil surface in order to subsequently allow for water content correction by reverse modelling.MethodsWe present here a realisation of a mathematical model that is based on the ‘King‐equation’, but additionally introduces the soil science concept of horizons, that is, a finite number of strata of various vertical thicknesses, with homogeneous properties within each horizon. This approach allows the use of radial symmetry as concept for the three‐dimensional integration of the gamma signal. Input data for the model are horizon vertical thickness, total content of radiating and attenuating materials, and bulk density. Additionally, used parameters concern the decay chains of the radioactive elements.ResultsModel tests with real soil produced count rates in the expected order of magnitude. Due to the instrumental setup of the field spectrometer, it was necessary to replace full spectrum analysis by the concept of regions of relevance (ROR) in order to be able to compare the counts predicted by our model and the counts registered by the spectrometer. The ROR concept is based on the computation of the relevant elements' decay steps and includes Compton scattering.ConclusionUsing this approach, a deviation between modelled and measured gamma radiation is reasonable for and . The reasons for still larger deviations with respect to the ‐signal are discussed.- Book : ()
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2025
- Book : ()
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2025
Background: In pulmonary arterial hypertension (PAH), there is still a need for new prognostic markers to precisely identify patients before clinical deterioration. We investigated the right ventricle cardiac power index (RV CPI) as a tool to assess RV function. We also hypothesized that hemodynamic changes occurring in PAH assessed with the RV CPI are related with cardiac metabolism alterations in PET imaging, which affects prognosis. Methods: Twenty-eight stable PAH patients (51.4 ± 15.9 years old) had PET/CMR and heart catheterization performed at baseline and after 24 months. The PET-derived SUV RV/LV ratio was used to estimate cardiac glucose uptake. Clinical endpoints (CEPs—death or clinical deterioration) were assessed between visits. The RV CPI was defined as cardiac index × mean pulmonary artery pressure × 2.22 × 10−3. Results: The baseline RV CPI was 0.28 ± 0.09 W/m2 and correlated significantly with the SUV RV/LV ratio (r = 0.55, p = 0.002), confirming a relationship between RV hemodynamics and glucose metabolism. After 24 months of PAH-specific therapy, we observed significant improvement in the follow-up RV CPI—0.23 ± 0.04 W/m2 (p = 0.04). During 2-year observations, 16 patients (57%) experienced CEPs (including four deaths). Patients with CEPs had a higher baseline CPI than stable patients (0.32 ± 0.09 vs. 0.21 ± 0.05, p = 0.0006). The cut-off value of the RV CPI to predict worse prognosis was 0.24 W/m2 (log-rank test, p = 0.003). Conclusions: To sum up, the indexed cardiac power output parameter may reflect RV efficiency and is related to its glucose metabolism alterations in PAH. Its low value may help to identify stable patients at higher risk of death or clinical deterioration in long-term prognosis.- Book : 14(4)
- Pub. Date : 2025
- Page : pp.1062-1062
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2025
Abstract
Natural killer (NK) cell development and functionality rely on precise regulation by specific transcription factors (TFs). Our study demonstrates that the nuclear orphan receptor NR2F6 represses the expression of the activating receptor NKp46, an established key player in NK cell-mediated cytotoxicity during infection and tumor rejection. Despite normal NK cell development in the bone marrow, germline Nr2f6-deficient mice exhibit impaired terminal maturation of NK cells in the periphery. Short-term NK cell responses to lipopolysaccharide (LPS) activation, independent of NKp46, are subsequently reduced in Nr2f6-deficient mice. Conventional type 1 dendritic cells (cDC1) and macrophage populations are decreased in spleens of Nr2f6-deficient mice, subsequently, IL-15-dependent NK cell priming is limited. Administration of exogenous IL-15 in vitro and as IL-15 complex in vivo can compensate for these deficits, promoting terminal maturation of NK cells in Nr2f6-deficient mice. Subsequent transcriptome analysis reveals significant changes in gene expression profiles of NK cells from IL-15 complex treated Nr2f6-deficient mice, with notable alterations in essential NK genes such as Klrg1, Prdm1, Stat5a, Zeb2, and Prf1. Consequently, Nr2f6-deficient IL-15 complex-treated NK cells raise enhanced effector responses of IFNγ, Perforin, and Granzyme B upon ex vivo activation. Of importance, Nr2f6-deficient mice are protected against MHC-I negative B16-F10 melanoma lung metastasis formation, especially with IL-15 complex treatment, indicating the potential of NR2F6 to affect NKp46-dependent NK cell-mediated tumor surveillance. The therapeutic targeting of NR2F6 may be a promising strategy for boosting NKp46-dependent NK-cell-mediated tumor surveillance and metastasis.- Book : 16(1)
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- Book : 68(2)
- Pub. Date : 2025
- Page : pp.60-65
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2025
Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases.- Book : 14(4)
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- Page : pp.1381-1381
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2025
The emergence of the atomic bomb prompted the U.S. Marine Corps to develop tactics and procedures to maneuver within a nuclear environment. This led to the establishment of Marine Corps Test Unit no. 1 (MCTU 1), which represented a unique chapter in the history of the Corps. Established in 1954, this experimental unit served as a testing ground for developing tactics and doctrines in the nascent age of nuclear warfare. This article explores the motivations behind the MCTU’s creation, analyzing what the Marine Corps hoped to achieve in this new strategic landscape. It explores the training conducted during Exercises Desert Rock IV (1952) and V (1953) with provisional atomic brigades, then examines the MCTU’s development and accomplishments, including its participation in Exercises Desert Rock VI (1955) and VII (1957) and its role in refining doctrine. Finally, the article delves into the long-term impacts of both MCTU 1 and atomic testing, assessing its influence on the evolution of Marine Corps force reconnaissance, heliborne tactics, and the enduring legacy of its research on nuclear combat scenarios.- Book : 10(2)
- Pub. Date : 2025
- Page : pp.33-44
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2025
Electricity consumption data form the foundation for the efficient and reliable operation of smart grids and are a critical component for ensuring effective data mining. However, due to factors such as meter failures and extreme weather conditions, anomalies frequently occur in the data, which adversely impact the performance of data-driven applications. Given the near full-rank nature of low-voltage distribution area electricity consumption data, this paper employs clustering to enhance the low-rank property of the data. Addressing common issues such as missing data, sparse noise, and Gaussian noise in electricity consumption data, this paper proposes a multi-norm optimization model based on low-rank matrix theory. Specifically, the truncated nuclear norm is used as an approximation of matrix rank, while the L1-norm and F-norm are employed to constrain sparse noise and Gaussian noise, respectively. The model is solved using the Alternating Direction Method of Multipliers (ADMM), achieving a unified framework for handling missing data and noise processing within the model construction. Comparative experiments on both synthetic and real-world datasets demonstrate that the proposed method can accurately recover measurement data under various noise contamination scenarios and different distributions of missing data. Moreover, it effectively separates principal components of the data from noise contamination.- Book : 18(4)
- Pub. Date : 2025
- Page : pp.944-944
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