Background
Before the year 2000, there was no dedicated childhood cancer service in Cameroon. The aim of this study was to investigate the progress made with pediatric oncology care in Cameroon from ...2000 to 2020.
Method
A literature search was conducted for published articles on childhood cancer in Cameroon and relevant documents, and conference s were reviewed. The articles were analyzed under the themes: awareness, diagnosis, epidemiology, treatment, outcome, advocacy, partnerships, traditional and complementary medicine, palliative care, and capacity building.
Results
Low awareness on childhood cancer was addressed with education activities targeting the general population and health care professionals. Cancer diagnosis was achieved with cytology, histology, and simple imaging. Management for common and curable cancers was implemented with use of modified treatment regimens for low‐ and middle‐income settings. Nutritional support was shown to mitigate the effects of malnutrition on treatment toxicity, and support was provided for transportation and accommodation. There was good collaboration between the pediatric oncology professionals nationally and twinning with international partners. Capacity building activities led to the availability of three pediatric oncologists and pediatric oncology‐trained nurses. Advocacy nationally led to the support of the Ministry of Health with pediatric oncology‐specific priority actions in the latest national cancer control plan.
Conclusion
Childhood cancer should receive the necessary attention of health care policymakers in Cameroon. With continued commitment of government, nongovernmental organizations, charities, childhood cancer specialists, patient and parent groups, there should be an improved future for children with cancer in Cameroon.
Early osteoarthritis (OA), characterised by cartilage defects, is a degenerative disease that greatly affects the adult population. Cell-based tissue engineering methods are being explored as a ...solution for the treatment of these chondral defects. Chondrocytes are already in clinical use but other cell types with chondrogenic properties, such as mesenchymal stem cells (MSCs), are being researched. However, present methods for differentiating these cells into stable articular-cartilage chondrocytes that contribute to joint regeneration are not effective, despite extensive investigation. Environmental stimuli, such as mechanical forces, influence chondrogenic response and are beneficial with respect to matrix formation. In vivo, the cartilage is subjected to multiaxial loading involving compressive, tensile, shear and fluid flow and cellular response. Tissue formation mechanobiology is being intensively studied in the cartilage tissue-engineering research field. The study of the effects of hydrostatic pressure on cartilage formation belongs to the large area of mechanobiology. During cartilage loading, interstitial fluid is pressurised and the surrounding matrix delays pressure loss by reducing fluid flow rate from pressurised regions. This fluid pressurisation is known as hydrostatic pressure, where a uniform stress around the cell occurs without cellular deformation. In vitro studies, examining chondrocytes under hydrostatic pressure, have described its anabolic effect and similar studies have evaluated the effect of hydrostatic pressure on MSC chondrogenesis. The present review summarises the results of these studies and discusses the mechanisms through which hydrostatic pressure exerts its effects.
The clumped isotopic composition of carbonate‐derived CO2 (denoted Δ47) is a function of carbonate formation temperature and in natural samples can act as a recorder of paleoclimate, burial, or ...diagenetic conditions. The absolute abundance of heavy isotopes in the universal standards VPDB and VSMOW (defined by four parameters: R13VPDB, R17VSMOW, R18VSMOW, and λ) impact calculated Δ47 values. Here, we investigate whether use of updated and more accurate values for these parameters can remove observed interlaboratory differences in the measured T‐Δ47 relationship. Using the updated parameters, we reprocess 14 published calibration data sets measured in 11 different laboratories, representing many mineralogies, bulk compositions, sample types, reaction temperatures, and sample preparation and analysis methods. Exploiting this large composite data set (n = 1,253 sample replicates), we investigate the possibility for a “universal” clumped isotope calibration. We find that applying updated parameters improves the T‐Δ47 relationship (reduces residuals) within most labs and improves overall agreement but does not eliminate all interlaboratory differences. We reaffirm earlier findings that different mineralogies do not require different calibration equations and that cleaning procedures, method of pressure baseline correction, and mass spectrometer type do not affect interlaboratory agreement. We also present new estimates of the temperature dependence of the acid digestion fractionation for Δ47 (Δ*25‐X), based on combining reprocessed data from four studies, and new theoretical equilibrium values to be used in calculation of the empirical transfer function. Overall, we have ruled out a number of possible causes of interlaboratory disagreement in the T‐Δ47 relationship, but many more remain to be investigated.
Plain Language Summary
Measured stable and clumped isotope values are fundamentally tied to established compositions of international standard materials. When these standard compositions are updated, it impacts previously published isotope measurements such as those used to define the clumped isotope calibration relationship (the foundation for use of this isotopic proxy as a paleothermometer, recorder of burial history or past diagenetic conditions). Here we reprocess 14 published clumped isotope calibration studies using updated international standard compositions and identical data processing procedures to see if these changes would eliminate previously observed interlaboratory discrepancies in clumped isotope calibration relationships. We find that this update tightens the clumped isotope calibration relationship within most laboratories and improves overall agreement between laboratories but does not eliminate all interlaboratory differences. We also propose “best practices” for data processing and dissemination going forward. This study makes progress toward resolving discrepancies in clumped isotope calibration relationships between laboratories by eliminating a number of possible causes and moves the clumped isotope community closer toward our ultimate goal of applying this powerful new proxy routinely to exciting science questions.
Key Points
Updates to 17O correction parameters and international standard compositions affect clumped isotopic compositions
Reprocessing published calibration data using new parameters and consistent methodology slightly improves interlaboratory agreement
There is no evidence (within error) for mineral‐specific offsets in calibration equation or temperature dependence of acid digestion fractionation
Dark matter (DM)-electron scattering is a prime target of a number of direct DM detection experiments and constitutes a promising avenue for exploring interactions of DM in the sub-GeV mass-range, ...challenging to probe with nuclear recoils. We extend the recently proposed halo-independent analysis method for DM-electron scattering, which allows to infer the local DM halo properties without any additional assumptions about them, to include in-medium effects through dielectric functions of the target material. We show that in-medium effects could significantly affect halo-independent analysis response functions for germanium and silicon and thus are essential for proper inference of local DM halo characteristics from direct DM detection data.
Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers ...to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC.
CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28).
Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001).
Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.
Metastasis is the major cause of death in cancer patients. Whereas colorectal cancer (CRC) incidence increases with age, metastatic spread seems to decline. Furthermore, the epidemiology of CRC is ...changing. There is an increase in CRC incidence in the young, presenting at an advanced stage with higher likelihood of synchronous or metachronous metastases, and a decline in CRC incidence and metastatic spread in the oldest-old. Emerging data suggest that age-related changes with regard to tumor biology (e.g. genomic instability), the tumor microenvironment (e.g. inflammaging) and the immune system (e.g. immunosenescence), complemented by interaction between the genome and exposome might contribute to the observed metastatic patterns. As aging is a key prognostic factor, this highlights the need for further studies investigating age-related patterns and underlying mechanisms of tumor growth and dissemination. Eventually, this might allow for better risk stratification, refinement of screening strategies and follow-up care as well as therapies tailored to reflect patient age and that might possibly target responsible biomarkers in a precision medicine approach. This review aims to discuss the influence of aging on metastatic spread in colorectal cancer and elucidate underlying mechanisms responsible for the observed metastatic patterns.
•Colorectal cancer incidence increases with age whereas metastatic spread declines.•Age-related changes in primary tumor and microenvironment drive metastatic spread.•Aging impacts metastasis via changes in tumor biology, inflammaging, immunosenescence.
Elucidation of whether miRs are involved in mechanotransduction pathways by which cartilage is maintained or disturbed has a particular importance in our understanding of osteoarthritis (OA) ...pathophysiology. The aim was to investigate whether mechanical loading influences global miR-expression in human chondrocytes and to identify mechanosensitive miRs responding to beneficial and non-beneficial loading regimes as potential to obtain valuable diagnostic or therapeutic targets to advance OA-treatment.
Mature tissue-engineered human cartilage was subjected to two distinct loading regimes either stimulating or suppressing proteoglycan-synthesis, before global miR microarray analysis. Promising candidate miRs were selected, re-evaluated by qRT-PCR and tested for expression in human healthy vs OA cartilage samples.
After anabolic loading, miR microarray profiling revealed minor changes in miR-expression while catabolic stimulation produced a significant regulation of 80 miRs with a clear separation of control and compressed samples by hierarchical clustering. Cross-testing of selected miRs revealed that miR-221, miR-6872-3p, miR-6723-5p were upregulated by both loading conditions while others (miR-199b-5p, miR-1229-5p, miR-1275, miR-4459, miR-6891-5p, miR-7150) responded specifically after catabolic loading. Mechanosensitivity of miR-221 correlated with pERK1/2-activation induced by both loading conditions. The miR-response to loading was transient and a constitutive deregulation of mechano-miRs in OA vs healthy articular cartilage was not observed.
MiRs with broader vs narrower mechanosensitivity were discovered and the first group of mechanosensitive miRs characteristic for non-beneficial loading was defined that may shape the proteome differentially when cartilage tissue is disturbed. The findings prompt future investigations into miR-relevance for mechano-responsive pathways and the corresponding miR-target molecules.
A simple extension of the Standard Model consists of a scalar field that can potentially constitute the dark matter (DM). Significant attention has been devoted to probing light O(≲10eV) scalar DM, ...with a multitude of experimental proposals based on condensed matter systems as well as novel materials. However, the previously overlooked effective in-medium mixing of light scalars with longitudinal plasmons can strongly modify the original sensitivity calculations of the direct detection experiments. We implement the in-medium effects for scalar DM detection, using thermal field theory techniques, and show that the reach of a large class of direct DM detection experiments searching for light scalars is significantly reduced. This development identifies setups based on Dirac materials and tunable plasma haloscopes as particularly promising for scalar DM detection. Further, we also show that scalars with significant boost with respect to halo DM, such as those produced in the Sun, decay of other particles or by cosmic rays, will not suffer from in-medium suppression. Hence, multi-tonne direct DM detection experiments, such as those based on xenon or argon, also constitute a favorable target. We also discuss scalar mediated DM scattering.
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