Epidemiology of Cancers in Zambia: A significant variation in Cancer incidence and prevalence across the nation

BackgroundCancer is one of the leading causes of death worldwide. More than two-thirds of deaths due to cancers occur in low- and middle-income countries where Zambia belongs. This study, therefore, sought to assess the epidemiology of various types of cancers in Zambia.MethodsWe conducted a retrospective observational study using the Zambia National Cancer Registry (ZNCR) population based data from 2007 to 2014. Zambia Central Statistics Office (CSO) demographic data were used to determine catchment area denominator used to calculate prevalence and incidence rates of cancers. Age-adjusted rates and case fatality rates were estimated using standard methods. We used a Poisson Approximation for calculating 95% confidence intervals (CI). ResultsThe seven most cancer prevalent districts in Zambia were Luangwa, Kabwe, Lusaka, Monze, Mongu, Katete and Chipata. Cervical cancer, prostate cancer, breast cancer and Kaposi’s sarcoma were the four most prevalent cancers as well as major causes of cancer related deaths in Zambia. Age adjusted rates and 95% CI for these cancers were: cervix uteri (186.3; CI = 181.77 – 190.83), prostate (60.03; CI = 57.03 – 63.03), breast (38.08; CI = 36.0 – 40.16) and Kaposi’s sarcoma (26.18; CI = 25.14 – 27.22). CFR were: Leukaemia (38.1%); pancreatic cancer (36.3%); lung cancer (33.3%); and brain, nervous system (30.2%). The cancer population was associated with HIV with p- value of 0.000 and a Pearson correlation coefficient of 0.818.ConclusionsThe widespread distribution of cancers with high prevalence observed in the southern zone may have been perpetrated by lifestyle and sexual culture (traditional male circumcision known to prevent STIs is practiced in the northern belt) as well as geography. Intensifying cancer screening and early detection countrywide as well as changing the lifestyle and sexual culture would greatly help in the reduction of cancer cases in Zambia

Towards Balanced Active Learning for Multimodal Classification

Training multimodal networks requires a vast amount of data due to their larger parameter space compared to unimodal networks. Active learning is a widely used technique for reducing data annotation costs by selecting only those samples that could contribute to improving model performance. However, current active learning strategies are mostly designed for unimodal tasks, and when applied to multimodal data, they often result in biased sample selection from the dominant modality. This unfairness hinders balanced multimodal learning, which is crucial for achieving optimal performance. To address this issue, we propose three guidelines for designing a more balanced multimodal active learning strategy. Following these guidelines, a novel approach is proposed to achieve more fair data selection by modulating the gradient embedding with the dominance degree among modalities. Our studies demonstrate that the proposed method achieves more balanced multimodal learning by avoiding greedy sample selection from the dominant modality. Our approach outperforms existing active learning strategies on a variety of multimodal classification tasks. Overall, our work highlights the importance of balancing sample selection in multimodal active learning and provides a practical solution for achieving more balanced active learning for multimodal classification.Comment: 12 pages, accepted by ACMMM 202

Molecularly Tracing of Children Exposure Pathways to Environmental Persistent Organic Pollutants and the Autism Spectrum Disorder Risk

Organic pollutants (OPs) including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) have showed neuro-damaging effects, but studies concerning the autism spectrum disorder (ASD) risk are limited. A case-control study with ASD (n=125) and healthy control (n=125) children was conducted on the different land use settings across Punjab, Pakistan. Serum concentrations of 26 OCPs, 29 PCB congeners, 11 PBDEs and 32 PAHs were measured. Serum PCB77 (AOR = 2.00; 95% CI: 1.43, 2.18), PCB118 (AOR = 1.49; 95% CI: 1.00, 2.00), PCB128 (AOR = 1.65; 95% CI: 1.01, 1.91), PCB153 (AOR = 1.80; 95% CI: 1.55, 1.93) were significantly higher, but PCB187 (AOR = 0.37; 95% CI: 0.24, 0.49) was significantly lower in the ASD cases when compared to the controls. Serum BDE99 (AOR = 0.48; 95% CI: 0.26, 0.89) was significantly higher in the healthy controls than in the ASD cases. Among the analysed OCPs, p,p′-DDE (AOR = 1.50; 95% CI: 1.00, 1.85) was significantly elevated in the ASD cases with comparison in the controls. For PAHs, serum dibenzothiophene (AOR = 7.30; 95% CI: 1.49, 35.85) was significantly higher in the ASD, while perylene (AOR = 0.25; 95% CI: 0.06, 1.10) and fluorene (AOR = 0.21; 95% CI: 0.06, 0.72) were significantly higher in the controls. In addition, many of the serum pollutants were significantly associated with GSTT1, GSTM1 (null/present polymorphism) and presented the genotypic variation to respond xenobiotics in children. The children living in proximity to urban and industrial areas had a greater exposure to most of the studied pollutants when compared to the rural children, however children residing in rural areas showed higher exposure to OCPs. This comprehensive study documents an association between environmental exposure risk of several organic pollutants (OPs) from some contaminated environmental settings with ASD risk in children from Pakistan

Sensitization of Glioma Cells to Tamoxifen-Induced Apoptosis by Pl3-Kinase Inhibitor through the GSK-3β/β-Catenin Signaling Pathway

Malignant gliomas represent one of the most aggressive types of cancers and their recurrence is closely linked to acquired therapeutic resistance. A combination of chemotherapy is considered a promising therapeutic model in overcoming therapeutic resistance and enhancing treatment efficacy. Herein, we show by colony formation, Hochest 33342 and TUNEL staining, as well as by flow cytometric analysis, that LY294002, a specific phosphatidylinositide-3-kinase (PI3K) inhibitor, enhanced significantly the sensitization of a traditional cytotoxic chemotherapeutic agent, tamoxifen-induced apoptosis in C6 glioma cells. Activation of PI3K signaling pathway by IGF-1 protected U251 cells from apoptosis induced by combination treatment of LY294002 and tamoxifen. Interference of PI3K signaling pathway by PI3K subunit P85 siRNA enhanced the sensitization of U251 glioma cells to tamoxifen -induced apoptosis. By Western blotting, we found that combination treatment showed lower levels of phosphorylated AktSer473 and GSK-3βSer9 than a single treatment of LY294002. Further, we showed a significant decrease of nuclear β-catenin by combination treatment. In response to the inhibition of β-catenin signaling, mRNA and protein levels of Survivin and the other three antiapoptotic genes Bcl-2, Bcl-xL, and Mcl-1 were significantly decreased by combination treatment. Our results indicated that the synergistic cytotoxic effect of LY294002 and tamoxifen is achieved by the inhibition of GSK-3β/β-catenin signaling pathway

Biphasic effects of perfluorooctanoic acid on steroidogenesis in mouse Leydig tumour cells

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant, which may possess endocrine disrupting properties. Herein, we investigated the possible mechanism(s) of toxicity and steroidogenesis in mouse Leydig cells. MLTC-1 (mouse Leydig tumour cells) cells were exposed to 0, 50, 100 or 200 μM PFOA for 48 h to ascertain their effects on the nuclear (membrane) receptor responses, steroidogenesis pathway and related regulated gene expression and steroid hormone secretion profiles. Our results reveal that nuclear receptors PXR, SR-B1 and LHR are sensitive to PFOA exposure. PFOA can accumulate in mitochondria and alter cholesterol precursor (fatty acid) mitochondrial transport process-related gene expression and thus inhibit steroid hormone precursor (cholesterol) production. In particular, PFOA exhibits biphasic effects on testosterone and progesterone production at differing levels of exposure. These findings indicate the potential endocrine-related effects of PFOA on steroid hormone secretion in Leydig cells and point to a novel disruption model. [Abstract copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Diet-sourced carbon-based nanoparticles induce lipid alterations in tissues of zebrafish (Danio rerio) with genomic hypermethylation changes in brain

With rising environmental levels of carbon-based nanoparticles (CBNs), there is an urgent need to develop an understanding of their biological effects in order to generate appropriate risk assessment strategies. Herein, we exposed zebrafish via their diet to one of four different CBNs: C60 fullerene (C60), single-walled carbon nanotubes (SWCNT), short multi-walled carbon nanotubes (MWCNTs) or long MWCNTs. Lipid alterations in male and female zebrafish were explored post-exposure in three target tissues (brain, gonads and gastrointestinal tract) using ‘omic’ procedures based in liquid chromatography coupled with mass spectrometry (LC-MS) data files. These tissues were chosen as they are often target tissues following environmental exposure. Marked alterations in lipid species are noted in all three tissues. To further explore CBN-induced brain alterations, Raman microspectroscopy analysis of lipid extracts was conducted. Marked lipid alterations are observed with males responding differently to females; in addition, there also appears to be consistent elevations in global genomic methylation. This latter observation is most profound in female zebrafish brain tissues post-exposure to short MWCNTs or SWCNTs (P < 0.05). This study demonstrates that even at low levels, CBNs are capable of inducing significant cellular and genomic modifications in a range of tissues. Such alterations could result in modified susceptibility to other influences such as environmental exposures, pathology and, in the case of brain, developmental alterations

Phthalates Induce Androgenic Effects at Exposure Levels That Can Be Environmentally Relevant in Humans

Although anti-androgenic activity of various lipophilic chain phthalate acid esters (PAEs) has been reported in high-dose animal studies, their male reproductive risk remains a matter of debate because of conflicting epidemiological observations. Recently, we showed that PAEs acted as a preventative factor in male infertility, which implies these chemicals are androgenic in human steroidogenesis. To verify the androgenic observation, a reproductive age healthy male cohort (n = 84) was recruited by following a cross-sectional study design, in which infertility or clinical selection-introduced bias was avoided. Urine was used for both PAE exposure monitoring and androgen measurements, and sampling uncertainty was greatly reduced. Eight selected metabolites (i.e., MMP, MEP, MBP, MEHP, MBzP, MEHHP, MECPP, and MEOHP) and two androgens, i.e., androstenedione (ASD) and testosterone, were measured by using HPLC–MS/MS. Except for MBzP, the selected phthalates can be detected in all samples at concentrations (median [5th–95th percentile]) of 36.4 [2.0–261.0], 36.7 [5.6–318.5], 75.3 [13.1–301.0], 3.2 [1.1–10.2], 3.8 [0.6–11.9], 13.6 [1.6–51.1], and 7.4 [0.9–31.8] ng/mL for MMP, MEP, MBP, MEHP, MEOHP, MECPP, and MEHHP, respectively. Urinary PAE metabolites generally correlated with ASD and testosterone in positive ways; the trends are most significant for MMP, MEP, MBP, and ∑DEHP versus ASD and for ∑DEHP versus testosterone. This study reveals that the phenotypic effect of our participants’ exposure to PAEs at the typical environmental relevant exposure level is androgenic, which counters the notion of the well-accepted anti-androgenic effect

High-performance quantum entanglement generation via cascaded second-order nonlinear processes

In this paper, we demonstrate the generation of high-performance entangled photon-pairs in different degrees of freedom from a single piece of fiber pigtailed periodically poled LiNbO$_3$ (PPLN) waveguide. We utilize cascaded second-order nonlinear optical processes, i.e. second-harmonic generation (SHG) and spontaneous parametric down conversion (SPDC), to generate photon-pairs. Previously, the performance of the photon pairs is contaminated by Raman noise photons from the fiber pigtails. Here by integrating the PPLN waveguide with noise rejecting filters, we obtain a coincidence-to-accidental ratio (CAR) higher than 52,600 with photon-pair generation and detection rate of 52.3 kHz and 3.5 kHz, respectively. Energy-time, frequency-bin and time-bin entanglement is prepared by coherently superposing correlated two-photon states in these degrees of freedom, respectively. The energy-time entangled two-photon states achieve the maximum value of CHSH-Bell inequality of S=2.708$\pm$0.024 with a two-photon interference visibility of 95.74$\pm$0.86%. The frequency-bin entangled two-photon states achieve fidelity of 97.56$\pm$1.79% with a spatial quantum beating visibility of 96.85$\pm$2.46%. The time-bin entangled two-photon states achieve the maximum value of CHSH-Bell inequality of S=2.595$\pm$0.037 and quantum tomographic fidelity of 89.07$\pm$4.35%. Our results provide a potential candidate for quantum light source in quantum photonics.Comment: 29 pages,7 figure

Persistent Pesticides in Human Breast Milk and Cryptorchidism

INTRODUCTION: Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. DESIGN: Within a prospective birth cohort, we performed a case–control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. RESULTS: Eight organochlorine pesticides were measurable in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p′-DDE): 97.3/83.8; β-hexachlorocyclohexane (β-HCH): 13.6/12.3; hexachlorobenzene (HCB): 10.6/8.8; α -endosulfan: 7.0/6.7; oxychlordane: 4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDT): 4.6/4.0; dieldrin: 4.1/3.1; cis-heptachloroepoxide (cis-HE): 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p′-DDD); o,p′-DDT; mirex] were measurable in most samples (detection rates 90.8–99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA), γ -HCH, 1,1-dichloro-2-(2-chlorophenyl)-2,2(4-chlorophenyl)ethane, trans-chlordane, α -HCH, and o,p′-DDE, both concentrations and detection rates were low (26.5–71.5%). Heptachlor, HCH (δ, ɛ ), aldrin, β-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p′-DDT, p,p′-DDE, p,p′-DDD, o,p′-DDT, HCH (α , β, γ ), HCB, PCA, α -endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012), there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism (p = 0.032). CONCLUSION: The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected