Relationship of CD147 kidney expression with various pathologic lesions, biochemical and demographic data in patients with classes III and IV of lupus nephritis

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that affects the kidney in around 50% of patients Objectives: The aim of this study was to assess CD147 expression with various pathologic lesions, biochemical and demographic data in patients with classes III and IV lupus nephritis. Patients and Methods: These patients with lupus nephritis classes II and IV by renal biopsy and pathology were enrolled in this study. The strength of CD147 staining on tubules, Bowman’s capsules, vessels and tuft of glomeruli was expressed as proportion of involvement. Results: In this study, 23 renal biopsies for lupus nephritis of classes III and IV (documented by immunofluorescence and light microscopic studies) were included. No significant difference of CD147 staining between classes was detected (P > 0.05). In addition, proportion of proteinuria was not related to CD147 staining in tubules, Bowman’s capsules, vessels and tuft of glomeruli in classes III and IV lupus nephritis (P > 0.05). There was no significant association of CD147 staining in tubules, Bowman’s capsules and vessels with serum creatinine (P > 0.05). However, an association between CD147 staining in tuft of glomeruli with serum creatinine was detected (r=0.623, P = 0.002). None of chronicity or activity percent of glomerular involvement in two classes of III or IV had a significant association with CD147 staining (P > 0.05). Conclusions: The significant association between CD147 staining in glomeruli with serum creatinine in lupus nephritis of classes III and IV revealed that inflammation at this area may have prognostic implication

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Performance of Wayne assay for detection of pyrazinamide resistance in Mycobacterium tuberculosis: a meta-analysis study

Conventional culture-based drug susceptibility testing (DST) of Mycobacterium tuberculosis to pyrazinamide (PZA) is time-consuming and difficult to perform. The current systematic review and meta-analysis was aimed to evaluate the diagnostic accuracy of Wayne assay against culture-based DSTs as the reference standard. We searched the MEDLINE/Pubmed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. Statistical analyses were performed with STATA (version 14, Stata Corporation, College Station, TX, USA), RevMan (version 5.3; The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark), and Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain). A total of 31 articles comprising data for 2457 isolates of M. tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the Wayne assay against all reference tests (the combination of BACTEC MGIT 960, BACTEC 460, and proportion method) were 86.6% (95% CI: 84.3-88.7) and 96.0% (95% CI: 94.8-97). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) estimates were found to be 17.6 (95% CI: 10.5-29.3), 0.11 (95% CI: 0.06-0.20), 164 (95% CI: 83-320) and 97%, respectively. Deek's test result indicated no evidence for publication bias (P > 0.05).Although the current study shows that the Wayne test is sensitive and specific for detecting PZA resistance, it may be used in combination with conventional DSTs to diagnose PZA resistance accurately

Risk-avoidant decision making increased by threat of electric shock.

Threat cues elicit defensive reactions mediated by limbic brain circuitry that is also implicated in risk-sensitive decision making. Building upon research looking at stress effects on decision making, a gambling task was administered to 65 healthy adults, comparing decision making on trials on which a red screen background signalled threat of shocks against trials when shocks could not occur. The threat cues elicited increased electrodermal activity and a sustained decrease in heart rate, consistent with defensive vigilance. The threat condition was associated with risk-avoidant choices, on trials where the risky option involved moderate losses and when choosing between options involving only losses. These effects were not explained by changes in latency. Threat exerts immediate effects on decision making and physiological arousal, biasing subjects towards safer alternatives, potentially through a magnified processing of loss information

Mapping the intrinsic photocurrent streamlines through micromagnetic heterostructure devices

Photocurrent in quantum materials is often collected at global contacts far away from the initial photoexcitation. This collection process is highly nonlocal. It involves an intricate spatial pattern of photocurrent flow (streamlines) away from its primary photoexcitation that depends sensitively on the configuration of current collecting contacts as well as the spatial nonuniformity and tensor structure of conductivity. Direct imaging to track photocurrent streamlines is challenging. Here, we demonstrate a microscopy method to image photocurrent streamlines through ultrathin heterostructure devices comprising platinum on yttrium iron garnet (YIG). We accomplish this by combining scanning photovoltage microscopy with a uniform rotating magnetic field. Here, local photocurrent is generated through a photo-Nernst type effect with its direction controlled by the external magnetic field. This enables the mapping of photocurrent streamlines in a variety of geometries that include conventional Hall bar-type devices, but also unconventional wing-shaped devices called electrofoils. In these, we find that photocurrent streamlines display contortion, compression, and expansion behavior depending on the shape and angle of attack of the electrofoil devices, much in the same way as tracers in a wind tunnel map the flow of air around an aerodynamic airfoil. This affords a powerful tool to visualize and characterize charge flow in optoelectronic devices.Ministry of Education (MOE)Published versionThis work was supported by the Presidential Early Career Award for Scientists and Engineers through the Air Force Office of Scientific Research award no. FA9550- 20- 1- 0097 (D.M. and N.M.G.), through support from the NSF Division of Materials Research CAREER award no. 1651247 (D.M., F.F., M.G., and N.M.G.), through support from the Army Research Office Electronics Division Award no. W911NF2110260 (F.F., V.A., and N.M.G.). D.M., M.G., M.L., M.A., J.L., and J.S., were supported as part of the SHINES, an Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Basic Energy Sciences under Award No. SC0012670. J.C.W.S. acknowledges support from the Singapore Ministry of Education Academic Research Fund Tier 3 Grant MOE2018-T3-1-002

Proteomic analysis of Src family kinase phosphorylation states in cancer cells suggests deregulation of the unique domain

The Src family of kinases (SFKs) are homologs of retroviral oncogenes, earning them the label of proto-oncogenes. Their functions are influenced by positive and negative regulatory tyrosine phosphorylation events and inhibitory and activating intramolecular and extramolecular interactions. This regulation is disrupted in their viral oncogene counterparts. However, in contrast to most other proto-oncogenes, the genetic alteration of these genes does not seem to occur in human tumors and how and if their functions are altered in human cancers remains to be determined. To look for proteomic level alterations, we took a more granular look at the activation states of SFKs based on their two known regulatory tyrosine phosphorylations but find no significant differences in their activity states when comparing immortalized epithelial cells to cancer cells. SFKs are known to have other less well studied phosphorylations, particularly within their unstructured N-terminal unique domains (UD), although their role in cancers has not been explored. In comparing panels of epithelial cells to cancer cells we find a decrease in S17 phosphorylation in the UD of Src in cancer cells. Dephosphorylated S17 favors the dimerization of Src that is mediated through the UD and suggests increased Src dimerization in cancers. These data highlight the important role of the UD of Src and suggest that a deeper understanding of proteomic level alterations of the unstructured UD of SFKs may provide considerable insights into how SFKs are deregulated in cancers. IMPLICATIONS: This work highlights the role of the N-terminal unique domain of Src kinases in regulating their signaling functions and possibly in their deregulation in human cancers

Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells

Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM