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Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H 2 O 2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism. Tumour cells sustain high levels of glycolysis even in presence of oxygen, which is known as the Warburg effect. Here the authors show that MnSOD contributes to the Warburg effect by increasing the levels of H 2 O 2 released from mitochondria, which sustains glycolysis by activating AMPK.

In the mountains, snowmelt often provides most of the runoff. Operational estimates use imagery from optical and passive microwave sensors, but each has its limitations. An accurate approach, which we validate in Afghanistan and the Sierra Nevada USA, reconstructs spatially distributed snow water equivalent (SWE) by calculating snowmelt backward from a remotely sensed date of disappearance. However, reconstructed SWE estimates are available only retrospectively; they do not provide a forecast. To estimate SWE throughout the snowmelt season, we consider physiographic and remotely sensed information as predictors and reconstructed SWE as the target. The period of analysis matches the AMSR-E radiometer's lifetime from 2003 to 2011, for the months of April through June. The spatial resolution of the predictions is 3.125 km, to match the resolution of a microwave brightness temperature product. Two machine learning techniques – bagged regression trees and feed-forward neural networks – produced similar mean results, with 0–14 % bias and 46–48 mm RMSE on average. Nash–Sutcliffe efficiencies averaged 0.68 for all years. Daily SWE climatology and fractional snow-covered area are the most important predictors. We conclude that these methods can accurately estimate SWE during the snow season in remote mountains, and thereby provide an independent estimate to forecast runoff and validate other methods to assess the snow resource.

Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), but its interpretation is generally variable due to its relatively subjective nature. Radiomics and classification methods have shown potential for improving the accuracy and objectivity of mpMRI-based PCa assessment. However, these studies are limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and classification methods. This paper presents a systematic and rigorous framework comprised of classification, cross-validation and statistical analyses that was developed to identify the best performing classifier for PCa risk stratification based on mpMRI-derived radiomic features derived from a sizeable cohort. This classifier performed well in an independent validation set, including performing better than PI-RADS v2 in some aspects, indicating the value of objectively interpreting mpMRI images using radiomics and classification methods for PCa risk assessment.

Purpose To assess the impact of 3D printed models of renal tumor on patient’s understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education. Methods A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients’ satisfaction with their specific 3D printed model was also assessed through a visual scale. Results After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % ( p  = 0.018), kidney anatomy by 50 % ( p  = 0.026), tumor characteristics by 39.3 % ( p  = 0.068) and the planned surgical procedure by 44.6 % ( p  = 0.026). Conclusion Presented herein is the initial clinical experience with 3D printing to facilitate patient’s pre-surgical understanding of their kidney tumor and surgery.

The US Preventive Services Task Force (USPSTF) has recommended against routine prostate-specific antigen (PSA)-based prostate cancer (PCa) screening, initially for men older than 75 years in 2008, and then for all men in 2012. Concern has been raised that, by recommending against screening, and thus early detection, the USPSTF recommendations may be associated with an increase in the incidence of metastatic PCa (mPCa). To explore the incidence of mPCa before and after the USPSTF recommendations against routine PCa screening. This population-based cohort study used the recently released Surveillance, Epidemiology, and End Results (SEER) 18 registry incidence data to identify men aged 45 years and older with a diagnosis of invasive PCa from 2004 through 2018. Data were analyzed from January 1, 2004 to December 31, 2018. Outcomes were assessed before vs after the USPSTF recommendations against routine screening. Annual age-adjusted incidence rates per 100 000 population of mPCa (defined using SEER Summary Stage and American Joint Committee on Cancer [AJCC] staging systems), with adjustments for age structure and reporting delay from 2004 to 2011, according to race and age were examined. Annual percentage changes (APCs) were calculated to quantify changes in the annual incidence rates. From 2004 to 2018, a total of 836 282 patients with PCa were recorded in the SEER database; 26 642 (56.5%) distant mPCa cases were reported in men aged 45 to 74 years, and 20 507 (43.5%) cases were reported in men aged 75 years or older. Among men aged 45 to 74 years, the incidence rate of distant mPCa (SEER Summary staging) remained stable during 2004 to 2010 (APC, -0.4%; 95% CI, -1.7% to 1.1%; P = .60), then increased significantly during 2010 to 2018 (APC, 5.3%; 95% CI, 4.5% to 6.0%; P < .001). In men aged 75 years or older, the incidence rate of distant mPCa decreased from 2004 to 2011 (APC, -1.5%; 95% CI, -3.0% to 0%; P = .046), and then increased from 2011 to 2018 (APC, 6.5%; 95% CI, 5.1% to 7.8%; P < .001). Similar trends were also seen for M1 mPCa defined per the AJCC staging system. These increased trends in mPCa incidence were particularly significant in non-Hispanic White men (2010-2018 APC, 6.9%; 95% CI, 5.4% to 8.4%; P < .001). Analysis of the emerging trends from the most recently released SEER data set (2004-2018) suggests that the incidence rates of mPCa have increased significantly and coincide temporally with the USPSTF recommendations against PCa screening across races and age groups. These mPCa trends are associated with reported changes in screening practices following the USPSTF recommendations.

Annually, about 300 million surgeries lead to significant intraoperative adverse events (iAEs), impacting patients and surgeons. Their full extent is underestimated due to flawed assessment and reporting methods. Inconsistent adoption of new grading systems and a lack of standardization, along with litigation concerns, contribute to underreporting. Only half of relevant journals provide guidelines on reporting these events, with a lack of standards in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems’ reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. Invitation to participate are extended to all the surgical specialties, interventional cardiology, interventional radiology, OR Staffs and anesthesiology. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.

The emergence of chikungunya virus (CHIKV) has raised serious concerns due to the virus' rapid dissemination into new geographic areas and the clinical features associated with infection. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. Our phylogenetic reconstructions indicated the circulation of the East-Central-South-African (ECSA) lineage in Rio de Janeiro. Time-measured phylogenetic analysis combined with CHIKV notified case numbers revealed the ECSA lineage was introduced in Rio de Janeiro around June 2015 (95% Bayesian credible interval: May to July 2015) indicating the virus was circulating unnoticed for 5 months before the first reports of CHIKV autochthonous transmissions in Rio de Janeiro, in November 2015. These findings reinforce that continued genomic surveillance strategies are needed to assist in the monitoring and understanding of arbovirus epidemics, which might help to attenuate public health impact of infectious diseases.

Epidemiologic studies in diabetic patients as well as research in model organisms have indicated the potential of metformin as a drug candidate for the treatment of various types of cancer, including breast cancer. To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK). However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it. Here, we demonstrate that AMPK opposes the detrimental effects of mitochondrial complex I inhibition by enhancing glycolysis at the expense of, and in a manner dependent on, pyruvate availability. We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis. In fact, while the killing effects of metformin were largely rescued by pyruvate in AMPKcompetent cells, AMPK-deficient cells required instead acetoacetate, a product of fatty acid catabolism indicating a switch from sugar to fatty acid metabolism as a central resource for ATP production in these cells. In summary, our results indicate that AMPK activation is not responsible for metformin anticancer activity and may instead alleviate energetic stress by activating glycolysis.

Purpose To compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS. Methods Pre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010–09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason score ≥7 and/or maximum cancer core length ≥5 mm. Results Targeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41 %; p  = 0.007), sPCa detection rate (43 vs. 23 %; p  = 0.0013), cancer core length (7.5 vs. 3.9 mm; p  = 0.0002), and cancer rate per core (56 vs. 12 %; p  < 0.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate ( p  < 0.0001), higher Gleason score ( p  = 0.018), and greater cancer core length ( p  < 0.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield ( p  < 0.0001) and higher sPCa detection rate ( p  < 0.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate. Conclusions MR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.

Annually, about 300 million surgeries lead to significant intraoperative adverse events (iAEs), impacting patients and surgeons. Their full extent is underestimated due to flawed assessment and reporting methods. Inconsistent adoption of new grading systems and a lack of standardization, along with litigation concerns, contribute to underreporting. Only half of relevant journals provide guidelines on reporting these events, with a lack of standards in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems' reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. Invitation to participate are extended to all the surgical specialties, interventional cardiology, interventional radiology, OR Staffs and anesthesiology. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.